Patients with HCV-associated cirrhosis are at high risk of developing hepatic decompensation, manifesting as hepatic synthetic dysfunction or complications of portal hypertension. Clinical signs of decompensation include ascites, encephalopathy, and upper gastrointestinal hemorrhage caused by variceal bleeding.

In an analysis of data from 1000 HCV patients with mild to advanced fibrosis, the incidence of decompensated cirrhosis after 5–7 years of follow-up was 43.5/10,000 person-years or about 1 in 230 patients/year. Similarly, a retrospective study reported the 5-year risk of decompensation to be 18% in 384 HCV patients with compensated cirrhosis (incidence, 3.9%/year), and a recent estimate suggests decompensation is currently present in 11.7% of CHC patients with cirrhosis. Decompensation has become more common since 1995, and because the proportion of CHC patients with cirrhosis is expected to increase through 2030, the incidence of decompensation can be expected to increase accordingly. It should be noted, however, that this model estimates that the majority of cirrhotic patients with chronic HCV infection will not develop decompensation during the first 3 decades of infection. Annual incidence rates for ascites (2.9%), jaundice (2.0%), upper gastrointestinal bleeding (0.7%), and encephalopathy (0.1%) were established in a later prospective study of 214 HCV-RNA seropositive patients after 114 months of follow-up.

Age at HCV acquisition is relevant, with decompensation risk as high as 133/10,000 person-years in patients infected after 39 years of age. In addition, the presence of the human leukocyte antigen DRB1*1201–3 allele might be associated with a higher rate of progression toward decompensated cirrhosis and HCC. The identification of reliable proteomic/genomic markers for risk of advanced HCV-related liver disease would aid prognostication and therapeutic decision-making.