Infectious Diseases

Staging of liver fibrosis, important for determining prognosis in patients with chronic liver disease and for the need to start screening for complications of cirrhosis, was traditionally done only by liver biopsy. While biopsy is still the gold standard method to stage fibrosis, noninvasive methods have been developed that can also assess disease severity.

This article briefly reviews the epidemiology and physiology of chronic liver disease and the traditional role of liver biopsy. Pros and cons of alternative fibrosis assessment methods are discussed, with a focus on their utility for patients with nonalcoholic fatty liver disease (NAFLD) and hepatitis C virus (HCV) infection.

CHRONIC LIVER DISEASE: A HUGE HEALTH BURDEN

Chronic liver disease is associated with enormous health and financial costs in the United States. Its prevalence is about 15%,¹ and it is the 12th leading cause of death.² Hospital costs are estimated at about $4 billion annually.³

The most common causes of chronic liver disease are NAFLD (which may be present in up to one-third of the US population and is increasing with the epidemic of obesity), its aggressive variant, nonalcoholic steatohepatitis (NASH) (present in about 3% of the population), and HCV infection (1%).^4,5

Since direct-acting antiviral agents were introduced, HCV infection dropped from being the leading cause of liver transplant to third place.⁶ But at the same time, the number of patients on the transplant waiting list who have NASH has risen faster than for any other cause of chronic liver disease.⁷

FIBROSIS: A KEY INDICATOR OF DISEASE SEVERITY

In HCV infection, advanced fibrosis is defined as either stage 4 to 6 using the Ishak system¹⁰ or stage 3 to 4 using the Meta-analysis of Histological Data in Viral Hepatitis (METAVIR) system.¹¹

In NAFLD, advanced fibrosis is defined as stage 3 to 4 using the NASH Clinical Research Network system.¹²

Staging fibrosis is also important so that patients with cirrhosis can be identified early to begin screening for hepatocellular carcinoma and esophageal varices to reduce the risks of illness and death. In addition, insurance companies often require documentation of fibrosis stage before treating HCV with the new direct-acting antiviral agents.

LIVER BIOPSY IS STILL THE GOLD STANDARD

Although invasive, liver biopsy remains the gold standard for determining fibrosis stage. Liver biopsies were performed “blindly” (without imaging) until the 1990s, but imaging-guided biopsy using ultrasonography was then developed, which entailed less pain and lower complication and hospitalization rates. Slightly more hepatic tissue is obtained with guided liver biopsy, but the difference was deemed clinically insignificant.¹³ Concern initially arose about the added cost involved with imaging, but imaging-guided biopsy was actually found to be more cost-effective.¹⁴

In the 2000s, transjugular liver biopsy via the right internal jugular vein became available. This method was originally used primarily in patients with ascites or significant coagulopathy. At first, there were concerns about the adequacy of specimens obtained to make an accurate diagnosis or establish fibrosis stage, but this limitation was overcome with improved techniques.^15,16 Transjugular liver biopsy has the additional advantage of enabling one to measure the hepatic venous pressure gradient, which also has prognostic significance; a gradient greater than 10 mm Hg is associated with worse prognosis.¹⁷

Disadvantages of biopsy: Complications, sampling errors

Liver biopsy has disadvantages. Reported rates of complications necessitating hospitalization using the blind method were as high as 6% in the 1970s,¹⁸ dropping to 3.2% in a 1993 study.¹⁹ Bleeding remains the most worrisome complication. With the transjugular method, major and minor complication rates are less than 1% and 7%, respectively.^15,16 Complication rates with imaging-guided biopsy are also low.

Liver biopsy is also prone to sampling error. The number of portal tracts obtained in the biopsy correlates with the accuracy of fibrosis staging, and smaller samples may lead to underestimating fibrosis stage. In patients with HCV, samples more than 15 mm long led to accurate staging diagnosis in 65% of patients, and those longer than 25 mm conferred 75% accuracy.²⁰ Also, different stages can be diagnosed from samples obtained from separate locations in the liver, although rarely is the difference more than a single stage.²¹

Histologic evaluation of liver biopsies is operator-dependent. Although significant interobserver variation has been reported for degree of inflammation, there tends to be good concordance for fibrosis staging.^22,23

Several scores based on patient characteristics and laboratory values have been developed for assessing liver fibrosis and have been specifically validated for HCV infection, NAFLD, or both. They can serve as inexpensive initial screening tests for the presence or absence of advanced fibrosis.

FIB-4 index for HCV, NAFLD

The FIB-4 index predicts the presence of advanced fibrosis using, as its name indicates, a combination of 4 factors in fibrosis: age, platelet count, and the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), according to the formula:

FIB-4 index = (age × AST [U/L]) /
(platelet count [× 10⁹/L] × √ALT [U/L]).

The index was derived from data from 832 patients co-infected with HCV and human immunodeficiency virus.²⁴ The Ishak staging system¹⁰ for fibrosis on liver biopsy was used for confirmation, with stage 4 to 6 defined as advanced fibrosis. A cutoff value of more than 3.25 had a positive predictive value of 65% for advanced fibrosis, and to exclude advanced fibrosis, a cutoff value of less than 1.45 had a negative predictive value of 90%.

The FIB-4 index has since been validated in patients with HCV infection²⁵ and NAFLD.²⁶ In a subsequent study in 142 patients with NAFLD, the FIB-4 index was more accurate in diagnosing advanced fibrosis than the other noninvasive prediction models discussed below.²⁷

NAFLD fibrosis score

The NAFLD fibrosis score, constructed and validated only in patients with biopsy-confirmed NAFLD, incorporates age, body mass index, presence of diabetes or prediabetes, albumin level, platelet count, and AST and ALT levels.

A group of 480 patients was used to construct the score, and 253 patients were used to validate it. Using the high cutoff value of 0.676, the presence of advanced fibrosis was diagnosed with a positive predictive value of 90% in the group used to construct the model (82% in the validation group). Using the low cutoff score of –1.455, advanced fibrosis could be excluded with a negative predictive value of 93% in the construction group and 88% in the validation group.²⁸ A score between the cutoff values merits liver biopsy to determine fibrosis stage. The score is more accurate in patients with diabetes.²⁹ When used by primary care physicians, the NAFLD fibrosis score is more cost-effective than transient elastography and liver biopsy for accurately predicting advanced fibrosis.³⁰

AST-to-platelet ratio index score for HCV, NAFLD

The AST-to-platelet ratio index (APRI) score was developed in 2003 using a cohort of 270 patients with HCV and liver biopsy as the standard. A cutoff value of less than or equal to 0.5 had a negative predictive value of 86% for the absence of significant fibrosis, while a score of more than 1.5 detected the presence of significant fibrosis with a positive predictive value of 88%.³¹ The APRI score was subsequently validated for NAFLD.^27,32

FibroSure uses a patented formula

FibroSure (LabCorp; labcorp.com) uses a patented mathematical formula that takes into account age, sex, and levels of gamma-glutamyl transferase, total bilirubin, haptoglobin, apolipoprotein-A, and alpha-2 macroglobulin to assess fibrosis. Developed in 2001 for use in patients with HCV infection, it was reported to have a positive predictive value of greater than 90% and a negative predictive value of 100% for clinically significant fibrosis, defined as stage 2 to 4 based on the METAVIR staging system in the prediction model.³³ The use of FibroSure in patients with HCV was subsequently validated in various meta-analyses and systematic reviews.^34,35 It is less accurate in patients with normal ALT levels.³⁶

FibroSure also has good accuracy for predicting fibrosis stage in chronic liver disease due to other causes, including NAFLD.³⁷

The prediction models discussed above use routine laboratory tests for chronic liver disease and thus are inexpensive. The high cost of additional testing needed for FibroSure, coupled with the risk of misdiagnosis, makes its cost-effectiveness questionable.³⁸

Conventional ultrasonography (with or without vascular imaging) and computed tomography can detect cirrhosis on the basis of certain imaging characteristics,^39,40 including the nodular contour of the liver, caudate lobe hypertrophy, ascites, reversal of blood flow in the portal vein, and splenomegaly. However, they cannot detect fibrosis in its early stages.

The 3 methods discussed below provide more accurate fibrosis staging by measuring the velocity of shear waves sent across hepatic tissue. Because shear-wave velocity increases with liver stiffness, the fibrosis stage can be estimated from this information.⁴¹

Transient elastography

Transient elastography uses a special ultrasound transducer. It is highly accurate for predicting advanced fibrosis for almost all causes of chronic liver disease, including HCV infection^42,43 and NAFLD.⁴⁴ The cutoff values of wave velocity to estimate fibrosis stage differ by liver disease etiology.

Transient elastography should not be used to evaluate fibrosis in patients with acute hepatitis, which transiently increases liver stiffness, resulting in a falsely high fibrosis stage diagnosis.⁴⁵ It is also not a good method for evaluating fibrosis in patients with biliary obstruction or extrahepatic venous congestion. Because liver stiffness can increase after eating,⁴⁶ the test should be done under fasting conditions.

A significant limitation of transient elastography has been its poor accuracy in patients with obesity.⁴⁷ This has been largely overcome with the use of a more powerful (XL) probe but is still a limitation for those with morbid obesity.⁴⁸ Because many patients with NAFLD are obese, this limitation can be significant.

Transient elastography has gained popularity for evaluating fibrosis in patients with chronic liver disease for multiple reasons: it is cost-effective and results are highly reproducible, with low variation in results among different observers and in individual observers.⁴⁹ Combined with a platelet count, it can also be used to detect the development of clinically significant portal hypertension in patients with cirrhosis, thus determining the need to screen for esophageal varices using endoscopy.⁵⁰ Screening endoscopy can be avoided in patients whose liver stiffness remains below 20 kPa or whose platelet count is above 150 × 10⁹/L.

Acoustic radiation force imaging

Unlike transient elastography, which requires a separate transducer probe to assess shear- wave velocity, acoustic radiation force imaging uses the same transducer for both this function and imaging. Different image modes are available when testing for liver stiffness, so a region of interest that is optimal for avoiding vascular structures or masses can be selected, increasing accuracy.⁵¹

Acoustic radiation force imaging has been tested in different causes of chronic liver disease, including HCV and NAFLD,⁵² with accuracy similar to that of transient elastography.⁵³ For overweight and obese patients, acoustic radiation force imaging is more accurate than transient elastography using the XL probe.⁵⁴ However, this method is still new, and we need more data to support using one method over the other.

Magnetic resonance elastography

Magnetic resonance elastography uses a special transducer placed under the rib cage to transmit shear waves concurrently with magnetic resonance imaging. It has been tested in patients with HCV and NAFLD and has been found to have better diagnostic accuracy than transient elastography and acoustic radiation force imaging.^55,56 Patients must be fasting for better diagnostic accuracy⁵⁷ and must hold their breath while elastography is performed. The need for breath-holding and the high cost limit the use of this method for assessing fibrosis.

BOTTOM LINE FOR ASSESSING FIBROSIS

Staging of liver fibrosis, important for determining prognosis in patients with chronic liver disease and for the need to start screening for complications of cirrhosis, was traditionally done only by liver biopsy. While biopsy is still the gold standard method to stage fibrosis, noninvasive methods have been developed that can also assess disease severity.

This article briefly reviews the epidemiology and physiology of chronic liver disease and the traditional role of liver biopsy. Pros and cons of alternative fibrosis assessment methods are discussed, with a focus on their utility for patients with nonalcoholic fatty liver disease (NAFLD) and hepatitis C virus (HCV) infection.

CHRONIC LIVER DISEASE: A HUGE HEALTH BURDEN

Chronic liver disease is associated with enormous health and financial costs in the United States. Its prevalence is about 15%,¹ and it is the 12th leading cause of death.² Hospital costs are estimated at about $4 billion annually.³

The most common causes of chronic liver disease are NAFLD (which may be present in up to one-third of the US population and is increasing with the epidemic of obesity), its aggressive variant, nonalcoholic steatohepatitis (NASH) (present in about 3% of the population), and HCV infection (1%).^4,5

Since direct-acting antiviral agents were introduced, HCV infection dropped from being the leading cause of liver transplant to third place.⁶ But at the same time, the number of patients on the transplant waiting list who have NASH has risen faster than for any other cause of chronic liver disease.⁷

FIBROSIS: A KEY INDICATOR OF DISEASE SEVERITY

In HCV infection, advanced fibrosis is defined as either stage 4 to 6 using the Ishak system¹⁰ or stage 3 to 4 using the Meta-analysis of Histological Data in Viral Hepatitis (METAVIR) system.¹¹

In NAFLD, advanced fibrosis is defined as stage 3 to 4 using the NASH Clinical Research Network system.¹²

Staging fibrosis is also important so that patients with cirrhosis can be identified early to begin screening for hepatocellular carcinoma and esophageal varices to reduce the risks of illness and death. In addition, insurance companies often require documentation of fibrosis stage before treating HCV with the new direct-acting antiviral agents.

LIVER BIOPSY IS STILL THE GOLD STANDARD

Although invasive, liver biopsy remains the gold standard for determining fibrosis stage. Liver biopsies were performed “blindly” (without imaging) until the 1990s, but imaging-guided biopsy using ultrasonography was then developed, which entailed less pain and lower complication and hospitalization rates. Slightly more hepatic tissue is obtained with guided liver biopsy, but the difference was deemed clinically insignificant.¹³ Concern initially arose about the added cost involved with imaging, but imaging-guided biopsy was actually found to be more cost-effective.¹⁴

In the 2000s, transjugular liver biopsy via the right internal jugular vein became available. This method was originally used primarily in patients with ascites or significant coagulopathy. At first, there were concerns about the adequacy of specimens obtained to make an accurate diagnosis or establish fibrosis stage, but this limitation was overcome with improved techniques.^15,16 Transjugular liver biopsy has the additional advantage of enabling one to measure the hepatic venous pressure gradient, which also has prognostic significance; a gradient greater than 10 mm Hg is associated with worse prognosis.¹⁷

Disadvantages of biopsy: Complications, sampling errors

Liver biopsy has disadvantages. Reported rates of complications necessitating hospitalization using the blind method were as high as 6% in the 1970s,¹⁸ dropping to 3.2% in a 1993 study.¹⁹ Bleeding remains the most worrisome complication. With the transjugular method, major and minor complication rates are less than 1% and 7%, respectively.^15,16 Complication rates with imaging-guided biopsy are also low.

Liver biopsy is also prone to sampling error. The number of portal tracts obtained in the biopsy correlates with the accuracy of fibrosis staging, and smaller samples may lead to underestimating fibrosis stage. In patients with HCV, samples more than 15 mm long led to accurate staging diagnosis in 65% of patients, and those longer than 25 mm conferred 75% accuracy.²⁰ Also, different stages can be diagnosed from samples obtained from separate locations in the liver, although rarely is the difference more than a single stage.²¹

Histologic evaluation of liver biopsies is operator-dependent. Although significant interobserver variation has been reported for degree of inflammation, there tends to be good concordance for fibrosis staging.^22,23

Several scores based on patient characteristics and laboratory values have been developed for assessing liver fibrosis and have been specifically validated for HCV infection, NAFLD, or both. They can serve as inexpensive initial screening tests for the presence or absence of advanced fibrosis.

FIB-4 index for HCV, NAFLD

The FIB-4 index predicts the presence of advanced fibrosis using, as its name indicates, a combination of 4 factors in fibrosis: age, platelet count, and the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), according to the formula:

FIB-4 index = (age × AST [U/L]) /
(platelet count [× 10⁹/L] × √ALT [U/L]).

The index was derived from data from 832 patients co-infected with HCV and human immunodeficiency virus.²⁴ The Ishak staging system¹⁰ for fibrosis on liver biopsy was used for confirmation, with stage 4 to 6 defined as advanced fibrosis. A cutoff value of more than 3.25 had a positive predictive value of 65% for advanced fibrosis, and to exclude advanced fibrosis, a cutoff value of less than 1.45 had a negative predictive value of 90%.

The FIB-4 index has since been validated in patients with HCV infection²⁵ and NAFLD.²⁶ In a subsequent study in 142 patients with NAFLD, the FIB-4 index was more accurate in diagnosing advanced fibrosis than the other noninvasive prediction models discussed below.²⁷

NAFLD fibrosis score

The NAFLD fibrosis score, constructed and validated only in patients with biopsy-confirmed NAFLD, incorporates age, body mass index, presence of diabetes or prediabetes, albumin level, platelet count, and AST and ALT levels.

A group of 480 patients was used to construct the score, and 253 patients were used to validate it. Using the high cutoff value of 0.676, the presence of advanced fibrosis was diagnosed with a positive predictive value of 90% in the group used to construct the model (82% in the validation group). Using the low cutoff score of –1.455, advanced fibrosis could be excluded with a negative predictive value of 93% in the construction group and 88% in the validation group.²⁸ A score between the cutoff values merits liver biopsy to determine fibrosis stage. The score is more accurate in patients with diabetes.²⁹ When used by primary care physicians, the NAFLD fibrosis score is more cost-effective than transient elastography and liver biopsy for accurately predicting advanced fibrosis.³⁰

AST-to-platelet ratio index score for HCV, NAFLD

The AST-to-platelet ratio index (APRI) score was developed in 2003 using a cohort of 270 patients with HCV and liver biopsy as the standard. A cutoff value of less than or equal to 0.5 had a negative predictive value of 86% for the absence of significant fibrosis, while a score of more than 1.5 detected the presence of significant fibrosis with a positive predictive value of 88%.³¹ The APRI score was subsequently validated for NAFLD.^27,32

FibroSure uses a patented formula

FibroSure (LabCorp; labcorp.com) uses a patented mathematical formula that takes into account age, sex, and levels of gamma-glutamyl transferase, total bilirubin, haptoglobin, apolipoprotein-A, and alpha-2 macroglobulin to assess fibrosis. Developed in 2001 for use in patients with HCV infection, it was reported to have a positive predictive value of greater than 90% and a negative predictive value of 100% for clinically significant fibrosis, defined as stage 2 to 4 based on the METAVIR staging system in the prediction model.³³ The use of FibroSure in patients with HCV was subsequently validated in various meta-analyses and systematic reviews.^34,35 It is less accurate in patients with normal ALT levels.³⁶

FibroSure also has good accuracy for predicting fibrosis stage in chronic liver disease due to other causes, including NAFLD.³⁷

The prediction models discussed above use routine laboratory tests for chronic liver disease and thus are inexpensive. The high cost of additional testing needed for FibroSure, coupled with the risk of misdiagnosis, makes its cost-effectiveness questionable.³⁸

Conventional ultrasonography (with or without vascular imaging) and computed tomography can detect cirrhosis on the basis of certain imaging characteristics,^39,40 including the nodular contour of the liver, caudate lobe hypertrophy, ascites, reversal of blood flow in the portal vein, and splenomegaly. However, they cannot detect fibrosis in its early stages.

The 3 methods discussed below provide more accurate fibrosis staging by measuring the velocity of shear waves sent across hepatic tissue. Because shear-wave velocity increases with liver stiffness, the fibrosis stage can be estimated from this information.⁴¹

Transient elastography

Transient elastography uses a special ultrasound transducer. It is highly accurate for predicting advanced fibrosis for almost all causes of chronic liver disease, including HCV infection^42,43 and NAFLD.⁴⁴ The cutoff values of wave velocity to estimate fibrosis stage differ by liver disease etiology.

Transient elastography should not be used to evaluate fibrosis in patients with acute hepatitis, which transiently increases liver stiffness, resulting in a falsely high fibrosis stage diagnosis.⁴⁵ It is also not a good method for evaluating fibrosis in patients with biliary obstruction or extrahepatic venous congestion. Because liver stiffness can increase after eating,⁴⁶ the test should be done under fasting conditions.

A significant limitation of transient elastography has been its poor accuracy in patients with obesity.⁴⁷ This has been largely overcome with the use of a more powerful (XL) probe but is still a limitation for those with morbid obesity.⁴⁸ Because many patients with NAFLD are obese, this limitation can be significant.

Transient elastography has gained popularity for evaluating fibrosis in patients with chronic liver disease for multiple reasons: it is cost-effective and results are highly reproducible, with low variation in results among different observers and in individual observers.⁴⁹ Combined with a platelet count, it can also be used to detect the development of clinically significant portal hypertension in patients with cirrhosis, thus determining the need to screen for esophageal varices using endoscopy.⁵⁰ Screening endoscopy can be avoided in patients whose liver stiffness remains below 20 kPa or whose platelet count is above 150 × 10⁹/L.

Acoustic radiation force imaging

Unlike transient elastography, which requires a separate transducer probe to assess shear- wave velocity, acoustic radiation force imaging uses the same transducer for both this function and imaging. Different image modes are available when testing for liver stiffness, so a region of interest that is optimal for avoiding vascular structures or masses can be selected, increasing accuracy.⁵¹

Acoustic radiation force imaging has been tested in different causes of chronic liver disease, including HCV and NAFLD,⁵² with accuracy similar to that of transient elastography.⁵³ For overweight and obese patients, acoustic radiation force imaging is more accurate than transient elastography using the XL probe.⁵⁴ However, this method is still new, and we need more data to support using one method over the other.

Magnetic resonance elastography

Magnetic resonance elastography uses a special transducer placed under the rib cage to transmit shear waves concurrently with magnetic resonance imaging. It has been tested in patients with HCV and NAFLD and has been found to have better diagnostic accuracy than transient elastography and acoustic radiation force imaging.^55,56 Patients must be fasting for better diagnostic accuracy⁵⁷ and must hold their breath while elastography is performed. The need for breath-holding and the high cost limit the use of this method for assessing fibrosis.

BOTTOM LINE FOR ASSESSING FIBROSIS

Staging of liver fibrosis, important for determining prognosis in patients with chronic liver disease and for the need to start screening for complications of cirrhosis, was traditionally done only by liver biopsy. While biopsy is still the gold standard method to stage fibrosis, noninvasive methods have been developed that can also assess disease severity.

This article briefly reviews the epidemiology and physiology of chronic liver disease and the traditional role of liver biopsy. Pros and cons of alternative fibrosis assessment methods are discussed, with a focus on their utility for patients with nonalcoholic fatty liver disease (NAFLD) and hepatitis C virus (HCV) infection.

CHRONIC LIVER DISEASE: A HUGE HEALTH BURDEN

Chronic liver disease is associated with enormous health and financial costs in the United States. Its prevalence is about 15%,¹ and it is the 12th leading cause of death.² Hospital costs are estimated at about $4 billion annually.³

The most common causes of chronic liver disease are NAFLD (which may be present in up to one-third of the US population and is increasing with the epidemic of obesity), its aggressive variant, nonalcoholic steatohepatitis (NASH) (present in about 3% of the population), and HCV infection (1%).^4,5

Since direct-acting antiviral agents were introduced, HCV infection dropped from being the leading cause of liver transplant to third place.⁶ But at the same time, the number of patients on the transplant waiting list who have NASH has risen faster than for any other cause of chronic liver disease.⁷

FIBROSIS: A KEY INDICATOR OF DISEASE SEVERITY

In HCV infection, advanced fibrosis is defined as either stage 4 to 6 using the Ishak system¹⁰ or stage 3 to 4 using the Meta-analysis of Histological Data in Viral Hepatitis (METAVIR) system.¹¹

In NAFLD, advanced fibrosis is defined as stage 3 to 4 using the NASH Clinical Research Network system.¹²

Staging fibrosis is also important so that patients with cirrhosis can be identified early to begin screening for hepatocellular carcinoma and esophageal varices to reduce the risks of illness and death. In addition, insurance companies often require documentation of fibrosis stage before treating HCV with the new direct-acting antiviral agents.

LIVER BIOPSY IS STILL THE GOLD STANDARD

Although invasive, liver biopsy remains the gold standard for determining fibrosis stage. Liver biopsies were performed “blindly” (without imaging) until the 1990s, but imaging-guided biopsy using ultrasonography was then developed, which entailed less pain and lower complication and hospitalization rates. Slightly more hepatic tissue is obtained with guided liver biopsy, but the difference was deemed clinically insignificant.¹³ Concern initially arose about the added cost involved with imaging, but imaging-guided biopsy was actually found to be more cost-effective.¹⁴

In the 2000s, transjugular liver biopsy via the right internal jugular vein became available. This method was originally used primarily in patients with ascites or significant coagulopathy. At first, there were concerns about the adequacy of specimens obtained to make an accurate diagnosis or establish fibrosis stage, but this limitation was overcome with improved techniques.^15,16 Transjugular liver biopsy has the additional advantage of enabling one to measure the hepatic venous pressure gradient, which also has prognostic significance; a gradient greater than 10 mm Hg is associated with worse prognosis.¹⁷

Disadvantages of biopsy: Complications, sampling errors

Liver biopsy has disadvantages. Reported rates of complications necessitating hospitalization using the blind method were as high as 6% in the 1970s,¹⁸ dropping to 3.2% in a 1993 study.¹⁹ Bleeding remains the most worrisome complication. With the transjugular method, major and minor complication rates are less than 1% and 7%, respectively.^15,16 Complication rates with imaging-guided biopsy are also low.

Liver biopsy is also prone to sampling error. The number of portal tracts obtained in the biopsy correlates with the accuracy of fibrosis staging, and smaller samples may lead to underestimating fibrosis stage. In patients with HCV, samples more than 15 mm long led to accurate staging diagnosis in 65% of patients, and those longer than 25 mm conferred 75% accuracy.²⁰ Also, different stages can be diagnosed from samples obtained from separate locations in the liver, although rarely is the difference more than a single stage.²¹

Histologic evaluation of liver biopsies is operator-dependent. Although significant interobserver variation has been reported for degree of inflammation, there tends to be good concordance for fibrosis staging.^22,23

Several scores based on patient characteristics and laboratory values have been developed for assessing liver fibrosis and have been specifically validated for HCV infection, NAFLD, or both. They can serve as inexpensive initial screening tests for the presence or absence of advanced fibrosis.

FIB-4 index for HCV, NAFLD

The FIB-4 index predicts the presence of advanced fibrosis using, as its name indicates, a combination of 4 factors in fibrosis: age, platelet count, and the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), according to the formula:

FIB-4 index = (age × AST [U/L]) /
(platelet count [× 10⁹/L] × √ALT [U/L]).

The index was derived from data from 832 patients co-infected with HCV and human immunodeficiency virus.²⁴ The Ishak staging system¹⁰ for fibrosis on liver biopsy was used for confirmation, with stage 4 to 6 defined as advanced fibrosis. A cutoff value of more than 3.25 had a positive predictive value of 65% for advanced fibrosis, and to exclude advanced fibrosis, a cutoff value of less than 1.45 had a negative predictive value of 90%.

The FIB-4 index has since been validated in patients with HCV infection²⁵ and NAFLD.²⁶ In a subsequent study in 142 patients with NAFLD, the FIB-4 index was more accurate in diagnosing advanced fibrosis than the other noninvasive prediction models discussed below.²⁷

NAFLD fibrosis score

The NAFLD fibrosis score, constructed and validated only in patients with biopsy-confirmed NAFLD, incorporates age, body mass index, presence of diabetes or prediabetes, albumin level, platelet count, and AST and ALT levels.

A group of 480 patients was used to construct the score, and 253 patients were used to validate it. Using the high cutoff value of 0.676, the presence of advanced fibrosis was diagnosed with a positive predictive value of 90% in the group used to construct the model (82% in the validation group). Using the low cutoff score of –1.455, advanced fibrosis could be excluded with a negative predictive value of 93% in the construction group and 88% in the validation group.²⁸ A score between the cutoff values merits liver biopsy to determine fibrosis stage. The score is more accurate in patients with diabetes.²⁹ When used by primary care physicians, the NAFLD fibrosis score is more cost-effective than transient elastography and liver biopsy for accurately predicting advanced fibrosis.³⁰

AST-to-platelet ratio index score for HCV, NAFLD

The AST-to-platelet ratio index (APRI) score was developed in 2003 using a cohort of 270 patients with HCV and liver biopsy as the standard. A cutoff value of less than or equal to 0.5 had a negative predictive value of 86% for the absence of significant fibrosis, while a score of more than 1.5 detected the presence of significant fibrosis with a positive predictive value of 88%.³¹ The APRI score was subsequently validated for NAFLD.^27,32

FibroSure uses a patented formula

FibroSure (LabCorp; labcorp.com) uses a patented mathematical formula that takes into account age, sex, and levels of gamma-glutamyl transferase, total bilirubin, haptoglobin, apolipoprotein-A, and alpha-2 macroglobulin to assess fibrosis. Developed in 2001 for use in patients with HCV infection, it was reported to have a positive predictive value of greater than 90% and a negative predictive value of 100% for clinically significant fibrosis, defined as stage 2 to 4 based on the METAVIR staging system in the prediction model.³³ The use of FibroSure in patients with HCV was subsequently validated in various meta-analyses and systematic reviews.^34,35 It is less accurate in patients with normal ALT levels.³⁶

FibroSure also has good accuracy for predicting fibrosis stage in chronic liver disease due to other causes, including NAFLD.³⁷

The prediction models discussed above use routine laboratory tests for chronic liver disease and thus are inexpensive. The high cost of additional testing needed for FibroSure, coupled with the risk of misdiagnosis, makes its cost-effectiveness questionable.³⁸

Conventional ultrasonography (with or without vascular imaging) and computed tomography can detect cirrhosis on the basis of certain imaging characteristics,^39,40 including the nodular contour of the liver, caudate lobe hypertrophy, ascites, reversal of blood flow in the portal vein, and splenomegaly. However, they cannot detect fibrosis in its early stages.

The 3 methods discussed below provide more accurate fibrosis staging by measuring the velocity of shear waves sent across hepatic tissue. Because shear-wave velocity increases with liver stiffness, the fibrosis stage can be estimated from this information.⁴¹

Transient elastography

Transient elastography uses a special ultrasound transducer. It is highly accurate for predicting advanced fibrosis for almost all causes of chronic liver disease, including HCV infection^42,43 and NAFLD.⁴⁴ The cutoff values of wave velocity to estimate fibrosis stage differ by liver disease etiology.

Transient elastography should not be used to evaluate fibrosis in patients with acute hepatitis, which transiently increases liver stiffness, resulting in a falsely high fibrosis stage diagnosis.⁴⁵ It is also not a good method for evaluating fibrosis in patients with biliary obstruction or extrahepatic venous congestion. Because liver stiffness can increase after eating,⁴⁶ the test should be done under fasting conditions.

A significant limitation of transient elastography has been its poor accuracy in patients with obesity.⁴⁷ This has been largely overcome with the use of a more powerful (XL) probe but is still a limitation for those with morbid obesity.⁴⁸ Because many patients with NAFLD are obese, this limitation can be significant.

Transient elastography has gained popularity for evaluating fibrosis in patients with chronic liver disease for multiple reasons: it is cost-effective and results are highly reproducible, with low variation in results among different observers and in individual observers.⁴⁹ Combined with a platelet count, it can also be used to detect the development of clinically significant portal hypertension in patients with cirrhosis, thus determining the need to screen for esophageal varices using endoscopy.⁵⁰ Screening endoscopy can be avoided in patients whose liver stiffness remains below 20 kPa or whose platelet count is above 150 × 10⁹/L.

Acoustic radiation force imaging

Unlike transient elastography, which requires a separate transducer probe to assess shear- wave velocity, acoustic radiation force imaging uses the same transducer for both this function and imaging. Different image modes are available when testing for liver stiffness, so a region of interest that is optimal for avoiding vascular structures or masses can be selected, increasing accuracy.⁵¹

Acoustic radiation force imaging has been tested in different causes of chronic liver disease, including HCV and NAFLD,⁵² with accuracy similar to that of transient elastography.⁵³ For overweight and obese patients, acoustic radiation force imaging is more accurate than transient elastography using the XL probe.⁵⁴ However, this method is still new, and we need more data to support using one method over the other.

Magnetic resonance elastography

Magnetic resonance elastography uses a special transducer placed under the rib cage to transmit shear waves concurrently with magnetic resonance imaging. It has been tested in patients with HCV and NAFLD and has been found to have better diagnostic accuracy than transient elastography and acoustic radiation force imaging.^55,56 Patients must be fasting for better diagnostic accuracy⁵⁷ and must hold their breath while elastography is performed. The need for breath-holding and the high cost limit the use of this method for assessing fibrosis.

BOTTOM LINE FOR ASSESSING FIBROSIS

A 62-year-old woman presented to our emergency department with fever, chills, hoarseness, pain on swallowing, and a painful neck. Her symptoms had begun 1 day earlier. Because acetaminophen brought no improvement, she went to an urgent care facility, where a nasal swab polymerase chain reaction test was positive for influenza A, and a throat swab rapid test was positive for group A streptococci. She was then referred to our emergency department.

She reported no pre-existing conditions predisposing her to infection. Her temperature was 99.9°F (37.7°C), pulse 112 beats per minute, and respiratory rate 24 breaths per minute. The physical examination was unremarkable except for bilateral anterior cervical adenopathy and bilateral anterior neck tenderness. Her pharynx was not injected, and no exudate, palatal edema, or petechiae were noted.

Results of initial laboratory testing were as follows:

• White blood cell count 20.5 × 10⁹/L (reference range 3.9–11)
• Neutrophils 76% (42%–75%)
• Bands 15% (0%–5%)
• Lymphocytes 3% (21%–51%)
• Erythrocyte sedimentation rate 75 mm/h (< 20 mm/h)
• C-reactive protein 247.14 mg/L (≤ 3 mg/L)
• Serum aminotransferase levels were normal.
• Polymerase chain reaction testing of a nasal swab was negative for viral infection.

Throat swabs and blood samples were sent for culture.

She was started on ceftriaxone 1 g intravenously every 24 hours, with close observation in the medical intensive care unit, where she was admitted because of epiglottitis. On hospital day 3, the throat culture was reported as negative, but the blood culture was reported as positive for Haemophilus influenzae. Thus, the clinical diagnosis was acute epiglottitis due to H influenzae, not group A streptococci.

The patient completed 10 days of ceftriaxone therapy; her recovery was uneventful, and she was discharged on hospital day 10.

INFLUENZA: CHALLENGES TO PROMPT, ACCURATE DIAGNOSIS

During influenza season, emergency departments are inundated with adults with influenza A and other viral respiratory infections. This makes prompt, accurate diagnosis a challenge,¹ given the broad differential diagnosis.^2,3 Adults with influenza and its complications as well as unrelated conditions can present a special challenge.⁴

Our patient presented with acute-onset influenza A and was then found to have acute epiglottitis, an unexpected complication of influenza A.⁵ A positive rapid test for group A streptococci done at an urgent care facility led emergency department physicians to assume that the acute epiglottitis was due to group A streptococci. Unless correlated with clinical findings, results of rapid diagnostic tests may mislead the unwary practitioner. Accurate diagnosis should be based mainly on the history and physical findings. Results of rapid diagnostic tests can be helpful if interpreted in the clinical context.^6–8

The rapid test for streptococci is appropriate for the diagnosis of pharyngitis due to group A streptococci in people under age 30 with acute-onset sore throat, fever, and bilateral acute cervical adenopathy, without fatigue or myalgias. However, the rapid test does not differentiate colonization from infection. Group A streptococci are common colonizers with viral pharyngitis. In 30% of cases of Epstein-Barr virus pharyngitis, there is colonization with group A streptococci. A positive rapid test in such cases can result in the wrong diagnosis, ie, pharyngitis due to group A streptococci rather than Epstein-Barr virus.

A 62-year-old woman presented to our emergency department with fever, chills, hoarseness, pain on swallowing, and a painful neck. Her symptoms had begun 1 day earlier. Because acetaminophen brought no improvement, she went to an urgent care facility, where a nasal swab polymerase chain reaction test was positive for influenza A, and a throat swab rapid test was positive for group A streptococci. She was then referred to our emergency department.

She reported no pre-existing conditions predisposing her to infection. Her temperature was 99.9°F (37.7°C), pulse 112 beats per minute, and respiratory rate 24 breaths per minute. The physical examination was unremarkable except for bilateral anterior cervical adenopathy and bilateral anterior neck tenderness. Her pharynx was not injected, and no exudate, palatal edema, or petechiae were noted.

Results of initial laboratory testing were as follows:

• White blood cell count 20.5 × 10⁹/L (reference range 3.9–11)
• Neutrophils 76% (42%–75%)
• Bands 15% (0%–5%)
• Lymphocytes 3% (21%–51%)
• Erythrocyte sedimentation rate 75 mm/h (< 20 mm/h)
• C-reactive protein 247.14 mg/L (≤ 3 mg/L)
• Serum aminotransferase levels were normal.
• Polymerase chain reaction testing of a nasal swab was negative for viral infection.

Throat swabs and blood samples were sent for culture.

She was started on ceftriaxone 1 g intravenously every 24 hours, with close observation in the medical intensive care unit, where she was admitted because of epiglottitis. On hospital day 3, the throat culture was reported as negative, but the blood culture was reported as positive for Haemophilus influenzae. Thus, the clinical diagnosis was acute epiglottitis due to H influenzae, not group A streptococci.

The patient completed 10 days of ceftriaxone therapy; her recovery was uneventful, and she was discharged on hospital day 10.

INFLUENZA: CHALLENGES TO PROMPT, ACCURATE DIAGNOSIS

During influenza season, emergency departments are inundated with adults with influenza A and other viral respiratory infections. This makes prompt, accurate diagnosis a challenge,¹ given the broad differential diagnosis.^2,3 Adults with influenza and its complications as well as unrelated conditions can present a special challenge.⁴

Our patient presented with acute-onset influenza A and was then found to have acute epiglottitis, an unexpected complication of influenza A.⁵ A positive rapid test for group A streptococci done at an urgent care facility led emergency department physicians to assume that the acute epiglottitis was due to group A streptococci. Unless correlated with clinical findings, results of rapid diagnostic tests may mislead the unwary practitioner. Accurate diagnosis should be based mainly on the history and physical findings. Results of rapid diagnostic tests can be helpful if interpreted in the clinical context.^6–8

The rapid test for streptococci is appropriate for the diagnosis of pharyngitis due to group A streptococci in people under age 30 with acute-onset sore throat, fever, and bilateral acute cervical adenopathy, without fatigue or myalgias. However, the rapid test does not differentiate colonization from infection. Group A streptococci are common colonizers with viral pharyngitis. In 30% of cases of Epstein-Barr virus pharyngitis, there is colonization with group A streptococci. A positive rapid test in such cases can result in the wrong diagnosis, ie, pharyngitis due to group A streptococci rather than Epstein-Barr virus.

A 62-year-old woman presented to our emergency department with fever, chills, hoarseness, pain on swallowing, and a painful neck. Her symptoms had begun 1 day earlier. Because acetaminophen brought no improvement, she went to an urgent care facility, where a nasal swab polymerase chain reaction test was positive for influenza A, and a throat swab rapid test was positive for group A streptococci. She was then referred to our emergency department.

She reported no pre-existing conditions predisposing her to infection. Her temperature was 99.9°F (37.7°C), pulse 112 beats per minute, and respiratory rate 24 breaths per minute. The physical examination was unremarkable except for bilateral anterior cervical adenopathy and bilateral anterior neck tenderness. Her pharynx was not injected, and no exudate, palatal edema, or petechiae were noted.

Results of initial laboratory testing were as follows:

• White blood cell count 20.5 × 10⁹/L (reference range 3.9–11)
• Neutrophils 76% (42%–75%)
• Bands 15% (0%–5%)
• Lymphocytes 3% (21%–51%)
• Erythrocyte sedimentation rate 75 mm/h (< 20 mm/h)
• C-reactive protein 247.14 mg/L (≤ 3 mg/L)
• Serum aminotransferase levels were normal.
• Polymerase chain reaction testing of a nasal swab was negative for viral infection.

Throat swabs and blood samples were sent for culture.

She was started on ceftriaxone 1 g intravenously every 24 hours, with close observation in the medical intensive care unit, where she was admitted because of epiglottitis. On hospital day 3, the throat culture was reported as negative, but the blood culture was reported as positive for Haemophilus influenzae. Thus, the clinical diagnosis was acute epiglottitis due to H influenzae, not group A streptococci.

The patient completed 10 days of ceftriaxone therapy; her recovery was uneventful, and she was discharged on hospital day 10.

INFLUENZA: CHALLENGES TO PROMPT, ACCURATE DIAGNOSIS

During influenza season, emergency departments are inundated with adults with influenza A and other viral respiratory infections. This makes prompt, accurate diagnosis a challenge,¹ given the broad differential diagnosis.^2,3 Adults with influenza and its complications as well as unrelated conditions can present a special challenge.⁴

Our patient presented with acute-onset influenza A and was then found to have acute epiglottitis, an unexpected complication of influenza A.⁵ A positive rapid test for group A streptococci done at an urgent care facility led emergency department physicians to assume that the acute epiglottitis was due to group A streptococci. Unless correlated with clinical findings, results of rapid diagnostic tests may mislead the unwary practitioner. Accurate diagnosis should be based mainly on the history and physical findings. Results of rapid diagnostic tests can be helpful if interpreted in the clinical context.^6–8

The rapid test for streptococci is appropriate for the diagnosis of pharyngitis due to group A streptococci in people under age 30 with acute-onset sore throat, fever, and bilateral acute cervical adenopathy, without fatigue or myalgias. However, the rapid test does not differentiate colonization from infection. Group A streptococci are common colonizers with viral pharyngitis. In 30% of cases of Epstein-Barr virus pharyngitis, there is colonization with group A streptococci. A positive rapid test in such cases can result in the wrong diagnosis, ie, pharyngitis due to group A streptococci rather than Epstein-Barr virus.

DIAGNOSIS, TREATMENT, CONTROL

The differential diagnosis of Norwegian scabies includes psoriasis, eczema, contact dermatitis, insect bites, seborrheic dermatitis, lichen planus, systemic infection, palmoplantar keratoderma, and cutaneous lymphoma.²

Treatment involves eradicating the infestation with a topical ointment consisting of permethrin, crotamiton, lindane, benzyl benzoate, and sulfur, applied directly to the skin. However, topical treatments often cannot penetrate the crusted and thickened skin, leading to treatment failure. A dose of oral ivermectin 200 µg/kg on days 1, 2, and 8 is a safe, effective, first-line treatment for Norwegian scabies, rapidly reducing scabies symptoms.³ Adverse effects of oral ivermectin are rare and usually minor.

Norwegian scabies is extremely contagious, spread by close physical contact and sharing of contaminated items such as clothing, bedding, towels, and furniture. Scabies mites can survive off the skin for 48 to 72 hours at room temperature.⁴ Potentially contaminated items should be decontaminated by washing in hot water and drying in a drying machine or by dry cleaning. Body contact with other contaminated items should be avoided for at least 72 hours.

Outbreaks can spread among patients, visitors, and medical staff in institutions such as nursing homes, day care centers, long-term-care facilities, and hospitals.⁵ Early identification facilitates appropriate management and treatment, thereby preventing infection and community-wide scabies outbreaks.          

Acknowledgment: The authors would like to sincerely thank Paul Williams for his editing of the article.

DIAGNOSIS, TREATMENT, CONTROL

The differential diagnosis of Norwegian scabies includes psoriasis, eczema, contact dermatitis, insect bites, seborrheic dermatitis, lichen planus, systemic infection, palmoplantar keratoderma, and cutaneous lymphoma.²

Treatment involves eradicating the infestation with a topical ointment consisting of permethrin, crotamiton, lindane, benzyl benzoate, and sulfur, applied directly to the skin. However, topical treatments often cannot penetrate the crusted and thickened skin, leading to treatment failure. A dose of oral ivermectin 200 µg/kg on days 1, 2, and 8 is a safe, effective, first-line treatment for Norwegian scabies, rapidly reducing scabies symptoms.³ Adverse effects of oral ivermectin are rare and usually minor.

Norwegian scabies is extremely contagious, spread by close physical contact and sharing of contaminated items such as clothing, bedding, towels, and furniture. Scabies mites can survive off the skin for 48 to 72 hours at room temperature.⁴ Potentially contaminated items should be decontaminated by washing in hot water and drying in a drying machine or by dry cleaning. Body contact with other contaminated items should be avoided for at least 72 hours.

Outbreaks can spread among patients, visitors, and medical staff in institutions such as nursing homes, day care centers, long-term-care facilities, and hospitals.⁵ Early identification facilitates appropriate management and treatment, thereby preventing infection and community-wide scabies outbreaks.          

Acknowledgment: The authors would like to sincerely thank Paul Williams for his editing of the article.

DIAGNOSIS, TREATMENT, CONTROL

The differential diagnosis of Norwegian scabies includes psoriasis, eczema, contact dermatitis, insect bites, seborrheic dermatitis, lichen planus, systemic infection, palmoplantar keratoderma, and cutaneous lymphoma.²

Treatment involves eradicating the infestation with a topical ointment consisting of permethrin, crotamiton, lindane, benzyl benzoate, and sulfur, applied directly to the skin. However, topical treatments often cannot penetrate the crusted and thickened skin, leading to treatment failure. A dose of oral ivermectin 200 µg/kg on days 1, 2, and 8 is a safe, effective, first-line treatment for Norwegian scabies, rapidly reducing scabies symptoms.³ Adverse effects of oral ivermectin are rare and usually minor.

Norwegian scabies is extremely contagious, spread by close physical contact and sharing of contaminated items such as clothing, bedding, towels, and furniture. Scabies mites can survive off the skin for 48 to 72 hours at room temperature.⁴ Potentially contaminated items should be decontaminated by washing in hot water and drying in a drying machine or by dry cleaning. Body contact with other contaminated items should be avoided for at least 72 hours.

Outbreaks can spread among patients, visitors, and medical staff in institutions such as nursing homes, day care centers, long-term-care facilities, and hospitals.⁵ Early identification facilitates appropriate management and treatment, thereby preventing infection and community-wide scabies outbreaks.          

Acknowledgment: The authors would like to sincerely thank Paul Williams for his editing of the article.

Delaying or withholding antibiotics in elderly patients with a urinary tract infection (UTI) increases the risk of sepsis and death, results of a large, population-based study suggest.

andresr/Getty Images

The risk of bloodstream infection was more than seven times greater in patients who did not receive antibiotics immediately after seeing a general practitioner for a UTI versus those who did, according to results of the study based on primary care records and other data for nearly 160,000 U.K. patients aged 65 years or older. Death rates and hospital admissions were significantly higher for these patients, according to the study published in The BMJ by Myriam Gharbi, PharmD, Phd, Imperial College London, and her colleagues.

The publication of these findings coincides with an increase in Escherichia coli bloodstream infections in England.

“Our study suggests the early initiation of antibiotics for UTI in older high risk adult populations (especially men aged [older than] 85 years) should be recommended to prevent serious complications,” Dr. Gharbi and her coauthors said in their report.

The population-based cohort study comprised 157,264 adult primary care patients at least 65 years of age who had one or more suspected or confirmed lower UTIs from November 2007 to May 2015. The researchers found that health care providers had diagnosed a total of 312,896 UTI episodes in these patients during the period they studied. In 7.2% (22,534) of the UTI episodes, the researchers were unable to find records of the patients having been prescribed antibiotics by a general practitioner within 7 days of the UTI diagnosis. These 22,534 episodes included those that occurred in patients who had a complication before an antibiotic was prescribed. An additional 6.2% (19,292) of the episodes occurred in patients who were prescribed antibiotics, but not during their first UTI-related visit to a general practitioner or on the same day of such a visit. The researchers classified this group of patients as having been prescribed antibiotics on a deferred or delayed basis, as they were not prescribed such drugs within 7 days of their visit.

Overall, there were 1,539 cases (0.5% of the total number of UTIs) of bloodstream infection within 60 days of the initial urinary tract infection diagnosis, the researchers reported.

The bloodstream infection rate was 2.9% for patients who were not prescribed antibiotics ever or prior to an infection occurring, 2.2% in those who were prescribed antibiotics on a deferred basis, and 0.2% in those who were prescribed antibiotics immediately, meaning during their first visit to a general practitioner for a UTI or on the same day of such a visit (P less than .001). After adjustment for potential confounding variables such as age, sex, and region, the patients classified as having not been prescribed antibiotics or having been prescribed antibiotics on a deferred basis were significantly more likely to have a bloodstream infection within 60 days of their visit to a health care provider, compared with those who received antibiotics immediately, with odds ratios of 8.08 (95% confidence interval, 7.12-9.16) and 7.12 (95% CI, 6.22-8.14), respectively.

Hospital admissions after a UTI episode were nearly twice as high in the no- or deferred-antibiotics groups (27.0% and 26.8%, respectively), compared with the group that received antibiotics right away (14.8%), the investigators reported. The lengths of hospital stays were 12.1 days for the group classified as having not been prescribed antibiotics, 7.7 days for the group subject to delayed antibiotic prescribing, and 6.3 days for the group who received antibiotics immediately.

Deaths within 60 days of experiencing a urinary tract infection occurred in 5.4% of patients in the no-antibiotics group, 2.8% of the deferred-antibiotics group, and 1.6% of the immediate-antibiotics group. After adjustment for covariates, a regression analysis showed the risks for all-cause mortality were 1.16 and 2.18 times higher in the deferred-antibiotics group and the no-antibiotics group, respectively, according to the paper.

In the immediate-antibiotics group, those patients who received nitrofurantoin had a “small but significant increase” in 60-day survival versus those who received trimethoprim, the investigators noted in the discussion section of their report.

“This increase could reflect either higher levels of resistance to trimethoprim or a healthier population treated with nitrofurantoin, the latest being not recommended for patients with poor kidney function,” the researchers wrote.

This study was supported by the National Institute for Health Research and other U.K. sources. One study coauthor reported working as an epidemiologist with GSK in areas not related to the study.

SOURCE: Gharbi M et al. BMJ. 2019 Feb 27. doi: 10.1136/bmj.l525.

Delaying or withholding antibiotics in elderly patients with a urinary tract infection (UTI) increases the risk of sepsis and death, results of a large, population-based study suggest.

andresr/Getty Images

The risk of bloodstream infection was more than seven times greater in patients who did not receive antibiotics immediately after seeing a general practitioner for a UTI versus those who did, according to results of the study based on primary care records and other data for nearly 160,000 U.K. patients aged 65 years or older. Death rates and hospital admissions were significantly higher for these patients, according to the study published in The BMJ by Myriam Gharbi, PharmD, Phd, Imperial College London, and her colleagues.

The publication of these findings coincides with an increase in Escherichia coli bloodstream infections in England.

“Our study suggests the early initiation of antibiotics for UTI in older high risk adult populations (especially men aged [older than] 85 years) should be recommended to prevent serious complications,” Dr. Gharbi and her coauthors said in their report.

The population-based cohort study comprised 157,264 adult primary care patients at least 65 years of age who had one or more suspected or confirmed lower UTIs from November 2007 to May 2015. The researchers found that health care providers had diagnosed a total of 312,896 UTI episodes in these patients during the period they studied. In 7.2% (22,534) of the UTI episodes, the researchers were unable to find records of the patients having been prescribed antibiotics by a general practitioner within 7 days of the UTI diagnosis. These 22,534 episodes included those that occurred in patients who had a complication before an antibiotic was prescribed. An additional 6.2% (19,292) of the episodes occurred in patients who were prescribed antibiotics, but not during their first UTI-related visit to a general practitioner or on the same day of such a visit. The researchers classified this group of patients as having been prescribed antibiotics on a deferred or delayed basis, as they were not prescribed such drugs within 7 days of their visit.

Overall, there were 1,539 cases (0.5% of the total number of UTIs) of bloodstream infection within 60 days of the initial urinary tract infection diagnosis, the researchers reported.

The bloodstream infection rate was 2.9% for patients who were not prescribed antibiotics ever or prior to an infection occurring, 2.2% in those who were prescribed antibiotics on a deferred basis, and 0.2% in those who were prescribed antibiotics immediately, meaning during their first visit to a general practitioner for a UTI or on the same day of such a visit (P less than .001). After adjustment for potential confounding variables such as age, sex, and region, the patients classified as having not been prescribed antibiotics or having been prescribed antibiotics on a deferred basis were significantly more likely to have a bloodstream infection within 60 days of their visit to a health care provider, compared with those who received antibiotics immediately, with odds ratios of 8.08 (95% confidence interval, 7.12-9.16) and 7.12 (95% CI, 6.22-8.14), respectively.

Hospital admissions after a UTI episode were nearly twice as high in the no- or deferred-antibiotics groups (27.0% and 26.8%, respectively), compared with the group that received antibiotics right away (14.8%), the investigators reported. The lengths of hospital stays were 12.1 days for the group classified as having not been prescribed antibiotics, 7.7 days for the group subject to delayed antibiotic prescribing, and 6.3 days for the group who received antibiotics immediately.

Deaths within 60 days of experiencing a urinary tract infection occurred in 5.4% of patients in the no-antibiotics group, 2.8% of the deferred-antibiotics group, and 1.6% of the immediate-antibiotics group. After adjustment for covariates, a regression analysis showed the risks for all-cause mortality were 1.16 and 2.18 times higher in the deferred-antibiotics group and the no-antibiotics group, respectively, according to the paper.

In the immediate-antibiotics group, those patients who received nitrofurantoin had a “small but significant increase” in 60-day survival versus those who received trimethoprim, the investigators noted in the discussion section of their report.

“This increase could reflect either higher levels of resistance to trimethoprim or a healthier population treated with nitrofurantoin, the latest being not recommended for patients with poor kidney function,” the researchers wrote.

This study was supported by the National Institute for Health Research and other U.K. sources. One study coauthor reported working as an epidemiologist with GSK in areas not related to the study.

SOURCE: Gharbi M et al. BMJ. 2019 Feb 27. doi: 10.1136/bmj.l525.

Delaying or withholding antibiotics in elderly patients with a urinary tract infection (UTI) increases the risk of sepsis and death, results of a large, population-based study suggest.

andresr/Getty Images

The risk of bloodstream infection was more than seven times greater in patients who did not receive antibiotics immediately after seeing a general practitioner for a UTI versus those who did, according to results of the study based on primary care records and other data for nearly 160,000 U.K. patients aged 65 years or older. Death rates and hospital admissions were significantly higher for these patients, according to the study published in The BMJ by Myriam Gharbi, PharmD, Phd, Imperial College London, and her colleagues.

The publication of these findings coincides with an increase in Escherichia coli bloodstream infections in England.

“Our study suggests the early initiation of antibiotics for UTI in older high risk adult populations (especially men aged [older than] 85 years) should be recommended to prevent serious complications,” Dr. Gharbi and her coauthors said in their report.

The population-based cohort study comprised 157,264 adult primary care patients at least 65 years of age who had one or more suspected or confirmed lower UTIs from November 2007 to May 2015. The researchers found that health care providers had diagnosed a total of 312,896 UTI episodes in these patients during the period they studied. In 7.2% (22,534) of the UTI episodes, the researchers were unable to find records of the patients having been prescribed antibiotics by a general practitioner within 7 days of the UTI diagnosis. These 22,534 episodes included those that occurred in patients who had a complication before an antibiotic was prescribed. An additional 6.2% (19,292) of the episodes occurred in patients who were prescribed antibiotics, but not during their first UTI-related visit to a general practitioner or on the same day of such a visit. The researchers classified this group of patients as having been prescribed antibiotics on a deferred or delayed basis, as they were not prescribed such drugs within 7 days of their visit.

Overall, there were 1,539 cases (0.5% of the total number of UTIs) of bloodstream infection within 60 days of the initial urinary tract infection diagnosis, the researchers reported.

The bloodstream infection rate was 2.9% for patients who were not prescribed antibiotics ever or prior to an infection occurring, 2.2% in those who were prescribed antibiotics on a deferred basis, and 0.2% in those who were prescribed antibiotics immediately, meaning during their first visit to a general practitioner for a UTI or on the same day of such a visit (P less than .001). After adjustment for potential confounding variables such as age, sex, and region, the patients classified as having not been prescribed antibiotics or having been prescribed antibiotics on a deferred basis were significantly more likely to have a bloodstream infection within 60 days of their visit to a health care provider, compared with those who received antibiotics immediately, with odds ratios of 8.08 (95% confidence interval, 7.12-9.16) and 7.12 (95% CI, 6.22-8.14), respectively.

Hospital admissions after a UTI episode were nearly twice as high in the no- or deferred-antibiotics groups (27.0% and 26.8%, respectively), compared with the group that received antibiotics right away (14.8%), the investigators reported. The lengths of hospital stays were 12.1 days for the group classified as having not been prescribed antibiotics, 7.7 days for the group subject to delayed antibiotic prescribing, and 6.3 days for the group who received antibiotics immediately.

Deaths within 60 days of experiencing a urinary tract infection occurred in 5.4% of patients in the no-antibiotics group, 2.8% of the deferred-antibiotics group, and 1.6% of the immediate-antibiotics group. After adjustment for covariates, a regression analysis showed the risks for all-cause mortality were 1.16 and 2.18 times higher in the deferred-antibiotics group and the no-antibiotics group, respectively, according to the paper.

In the immediate-antibiotics group, those patients who received nitrofurantoin had a “small but significant increase” in 60-day survival versus those who received trimethoprim, the investigators noted in the discussion section of their report.

“This increase could reflect either higher levels of resistance to trimethoprim or a healthier population treated with nitrofurantoin, the latest being not recommended for patients with poor kidney function,” the researchers wrote.

This study was supported by the National Institute for Health Research and other U.K. sources. One study coauthor reported working as an epidemiologist with GSK in areas not related to the study.

SOURCE: Gharbi M et al. BMJ. 2019 Feb 27. doi: 10.1136/bmj.l525.

A booster dose for pre-exposure prophylaxis with an anthrax vaccine may be given at 3 years after an initial series for individuals not currently at risk who wish to maintain protection, according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

Carolina K. Smith, MD/Fotolia.com

In a unanimous 15-0 vote at the February meeting, ACIP committee members agreed on the recommendation after adjusting the wording to reflect a permissive, rather than mandated, guidance.

William Bower, MD, of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), presented data on Anthrax Vaccine Adsorbed (AVA) to support its protective effects over a longer booster dose interval.

The recommendations apply to persons aged 18 years or older who are not currently at high risk of exposure to Bacillus anthracis, but who might need to deploy to a high-risk area quickly, such as military personnel, Dr. Bower said.

In addition, data suggest that adults who have started, but not completed the pre-exposure priming series, can transition to the postexposure schedule prior to entering a high-risk area, he noted.

The previous pre-exposure anthrax vaccination schedule was a three-dose priming series at 0, 1, and 3 months, followed by a booster at 12 months and 18 months, then annually.

Data from several human immunogenicity studies showed a robust immune response following a delayed anthrax booster dose, with “sustained immunological memory to at least month 42,” and suggested that even longer intervals between boosters may be possible, Dr. Bower said.

A dosing schedule of intramuscular injections at 0 and at 1 month and 6 months, with a booster at 42 months yielded survival estimates of approximately 84%-93%.

Dr. Bower noted that a new vaccine, AV7909, has demonstrated safety and effectiveness similar to AVA and could be used for pre-exposure prophylaxis if AVA is not available. AVA remains the preferred option, but ultimately will be replaced by AV7909, when the current AVA stockpile is exhausted.

Additional safety data on AV7909 will be reviewed by ACIP as they become available, and future guidance from the CDC will include statements on dosing for special populations including pregnant and breastfeeding women, said Dr. Bower.

“We anticipate that this [anthrax vaccine] work group will reconvene in 2021 to review data from pending studies” of AV7909, he said.

The ACIP members had no financial conflicts to disclose.

A booster dose for pre-exposure prophylaxis with an anthrax vaccine may be given at 3 years after an initial series for individuals not currently at risk who wish to maintain protection, according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

Carolina K. Smith, MD/Fotolia.com

In a unanimous 15-0 vote at the February meeting, ACIP committee members agreed on the recommendation after adjusting the wording to reflect a permissive, rather than mandated, guidance.

William Bower, MD, of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), presented data on Anthrax Vaccine Adsorbed (AVA) to support its protective effects over a longer booster dose interval.

The recommendations apply to persons aged 18 years or older who are not currently at high risk of exposure to Bacillus anthracis, but who might need to deploy to a high-risk area quickly, such as military personnel, Dr. Bower said.

In addition, data suggest that adults who have started, but not completed the pre-exposure priming series, can transition to the postexposure schedule prior to entering a high-risk area, he noted.

The previous pre-exposure anthrax vaccination schedule was a three-dose priming series at 0, 1, and 3 months, followed by a booster at 12 months and 18 months, then annually.

Data from several human immunogenicity studies showed a robust immune response following a delayed anthrax booster dose, with “sustained immunological memory to at least month 42,” and suggested that even longer intervals between boosters may be possible, Dr. Bower said.

A dosing schedule of intramuscular injections at 0 and at 1 month and 6 months, with a booster at 42 months yielded survival estimates of approximately 84%-93%.

Dr. Bower noted that a new vaccine, AV7909, has demonstrated safety and effectiveness similar to AVA and could be used for pre-exposure prophylaxis if AVA is not available. AVA remains the preferred option, but ultimately will be replaced by AV7909, when the current AVA stockpile is exhausted.

Additional safety data on AV7909 will be reviewed by ACIP as they become available, and future guidance from the CDC will include statements on dosing for special populations including pregnant and breastfeeding women, said Dr. Bower.

“We anticipate that this [anthrax vaccine] work group will reconvene in 2021 to review data from pending studies” of AV7909, he said.

The ACIP members had no financial conflicts to disclose.

A booster dose for pre-exposure prophylaxis with an anthrax vaccine may be given at 3 years after an initial series for individuals not currently at risk who wish to maintain protection, according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

Carolina K. Smith, MD/Fotolia.com

In a unanimous 15-0 vote at the February meeting, ACIP committee members agreed on the recommendation after adjusting the wording to reflect a permissive, rather than mandated, guidance.

William Bower, MD, of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), presented data on Anthrax Vaccine Adsorbed (AVA) to support its protective effects over a longer booster dose interval.

The recommendations apply to persons aged 18 years or older who are not currently at high risk of exposure to Bacillus anthracis, but who might need to deploy to a high-risk area quickly, such as military personnel, Dr. Bower said.

In addition, data suggest that adults who have started, but not completed the pre-exposure priming series, can transition to the postexposure schedule prior to entering a high-risk area, he noted.

The previous pre-exposure anthrax vaccination schedule was a three-dose priming series at 0, 1, and 3 months, followed by a booster at 12 months and 18 months, then annually.

Data from several human immunogenicity studies showed a robust immune response following a delayed anthrax booster dose, with “sustained immunological memory to at least month 42,” and suggested that even longer intervals between boosters may be possible, Dr. Bower said.

A dosing schedule of intramuscular injections at 0 and at 1 month and 6 months, with a booster at 42 months yielded survival estimates of approximately 84%-93%.

Dr. Bower noted that a new vaccine, AV7909, has demonstrated safety and effectiveness similar to AVA and could be used for pre-exposure prophylaxis if AVA is not available. AVA remains the preferred option, but ultimately will be replaced by AV7909, when the current AVA stockpile is exhausted.

Additional safety data on AV7909 will be reviewed by ACIP as they become available, and future guidance from the CDC will include statements on dosing for special populations including pregnant and breastfeeding women, said Dr. Bower.

“We anticipate that this [anthrax vaccine] work group will reconvene in 2021 to review data from pending studies” of AV7909, he said.

The ACIP members had no financial conflicts to disclose.

Vaccination against Japanese encephalitis is recommended for persons moving to endemic areas, or who travel to these areas frequently or for long-term visits, according to a vote at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

Japanese encephalitis (JE) virus is a mosquito-borne flavivirus and those at risk for infection include travelers to countries where JE is endemic, as well as laboratory personnel who work with the virus.

The committee voted unanimously 15-0 in favor of the recommendations, which also advised vaccination for those whose travels in endemic areas are uncertain, but not for travelers with low-risk itineraries “such as shorter term travel limited to urban areas or travel that occurs outside of a well-defined JE virus transmission season.”

Susan Hills, MD, of the of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases, presented data in support of the recommendations.

A second unanimous vote confirmed recommendations for a primary series schedule for JE vaccination for adults aged 18-65 years as “two doses of vaccine administered on days 0 and 7-28.”

The third vote, also a unanimous 15-0, updated recommendations for a JE booster dose. The new recommendation is that adults and children receive a booster dose (a third dose) at least a year after completion of the primary JE vaccine series “if ongoing exposure or re-exposure to JE virus is expected.”

The currently available Japanese encephalitis vaccine in the United States is an inactivated Vero cell culture-derived vaccine marketed as IXIARO that was approved in March 2009 for individuals aged 17 years and older and approved in May 2013 for children aged 2 months through 16 years.

The ACIP members had no financial conflicts to disclose.
 

Vaccination against Japanese encephalitis is recommended for persons moving to endemic areas, or who travel to these areas frequently or for long-term visits, according to a vote at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

Japanese encephalitis (JE) virus is a mosquito-borne flavivirus and those at risk for infection include travelers to countries where JE is endemic, as well as laboratory personnel who work with the virus.

The committee voted unanimously 15-0 in favor of the recommendations, which also advised vaccination for those whose travels in endemic areas are uncertain, but not for travelers with low-risk itineraries “such as shorter term travel limited to urban areas or travel that occurs outside of a well-defined JE virus transmission season.”

Susan Hills, MD, of the of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases, presented data in support of the recommendations.

A second unanimous vote confirmed recommendations for a primary series schedule for JE vaccination for adults aged 18-65 years as “two doses of vaccine administered on days 0 and 7-28.”

The third vote, also a unanimous 15-0, updated recommendations for a JE booster dose. The new recommendation is that adults and children receive a booster dose (a third dose) at least a year after completion of the primary JE vaccine series “if ongoing exposure or re-exposure to JE virus is expected.”

The currently available Japanese encephalitis vaccine in the United States is an inactivated Vero cell culture-derived vaccine marketed as IXIARO that was approved in March 2009 for individuals aged 17 years and older and approved in May 2013 for children aged 2 months through 16 years.

The ACIP members had no financial conflicts to disclose.
 

Vaccination against Japanese encephalitis is recommended for persons moving to endemic areas, or who travel to these areas frequently or for long-term visits, according to a vote at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

Japanese encephalitis (JE) virus is a mosquito-borne flavivirus and those at risk for infection include travelers to countries where JE is endemic, as well as laboratory personnel who work with the virus.

The committee voted unanimously 15-0 in favor of the recommendations, which also advised vaccination for those whose travels in endemic areas are uncertain, but not for travelers with low-risk itineraries “such as shorter term travel limited to urban areas or travel that occurs outside of a well-defined JE virus transmission season.”

Susan Hills, MD, of the of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases, presented data in support of the recommendations.

A second unanimous vote confirmed recommendations for a primary series schedule for JE vaccination for adults aged 18-65 years as “two doses of vaccine administered on days 0 and 7-28.”

The third vote, also a unanimous 15-0, updated recommendations for a JE booster dose. The new recommendation is that adults and children receive a booster dose (a third dose) at least a year after completion of the primary JE vaccine series “if ongoing exposure or re-exposure to JE virus is expected.”

The currently available Japanese encephalitis vaccine in the United States is an inactivated Vero cell culture-derived vaccine marketed as IXIARO that was approved in March 2009 for individuals aged 17 years and older and approved in May 2013 for children aged 2 months through 16 years.

The ACIP members had no financial conflicts to disclose.
 

The annual number of new HIV infections has remained stable in recent years, and the Centers for Disease Control and Prevention says that’s not good – but solutions are at hand.

Centers for Disease Control and Prevention

[email protected]

SOURCE: Centers for Disease Control. CDC Report: www.cdc.gov/hiv/library/reports/hiv-surveillance.html.

The annual number of new HIV infections has remained stable in recent years, and the Centers for Disease Control and Prevention says that’s not good – but solutions are at hand.

Centers for Disease Control and Prevention

[email protected]

SOURCE: Centers for Disease Control. CDC Report: www.cdc.gov/hiv/library/reports/hiv-surveillance.html.

The annual number of new HIV infections has remained stable in recent years, and the Centers for Disease Control and Prevention says that’s not good – but solutions are at hand.

Centers for Disease Control and Prevention

[email protected]

SOURCE: Centers for Disease Control. CDC Report: www.cdc.gov/hiv/library/reports/hiv-surveillance.html.

Officials from the Centers for Disease Control and Prevention and the National Institute for Allergy and Infectious Diseases stressed the safety of measles vaccines and warned that misinformation is among the factors keeping more children from being vaccinated.

Courtesy House Energy and Commerce Committee

With nearly 160 cases of measles in 10 states during Jan. 1–Feb. 21, a disease once eradicated from the United States is resurfacing, with most cases affecting those who have not been vaccinated.

“Measles outbreaks have been and continue to be a constant threat to the health of the American people,” Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the CDC, testified at a Feb. 27 hearing of the Oversight and Investigations Subcommittee of the House Energy and Commerce Committee.

She noted that unvaccinated Americans traveling abroad are at risk for contracting the infection, and thus are at risk of spreading it when they return home. Foreigners coming to the country also carry the potential to spread the infection.

“Nationally, we enjoy high measles vaccination coverage,” Dr. Messonnier said.”There are pockets of people who are vaccine hesitant, who delay or even refuse to vaccinate themselves and their children. Outbreaks of measles occur when measles gets into these communities of unvaccinated people.”

She noted that those who eschew vaccination tend to live near one another and share common religious beliefs or racial or ethnic backgrounds.

She continued that vaccine hesitancy “is the result of the misunderstanding of the risk and seriousness of disease, combined with misinformation of the safety and effectiveness of vaccines. However, the specific issues fueling hesitancy varies by community.”

Strategies to increase vaccination need to be localized with national support from the CDC, Dr. Messonnier said, adding that rapid response is critical to control outbreaks.

Anthony Fauci, MD, director of the National Institute for Allergy and Infectious Diseases at NIH, agreed.

“I consider it really an irony that you have one of the most contagious viruses known to man juxtaposed against one of the most effective vaccines that we have and yet we don’t do and have not done what could be done, namely completely eliminate and eradicate this virus,” Dr. Fauci said.

Dr. Messonnier stressed that the only way to protect against measles is to get vaccinated.

“If they have questions, they should talk to their doctor,” she added. “Their doctor can provide them with more information about measles, answer their questions and reassure them so they go ahead and get vaccinated.”

Dr. Fauci concurred and added that “we should look upon it in two approaches. One, it’s for the safety of your own child. The other is a responsibility to the community. ... We all have a responsibility to be part of that umbrella of herd immunity and once it goes down below a certain percentage, then you have danger to the entire society.”

He stressed that the CDC is a good website to combat much of the misinformation that is floating around on the Internet.

The committee panel, while taking an interest in the recent outbreaks, did not hint at any specific legislative actions were being considered.
 

[email protected]

Officials from the Centers for Disease Control and Prevention and the National Institute for Allergy and Infectious Diseases stressed the safety of measles vaccines and warned that misinformation is among the factors keeping more children from being vaccinated.

Courtesy House Energy and Commerce Committee

With nearly 160 cases of measles in 10 states during Jan. 1–Feb. 21, a disease once eradicated from the United States is resurfacing, with most cases affecting those who have not been vaccinated.

“Measles outbreaks have been and continue to be a constant threat to the health of the American people,” Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the CDC, testified at a Feb. 27 hearing of the Oversight and Investigations Subcommittee of the House Energy and Commerce Committee.

She noted that unvaccinated Americans traveling abroad are at risk for contracting the infection, and thus are at risk of spreading it when they return home. Foreigners coming to the country also carry the potential to spread the infection.

“Nationally, we enjoy high measles vaccination coverage,” Dr. Messonnier said.”There are pockets of people who are vaccine hesitant, who delay or even refuse to vaccinate themselves and their children. Outbreaks of measles occur when measles gets into these communities of unvaccinated people.”

She noted that those who eschew vaccination tend to live near one another and share common religious beliefs or racial or ethnic backgrounds.

She continued that vaccine hesitancy “is the result of the misunderstanding of the risk and seriousness of disease, combined with misinformation of the safety and effectiveness of vaccines. However, the specific issues fueling hesitancy varies by community.”

Strategies to increase vaccination need to be localized with national support from the CDC, Dr. Messonnier said, adding that rapid response is critical to control outbreaks.

Anthony Fauci, MD, director of the National Institute for Allergy and Infectious Diseases at NIH, agreed.

“I consider it really an irony that you have one of the most contagious viruses known to man juxtaposed against one of the most effective vaccines that we have and yet we don’t do and have not done what could be done, namely completely eliminate and eradicate this virus,” Dr. Fauci said.

Dr. Messonnier stressed that the only way to protect against measles is to get vaccinated.

“If they have questions, they should talk to their doctor,” she added. “Their doctor can provide them with more information about measles, answer their questions and reassure them so they go ahead and get vaccinated.”

Dr. Fauci concurred and added that “we should look upon it in two approaches. One, it’s for the safety of your own child. The other is a responsibility to the community. ... We all have a responsibility to be part of that umbrella of herd immunity and once it goes down below a certain percentage, then you have danger to the entire society.”

He stressed that the CDC is a good website to combat much of the misinformation that is floating around on the Internet.

The committee panel, while taking an interest in the recent outbreaks, did not hint at any specific legislative actions were being considered.
 

[email protected]

Officials from the Centers for Disease Control and Prevention and the National Institute for Allergy and Infectious Diseases stressed the safety of measles vaccines and warned that misinformation is among the factors keeping more children from being vaccinated.

Courtesy House Energy and Commerce Committee

With nearly 160 cases of measles in 10 states during Jan. 1–Feb. 21, a disease once eradicated from the United States is resurfacing, with most cases affecting those who have not been vaccinated.

“Measles outbreaks have been and continue to be a constant threat to the health of the American people,” Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the CDC, testified at a Feb. 27 hearing of the Oversight and Investigations Subcommittee of the House Energy and Commerce Committee.

She noted that unvaccinated Americans traveling abroad are at risk for contracting the infection, and thus are at risk of spreading it when they return home. Foreigners coming to the country also carry the potential to spread the infection.

“Nationally, we enjoy high measles vaccination coverage,” Dr. Messonnier said.”There are pockets of people who are vaccine hesitant, who delay or even refuse to vaccinate themselves and their children. Outbreaks of measles occur when measles gets into these communities of unvaccinated people.”

She noted that those who eschew vaccination tend to live near one another and share common religious beliefs or racial or ethnic backgrounds.

She continued that vaccine hesitancy “is the result of the misunderstanding of the risk and seriousness of disease, combined with misinformation of the safety and effectiveness of vaccines. However, the specific issues fueling hesitancy varies by community.”

Strategies to increase vaccination need to be localized with national support from the CDC, Dr. Messonnier said, adding that rapid response is critical to control outbreaks.

Anthony Fauci, MD, director of the National Institute for Allergy and Infectious Diseases at NIH, agreed.

“I consider it really an irony that you have one of the most contagious viruses known to man juxtaposed against one of the most effective vaccines that we have and yet we don’t do and have not done what could be done, namely completely eliminate and eradicate this virus,” Dr. Fauci said.

Dr. Messonnier stressed that the only way to protect against measles is to get vaccinated.

“If they have questions, they should talk to their doctor,” she added. “Their doctor can provide them with more information about measles, answer their questions and reassure them so they go ahead and get vaccinated.”

Dr. Fauci concurred and added that “we should look upon it in two approaches. One, it’s for the safety of your own child. The other is a responsibility to the community. ... We all have a responsibility to be part of that umbrella of herd immunity and once it goes down below a certain percentage, then you have danger to the entire society.”

He stressed that the CDC is a good website to combat much of the misinformation that is floating around on the Internet.

The committee panel, while taking an interest in the recent outbreaks, did not hint at any specific legislative actions were being considered.
 

[email protected]

A substantial proportion of non–AIDS-defining cancers, and other noninfectious comorbid diseases, could be prevented with interventions on traditional risk factors in HIV-infected patients, according to the results of large database analysis published online in The Lancet HIV.

alexskopje/ThinkStock

The researchers analyzed traditional and HIV-related risk factors for four validated noncommunicable disease outcomes (non–AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease) among participants of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), according to Keri N. Althoff, PhD, of Johns Hopkins University, Baltimore, and her colleagues on behalf of the NA-ACCORD.

The study comprised individuals with the assessed disease conditions from among more than 180,000 adults (aged 18 years or older) with HIV from more than 200 sites who had at least two care visits within 12 months. The researchers used a population attributable fraction (PAF) approach to quantify the proportion of noncommunicable diseases that could be eliminated if particular risk factors were not present. According to the researchers, PAF can be used to inform prioritization of interventions.

Dr. Althoff and her colleagues found that, for non–AIDS-defining cancer, the significant preventable or modifiable risk factors were smoking, low CD4 cell count, detectable HIV RNA, a history of clinical AIDS diagnosis, and hepatitis B infection.

For myocardial infarction, the significant factors were smoking, elevated total cholesterol, hypertension, stage 4 chronic kidney disease, a low CD4 cell count, detectable HIV RNA, and hepatitis C infection.

For end-stage liver disease, the significant factors were low CD4 cell count, detectable HIV RNA, a history of a clinical AIDS diagnosis, and hepatitis B or C infection.

For end-stage renal disease, the significantly associated risk factors were elevated total cholesterol, hypertension, diabetes, low CD4 cell count, detectable HIV RNA, and a history of clinical AIDS diagnosis.

The most substantial PAF for each of the respective diseases was as follows: smoking for non–AIDS-related cancers (24%; 95% confidence interval, 13%-35%), elevated total cholesterol for myocardial infarction (44%; 95% CI, 30%-58%), and hepatitis C infection for end-stage liver disease (30%; 95% CI, 21%-39%). In addition, hypertension had the highest PAF for end-stage renal disease (39%; 95% CI, 26%-51%).

“Modifications to individual-level interventions and models of HIV care, and the implementation of structural and policy-level interventions that focus on prevention and modification of traditional risk factors are necessary to avoid noncommunicable diseases and preserve health among successfully antiretroviral-treated adults aging with HIV,” the researchers concluded.

The study was funded by the National Institutes of Health and the NA-ACCORD. Dr. Althoff reported having no relevant disclosures.

[email protected]

SOURCE: Althoff KN et al. The Lancet HIV. 2019 Jan 22. doi: 10.1016/S2352-3018(18)30295-9.

A substantial proportion of non–AIDS-defining cancers, and other noninfectious comorbid diseases, could be prevented with interventions on traditional risk factors in HIV-infected patients, according to the results of large database analysis published online in The Lancet HIV.

alexskopje/ThinkStock

The researchers analyzed traditional and HIV-related risk factors for four validated noncommunicable disease outcomes (non–AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease) among participants of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), according to Keri N. Althoff, PhD, of Johns Hopkins University, Baltimore, and her colleagues on behalf of the NA-ACCORD.

The study comprised individuals with the assessed disease conditions from among more than 180,000 adults (aged 18 years or older) with HIV from more than 200 sites who had at least two care visits within 12 months. The researchers used a population attributable fraction (PAF) approach to quantify the proportion of noncommunicable diseases that could be eliminated if particular risk factors were not present. According to the researchers, PAF can be used to inform prioritization of interventions.

Dr. Althoff and her colleagues found that, for non–AIDS-defining cancer, the significant preventable or modifiable risk factors were smoking, low CD4 cell count, detectable HIV RNA, a history of clinical AIDS diagnosis, and hepatitis B infection.

For myocardial infarction, the significant factors were smoking, elevated total cholesterol, hypertension, stage 4 chronic kidney disease, a low CD4 cell count, detectable HIV RNA, and hepatitis C infection.

For end-stage liver disease, the significant factors were low CD4 cell count, detectable HIV RNA, a history of a clinical AIDS diagnosis, and hepatitis B or C infection.

For end-stage renal disease, the significantly associated risk factors were elevated total cholesterol, hypertension, diabetes, low CD4 cell count, detectable HIV RNA, and a history of clinical AIDS diagnosis.

The most substantial PAF for each of the respective diseases was as follows: smoking for non–AIDS-related cancers (24%; 95% confidence interval, 13%-35%), elevated total cholesterol for myocardial infarction (44%; 95% CI, 30%-58%), and hepatitis C infection for end-stage liver disease (30%; 95% CI, 21%-39%). In addition, hypertension had the highest PAF for end-stage renal disease (39%; 95% CI, 26%-51%).

“Modifications to individual-level interventions and models of HIV care, and the implementation of structural and policy-level interventions that focus on prevention and modification of traditional risk factors are necessary to avoid noncommunicable diseases and preserve health among successfully antiretroviral-treated adults aging with HIV,” the researchers concluded.

The study was funded by the National Institutes of Health and the NA-ACCORD. Dr. Althoff reported having no relevant disclosures.

[email protected]

SOURCE: Althoff KN et al. The Lancet HIV. 2019 Jan 22. doi: 10.1016/S2352-3018(18)30295-9.

A substantial proportion of non–AIDS-defining cancers, and other noninfectious comorbid diseases, could be prevented with interventions on traditional risk factors in HIV-infected patients, according to the results of large database analysis published online in The Lancet HIV.

alexskopje/ThinkStock

The researchers analyzed traditional and HIV-related risk factors for four validated noncommunicable disease outcomes (non–AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease) among participants of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), according to Keri N. Althoff, PhD, of Johns Hopkins University, Baltimore, and her colleagues on behalf of the NA-ACCORD.

The study comprised individuals with the assessed disease conditions from among more than 180,000 adults (aged 18 years or older) with HIV from more than 200 sites who had at least two care visits within 12 months. The researchers used a population attributable fraction (PAF) approach to quantify the proportion of noncommunicable diseases that could be eliminated if particular risk factors were not present. According to the researchers, PAF can be used to inform prioritization of interventions.

Dr. Althoff and her colleagues found that, for non–AIDS-defining cancer, the significant preventable or modifiable risk factors were smoking, low CD4 cell count, detectable HIV RNA, a history of clinical AIDS diagnosis, and hepatitis B infection.

For myocardial infarction, the significant factors were smoking, elevated total cholesterol, hypertension, stage 4 chronic kidney disease, a low CD4 cell count, detectable HIV RNA, and hepatitis C infection.

For end-stage liver disease, the significant factors were low CD4 cell count, detectable HIV RNA, a history of a clinical AIDS diagnosis, and hepatitis B or C infection.

For end-stage renal disease, the significantly associated risk factors were elevated total cholesterol, hypertension, diabetes, low CD4 cell count, detectable HIV RNA, and a history of clinical AIDS diagnosis.

The most substantial PAF for each of the respective diseases was as follows: smoking for non–AIDS-related cancers (24%; 95% confidence interval, 13%-35%), elevated total cholesterol for myocardial infarction (44%; 95% CI, 30%-58%), and hepatitis C infection for end-stage liver disease (30%; 95% CI, 21%-39%). In addition, hypertension had the highest PAF for end-stage renal disease (39%; 95% CI, 26%-51%).

“Modifications to individual-level interventions and models of HIV care, and the implementation of structural and policy-level interventions that focus on prevention and modification of traditional risk factors are necessary to avoid noncommunicable diseases and preserve health among successfully antiretroviral-treated adults aging with HIV,” the researchers concluded.

The study was funded by the National Institutes of Health and the NA-ACCORD. Dr. Althoff reported having no relevant disclosures.

[email protected]

SOURCE: Althoff KN et al. The Lancet HIV. 2019 Jan 22. doi: 10.1016/S2352-3018(18)30295-9.

People living with HIV (PLHIV) who have a low CD4 count or detectable viral load (VL) have an increased 30-day heart failure (HF) readmission rate as well as increased cardiovascular and all-cause mortality, compared with uninfected controls, according to Raza M. Alvi, MD, of Massachusetts General Hospital and Harvard Medical School, Boston, and his colleagues.

Thinkstock

Overall, the 30-day HF hospital readmission rate was higher among PLHIV versus non-HIV–infected individuals (49% vs. 32%, P less than .001), according to the results of their cohort study of 2,308 individuals admitted to the hospital with decompensated HF.

PLHIV and the non-HIV control groups were both followed over 2 years with a median follow-up period of 19 months, the authors wrote in the American Heart Journal. Demographic make-up of the two groups was similar; in particular, there was no difference in blood pressure and heart rate between the PLHIV and non-HIV controls, suggesting that adherence with HF medications may be similar between groups. The cohorts differed primarily in that pulmonary artery systolic pressure was significantly higher (45 vs. 40 mm Hg; P less than .001) in the HIV group, as was cocaine use (36% vs. 19%; P less than .001) and hepatitis C virus (HCV) infection (13% vs. 7%; P less than .001).

The differing results between the two cohorts were primarily caused by the fact that, for PLHIV with HF, CD4 count and VL were risk factors for adverse outcomes among patients with all types of HF. Specifically, the subset of PLHIV with HF with a CD4 count of less than 200 cells/mm³ had worse outcomes (30-day HF readmission, cardiovascular [CV] mortality, and all-cause mortality), compared with those with CD4 count greater than or equal to 200 cells/mm^{3. In addition,} a low CD4 count/high VL independently related to an increased 30-day HF readmission rate even after the researchers controlled for major traditional and nontraditional HF risk factors.

“Rates of 30-day HF readmission, CV mortality, and all-cause mortality are worse among individuals with a low CD4 count or nonsuppressed viral load,” the researchers concluded.

The National Institutes of Health sponsored the study. The authors reported that they had no conflicts.

[email protected]

SOURCE: Alvi RM et al. Am Heart J. 2019 Apr;210:39-48.

People living with HIV (PLHIV) who have a low CD4 count or detectable viral load (VL) have an increased 30-day heart failure (HF) readmission rate as well as increased cardiovascular and all-cause mortality, compared with uninfected controls, according to Raza M. Alvi, MD, of Massachusetts General Hospital and Harvard Medical School, Boston, and his colleagues.

Thinkstock

Overall, the 30-day HF hospital readmission rate was higher among PLHIV versus non-HIV–infected individuals (49% vs. 32%, P less than .001), according to the results of their cohort study of 2,308 individuals admitted to the hospital with decompensated HF.

PLHIV and the non-HIV control groups were both followed over 2 years with a median follow-up period of 19 months, the authors wrote in the American Heart Journal. Demographic make-up of the two groups was similar; in particular, there was no difference in blood pressure and heart rate between the PLHIV and non-HIV controls, suggesting that adherence with HF medications may be similar between groups. The cohorts differed primarily in that pulmonary artery systolic pressure was significantly higher (45 vs. 40 mm Hg; P less than .001) in the HIV group, as was cocaine use (36% vs. 19%; P less than .001) and hepatitis C virus (HCV) infection (13% vs. 7%; P less than .001).

The differing results between the two cohorts were primarily caused by the fact that, for PLHIV with HF, CD4 count and VL were risk factors for adverse outcomes among patients with all types of HF. Specifically, the subset of PLHIV with HF with a CD4 count of less than 200 cells/mm³ had worse outcomes (30-day HF readmission, cardiovascular [CV] mortality, and all-cause mortality), compared with those with CD4 count greater than or equal to 200 cells/mm^{3. In addition,} a low CD4 count/high VL independently related to an increased 30-day HF readmission rate even after the researchers controlled for major traditional and nontraditional HF risk factors.

“Rates of 30-day HF readmission, CV mortality, and all-cause mortality are worse among individuals with a low CD4 count or nonsuppressed viral load,” the researchers concluded.

The National Institutes of Health sponsored the study. The authors reported that they had no conflicts.

[email protected]

SOURCE: Alvi RM et al. Am Heart J. 2019 Apr;210:39-48.

People living with HIV (PLHIV) who have a low CD4 count or detectable viral load (VL) have an increased 30-day heart failure (HF) readmission rate as well as increased cardiovascular and all-cause mortality, compared with uninfected controls, according to Raza M. Alvi, MD, of Massachusetts General Hospital and Harvard Medical School, Boston, and his colleagues.

Thinkstock

Overall, the 30-day HF hospital readmission rate was higher among PLHIV versus non-HIV–infected individuals (49% vs. 32%, P less than .001), according to the results of their cohort study of 2,308 individuals admitted to the hospital with decompensated HF.

PLHIV and the non-HIV control groups were both followed over 2 years with a median follow-up period of 19 months, the authors wrote in the American Heart Journal. Demographic make-up of the two groups was similar; in particular, there was no difference in blood pressure and heart rate between the PLHIV and non-HIV controls, suggesting that adherence with HF medications may be similar between groups. The cohorts differed primarily in that pulmonary artery systolic pressure was significantly higher (45 vs. 40 mm Hg; P less than .001) in the HIV group, as was cocaine use (36% vs. 19%; P less than .001) and hepatitis C virus (HCV) infection (13% vs. 7%; P less than .001).

The differing results between the two cohorts were primarily caused by the fact that, for PLHIV with HF, CD4 count and VL were risk factors for adverse outcomes among patients with all types of HF. Specifically, the subset of PLHIV with HF with a CD4 count of less than 200 cells/mm³ had worse outcomes (30-day HF readmission, cardiovascular [CV] mortality, and all-cause mortality), compared with those with CD4 count greater than or equal to 200 cells/mm^{3. In addition,} a low CD4 count/high VL independently related to an increased 30-day HF readmission rate even after the researchers controlled for major traditional and nontraditional HF risk factors.

“Rates of 30-day HF readmission, CV mortality, and all-cause mortality are worse among individuals with a low CD4 count or nonsuppressed viral load,” the researchers concluded.

The National Institutes of Health sponsored the study. The authors reported that they had no conflicts.

[email protected]

SOURCE: Alvi RM et al. Am Heart J. 2019 Apr;210:39-48.