Reduction therapy of alanine aminotransferase levels prevent HCC development in patients with HCV-associated cirrhosis.

BACKGROUND: To find a way to prevent the development of hepatocellular carcinoma (HCC) from hepatitis C virus-associated liver cirrhosis (HCV-LC), an analysis of the HCV-LC patients who had received reduction therapy of the alanine aminotransferase (ALT) levels was performed. PATIENTS AND METHODS: Seventy-four consecutive HCV-LC patients of Child Stage A were followed for >10 years for the development of HCC. They were divided into two groups: in group A, the reduction therapy for the ALT levels was aggressively performed, while in group B, the reduction therapy was not performed aggressively. The patients were subdivided into three sub-groups according to their serum ALT levels. In groups A and B, the high ALT group was comprised, respectively, of nine and five patients whose annual average serum ALT levels were persistently high (> or =80 IU), while the low ALT group was comprised of 19 and 20 patients whose annual average serum ALT levels were persistently low (<80 IU). The remaining eleven and ten patients had annual average serum ALT levels which fluctuated and were unclassified (unclassified group). RESULTS: In group B, 65.7% of the patients had developed HCC in 13 years, in contrast to only 41.0% of group A (p=0.039). In group A, the median HCC development time was 12.8 years, in contrast to only 3.8 years in group B (p=0.0013). Multivariate analysis demonstrated that the mode of reduction therapy and ALT levels were the significant factors affecting HCC development. CONCLUSION: The chances of surviving for more than ten years without developing HCC for HCV-LC patients

Ursodiol use is possibly associated with lower incidence of hepatocellular carcinoma in hepatitis C virus-associated liver cirrhosis.

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.