- Chronic hepatitis C can damage the liver, but treatments cure 95% of infections
- Hepatitis C cure reduces liver cancer risk, but most studies have focused on HIV-negative people
- A six-year study found decreased liver cancer risk among people with HIV cured of hepatitis C
Due to shared routes of transmission, some people with HIV are also infected with hepatitis C virus (HCV).
Acute HCV can infect the liver and cause severe inflammation of this organ. If left undiagnosed or untreated, HCV infection can become a chronic condition, and inflammation and liver injury persist. Over many years, HCV causes healthy liver tissue to be replaced with useless scar tissue. As the amount of scar tissue accumulates and the liver degrades, symptoms can appear, including severe fatigue, fluid buildup in the abdomen, internal bleeding, severe abdominal infections, yellowing of the skin (jaundice), and subsequently, difficulty thinking clearly and memory problems. Eventually, the liver can stop functioning. The accumulation of scar tissue increases the risk of liver cancer and dying.
Chronic HCV can be diagnosed with blood tests. Additional blood tests and abdominal scans can reveal more about the health of the liver. Once-daily oral treatments for HCV are available in Canada and other high-income countries. These treatments—called direct-acting antivirals (DAAs)—are highly effective, with cure rates of 95% or greater. DAAs are generally well tolerated and safe.
In studies of people who were cured of HCV because of DAAs, researchers have found that such treatment results in improved liver health and reduces the risk of subsequently developing liver cancer. However, most post-HCV cure studies have been done in people without HIV.
To explore the risk of liver cancer in people with HIV who were cured of HCV, a team of researchers has been monitoring the health of several thousand people. Study participants were in Canada (at major clinics in Calgary and Montreal), Europe and the U.S. The research team labelled its project the HepCAUSAL collaboration.
Over the course of six years after participants were cured of HCV, researchers estimated that about 2.5% of people with HIV who had a large degree of scar tissue in their liver were diagnosed with liver cancer. The risk of liver cancer decreased over time. For instance, after three years of being cured of HCV, the risk of liver cancer was less than 0.4%.
Study details
Researchers began collecting health-related information from medical charts and lab tests in 2013. They focused on 3,824 participants who were coinfected with HIV and HCV. Of this population, 2,373 people completed treatment with DAAs. Their average profile upon study entry was as follows:
- age – 60 years
- 92% were assigned male at birth and 8% were assigned female at birth
- 48% had a history of injection drug use
- 82% had a history of tobacco smoking
- CD4+ count – 473 cells/mm3
- all participants had an HIV viral load of less than 50 copies/mL
- duration of HCV infection – 11 years
- most common HCV subtype – genotype 1 (70%)
- history of interferon treatment – 17%
- degree of liver scarring – 35% had a severe extent of scarred liver tissue (graded as F3 by the researchers); 65% had even more scarred liver tissue or cirrhosis (graded as F4 by the researchers)
- 38% had diabetes
Once participants were cured of HCV, they underwent abdominal ultrasound scans every six months to check for the presence of new tumours. Some participants also had the levels of a protein in their blood called alfa-fetoprotein measured. Elevated levels of this protein are associated with an increased risk of liver cancer.
Results
After DAA initiation, over the course of the study there were 43 new cases of liver cancer and 301 people died.
The researchers found that about 2.5% of people with HIV who were cured of HCV developed liver cancer up to six years after being cured.
However, this overall figure masks changes that were occurring throughout the study. That is, once participants were cured, their risk of liver cancer fell and continued to fall over time. The risk of liver cancer was greatest in the first year after being cured of HCV (0.81%), then fell to less than 0.34% in the third year after being cured, and the risk fell even further (to 0.1%) six years after being cured.
Bear in mind
The study’s findings are encouraging and confirm general trends reported in studies of people without HIV who were cured of HCV.
In the time before DAAs were available, the mainstay of HCV treatment was regular injections of interferon. This treatment was not highly effective. Nevertheless, data from that era suggested that the risk of liver cancer was at least 2% up to a decade after cure.
The current study demonstrates a declining risk of liver cancer after the use of DAAs in people with HIV who were cured of HCV. Importantly, the researchers state that their analysis underscores the critical importance of screening people for liver cancer “in the first few years after DAA initiation.”
—Sean R. Hosein
Resources
Researchers encourage simultaneous testing for three viruses—HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) – CATIE News
Increased risk of death in Canadian study of people who fall out of care for HIV and hepatitis C – CATIE News
Alberta researchers find high rates of hepatitis C virus and syphilis co-infection during pregnancy – CATIE News
‘One-stop’ health service in England achieves high rates of hepatitis C cure – CATIE News
Interventions drive down rates of hepatitis C among gay and bisexual men with HIV – CATIE News
REFERENCES:
- van Santen DK, Chalouni M, Berenguer J, et al. Risk of hepatocellular carcinoma after direct-acting antiviral treatment for hepatitis C virus infection in people with HIV. Clinical Infectious Diseases. 2025; in press.
- Ioannou GN, Beste LA, Green PK, et al. Increased risk for hepatocellular carcinoma persists up to 10 years after HCV eradication in patients with baseline cirrhosis or high FIB-4 scores. Gastroenterology. 2019 Nov;157(5):1264-1278.e4.