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The medications are only contraindicated in patients with decompensated cirrhosis and statin-induced liver injury, Elizabeth Speliotes, MD, PhD, MPH, and her colleagues wrote in an expert review published in Clinical Gastroenterology and Hepatology. In these patients, statin treatment can compound liver damage and should be avoided, wrote Dr. Speliotes and her coauthors.
Because the liver plays a central role in cholesterol production, many clinicians shy away from treating hyperlipidemia in patients with liver disease. But studies consistently show that lipid-lowering drugs improve dyslipidemia in these patients, which significantly improves both high- and low-density lipoproteins and thereby reduces the long-term risk of cardiovascular disease, the authors wrote.
“Furthermore, the liver plays a role in the metabolism of many drugs, including those that are used to treat dyslipidemia,” wrote Dr. Speliotes of the University of Michigan, Ann Arbor. “It is not surprising, therefore, that many practitioners are hesitant to prescribe medicines to treat dyslipidemia in the setting of liver disease.”
Cholesterol targets described in the 2013 American College of Cardiology/American Heart Association guidelines can safely be applied to patients with liver disease. “The guidelines recommend that adults with cardiovascular disease or LDL of 190 mg/dL or higher be treated with high-intensity statins with the goal of reducing LDL levels by 50%,” they said. Patients whose LDL is 189 mg/dL or lower will benefit from moderate-intensity statins, with a target of a 30%-50% decrease in LDL.
The authors described best practice advice for dyslipidemia treatment in six liver diseases: drug-induced liver injury (DILI), nonalcoholic fatty liver disease (NAFLD), viral hepatitis B and C (HBV and HCV), primary biliary cholangitis (PBC), cirrhosis, and posttransplant dyslipidemia.
DILI
DILI is characterized by elevations of threefold or more in serum alanine aminotransferase (ALT) or aspartate aminotransferase and at least a doubling of total serum bilirubin with no other identifiable cause of these aberrations except the suspect drug. Statins rarely cause a DILI (1 in 100,000 patients), but can cause transient, benign ALT elevations. Statins should be discontinued if ALT or aspartate aminotransferase levels exceed a tripling of the upper limit of normal with concomitant bilirubin elevations. They should not be prescribed to patients with acute liver failure or decompensated liver disease, but otherwise they are safe for most patients with liver disease.
NAFLD
Many patients with NAFLD also have dyslipidemia. All NAFLD patients have an increased risk of cardiovascular disease, although NAFLD and nonalcoholic steatohepatitis are not traditional cardiovascular risk factors. Nevertheless, statins and the accompanying improvement in dyslipidemia have been shown to decrease cardiovascular mortality in these patients. The IDEAL study, for example, showed that moderate statin treatment with 80 mg atorvastatin was associated with a 44% decreased risk in secondary cardiovascular events. Other studies show similar results.
NAFLD patients with elevated LDL may benefit from ezetimibe as primary or add-on therapy. However, none of the drugs used to treat dyslipidemia will improve NAFLD or nonalcoholic steatohepatitis histology.
Viral hepatitis
Hepatitis C virus
Patients with HCV infection often experience decreased serum LDL and total cholesterol. However, these are virally mediated and don’t confer cardiovascular protection. In fact, HCV infections are associated with an increased risk of myocardial infarction. If the patient spontaneously clears the virus, lipids may rebound, so levels should be regularly monitored even if the patient does not need statin therapy.
Hepatitis B virus
HBV also interacts with lipid metabolism and can lead to hyperlipidemia. The American College of Cardiology/American Heart Association guidelines for cardiovascular risk assessment and statin therapy apply to these patients. Statins are safe in patients with either HCV or HBV, who tolerate them well.
PBC
PBC is a chronic autoimmune inflammatory cholestatic disease that is associated with dyslipidemia. These patients exhibit increased serum triglyceride and HDL levels that vary according to PBC stage. About 10% have a significant risk of cardiovascular disease. PBC patients with compensated liver disease can safely tolerate statin treatment, but the drugs should not be given to PBC patients with decompensated liver disease.
Obeticholic acid (OCA) is sometimes used as second-line therapy for PBC; it affects genes that regulate bile acid synthesis, transport, and action. However, the POISE study showed that, while OCA improved PBC symptoms, it was associated with an increase in LDL and total cholesterol and a decrease in HDL. No follow-up studies have determined cardiovascular implications of that change, but OCA should be avoided in patients with active cardiovascular disease or with cardiovascular risk factors.
Cirrhosis
Recent work suggests that patients with cirrhosis may face a higher risk of coronary artery disease than was previously thought, although that risk varies widely according to the etiology of the cirrhosis.
Statins are safe and effective in patients with Child-Pugh class A cirrhosis; there are few data on their safety in patients with decompensated cirrhosis. Some guidance for these patients exists in the 2014 recommendations of the Liver Expert Panel, which advised against statin use in patients with Child-Pugh class B or C cirrhosis.
There’s some evidence that statins reduce portal pressure and may reduce the risk of decompensation in patients whose cirrhosis is caused by HCV or HBV infections, but they should not be used for this purpose.
Posttransplant dyslipidemia
After liver transplant, more than 60% of patients will develop dyslipidemia; these patients often have obesity or diabetes.
Statins are safe for patients with liver transplant. Concomitant use of calcineurin inhibitors and statins that are metabolized by cytochrome P450 may increase the risk of statin-associated myopathy. Pravastatin and fluvastatin are preferable, because they are metabolized by cytochrome P450 34A.
Neither Dr. Speliotes nor her coauthors had any financial disclosures.
SOURCE: Speliotes EK et al. Clin Gastroenterol Hepatol. 2018 Apr 21. doi: 10.1016/j.cgh.2018.04.023.
The medications are only contraindicated in patients with decompensated cirrhosis and statin-induced liver injury, Elizabeth Speliotes, MD, PhD, MPH, and her colleagues wrote in an expert review published in Clinical Gastroenterology and Hepatology. In these patients, statin treatment can compound liver damage and should be avoided, wrote Dr. Speliotes and her coauthors.
Because the liver plays a central role in cholesterol production, many clinicians shy away from treating hyperlipidemia in patients with liver disease. But studies consistently show that lipid-lowering drugs improve dyslipidemia in these patients, which significantly improves both high- and low-density lipoproteins and thereby reduces the long-term risk of cardiovascular disease, the authors wrote.
“Furthermore, the liver plays a role in the metabolism of many drugs, including those that are used to treat dyslipidemia,” wrote Dr. Speliotes of the University of Michigan, Ann Arbor. “It is not surprising, therefore, that many practitioners are hesitant to prescribe medicines to treat dyslipidemia in the setting of liver disease.”
Cholesterol targets described in the 2013 American College of Cardiology/American Heart Association guidelines can safely be applied to patients with liver disease. “The guidelines recommend that adults with cardiovascular disease or LDL of 190 mg/dL or higher be treated with high-intensity statins with the goal of reducing LDL levels by 50%,” they said. Patients whose LDL is 189 mg/dL or lower will benefit from moderate-intensity statins, with a target of a 30%-50% decrease in LDL.
The authors described best practice advice for dyslipidemia treatment in six liver diseases: drug-induced liver injury (DILI), nonalcoholic fatty liver disease (NAFLD), viral hepatitis B and C (HBV and HCV), primary biliary cholangitis (PBC), cirrhosis, and posttransplant dyslipidemia.
DILI
DILI is characterized by elevations of threefold or more in serum alanine aminotransferase (ALT) or aspartate aminotransferase and at least a doubling of total serum bilirubin with no other identifiable cause of these aberrations except the suspect drug. Statins rarely cause a DILI (1 in 100,000 patients), but can cause transient, benign ALT elevations. Statins should be discontinued if ALT or aspartate aminotransferase levels exceed a tripling of the upper limit of normal with concomitant bilirubin elevations. They should not be prescribed to patients with acute liver failure or decompensated liver disease, but otherwise they are safe for most patients with liver disease.
NAFLD
Many patients with NAFLD also have dyslipidemia. All NAFLD patients have an increased risk of cardiovascular disease, although NAFLD and nonalcoholic steatohepatitis are not traditional cardiovascular risk factors. Nevertheless, statins and the accompanying improvement in dyslipidemia have been shown to decrease cardiovascular mortality in these patients. The IDEAL study, for example, showed that moderate statin treatment with 80 mg atorvastatin was associated with a 44% decreased risk in secondary cardiovascular events. Other studies show similar results.
NAFLD patients with elevated LDL may benefit from ezetimibe as primary or add-on therapy. However, none of the drugs used to treat dyslipidemia will improve NAFLD or nonalcoholic steatohepatitis histology.
Viral hepatitis
Hepatitis C virus
Patients with HCV infection often experience decreased serum LDL and total cholesterol. However, these are virally mediated and don’t confer cardiovascular protection. In fact, HCV infections are associated with an increased risk of myocardial infarction. If the patient spontaneously clears the virus, lipids may rebound, so levels should be regularly monitored even if the patient does not need statin therapy.
Hepatitis B virus
HBV also interacts with lipid metabolism and can lead to hyperlipidemia. The American College of Cardiology/American Heart Association guidelines for cardiovascular risk assessment and statin therapy apply to these patients. Statins are safe in patients with either HCV or HBV, who tolerate them well.
PBC
PBC is a chronic autoimmune inflammatory cholestatic disease that is associated with dyslipidemia. These patients exhibit increased serum triglyceride and HDL levels that vary according to PBC stage. About 10% have a significant risk of cardiovascular disease. PBC patients with compensated liver disease can safely tolerate statin treatment, but the drugs should not be given to PBC patients with decompensated liver disease.
Obeticholic acid (OCA) is sometimes used as second-line therapy for PBC; it affects genes that regulate bile acid synthesis, transport, and action. However, the POISE study showed that, while OCA improved PBC symptoms, it was associated with an increase in LDL and total cholesterol and a decrease in HDL. No follow-up studies have determined cardiovascular implications of that change, but OCA should be avoided in patients with active cardiovascular disease or with cardiovascular risk factors.
Cirrhosis
Recent work suggests that patients with cirrhosis may face a higher risk of coronary artery disease than was previously thought, although that risk varies widely according to the etiology of the cirrhosis.
Statins are safe and effective in patients with Child-Pugh class A cirrhosis; there are few data on their safety in patients with decompensated cirrhosis. Some guidance for these patients exists in the 2014 recommendations of the Liver Expert Panel, which advised against statin use in patients with Child-Pugh class B or C cirrhosis.
There’s some evidence that statins reduce portal pressure and may reduce the risk of decompensation in patients whose cirrhosis is caused by HCV or HBV infections, but they should not be used for this purpose.
Posttransplant dyslipidemia
After liver transplant, more than 60% of patients will develop dyslipidemia; these patients often have obesity or diabetes.
Statins are safe for patients with liver transplant. Concomitant use of calcineurin inhibitors and statins that are metabolized by cytochrome P450 may increase the risk of statin-associated myopathy. Pravastatin and fluvastatin are preferable, because they are metabolized by cytochrome P450 34A.
Neither Dr. Speliotes nor her coauthors had any financial disclosures.
SOURCE: Speliotes EK et al. Clin Gastroenterol Hepatol. 2018 Apr 21. doi: 10.1016/j.cgh.2018.04.023.
The medications are only contraindicated in patients with decompensated cirrhosis and statin-induced liver injury, Elizabeth Speliotes, MD, PhD, MPH, and her colleagues wrote in an expert review published in Clinical Gastroenterology and Hepatology. In these patients, statin treatment can compound liver damage and should be avoided, wrote Dr. Speliotes and her coauthors.
Because the liver plays a central role in cholesterol production, many clinicians shy away from treating hyperlipidemia in patients with liver disease. But studies consistently show that lipid-lowering drugs improve dyslipidemia in these patients, which significantly improves both high- and low-density lipoproteins and thereby reduces the long-term risk of cardiovascular disease, the authors wrote.
“Furthermore, the liver plays a role in the metabolism of many drugs, including those that are used to treat dyslipidemia,” wrote Dr. Speliotes of the University of Michigan, Ann Arbor. “It is not surprising, therefore, that many practitioners are hesitant to prescribe medicines to treat dyslipidemia in the setting of liver disease.”
Cholesterol targets described in the 2013 American College of Cardiology/American Heart Association guidelines can safely be applied to patients with liver disease. “The guidelines recommend that adults with cardiovascular disease or LDL of 190 mg/dL or higher be treated with high-intensity statins with the goal of reducing LDL levels by 50%,” they said. Patients whose LDL is 189 mg/dL or lower will benefit from moderate-intensity statins, with a target of a 30%-50% decrease in LDL.
The authors described best practice advice for dyslipidemia treatment in six liver diseases: drug-induced liver injury (DILI), nonalcoholic fatty liver disease (NAFLD), viral hepatitis B and C (HBV and HCV), primary biliary cholangitis (PBC), cirrhosis, and posttransplant dyslipidemia.
DILI
DILI is characterized by elevations of threefold or more in serum alanine aminotransferase (ALT) or aspartate aminotransferase and at least a doubling of total serum bilirubin with no other identifiable cause of these aberrations except the suspect drug. Statins rarely cause a DILI (1 in 100,000 patients), but can cause transient, benign ALT elevations. Statins should be discontinued if ALT or aspartate aminotransferase levels exceed a tripling of the upper limit of normal with concomitant bilirubin elevations. They should not be prescribed to patients with acute liver failure or decompensated liver disease, but otherwise they are safe for most patients with liver disease.
NAFLD
Many patients with NAFLD also have dyslipidemia. All NAFLD patients have an increased risk of cardiovascular disease, although NAFLD and nonalcoholic steatohepatitis are not traditional cardiovascular risk factors. Nevertheless, statins and the accompanying improvement in dyslipidemia have been shown to decrease cardiovascular mortality in these patients. The IDEAL study, for example, showed that moderate statin treatment with 80 mg atorvastatin was associated with a 44% decreased risk in secondary cardiovascular events. Other studies show similar results.
NAFLD patients with elevated LDL may benefit from ezetimibe as primary or add-on therapy. However, none of the drugs used to treat dyslipidemia will improve NAFLD or nonalcoholic steatohepatitis histology.
Viral hepatitis
Hepatitis C virus
Patients with HCV infection often experience decreased serum LDL and total cholesterol. However, these are virally mediated and don’t confer cardiovascular protection. In fact, HCV infections are associated with an increased risk of myocardial infarction. If the patient spontaneously clears the virus, lipids may rebound, so levels should be regularly monitored even if the patient does not need statin therapy.
Hepatitis B virus
HBV also interacts with lipid metabolism and can lead to hyperlipidemia. The American College of Cardiology/American Heart Association guidelines for cardiovascular risk assessment and statin therapy apply to these patients. Statins are safe in patients with either HCV or HBV, who tolerate them well.
PBC
PBC is a chronic autoimmune inflammatory cholestatic disease that is associated with dyslipidemia. These patients exhibit increased serum triglyceride and HDL levels that vary according to PBC stage. About 10% have a significant risk of cardiovascular disease. PBC patients with compensated liver disease can safely tolerate statin treatment, but the drugs should not be given to PBC patients with decompensated liver disease.
Obeticholic acid (OCA) is sometimes used as second-line therapy for PBC; it affects genes that regulate bile acid synthesis, transport, and action. However, the POISE study showed that, while OCA improved PBC symptoms, it was associated with an increase in LDL and total cholesterol and a decrease in HDL. No follow-up studies have determined cardiovascular implications of that change, but OCA should be avoided in patients with active cardiovascular disease or with cardiovascular risk factors.
Cirrhosis
Recent work suggests that patients with cirrhosis may face a higher risk of coronary artery disease than was previously thought, although that risk varies widely according to the etiology of the cirrhosis.
Statins are safe and effective in patients with Child-Pugh class A cirrhosis; there are few data on their safety in patients with decompensated cirrhosis. Some guidance for these patients exists in the 2014 recommendations of the Liver Expert Panel, which advised against statin use in patients with Child-Pugh class B or C cirrhosis.
There’s some evidence that statins reduce portal pressure and may reduce the risk of decompensation in patients whose cirrhosis is caused by HCV or HBV infections, but they should not be used for this purpose.
Posttransplant dyslipidemia
After liver transplant, more than 60% of patients will develop dyslipidemia; these patients often have obesity or diabetes.
Statins are safe for patients with liver transplant. Concomitant use of calcineurin inhibitors and statins that are metabolized by cytochrome P450 may increase the risk of statin-associated myopathy. Pravastatin and fluvastatin are preferable, because they are metabolized by cytochrome P450 34A.
Neither Dr. Speliotes nor her coauthors had any financial disclosures.
SOURCE: Speliotes EK et al. Clin Gastroenterol Hepatol. 2018 Apr 21. doi: 10.1016/j.cgh.2018.04.023.
EXPERT ANALYSIS FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY