Vol:.(1234567890) Hepatology International (2021) 15:1028–1029 https://doi.org/10.1007/s12072-021-10225-3 1 3 LETTER TO THE EDITOR Evidence of nucleos(t)ide analogue (NUC) therapy in HBV DNA negative decompensated cirrhosis Shahinul Alam 1  · Md. Abdullah Saeed Khan 2  · Mobin Khan 3 Received: 4 May 2021 / Accepted: 18 June 2021 / Published online: 16 July 2021 © Asian Pacific Association for the Study of the Liver 2021 To the editor: To fnd an answer to the question of starting nucleos(t)ide analogues (NUC) in hepatitis B virus (HBV) DNA nega- tive (< 200 IU/ml) decompensated cirrhosis patients, we looked into the three most commonly used guidelines for the prevention, diagnosis, and treatment of chronic hepa- titis B published by American Association for the Study of Liver Disease (AASLD), European Association for the Study of Liver (EASL), and Asian-Pacifc Association for the Study of Liver (APASL). All of these guidelines recom- mended starting anti-viral treatment irrespective of HBV DNA counts for HBV-associated decompensated cirrhosis. Although the evidence grading for these recommendations varied from cohort or case–control analytic studies to meta- analyses, the grade of recommendations was invariably strong. However, none of the studies seem to provide con- crete systematic proof for the benefts of using NUC in the HBV DNA negative decompensated cirrhosis. The meta-analyses by Singal et al. [1] and Peng et al. [2] gathered pieces of evidence on the efcacy and safety of oral anti-viral agents in HBV-related decompensated cirrhosis patients published before 2012. However, their studies do not provide a separate analysis on the beneft of NUC in patients who were HBV DNA negative. In fact, most of the studies either explicitly excluded cases with undetectable HBV DNA or used HBV DNA negativity as an outcome. We found only one study by Das et al. [3] providing evidence for the inclusion of HBV DNA negative decompensated cases [3]. This study conducted a comparative analysis of untreated and treated HBV infected decompensated cirrhotic patients using a retrospective-prospective cohort design in West Bengal, India. The HBV DNA count was available in 23% cases and the described ranges suggest inclusion of patients with HBV DNA level as low as 50 copies/ml. How- ever, an analysis of only those patients is unavailable from their results. To further our exploration of the latest evidence regard- ing the question, we searched the freely available databases using the following keywords: “Nucleoside Analogue or Oral Antiviral” AND “Decompensated Cirrhosis” AND “baseline” AND “HBV DNA” AND “Negative OR Unde- tectable”. Unfortunately, the search yielded no studies with a specifc enrollment of HBA DNA negative decompensated cirrhosis patients or describing separate analyses for such cases. Furthermore, among the guidelines mentioned ear- lier, only the 2015 guidelines [4] by APASL reasoned that anti-viral treatment is indicated in decompensated cirrhosis patients irrespective of HBV DNA level to prevent reactiva- tion. Still, evidence of reactivation in patients with DNA negativity is not clear. However, prolonged suppression of covalently closed circular DNA (ccc DNA) has the potential of preventing further damage of liver by inhibiting reactiva- tion of the virus and reducing production of viral proteins thus improving immune function [5]. Hence, we recommend that specifc studies on the beneft of using NUC in HBV DNA negative decompensated cir- rhosis should be carried out before giving strong positive recommendations. References 1. Singal AK, Fontana RJ. Meta-analysis: Oral anti-viral agents in adults with decompensated hepatitis B virus cirrhosis. Aliment Pharmacol Ther. 2012;35(6):674–89. 2. Peng CY, Chien RN, Liaw YF. Hepatitis B virus-related decom- pensated liver cirrhosis: benefts of antiviral therapy. J Hepatol. 2012;57(2):442–50. https://doi.org/10.1016/j.jhep.2012.02.033. * Shahinul Alam shahainul67@yahoo.com 1 Bangabandhu Sheikh Mujib Medical University, Shahbag, Dhaka 1000, Bangladesh 2 Infectious Disease Hospital, Dhaka, Bangladesh 3 The Liver Center, Dhaka 1209, Bangladesh