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81.
Robert J. Fontana Paul Hayashi Herbert L. Bonkovsky David E. Kleiner Sweta Kochhar Jiezhun Gu Marwan Ghabril 《Digestive diseases and sciences》2013,58(6):1766-1775
Aims
The aim of this study was to describe the presenting features and outcomes of consecutive patients with liver injury attributed to interferon beta.Methods
The presenting features of eight subjects with clinically apparent liver injury attributed to interferon beta enrolled in the U.S. Drug-Induced Liver Injury Network (DILIN) prospective registry between 2004 and 2010 were reviewed and compared to 11 published reports of symptomatic hepatotoxicity.Results
All eight of the DILIN patients were women, 75 % were Caucasian and the mean age was 49 years. Most subjects presented with an acute hepatocellular injury pattern and mean serum alanine aminotransferase (ALT) levels were 725 ± 593 U/L. The median duration of interferon beta use before injury onset was 462 days, and four patients had been treated for more than a year. No patient had detectable antinuclear or smooth muscle antibodies. One patient died of acute liver failure and the remaining patients usually recovered within 2–3 months. Causality assessment scored three cases as definite, three highly likely, one probable and one possible. Eleven additional published cases were all women, mean age was 40 years, mean ALT at onset 840 U/L, and 7 (63 %) had autoantibodies. Liver histology in three cases from DILIN and nine from the literature commented upon centrilobular (zone 3) necrosis and infiltrates with lymphocytes and plasma cells.Conclusions
Interferon beta hepatotoxicity occurs mostly in women and has a variable, but often prolonged time to onset. Most patients have self-limited acute hepatocellular liver injury but several have required liver transplantation or died of acute liver failure. Liver histology available in three cases demonstrated zone 3 necrosis and autoimmune features suggestive of an immunologic basis to this adverse drug reaction. 相似文献82.
83.
Hossein Sendi Marjan Mehrab-Mohseni Saeid Shahraz Helene Norder Seyed-Moayed Alavian Babak Noorinayer Mohammad R. Zali Paul Pumpens Herbert L. Bonkovsky Lars O. Magnius 《Journal of clinical virology》2009,46(3):259-264
BackgroundRecent studies have suggested that Cytotoxic T lymphocytes (CTL) play a key role in eliminating hepatitis B virus (HBV).ObjectivesWe aimed to investigate the role of mutations in different immune epitopes of hepatitis B core antigen (HBcAg) among Iranians with hepatitis B e antigen negative chronic hepatitis B (e-CHB), and asymptomatic carriers (ASCs).Study designAmino acids 1–150 of HBcAg were characterized for HBV strains from 29 e-CHB patients and 48 ASCs from Iran. All patients were infected with HBV genotype D and had previously been investigated for the presence of pre-core and basic core promoter (BCP) mutants.ResultsAmino acid mutations of core protein were observed more frequently in HBV strains from ASCs than e-CHB patients (p = 0.014). Asn67 mutation was mutually exclusive to the combination Ile66 and Ser69 (P < 0.001). Substitutions for Ser21 and Thr12Ser were associated with lower serum levels of HBV DNA (p < 0.001). None of the patients with mutations in HLA-A2 CTL epitope, 18–27, had serum HBV DNA more than 105 copies/mL (p < 0.001). By multivariate analysis, high level (>105 copies/mL) of serum HBV DNA was inversely associated with the presence of mutations in CTL epitopes of HBc (OR: 0.11, p = 0.015), while it was directly associated with the presence of promoter double T1762A1764 mutations together with G1757 (OR: 16.87, p = 0.004).ConclusionThe inverse correlation between serum levels of HBV DNA and CTL escape mutations of the core protein in HBeAg seroconverted patients, supports the notion that selection of CTL escape mutations consolidates the persistence of HBV infection despite reducing viral fitness. 相似文献
84.
Tarun K. Narang Hossein Sendi Martin W. Scobey Herbert L. Bonkovsky 《Current hepatitis reports》2010,9(3):169-177
Hepatitis C virus (HCV) is a major cause of chronic hepatitis worldwide. Iron may play a comorbid role in HCV disease and
other liver diseases. Although adjunctive treatment of HCV disease with iron reduction is popular in east Asia, especially
Japan, it is less popular in the United States. However, iron reduction may be of importance, especially for certain HCV patient
subgroups that have not responded to or cannot tolerate standard therapy. This review focuses on recent advances in understanding
how iron may influence HCV infection and vice versa. A key is effects on levels of expression of the hepcidin gene in hepatocytes,
because hepcidin has emerged as the key regulator of iron homeostasis. This review also summarizes prior clinical studies
involving iron reduction therapy and clinical implications. 相似文献
85.
86.
Ghaziani T Shan Y Lambrecht RW Donohue SE Pietschmann T Bartenschlager R Bonkovsky HL 《Journal of hepatology》2006,45(1):5-12
BACKGROUND/AIMS: Hepatitis C infection induces hepatic oxidative stress. Heme oxygenase (HO), the rate-controlling enzyme of heme catabolism, plays a key role as a protector against oxidative, and other stresses. Other recent work has implicated Bach1, a heme binding protein that represses gene expression, in the regulation of HO-1 gene expression. METHODS: We investigated the effects of HCV polyprotein expression on expression of HO-1 and Bach1 genes in human hepatoma cells (Huh-7 cells). RESULTS: HO-1 was up-regulated in the cell line expressing HCV proteins from core up to the aminoterminal domain of NS3. Addition of increasing concentrations of N-acetylcysteine (NAC) led to down-regulation of HO-1 in cells expressing HCV proteins. In contrast, Bach1 was significantly down-regulated in these cells. Sodium arsenite, a strong inducer of oxidative stress and HO-1, reduced Bach1 expression in wild type Huh-7 cells, and NAC partially abrogated this decrease. CONCLUSIONS: Huh-7 cells expressing HCV proteins show significant up-regulation of the HO-1 gene, and reciprocal down-regulation of the Bach1 gene. Exogenous oxidative stressors and anti-oxidants can modulate expression of these genes. These and other results suggest a key role of down-regulation of Bach1 and up-regulation of HO-1 in diminishing cytotoxic effects of HCV proteins in human hepatocytes. 相似文献
87.
Management of nonalcoholic steatohepatitis: an analytic review 总被引:6,自引:0,他引:6
Nonalcoholic steatohepatitis (NASH) is a metabolic disorder of the liver, which, although usually relatively mild, may in some cause fibrosis, cirrhosis, and premature death resulting from liver failure. Its prevalence is increasing, and it is probably underestimated as a cause for cirrhosis. The need for an effective treatment is clear and urgent. Although several small, pilot, and randomized studies have been reported, large-scale studies are yet to be performed in patients with NASH. The aim of therapy is to intervene early in patients at risk of progression of liver disease. In this review, we summarize the extant literature on the management of NASH and discuss the potential future therapies and prophylactic recommendations in patients with NASH. 相似文献
88.
Optimal management of nonalcoholic fatty liver/steatohepatitis 总被引:1,自引:0,他引:1
Bonkovsky HL 《Journal of clinical gastroenterology》2003,36(3):193-195
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90.