Secondary prevention for hepatocellular carcinoma in patients with chronic hepatitis B: are all the nucleos(t)ide analog
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REVIEW
Secondary prevention for hepatocellular carcinoma in patients with chronic hepatitis B: are all the nucleos(t)ide analogues the same? Terry Cheuk-Fung Yip1,2,3 • Jimmy Che-To Lai1,2,3 • Grace Lai-Hung Wong1,2,3
Received: 7 August 2020 / Accepted: 24 August 2020 Ó The Author(s) 2020
Abstract Reducing the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) is the key ultimate goal set in essentially all treatment guidelines. There has been solid evidence supporting the relationship between serum hepatitis B virus (HBV) DNA level and risk of HCC. Antiviral treatment with oral nucleos(t)ide analogues (NAs) leads to sustained viral suppression and hence is often adopted as the secondary prevention for HCC in CHB patients. The first-generation NA, lamivudine, reduced the risk of HCC at 3 years compared to placebo; yet, its high emergence of antiviral resistance has made it no longer recommended in the international guidelines. Recent heated debate is about the two current first-line NAs—entecavir and tenofovir disoproxil fumarate (TDF)—Are they just as good to reduce HCC risk in CHB patients? A handful of cohort studies show two different kinds of observations—TDF is better than entecavir in lowering HCC risk, or these two NAs have led to similarly low risk of HCC. Tenofovir alafenamide (TAF), a modified version of TDF higher rate of ALT normalization, would be another potent nucleotide analogue is the treatment of choice for secondary prevention for HCC.
& Grace Lai-Hung Wong [email protected] 1
Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30-32 NganShing Street, Shatin, Hong Kong SAR, China
2
Medical Data Analytic Centre (MDAC), Hong Kong SAR, China
3
Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
Keywords Cirrhosis Entecavir Tenofovir disoproxil fumarate Tenofovir alafenamide Abbreviations ALT Alanine aminotransferase CHB Chronic hepatitis B CI Confidence intervals DM Diabetes mellitus HBeAg Hepatitis B e antigen HBsAg Hepatitis B surface antigen HBV Hepatitis B virus HCC Hepatocellular carcinoma INR International normalized ratio IQR Interquartile range SHR Subdistribution hazard ratio TDF Tenofovir disoproxil fumarate TAF Tenofovir alafenamide
Introduction Hepatocellular carcinoma (HCC) is a major global health problem because of its high incidence rate and unfavorable clinical course [1]. In 2018, it was the sixth commonest cancer worldwide, with incidence of more than 841,000 cases/year, and the fourth leading cause of cancer-related deaths, with an estimated 781,000 deaths/ year [2]. While HCC has a diverse etiology, chronic hepatitis B virus (HBV) infection is the key determinants in the most high-risk HCC areas (China, Eastern Africa) [2]. Although the risk factors for HCC development are well-known and great advances have been made through
123
J Gastroenterol
HBV vaccinations as primary prevention for HCC, the overall incidence and mortality rates of HCC
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