Doctors in Europe and the US disagree over the pace of liver fibrosis in men co-infected with HIV and hepatitis C

Doctors in Europe and the US have conflicting opinions about the pace of liver fibrosis in HIV-positive men with hepatitis C infection. In a study published in Clinical Infectious Diseases, European investigators showed that the pace of liver fibrosis slowed after the acute phase of infection. However, doctors from the US have published contrasting findings, showing that fibrosis continued to worsen with longer duration of co-infection.

The discrepancy between the studies could be a result of the methods used to evaluate liver fibrosis. The European investigators used Fibroscan, evaluating liver stiffness, whereas patients in the US study were monitored using liver biopsies.

There is an epidemic of sexually transmitted hepatitis C in HIV-positive gay men in Europe, the US and Australia. There is some evidence that co-infected patients experience an accelerated course of liver disease, with fibrosis developing soon after infection with hepatitis C. If this accelerated course of disease is maintained, then early hepatitis C therapy is a priority for co-infected HIV-positive people.

Therefore, investigators from Europe wished to gain a clearer understanding of the progression of fibrosis in co-infected men after the acute phase of hepatitis C infection.

They designed a study involving 38 HIV-positive men who were diagnosed with acute hepatitis C infection between 2005 and 2011. The progression of liver fibrosis was assessed using Fibroscan. This non-invasive test monitors liver stiffness, an accurate marker of fibrosis.

Patients were monitored for a median of 0.4 years. The mean fibrosis progression rate was 3.6 METAVIR  fibrosis units per year. Both longer duration of follow-up and higher ALT were associated with the progression of fibrosis.

The investigators found that it was a shorter, rather than a longer, period of follow-up from the estimated time of acute hepatitis C infection that was associated with faster progression of fibrosis.

The authors calculated that prolonging the period of follow-up from one to ten years would result in a reduction in the rate of fibrosis progression to approximately 10% of its starting value.

“We observed a strong influence of observation time on the fibrosis progression rate,” comment the researchers. Limiting analysis to patients with longer follow-up (over nine months) showed that the rate of fibrosis progression slowed to that seen in patients with chronic hepatitis C infection.

The authors suggest that the rapid progression of fibrosis seen during acute infection is most likely due to the huge elevations in ALT and AST levels that occur at this time. “Once chronic HCV [hepatitis C virus] infection is established, fibrogenesis may continue at an individual set level,” write the investigators. “This would be far lower, however, than that observed during the weeks of acute hepatitis, because inflammation and thus fibrogenesis may have declined.”

These findings could have clinical significance. Hepatitis C therapy is most likely to work if it is taken soon after infection with the virus. The authors therefore stress that “every HIV-infected patient should be advised to consider early treatment for acute hepatitis C if spontaneous clearance does not occur".

However, they believe their findings show that early treatment is not vital, commenting: “There may be room for delaying treatment among those who prefer to wait for new HCV therapies without the risk of rapidly developing cirrhosis.”

This is not the opinion of doctors in New York. They believe that the European doctors’ reliance on Fibroscan meant that they significantly over-estimated the progression of fibrosis in patients during the acute phase of infection.

Doctors in the US performed liver biopsies on 29 HIV-positive men with hepatitis C.

They found that longer length of infection with hepatitis C was associated with the worsening of fibrosis (p = 0.04). “There is rapid onset of fibrosis in the first 1 or 2 years of primary HCV infection that does not appear to resolve,” write the US doctors.

Although they are optimistic that newer hepatitis C therapies will bring a cure for most patients within two to five years, they emphasise that this may be too long for some people. The US investigators therefore urge their colleagues in Europe “to perform long-term follow-up of their enrolled patients as we plan to do with ours so we can directly monitor liver disease progression in these patients”.