The natural history of compensated cirrhosis due to hepatitis C virus

Abstract

Large databases of consecutive patients followed for sufficiently long periods are needed to establish the rates, chronology, and hierarchy of complications of cirrhosis as well as the importance of other potential causes of liver disease. In accordance with this goal, a cohort of patients with compensated cirrhosis due to hepatitis C virus (HCV) was followed for 17 years. Two hundred and fourteen HCV RNA-seropositive patients with Child-Pugh class A cirrhosis who had no previous clinical decompensation were prospectively recruited and followed up with periodic clinical and abdominal ultrasound examinations. During 114 months (range 1-199), hepatocellular carcinoma (HCC) developed in 68 (32%), ascites in 50 (23%), jaundice in 36 (17%), upper gastrointestinal bleeding in 13 (6%), and encephalopathy in 2 (1%), with annual incidence rates of 3.9%, 2.9%, 2.0%, 0.7%, and 0.1%, respectively. Clinical status remained unchanged in 154 (72%) and progressed to Child-Pugh class B in 45 (21%) and class C in 15 (7%). HCC was the main cause of death (44%) and the first complication to develop in 58 (27%) patients, followed by ascites in 29 (14%), jaundice in 20 (9%), and upper gastrointestinal bleeding in 3 (1%). The annual mortality rate was 4.0% per year and was higher in patients with other potential causes of liver disease than in those without them (5.7% vs. 3.6%; P ‫؍‬ .04). In conclusion, hepatitis C-related cirrhosis is a slowly progressive disease that may be accelerated by other potential causes of liver disease. HCC was the first complication to develop and the dominant cause for increased mortality.

Sustained virological response to interferon-α is associated with improved outcome in HCV-related cirrhosis: A retrospective study

“…29 Our data suggest that the reduction of liver-related mortality among SVR patients resulted from the combined efficacy of IFN against decompensation or bleeding and HCC, because these complications are the leading causes of death in patients with early cirrhosis due to HCV. 30,31 Data indicate that IFN may prevent the worsening of the disease by suppressing HCV-related liver inflammation which favors hepatocellular failure and the progression of portal hypertension, and by modulating several cell factors involved in neoplastic transformation, such as RNA-dependent PKR and 2Ј,5Ј oligo adenyl synthetase. 32 In murine models, IFN inhibits liver cell proliferation and stimulates apoptosis of preneoplastic hepatocytes.…”

Liver fibrosis: mechanisms of immune-mediated liver injury

“…In patients infected with the chronic hepatitis C virus, the annual mortality rate is greater than 4%. 3 Among patients with cirrhosis, approximately 70% of deaths are directly attributable to liver disease. 4 Fibrosis and cirrhosis of the liver remain major causes of morbidity and mortality worldwide and are associated with increasing economic and social impact.…”

Rebamipide retards CCl4-induced hepatic fibrosis in rats: Possible role for PGE2

“…Hepatic inflammation helps to drive fibrogenesis by causing increases in leukocytehepatic stellate cells (HSC) interactions, activity of cytokine networks and formation of small (pro-inflammatory) molecules such as reactive oxygen species (ROS) (Maher 2001). HSC are perisinusoidal cells located in the sub-endothelial space between hepatocytes and sinusoidal endothelial cells (Sangiovanni et al 2006).…”