BACKGROUNDHepatic steatosis is one of the histopathologic features of chronic hepatitis C. It was reported recently that the expression of hepatitis C virus (HCV) core protein in transgenic mice induced hepatocellular carcinoma (HCC) in association with steatosis. The objective of this study was to determine the relation between hepatic steatosis and hepatocarcinogenesis in patients with chronic HCV infection.METHODSThe authors studied 161 patients with chronic HCV infection who were diagnosed at Nagasaki University Hospital, Nagasaki, Japan, between January 1980 and December 1999. Age, gender, body mass index (BMI), habitual drinking, diabetes mellitus, serum alanine aminotransferase (ALT) level, HCV serotype, serum level of HCV core protein, interferon (IFN) treatment, hepatic fibrosis inflammation, and hepatic steatosis were studied with regard to their significance in the development of HCC using univariate and multivariate analyses.RESULTSThe cumulative incidence rates of HCC were 24%, 51%, and 63% at 5 years, 10 years, and 15 years, respectively. Multivariate analysis identified hepatic steatosis, together with aging, cirrhosis, and no IFN treatment, as independent and significant risk factors for HCC (P = 0.0135, P = 0.0390, P = 0.0068, and P = 0.0142, respectively). In addition, hepatic steatosis was correlated with BMI, serum ALT levels, and triglyceride levels.CONCLUSIONSThe findings of the current study indicate that hepatic steatosis is a risk factor for HCC in patients with chronic HCV infection. Patients with chronic HCV and hepatic steatosis should be monitored carefully for HCC. Cancer 2003;97:3036–43. © 2003 American Cancer Society.DOI 10.1002/cncr.11427
We conducted a phylogenetic analysis of 19 hepatitis B virus strains from Laos that belonged to 2 subgenotypes of a new genotype I. This emerging new genotype likely developed outside Southeast Asia and is now found in mixed infections and in recombinations with local strains in a geographically confi ned region.A s a result of mutations and recombinations, hepatitis B virus (HBV) has evolved into 8 known genotypes (A-H), with a putative new genotype I recently found in Asia (1,2). Some genotypes have been associated with distinct clinical patterns, and their detection and identifi cation are important for virus and disease surveillance.In Laos, 8.7% of the population are chronically infected with HBV, and perinatal transmission is the most common route of infection. Here, we present the phylogenetic analysis of 19 related strains found in voluntary blood donors from Laos that cluster with the new genotype I. The StudyPhylogenetic analysis of sequences obtained from hepatitis B surface antigen-positive fi rst-time blood donors from donation centers in Vientiane City and central provinces of Laos showed that 163 (42.2%) strains were of genotype B, and 204 (55.4%) were of genotype C. Subgenotypes included B2 (18), B3 (1), B4 (128), and B5 (16), as well as C2 (190), C3 (1), and C5 (13) ( Figure 1, panel A). Nineteen strains, including 15 complete sequences, did not group with any of the known genotypes A-H. These sequences formed 2 clusters, which were emerging from a common node (bootstrap value of 100%; Figure 1, panel A). One of the clusters grouped with a recently reported single strain from Vietnam, for which we had previously defi ned a new genotype I (2). The 2 new groups from Laos will be referred to here as subgenotypes I1 and I2. Notably, all I1 strains were of serotype adw, whereas all I2 subgenotypes were of serotype ayw. With 1 exception, all genotype I strains were found in donors living in Vientiane City. Strains recovered from Hanoi, Vietnam, 8 years ago and reported as aberrant strains (3) also group with subgenotype I1.Detailed analysis of full genome sequences showed that genotype C strains as a group were most closely related to genotype I (average Kimura distance of 7.89%, Table 1). The closest subgenotype was C3 with a 7.0% average Kimura distance (data not shown). The bootstrap value of the separating node was 92% (Figure 1, panel A), which is well above the bootstrap value of the G/DE node. On the S gene level, genotype I was most closely related to genotype G with a distance of 4.23% and a bootstrap value of 96% at the separating node (data not shown). Within the 2 subgenotypes I1 and I2, an average diversity over the complete genome of 1.19% and 0.94% was calculated; this difference increased to 2.33% when all strains were considered as a single group. The maximal genetic distance between 2 full-length genotype I strains was 4.3%. All clusterEmerging Infectious Diseases • www
GH, IGF-1 and IGFBP-3 are associated with hepatic fibrosis and steatosis in NAFLD. Low levels of IGF-1 might be associated with fibrosis while low level of GH with hepatic steatosis.
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