medigraphic.com
Órgano Oficial de la Asociación Mexicana de Hepatología

2014, Number 4

<< Back Next >>

Ann Hepatol 2014; 13 (4)

Long term nucleotide and nucleoside analogs treatment in chronic hepatitis B HBeAg negative genotype D patients and risk for hepatocellular carcinoma

Pellicelli AM, Vignally P, Messina V, Izzi A, Mazzoni E, Barlattani A, Bacca D, Romano M, Mecenate F, Stroffolini T, Furlan C, Picardi A, Gentilucci UV, Gulminetti R, Bonaventura ME, Villani R, D’Ambrosio C, Paffetti A, Mastropietro C, Marignani M, Fondacaro L, Cerasari G, Andreoli A, Barbarini G

Language: English
References: 21
Page: 376-385
PDF size: 116.31 Kb.


ABSTRACT

Background and rationale of the study. Effect of Long-term nucleoside/nucleotide (NUC) on hepatocellular carcinoma (HCC) incidence in a population of HBeAg-negative genotype D patients has not been adequately studied in real-life cohorts. Our aim was to evaluate the impact of liver fibrosis and other variables on HCC incidence in this population of patients. Of 745 patients with chronic hepatitis B (CHB), 306 HBeAg-negative genotype D were selected and included in this study. All patients received treatment with NUC for at least 18 months. Patients with CHB or compensated cirrhosis were included. Patients with HCC diagnosed before or during the first 18 months of NUC therapy were excluded. Results. HCC was diagnosed in 2 CHB patients (1.0%) and 23 cirrhosis patients (20%) (OR = 24.41, 95% CI 5.40 ‹ OR ‹ 153.2; p ‹ 0.0001). Multivariate analysis revealed that HCC risk was independently associated with age ≥ 60 years (OR = 6.45, 95% CI 1.22 to 34.0; p = 0.02) and liver cirrhosis (OR = 12.1, 95% CI 1.39 to 106.2; p = 0.02), but not with virological response (VR), and previous resistance to NUC, or rescue therapy. Multivariate analysis in cirrhosis patients revealed that only age ≥ 60 years was an independent risk factor associated with HCC (p = 0.003). Conclusions. Liver cirrhosis and age ≥ 60 years are the stronger risk factors for HCC in genotype D HBeAgnegative patients. Previous resistance to NUC in patients that achieved a VR after rescue therapy was not a predictive factor regarding HCC. VR does not appear to significantly reduce the overall incidence of HCC when a patient has already progressed to liver cirrhosis.


REFERENCES

  1. Fattovich G, Stroffolini T, Zagni I, Di Donato F. Hepatocellular carcinoma in cirrhosis:incidence and risk factors. Gastreoneterology 2004; 127: S35-S50.

  2. Stroffolini T, Andreone P, Andriulli A, Ascione A, Craxi A, Chiaramonte M, Galante D, et al. Characteristics of hepatocellular carcinoma in Italy. J Hepatol 1998; 29: 944-52.

  3. Chih LL, Jia-Horng K. The clinical implications of hepatitis B virus genotype: recent advances. J Gastroenterol Hepatol 2011; 26: 123-30.

  4. Poustchi H, Mohamadkhani A, Bowden S, Montazeri G, Ayres A, Revill P, Farrell GC, et al. Clinical significance of precore and core promoter mutations in genotype D hepatitis B-related chronic liver disease. J Viral Hepat 2008; 15: 753-60.

  5. Lai CL, Yuen MF. Prevention of hepatitis B virus-related hepatocellular carcinoma with antiviral therapy. Hepatology 2013; 57: 399-408.

  6. Della Corte C, Aghemo A, Colombo M. Individualized hepatocellular carcinoma risk: the challenge for designing successful chemoprevention strategies. World J Gastroenterol 2013; 19: 1359-71.

  7. Hosaka T, Suzuki F, Kobayashi M, Seko Y, Kawamura Y, Sezaki H, Akuta N, et al. Long- term entecavir treatment reduces hepatocellular carcinoma incidence in patients with HBV infection. Hepatology 2013; 58: 98-107.

  8. European Association For The Study Of The Liver. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol 2012; 57: 167-85.

  9. Saldanha J, Gerlich W, Lelie N, Dawson P, Heermann K, Heath A. An international collaborative study to establish a world health organization international standard for hepatitis B virus DNA nucleic acid amplification techniques. Vox Sanguinis 2001; 80: 63-71.

  10. Ishak K, Baptista A, Bianchi L, Burt A, Callea F, Denk H, De Groote J, et al. Histological grading and staging of chronic hepatitis. J Hepatol 1995; 22: 696-9.

  11. Castéra L, Le Bail B, Roudot-Thoraval F, Bernard PH, Foucher J, Merrouche W, Couzigou P, et al. Early detection in routine clinical practice of cirrhosis and oesophageal varices in chronic hepatitis C: comparison of transientelastography (FibroScan) with standard laboratory tests and non-invasive scores. J Hepatol 2009; 50: 59-68.

  12. European Association For The Study Of The Liver; European Organisation For Research And Treatment Of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 2012; 56: 908-43.

  13. Liaw YF, Sung JY, Chow WC, Farrell G, Lee CZ, Yuen H, Tanwandee T, et al. Lamivudine for Patients with Chronic Hepatitis B and Advanced Liver Disease. N Engl J Med 2004; 351: 1521-31.

  14. Kumada T, Toyoda H, Tada T, Kiriyama S, Tanikawa M, Kanamori A, Niinomi T et al. Effect of nucleos(t)ide analogue therapy on hepatocarcinogenesis in chronic hepatits B patients: a propensity score analysis. J Hepatol 2013; 58: 427-33.

  15. Di Marco V, Marzano A, Lampertico P, Andreone P, Santantonio T, Almasio PL, Rizzetto M, et al. Clinical outcome of HBeAg negative chronic hepatitis B in relation to virological response to Lamivudine. Hepatology 2004; 40: 883-91.

  16. Eun JR, Lee HJ, Kim TN, Lee KS. Risk assessment for the development of hepatocellular carcinoma: according to ontreatment viral response during long term lamivudine therapy in hepatitis B virus-related liver disease. J Hepatol 2010; 53: 118-25.

  17. Yang SC, Lee CM, Hu TH, Wang JH, Lu SN, Hung CH, Changchien CS, et al. Virological response to entecavir reduces the risk of liver disease progression in nucleos(t)ide analogue- experienced HBV-infected patients with prior resistant mutants. J Antimicrob Chemother 2013; 68(9): 2154-63.

  18. Papatheodoridis GV, Manolakopoulos S, Touloumi G, Vourli G, Raptopoulou-Gigi M, Vafladis-Zoumbouli I, Vasiliadis T, et al. Virological suppression does not prevent the development of hepatocellular carcinoma in HBeAg-negative chronic hepatitis B patients with cirrhosis receiving oral antiviral starting with lamivudine monotherapy: results of the nationwide HEPNET. Greece cohort study. GUT 2011; 60: 1109-16.

  19. Lampertico P, Soffredini R, Viganò M. 5-year entecavir treatment in NUC-naive, field practice patients with chronic hepatitis B showed excellent viral suppression and safety profile but no prevention of HCC in cirrhotics. J Hepatol 2013; 58: S306-S307.

  20. Abdo AA, Al-Jarallah BM, Sanai FM, Hersi AS, Al-Swat K, Azzam NA, Al-Dukhayil M, et al. Hepatitis B genotypes: Relation to clinical outcome in patients with chronic hepatitis B in Saudi Arabia. World J Gastroenterol 2006; 12: 7019-24.

  21. Thakur V, Guptan RC, Kazim SN, Malhotra V, Sarin SK. Profile, spectrum and significance of HBV genotypes in chronic liver disease patients in the Indian subcontinent. J Gastroenter Hepatol 2002; 17: 165-70.




2020     |     www.medigraphic.com