Lower liver cancer risk with antiviral therapy in chronic hepatitis B patients with normal to minimally elevated ALT and no cirrhosis

Abstract

For chronic hepatitis B (CHB), alanine aminotransferase (ALT) ≥2 × upper limit of normal (ULN) is often used as a major criteria to initiate treatment in absence of cirrhosis, though patients with lower ALT may not be free from future risk of hepatocellular carcinoma (HCC). We aimed to examine the effect of antiviral therapy on HCC incidence based on ALT levels.We performed a retrospective study on 3665 patients consisting of United States and Taiwanese REVEAL-HBV cohort who were consecutive, treatment-naïve, noncirrhotic CHB patients aged ≥40 years. Patients were categorized by ALT cutoffs (≥2 × ULN vs <2 × ULN) and subgrouped by treatment status. Kaplan–Meier and Cox proportional hazards models were used to calculate cumulative incidence and hazard ratio (HR) of HCC adjusting for REACH-B scores.A total of 202 patients developed HCC. Antiviral treatment significantly reduced HCC risk: HR 0.24, 95% confidence interval 0.10–0.58; P = 0.001. HCC incidence per 100,000 person-years was significantly higher in untreated versus treated patients, even for those with ALT < 2 × ULN: 314.46 versus 0 per 100,000 person-years, P = 0.0042. For patients with Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) ≥ 2000 IU/mL, the number-needed-to-treat (NNT) were 15 and 14 to prevent 1 incident HCC at year 10 for patients with ALT < 2 × ULN and ≥2 × ULN, respectively.After adjustment by REACH-B score, antiviral treatment significantly decreased HCC incidence even in patients with ALT < 2 × ULN. NNT to prevent 1 incident HCC after 10 years of therapy was low (14–15) in patients with mildly elevated HBV DNA ≥ 2000 IU/mL regardless of ALT levels.

High risk of clinical events in untreated HBeAg‐negative chronic hepatitis B patients with high viral load and no significant ALT elevation

“…The 3‐year preliminary results of paired biopsies showed that TDF was associated with significantly reduced risks of fibrosis progression and significantly lower median necroinflammatory scores, compared to placebo. Our results are also consistent with a recent observational study, which showed that antiviral treatment significantly decreased HCC incidence in noncirrhotic patients with ALT < 2 ULN if they were older than 40 years with HBV DNA > 2000 IU/mL . Another study in both community and real‐life clinical cohorts also reported a significant reduction in HCC incidence with NUC therapy regardless of ALT elevation .…”

Gamma‐glutamyl transpeptidase‐to‐platelet ratio is an independent predictor of hepatitis B virus‐related liver cancer

“…In addition, well‐known risk factors of HCC development, such as high HBV DNA level, HBeAg, and high ALT levels were not selected as independent factors in our study. This phenomenon can be explained in part by that the potent antiviral agents can suppress viral replication and necroinflammation promptly and completely in this era of active antiviral therapy . However, our study is still not free from false negativity because of the potential selection bias of retrospective study design.…”

“…This phenomenon can be explained in part by that the potent antiviral agents can suppress viral replication and necroinflammation promptly and completely in this era of active antiviral therapy. 21,22 However, our study is still not free from false negativity because of the potential selection bias of retrospective study design.…”

Mechanisms and clinical behavior of hepatocellular carcinoma in HBV and HCV infection and alcoholic and non-alcoholic fatty liver disease

“…Treatment does not appear to have a significant clinical impact on patients with low levels of viremia (HBV-DNA < 2000 IU/mL) [67] . A large retrospective study of non-cirrhotic positive HBV patients showed that the incidence of HCC is significantly lower in patients receiving antiviral therapy regardless of the levels of ALT [68] . In addition, the required number of patients to be treated (NNT) to prevent 1 case of HCC 10 years after initiation of treatment was found to be similar both in the group of patients with ALT < 2 ULN (NNT = 14) and in those with ALT ≥ 2 ULN (NNT = 15) [68] .…”

“…A large retrospective study of non-cirrhotic positive HBV patients showed that the incidence of HCC is significantly lower in patients receiving antiviral therapy regardless of the levels of ALT [68] . In addition, the required number of patients to be treated (NNT) to prevent 1 case of HCC 10 years after initiation of treatment was found to be similar both in the group of patients with ALT < 2 ULN (NNT = 14) and in those with ALT ≥ 2 ULN (NNT = 15) [68] . These data appear to confirm that hyper-ALT should not be considered a necessary requirement for antiviral treatment in patients with HBV-DNA > 2000 IU/mL [69] .…”