Introduction. Moldova is the European country with the highest incidence of hepatocellular carcinoma (HCC) in both sexes. There is, however, no data comprehensively describing the presentation and the risk factors of HCC in the country. We decided to analyze cases of HCC recently received in a tertiary healthcare Institution from Chisinau, the Moldovian capital.
Methods. A series of 148 primary liver tumors including 139 cases of HCC were retrospectively analyzed for demographic features, serological and biochemical data, and clinical presentation.
Results. The mean age of patients was 59 ± 10 years (range: 19-66) with a M:F sex ratio of 1.9. Tumors appeared on full-blown liver cirrhosis in 83% of cases and were composed of multiple nodules at diagnosis in 36% of patients. Serum Alpha-fetoprotein was exceeding 10ng/mL in 76% of cases. Liver tumor and hepatitis were co-discovered in 34% of cases. More than 81% of hepatocellular carcinomas were associated with at least one hepatitis virus. Carriers of anti-hepatitis C virus were predominating (55% of cases) over patients seropositive for hepatitis B virus surface antigen (36%). Half of the latter were also infected with hepatitis Delta virus. In total, dual or triple infections were present in 24% and 7% of cases.
Conclusions. The burden of infections with hepatitis viruses is particularly important in Moldova and corresponds to a situation commonly observed in countries of the Southern hemisphere. A pro-active policy of screening for persistent liver infection targeting population at risk of HCC (> 50 years) and coupled with the distribution of antivirals in positive cases should be rapidly implemented in Moldova to reduce incidence or primary liver cancer.
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1. FERLAY J. SOERJOMATARAM I. ERVIK M. DIKSHIT R. ESER S. MATHERS C. et al. GLOBOCAN 2012 v1.0 Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Journal. 2013.
2. MCGLYNN K. TSAO L. HSING A. DEVESA S. and FRAUMENI J. International trends and patterns of primary liver cancer. Int J Cancer. 2001; 94:290-6.
3. SOMOVA A. GOLOSOVA T. MARGOLINA A. and BAGRIANTSEVA S. The serodiagnosis of viral hepatitis C and B in different population groups. Voprosy Virusologii (Questions in Virology). 1992; 37:191-3.
4. KOSTRITSA S. KUZIN S. KHUKHLOVICH P. SHAKHGIL’DIAN I. DOROSHENKO N. BLINOV V. et al. The detection of antibodies to the hepatitis C virus and to HBsAg in donors with viral hepatitis and cancerous diseases in the Republic of Moldova. Voprosy Virusologii (Questions in Virology). 1994; 39:93-4.
5. STEPANOV G. BONDARENKO M. and LAROVOĬ P. Role of the instrument transmission factor in the epidemiology of viral hepatitis. II. Methods materials chief results. Zh Mikrobiol Epidemiol Immunobiol. 1977; 4:133-9.
6. NEGRESKU G. IASHINA T. BURKOV A. and FAVOROV M. The clinical picture and outcome of acute delta infection. Klin Med (Mosk). 1992; 70:80-4.
7. L’VOV D. MISHIRO S. SELIVANOV N. SAMOKHVALOV E. SHAKHGIL’DIAN I. STAKHANOVA V. et al. Prevalence of genotypes of the hepatitis C virus circulating in northwestern and central parts of Russia. Voprosy Virusologii (Questions in Virology). 1995; 40:251-3.
8. WORLD HEALTH ORGANIZATION. Global status report on alcohol and health 2014.
9. LACHENMEIER D. SCHOEBERL K. KANTERES F. KUBALLA T. SOHNIUS E. REHM J. et al. Is contaminated unrecorded alcohol a health problem in the European Union? A review of existing and methodological outline for future studies. Addiction. 2011; 106:Suppl 1:20-30.
10. WHO W.H.O. Age-standardized death rates of liver cirrhosis. 2017.
11. TURCANU G. DOMENTE S. BUGA M. and RICHARDSON E. Republic of Moldova health system review. 2012; 14.
12. TANASE A. MARCHIO A. DUMITRASCU T. DIMA S. HERLEA V. OPRISAN G. et al. Mutation Spectrum of Hepatocellular Carcinoma from Eastern-European Patients betrays the Impact of a complex Exposome. J Exp Sci Env Epidemiol. 2014; 25:256-63.
13. SCHIAVON L. SCHIAVON J. CARVALHO FILHO R. SAMPAIO J. LANZONI V. SILVA A. et al. Simple blood tests as noninvasive markers of liver fibrosis in hemodialysis patients with chronic hepatitis C virus infection. Hepatology. 2007; 46:307-14.
14. VALLET PICHARD A. MALLET V. NALPAS B. VERKARRE V. NALPAS A. DHALLUIN VENIER V. et al. FIB 4: An inexpensive and accurate marker of fibrosis in HCV infection. comparison with liver biopsy and fibrotest. Hepatology. 2007; 46:32-6.
15. KINOSHITA A. ONODA H. FUSHIYA N. KOIKE K. NISHINO H. and TAJIRI H. Staging systems for hepatocellular carcinoma: current status and future perspectives. World J Hepatol. 2015; 7:406.
16. JOHNSON P. BERHANE S. KAGEBAYASHI C. SATOMURA S. TENG M. REEVES H. et al. Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach—the ALBI grade. J Clin Oncol. 2014; 33:550-8.
17. DE MARTEL C. MAUCORT-BOULCH D. PLUMMER M. and FRANCESCHI S. World-wide relative contribution of hepatitis B and C viruses in hepatocellular carcinoma. Hepatology. 2015; 62:1190-200.
18. RAZA S. CLIFFORD G. and FRANCESCHI S. Worldwide variation in the relative importance of hepatitis B and hepatitis C viruses in hepatocellular carcinoma: a systematic review. Br J Cancer. 2007; 96:1127-34.
19. PERZ J. ARMSTRONG G. FARRINGTON L. HUTIN Y. and BELL B. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol. 2006; 45:529-38.
20. SHAKHGIL’DIAN I. FARBER N. KUZIN S. CHESHIK S. DROBENIUK Z. MIKHAILOV M. et al. Perinatal infection with hepatitis B virus and the problem of its specific prevention. Vestn Akad Med Nauk SSSR (Ann Russian Acad Med Sci). 1990; 7:29-32.
21. VOICULESCU M. ILIESCU L. IONESCU C. MICU L. ISMAIL G. ZILISTEANU D. et al. A cross-sectional epidemiological study of HBV HCV HDV and HEV prevalence in the SubCarpathian and South-Eastern regions of Romania. J Gastrointestin Liver Dis. 2010; 19:43-8.
22. BLACHIER M. LELEU H. PECK-RADOSAVLJEVIC M. VALLA D. and ROUDOT-THORAVAL F. The burden of liver disease in Europe: a review of available epidemiological data. J Hepatol. 2013; 58:593-608.
23. GRIGORIE R. ALEXANDRESCU S. SMIRA G. IONESCU M. HREHOREŢ D. BRAŞOVEANU V. et al. Curative Intent Treatment of Hepatocellular Carcinoma - 844 Cases Treated in a General Surgery and Liver Transplantation Center. Chirurgia (Bucur). 2017; 112:289-300.
24. HEIDRICH B. DETERDING K. TILLMANN H. RAUPACH R. MANNS M. and WEDEMEYER H. Virological and clinical characteristics of delta hepatitis in Central Europe. J Viral Hepat. 2009; 16:883-94.
25. WEDEMEYER H. and MANNS M. Epidemiology pathogenesis and management of hepatitis D: update and challenges ahead. Nat Rev Gastroenterol Hepatol. 2010; 7:31-40.
26. WRANKE A. PINHEIRO BORZACOV L. PARANA R. LOBATO C. HAMID S. CEAUSU E. et al. Clinical and virological heterogeneity of hepatitis delta in different regions world-wide: The Hepatitis Delta International Network (HDIN). Liver Int. 2017; 38:842-50.
27. NEGRO F. Hepatitis D Virus Coinfection and Superinfection. Cold Spring Harb Perspect Med. 2014; 4:a021550.
28. TSATSRALT-OD B. TAKAHASHI M. NISHIZAWA T. ENDO K. INOUE J. and OKAMOTO H. High prevalence of dual or triple infection of hepatitis B C and delta viruses among patients with chronic liver disease in Mongolia. J Med Virol. 2005; 77:491-9.
29. DEGERTEKIN H. YALÇIN K. and YAKUT M. The prevalence of hepatitis delta virus infection in acute and chronic liver diseases in Turkey: An analysis of clinical studies. Turk J Gastroenterol. 2006; 17:25-34.
30. AMOUGOU ATSAMA M. NOAH NOAH D. FEWOU MOUNDIPA P. PINEAU P. and NJOUOM R. A prominent role of Hepatitis D Virus in liver cancers documented in Central Africa. BMC Infect Dis. 2016; 16:647.