Faculty Bibliography

BACKGROUND & AIMS:We investigated the real-world effectiveness of sofosbuvir, ledipasvir/sofosbuvir, and paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD) in treatment of different subgroups of patients infected with hepatitis C virus (HCV) genotypes 1, 2, 3, or 4. METHODS:We performed a retrospective analysis of data from 17,487 patients with HCV infection (13,974 with HCV genotype 1; 2131 with genotype 2; 1237 with genotype 3; and 135 with genotype 4) who began treatment with sofosbuvir (n = 2986), ledipasvir/sofosbuvir (n = 11,327), or PrOD (n = 3174), with or without ribavirin, from January 1, 2014 through June 20, 2015 in the Veterans Affairs health care system. Data through April 15, 2016 were analyzed to assess completion of treatments and sustained virologic response 12 weeks after treatment (SVR12). Mean age of patients was 61 ± 7 years, 97% were male, 52% were non-Hispanic white, 29% were non-Hispanic black, 32% had a diagnosis of cirrhosis (9.9% with decompensated cirrhosis), 36% had a Fibrosis-4 index score >3.25 (indicator of cirrhosis), and 29% had received prior antiviral treatment. RESULTS:An SVR12 was achieved by 92.8% (95% confidence interval [CI], 92.3%-93.2%) of subjects with HCV genotype 1 infection (no significant difference between ledipasvir/sofosbuvir and PrOD regimens), 86.2% (95% CI, 84.6%-87.7%) of those with genotype 2 infection (treated with sofosbuvir and ribavirin), 74.8% (95% CI, 72.2%-77.3%) of those with genotype 3 infection (77.9% in patients given ledipasvir/sofosbuvir plus ribavirin, 87.0% in patients given sofosbuvir and pegylated-interferon plus ribavirin, and 70.6% of patients given sofosbuvir plus ribavirin), and 89.6% (95% CI 82.8%-93.9%) of those with genotype 4 infection. Among patients with cirrhosis, 90.6% of patients with HCV genotype 1, 77.3% with HCV genotype 2, 65.7% with HCV genotype 3, and 83.9% with HCV genotype 4 achieved an SVR12. Among previously treated patients, 92.6% with genotype 1; 80.2% with genotype 2; 69.2% with genotype 3; and 93.5% with genotype 4 achieved SVR12. Among treatment-naive patients, 92.8% with genotype 1; 88.0% with genotype 2; 77.5% with genotype 3; and 88.3% with genotype 4 achieved SVR12. Eight-week regimens of ledipasvir/sofosbuvir produced an SVR12 in 94.3% of eligible patients with HCV genotype 1 infection; this regimen was underused. CONCLUSIONS:High proportions of patients with HCV infections genotypes 1-4 (ranging from 75% to 93%) in the Veterans Affairs national health care system achieved SVR12, approaching the results reported in clinical trials, especially in patients with genotype 1 infection. An 8-week regimen of ledipasvir/sofosbuvir is effective for eligible patients with HCV genotype 1 infection and could reduce costs. There is substantial room for improvement in SVRs among persons with cirrhosis and genotype 2 or 3 infections.

BACKGROUND & AIMS/OBJECTIVE:Epidemiologic factors have generated increased demand for liver transplantation among older patients. We aimed to describe trends in age among liver transplant registrants and recipients and the effect of age on waitlist and post-transplantation outcomes and on transplant-related survival benefit. METHODS:We obtained data from the United Network for Organ Sharing on adults who were listed for liver transplantation (N = 122,606) or underwent liver transplantation (N = 60,820) from 2002 to 2014 in the United States. Competing risks analysis was used to model waitlist outcomes and Cox proportional hazards analysis to model post-transplantation survival. These models were also used to estimate 5-year transplant-related survival benefit for different age groups, calculated as the difference between waitlist and post-transplantation life expectancy. RESULTS:Between 2002 and 2014, the mean age of liver transplant registrants increased from 51.2 to 55.7 years, with a more prominent increase in hepatitis C virus-positive (50.9-57.9 years) than hepatitis C virus-negative (51.3-54.3 years) registrants. The proportion of registrants aged ≥60 years increased from 19% to 41%. In hepatitis C virus-negative patients, aging trends were driven by increasing proportions of patients with hepatocellular carcinoma or nonalcoholic steatohepatitis. Among transplant registrants, increasing age was associated with increasing mortality before transplantation and decreasing likelihood of transplantation. Among transplant recipients, increasing age was associated with increasing post-transplantation mortality. There was little difference in 5-year transplant-related survival benefit between different age groups who had the same Model for End-Stage Liver Disease score. CONCLUSIONS:Dramatic aging of liver transplant registrants and recipients occurred from 2002 to 2014, driven by aging of the hepatitis C virus-positive cohort and increased prevalence of nonalcoholic steatohepatitis and hepatocellular carcinoma. Increasing age does not affect transplant-related survival benefit substantially because age diminishes both post-transplantation survival and waitlist survival approximately equally.