Liver scarring before treatment for hepatitis C predicts cancer risk
Study researchers tracked fibrosis markers after virus was cleared
People with hepatitis C who show higher values of liver scarring markers before starting antiviral therapy are significantly more likely to later develop hepatocellular carcinoma (HCC), the most common form of liver cancer, a study shows.
The higher risk persisted even after adjusting for post-treatment liver scarring markers, with patients with elevated liver scarring markers remaining at a higher risk even after showing significant reductions in these markers following antiviral therapy.
These findings highlight “the importance of continued HCC surveillance” in individuals who show signs of greater liver scarring before starting hepatitis C treatment, researchers wrote.
The study, “Pre‐Treatment Liver Stiffness Is a Stronger Predictor of Hepatocellular Carcinoma Development Than Post‐Treatment Liver Stiffness After Hepatitis C Virus Eradication,” was published in the journal Hepatology Research.
Chronic infection with hepatitis C virus a leading cause of liver inflammation
Chronic infection with the hepatitis C virus, or HCV, is a leading cause of liver inflammation and scarring (fibrosis), which can progress to HCC if left untreated.
Antiviral medications can now treat nearly all cases of hepatitis C, leading to what’s called a sustained virologic response (SVR) — meaning the virus is no longer detectable in the blood.
“Nevertheless, the risk of HCC is not entirely eliminated, even after achieving SVR, particularly in patients with advanced fibrosis or cirrhosis [irreversible liver fibrosis],” the researchers wrote. “Therefore, optimizing HCC surveillance strategies for patients with post‐SVR disease remains an important clinical challenge.”
Clinicians often rely on noninvasive markers that help assess liver damage and estimate liver cancer risk. These include the liver stiffness measurement (LSM), a test that estimates how hard or scarred the liver tissue is based on how quickly sound waves travel through it, and the fibrosis-4 (FIB-4) index, a blood test score calculated from a person’s age and routine liver enzyme levels.
However, “whether pre‐treatment or post‐treatment LSM and FIB‐4 values are more valuable in predicting post-SVR HCC risk” and whether “a reduction in these markers after SVR translates into a decreased risk of HCC development” remains unclear, the researchers wrote.
Risk of cancer can persist even when fibrosis lessens after treatment
To learn more, a team of researchers at the University of Tokyo retrospectively analyzed data from 501 people with chronic hepatitis C who achieved SVR after receiving antiviral therapy at their university hospital between March 2012 and February 2022.
The team tracked each patient’s liver stiffness and FIB-4 scores before treatment and again during follow-up visits after the virus was cleared. Participants were then monitored for an average of nearly six years to track the development of HCC.
Participants’ median age was 66 years, and 41.7% were men. A small proportion had diabetes (8.8%) or showed heavy alcohol use (4.8%). Both the median LSM values and FIB-4 index indicated mild to moderate liver fibrosis before treatment.
After therapy, most patients showed clear signs of liver recovery. LSM values dropped significantly at a rate of 4.6% per year, with 80.4% of participants showing reductions. The FIB-4 index declined at a rate of 2.6% per year, with reductions observed in 70.8% of cases.
Despite these gains, 28 individuals (about 6%) developed HCC during a mean follow-up of 5.7 years. Among them, 22 (78.6%) had shown decreases in liver stiffness and 20 (71.4%) had lower FIB-4 scores after treatment — showing that even when fibrosis lessens after treatment, the risk of cancer can persist.
Importantly, by the time the cancer appeared, 57.1% of those who developed HCC had LSM or FIB-4 values that had fallen below the usual thresholds for advanced fibrosis (10 kilopascals, or kPa, for LSM and 3.25 for FIB-4).
Likelihood of liver cancer closely tied to how scarred liver was before treatment
The likelihood of liver cancer was instead closely tied to how scarred the liver was before treatment began.
Participants with pretreatment LSM values of 10 kPa or higher were significantly more likely to develop HCC after five years than those with lower LSM values (13.6% vs. 1.2%).
Likewise, a significantly greater proportion of people with pretreatment FIB-4 scores of at least 3.25 were estimated to develop the cancer after five years relative to those with lower scores (11.1% vs. 2.7%).
“Elevated LSM or FIB‐4 level before treatment may reflect severe inflammation and advanced fibrosis, leading to the activation of [cancer-related] signaling and cumulative DNA damage, which persists after SVR,” the team wrote.
Further statistical analyses showed that higher pretreatment LSM values were significantly linked to an eightfold increase in the risk of developing HCC, while higher pretreatment FIB-4 index values were linked to a 29% higher risk. No such associations were found for post-treatment LSM or FIB-4 values.
“These results suggest that baseline LSM and FIB-4 are more important than follow-up values for predicting HCC development,” the researchers wrote.
Older age, higher body-mass index (a ratio of height and weight), and heavy alcohol use were also significantly associated with increased HCC risk.
“These results underscore the importance of monitoring patients with higher pre‐treatment LSM or FIB-4 values, as they remain at risk of HCC, even after showing significant reductions in LSM and FIB‐4 values at follow‐up after achieving SVR,” the researchers wrote.
While “LSM has superior predictive power for assessing post-SVR cancer risk,” FIB-4 may serve “as a valuable alternative for HCC risk stratification” in settings where liver stiffness testing is not readily available, they added.
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