Hepatocellular Carcinoma Risk of Compensated Cirrhosis Patients with Elevated HBV DNA Levels according to Serum Aminotransferase Levels

Abstract

Sometimes, hepatitis B virus (HBV)-related cirrhotic patients with normal aminotransferase levels are closely followed-up for the elevation of aminotransferase levels instead of prompt antiviral therapy (AVT). We analyzed the long-term hepatocellular carcinoma (HCC) risk according to the aminotransferase levels in a retrospective cohort of 1,468 treatment-naïve, HBV-related, compensated cirrhosis patients with elevated HBV DNA levels (≥2,000 IU/mL). Based on aminotransferase levels, patients were categorized into normal (< 40 U/L, n = 364) and elevated group (≥40 U/L, n = 1,104). During a median of 5.3 yr of follow-up (range: 1.0-8.2 yr), HCC developed in 296 (20%) patients. The 5-yr cumulative HCC incidence rate was higher in patients with elevated aminotransferase level, but was not low in normal aminotransferase level (17% vs. 14%, P = 0.004). During the follow-up, 270/364 (74%) patients with normal aminotransferase levels experienced elevation of aminotransferase levels, and AVT was initiated in 1,258 (86%) patients. Less patients with normal aminotransferase levels received AVT (70% vs. 91%, P < 0.001) and median time to start AVT was longer (17.9 vs. 2.4 months, P < 0.001). AVT duration was an independent factor associated with HCC, and median duration of AVT was shorter (4.0 vs. 2.6 yr, P < 0.001) in patients with normal aminotransferase levels. The HCC risk of compensated cirrhosis patients with normal aminotransferase level is not low, and AVT duration is associated with lowered HCC risk, indicating that prompt AVT should be strongly considered even for those with normal aminotransferase levels.

The risk of hepatocellular carcinoma among chronic hepatitis B virus‐infected patients outside current treatment criteria

“…When assessed by specific treatment criteria, the 5‐year cumulative HCC incidence rate was generally high for patients with cirrhosis [15.1%, 13.9% and 8.2% for those with elevated HBV DNA levels (>2000 IU/mL), low‐level viremia (20‐2000 IU/mL) and undetectable HBV DNA (<20 IU/mL)]. This finding suggests that cirrhotic patients require special attention for their increased HCC risk . Specifically, cirrhotic patients with low‐level viremia were at increased risk.…”

The Author's Response: Anti-Viral Therapy for Compensated Liver Cirrhosis Patients with Normal Alanine Aminotransferase

“…Decision to treat is based on an assessment of the risks and benefits of the treatment. Although there are still some concerns over long-term safety of NUCs, given the potential harms and potential benefits of AVT, and data from our study ( 1 ), prompt initiation of AVT seems reasonable approach for cirrhotic patients with elevated HBV DNA levels, even for those with normal ALT levels. Lastly, quantitative hepatitis B surface antigen levels are not measured for our cohort.…”

“…We appreciate the valuable comment by Khosravi et al on our recently published article ( 1 ). First, Khosravi et al, suggested analyzing the impact of body mass index (BMI) on the risk of hepatocellular carcinoma (HCC).…”

“…This recommendation is based on the well-documented observation that ALT levels can be normal in patients with cirrhosis ( 7 8 ). As we stated in the limitation part of the published article ( 1 ), randomized controlled trials are needed to provide higher level of evidence. Yet, nucleos(t)ide analogues (NUC) are generally safe and well-tolerated oral medications ( 10 ), and long-term NUC therapy has been shown to reverse cirrhosis ( 11 ), and reduce the incidence of HCC ( 12 13 ).…”

Letter to the Editor: Should We Really Take Anti-Viral Therapy into Account in Chronic Hepatitis B Patients with Normal Liver Function?

“…We read with a great interest the article written by Lee and colleagues entitled "Hepatocellular Carcinoma Risk of Compensated Cirrhosis Patients with Elevated HBV DNA Levels according to Serum Aminotransferase Levels" which was recently published in your Journal of Korean Medical Science ( 1 ). The authors concluded the beneficial effects of prescribing appropriate anti-viral therapy (AVT) for reducing HCC risk in cirrhotic patients with elevated HBV DNA and normal aminotransferase levels.…”