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Changes in liver scar tissue burden after hepatitis C virus cure in people with HIV

Hepatitis C virus (HCV) causes inflammation in the liver. In cases of chronic HCV infection, inflammation occurs as the immune system unsuccessfully attempts to rid the body of HCV. Over many years, healthy liver tissue is replaced with scar tissue in a process called fibrosis. This causes the liver to become less functional, and complications develop over time. These complications include: persistent fatigue, abdominal swelling, abdominal infections, yellowing of the skin and whites of the eyes, and difficulty with memory, concentration and thinking clearly. When the amount of scar tissue in the liver becomes extensive, the risk of liver cancer increases. 

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Diagnosis of chronic HCV can be done with simple blood tests, and daily treatment (in pill form) can cure up to 95% of people. 

Coinfection with HIV and HCV accelerates the course of HCV-related liver disease and the risk of dying prematurely. 

Recovery of the liver

Curing HCV increases the possibility that parts of the liver may begin to heal and reduce the burden of scar tissue. A reduction in scar tissue could reduce the risk of a person developing liver cancer. 

Researchers in Australia, Canada, France, the Netherlands, Spain and Switzerland cooperated and conducted a study with 1,470 people who were coinfected with HIV and HCV. All participants had their livers assessed using a specialized ultrasound scan called FibroScan prior to initiation of HCV treatment. These scans are useful in helping to determine the extent of liver injury (scar tissue) caused by the virus. Based on the scans, participants were placed into one of three subgroups:

  • F0 to F1 – no significant fibrosis; 50% of participants
  • F2 to F3 – significant fibrosis; 35% of participants 
  • F4 – cirrhosis (extensive scarring of the liver); 15% of participants 

People who had extensive liver injury (cirrhosis; F4) had a longer history of chronic HCV infection, were more likely to have a subtype of HCV called genotype 3 and tended to have a lower CD4+ cell count compared to people who did not have cirrhosis. 

Most participants (more than 90%) had a suppressed HIV viral load when they entered the study, indicating that they were on HIV treatment.

After HCV treatment cessation, 523 participants had one or more FibroScan assessments. According to the researchers, the changes in the amount of scar tissue after HCV treatment varied by the categories in which participants were first assigned. Researchers analysed data that were collected up to three years after HCV treatment cessation.

In people who had no significant fibrosis (F0 to F1) prior to HCV treatment, there was not much change because the level of scar tissue was very low initially. 

However, among people with some significant fibrosis (F2 to F3), the level of scar tissue decreased during HCV treatment and continued to do so during the first year after treatment cessation and for a bit after that. However, by the third year after treatment there was no further significant decline in fibrosis levels. 

Focus on cirrhosis

Among people with cirrhosis (F4), fibrosis levels fell significantly during treatment. However, once treatment ceased, there was no further decline in scar tissue. The researchers stated that “most participants with cirrhosis did not show meaningful fibrosis regression” after treatment cessation. What’s more, they stated that 70% of people with cirrhosis were expected to continue to have cirrhosis three years after treatment cessation. 

The researchers did a sub-analysis, taking into account factors that could have had an impact on scar tissue not regressing, such as detectable HIV, high body mass index (BMI), hazardous alcohol consumption or use of older HIV drugs. However, none of these factors had an impact on their findings. 

The researchers noted that, on average, the level of scar tissue and liver injury among people with cirrhosis was high prior to HCV therapy. These factors may have made it difficult for their livers to recover from the effects of chronic HCV-related inflammation. 

Considering these findings and conclusions, the researchers recommend that, in addition to curing HCV, additional strategies to try to help heal the livers of people with cirrhosis are needed.

Screening for liver cancer

As mentioned earlier, people with extensive scar tissue in the liver become at risk for the development of liver cancer. The researchers stated: “HCV cure substantially reduces the risk of [liver cancer]. However, all guidelines recommend ongoing [monitoring for liver cancer] for people with cirrhosis, as an appreciable of [liver cancer] remains after [HCV] cure.”

Much remains to be done

Although HCV therapy is highly effective, it does not always lead to resolution of extensive scar tissue in the liver. The researchers call for further studies to help “identify the characteristics of those with cirrhosis when starting treatment who do [show regression of fibrosis] and those who do regress and whether those who regress have a lower risk of [liver cancer]….” They add that this knowledge “could reduce the number of people who need to be monitored [for liver cancer development]....”

—Sean R. Hosein

REFERENCE:

Young J, Wang S, Sacks-Davis R, et al. Liver fibrosis regression in people living with HIV after successful treatment for hepatitis C. JAIDS. 2025 Jun 1;99(2):166-174.