Introduction: Patients with chronic hepatitis C infection and cirrhosis have an increased risk of developing severe liver-related complications, including hepatic decompensation, hepatocellular cancer, and death. Since nearly all patients with hepatocellular carcinoma have cirrhosis prior to developing hepatocellular carcinoma, the treatment of hepatitis C in patients with hepatocellular carcinoma is included in this overall discussion of treatment of hepatitis C in patients with cirrhosis. Multiple studies have shown that successful treatment of hepatitis C in patients with compensated cirrhosis will decrease subsequent cirrhosis-related complications. Accordingly, any patient with chronic hepatitis C infection who is diagnosed with compensated cirrhosis should be considered at a high priority for hepatitis C treatment. For HCV-infected patients with decompensated cirrhosis or hepatocellular cancer, treatment of HCV may provide benefit, but the treatment plans and goals may need modifying if the patient is planning to undergo liver transplantation.
Distinguishing Compensated and Decompensated Cirrhosis: One important step in treating hepatitis C in patients with cirrhosis is to determine whether the cirrhosis is compensated or decompensated. The treatment approach and goals are divergent based on the classification of compensated versus decompensated cirrhosis. In general, patients with compensated cirrhosis only have mild hepatic impairment (Child-Turcotte-Pugh class A) (Figure 1) and do not have jaundice, ascites, variceal hemorrhage, or hepatic encephalopathy. In contrast, the patient should be considered to have decompensated cirrhosis if they have moderate or severe liver disease (Child-Turcotte-Pugh class B or C); patients with decompensated cirrhosis have experienced one or more of the following: ascites, jaundice, variceal hemorrhage, or hepatic encephalopathy. Patients who have become asymptomatic and completely stabilized after experiencing one feature of hepatic decompensation should be evaluated on a case-by-case basis to determine whether they could be considered for treatment similar to patients with compensated cirrhosis.
Impact of Hepatitis C Treatment in Patients with Cirrhosis: Multiple studies have shown that patients with hepatitis C and cirrhosis have significant improvement in inflammatory grade and have reversal of fibrosis following hepatitis C therapy, particularly when an SVR is attained. In one very extensive study, Poynard and coworkers pooled data involving 3010 hepatitis C treatment-naïve patients who received standard interferon (with or without ribavirin) or peginterferon (with or without ribavirin). Overall, 590 (20%) of the 3010 patients had improvement in fibrosis, but among the 153 patients with cirrhosis, 75 (49%) had reversal of cirrhosis. In a separate study, among cirrhotic patients treated with standard interferon who achieved an SVR, 108 (53%) of 183 had improvement in fibrosis, whereas only 19% of patients those who did not achieve an SVR had improvement in fibrosis. The long-term impact of newer direct-acting antiviral agents on fibrosis has not been adequately studied, but achievement of SVR with these regimens would presumably translate into a similar benefit as SVR seen with older regimens. In a separate study, van der Meer and coworkers followed 530 patients with advanced fibrosis or cirrhosis in Europe and Canada; all patients had interferon-based treatment for hepatitis C and SVR was clearly associated with lower all-cause mortality (Figure 2). Further, a meta-analysis performed by Singal et al. analyzed 26 studies and concluded that achieving an SVR was associated with substantially lower liver-related morbidity and mortality.
Impact of Hepatitis C Treatment on Risk of Hepatocellular Cancer: Several studies have shown that treatment of hepatitis C in patients with cirrhosis with achievement of SVR lowers the subsequent risk of developing hepatocellular cancer. In the large study conducted by van der Meer that examined 530 patients with chronic hepatitis C infection and advanced fibrosis, after 10 years of follow-up, the cumulative occurrence of hepatocellular cancer was 5.1% in patients who achieved an SVR compared with 21.8% in those who did not achieve an SVR. In addition, Shiratori and colleagues found that interferon therapy for 271 cirrhotic patients with chronic hepatitis C reduced the incidence of hepatocellular carcinoma, especially for those who achieved SVR with therapy (Figure 3).
Safety Concerns: Experience with peginterferon (or interferon) plus ribavirin in the treatment of patients with compensated cirrhosis has shown a higher rate of treatment-related adverse effects than with patients who do not have cirrhosis. With the use of peginterferon-based therapies, treatment of decompensated cirrhosis has been problematic due to potential severe treatment-related adverse effects, such as development of anemia, neutropenia, thrombocytopenia, severe infections, bleeding, renal insufficiency, and hepatic decompensation. Among these potential serious adverse effects, the development of hepatic decompensation is the most important and is associated with a high mortality.