Increased Mortality With Moderate, Severe Hep C-related Liver Disease

By Will Boggs MD

March 24, 2017

NEW YORK (Reuters Health) - Mortality is increased in patients with moderate or severe liver disease related to chronic hepatitis C, and progression from mild/moderate to severe disease cannot be predicted reliably, according to the ALIVE study.

"We were surprised by the amount of morbidity and mortality in the group with moderate fibrosis, many of whom would have difficulties receiving highly curative treatment,” Dr. Javier A. Cepeda from the University of California, San Diego, in La Jolla, told Reuters Health by email.

Despite expert-group recommendations to treat nearly everyone chronically infected with hepatitis C virus (HCV), most U.S. states restrict the use of oral direct-acting antivirals (DAAs) to patients with advanced fibrosis or cirrhosis, Dr. Cepeda and colleagues note in Clinical Infectious Diseases, online March 10. This is based on an assumption of no medical consequence to low-stage HCV infection and that liver fibrosis progression can be safely monitored until advanced fibrosis/cirrhosis is detected, they add.

The team used data from 964 individuals chronically infected with HCV with a history of injection drug use to characterize mortality rates by liver disease severity before widespread availability of DAAs.

At baseline, 63% of participants had no or mild liver fibrosis, 23% had moderate fibrosis, and 15% had severe fibrosis/cirrhosis.

During a median 5.9 years of follow-up, all-cause mortality was highest among participants with severe fibrosis/cirrhosis at baseline (6.21 deaths/100 person-years), intermediate among those with moderate fibrosis at baseline (3.59 deaths/100 py) and not elevated among those with no/mild fibrosis at baseline (2.21 deaths/100 py).

After adjusting for all other prognostic variables, severe fibrosis/cirrhosis remained associated with significantly elevated mortality risk, whereas the association with moderate fibrosis was attenuated and lost statistical significance.

Among individuals with no/mild fibrosis at baseline, 19% experienced significant progression during follow-up. Factors associated with an increased risk of progression had low predictive accuracy (C statistic=0.66), and a risk score in the top quintile was only 32% sensitive for predicting transition from no/mild to moderate fibrosis at five years.

“Although increased mortality was evident among individuals with severe fibrosis/cirrhosis, we observed some increased risk of mortality even among those with moderate fibrosis,” the researchers note. “These findings, and our inability to identify with sufficiently high prognostic accuracy individuals who would transition from a lower mortality risk state (minimal liver disease) to a higher mortality risk state (moderate or severe liver disease), may not support withholding HCV treatment until that transition occurs.”

“Fight to treat your patients as early as possible,” Dr. Cepeda urged.


Clin Infect Dis 2017.