Virologic Response Protects Against Death in Liver Transplant Patients With HCV

BOSTON – Achieving sustained virologic response to antiviral therapy was highly protective against liver-related death in liver transplant patients with chronic hepatitis C, according to an analysis of data collected over a 20-year period from 12 liver transplant centers in Italy.

Patients with recurrent HCV who were unable to achieve sustained virologic response (SVR) were at a significantly higher risk of liver-related mortality than were those for whom the virus remained suppressed 6 weeks after treatment, Dr. Maria Rendina reported at the annual meeting of the American Association for the Study of Liver Diseases.

For the study, the investigators retrospectively analyzed data on 464 patients who underwent liver transplantation between 1989 and 2008. All of the patients had viral and histologic confirmation of HCV recurrence and all were treated with recombinant or pegylated interferon plus ribavirin at standard doses for at least 1 year, Dr. Rendina said. Of the study population, 35% achieved SVR, defined as undetectable HCV RNA 6 weeks after the end of treatment, and approximately 30% died during the mean 6.8 years of posttreatment follow-up. "Liver-related mortality was the cause of death in 73% of the patients who did not survive, and all of the liver-related deaths except for one were in the group of patients who did not attain [SVR]," she said.

A comparison of the SVR and non-SVR patient characteristics showed no differences in immunosuppressive strategies between the two groups, according to Dr. Rendina of the University of Bari in Italy. Overall, the SVR patients received livers from younger donors. They also had longer treatment durations, higher cumulative doses of interferon, lower dropout rates, and lower diabetes incidence, she said.

In univariate analysis, older donor age, viral genotypes 1 or 4, diabetes, and lack of SVR to antiviral therapy were significant risk factors for death, Dr. Rendina reported. In a multivariate analysis, after adjustment for donor, viral, and recipient variables including age, gender, genotype, immunosuppression, creatinine, hepatocellular carcinoma, and diabetes, failure to achieve SVR remained "significantly and independently associated with a very high risk of liver-related death," she said, noting that the hazard ratio for liver-related death in the non-SVR group was 3.3.

"Antiviral therapy should be strongly pursued in liver transplant patients with recurrent hepatitis C infection because of the protective role of [SVR]," she said.

The hesitancy to pursue antiviral therapy for HCV recurrence after liver transplantation stems, in large part, from the absence of data regarding the relationship between viral eradication and long-term clinical outcome, said Dr. Rendina. It is further exacerbated by the frequency and severity of adverse events associated with the pegylated interferon/ribavirin standard of care – most notably flulike symptoms, hemolytic anemia, neutropenia, depression, and neurologic symptoms, she said, noting that more than 25% of the patients in the current study stopped treatment because of intolerable side effects.

Despite the drawbacks, antiviral therapy holds the most promise for improving HCV-infected patients’ long-term outcome post transplantation and should be used in clinical practice, Dr. Rendina stated. At the same time, "further randomized trials aimed at exploring various treatment options and the efficacy of new antiviral drugs should be undertaken," she said.

Dr. Rendina disclosed having no financial conflicts of interest with respect to her presentation.

BOSTON – Achieving sustained virologic response to antiviral therapy was highly protective against liver-related death in liver transplant patients with chronic hepatitis C, according to an analysis of data collected over a 20-year period from 12 liver transplant centers in Italy.

Patients with recurrent HCV who were unable to achieve sustained virologic response (SVR) were at a significantly higher risk of liver-related mortality than were those for whom the virus remained suppressed 6 weeks after treatment, Dr. Maria Rendina reported at the annual meeting of the American Association for the Study of Liver Diseases.

For the study, the investigators retrospectively analyzed data on 464 patients who underwent liver transplantation between 1989 and 2008. All of the patients had viral and histologic confirmation of HCV recurrence and all were treated with recombinant or pegylated interferon plus ribavirin at standard doses for at least 1 year, Dr. Rendina said. Of the study population, 35% achieved SVR, defined as undetectable HCV RNA 6 weeks after the end of treatment, and approximately 30% died during the mean 6.8 years of posttreatment follow-up. "Liver-related mortality was the cause of death in 73% of the patients who did not survive, and all of the liver-related deaths except for one were in the group of patients who did not attain [SVR]," she said.

A comparison of the SVR and non-SVR patient characteristics showed no differences in immunosuppressive strategies between the two groups, according to Dr. Rendina of the University of Bari in Italy. Overall, the SVR patients received livers from younger donors. They also had longer treatment durations, higher cumulative doses of interferon, lower dropout rates, and lower diabetes incidence, she said.

In univariate analysis, older donor age, viral genotypes 1 or 4, diabetes, and lack of SVR to antiviral therapy were significant risk factors for death, Dr. Rendina reported. In a multivariate analysis, after adjustment for donor, viral, and recipient variables including age, gender, genotype, immunosuppression, creatinine, hepatocellular carcinoma, and diabetes, failure to achieve SVR remained "significantly and independently associated with a very high risk of liver-related death," she said, noting that the hazard ratio for liver-related death in the non-SVR group was 3.3.

"Antiviral therapy should be strongly pursued in liver transplant patients with recurrent hepatitis C infection because of the protective role of [SVR]," she said.

The hesitancy to pursue antiviral therapy for HCV recurrence after liver transplantation stems, in large part, from the absence of data regarding the relationship between viral eradication and long-term clinical outcome, said Dr. Rendina. It is further exacerbated by the frequency and severity of adverse events associated with the pegylated interferon/ribavirin standard of care – most notably flulike symptoms, hemolytic anemia, neutropenia, depression, and neurologic symptoms, she said, noting that more than 25% of the patients in the current study stopped treatment because of intolerable side effects.

Despite the drawbacks, antiviral therapy holds the most promise for improving HCV-infected patients’ long-term outcome post transplantation and should be used in clinical practice, Dr. Rendina stated. At the same time, "further randomized trials aimed at exploring various treatment options and the efficacy of new antiviral drugs should be undertaken," she said.

Dr. Rendina disclosed having no financial conflicts of interest with respect to her presentation.

BOSTON – Achieving sustained virologic response to antiviral therapy was highly protective against liver-related death in liver transplant patients with chronic hepatitis C, according to an analysis of data collected over a 20-year period from 12 liver transplant centers in Italy.

Patients with recurrent HCV who were unable to achieve sustained virologic response (SVR) were at a significantly higher risk of liver-related mortality than were those for whom the virus remained suppressed 6 weeks after treatment, Dr. Maria Rendina reported at the annual meeting of the American Association for the Study of Liver Diseases.

For the study, the investigators retrospectively analyzed data on 464 patients who underwent liver transplantation between 1989 and 2008. All of the patients had viral and histologic confirmation of HCV recurrence and all were treated with recombinant or pegylated interferon plus ribavirin at standard doses for at least 1 year, Dr. Rendina said. Of the study population, 35% achieved SVR, defined as undetectable HCV RNA 6 weeks after the end of treatment, and approximately 30% died during the mean 6.8 years of posttreatment follow-up. "Liver-related mortality was the cause of death in 73% of the patients who did not survive, and all of the liver-related deaths except for one were in the group of patients who did not attain [SVR]," she said.

A comparison of the SVR and non-SVR patient characteristics showed no differences in immunosuppressive strategies between the two groups, according to Dr. Rendina of the University of Bari in Italy. Overall, the SVR patients received livers from younger donors. They also had longer treatment durations, higher cumulative doses of interferon, lower dropout rates, and lower diabetes incidence, she said.

In univariate analysis, older donor age, viral genotypes 1 or 4, diabetes, and lack of SVR to antiviral therapy were significant risk factors for death, Dr. Rendina reported. In a multivariate analysis, after adjustment for donor, viral, and recipient variables including age, gender, genotype, immunosuppression, creatinine, hepatocellular carcinoma, and diabetes, failure to achieve SVR remained "significantly and independently associated with a very high risk of liver-related death," she said, noting that the hazard ratio for liver-related death in the non-SVR group was 3.3.

"Antiviral therapy should be strongly pursued in liver transplant patients with recurrent hepatitis C infection because of the protective role of [SVR]," she said.

The hesitancy to pursue antiviral therapy for HCV recurrence after liver transplantation stems, in large part, from the absence of data regarding the relationship between viral eradication and long-term clinical outcome, said Dr. Rendina. It is further exacerbated by the frequency and severity of adverse events associated with the pegylated interferon/ribavirin standard of care – most notably flulike symptoms, hemolytic anemia, neutropenia, depression, and neurologic symptoms, she said, noting that more than 25% of the patients in the current study stopped treatment because of intolerable side effects.

Despite the drawbacks, antiviral therapy holds the most promise for improving HCV-infected patients’ long-term outcome post transplantation and should be used in clinical practice, Dr. Rendina stated. At the same time, "further randomized trials aimed at exploring various treatment options and the efficacy of new antiviral drugs should be undertaken," she said.

Dr. Rendina disclosed having no financial conflicts of interest with respect to her presentation.