Hepatitis: Koay LB

Koay LB, Tsai SL, Sun CS, Wu KT. · Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi-Mei Medical Center, 901 Chung Hwa Road, Yung Kang City, Tainan, Taiwan. · Hepatogastroenterology. · Pubmed #19102393 No free full text.

Abstract: A 66-year-old female presented with acute illness of severe hepatic dysfunction. She had a past history of chronic hepatitis of low disease activity. After admission and clinical investigation including liver biopsy, it showed an underlying chronic liver disease suggestive of autoimmune hepatitis (AIH) with early liver cirrhosis. Together with other clinical features, this patient was diagnosed as definite AIH type 1 by using the IAIHG (International Autoimmune Hepatitis Group) criteria. During this episode, superinfection by Epstein-Barr virus (EBV) was evidenced by positive PCR (polymerase chain reaction) test, and serial changes of EBV VCA IgM and IgG tests. Severe hepatic impairment was evidenced by markedly elevated AST level 3090 IU/L, high bilirubin level 26.4 mg/dL, and presence of ascites. The patient gradually recovered and liver function improved in agreement with the decline of EBV VCA titers. Immunosuppressive therapy resulted in further improvement of the aminotransferases levels. This is an unusual case of EBV superinfection on pre-existing AIH with early cirrhosis, which caused enhancement of the autoimmune disease process and resulted in severe hepatic decompensation and jaundice. We herein describe the case and briefly review the literature.

Feng IC, Koay LB, Sheu MJ, Kuo HT, Sun CS, Lee C, Chuang WL, Liao SK, Wang SL, Tang LY, Cheng CJ, Tsai SL. · Hepatogastroenterology Section, Department of Internal Medicine, Chi Mei Medical Center, Yung-Kang City, Tainan, Taiwan. · J Biomed Sci. · Pubmed #17109186 No free full text.

Abstract: Acute exacerbations (AEs) of chronic hepatitis B (CH-B) are accompanied by increased T cell responses to hepatitis B core and e antigens (HBcAg/HBeAg). Why patients are immunotolerant (IT) to the virus and why AEs occur spontaneously on the immunoactive phase remain unclear. The role of HBcAg-specific CD4(+)CD25(+) regulatory T (T(reg)) cells in AE and IT phases was investigated in this study. The SYFPEITHI scoring system was employed to predict MHC class II-restricted epitope peptides on HBcAg overlapping with HBeAg that were used for T(reg)-cell cloning and for the construction of MHC class II tetramers to measure T(reg) cell frequencies (T(reg) f). The results showed that HBcAg-specific T(reg) f declined during AE accompanied by increased HBcAg peptide-specific cytotoxic T lymphocyte frequencies. Predominant Foxp3-expressing T(reg) cell clones were generated from patients on the immune tolerance phase, while the majority of Th1 clones were obtained from patients on the immunoactive phase. T(reg) cells from liver and peripheral blood of CH-B patients express CD152 and PD1 antigens that exhibit suppression on PBMCs proliferation to HBcAg. These data suggest that HBcAg peptide-specific T(reg) cells modulate the IT phase, and that their decline may account for the spontaneous AEs on the natural history of chronic hepatitis B virus infection.

Lee HH, Uen YH, Tian YF, Sun CS, Sheu MJ, Kuo HT, Koay LB, Lin CY, Tzeng CC, Cheng CJ, Tang LY, Tsai SL, Wang AH. · Department of Medical Research, Chi-Mei Medical Center, Tainan 710, Taiwan. · Cancer Epidemiol Biomarkers Prev. · Pubmed #19423534 No free full text.

Abstract: BACKGROUND: Up-regulation of Wnt-1 protein has been reported in hepatitis B virus (HBV)-related and hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) tissues and cell lines. It is known to play a fundamental role in signaling cancer progression, whereas its prognostic role in HCC remains unexplored. METHODS: As a prognostic biomarker, this study analyzed Wnt-1 protein expression in 63 histology-verified HCC patients receiving curative resection. In each paired tumor and nontumor specimen, Wnt-1 levels were semiquantitatively measured by Western blotting and expressed by tumor/nontumor ratio. The data were further correlated with quantitative real-time PCR as well as with beta-catenin and E-cadherin expression by immunohistochemistry. Cumulative tumor recurrence-free survival curves were constructed using the Kaplan-Meier method and compared by the log-rank test. RESULTS: The results showed that 26 (group I) and 37 (group II) HCC patients had an expression ratio of Wnt-1 > or =1.5 and <1.5, respectively. The amount of Wnt-1 estimated by tumor/nontumor ratio correlated with the results by quantitative real-time PCR. High tumor Wnt-1 expression correlated with enhanced nuclear beta-catenin accumulation, diminished membranous E-cadherin expression, and increased tumor recurrence after curative tumor resection. CONCLUSIONS: These results suggest that Wnt-1 may be used as a predisposing risk factor for HCC recurrence. The use of tumor Wnt-1 as prognostic biomarker may identify patients with HBV- and/or HCV-related HCC patients with a high risk of tumor recurrence who may then benefit from further intensive therapy after surgery.

Sheu MJ, Kuo HT, Lin CY, Koay LB, Lee C, Chen JJ, Tang LY, Tsai SL. · Division of Hepatogastroenterology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan. · Eur J Gastroenterol Hepatol. · Pubmed #19190496 No free full text.

Abstract: BACKGROUND: Acute exacerbation (AE) of chronic hepatitis B virus (HBV) infection in cancer chemotherapy patients and in organ transplant recipients receiving immunosuppressants may cause catastrophe and high mortality. Hence, immediate treatment with nucleoside analogues for such patients has become a consensus. Anti-HBV therapeutic trials in Asia have shown that AE of chronic hepatitis B (CH-B) may result in increased sustained remission (SR) rate with lamivudine monotherapy. Nonetheless, AE episodes in CH-B patients may evolve uneventfully and lead to spontaneous remission. Thus, the policy of immediate anti-HBV therapy for AE patients reaches an impasse. Once treatment is initiated, life long HBV suppression may be necessary. OBJECTIVE: To determine whether lamivudine monotherapy during an AE of CH-B results in an increase in SR compared with no therapy. METHODS: A cohort of 154 CH-B patients seropositive for hepatitis B e antigen with AE formed the study group. This included 102 cases receiving a nationwide therapeutic trial of 18-month lamivudine monotherapy that were compared with 52 cases with no therapy. All were observed for at least 30 months, which encompassed the 18-month on treatment period and a 12-month posttreatment follow-up. RESULTS: No significant increase was observed in the SR rate in the lamivudine treatment group compared with the spontaneous remission rate in the untreated patients (P=0.782, Fisher's exact test). CONCLUSION: AE does not increase the SR rate during 18-month lamivudine monotherapy. Immediate lamivudine therapy for AE patients is not justified as mandatory. The policy should be only applied to AE patients with impending liver failure.

Koay LB, Lin CY, Tsai SL, Lee C, Lin CN, Sheu MJ, Kuo HT, Sun CS. · Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, 901 Chung Hwa Road, Yung Kang City, Tainan, Taiwan, ROC. · Dig Dis Sci. · Pubmed #17053960 No free full text.

Abstract: Autoimmune hepatitis (AIH) is rare in Asian countries compared to the West, and an exceptionally low prevalence was noted previously in Taiwan. Using the revised criteria of the IAIHG, 48 cases of AIH patients were diagnosed. All patients were consecutively diagnosed over a period of 5 years. Detailed medical histories including disease onset, hepatitis B and C, alcohol, drugs, blood transfusion, and family history of autoimmune disease were recorded. Clinical manifestations, result of steroid therapy, outcome, and survival rate were investigated and analyzed. Clinical data on AIH patients with cirrhosis and without cirrhosis were compared and analyzed for their outcome. The statistical methods used were Fisher's exact test, Wilcoxon rank sum test, and Kaplan-Meier curve. Forty-eight patients were diagnosed as AIH type 1, with a median age of 58 years and a female:male ratio of 37:11. The most common clinical features at presentation were fatigue, jaundice, and anorexia. Ninety-eight percent of patients were ANA positive, and most of the patients showed elevated values of AST, ALT, serum globulin, and bilirubin. A substantial proportion of patients presented with poor liver function at entry and 35% of patients had liver cirrhosis, with relatively prolonged PT (P=0.001) and poorer outcome (P=0.005) compared to the noncirrhotics. As a whole there was a favorable treatment response and the overall survival rate was 85%. We conclude that the incidence of AIH in Taiwan is much higher than previously presumed and AIH type 1 is the predominant type of the disease. Although a substantial proportion of AIH patients presented with poor hepatic function at entry, as a whole there was a favorable clinical outcome.

Sheu MJ, Lin CY, Sun CS, Kuo HT, Koay LB, Lee C, Chen JJ, Tang LY, Tsai SL. · Department of Internal Medicine, Division of Hepatogastroenterology, Chi Mei Medical Center, Tainan, Taiwan. · J Formos Med Assoc. · Pubmed #16877240 links to  free full text

Abstract: Molecular epidemiologic studies have indicated the possible existence of mixed infection of different hepatitis B virus (HBV) genotypes in chronic hepatitis B (CH-B) carriers, but the effect of dual HBV genotype B and C infection on the efficacy of lamivudine therapy remains unclear. We report four CH-B patients with dual HBV genotype B and C infection and acute exacerbation who received lamivudine monotherapy for about 18 months. None of them had achieved a sustained response at the end of the 18-month trial of treatment.

Koay LB, Sun CS, Tsai SL, Lin CY. · Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan. · J Formos Med Assoc. · Pubmed #18194915 links to  free full text

Abstract: Genetic predisposition is known to be an important etiopathogenic factor of autoimmune hepatitis (AIH). HLA antigens associated with AIH have been well studied in Western countries and Japan, but there is no HLA typing data of AIH patients in Taiwan. We therefore investigated HLA phenotypes and their association with AIH patients and compared the results with those of normal subjects and patients with chronic liver disease. Group 1 consisted of 22 AIH patients. All were born in Taiwan with no history of blood transfusion. Group 2 consisted of 19 chronic liver disease patients. Group 3 consisted of 81 unrelated healthy subjects who were normal blood donors. All three groups were tested for HLA phenotypes (HLAA, B, C, DR, DQ) using the polymerase chain reaction-sequence specific probe method. The statistical method used was Fisher's exact test. We found that HLA-DQ5 was significantly more frequent in the AIH group compared to the control group (RR, 2.03; p = 0.034). Low frequency of A1 (n = 2/22), B8 (n = 1/22) and DR3 (n = 0/22) were noted compared to results from the West; only HLA-DR4 showed a higher rate in our AIH patients (n = 8/22). This is a preliminary report of our study of HLA antigens in AIH patients. Further investigation to characterize AIH patients into HLA allelic subgroups is being done.