Deng-Yn Lin

Clinical and Histological Events Preceding Hepatitis B e Antigen Seroconversion in Chronic Type B Hepatitis

A 60-mo longitudinal study has been undertaken in 99 HBeAg-positive patients with clinicopathologically verified chronic hepatitis. Hepatitis B e antigen clearance occurred in 30 patients at a rate of approximately 17% per year. A phenomenon of abrupt elevation of serum glutamic pyruvic transaminase (greater than 300 IU/L) with histological changes compatible with chronic lobular hepatitis was observed in 13 of 20 patients (65%) preceding spontaneous HBeAg clearance. In contrast, 8 of 10 patients on immunosuppressive or antiviral therapy, or both, had uneventful HBeAg clearance. It was concluded that HBeAg clearance can occur in patients with varying immunologic status. The mechanism responsible for HBeAg clearance awaits further study.

Prospective Randomized Controlled Study of Interferon-Alpha in Preventing Hepatocellular Carcinoma Recurrence after Medical Ablation Therapy for Primary Tumors

Hepatocellular carcinoma (HCC) recurrence after ablation therapy for primary tumors is common.

Metastatic septic endophthalmitis in pyogenic liver abscess

In a consecutive series of 180 patients with pyogenic liver abscess, three patients (two men and one woman, between 46 and 75 years of age) had metastatic Klebsiella endophthalmitis. The incidence of metastatic endophthalmitis was 1.7% in patients with pyogenic liver abscess, 5.2% in patients with Klebsiella liver abscess, and 7.8% in patients with Klebsiella liver abscess having Klebsiella bacteremia. Despite aggressive therapeutic measures, the men permanently lost their vision and the woman eventually required an evisceration of her right eye. Delayed recognition and/or treatment as well as the nature of bacteria probably contributed to the tragic outcome. The findings suggest that a high index of suspicion is critical and a combined effort of the internist and ophthalmologist is mandatory.

Altered expression patterns of lipid metabolism genes in an animal model of HCV core-related, nonobese, modest hepatic steatosis

BackgroundBecause the gene expression patterns of nonobese hepatic steatosis in affected patients remain unclear, we sought to explore these patterns using an animal model of nonobese hepatic steatosis.MethodsWe developed mice that conditionally express the hepatitis C virus (HCV) core protein regulated by the tetracycline transactivator (tTA). Microarray analyses and reverse-transcription polymerase chain reaction were performed using liver samples of both the double transgenic mice (DTM), which express both the HCV core and tTA, and single transgenic mice (STM), which express tTA alone, at 2 months of age. Functional categories of genes with altered expression were classified using gene ontology programs. Serum glucose, lipid levels, and systemic blood pressure were also measured.ResultsApproximately 20–30% of hepatocytes from the DTM were steatotic. No significant differences were observed in the serum glucose, lipid content, or blood pressure levels between the DTM and STM. Gene expression analyses revealed Sterol-regulatory element-binding protein (SREBP) pathway activation and dysregulation of the following genes involved in lipid metabolism: 3-hydroxy-3-methylglutaryl-coenzyme A synthase 1, Apolipoprotein AII, Apolipoprotein CI, acyl-CoA thioesterase I, and fatty acid binding protein 1; in mitochondrial function: solute carrier family 25 member 25 and cytochrome c oxidase subunit II; in immune reaction: complement component 3, lymphocyte antigen 6 complex, locus A, lymphocyte antigen 6 complex, locus C, lymphocyte antigen 6 complex, locus D, and lymphocyte antigen 6 complex, locus E.ConclusionSome genes of lipid metabolism, mitochondrial function, and immune reaction and the SREBP pathway are involved in HCV core-related, nonobese, modest hepatic steatosis.

Prevalence of Antibodies to Hepatitis C Virus in the Hemodialysis Unit

An enzyme immunoassay was used to detect antibodies to hepatitis C virus (anti-HCV) in 261 patients and 69 staff members of a hemodialysis unit. The prevalence of anti-HCV was 46.7% in patients and 2.9% in staff members (p less than 0.001). The prevalence of anti-HCV increased significantly with increasing duration of hemodialysis (p less than 0.001), but was not related to age, sex, history of blood transfusion, status of hepatitis B or hepatitis A virus infection, or serum ALT. Patients with hepatitis episode increased with increasing duration of hemodialysis and showed a significantly higher prevalence of anti-HCV than those without (63.1 vs. 34.7%, p less than 0.001). The prevalence of anti-HCV in patients with hepatitis also increased with increasing duration of hemodialysis (p = 0.05). Thus, HCV appears to be the major cause of hepatitis in hemodialysis patients. Besides strict infection control measures, further studies are needed to determine the mode of HCV infection and its prevention in the hemodialysis unit.

Etiology of sporadic acute viral hepatitis in Taiwan : The role of hepatitis C virus, hepatitis E virus and GB virus-C/hepatitis G virus in an endemic area of hepatitis A and B

The etiology of sporadic acute hepatitis was studied in 334 consecutive patients from Taiwan (237 men and 97 women, aged 16–81 years), with emphasis on the role of hepatitis C virus (HCV), hepatitis E virus (HEV), and GB virus‐C/hepatitis G virus (GBV‐C/HGV) in acute non‐A, non‐B (NANB) hepatitis and in HBsAg carriers with superimposed acute hepatitis. According to the conventional diagnostic criteria, there were 12 cases (3.6%) of acute hepatitis A, 17 cases (5.1%) of acute hepatitis B, 128 cases (38.3%) of acute NANB hepatitis, and 177 cases (53.0%) of acute hepatitis in HBsAg carriers (those who were HBsAg positive but IgM anti‐HBc negative). Among 128 cases of acute NANB hepatitis, 70 (54.7%) had acute hepatitis C (HCV RNA positive), 5 (3.9%) had acute hepatitis E (IgM anti‐HEV positive), and the other 53 (41.4%) were presumably acute hepatitis non‐A‐E. The prevalence of acute hepatitis A, B, E, and non‐A‐E showed no significant sex difference, whereas acute hepatitis C was significantly more prevalent in females. The prevalence of acute hepatitis A and B decreased and that of acute hepatitis C increased significantly with increasing age. In contrast, acute hepatitis E and non‐A‐E showed no significant age predominance. Of 177 HBsAg carriers with acute hepatitis, 64 (36.1%) demonstrated non‐B hepatotropic virus superinfection, with HCV being the most common (60.9%), followed by hepatitis D, E, and A viruses, and the other 55 (31.1%) and 58 (32.8%) were presumed to have acute exacerbation of chronic hepatitis B or superimposed acute hepatitis non‐A‐E, respectively. Serum GBV‐C/HGV RNA was detected in 3–4% of acute hepatitis non‐A‐E cases, suggesting its limited role in these cases. J. Med. Virol. 58:154–159, 1999.

Hepatitis C virus infection facilitates gallstone formation.

Background:  Bile duct damage and hepatic steatosis are two characteristic histological findings in hepatitis C virus infection; and high prevalence of hepatitis C antibody is noted in patients with cholangiocarcinoma. The purpose of the present study was to examine the relationship between biliary diseases and hepatitis C virus infection.

Correlation of mutational analysis to clinical features in Taiwanese patients with Gilbert's syndrome

OBJECTIVES:Mutations in the promoter as well as in the coding region of the bilirubin UDP-glucuronosyltransferase gene (UGT1A1) have been found to be associated with Gilberts syndrome. However, the genetic basis of Gilberts syndrome in our population and correlation of these mutations to fasting serum bilirubin levels in patients with Gilberts syndrome remain to be clarified.METHODS:We applied polymerase chain reaction–based direct-sequencing assays to examine mutations in UGT1A1 gene in 20 unrelated Gilberts patients and in a family with Gilberts syndrome.RESULTS:We studied three mutations that were previously reported to be associated with Gilberts syndrome (i.e., the TATAA-box mutation, Gly71Arg, and Pro229Gln) in 20 patients with Gilberts syndrome. Of the patients, 16, five, and six were found to have the TATAA-box, Gly71Arg and Pro229Gln mutations, respectively. Seven patients had simultaneous mutations both in the TATAA box and in the coding region. Of note, all six patients with Pro229Gln also had the TATAA-box mutation. Localization of Pro229Gln on the allele containing the TATAA-box mutation was demonstrated in a family with Gilberts syndrome. The patients simultaneously heterozygous for both the TATAA-box mutation and Gly71Arg usually had serum bilirubin levels similar to those found in the patients homozygous for the TATAA-box mutation, but usually higher than those found in the patients heterozygous for the TATAA-box mutation alone. On the other hand, concurrence of Pro229Gln in patients with TATAA-box mutation or with Gly71Arg did not significantly affect serum bilirubin levels.CONCLUSIONS:The TATAA-box mutation and Gly71Arg are the major causes for Gilberts syndrome in our population. Concurrence of mutations of Gly71Arg and TATAA-box usually exerts a synergistic effect on hyperbilirubinemia. Pro229Gln, which is regularly linked to the TATAA-box mutation, may not have a significant effect on serum bilirubin levels.

Eight-year nationwide survival analysis in relatives of patients with hepatocellular carcinoma: Role of viral infection

Abstract Background: Families of patients with hepatocellular carcinoma (HCC) carry a high risk of developing HCC. We determine the number of fatalities in relatives of HCC patients during an 8‐year period to understand the risk and cause of HCC in relatives of patients with HCC.

Hepatic inflammation mediated by hepatitis C virus core protein is ameliorated by blocking complement activation

BackgroundThe pathogenesis of inflammation and fibrosis in chronic hepatitis C virus (HCV) infection remains unclear. Transgenic mice with constitutive HCV core over-expression display steatosis only. While the reasons for this are unclear, it may be important that core protein production in these models begins during gestation, in contrast to human hepatitis C virus infection, which occurs post-natally and typically in adults. AIMS: To more realistically model the effect of core protein production in the adult liver, we developed a mouse with conditional expression of HCV core and examined the effect of core protein production in the adult liver.MethodsLiver biopsy samples from transgenic mice with tetracycline(tet)-regulated conditional core protein expression were evaluated immunohistologically. Microarray analysis of HCV core transgenic mice with steatohepatitis pointed to a role of the complement pathway. This was further explored by blocking complement activation by in vivo administration of CD55 (decay accelerating factor for complement), which inhibits activation of C3.ResultsTransgenic mice exhibited low, intermediate, or high HCV core protein expression when fed a permissive diet of standard chow. Aside from hepatic steatosis, hepatic inflammation and fibrosis were seen in mice with intermediate levels of core protein. Microarray analyses of inflamed liver demonstrated activation of both the complement (C3 up-regulation) and coagulation pathways (fibrinogen B up-regulation). Administration of CD55 reduced hepatic inflammation.ConclusionTransgenic mice that conditionally express intermediate HCV core protein develop inflammation, steatosis, and fibrosis. These effects mediated by HCV core are reduced by administration of CD55, a regulator of the complement pathway. The model may be valuable in investigating the pathogenesis of liver inflammation in chronic hepatitis C.