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AASLD 2014: Many Hepatitis C Patients with Cirrhosis or Advanced Fibrosis Face Liver Failure


Nearly one-third of chronic hepatitis C patients with liver cirrhosis and 12% with advanced fibrosis progressed to decompensation within 5 years, and 23% and 11%, respectively, died, according to a study presented at the American Association for the Study of Liver Diseases (AASLD) Liver Meetinglast month in Boston. These findings underscore the urgent need for treatment for such individuals.

Over years or decades, chronic hepatitis C virus (HCV) infection can progress to serious liver disease including cirrhosis, hepatocellular carcinoma (HCC), liver decompensation (when the liver can no longer carry out its vital function), and liver-related death.

Successful treatment that leads to sustained virological response (SVR) can slow or halt liver disease progression and may allow for some degree of recovery. When the standard of care was interferon-based therapy -- which lasted up to a year, caused difficult side effects, and cured only about half of patients -- treatment was recommended only for people with evidence of progressive liver damage.

Now that highly effective and well-tolerated interferon-free direct-acting antiviral regimens are available, some experts have called for universal treatment. But given the drugs' high cost, current guidelines state that people with advanced liver disease should be prioritized, and many private insurers and national health systems are limiting treatment to the sickest patients.

Anne Moorman from the U.S. Centers for Disease Control and Prevention (CDC) and colleagues looked at liver disease progression to decompensation or HCC and all-cause mortality among patients in the Chronic Hepatitis Cohort Study. CHeCS isan ongoing observational study of more than 14,000 hepatitis C patients at 4 integrated healthcare systems: Henry Ford Health System in Detroit, Geisinger Health System in Danville, PA, Kaiser Permanente Hawaii in Honolulu, and Kaiser Permanente Northwest in Portland, OR.

This analysis included 2839 chronic hepatitis C patients with biopsy-confirmed fibrosis in the era prior to direct-acting antivirals. Participants had liver biopsies performed during 2001-2012, before the onset of HCC or decompensation, and before receiving hepatitis C treatment.

A majority of participants (about 60%) were men, two-thirds were white, and the median age was just over 50 years; more than 80% were in the highest-risk 1945-1965 birth cohort. Baseline biopsies revealed that 1204 (42%) had absent or mild fibrosis (Metavir stage F0-F1), 810 (29%) had moderate fibrosis (stage F2), 461 (16%) had advanced fibrosis (stage F3), and 364 had cirrhosis (stage F4).

The researchers analyzed the number of cases of HCC, decompensation, liver transplantation, and death over an average follow-up period of 5.5 years. Decompensation was defined as the first occurrence of portal hypertension, ascites (abdominal fluid accumulation), esophageal varices (distended veins), hepatic encephalopathy (brain impairment), or liver failure with hepato-renal syndrome.


  • Among people with cirrhosis at baseline:

o   29% experienced decompensation;

o   11% developed HCC;

o   5% underwent liver transplantation;

o   23% died due to any cause.

  • Among people with advanced fibrosis (F3) at baseline:

o   12% experienced decompensation;

o   5% developed HCC;

o   2% underwent liver transplantation;

o   11% died due to any cause.

  • Among people with moderate fibrosis (F2) at baseline:

o   4% experienced decompensation;

o   1% developed HCC;

o   1% underwent liver transplantation;

o   6% died due to any cause.

  • Looking at treatment, 62% of patients with cirrhosis, 72% with advanced fibrosis, and 46% with moderate fibrosis were ever treated after the baseline biopsy.
  • Among the subset of patients with known treatment outcomes, 47%, 55%, and 75%, respectively, achieved sustained virological response.
  • Among people with cirrhosis, the risk of decompensation was significantly lower among treated compared with untreated patients -- approximately 25% vs 50% at the maximum follow-up of 7 years; the risk of HCC was also significantly lower, about 7% vs 15%.
  • Among people with stage F3 fibrosis, the difference in decompensation rates between treated and untreated patients was also significant, 10% vs 25% at 7 years; fewer treated patients developed HCC (approximately 4% vs 7%), but the difference did not reach statistical significance.
  • There was no significant difference in decompensation or HCC rates between treated and untreated patients with F2 fibrosis, but rates were low -- under 4% for decompensation and under 2% for HCC -- in both groups.
  • In a multivariate analysis, people with cirrhosis were about 5 times more likely to experience decompensation, and those with F3 fibrosis were nearly 3 times more likely, compared to those with F2 fibrosis (adjusted hazard ratio [HR] 4.8 and 2.7).
  • Low platelet level and elevated bilirubin at baseline were also associated with a greater risk of decompensation (adjusted HR 3.9 and 2.4), while receiving treatment was associated with a 30% lower risk (adjusted HR 0.7).

"We observed substantial liver disease progression in a population-based observational cohort among patients meeting liver disease stage criteria that now confer 'high' or 'highest' recommendation for treatment," the researchers concluded.

These findings show that people with advanced fibrosis, in addition to those with cirrhosis, are at substantial risk of liver-related complications as should receive treatment. People with moderate fibrosis are at lower risk, but still 4 in 100 may progress to decompensation without treatment.



AC Moorman, F Xu, X Tong, et al. Mortality and progression to decompensated cirrhosis in chronic hepatitis C patients with liver biopsy confirmed fibrosis in the Chronic Hepatitis Cohort Study (CHeCS). American Association for the Study of Liver Diseases (AASLD) Liver Meeting. Boston, November 7-12, 2014. Abstract 174.