Clinico-epidemiology of hepatitis B viral infection in Northeastern Thailand

Hepatitis B viral (HBV) infection is a common disease world wide. A study of clinico-epidemiology of HBV infection was conducted in 381 patients who seropositive for hepatitis B surface antigen (HBsAg) in Srinagarind Hospital, Khon Kaen University, Northeastern Thailand, during August 1997 to December 1998. 293 males, 88 females and their mean age was 30.96 +/- 12.78 years with a range from 15 to 77 years. The clinical features of acute hepatitis, chronic hepatitis, liver cirrhosis, hepatocellular carcinoma (HCC) and asymptomatic carrier were 2.36, 34.12, 4.99, 1.05 and 57.48% of cases. Possible routes for HBV transmission were family history of hepatitis, tattooing, intravenous drug addict and blood transfusion in 20.3, 11.3, 8.2 and 6.9% of cases, respectively. Signs of chronic liver disease were common in liver cirrhosis and HCC. Acute fulminating hepatitis was not found in this study.     

Causes of thrombocytopenia in chronic hepatitis C viral infection

We retrospectively studied 89 patients with chronic hepatitis C virus (HCV) infection, including 50 chronic hepatitis (CH) cases, 18 liver cirrhosis (LC) cases, and 21 LC with hepatocellular carcinoma (LC + HCC) cases, with regard to various factors related with thrombocytopenia. The platelet count decreased with the stage advancement of liver diseases. Multiple regression analysis revealed that splenomegaly and von Willebrand factor (vWF) were explanatory variables that correlated with thrombocytopenia. Splenomegaly appears to be the most responsible factor, although there are a considerable number of thrombocytopenic cases without splenomegaly, suggesting other factors may also be responsible. The vWF level is inversely correlated with the platelet count. Soluble thrombomodulin, a marker of endothelial dysfunction, increases with the advancement of liver fibrosis. It is positively correlated with vWF and inversely with the platelet count. Our present results imply that vascular endothelial dysfunction is also involved in thrombocytopenia during chronic HCV infection.     

The natural history of hepatitis C viral infection

Although early data suggested that chronic hepatitis C virus infection carried little risk, studies with longer duration of infection have reported concerning results. Of patients with acute infection, approximately 80% will develop chronic infection. The greatest risk of morbidity comes with cirrhosis and the resulting increased risk of hepatocellular carcinoma. The true risk of progression to cirrhosis, however, has emerged as an area of controversy. Both host and viral factors seem to impact susceptibility to chronic infection, cirrhosis, and hepatocellular carcinoma. Hepatitis C virus has become the most common indication for liver transplantation, but the infection routinely recurs and may have a more aggressive course after transplantation. Given that current treatment options for hepatitis C virus infection are clearly not optimal, informed decisions regarding treatment require an in depth understanding of the natural history.     

Oxidative stress and hepatitis C viral infection.

The involvement of oxidative stress in the pathogenesis of hepatitis and hepatocellular carcinoma has been strongly suggested. Oxidative stress is produced by inflammatory processes that occur in hepatitis via immunological mechanisms. In addition, in hepatitis C virus (HCV) infectious disease, some role has been assigned to viral proteins in the induction of oxidative stress. In the presence of hepatic steatosis, insulin resistance and increased levels of some cytokines, all of which are also induced by viral protein expression, oxidative stress is enhanced in HCV infection. In this sense, the role of oxidative stress in the progression of chronic hepatitis and hepatocarcinogenesis is greater in hepatitis C than in other types of hepatitis such as hepatitis B or autoimmune hepatitis. The additive effects of oxidative stress caused by the inflammatory process and that induced by HCV proteins may, furthermore, exert synergistic effects with alterations in intracellular signaling systems such as mitogen-activated protein kinases (MAPK), which are also induced by HCV proteins. These synergistic effects may be responsible for rare characteristics, that is, the high incidence and multicentric nature of hepatocarcinogenesis in HCV infection.     

IgM antibody response in acute hepatitis C viral infection.

IgM antibody against hepatitis C virus (IgM anti-HCV) was measured in serial samples from 15 transfusion recipients in whom posttransfusion chronic non-A, non-B hepatitis (NANBH) developed and three plasmapheresis donors during acute HCV infection using recombinant proteins derived from three immunodominant regions: core, NS-3, and NS-4 (c100). IgM anti-HCV core was detected in 13 of 15 posttransfusion patients. Nine of these patients had transient, acute-phase IgM anti-HCV core detected coincidentally or earlier than active IgG anti-HCV core response. The average duration of IgM anti-HCV core reactivity was 8.1 +/- 3.7 weeks. One patient lacking an IgM anti-HCV core response had detectable IgM anti-HCV NS-3 during the acute phase. Passive transfer of IgM anti-HCV was not observed in these posttransfusion cases, in contrast to the high frequency observed for IgG anti-HCV. Late IgM anti-HCV was detectable against core, c100, and NS-3 in three, two, and one posttransfusion patients, respectively. These data indicate that IgM anti-HCV core is a useful acute-phase marker in HCV infection.     

New treatment strategies against hepatitis C viral infection.

Treatment of hepatitis C virus infection is currently based on a combination of pegylated interferon and ribavirin. Because efficacy of this therapy remains suboptimal and side effects sometimes problematic, major efforts have been put forward by scientists and the pharmaceutical industry to develop alternative treatments for this chronic infection. Over the past few years, clinical studies performed with some of these new agents have been presented at major international meetings. The present paper aims to review the rationale underlying the development of these new forms of treatment as well as the current available data concerning their clinical efficacy.     

Asian perspectives on viral hepatitis: Hepatitis C virus infection

Abstract Hepatitis C virus (HCV) infection is widespread throughout Asia. Unusual features of HCV in Asia include a novel genotype distribution with a significant representation of 3a. This is particularly important as genotype 3 is very sensitive to interferon-based therapies. A major concern in the Asian region is the high prevalence of hepatocellular cancer complicating HCV-associated cirrhosis, particularly in Japan. Finally, liver transplantation for advanced HCV infection with cirrhosis is an option via cadaveric and living donor programmes.     

HFE基因多态性检测判断慢性丙型肝炎患者疾病活动的价值*

目的 观察遗传性血色素沉着症候选基因HFE多态性检测判断CHC疾病活动的价值。方法 2016年11月～2018年11月我院收治的257例丙型肝炎病毒感染者,其中病毒感染者131例和慢性丙型肝炎(CHC)患者126例。采用酶结合免疫吸附法测定血清铁蛋白(SF)水平,使用ABIPrismsTM-7900实时荧光定量PCR仪和TaqMan-MGB荧光探针,以实时定量PCR法检测HFE基因rs2071303和rs9366637位点基因型。结果 病毒感染者SF水平为(97.5±4.1)μg/L,显著低于CHC患者【(202.1±24.5)μg/L,P＜0.05】,血清ALT水平为(34.0±4.5)U/L,显著低于CHC患者【(88.4±5.6)U/L,P＜0.05】,AST为(37.5±4.2)U/L,显著低于CHC患者【(70.0±5.4)U/L,P＜0.05】;病毒感染者HCV基因非Ⅰb型频率为29.8%,显著高于CHC患者13.5%(P＜0.05),病毒感染者HCV基因型中混合型频率为9.1%,显著低于CHC患者的21.4%(P＜0.05);病毒感染者rs2071303位点GG基因型患者SF水平为(97.6±4.2)μg/L,显著低于CHC患者【(199.5±45.4)μg/L,P＜0.05】,GA基因型SF水平为(97.6±4.1)μg/L,显著低于CHC患者【(207.5±34.7)μg/L,P＜0.05】,AA基因型SF水平为(96.7±3.7)μg/L,显著低于CHC患者【(198.0±44.8)μg/L,P＜0.05】;病毒感染者rs9366637位点TT基因型患者SF水平为(97.4±4.0)μg/L,显著低于CHC患者【(206.4±35.6)μg/L,P＜0.05】,TC基因型SF水平为(97.2±4.0)μg/L,显著低于CHC患者【(208.5±34.0)μg/L,P＜0.05】,CC基因型SF水平为(99.1±4.5)μg/L,显著低于CHC患者【(178.5±58.6)μg/L,P＜0.05】;病毒感染者rs2071303位点AA基因型频率为13.7%,显著低于CHC患者的21.4%(P＜0.05),病毒感染者AC单倍型频率为3.1%,显著低于CHC患者的8.3%(P＜0.05)。结论 HFE基因多态性与CHC疾病活动密切相关,临床应引起足够的重视。     

Three-dimensional reconstruction of hepatic bridging fibrosis in chronic hepatitis C viral infection

BACKGROUND/AIMS: Fibrosis in chronic hepatitis C infection begins in portal tracts, and can progress to 'bridging fibrosis' and eventually lead to cirrhosis. All current fibrosis staging systems are based on these three conceptual fibrosis stages (portal fibrosis, bridging fibrosis, cirrhosis) and vary only in how these stages are further subdivided. Despite the importance of bridging fibrosis, little is known about its three-dimensional characteristics. METHODS: Foci of bridging fibrosis were digitally reconstructed in three dimensions on two separate liver specimens with chronic hepatitis C viral infection. The amount of portal fibrosis was then correlated with bile duct diameter on trichrome-stained sections. RESULTS: After three-dimensional reconstruction, the bridges were seen to represent webs or membranes of fibrosis located at branch points of the portal tracts that extended between two portal branches, much like the webbing between the thumb and forefinger in a baseball-mitt. Direct measurements indicated that early portal fibrosis was associated with portal tracts containing bile ducts of approximately 18-19 mum diameter. CONCLUSIONS: Fibrosis bridges are located at branch points of portal tracts and are composed of three-dimensional webs or membranes that extend between portal tracts; when viewed as two dimensions on a glass slide, a 'bridge' of fibrosis is seen.     

Prevention of hepatocellular carcinoma in chronic viral hepatitis B and C infection

Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality worldwide,with the majority of cases associated with persistent infection from hepatitis B virus(HBV)or hepatitis C virus(HCV).Natural history studies have identified risk factors associated with HCC development among chronic HBV and HCV infection.High-risk infected individuals can now be identified by the usage of risk predictive scores.Vaccination plays a central role in the prevention of HBV-related HCC.Treatment of chronic HBV infection,especially by nucleoside analogue therapy,could also reduce the risk of HBV-related HCC.Concerning HCV infection,besides the advocation of universal precautions to reduce the rate of infection,pegylated interferon and ribavirin could also reduce the risk of HCV-related HCC among those achieving a sustained virologic response.Recently there has been mounting evidence on the role of chemopreventive agents in reducing HBV-and HCV-related HCC.The continued advances in the understanding of the molecular pathogenesis of HCC would hold promise in preventing this highly lethal cancer.     

Autoimmune hepatitis versus viral hepatitis C

Abstract: Numerous viruses are capable of inducing the syndrome of chronic hepatitis. Among them are the hepatitis B, C and D viruses. Out of the most common agents of chronic hepatitis, the hepatitis C virus has been found to be strikingly associated with autoimmune diseases and serological markers of autoimmunity. Conversely, the syndrome of genuine autoimmune hepatitis lacks evidence of previous or ongoing virus infection and is diagnosed by additionally excluding metabolic, toxic, and genetic causes of chronic hepatitis, and by the response to immunosuppressive treatment. This review article summarizes the current knowledge of hepatotropic virus-induced autoimmunity. It focuses on the present molecular and immunological definitions, the clinical and molecular distinction between autoimmune hepatitis and chronic viral hepatitis and the implications for the safe and efficacious therapy of these disease entities.     

Haplorchis pumilio (Looss) infection in man in northeastern Thailand

During a clinical trial of praziquantel for human opisthorchiasis, Haplorchis pumilio Looss were recovered from the stools of 12 patients. This is the third species of Haplorchis spp. reported from man in Thailand.     

Recurrent and acquired hepatitis C viral infection in liver transplant recipients.

To examine the postliver transplant recurrence of hepatitis C virus (HCV) infection in patients with pretransplant infection, as well as its acquisition in patients without prior infection, we used the polymerase chain reaction to amplify HCV RNA in serum and/or liver samples of 89 patients with alcoholic and cryptogenic cirrhosis undergoing liver transplantation. Results were correlated with histologic findings from posttransplant liver biopsies. Ninety-five percent of patients with pretransplant infection had posttransplant viremia. In contrast, 35% of patients without pretransplant infection acquired the virus (P less than 0.0001). Pretransplant HCV infection predisposed patients to hepatitis in the new graft. HCV RNA was present in serum of 96% of patients with posttransplant hepatitis. Fifty-six percent of patients with posttransplant HCV infection had no evidence of liver damage at least 1 year posttransplant. However, of those patients with histologic hepatitis, chronic active hepatitis was common. It is concluded that although HCV infection recurs posttransplant in almost all infected patients, acquisition of the HCV infection with transplant is common. Pretransplant HCV infection is an independent risk factor for the development of posttransplant hepatitis. HCV infection accounts for the majority of posttransplant hepatitis not due to cytomegalovirus, and although many patients with posttransplant viremia have little evidence of histologic hepatitis, significant hepatic damage may occur.     

Diagnostic testing in hepatitis C virus infection: viral kinetics and genomics

Virological tools play a major role in the diagnosis of hepatitis C virus (HCV) infection and in ongoing decision-making based on the patient's virological response to therapy. Virological tools used to assess viral kinetics and viral genomics can also be applied to clinical and translational research, especially in studies aimed at understanding the mechanisms underlying HCV treatment failure. Viral kinetics studies are based on quantification of HCV RNA at prescribed intervals during treatment and mathematical modeling of HCV RNA dynamics. These studies require sensitive and specific HCV RNA assays with an extended dynamic range of quantification. Viral genomics methods are useful to correlate viral kinetics with the intrinsic genomic characteristics of the HCV infecting strain. The interpretation of results utilizing various viral genomics tools is difficult, however, and must include predictive structural and functional genomic analyses. These approaches will be particularly useful in studying the mechanisms of HCV treatment failure with new HCV inhibitors currently under development.     

New animal models for hepatitis C viral infection and pathogenesis studies

Hepatitis C virus (HCV) is a major cause of chronic live disease, cirrhosis and hepatocellular carcinoma (HCC) In man, the pathobiological changes associated wit HCV infection have been attributed to both the immun system and direct viral cytopathic effects. Until now, th lack of simple culture systems to infect and propagat the virus has hampered progress in understandin the viral life cycle and pathogenesis of HCV infection including the molecular mechanisms implicated in HCV induced HCC. This clearly demonstrates the need t develop small animal models for the study of HCV associated pathogenesis. This review describes an discusses the development of new HCV animal models t study viral infection and investigate the direct effects o viral protein expression on liver disease.     

丙氨酸氨基转移酶持续正常的慢性丙型肝炎病毒感染的研究进展

丙型肝炎病毒(HCV)感染极易慢性化,研究表明,约有20％~30％的HCV慢性感染患者丙氨酸氨基转移酶(ALT)持续正常,临床症状缺失或非常轻微。所谓ALT持续性正常,即为在6个月内间断1个月以上复查3次,ALT均在正常范围以内。对于此类患者是否进行抗病毒治疗一直存在争议。现就ALT持续性正常HCV感染的自然病史、肝脏病理变化、病毒载量、