Back HCV Disease Progression Fibrosis/Cirrhosis HIV Coinfection Not a Risk Factor for Liver Fibrosis Progression in People with Hepatitis C

HIV Coinfection Not a Risk Factor for Liver Fibrosis Progression in People with Hepatitis C


HIV coinfection is not associated with accelerated progression of liver fibrosis in people with hepatitis C virus (HCV) infection, according to U.S. research published in the October 15 edition of the Journal of Infectious Diseases. Factors linked with fibrosis progression were low fibrosis stage at baseline and flares in alanine aminotransferase (ALT) levels.

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The major strengths of the study were its large sample size and the fact that participants had at least 2 liver biopsy results during follow-up, Daniel Fierer from the Icahn School of Medicine at Mount Sinai commented in an accompanying editorial.

Hepatitis C is a leading cause of serious liver disease. Chronic HCV infection can cause progressive liver fibrosis, cirrhosis, liver cancer, and death. Effective direct-acting antiviral therapies are now available. However, these treatments are costly and it is therefore necessary to prioritize the people in greatest need, especially those experiencing rapid fibrosis progression.

As the factors associated with the progression of liver fibrosis in the context of HCV infection are poorly understood, investigators from Weill Cornell Medical College designed a retrospective study to determine the rates and risk factors for liver disease progression. The research involved 378 people with HCV infection who had 2 or more liver biopsies between 1997 and 2013. The investigators analyzed the effect of demographic, epidemiological, and virological factors on fibrosis progression.

Participants had a mean age of 48 years, 59% were male, 60% were white, and 87% had HCV genotype 1. Approximately a third -- 31% -- were coinfected with HIV.

At the time of the first biopsy, 36% of participants had mild (grade 1) liver inflammation, 57% had moderate (grade 2) inflammation, and 7% had severe (grade 3) inflammation. Fibrosis was absent in 12% of participants (stage 0), whereas 32% had mild (stage 1) fibrosis, 39% had moderate (stage 2) fibrosis, and 16% had severe (stage 3) fibrosis.

Fibrosis stage 2 and above was associated with elevated liver inflammation at the time of the first biopsy (OR 9.00; p<0.001). Fatty liver disease (steatosis) was present in the majority -- 59% -- of participants, and this was associated with both higher fibrosis stage (OR 2.39; p=0.002) and higher inflammation (OR 4.07; p<0.001) at initial biopsy.

A total of 558 consecutive biopsy pairs were available for analysis. The mean duration between the first and last biopsies was 7 years, and the mean period between adjacent biopsies was 4 years.

During follow-up, 57% of people advanced at least 1 biopsy stage, 16% progressed 2 stages, and 7% developed cirrhosis (stage 4).

After controlling for potential confounders, factors associated with fibrosis progression were absent or mild fibrosis at first biopsy (OR 13.51; p<0.001) and at least 1 ALT flare (200 U/L threshold) during follow-up (OR 2.64; p=0.007).

The estimated progression rate from fibrosis stages 0 to 1 was highest -- 3 times higher than the rate of progression between stages 2 and 3. Individuals remained at stage 0 for an average of 2.55 years and at stage 2 for an average of 18.4 years.

Analysis of the subset of people who developed cirrhosis showed that progression occurred in a mean of 8 years of follow-up. Factors associated with progression were HCV genotype 3 (p=0.04) and ALT level (p<0.001). Higher fibrosis stage at the first biopsy and lower baseline platelet count were both of borderline significance.

"We did not observe an association between fibrosis progression and HIV coinfection," commented the investigators. "This could potentially be explained by well-controlled HIV viremia in co-infected patients."

The authors also point out that their findings call into question the assumption that fibrosis progresses at a steady, or linear, rate, and they concluded, "we found varying stage-specific progression rates in patients with chronic hepatitis C."

In his accompanying editorial, Fierer said that understanding factors associated with fibrosis progression in people with HCV infection was "a crucial medical issue." However, he was not convinced that all people with HIV/HCV coinfection, even in the modern antiretroviral era, have a low risk of fibrosis progression. Citing his own research looking at HIV-positive gay men who acquired HCV via sexual transmission, he noted that many of these people experienced rapid fibrosis progression, suggesting that the acquisition of HCV after HIV is more harmful to the liver than vice versa.

"The available evidence is that they rapidly progress to having moderate levels of fibrosis, and some of those with the most immunocompromise experience further rapid progression to cirrhosis," Fierer wrote.

Yet Zeremski and colleagues report that progression from mild or no cirrhosis to moderate fibrosis was the most frequently observed form of progression in their study, suggesting that what Fierer and colleagues are observing is a common pattern regardless of HIV status, and that Fierer's cohort is distinctive more for having well-established dates of HCV infection than for their previous HIV infection.



M Zeremski, RM Dimova, J Pillardy, et al. Fibrosis Progression in Patients with Chronic Hepatitis C Virus Infection. Journal of Infectious Diseases 214(8):1164-1170. October 15, 2016.

DS Fierer. The Order of Addition of Immunocompromise: The Effects of HIV Infection on Fibrosis Progression of Hepatitis C-Infected Patients. Journal of Infectious Diseases 214(8):1134-1136. October 15, 2016.