Who is at risk for liver cancer after hepatitis C treatment?
Some people with cirrhosis of the liver remain at risk of developing liver cancer even after treatment for hepatitis C, according to the results of a study presented at the AASLD Liver Meeting. The biggest risk factor is unsuccessful treatment that did not lead to a cure. A related study found that among people who were cured, risk factors differ for people with and without cirrhosis.
Over years or decades, chronic infection with hepatitis C virus (HCV) can lead to the development of cirrhosis and hepatocellular carcinoma (HCC), the most common type of liver cancer. . People who are successfully treated for hepatitis C are less likely to develop HCC, but there are still some risks, especially for those who have already progressed to advanced fibrosis or cirrhosis. Liver cancer is often diagnosed late, when it is more difficult to treat, and being able to predict who is at risk could allow for targeted surveillance and prompt treatment.
Liver cancer and cirrhosis
In the first study, Loreta Kondili, MD, PhD, of the Istituto Superiore Di Sanità in Rome, and colleagues assessed the medium and long-term impact of direct-acting antiviral therapy (DAA) on the development of cancer of the liver in patients with hepatitis C. with cirrhosis.
This analysis included 2,214 participants from the Italian PITER cohort who were treated with DAAs after developing cirrhosis and were followed for at least one year. Most (93%) achieved a sustained virologic response (SVR), which is considered a cure. The median age was 64. People who had received a liver transplant or who had already been diagnosed with HCC were excluded.
At a median follow-up of 30 months after the end of treatment, 149 people (6.7%) developed HCC for the first time, including 119 (5.8%) who had achieved SVR and 30 (20%) who had not done so. This meant that those who weren’t cured had a more than seven times higher risk of new liver cancer. In addition, people without SVR developed liver cancer sooner after stopping treatment. Two years after treatment, 98% of people who achieved SVR were still alive without HCC, compared with only 65% of those who were not cured.
Among people who achieved SVR, other risk factors for liver cancer included HCV genotype 3, low platelet count, low albumin levels, and advanced age. Male sex, hepatitis B coinfection, and diabetes were also linked to an increased risk of HCC, but these associations did not reach statistical significance. No association was observed with liver stiffness (a measure of the severity of fibrosis), body mass index, alcohol consumption, HIV co-infection, liver fat, l use of sofosbuvir or ribavirin, or previous treatment with interferon therapy.
At the time of diagnosis, 80% of people with liver cancer had intermediate to advanced liver cancer. During follow-up, 26% of patients with HCC died and 7.6% received a liver transplant. Having more advanced fibrosis prior to DAA treatment, as determined by measurements of hepatic stiffness, was an independent predictor of death.
“Failure to achieve SVR after DAA treatment is significantly associated with the likelihood of developing de novo HCC in the first two years, ”the researchers concluded, stressing the importance of continuous monitoring and prompt treatment of cancer.
Liver cancer after SVR
A second study, led by Jennifer Kramer, PhD, MPH, of the Center for Innovations in Quality, Effectiveness and Safety, and colleagues looked at risk factors for liver cancer in people cured of hepatitis C, assessed one year and two years after treatment. .
This analysis included 98,612 US veterans with hepatitis C who achieved SVR with DAA treatment between January 2014 and December 2018. Almost all were men, half were white, 39% were black, and the average age was 61 years old. Almost a third had cirrhosis at the time. treatment. People with and without cirrhosis were demographically similar, but the first group had higher bilirubin and albumin levels and higher rates of diabetes, hypertension, and obesity.
A total of 2,298 people developed HCC during the study period. Annual incidence rates for people with cirrhosis were 1.6% in the first year after treatment and 1.9% in the second year, compared to 0.21% and 0.27% , respectively, for people without cirrhosis.
The researchers found that the risk factors for liver cancer differed depending on the state of the cirrhosis.
Among people with cirrhosis, predictors of HCC at 12 months included male sex, Caucasian race, HCV genotype 3, longer duration of cirrhosis, higher bilirubin levels, and the presence of esophageal varices (veins enlarged). Changes in albumin levels and worsening fibrosis also predicted the risk of HCC. However, race, HCV genotype and bilirubin were no longer significant predictors at 24 months as changes in hemoglobin became a significant factor. Non-smokers had a lower risk of liver cancer.
In people without cirrhosis, in contrast, metabolic factors such as diabetes and hypertension, as well as worsening fibrosis, were strongly associated with the risk of liver cancer at both time points.
“In a cohort of patients with virologically cured HCV infection, the risk factors for HCC were different in patients with and without cirrhosis,” the researchers concluded. “In patients with cirrhosis, they were primarily related to disease severity, while metabolic traits were important in patients without cirrhosis.”
These findings, they added, could inform decisions about liver cancer surveillance in people recovered from hepatitis C. Since risk factors can change over time, they suggested that repeated evaluation at two years “is practical and may improve risk stratification” regardless of their state of cirrhosis. .
Click here to read Kondili’s summary.
Click here to read Kramer’s summary.
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