HBV Genotyping, Histopathology May Aid HCC Risk Assessment

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Genotyping and histological assessment may improve outcome prediction and help guide decisions about hepatocellular carcinoma (HCC) screening in patients with chronic hepatitis B, according to findings from a recent study.¹

Results suggest histopathology and hepatitis B virus (HBV) genotype are strongly associated with clinical outcomes, potentially aiding risk assessment and helping to identify patients who would benefit from HCC screening.¹

“Chronic HBV infection is a major cause of liver cirrhosis and HCC,” Magnus Lindh, a professor and chief physician in the department of infectious diseases at the University of Gothenburg in Sweden, and colleagues wrote.¹ “The course of the infection is highly variable, and the main task for clinicians is to identify patients who are at risk for complications, in order to prevent necroinflammation and HCC by antiviral therapy and identify curable HCC by screening programs.”

According to the World Health Organization, an estimated 254 million people were living with chronic hepatitis B infection in 2022, with 1.2 million new infections occurring each year and resulting in an estimated 1.1 million deaths, mostly from cirrhosis and HCC.²

To investigate the impact of HBV genotype, histopathology, and HBV DNA level at baseline on clinical outcomes, investigators conducted a long-term follow-up study of patients who participated in a previous cross-sectional study at the Infectious Diseases Clinic of Sahlgrenska University Hospital in Sweden. The study was conducted from 1993-1995 and included 160 patients with chronic HBV who were HBsAg positive for > 6 months and not co-infected with hepatitis C or D viruses, or HIV.¹

The present analysis included 100 of these participants with virological and biochemical data from ≥ 1 time point between 2000 and 2023. Investigators divided these patients into 4 groups based on clinical outcomes: loss of HBsAg; HBeAg-negative infection (ENI, previously termed ‘inactive carrier’); ongoing long-term nucleoside analogue treatment (NUC); and HCC or liver transplant.¹

At baseline, the mean age was 35.9 years and 23% of patients were HBeAg-positive, 67% of whom had genotype C. Investigators noted 43% of patients experienced HBsAg loss and 30% achieved ENI, but 7% developed HCC. HBsAg loss or ENI was achieved by 26% of HBeAg-positive patients compared with 88% of HBeAg-negative patients.¹

Among 20 patients with genotype A, 75% showed HBsAg loss and 20% had ENI at follow-up. In 53 patients with genotype D, loss of HBsAg was achieved in 42% and ENI in 38%, 19% were on long-term NUC treatment, and a single patient developed HCC. Among 18 patients with genotype B, 33% lost HBsAg, 28% reached ENI, 22% were on NUC, and 17% developed HCC. Investigators pointed out none of the 9 patients with genotype C achieved HBsAg loss, 22% reached ENI, 44% were on long-term NUC, and 33% developed HCC.¹

In univariate analysis, the histological activity index (HAI) (P <.001) and the individual inflammation (P = .004) and fibrosis (P = .002) scores were associated with the NUC or HCC outcomes. In multiple logistic regression analyses including the genotype or the HBV DNA level as an independent parameter, HAI was associated with HCC.¹

Further analysis revealed both HBsAg loss and HCC were associated with HBV genotype and baseline HBV DNA level, and HCC was also linked to histological score.¹

Investigators applied ROC curve analyses for different outcomes and found both PAGE-B and REACH-B risk scores were relatively poor predictors of HBsAg loss and relatively good predictors of HCC outcome. Of note, they found models based on the baseline parameters that were significantly associated with outcomes in the multiple logistic regression analysis were better predictors. A model based only on HBV genotype and histological score was found to be better for HCC prediction than both the REACH-B and PAGE-B risk scores.1

“This long-term follow-up study of patients with chronic hepatitis B revealed a strong impact of both histopathology and HBV genotype on clinical outcomes, suggesting that genotyping and liver biopsy may improve decisions about follow-up and HCC surveillance,” investigators concluded.¹ “Additional long-term follow-up studies are required to corroborate our findings, and to evaluate if the addition of genotype and histopathology to the risk assessment might improve the identification of patients who do not need HCC screening at all and of high-risk patients who might benefit from screening with magnetic resonance imaging.”

References

1. ^{Eilard A, Ringlander J, Andersson ME, et al. Long-Term Outcome of Chronic Hepatitis B—Histological Score and Viral Genotype Are Important Predictors of Hepatocellular Carcinoma. Journal of Viral Hepatitis. https://doi.org/10.1111/jvh.70008}
2. ^{World Health Organization. Hepatitis B. April 9, 2024. Accessed February 5, 2025. https://www.who.int/news-room/fact-sheets/detail/hepatitis-b}