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Antiviral therapy after curative treatment of hepatocellular carcinoma in patients with chronic hepatitis B infection: Is tenofovir or entecavir preferred?

      Hepatitis B remains a major health problem. Globally, approximately 240 million persons are chronically infected (HBsAg positive). Prevalence is decreasing in highly endemic countries due to better socioeconomic circumstances and vaccination programs. However, prevalence and incidence in several low-endemic European countries are changing, owing to higher HBsAg prevalence rates in migrants and refugees from outside Europe compared with the indigenous population. Hepatocellular carcinoma (HCC) is one of the major and most deadly consequences of chronic hepatitis B. Globally, deaths from HCC are estimated at 340,000 per year [
      • Lozano R
      • Naghavi M
      • Foreman K
      • Lim S
      • Shibuya K
      • Aboyans V
      • et al.
      Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: A systematic analysis for the Global Burden of Disease Study 2010.
      ]. Although several new treatment options such as transarterial chemo- or radioembolization and systemic therapies have been introduced in the last decades with promising results, these treatments are generally used in a palliative setting. Only a minority of patients are elegible for curative treatment (liver transplantation, surgical resection and -sometimes- radiofrequency ablation). In a nationwide cohort study conducted in the Netherlands between 2009-and 2016, these curative treatment options were applied in only 6%, 15% and 14% of patients [
      • Reinders MTM
      • van Meer S
      • Burgmans MC
      • de Jong KP
      • Klümpen HJ
      • de Man RA
      • et al.
      Trends in incidence, diagnosis, treatment and survival of hepatocellular carcinoma in a low-incidence country: data from the Netherlands in the period 2009–2016.
      ]. Unfortunately, even in case of resection or radiofrequency ablation, risk of recurrent intrahepatic HCC is high due to persistence of the underlying liver disease. High levels of hepatitis B virus (HBV) viremia are associated with higher rates of HCC recurrence after surgical resection [
      • Wang M
      • Li C
      • Liang L
      • Xing H
      • Sun L
      • Quan B
      • et al.
      Early and late recurrence of hepatitis B virus-associated hepatocellular carcinoma.
      ] and suppressing HBV DNA levels with nucleos(t)ide analogues (NUCs) may lower the risk of HCC recurrence with improved survival [
      • Chan ACY
      • Chok KSH
      • Yuen WK
      • Chan SC
      • Poon RTP
      • Lo CM
      • et al.
      Impact of antiviral therapy on the survival of patients after major hepatectomy for hepatitis B virus-related hepatocellular carcinoma.
      ,
      • Wu CY
      • Chen YJ
      • Ho HJ
      • Hsu YC
      • Kuo KN
      • Wu MS
      • et al.
      Association between nucleoside analogues and risk of hepatitis B virus-related hepatocellular carcinoma recurrence following liver resection.
      ,
      • Yin J
      • Li N
      • Han Y
      • Xue J
      • Deng Y
      • Shi J
      • et al.
      Effect of antiviral treatment with nucleotide/nucleoside analogs on postoperative prognosis of hepatitis B virus-related hepatocellular carcinoma: a two-stage longitudinal clinical study.
      ,
      • Huang G
      • Lau WY
      • Wang ZG
      • Pan ZY
      • Yuan SX
      • Shen F
      • et al.
      Antiviral therapy improves postoperative survival in patients with hepatocellular carcinoma.
      ]. The persistent risk of HCC recurrence despite NUC therapy-mediated HBV DNA suppression may be partially attributed to persistent intrahepatic replication, as illustrated by the observation that higher serum viral antigen levels are associated with reduced recurrence-free survival independent from HBV DNA load [
      • Beudeker BJB
      • Groothuismink ZMA
      • de Man RA
      • Witjes CDM
      • van der Eijk AA
      • Boonstra A
      • et al.
      Hepatitis B core-related antigen levels predict recurrence-free survival in patients with HBV-associated early-stage hepatocellular carcinoma: results from a Dutch long-term follow-up study.
      ]. Pending the availability of novel antiviral agents that specifically target other aspects of the viral life-cycle, optimizing NUC therapy remains the primary focus.

      Keywords

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