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Results of US research suggest all people with chronic HCV need treatment to reduce mortality risk

Michael Carter
22 March 2017

All people with chronic hepatitis C virus (HCV) infection should start therapy with direct-acting antivirals, research published in the online edition of Clinical Infectious Diseases suggests. Investigators from the United States found that individuals with moderate fibrosis had an increased risk of mortality, and that there was no accurate way of predicting disease progression of fibrosis from mild to moderate.

“Although increased mortality was evident among individuals with severe fibrosis/cirrhosis, we observed some increased risk of mortality, even among those with moderate fibrosis,” comment the authors. “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 to severe liver disease), may not support withholding HCV treatment until that transition occurs.”

An estimated 3 million individuals in the United States have chronic HCV infection. If left untreated, the infection significantly increases the risk of liver-related death and also several cancers.

Curative therapy using direct-acting antivirals is now available. However, because of its high cost, access is often limited to patients with at least moderate fibrosis. Guidelines from the American Association for the Study of Liver Diseases (AASLD) and Infectious Diseases Society of America (IDSA), however, recommend treatment for almost all individuals with chronic infection. Denial of therapy to people with mild fibrosis is justified by the assumption that this has no significant medical consequences and that disease progression can be accurately and reliably predicted.

Investigators from the ALIVE study in Baltimore wanted to see if this was indeed the case. They therefore designed an observational study involving 964 people with chronic HCV infection and a history of injecting drug use who received follow-up before effective treatment became available. Fibrosis was regularly assessed using liver stiffness testing. The relationship between fibrosis stage and mortality was calculated and the investigators explored whether individual or combinations of risk factors could predict fibrosis progression.

No/mild fibrosis was a liver-stiffness score below 8; moderate fibrosis a score between 8-12.3; and severe fibrosis a score above 12.3.

Median age at baseline was 49 years. Most study participants were male (72%) and African American (87%). Over half (52%) were current injecting drug users and 14% abused alcohol. The median duration of injecting was 28 years. A third had co-infection with HIV, 52% of whom were taking antiretroviral therapy.

Individuals were followed for a median of 5.9 years (follow-up was between 2006 and 2014) after first liver stiffness measurement. During this time, there were 155 deaths, an overall mortality rate of 3.06 deaths per 100 person-years. Mortality was highest among people with severe fibrosis (6.21 deaths per 100 person-years), but was still significantly elevated (trend, p < 0.001) among people with moderate fibrosis (3.59 per 100 person-years) compared to those with no/mild fibrosis (2.21 per 100 person-years).

After taking into account socio-demographic factors, substance use and HIV status, both all-cause and non-accidental mortality were elevated, the later significantly, among people with moderate fibrosis (aHR: 1.42; 95% CI 0.96-2.11; aHR: 1.66; 95% CI: 1.06-2.59, respectively).

Factors associated with disease progression were being overweight and a HIV viral load above 10,000 copies/ml. But their sensitivity for predicting progression from mild/moderate fibrosis was only 32%.

A one-year change in liver stiffness was also associated with progression to moderate fibrosis. For people with no/mild fibrosis at baseline, each one point increase in liver stiffness increased the risk of progression over 40-fold (aHR: 41,3; 95% CI3.15-542.3). However, this had only fair predictive accuracy (72%).

“We observed increased mortality among persons with severe and moderate fibrosis and transitions to moderate fibrosis could not be predicted with high accuracy,” conclude the authors. “These data support the AASLD/IDSA guidelines for treatment of all persons with chronic HCV infection and not support withholding treatment from those with mild disease.”


Cepeda JA et al. Increased mortality among persons with chronic hepatitis C with moderate or severe liver disease: a cohort study. Clin Infect Dis, online edition, 2017.