HBV and HCV infection and pancreatic ductal adenocarcinoma

Introduction Pancreatic ductal adenocarcinoma(PDAC)is a highly lethal malignancy,with a poor overall fiveyear survival.Its dismal prognosis,even after curative resection,depends on its advanced stage at diagnosis,early metastatic spread,aggressive biological behavior and inefficacy of available systemic therapies.[1]To date,epidemiological studies have identified some risk factors for this cancer,including cigarette smoking habit,family history as well as high dietary fat consumption,alcohol abuse,diabetes mellitus,metabolic syndrome and chronic pancreatitis history.[1]

The Diagnostic Value of Anti-HCV Test in HCV Infection

Two hundred and ninety-six samples of patient serum and 28 samples of donor serum were tested for anti-HCV with second generation domestic made testing kit,and for HCV RNA with PCR assay.The purpose of the study was

Hepatitis C virus infections and genotypes in China

Objective: To define the conditions of hepatitis C vi- rus (HCV) infections, and geographic and demo- graphic distributions of genotypes in China. Methods: HCV infected patients were selected from individuals with different patterns of liver diseases and high risk populations in different parts of China. Genotypes of HCV in some isolates were further ana- lyzed, based on the data from our laboratory studies and some carefully selected published literatures. Results: The anti-HCV positive rates were 9.7% in patients with acute hepatitis, 13.3% in patients with chronic hepatitis, 18.3% in patients with hepatocel- lular carcinoma, 33.0% in patients with liver cirrho- sis, and 43.2% in patients with posttransfusional hepatitis (average, 16.2% in patients with liver di- seases). The anti-HCV positive rates in the high risk populations were 36.4% in leukemic patients, 43.0% in hemodialysis patients, 12.7% in blood do- nors, 64.1% in drug abusers, 13.1% in prostitutes, and 2.57% in naturally healthy people. At least 4 clades (clades 1, 2, 3 and 6) of HCV were found in China with different geographic and demographic distributions. Genotype 1b was the most widely dis- tributed genotype, and genotype 3 was mainly found in Yunnan Province, Southwest China. Conclusion: China has a high incidence of HCV in- fection. Our results will provide a strategic basis for diagnosis, treatment and possibly prophylaxis of he- patitis C virus diseases.

Impact of parietal cell autoantibodies and non-organ-specific autoantibodies on the treatment outcome of patients with hepatitis C virus infection: A pilot study

AIM: Various side effects have been reported in patients infected with hepatitis C virus (HCV) who were treated with interferon-alpha (IFN-α), including the appearance or exacerbation of underlying autoimmune diseases and the development of a variety of organ and non-organ specific autoantibodies (NOSA). However, very few studies in adults have been strictly designed to address: whether the prevalence and the titre of organ and NOSA in serial samples of HCV-treated patients were affected by IFN-α, and the impact of these autoantibodies on the treatment outcome of HCV patients. METHODS: We investigated whether parietal cell autoantibodies (PCA) and/or NOSA were related with treatment-outcome in 57 HCV-treated patients (19 sustained-responders, 16 relapsers, 22 non-responders). Serum samples from patients were studied blindly at three time-points (entry, end of treatment and end of followup). For the detection of autoantibodies we used indirect immunofluorescence, commercial and in-house ELISAs. RESULTS: Sustained biochemical response was associated with ANA-negativity at the entry or end of follow up. Sustained virological response was associated with the absence of PCA at the entry. Combined virological and biochemical sustained response (CVBSR) was associated with the absence of antinuclear antibodies (ANA) at the end of follow up and PCA-negativity at the entry. Sustained virological and CVBSR were associated with a reduction of ANA and SMA titers during therapy. CONCLUSION: Although PCA and/or NOSA seropositivity should not affect the decision to treat HCV patients, the presence of some of them such as ANA, PCA and SMA before treatment or their increase during therapy with IFN- a may predict a worse response, indicating the need for a closer monitoring during treatment of HCV patients positive for these autoantibodies.

Long term immunological perturbations post DAA therapy in chronic HCV/HIV co-infected patients

Direct-acting antiviral(DAA)therapies are efficacious for the achievement of sustained virologic response(SVR)in almost all treated hepatitis C virus(HCV)-infected patients.However,the impacts of HCV eradication on immune function and chronic immune activation in the long-term remain controversial and limited,especially in patients co-infected with human immunodeficiency virus(HIV).Indeed,although restoration of many immune responses clearly can be observed,several features of immune perturbations persist over time after HCV clearance.Understanding the degree and reasons of the partial recovery of the immune system in chronic HCV/HIV coinfection after HCV elimination is pivotal to avoid disease progression and possible long-term clinical outcomes in cured patients,as well as contributing to the development of immunotherapy drug design.

Is osteoporosis a peculiar association with primary biliary cirrhosis?

AIM： （1） To compare the prevalence of osteoporosis （t-score ≤-2.5 SD） between stage IV PBC patients, and two groups of age- and sex-matched controls： one with hepatitis C virus （HCV）-related cirrhosis, and the other one consisting of a group of healthy subjects from the general population, （2） to identify the main risk factors for the development of bone loss. METHODS： Thirty-five stage IV PBC patients （mean age 52.5±10 years）, 49 females with HCV-related cirrhosis （mean age 52.9±5.8 years） and 33 healthy females （mean age 51.8±2.22 years） were enrolled in the study. Bone metabolism was evaluated by measuring serum calcium corrected for serum albumin （Ca corr.）, 25-hydroxy vitamin D （25-OH vit D）, parathyroid hormone, osteocaldn. Bone mineral density （BMD） was assessed at the lumbar spine by dual-photon X-ray absorptiometry. RESULTS： Osteoporosis was present in 5/35 PBC patients （14.2%） and in 7/49 HCV-related drrhotic patients （14.3%）, without any statistical difference between the two groups. Among healthy control subjects, none had osteoporosis. No difference was found between the three groups in serum parameters of bone metabolism. Univariate analysis showed that menopausal state and low BMI were significantly correlated with osteoporosis. Multivariate regression analysis showed that menopausal status, BMI〈23, and old age were independent variables significantly correlated with osteoporosis. CONCLUSION： PBC in itself has no negative influence on BMD. End-stage liver disease patients carry a disease-specific risk for osteoporosis, but have an effective risk of bone loss in relation to individual potential risk for each patient. A practical message should be taken into account, that is, every effort should be made to prevent osteoporosis when a patient has simple osteopenia, or if it is a woman in or near menopausal age.

Dementia Caused by Heptatis C Virus--Case Report

HCV （hepatitis C virus） infection produces a chronic systemic disease that induces chronic hepatitis, cirrhosis and hepatocellular carcinoma, and also can induce dementia. Dementia can be defined as a syndrome of global and progressive impairment of acquired cognitive abilities. Importance of early detection of HCV infection in prevention of cognition decline in infected patients is emphasized along with the fast progressive form of dementia caused by HCV trough possible patogenetic mechanismas presented in this paper.

Occult Hepatitis C Virus Infection:A Review

Occult hepatitis C virus(HCV)infection(OCI),first described in 2004,is defined as the presence of HCV RNA in hepatocytes or peripheral blood mononuclear cells without detectable HCV RNA in the serum.Here,we aimed to review the epidemiology,diagnostic methods,clinical implications and potential man-agement recommendations currently described in the litera-ture,as well as the future directions for investigation of this entity.PubMed and Cochrane databases were searched with combination of the following keywords:"occult","hepatitis C virus",and"occult HCV infection".There are data to support OCI as a potential culprit in cryptogenic liver disease.There are also consistent data demonstrating the existence of OCI in specific populations,such as dialysis,human immunodefi-ciency virus-infected and hepatitis B virus-infected patients,and also in the general population.While the gold standard for diagnosis is liver biopsy,examination of peripheral blood mononuclear cells may be a reliable,safer alternative method of diagnosis.Occult HCV infection is likely associated with liver fibrosis and progression of liver disease.Additional studies are required to determine the infectivity of OCI patients,as well as clarify the natural course and specific clinical implications of OCI.Lastly,studies are needed to determine whether treat-ment of OCI leads to decreased morbidity and/or mortality.

Role of Ras-related Nuclear Protein/Polypyrimidine Tract Binding Protein in Facilitating the Replication of Hepatitis C Virus

Background and Aims:Ras-related nuclear(RAN)protein is a small GTP-binding protein that is indispensable for the translocation of RNA and proteins through the nuclear pore complex.Recent studies have indicated that RAN plays an important role in virus infection.However,the role of RAN in hepatitis C virus(HCV)infection is unclear.The objective of this study was to investigate the role and underlying mechanisms of RAN in HCV infection.Methods:Huh7.5.1 cells were infected with the JC1-Luc virus for 24 h and then were incubated with complete medium for an additional 48 h.HCV infection and RAN expression were determined using luciferase assay,quantitative reverse transcription-PCR and western blotting.Small interfering RNA was used to silence RAN.Western blotting and immunofluorescence were used to evaluate the cytoplasmic translocation of polypyrimidine tract-binding(PTB),and coimmunoprecipitation was used to examine the interaction between RAN and PTB.Results:HCV infection significantly induced RAN expression and cytoplasmic redistribution of PTB.Knockdown of RAN dramatically inhibited HCV infection and the cytoplasmic accumulation of PTB.Colocalization of RAN and PTB was determined by immunofluorescence,and a direct interaction of RAN with PTB was demonstrated by coimmunoprecipitation.Conclusions:PTB in the host cytoplasm is directly associated with HCV replication.These findings demonstrate that the involvement of RAN in HCV infection is mediated by influencing the cytoplasmic translocation of PTB.