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Virological suppression does not prevent the development of hepatocellular carcinoma in HBeAg-negative chronic hepatitis B patients with cirrhosis receiving oral antiviral(s) starting with lamivudine monotherapy: results of the nationwide HEPNET.Greece cohort study
  1. George V Papatheodoridis1,
  2. Spilios Manolakopoulos1,
  3. Giota Touloumi2,
  4. Georgia Vourli2,
  5. Maria Raptopoulou-Gigi3,
  6. Irini Vafiadis-Zoumbouli4,
  7. Themistoklis Vasiliadis5,
  8. Kostas Mimidis6,
  9. Charalambos Gogos7,
  10. Ioannis Ketikoglou8,
  11. Emanuel K Manesis9,
  12. for the HEPNET.Greece Cohort Study Group
  1. 12nd Department of Internal Medicine, Athens University Medical School, Hippokration General Hospital of Athens, Athens, Greece
  2. 2Department of Hygiene & Epidemiology, Athens University Medical School, Athens, Greece
  3. 32nd Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece
  4. 41st Department of Propedeutic Medicine, Athens University Medical School, Laikon General Hospital of Athens, Athens, Greece
  5. 52nd Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
  6. 61st Department of Internal Medicine, Democritus University of Thrace, Komotini, Greece
  7. 7Department of Internal Medicine, University of Patras, Patras, Greece
  8. 8Department of Internal Medicine, Hippokration General Hospital of Athens, Greece
  9. 9Division of Internal Medicine, Athens University Medical School, Athens, Greece
  1. Correspondence to Professor George V Papatheodoridis, 2nd Department of Internal Medicine, Athens University Medical School, Hippokration General Hospital, 114 Vas. Sophias ave., 115 27 Athens, Greece; gepapath{at}med.uoa.gr

Abstract

Objective To evaluate the risk and predictors of hepatocellular carcinoma (HCC) in HBeAg-negative chronic hepatitis B patients of the large HEPNET.Greece cohort study who received long-term oral antivirals starting with lamivudine monotherapy.

Design Retrospective analysis of HCC incidence in HBeAg-negative chronic hepatitis B patients from a retrospective–prospective cohort who were treated with nucleos(t)ide analogue(s) starting with lamivudine monotherapy for ≥12 months.

Setting A nationwide network of liver centres.

Patients 818 patients were included: 517 with chronic hepatitis B only; 160 with compensated cirrhosis; 56 with decompensated cirrhosis; 85 with unclassified disease severity.

Interventions All patients were treated with nucleos(t)ide analogue(s) starting with lamivudine monotherapy.

Main outcome measures Development of HCC.

Results During a median follow-up of 4.7 years, HCC developed in 49 (6.0%) patients. The 5-year cumulative incidence of HCC was higher in patients with cirrhosis than in those with chronic hepatitis B only (11.5% vs 3.2%, respectively; p<0.001). HCC developed in 0.7%, 6.7% and 11.7% of patients <50, 50–60 and >60 years old, respectively (p<0.001). Virological on-therapy remission did not significantly affect the incidence of HCC in all patients or those with cirrhosis, but it showed a trend for lower HCC incidence in patients with chronic hepatitis B only (p=0.076). In multivariate analysis, age, gender and cirrhosis were independently associated with HCC risk regardless of virological remission.

Conclusions Long-term therapy with nucleos(t)ide analogue(s) starting with lamivudine monotherapy does not eliminate HCC risk in HBeAg-negative chronic hepatitis B. The risk of HCC is particularly high in patients with cirrhosis, who should remain under HCC surveillance even during effective therapy. Older age and male gender remain independent risk factors for HCC, while virological on-therapy remission does not seem to significantly reduce the overall incidence of HCC.

  • Hepatocellular carcinoma
  • chronic hepatitis B
  • cirrhosis
  • nucleos(t)ide analogues
  • lamivudine
  • virological remission
  • antiviral therapy
  • cirrhosis
  • hepatitis B
  • hepatocellular carcinoma

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Footnotes

  • Funding Hellenic Center for Disease Control and Prevention (HCDCP, KEELPNO, Greece).

  • Competing interests GVP: Advisory Board and/or Speaker for Bristol-Myers Squibb, Gilead, Novartis Pharmaceuticals, Roche, Schering-Plough; Research grants from Bristol-Myers Squibb, Gilead, Roche. SM: Advisory Board and/or Speaker for Bristol-Myers Squibb, Gilead, Novartis Pharmaceuticals, Roche, Schering-Plough. TV: Advisory Board for Gilead, Roche. KM: Advisory Board for Bristol-Myers Squibb, Schering-Plough; Research grants from, Gilead, Novartis Pharmaceuticals, Roche. EKM: Speaker for Bristol-Myers Squibb; Research grants from Gilead, Roche. The remaining authors have no competing interests.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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