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Urinary nuclear magnetic resonance spectroscopy of a Bangladeshi cohort with hepatitis-B hepatocellular carcinoma: A biomarker corroboration study

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World Journal of Gastroenterology 2016年第16期22卷 4191-4200页

作者： I Jane Cox Abil E Aliev Mary ME Crossey Mahvish Dawood Mamun Al-Mahtab Sheikh M Akbar Salimur Rahman Antonio Riva Roger Williams Simon D Taylor-Robinson Institute of Hepatology London Foundation for Liver Research Department of Chemistry University College London Division of Digestive Diseases Department of Surgery and Cancer Imperial College London Department of Hepatology Bangabandhu Sheikh Mujib Medical University Department of Medical Sciences Toshiba General Hospital

AIM: To establish if a distinct urinary metabolic profile could be identified in Bangladeshi hepatitis-B hepatocellular carcinoma(HCC) patients compared to cirrhosis patients and controls. METHODS: Urine samples from 42 Bangladeshi patients with HCC(39 patients with hepatitis-B HCC), 47 with cirrhosis on a background of hepatitis B, 46 with chronic hepatitis B, and seven ethnically-matched healthy controls were analyzed using nuclear magnetic resonance(NMR) spectroscopy. A full dietary and medication history was recorded for each subject. The urinary NMR data were analyzed using principal component analysis(PCA) and orthogonal partial leastsquared discriminant analysis(OPLS-DA) techniques. Differences in relative signal levels of the most discriminatory metabolites identified by PCA and OPLSDA were compared between subject groups using an independent samples Kruskal-Wallis one-way analysis of variance(ANOVA) test with all pairwise multiple comparisons. Within the patient subgroups, the MannWhitney U test was used to compare metabolite levels depending on hepatitis B e-antigen(HBe Ag) status and treatment with anti-viral therapy. A BenjaminiHochberg adjustment was applied to acquire the level of significance for multiple testing, with a declared level of statistical significance of P < 0.05.RESULTS: There were significant differences in age(P < 0.001), weight(P < 0.001), and body mass index(P < 0.001) across the four clinical subgroups. Serum alanine aminotransferase(ALT) was significantly higher in the HCC group compared to controls(P < 0.001); serum α-fetoprotein was generally markedly elevated in HCC compared to controls; and serum creatinine levels were significantly reduced in the HCC group compared to the cirrhosis group(P = 0.004). A threefactor PCA scores plot showed clustering of the urinary NMR spectra from the four subgroups. Metabolites that contributed to the discrimination between the subgroups included acetate, creatine, creatinine, dimethyamine(DMA), formate, glycine, hippurate, and trimethylamine-

关键词： Urinary metabolic profiling Hepatocellular carcinoma Nuclear magnetic resonance spectroscopy hepatit

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Application of nucleoside analogues to liver transplant recipients with hepatitis B

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World Journal of Gastroenterology 2015年第42期21卷 12091-12100页

作者： Zhuo-Lun Song Yu-Jun Cui Wei-Ping Zheng Da-Hong Teng Hong Zheng Organ Transplantation Center Tianjin Key Laboratory of Organ Transplantation Tianjin First Center Hospital Swiss Hepato-Pancreato-Biliary Center Department of Visceral and Transplantation Surgery University Hospital Zurich

hepatitis B is a common yet serious infectious disease of the liver, affecting millions of people worldwide. Liver transplantation is the only possible treatment for those who advance to end-stage liver disease. Donors positive for hepatitis B virus(HBV) core antibody(HBc Ab) have previously been considered unsuitable for transplants. However, those who test negative for the more serious hepatitis B surface antigen can now be used as liver donors, thereby reducing organ shortages. Remarkable improvements have been made in the treatment against HBV, most notably with the development of nucleoside analogues(NAs), which markedly lessen cirrhosis and reduce post-transplantation HBV recurrence. However, HBV recurrence still occurs in many patients following liver transplantation due to the development of drug resistance and poor compliance with therapy. Optimized prophylactic treatment with appropriate NA usage is crucial prior to liver transplantation, and undetectable HBV DNA at the time of transplantation should be achieved. NA-based and hepatitis B immune globulin-based treatment regimens can differ between patients depending on the patients' condition, virus status, and presence of drug resistance. This review focuses on the current progress in applying NAs during the perioperative period of liver transplantation and the prophylactic strategies using NAs to prevent de novo HBV infection in recipients of HBc Ab-positive liver grafts.

关键词： Nucleoside analogues Liver transplantation hepatit

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Serum hepatitis B surface antigen levels predict treatment response to nucleos(t)ide analogues

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World Journal of Gastroenterology 2014年第24期20卷 7686-7695页

作者： Chien-Hung Chen Yi-Chun Chiu Sheng-Nan Lu Chuan-Mo Lee Jing-Houng Wang Tsung-Hui Hu Chao-Hung Hung Division of Hepato-Gastroenterology Department of Internal MedicineKaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine

Quantification of hepatitis B surface antigen(HBsAg)has been suggested to be helpful in the management of chronic hepatitis B(CHB)patients.Nucleos(t)ide analogs(NAs)are the therapy of choice for CHB and are used in the majority of CHB patients.NAs are able to induce hepatitis B virus(HBV)viral suppression,normalization of alanine aminotransferase(ALT)levels,and improvement in liver histology.Automated quantitative assays for serum HBsAg have recently become available,facilitating standardized quantification of serum HBsAg.This has led to increased interest in the clinical application of quantitative serum HBsAg for predicting therapeutic response to NAs.Recent studies have shown that a decline in serum HBsAg levels in patients receiving peginterferon may signal successful induction of immune control over HBV,and can therefore be used to predict therapeutic response.NA treatment typically induces a less rapid decline in HBsAg than interferon treatment;it has been estimated that full HBsAg clearance can require decades of NA treatment.However,a rapid HBsAg decline during NA therapy may identify patients who will show clearance of HBsAg.Currently,there is no consensus on the clinical utility of serum HBsAg monitoring for evaluating patient responses to NA therapy.This review focuses on recent findings regarding the potential application of HBsAg quantification in the management of CHB patients receiving NA therapy.

关键词： Alanine aminotransferase hepatitis B virus hepatit

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Molecular mechanism of hepatitis B virus X protein function in hepatocarcinogenesis

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World Journal of Gastroenterology 2015年第38期21卷 10732-10738页

作者： Ming Geng Xuan Xin Li-Quan Bi Lu-Ting Zhou Xiao-Hong Liu Department of Pathology General Hospital of Jinan Military Command

Many factors are considered to contribute to hepatitis B virus(HBV)-associated hepatocellular carcinoma(HCC),including products of HBV,HBV integration and mutation,and host susceptibility. HBV X protein(HBx) can interfere with several signaling pathways associated with cell proliferation and invasion,and HBx C-terminal truncation has been suggested to impact the development of HCC. This review focuses on the pathological functions of HBx in HBV-induced hepatocarcinogenesis. As a transactivator,HBx can affect regulatory non-coding RNAs(nc RNAs),including micro RNAs and long nc RNAs. HBx is also involved in epigenetic modification and DNA repair. HBx interacts with various signal-transduction pathways,such as the p53,Wnt,and nuclear factor-κB pathways. We conclude that HBx hastens the development of hepatoma.

关键词： Hepatocellular carcinoma hepatitis B virus hepatit

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Nonalcoholic fatty liver disease and hepatic cirrhosis: comparison with viral hepatitis-associated steatosis

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World Journal of Gastroenterology 2015年第46期21卷 12989-12995页

作者： Yuki Haga Tatsuo Kanda Reina Sasaki Masato Nakamura Shingo Nakamoto Osamu Yokosuka Department of Gastroenterology and Nephrology Chiba UniversityGraduate School of Medicine Department of Molecular Virology Chiba UniversityGraduate School of Medicine

Nonalcoholic fatty liver disease(NAFLD) including nonalcoholic steatohepatitis(NASH) is globally increasing and has become a world-wide health problem. Chronic infection with hepatitis B virus or hepatitis C virus(HCV) is associated with hepatic steatosis. Viral hepatitis-associated hepatic steatosis is often caused by metabolic syndrome including obesity,type 2 diabetes mellitus and/or dyslipidemia. It has been reported that HCV genotype 3 exerts direct metabolic effects that lead to hepatic steatosis. In this review,the differences between NAFLD/NASH and viral hepatitis-associated steatosis are discussed.

关键词： Hepatocellular carcinoma hepatitis B virus hepatit

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