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• W1968014503 abstract "Background & Aims: In the United States, hepatocellular carcinoma (HCC) is more common among Asians and African Americans than Caucasians, with chronic hepatitis C virus (HCV) infection accounting for up to half of the patients. Our study examined ethnicity as a potential risk factor for HCC among patients with chronic hepatitis C. Methods: We conducted a case-control study of 464 patients with chronic hepatitis C and cirrhosis (207 cancer patients and 257 controls) using medical records and pathology records at 4 medical centers. We estimated odds ratios with 95% confidence intervals by using conditional logistic regression on case-control sets, matched within study centers and study period on sex and age groups (≤45, 46–55, 56–65, >65 yr). To control for potential confounding caused by severity of cirrhosis and residual confounding caused by age, we also included Child-Turcotte-Pugh (CTP) scores and age (continuous variable) in all regression analyses. Results: Compared with Caucasians, the cancer risk was increased significantly among Asians (adjusted odds ratio, 4.3; 95% confidence interval, 2.1–9.0 for men, and 4.6; 1.2–18.5 for women) and somewhat increased among African-American men (adjusted odds ratio, 2.4; 95% confidence interval, 0.9–6.3). Conclusions: This study suggests that, among patients with chronic hepatitis C and cirrhosis, liver cancer risk is increased 4-fold in Asians and may be doubled in African-American men, compared with Caucasians. These results need confirmation in larger studies from racially diverse populations, but, if confirmed, these results point to high-risk populations that should be targeted for screening and preventive efforts. Background & Aims: In the United States, hepatocellular carcinoma (HCC) is more common among Asians and African Americans than Caucasians, with chronic hepatitis C virus (HCV) infection accounting for up to half of the patients. Our study examined ethnicity as a potential risk factor for HCC among patients with chronic hepatitis C. Methods: We conducted a case-control study of 464 patients with chronic hepatitis C and cirrhosis (207 cancer patients and 257 controls) using medical records and pathology records at 4 medical centers. We estimated odds ratios with 95% confidence intervals by using conditional logistic regression on case-control sets, matched within study centers and study period on sex and age groups (≤45, 46–55, 56–65, >65 yr). To control for potential confounding caused by severity of cirrhosis and residual confounding caused by age, we also included Child-Turcotte-Pugh (CTP) scores and age (continuous variable) in all regression analyses. Results: Compared with Caucasians, the cancer risk was increased significantly among Asians (adjusted odds ratio, 4.3; 95% confidence interval, 2.1–9.0 for men, and 4.6; 1.2–18.5 for women) and somewhat increased among African-American men (adjusted odds ratio, 2.4; 95% confidence interval, 0.9–6.3). Conclusions: This study suggests that, among patients with chronic hepatitis C and cirrhosis, liver cancer risk is increased 4-fold in Asians and may be doubled in African-American men, compared with Caucasians. These results need confirmation in larger studies from racially diverse populations, but, if confirmed, these results point to high-risk populations that should be targeted for screening and preventive efforts. Infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) are the major risk factors for hepatocellular carcinoma (HCC).1Szilagyi A. Alpert L. Clinical and histopathological variation in hepatocellular carcinoma.Am J Gastroenterol. 1995; 90: 15-23PubMed Google Scholar, 2Liang T.J. Jeffers L.J. Reddy K.R. De Medina M. Parker I.T. Cheinquer H. Idrovo V. Rabassa A. Schiff E.R. Viral pathogenesis of hepatocellular carcinoma in the United States.Hepatology. 1993; 18: 1326-1333PubMed Google Scholar, 3Tsukuma H. Hiyama T. Tanaka S. Nakao M. Yabuuchi T. Kitamura T. Nakanishi K. Fujimoto I. Inoue A. Yamazaki H. Kawashima T. Risk factors for hepatocellular carcinoma among patients with chronic liver disease.N Engl J Med. 1993; 328: 1797-1801Crossref PubMed Scopus (1057) Google Scholar, 4Di Bisceglie A.M. Malignant neoplasm of the liver.in: Schiff E.R. Sorrell M.F. Maddrey W.C. Diseases of the liver. 8th ed. Lippincott, Philadelphia1999: 1287-1292Google Scholar In the United States, the overall age-adjusted HCC incidence has increased from 1.4 per 100,000 between 1975 and 1977 to 3.0 per 100,000 between 1996 and 1998, with the greatest rate of increase among patients between 45 and 49 years of age (1.9 per 100,000 in 1975–1977 to 6.5 per 100,000 in 1996–1998), owing largely to the increasing rate of HCV-related HCC.5El-Serag H.B. Mason A.C. Rising incidence of hepatocellular carcinoma in the United States.N Engl J Med. 1999; 340: 745-750Crossref PubMed Scopus (2708) Google Scholar, 6El-Serag H.B. Mason A.C. Risk factors for the rising rates of primary liver cancer in the United States.Arch Intern Med. 2000; 160: 3227-3230Crossref PubMed Scopus (367) Google Scholar, 7El-Serag H.B. Hepatocellular carcinoma and hepatitis C in the U.S.Hepatology. 2002; 36: S74-S83Crossref PubMed Scopus (0) Google Scholar, 8Marrero J.A. Fontana R.J. Su G.L. Conjeevaram H.S. Emick D.M. Lok A.S. NAFLD may be a common underlying liver disease in patients with hepatocellular carcinoma in the United States.Hepatology. 2002; 36: 1349-1354Crossref PubMed Scopus (559) Google Scholar, 9El-Serag H.B. Davila J.A. Petersen N.J. McGlynn K.A. The continuing increase in the incidence of hepatocellular carcinoma in the United States: an update.Ann Intern Med. 2003; 139: 817-823Crossref PubMed Scopus (835) Google Scholar Given the burden of HCV infection in the United States, HCV-related HCC is predicted to be a major health problem in the next few decades.7El-Serag H.B. Hepatocellular carcinoma and hepatitis C in the U.S.Hepatology. 2002; 36: S74-S83Crossref PubMed Scopus (0) Google Scholar, 10Kim R.W. The burden of hepatitis C in the United States.Hepatology. 2002; 36: S30-S34Crossref PubMed Google Scholar Identification of high-risk patients among those infected with HCV may enhance our understanding of disease mechanisms and identify patients who may benefit the most from screening and chemopreventive efforts.11El-Serag H.B. Mason A.C. Key C. Trends in survival of patients with hepatocellular carcinoma between 1977 and 1996 in the United States.Hepatology. 2001; 33: 62-65Crossref PubMed Scopus (341) Google Scholar, 12Nguyen M.H. Keeffe E.B. Treatment of hepatocellular carcinoma.in: Rustgi A.K. Crawford J. Gastrointestinal cancer: biology and clinical management. 1st ed. Saunders, Philadelphia2003: 605-622Google Scholar, 13Nguyen M.H. Keeffe E.B. Screening for hepatocellular carcinoma.J Clin Gastroenterol. 2002; 35: S86-S91Crossref PubMed Scopus (89) Google Scholar, 14Camma C. Giunta M. Andreone P. Craxi A. Interferon and prevention of HCC in viral cirrhosis: an evidenced-based approach.J Hepatol. 2001; 34: 593-602Abstract Full Text Full Text PDF PubMed Scopus (353) Google ScholarAdvanced age, more severe liver disease, and male gender are known to be associated with an increased risk for HCC in patients with various chronic liver diseases including chronic hepatitis C.15Ikeda K. Saitoh S. Koida I. Arase Y. Tsubota A. Chayama K. Kumada H. Kawanishi M. A multivariate analysis of risk factors for hepatocellular carcinogenesis: a prospective observation of 795 patients with viral and alcoholic cirrhosis.Hepatology. 1993; 18: 47-53Crossref PubMed Google Scholar, 16Mori M. Hara M. Wada I. Hara T. Yamamoto K. Honda M. Naramoto J. Prospective study of hepatitis B and C viral infections, cigarette smoking, alcohol consumption, and other factors associated with HCC risk in Japan.Am J Epidemiol. 2000; 151: 131-139Crossref PubMed Scopus (125) Google Scholar, 17del Olmo J.A. Serra M.A. Rodriguez F. Escudero A. Gilabert S. Rodrigo J.M. Incidence and risk factors for hepatocellular carcinoma in 967 patients with cirrhosis.J Cancer Res Clin Oncol. 1998; 124: 560-564Crossref PubMed Scopus (51) Google Scholar, 18Aizawa Y. Shibamoto Y. Takagi I. Zeniya M. Toda G. Analysis of factors affecting the appearance of hepatocellular carcinoma in patients with chronic hepatitis C A long term follow-up study after histologic diagnosis.Cancer. 2000; 89: 53-59Crossref PubMed Scopus (100) Google Scholar On the other hand, results regarding HCV genotypes and alcohol and tobacco use as potential synergistic risk factors for HCC generally have been conflicting.16Mori M. Hara M. Wada I. Hara T. Yamamoto K. Honda M. Naramoto J. Prospective study of hepatitis B and C viral infections, cigarette smoking, alcohol consumption, and other factors associated with HCC risk in Japan.Am J Epidemiol. 2000; 151: 131-139Crossref PubMed Scopus (125) Google Scholar, 17del Olmo J.A. Serra M.A. Rodriguez F. Escudero A. Gilabert S. Rodrigo J.M. Incidence and risk factors for hepatocellular carcinoma in 967 patients with cirrhosis.J Cancer Res Clin Oncol. 1998; 124: 560-564Crossref PubMed Scopus (51) Google Scholar, 18Aizawa Y. Shibamoto Y. Takagi I. Zeniya M. Toda G. Analysis of factors affecting the appearance of hepatocellular carcinoma in patients with chronic hepatitis C A long term follow-up study after histologic diagnosis.Cancer. 2000; 89: 53-59Crossref PubMed Scopus (100) Google Scholar, 19Romeo R. Rumi M.G. Del Ninno E. Colombo M. Hepatitis C virus genotype 1b and risk of hepatocellular carcinoma.Hepatology. 1997; 26: 1077Crossref PubMed Scopus (31) Google Scholar, 20Tanaka K. Ikematsu H. Hirohata T. Kashiwagi S. Hepatitis C virus infection and risk of hepatocellular carcinoma among Japanese: possible role of type 1b (II) infection.J Natl Cancer Inst. 1996; 88: 742-746Crossref PubMed Scopus (74) Google Scholar, 21Zein N.N. Poterucha J.J. Gross Jr, J.B. Wiesner R.H. Therneau T.M. Gossard A.A. Wendt N.K. Mitchell P.S. Germer J.J. Persing D.H. Increased risk of hepatocellular carcinoma in patients infected with hepatitis C genotype 1b.Am J Gastroenterol. 1996; 9: 2560-2562Google Scholar, 22Bruno S. Silini E. Crosignani A. Borzio F. Leandro G. Bono F. Asti M. Rossi S. Larghi A. Cerino A. Podda M. Mondelli M.U. Hepatitis C genotypes and risk of hepatocellular carcinoma in cirrhosis: a prospective study.Hepatology. 1997; 25: 754-758Crossref PubMed Scopus (345) Google Scholar, 23Tagger A. Donato F. Ribero M.L. Chiesa R. Portera G. Gelatti U. Albertini A. Fasola M. Boffetta P. Nardi G. Case-control study on hepatitis C virus (HCV) as a risk factor for hepatocellular carcinoma: the role of HCV genotypes and the synergism with hepatitis B virus and alcohol Brescia HCC study.Int J Cancer. 1999; 8: 695-699Crossref Scopus (147) Google Scholar, 24Kuper H. Tzonou A. Kaklamani E. Hsieh C.C. Lagiou P. Adami H.O. Trichopoulos D. Stuver S.O. Tobacco smoking, alcohol consumption and their interaction in the causation of hepatocellular carcinoma.Int J Cancer. 2000; 85: 498-502Crossref PubMed Scopus (298) Google Scholar, 25Dutta U. Byth K. Kench J. Khan M.H. Coverdale S.A. Weltman M. Lin R. Liddle C. Farrell G.C. Risk factors for development of hepatocellular carcinoma among Australians with hepatitis C: a case-control study.Aust N Z J Med. 1999; 29: 300-307Crossref PubMed Scopus (23) Google Scholar, 26Silini E. Bottelli R. Asti M. Bruno S. Candusso M.E. Brambilla S. Bono F. Iamoni G. Tinelli C. Mondelli M.U. Ideo G. Hepatitis C virus genotypes and risk of hepatocellular carcinoma in cirrhosis: a case-control study.Gastroenterology. 1996; 111: 199-205Abstract Full Text Full Text PDF PubMed Scopus (166) Google Scholar, 27Nousbaum J.B. Pol S. Nalpas B. Landais P. Berthelot P. Brechot C. Hepatitis C virus type 1b (II) infection in France and Italy Collaborative Study Group.Ann Intern Med. 1995; 122: 161-168Crossref PubMed Scopus (517) Google Scholar, 28Reid A.E. Koziel M.J. Aiza I. Jeffers L. Reddy R. Schiff E. Lau J.Y. Dienstag J.L. Liang T.J. Hepatitis C virus genotypes and viremia and hepatocellular carcinoma in the United States.Am J Gastroenterol. 1999; 94: 1619-1626Crossref PubMed Scopus (42) Google Scholar, 29Fattovich G. Ribero M.L. Pantalena M. Diodati G. Almasio P. Nevens F. Tremolada F. Degos F. Rai J. Solinas A. Mura D. Tocco A. Zagni I. Fabris F. Lomonaco L. Noventa F. Realdi G. Schalm S.W. Tagger A. Eurohep Study Group on Viral HepatitisHepatitis C virus genotypes: distribution and clinical significance in patients with cirrhosis type C seen at tertiary referral centers in Europe.J Viral Hepat. 2001; 8: 206-216Crossref PubMed Scopus (32) Google Scholar, 30Degos F. Christidis C. Ganne-Carrie N. Farmachidi J.P. Degott C. Guettier C. Trinchet J.C. Beaugrand M. Chevret S. Hepatitis C virus related cirrhosis: time to occurrence of hepatocellular carcinoma and death.Gut. 2000; 47: 131-136Crossref PubMed Scopus (328) Google Scholar, 31Widell A. Verbaan H. Wejstal R. Kaczynski J. Kidd-Ljunggren K. Wallerstedt S. Hepatocellular carcinoma in Sweden: its association with viral hepatitis, especially with hepatitis C viral genotypes.Scand J Infect Dis. 2000; 32: 147-152Crossref PubMed Scopus (24) Google Scholar, 32Benvegnu L. Pontisso P. Cavalletto D. Noventa F. Chemello L. Alberti A. Lack of correlation between hepatitis C virus genotypes and clinical course of hepatitis C virus-related cirrhosis.Hepatology. 1997; 25: 211-215Crossref PubMed Google Scholar, 33Hassan M.M. Hwang L.-Y. Hatten C.J. Swaim M. Li D. Abbruzzese J.L. Beasley P. Patt Y.Z. Risk factors for hepatocellular carcinoma: synergism of alcohol with viral hepatitis and diabetes mellitus.Hepatology. 2002; 36: 1206-1213Crossref PubMed Scopus (631) Google Scholar In the United States, higher overall HCC incidence and mortality also have been observed in African Americans and Asians,5El-Serag H.B. Mason A.C. Rising incidence of hepatocellular carcinoma in the United States.N Engl J Med. 1999; 340: 745-750Crossref PubMed Scopus (2708) Google Scholar, 34Teo E.K. Fock K.M. Hepatocellular carcinoma: an Asian perspective.Dig Dis. 2001; 19: 263-268Crossref PubMed Scopus (76) Google Scholar, 35Chin P.L. Chu D.Z. Clarke K.G. Odom-Maryon T. Yen Y. Wagman L.D. Ethnic differences in the behavior of hepatocellular carcinoma.Cancer. 1999; 85: 1931-1936Crossref PubMed Google Scholar but few studies to date have examined ethnicity as a potential HCC risk factor in patients with chronic hepatitis C. Studies of Asians in the United States have suggested an association between excess HCC risk in Asians with chronic hepatitis B infection, but whether this excess risk also exists when Asian patients with chronic hepatitis C (without chronic hepatitis B) are compared with other racial/ethnic groups with chronic hepatitis C is unclear.36Do S. The natural history of hepatitis B in Asian Americans.Asian Am Pac Islander J Health. 2001; 9: 141-152PubMed Google Scholar, 37Di Bisceglie A.M. Lyra A.C. Schwartz M. Reddy R.K. Martin P. Gores G. Lok A.S. Hussain K.B. Gish R. Van Thiel D.H. Younossi Z. Tong M. Hassanein T. Balart L. Fleckenstein J. Flamm S. Blei A. Befeler A.S. Liver Cancer NetworkHepatitis C-related hepatocellular carcinoma in the United States: influence of ethnic status.Am J Gastroenterol. 2003; 98: 2060-2063PubMed Google Scholar, 38Blakely T.A. Bates M.N. Baker M.G. Tobias M. Hepatitis B carriage explains the excess rate of hepatocellular carcinoma for Maori, Pacific Island and Asian people compared to Europeans in New Zealand.Int J Epidemiol. 1999; 28: 204-210Crossref PubMed Scopus (35) Google Scholar, 39Hwang S.J. Tong M.J. Lai P.P. Ko E.S. Co R.L. Chien D. Kuo G. Evaluation of hepatitis B and C viral marker: clinical significance in Asian and Caucasian patients with hepatocellular carcinoma in the United States of America.J Gastroenterol Hepatol. 1996; 11: 949-954Crossref PubMed Scopus (58) Google ScholarMaterials and methodsStudy participantsTo examine ethnicity as a potential HCC risk factor in patients with chronic hepatitis C, we conducted a case-control study of patients with chronic hepatitis C and cirrhosis from 4 San Francisco Bay medical centers. Specifically, we reviewed medical and pathology records for diagnoses of chronic hepatitis C, cirrhosis, and HCC at Stanford University Medical Center during the period from January 1998 to December 2002, at the San Francisco Veterans Administration Medical Center from January 1995 to January 2001, at the University of California in San Francisco from January 1995 to July 2001, and at the San Francisco General Hospital from January 1996 to June 2001. All patient characteristics including ethnicity were obtained by chart review. We evaluated patient characteristics (e.g., age, serum α-fetoprotein [AFP], Child-Turcotte-Pugh [CTP] score)40Child III, C.G. Turcotte J.G. Surgery in portal hypertension.in: Child III, C.G. The liver and portal hypertension. WB Saunders, Philadelphia1964: 50Google Scholar, 41Pugh R.N.H. Murray-Lyon I.M. Dawson J.J. Pietroni N.C. Williams R. Transection of the oesophagus for bleeding oesophaeal varices.Br J Surg. 1973; 60: 646-649Crossref PubMed Scopus (6665) Google Scholar at a reference date, defined as the date of diagnosis for patients and as the date of first available AFP and imaging studies for controls.Eligible patients and control patients had chronic hepatitis C and cirrhosis (as determined by liver histology, clinical, and/or radiographic evidence of portal hypertension such as varices, ascites, encephalopathy, thrombocytopenia, and splenomegaly), no history of prior malignancy, no evidence of metabolic or autoimmune hepatitis, and no evidence of infection with HBV or human immunodeficiency virus. For case patients, we verified HCC diagnosis by cytology, histology, or by noninvasive criteria.42Nino-Murcia M. Olcott E.W. Jeffrey R.B. Lamm R.L. Beaulieu C.F. Jain K.A. Focal liver lesions: pattern-based classification scheme for enhancement at arterial phase CT.Radiology. 2000; 215: 746-751Crossref PubMed Scopus (161) Google Scholar, 43Bruix J. Sherman M. Llovet J.M. Beaugrand E. Lencioni R. Christensen E. Burroughs A. Christensen E. Pagliaro L. Colombo M. Rodes J. Clinical management of hepatocellular carcinoma Conclusions of the Barcelona-2000 EASL Conference.J Hepatol. 2001; 35: 421-430Abstract Full Text Full Text PDF PubMed Scopus (3753) Google Scholar, 44Gupta S. Bent S. Knowles J. Test characteristics of α-fetoprotein for detecting of hepatocellular carcinoma in patients with hepatitis C A systematic review and critical analysis.Ann Intern Med. 2003; 139: 46-50Crossref PubMed Scopus (319) Google Scholar, 45Nguyen M.H. Garcia R.T. Simpson P. Wright T.L. Keeffe E.B. Racial differences in effectiveness of α-fetoprotein for diagnosis of hepatocellular carcinoma in HCV cirrhosis.Hepatology. 2002; 36: 410-417Crossref PubMed Scopus (138) Google Scholar, 46Trevisani F. D’Intino P.E. Morselli-Labate A.M. Mazzella G. Accogli E. Caraceni P. Domenicali M. De Notariis S. Roda E. Bernardi M. Serum alpha-fetoprotein for diagnosis of hepatocellular in patients with chronic liver disease: influence of HBsAg and anti-HCV status.J Hepatol. 2001; 34: 570-575Abstract Full Text Full Text PDF PubMed Scopus (554) Google Scholar, 47Peng Y.C. Chan C.S. Chen G.H. The effectiveness of serum alpha-fetoprotein level in anti-HCV positive patients for screening hepatocellular carcinoma.Hepatogastroenterology. 1999; 46: 3208-3211PubMed Google Scholar, 48Cedrone A. Covino M. Caturelli E. Pompilli M. Lorenzelli G. Villani M.R. Valle D. Sperandeo M. Rapaccini G.L. Gasbarrini G. Utility of alpha-fetoprotein (AFP) in the screening of patients with virus-related chronic liver disease: does different viral etiology influence AFP levels in HCC? A study in 350 Western patients.Hepatogastroenterology. 2000; 47: 1654-1658PubMed Google Scholar, 49Tong M.J. Blatt L.M. Kao V.W. Surveillance for hepatocellular carcinoma in patients with chronic viral hepatitis in the United States of America.J Gastroenterol Hepatol. 2001; 16: 553-559Crossref PubMed Scopus (137) Google Scholar For control patients, we verified the absence of HCC by either negative explants, negative imaging studies and AFP level of 20 ng/mL or less,50Sherman M. Peltekian K.M. Lee C. Screening for hepatocellular carcinoma in chronic carriers of hepatitis B virus: incidence and prevalence of hepatocellular carcinoma in a North American urban population.Hepatology. 1995; 22: 432-438PubMed Google Scholar, 51Trevisani F. D’Intino P.E. Caraceni P. Pizzo M. Stefanini G.F. Mazziotti A. Grazi G.L. Gozzetti G. Gasbarrini G. Bernardi M. Etiologic factors and clinical presentation of hepatocellular carcinoma Difference between cirrhotic and non-cirrhotic Italian patients.Cancer. 1995; 75: 2220-2232Crossref PubMed Scopus (161) Google Scholar or negative imaging studies with at least one biphasic computed tomography, magnetic resonance image, and/or angiogram at least 6 months after the reference date if AFP level was greater than 20 but 200 ng/mL or less. Those with negative imaging studies but AFP level greater than 200 ng/mL have a high likelihood of occult HCC and were excluded.44Gupta S. Bent S. Knowles J. Test characteristics of α-fetoprotein for detecting of hepatocellular carcinoma in patients with hepatitis C A systematic review and critical analysis.Ann Intern Med. 2003; 139: 46-50Crossref PubMed Scopus (319) Google ScholarWe identified a total of 520 potentially eligible patients with chronic hepatitis C and cirrhosis. Of these, 48 (9.2%) could not be classified as patients or controls because of insufficient data and were excluded. Eight patients with ethnicity listed other than Caucasian, Hispanic, African American, and Asian also were excluded. The study included the remaining 464 patients with chronic hepatitis C and cirrhosis: 207 patients and 257 controls. The study protocol was approved by the institutional review boards at Stanford University and University of California, San Francisco.Statistical analysisWe estimated odds ratios with 95% confidence intervals by using conditional logistic regression on case-control sets, matched within study centers and study period, and sex and age group (≤45, 46–55, 56–65, >65 yr). To control for potential confounding caused by cirrhosis severity and residual confounding caused by age, we also included CTP scores and age (continuous variable) in all regressions. Statistical significance was defined as a 2-sided P value of less than 0.05. All statistical analyses were performed using STATA (version 7.0; STATA Corporation, College Station, TX).ResultsPatient characteristicsTable 1 shows the distribution of patient characteristics by sex. Among both sexes, patients were more likely than controls to be older, have higher CTP scores, higher AFP levels, and to be identified as Asian. Among men, patients also were more likely than controls to be identified as African American.Table 1Distribution of Patients’ Clinical Characteristics, by SexRisk factorsMenWomenHCC (N = 172)Controls (N = 197)HCC (N = 35)Controls (N = 60)Age (yr, mean ± SD)57.8 ± 9.752.1 ± 7.862.7 ± 9.555.7 ± 8.2CTP (1–15 points, mean ± SD)7.8 ± 2.47.3 ± 2.68.4 ± 2.57.2 ± 2.3AFP (ng/mL, median and range)51.5 (1.9–669,000)7.0 (0.25–137)183.0 (2.0–11,490)9.0 (2–128.6)Ethnicity, N (%) Caucasian95 (55)140 (71)9 (26)35 (58) Hispanic17 (10)34 (17)5 (14)8 (13) African American18 (11)8 (4)5 (14)7 (12) Asian42 (24)15 (8)16 (46)10 (17) Open table in a new tab The mean tumor size was 4.2 ± 3.3 cm (SD) among patients. African-American patients were more likely to have multilobar tumor involvement compared with Caucasians, Hispanics, and Asian Americans (57% vs. 27%, 43%, and 24%, respectively, P = 0.009) (Table 2) . Although there were no statistically significant differences in other tumor characteristics between the different ethnic groups, there is a trend for having larger or diffuse tumors, tumor vascular invasion, and multifocal tumors in African Americans (Table 2).Table 2Tumor Characteristics by EthnicityTumor characteristicsCaucasian (N = 104)Hispanic (N = 22)African American (N = 23)Asian (N = 58)P valueTumor size <5 cm65.1%71.4%39.1%64.9%0.089 ≥5 cm or diffuse34.9%28.6%60.9%35.1%Tumor number 154.8%68.2%30.4%52.6%0.095 2–322.1%22.7%21.8%24.6% ≥4 or diffuse23.1%9.1%47.8%22.8%Lobar involvement Unilobar76.0%57.1%43.5%73.2%0.009 Multilobar24.0%42.9%56.5%26.8%Vascular invasion No80.5%80.0%68.8%92.5%0.10 Yes19.5%20.0%31.2%7.5% Open table in a new tab Risk factors for hepatocellular carcinoma in hepatitis C virus cirrhosisTable 3 shows odds ratios adjusted for study center, reference age, and CTP score. Within each sex, Asians were more likely than Caucasians to develop HCC (odds ratio, 4.3; 95% confidence interval, 2.1–9.0 for men; odds ratio, 4.6; 95% confidence interval, 1.2–18.5 for women). There was also a trend toward increased HCC risk in African-American men (odds ratio, 2.4; 95% confidence interval, 0.89–6.3).Table 3HCC Risk According to Ethnicity on Case-Control Sets Matched Within Study Centers, Study Period, and Age Groups, by SexSex PredictorsHCC (N = 207) n (%)Controls (N = 257) n (%)Multivariate ORaAdjusted for severity of liver disease (CTP score) and age (continuous variable). (95% CI)Men, N = 369 Caucasian95 (55)140 (71)1.0 (referent) Hispanic17 (10)34 (17)0.9 (0.44–1.7) African American18 (11)8 (4)2.4 (0.89–6.3) Asian42 (24)15 (8)4.3 (2.1–9.0)Women, N = 95 Caucasian9 (26)35 (58)1.0 (referent) Hispanic5 (14)8 (13)1.2 (0.18–7.5) African American5 (14)7 (12)2.2 (0.43–12.1) Asian16 (46)10 (17)4.6 (1.2–18.5)a Adjusted for severity of liver disease (CTP score) and age (continuous variable). Open table in a new tab DiscussionThe present study indicates that, among patients with cirrhosis secondary to chronic hepatitis C, Asians and possibly African Americans have a higher risk for HCC than do Caucasians. After adjustment was made for age, sex, and severity of liver disease, Asian Americans were approximately 4 times more likely to have HCC than Caucasians (P < 0.0001). Published literature from Japan does report a much higher 5-year cumulative HCC incidence than the literature from Western patients.52Fattovich G. Ribero M.L. Pantalena M. Diodati G. Almasio P. Nevens F. Tremolada F. Degos F. Rai J. Solinas A. Mura D. Tocco A. Zagni I. Fabris F. Lomonaco L. Noventa F. Realdi G. Schalm S.W. Tagger A. Hepatitis C virus genotypes: distribution and clinical significance in patients with cirrhosis type C seen at tertiary referral centres in Europe.J Viral Hepat. 2001; 8: 206-216Crossref PubMed Scopus (43) Google Scholar, 53Ikeda K. Saitoh S. Koida I. Arase Y. Tsubota A. Chayama K. Kumada H. Kawanishi M. A multivariate analysis of risk factors for hepatocellular carcinogenesis: a prospective observation of 795 patients with viral and alcoholic cirrhosis.Hepatology. 2003; 18: 47-53Crossref Scopus (698) Google Scholar, 54Tanaka K. Sakai H. Hashizume M. Hirohata T. A long-term follow-up study on risk factors for hepatocellular carcinoma among Japanese patients with liver cirrhosis.Jpn J Cancer Res. 1998; 89: 1241-1250Crossref PubMed Scopus (37) Google Scholar A prospective study of Italian patients with HCV and compensated cirrhosis reported a 5-year cumulative HCC incidence of approximately 4% to 6%.52Fattovich G. Ribero M.L. Pantalena M. Diodati G. Almasio P. Nevens F. Tremolada F. Degos F. Rai J. Solinas A. Mura D. Tocco A. Zagni I. Fabris F. Lomonaco L. Noventa F. Realdi G. Schalm S.W. Tagger A. Hepatitis C virus genotypes: distribution and clinical significance in patients with cirrhosis type C seen at tertiary referral centres in Europe.J Viral Hepat. 2001; 8: 206-216Crossref PubMed Scopus (43) Google Scholar On the other hand, prospective studies of Japanese patients with HCV and cirrhosis reported a 5-year cumulative HCC incidence of up to 21.5% to 41%, albeit many if not the majority of these Japanese patients also had decompensated end-stage liver disease in addition to cirrhosis.53Ikeda K. Saitoh S. Koida I. Arase Y. Tsubota A. Chayama K. Kumada H. Kawanishi M. A multivariate analysis of risk factors for hepatocellular carcinogenesis: a prospective observation of 795 patients with viral and alcoholic cirrhosis.Hepatology. 2003; 18: 47-53Crossref Scopus (698) Google Scholar, 54Tanaka K. Sakai H. Hashizume M. Hirohata T. A long-term follow-up study on risk factors for hepatocellular carcinoma among Japanese patients with liver cirrhosis.Jpn J Cancer Res. 1998; 89: 1241-1250Crossref PubMed Scopus (37) Google Scholar Besides ethnicity-related genetic factors, other explanations for the observed increased HCC risk in Asians may involve potentially higher prevalences of occult HBV infection, longer duration of HCV infection, or differences in access to care or health-care-seeking behavior. Although the current analysis excluded patients with obvious HBV infection, traces of HBV still can be detected by sensitive polymerase chain reactions in serum and/or liver tissues of such patients.2Liang T.J. Jeffers L.J. Reddy K.R. De Medina M. Parker I.T. Cheinquer H. Idrovo V. Rabassa A. Schiff E.R. Viral pathogenesis of hepatocellular carcinoma in the United States.Hepatology. 1993; 18: 1326-1333PubMed Google Scholar Asian immigrants also may acquire HCV infection during childhood from unsanitary medical practices and living conditions.36Do S. The natural history of hepatitis B in Asian Americans.Asian Am Pac Islander J Health. 2001; 9: 141-152PubMed Google Scholar Thus, at the same reference age, Asian patients may have been infected with HCV for 2–3 decades longer than Caucasian patients, many of whom may not have acquired the infection until the second or third decade of life. In addition, when compared with the ethnic distribution of San Francisco and Santa Clara County whe" @default.
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