Multicenter, Double-Blind, Randomized Trial of Emricasan in Hepatitis C-Treated Liver Transplant Recipients With Residual Fibrosis or Cirrhosis.

Despite achieving sustained virologic response (SVR) to hepatitis C virus (HCV) therapy, there remains a post liver transplantation population with advanced fibrosis/cirrhosis. Emricasan is an orally active, pan-caspase inhibitor that suppresses apoptosis and inflammation, potentially decreasing hepatic inflammation and fibrosis. We aimed to determine the safety and efficacy of emricasan (IDN-6556-07) in a double-blind, randomized, placebo-controlled, multicenter study in reducing or preventing the progression of hepatic fibrosis in HCV liver transplant recipients with residual fibrosis or cirrhosis after achieving SVR. A total of 64 participants were randomly assigned to receive 25 mg twice daily of emricasan or placebo in a 2:1 ratio for 24 months. 41 participants were randomly assigned to emricasan and 23 to placebo; 32 participants in the emricasan group (78.0%) and 19 who took a placebo (82.6%) completed the study. There was no difference in the primary endpoint (Ishak fibrosis stages F2-F5, improvement in fibrosis or stability; Ishak fibrosis stage F6, improvement) between the emricasan (77.1%) and placebo groups (74.1%); P = NS. There was no difference between the emricasan (54.5%) and placebo (60.7%) arms in the rate of fibrosis improvement alone. However, those in the prespecified F3 to F5 subgroup had higher rates of stability or improvement in fibrosis in the emricasan group (95.2%) compared with placebo (54.6%) (P = 0.01). The tolerability and safety profiles were similar in both groups. In conclusion, overall stability in the Ishak fibrosis stage was similar between emricasan and placebo groups at 24 months. However, there was improvement and/or stability in fibrosis stage in the prespecified F3 to F5 subgroup with emricasan versus placebo, suggesting that patients with moderate fibrosis may benefit with emricasan.

Hepatitis B in Pregnant Women and their Infants.

Chronic hepatitis B is a global health problem affecting approximately 350 million to 400 million individuals worldwide, and mother to child transmission remains the major mode of transmission. Approximately 50% of chronically infected individuals acquire infection, either perinatally or early in childhood, predominantly in areas where hepatitis B virus (HBV) is endemic. Management of HBV in pregnancy presents a unique set of challenges. All infants born of hepatitis B surface antigen-positive mothers should receive postexposure immune prophylaxis with hepatitis B immunoglobulin and HBV vaccination within 24 hours of birth and need close follow-up for the first few years of life.

Chronic hepatitis C in the state prison system: insights into the problems and possible solutions.

The prevalence of chronic hepatitis C virus (HCV) within the correctional system is estimated to be 10-20-times greater than that which is reported in the general population. High-risk behavioral patterns probably account for the greater estimates in this population. Recent observations of more than 780 patient-inmates infected with HCV within the California Department of Corrections suggest a very high prevalence of advanced fibrosis in this population. Observational studies performed in Texas have shown that the rates of chronic liver disease-related deaths have increased significantly between 1989 and 2003, especially among Hispanic patient-inmates. Viral hepatitis accounts for a significant number of these chronic liver disease-related deaths. Identification of high-risk patient-inmates infected with HCV, as well as appropriation of funds for their treatment, should result in a decreased rate of liver-related complications. This should translate into reduced morbidity and cost to correctional institutions, as well as to improved public health and safety.

Retreatment of chronic hepatitis C virus infection.

Despite advances in antiviral therapy for chronic hepatitis C, approximately half of patients undergoing initial treatment fail to achieve a sustained virologic response (SVR), thus prompting consideration of retreatment with alternative regimens. The decision to re-treat should be based on the severity of liver disease, as well as the presence of clinical and virologic predictors of a successful outcome of additional therapy. Retreatment of patients who were prior nonresponders to interferon monotherapy with interferon plus ribavirin results in SVR rates of 13% to 15%, which can be increased to 25% to 40% if peginterferon plus ribavirin is used. Retreatment of patients who were prior nonresponders to interferon plus ribavirin with peginterferon plus ribavirin unfortunately achieves SVR rates of approximately 10%. The growing number of patients who have been treated and have failed initial therapy highlights the need for the development of more efficacious antiviral agents for the treatment of chronic hepatitis C.