Hepatic decompensation risk factors in APRICOT study reported

Advanced cirrhosis and concurrent treatment with ddI (didanosine) are the key risk factors for the development of decompensated cirrhosis (a marked and sometimes irreversible decline in liver function) during treatment of hepatitis C with pegylated interferon and ribavirin, according to an analysis of the APRICOT study published in the September 3^rd edition of AIDS.

People with advanced, hepatitis C-related liver damage (compensated cirrhosis) are more vulnerable to side effects and toxicities of therapy than persons with less advanced liver disease. If decompensated cirrhosis develops, hepatitis C treatment is contraindicated and liver transplantation is the only therapeutic option.

Decompensation is characterised by:

• Abnormal clearance of proteins absorbed from the intestine, leading to a build up of ammonia and hepatic encephalopathy (a build up of toxic substances such as ammonia that leads to nervous system changes and eventual brain damage).
• Elevated bilirubin levels, leading to jaundice.
• Fluid accumulation in the abdomen (ascites) that may become increasingly difficult to manage.
• Portal hypertension, or elevated blood pressure, potentially leading to rupture of varices, or enlarged veins, in the stomach wall or oesophagus, and life-threatening haemorrhages.

HIV coinfection accelerates hepatitis C disease progression, increasing the risk that coinfected patients will have cirrhosis. Safety and efficacy data on hepatitis C treatment in coinfected cirrhotics are critical, as coinfected persons have limited access to liver transplantation. Three recent studies—APRICOT (AIDS Pegasys Ribavirin International Co-infection Trial), the Adult AIDS Clinical Trials Group’s A5071 and RIBAVIC, from the ANRS—assessed safety and efficacy of hepatitis C treatment in people coinfected with HIV and hepatitis C virus (HCV). A subset of participants in each trial had compensated cirrhosis.

In APRICOT, 134 of 859 study participants were cirrhotic. Fourteen hepatic decompensations were reported during APRICOT. All decompensations occurred in people with cirrhosis, reflecting an incidence of 10.4%. Thirteen of fourteen hepatic decompensations happened during the first twenty-four weeks of treatment and were considered related to treatment. Six deaths were attributed to hepatic decompensation, while four of the eight remaining cases had resolved by week 78.

Mauss and colleagues assessed risk factors associated with hepatic decompensation in APRICOT. They considered baseline characteristics: weight, sex, age, HCV disease activity and stage of liver disease, HCV RNA, prothrombin time, and measurements of liver enzymes, albumin, haemoglobin, bilirubin and platelets. Baseline HIV disease parameters (CD4+ cell count, CD8+ cell count and HIV RNA) and use and classes of antiretroviral agents were included as well. After adjusting for these baseline characteristics, the effect of HCV treatment (pegylated interferon vs. standard interferon and ribavirin vs. placebo) was evaluated.

Increased bilirubin, decreased haemoglobin, and increased alkaline phosphatase or decreased platelets at baseline—all of which are indicators of advanced cirrhosis—were associated with hepatic decompensation in APRICOT. Use of ddI, with or without ribavirin, was also associated with increased risk of hepatic decompensation. The authors recommend avoiding ddI in co-infected cirrhotics when possible, vigilant monitoring of co-infected cirrhotics during HCV treatment, and consideration of hepatitis C treatment in HIV/HCV co-infected persons before development of advanced liver disease.