Close association between high serum alanine aminotransferase levels and multicentric hepatocarcinogenesis in patients with hepatitis C virus‐associated cirrhosis

Abstract

BACKGROUND. Multicentric development of hepatocellular carcinoma (HCC) is a characteristic feature of hepatitis C virus (HCV)-associated cirrhosis (HCV-LC). In this study, the objective was to determine whether the persistent elevation of the serum alanine aminotransferase (ALT) level, which represents the inflammatory necrosis of hepatocytes, is correlated with the multicentric development of hepatocellular carcinoma (HCC) in patients with early-stage HCV-LC. METHODS. Ninety-three consecutive patients with biopsy proven HCV-LC (Child Stage A) who had been followed for Ͼ 5 years for the development of HCC were studied. They were subdivided into three groups according to their serum ALT level: Group A included 33 patients with annual average serum ALT levels that were persistently high (Ն 80 IU; high ALT group), Group B included 41 patients with annual average serum ALT levels that were persistently low (Ͻ 80 IU; low ALT group), and Group C included 19 unclassified patients. The patients had been studied prospectively with frequent ultrasonography and magnetic resonance imaging or computed tomography (CT) scans for Ͼ 5years. When the development of HCC was suspected, angiography, infusion of lipiodol into the hepatic artery, and lipiodol-CT scans were performed in all patients to determine the number of HCC nodules. RESULTS. In Group A, 27 patients (81.8%) developed HCC. Seventeen of 27 patients (63.0%) had multiple nodules. In contrast, in Group B, only 12 patients (29.3%) developed HCC, and only 1 of these 12 patients (8.3%) had multiple nodules. There was a significant difference between Groups A and B in the incidence of developing HCC (P Ͻ 0.001) and developing multiple nodules (P ϭ 0.006). In addition, among the male patients, the incidence of developing multiple HCC nodules in Group A (12 of 19 patients; 63.2%) was significantly higher (P Ͻ 0.05) compared with the incidence in Group B (0 of 6 patients; 0%). The same tendency was observed among the female patients. CONCLUSIONS. These results showed a close correlation between multicentric hepatocarcinogenesis and sustained necroinflammation of the liver in patients

A new staging system for resectable hepatocellular carcinoma: comparison with six existing staging systems in a large Chinese cohort

“…Our data showed that patients with macroscopic vascular invasion had a median survival of 11 months, which is well above that with other or without any treatment in the literature. (Llovet et al 1999b(Llovet et al , 2008a In addition, a high serum AST level was also an independent risk predictor in our study, which has been demonstrated by Poon et al (2000a, b;Poon and Fan 2003) Presumably, hepatitis activity presenting with higher serum levels of liver enzymes from sustained necroinXammation of the liver is associated with multicentric hepatocarcinogenesis and with poorer outcomes (Tarao et al 2002). Surprisingly, performance statuswhich reXects the cancer patient's general condition and has been included in BCLC-also was one of the independent predictors in our series of HCC patients who underwent surgical resection.…”

Common Transcriptional Signature of Tumor-Infiltrating Mononuclear Inflammatory Cells and Peripheral Blood Mononuclear Cells in Hepatocellular Carcinoma Patients

“…29; >68 or V 68 years old), gender (30), and ALT(ref. 31; >50 or V50 IU/L), could not differentiate gene expression in PBMCs. AFP (>20 or V20 ng/mL) was actually significant but was a much less powerful classifier (P < 0.02, assigned with 301 classifier genes).…”

Alanine aminotransferase level as a predictor of hepatitis C virus‐associated hepatocellular carcinoma incidence in a community‐based population in Japan

“…ALT levels are known to be associated with HCC 7,11,12 ; however, the relationship has not been described prospectively in a community-based setting. The present study demonstrates that elevated ALT levels, measured on average 8 years before cancer diagnosis, were associated with an increased rate of HCC among subjects chronically infected with HCV.…”

“…Other studies in Japan have shown that sustained elevated ALT levels in HCV-infected liver disease patients lead to increased HCC risk and recurrence of HCC. 11,12 Since most individuals infected with HCV remain asymptomatic, studies based on clinic patients may overestimate the true effect of ALT on HCC risk. In contrast, the community-based setting offers a unique advantage, in that it is mostly composed of infected individuals who are asymptomatic, minimizing the bias introduced by using patients who may have more severe liver disease.…”