The Korean Journal of Gastroenterology (대한소화기학회지)

The Korean Society of Gastroenterology (대한소화기학회)
권호 표지

A Comparative Cross-sectional Study of the Development of Hepatocellular Carcinoma in Patients with Liver Cirrhosis Caused by Hepatitis B Virus, Alcohol, or Combination of Hepatitis B Virus and Alcohol

B형 간염바이러스, 음주, 그리고 B형 간염바이러스와 음주의 중복 원인에 의한 간경변증에서 간세포암종 발생에 관한 단면 비교연구

Chung, Nak-So;Kwon, Oh-Sang;Park, Cheul-Hee;Kim, Young-Nam;Cho, Gwon-Hyun;Lee, Jong-Jun;Kim, Gil-Hyun;Kim, Hyun-Ok;Ko, Kwang-Il;Yu, Sang-Kyun;Kwon, Kwang-An;Kim, Yun-Soo;Choi, Duck-Ju;Kim, Ju-Hyun
정낙소;권오상;박철희;김영남;조권현;이종준;김길현;김현옥;고광일;유상균;권광안;김연수;최덕주;김주현

  • Published : 20070600
⟨ Previous Next ⟩

Abstract

Background/Aims: Alcohol may be a cocarcinogen in patients with chronic viral hepatitis. We investigated the effect of alcohol on the development of hepatocellular carcinoma (HCC) in liver cirrhosis (LC) caused by hepatitis B virus (HBV). Methods: All patients with LC or HCC associated with HBV or alcohol, admitted between March 2001 and June 2005, were included. Patients were divided into three groups according to the etiology of LC: Alcohol (AL), HBV, or HBV+alcohol (HBV+AL). Age and laboratory data at the enrollment of study were analyzed. The logistic regression coefficiency for the prevalence of HCC was calculated by using variables such as age, gender, serologic markers, and etiology of LC. Results: In LC patients (n=342), the proportions of AL, HBV, and HBV+AL groups were 44%, 39%, and 17%, respectively. The proportions of HCC in AL, HBV and HBV+AL groups were 17%, 55%, and 76%, respectively. Age at the diagnosis of HCC was younger in HBV+AL than in AL group (p=0.036). In logistic regression analysis for the risk factor of HCC, odds ratio of age was 1.056 (p＜0.001). Odds ratios of HBV and HBV+AL group comparing AL were 8.449 (p＜0.001) and 17.609 (p＜0.001), respectively. Therefore, old age and chronic alcohol intake in patients with HBsAg were the risk factors of HCC. Conclusions: Chronic alcohol intake may be an additive factor for the development of HCC in patient with LC caused by HBV. However, a prospective cohort study is needed to confirm these findings. (Korean J Gastroenterol 2007;49:369-375)

목적: 만성 C형 간염 환자에서 음주는 간세포암종 발생을 증가시키는 것으로 알려져 있으나, 만성 B형 간염 환자에서 음주가 간세포암종 발생을 증가시키는지의 여부는 명확히 밝혀져 있지 않다. 이번 연구는 만성 B형 간염바이러스에 의한 간경변증 환자에서 음주가 간세포암종 발생을 증가시키는지에 대하여 알아보고자 하였다. 대상 및 방법: 2001년 3월부터 2005년 6월까지 B형 간염바이러스 또는 음주가 원인인 간경변증 또는 간세포암종 환자 342명을 대상으로 하여 단면 연구를 시행하였다. 간질환의 원인에 따라서 음주군(AL), B형 간염바이러스군(HBV), 그리고 B형 간염바이러스와 음주에 의한 중복 원인군(HBV AL) 등 3개의 군으로 분류하였다. 환자들의 등록 당시 나이, 검사실 결과, 그리고 간경변 원인을 조사하여 간세포암종의 위험인자를 다변량 로지스틱 회귀분석을 이용하여 분석하였다. 결과: 전체 간경변증 환자(n=342)에서 원인에 따른 비는 AL군 44%, HBV군 39%, 그리고 HBV AL군 17%로 음주가 원인인 경우가 가장 많았다. 각 원인별 간경변증에서 간세포암종이 차지하는 비가 HBV AL군(76%)이 AL군(17%)과 HBV군(55%)에 비해 높았다(p＜0.01). 간세포암종 진단 시의 나이는 HBV AL군(52 9세)이 AL군(60 11세)에 비해 젊었으나(p=0.036) HBV군(55 10세)과는 차이가 없었다. 간세포암 발생의 위험인자를 찾고자 시행한 다변량 로지스틱 회귀분석에서 독립적인 위험인자는 나이와 원인으로, 나이가 많을수록(odds ratio: 1.056, p＜0.001) 그리고 AL군에 비해 HBV군(odds ratio: 8.449, p＜0.001)이 HBV군에 비해 HBV AL군(odds ratio: 2.614, p=0.007)이 간세포암종 발생이 높았다. 결론: B형 간염바이러스에 의한 간경변증에서 음주가 간세포암종 발생을 촉진시킬 수 있는 것으로 생각하나, 향후 이를 증명하기 위한 전향 연구가 필요하다.

Keywords

References

  1. Lee CH. Perspective of chronic liver disease in Korea. In: Lee CH, ed. Hepatitis. Seoul: Kun Ja, 2005:1-7
  2. Lee CH, Kim JH, Paik SH, Jo KH. Prospective study about natural history of chronic hepatitis B in Korea. In: Lee CH, ed. The status and development of new therapy and prevention about chronic viral hepatitis B and C in Korea. Final report about intensive cooperative study (HMP-99-M-01-0008) Department of health and welfare 2002:33-37
  3. Seitz HK, Stickel F, Homann N. Pathogenetic mechanisms of upper aerodigestive tract cancer in alcoholics. Int J Cancer 2004;108:483-487 https://doi.org/10.1002/ijc.11600
  4. Doll R, Foeman D, La Vecchia C, Woutersen R. Alcoholic beverages and cancers of the digestive tract and larynx. In: Macdonald I, ed. Health issue related to alcohol consumption. Oxford: Blackwell, 1995:351-393
  5. Corrao G, Bagnardi V, Zambon A, La Vecchia C. A metaanalysis of alcohol consumption and the risk of 15 diseases. Prev Med 2004;38:613-619 https://doi.org/10.1016/j.ypmed.2003.11.027
  6. McKillop IH, Schrum LW. Alcohol and liver cancer. Alcohol 2005;35:195-203 https://doi.org/10.1016/j.alcohol.2005.04.004
  7. Voigt MD. Alcohol in hepatocellular cancer. Clin Liver Dis 2005;9:151-169 https://doi.org/10.1016/j.cld.2004.10.003
  8. Stickel F, Schuppan D, Hahn EG, Seitz HK. Cocarcinogenic effects of alcohol in hepatocarcinogenesis. Gut 2002;51:132- 139 https://doi.org/10.1136/gut.51.1.132
  9. Corrao G, Arico S. Independent and combined action of hepatitis C virus infection and alcohol consumption on the risk of symptomatic liver cirrhosis. Hepatology 1998;27: 914-919 https://doi.org/10.1002/hep.510270404
  10. Colombo M. Malignant neoplasm of the liver. In: Schiff ER, Sorrell MF, Maddrey WC, ed. Schiff`s disease of the liver, Vol 2. Philadelphia: Lippincott Williams & Wilkins, 2003: 1377-1403
  11. Benvegnu L, Fattovich G, Noventa F, et al. Concurrent hepatitis B and C virus infection and risk of the hepatocellular carcinoma in cirrhosis. A prospective study. Cancer 1994;74: 2442-2448
  12. Ikeda K, Saitoh S, Suzuki Y, et al. Disease progression and hepatocellular carcinogenesis in patients with chronic viral hepatitis: a prospective observation of 2215 patients. J Hepatol 1998;28:930-938 https://doi.org/10.1016/S0168-8278(98)80339-5
  13. Ohnishi K, Iida S, Iwama S, et al. The effect of chronic habitual alcohol intake on the development of liver cirrhosis and hepatocellular carcinoma: relation to hepatitis B surface antigen carriage. Cancer 1982;49:672-677 https://doi.org/10.1002/1097-0142(19820215)49:4<672::AID-CNCR2820490415>3.0.CO;2-#
  14. Hadengue A, N'Dri N, Benhamou JP. Relative risk of hepatocellular carcinoma in HBsAg positive vs. alcoholic cirrhosis. A cross-sectional study. Liver 1990;10:147-151
  15. Miyakawa H, Izumi N, Marumo F, Sato C. Roles of alcohol, hepatitis virus infection, and gender in the development of hepatocellular carcinoma in patients with liver cirrhosis. Alcohol Clin Exp Res 1996;20:91A-94A https://doi.org/10.1111/j.1530-0277.1996.tb01738.x
  16. Tsutsumi M, Ishizaki M, Takada A. Relative risk for the development of hepatocellular carcinoma in alcoholic patients with cirrhosis: a multiple logistic-regression coefficient analysis. Alcohol Clin Exp Res 1996;20:758-762 https://doi.org/10.1111/j.1530-0277.1996.tb01683.x
  17. Ikeda K, Saitoh S, Koida I, et al. A multivariate analysis of risk factors for hepatocellular carcinogenesis: a prospective observation of 795 patents with viral and alcoholic cirrhosis. Hepatology 1993;18:47-53 https://doi.org/10.1002/hep.1840180109
  18. 2001년도 국민건강 영양조사.총괄편.2002.12, 보건복지부, 한국보건사회연구원
  19. Sherlock S, Dooley J. Alcohol and the liver. In: Sherlock S, Dooley J, ed. Diseases of the liver and biliary system. Oxford: Blackwell Science, 2002: 381-398
  20. Lee HS, Lee JH, Choi MS, Kim CY. Comparison of the incidence of hepatocellular carcinoma in HBV-and HCVassociated liver cirrhoosis; A prospective study. Korean J Hepatology 1996;2:21-28
  21. Kato Y, Nakata K, Omagari K, et al. Risk of hepatocellular carcinoma in patients with cirrhosis in Japan. Analysis of infectious hepatitis viruses. Cancer 1994;74:2234-2238 https://doi.org/10.1002/1097-0142(19941015)74:8<2234::AID-CNCR2820740805>3.0.CO;2-6
  22. 김창민. 간세포암의 병인. In: 김정용, ed. 소화기계질환. 서울: 일조각, 2000:656-663
  23. Lee HS, Ryu JK, Jung SH, Kim CY. A prospective study on the incidence and risk factors of the development of hepatocellular carcinoma in patients with liver cirrhosis in Korea. Korean J Gastroenterol 1993;25:116-122
  24. Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: Incidence and risk factors. Gastroenterology 2004;127:S35-S50 https://doi.org/10.1053/j.gastro.2004.09.014
  25. Poschl G, Seitz HK. Alcohol and Cancer. Alcohol Alcohol 2004;39:155-165 https://doi.org/10.1093/alcalc/agh057
  26. Donato F, Tagger A, Chiesa R, et al. Hepatitis B and C virus infection, alcohol drinking, and hepatocellular carcinoma: a case-control study in Italy. Brescia HCC study. Hepatology 1997;26:579-584 https://doi.org/10.1002/hep.510260308
  27. Fattovich G. Natural history and prognosis of hepatitis B. Semin Liver Dis 2003;23:47-58
  28. Yang HI, Lu SN, Liaw YF, et al. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med 2002; 347:168-174 https://doi.org/10.1056/NEJMoa013215
  29. Ohata K, Hamasaki K, Toriyama K, Ishikawa H, Nakao K, Eguchi K. High viral load is a risk factor for hepatocellular carcinoma in patients with chronic hepatitis B virus infection. J Gastroenterol Hepatol 2004;19:670-675 https://doi.org/10.1111/j.1440-1746.2004.03360.x