title: Ursodiol use is possibly associated with lower incidence of hepatocellular carcinoma in hepatitis C virus-associated liver cirrhosis.
abstract: In a previous study of patients with hepatitis C virus (HCV)-associated liver cirrhosis (HCV-LC), we showed that increased liver inflammation, as assessed by higher serum alanine aminotransferase (ALT), was associated with increased risk for the development of hepatocellular carcinoma (HCC). This suggested that suppression of inflammation might inhibit HCC development in HCV-LC. Several agents have been suggested to possess chemopreventive potential against the development of HCC in chronic HCV-associated liver disease, including herbal medicines, such as Stronger-Neo-Minophagen C (glycyrrhizin) and Sho-saiko-to (TJ-9). Ursodiol [ursodeoxycholic acid (UDCA)], a bile acid widely used to treat cholestatic liver diseases, also possesses anti-inflammatory properties in liver disease. We hypothesized that suppression of liver inflammation, as assessed by decreases in serum ALT, might inhibit HCC occurrence in patients with HCV-LC. In this study, the preventive effect of UDCA on HCC was examined in patients with early-stage HCV-LC. One hundred two patients with HCV-LC (Child stage A) were treated with anti-inflammatory drugs, Stronger-Neo-Minophagen C,Sho-saiko-to, or UDCA, with the goal of lowering the average serum ALT level to <80 IU. Iftheaverage ALT level did not remain <80 IU after treatment with one agent, multiagent therapy was initiated. The patients were followed up for >5 years and were retrospectively subdivided into two groups: 56 UDCA users (group A) and 46 UDCA nonusers (group B). The mean +/- SD dosage of UDCA administered in group A was 473.7 +/- 183.0 mg/d. The average duration of UDCA administration in group A was 37.3 +/- 15.9 months over the 5-year study period. The cumulative incidence of HCC was recorded. The 5-year incidence of HCC in group A was 17.9% (10 of 56) and was significantly lower than that in group B (39.1%, 18 of 46; P = 0.025). The risk for HCC incidence, calculated by a logistic regression model, showed that the administration of UDCA significantly decreased hepatocarcinogenesis (P = 0.036). The herbal medicines used were comparable in dosage and treatment duration in the UDCA and non-UDCA groups. In conclusion, UDCA might prevent HCC development in HCV-LC. Interestingly, because the serum ALT trends over time were nearly the same in both groups, the chemopreventive effectiveness of UDCA was not accompanied by greater reductions in ALT compared with the UDCA nonusers.
authors.affiliation: Department of Gastroenterology, Kanagawa Cancer Center Hospital, 1-1-2, Nakao, Asahi-ku, Yokohama 241-0815, Japan. tarao@kcch.jp
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tarao
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Fujiyama
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ohkawa
authors.forename: Kaoru
authors.initials: K
authors.lastname: Miyakawa
authors.forename: Setsuo
authors.initials: S
authors.lastname: Tamai
authors.forename: Satoru
authors.initials: S
authors.lastname: Hirokawa
authors.forename: Takahiro
authors.initials: T
authors.lastname: Masaki
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000704:Analysis of Variance; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000517:prevention & control*; D002471:Cell Transformation, Neoplastic; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use; D005260:Female; D019695:Glycyrrhizic Acid / Q000627:therapeutic use; D016174:Hepacivirus / Q000472:pathogenicity; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D015994:Incidence; D007249:Inflammation; D008103:Liver Cirrhosis / Q000150:complications* / Q000821:virology*; D008113:Liver Neoplasms / Q000209:etiology / Q000517:prevention & control*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
chemical_list: D002756:Cholagogues and Choleretics; D004365:Drugs, Chinese Herbal; C461320:shosaiko-to; D019695:Glycyrrhizic Acid; D014580:Ursodeoxycholic Acid; D000410:Alanine Transaminase