Introduction A significant proportion of patients with chronic hepatitis C (HCV) progress to cirrhosis with its attendant complications. Most studies evaluating the natural history of HCV infection have taken development of cirrhosis as an endpoint. We therefore sought to establish, by means of a systematic review and analysis of the literature, the natural history of compensated HCV cirrhosis.

Methods A systematic literature review was performed. Where studies compared treated vs untreated patients, or HCV vs hepatitis B infection, only data regarding untreated, HCV monoinfected patients were included. Weighted mean annual percentage rates for death or transplantation, complications of cirrhosis and development of hepatocellular carcinoma (HCC) were calculated from the raw data.

Results Our search returned 12 papers which met the inclusion criteria. Despite some heterogeneity (inclusion of other causes of cirrhosis or HCV patients who had received antiviral therapy) we extracted data from these studies relating to 2138 patients. In compensated HCV cirrhosis the estimated rate of death or transplantation is 4.75% per annum, of decompensation is 5.61% per annum and of HCC is 3.76% per annum. Five studies reported combined outcomes for both treated and untreated patients. When considered together, these studies reported significantly lower annual percentage rates of HCC than those reporting untreated patients only (mean 2.51%±0.37 vs 5.20%±0.76, p=0.016), but not of decompensation (mean 5.34%±0.79 vs 9.58%±1.14, p=0.057) or death or transplantation (mean 3.84%±0.53 vs 4.76%±0.62, p=0.29).

Conclusion The estimated annual percentage rates of death or transplantation, decompensation and HCC confirm the relatively slow progress of compensated HCV cirrhosis, but highlight the need for continued vigilance for the occurrence of HCC. Heterogeneity in reporting, particularly the lack of distinction of outcomes according to treatment status or sustained virological response, means that the summary data presented may underestimate rate of disease progression, particularly HCC development. It will be important to ensure a clear distinction is made between treatment responders, partial responders and non-responders in future studies on the outcome of HCV cirrhosis.