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 [
[1]
]. 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 [
[2]
]. 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 [
[3]
] and suppressing HBV DNA levels with nucleos(t)ide analogues (NUCs) may lower the
risk of HCC recurrence with improved survival [
- 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.
Oncologist. 2020; 25https://doi.org/10.1634/theoncologist.2019-0944
4
,
5
,
6
,
7
]. 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 [
[8]
]. 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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References
- 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.Lancet. 2012; 380: 2095-2128https://doi.org/10.1016/S0140-6736(12)61728-0
- Trends in incidence, diagnosis, treatment and survival of hepatocellular carcinoma in a low-incidence country: data from the Netherlands in the period 2009–2016.Eur J Cancer. 2020; 137: 214-223https://doi.org/10.1016/j.ejca.2020.07.008
- Early and late recurrence of hepatitis B virus-associated hepatocellular carcinoma.Oncologist. 2020; 25https://doi.org/10.1634/theoncologist.2019-0944
- Impact of antiviral therapy on the survival of patients after major hepatectomy for hepatitis B virus-related hepatocellular carcinoma.Arch Surg. 2011; 146: 675-681https://doi.org/10.1001/archsurg.2011.125
- Association between nucleoside analogues and risk of hepatitis B virus-related hepatocellular carcinoma recurrence following liver resection.JAMA - J Am Med Assoc. 2012; 308: 1906-1913https://doi.org/10.1001/2012.jama.11975
- Effect of antiviral treatment with nucleotide/nucleoside analogs on postoperative prognosis of hepatitis B virus-related hepatocellular carcinoma: a two-stage longitudinal clinical study.J Clin Oncol. 2013; 31: 3647-3655https://doi.org/10.1200/JCO.2012.48.5896
- Antiviral therapy improves postoperative survival in patients with hepatocellular carcinoma.Ann Surg. 2015; 261: 56-66https://doi.org/10.1097/SLA.0000000000000858
- 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.J Viral Hepat. 2021; 28: 205-208https://doi.org/10.1111/jvh.13394
- Induction of IFN-λ 3 as an additional effect of nucleotide, not nucleoside, analogues: a new potential target for HBV infection.Gut. 2018; 67: 362-371https://doi.org/10.1136/gutjnl-2016-312653
- Immunomodulatory mechanism of acyclic nucleoside phosphates in treatment of hepatitis B virus infection.Hepatology. 2020; 71: 1533-1545https://doi.org/10.1002/hep.30956
- Prediction of sustained response after nucleo(s)tide analogue cessation using HBsAg and HBcrAg levels: a multicenter study (CREATE).Clin Gastroenterol Hepatol. 2020; https://doi.org/10.1016/j.cgh.2020.12.005
- Hepatocellular carcinoma incidence with tenofovir versus entecavir in chronic hepatitis B: a systematic review and meta-analysis.Lancet Gastroenterol Hepatol. 2020; 5: 1039-1052https://doi.org/10.1016/S2468-1253(20)30249-1
- The different effects of nucleotide and nucleoside analogues on the prognosis of HBV-related HCC after curative resection.J Gastrointest Surg. 2020; https://doi.org/10.1007/s11605-020-04633-3
- Tenofovir decrease hepatocellular carcinoma recurrence in chronic hepatitis B patients after liver resection.Infect Agent Cancer. 2018; 13https://doi.org/10.1186/s13027-018-0191-8
- Impact of tenofovir antiviral treatment on survival of chronic hepatitis B related hepatocellular carcinoma after hepatectomy in Chinese individuals from Qingdao municipality.Medicine (Baltimore). 2020; 99: e21454https://doi.org/10.1097/MD.0000000000021454
- The efficacies of entecavir and tenofovir in terms of enhancing prognosis after curative treatment of hepatitis B virus-related hepatocellular carcinoma.Eur J Intern Med. 2021; https://doi.org/10.1016/j.ejim.2021.02.019
- Tenofovir versus entecavir on recurrence of hepatitis B virus–related hepatocellular carcinoma after surgical resection.Hepatology. 2021; 73: 661-673https://doi.org/10.1002/hep.31289
- Low-level viremia and the increased risk of hepatocellular carcinoma in patients receiving entecavir treatment.Hepatology. 2017; 66: 335-343https://doi.org/10.1002/hep.28916
Article info
Publication history
Published online: May 19, 2021
Accepted:
May 1,
2021
Received:
April 27,
2021
Identification
Copyright
© 2021 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
