Molecular methods of measurement of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus infection: implications for occupational health practice

Over the past decade, several molecular techniques for the detection of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) have been developed that have implications for occupational health practice. This review describes the techniques used for qualitative and quantitative detection of the viral genome, and briefly explains nucleic acid sequencing and analysis of phylogenetic trees. The review also discusses the current and potential uses of these techniques in investigations of transmission of bloodborne viruses by patient to worker and worker to patient, in the management of occupational exposure to blood, in research, and in the development of guidance and policy on infected healthcare workers who perform procedures prone to exposure.     

Chronic hepatitis C virus infection

Following acute hepatitis C virus infection (HCV), a significant percentage of patients do not clear the virus and develop a chronic hepatitis C. The symptoms, when they exist, are usually unspecific. Besides, approximately one third of the patients present extrahepatic manifestations of the infection, basically due to the lymphotropism of HCV. Outstanding amongst these, due to their clear association with HCV, are mixed cryoglobulinaemia and the production of autoantibodies (autoAb). Other diseases such as non-Hodgkin lynphoma (NHL) or autoimmune thyroiditis do not have a clearly established association. Although the majority of patients with chronic hepatitis C have slight or moderately high levels and fluctuations of transaminases, as many as one third of those infected can show persistently normal levels of transaminases. The diagnosis of chronic HCV infection is based on serological tests, which detect the presence of antibodies against HCV, and on virological tests that detect RNA of the HCV, which confirm the existence of active infection. Finally, an important topic of chronic HCV infection, following diagnosis, is to ascertain the stage of fibrosis and the degree of inflammation, since both characteristics are very important for predicting the natural evolution and the need for treatment. Nowadays, this information can only be obtained through liver biopsy, which is recommended in patients with chronic HCV infection and high transaminases. Whether liver biopsy should be performed in patients with normal transaminases is still subject of controversy.     

隐匿性丙型肝炎病毒感染

隐匿性HCV感染作为一种特殊的感染形式正逐渐受到重视,此文就隐匿性HCV感染的发生机制、生物学特性及临床特征作了简要概括.     

Intrafamilial hepatitis C virus infection

The role of blood and other biological fluids in transmission of HCV is already proven. The infection is acquired mainly by uncontrolled transfusion of blood products, percutaneous inoculation by contaminated equipment, mother-to-infant as well as sexual exposures. Infection by common contact in the family is very rare, but data are present in the literature. AIM: The authors demonstrate a clinical case of possible intrafamilial spread of hepatitis C virus. CASE REPORT: Forty-seven-year-old woman with chronic hepatitis C has one anti-HCV positive daughter. DISCUSSION: Because of the long period of incubation, less specific symptoms of acute C-hepatitis and often development of symptom-free disease, the patients and their families can be long in living together without being unaware of potential infection. CONCLUSION: Intrafamilial spread of hepatitis C virus may occur. It is strongly suggested to inform the patients about the possible risk and the importance of personal hygiene.     

Acute hepatitis C virus infection

Acute hepatitis C virus infection produces clinical and biochemical features that is non-specific and indistinguishable from those caused by other hepatotropic viruses. The specific diagnosis of acute hepatitis C virus infection is based on the detection of serum RNA-HCV through a technique of PCR whose result will be positive after 1-2 weeks of the initial contact with the virus. The anti-bodies against HCV are detected later (after 7-8 weeks on average), and are not useful, as an isolated determination, in distinguishing acute infection from chronic infection or in clearing the virus (spontaneous or following treatment). Fifty-five to eighty-five percent of patients with acute HCV infection do not clear the virus and develop a chronic infection with risk of evolution to cirrhosis and of developing hepatocellular carcinoma. For this reason, the present tendency is to treat with interferon all those patients in whom RNA-HCV remains positive after 3-4 months following diagnosis of acute infection     

Pathogenesis of hepatitis C virus infection

The hepatitis C virus (HCV) is the leading cause of chronic liver disease worldwide. Chronic hepatitis C is a mayor cause of cirrhosis and hepatocellular carcinoma and HCV-related end-stage liver disease is, in many countries, the first cause of liver transplantation. HCV infection is characterized by its propensity to chronicity. Because of its high genetic variability, HCV has the capability to escape the immune response of the host. HCV is not directly cytopathic and liver lesions are mainly related to immune-mediated mechanisms that are characterized by a predominant type 1 helper cell response. Co-factor influencing the outcome of the disease including age, gender and alcohol consumption are poorly understood and other factors such as immunologic and genetic factors may play and important role. Recent studies have shown that the combination therapy with alpha interferon and ribavirin induces a sustained virological response in about 40% of patients with chronic hepatitis C. The lack of animal models and of in vitro cultures systems hampers the understanding of the pathogenesis of chronic hepatitis C and the development of new antivirals. The conjugation of polyethyleneglycol improved the pharmacodynamics and the efficacy of alpha interferon. The development of an effective vaccine remains the most difficult challenge. Because of the high protein variability of HCV, protective vaccines could be extremely difficult to produce and therapeutic vaccines seem more realistic. Considerable progress has been made in the field of HCV since its discovery 10 years ago but a major effort needs to be made in the next decade to control HCV-related disease.     

Iatrogenic GB virus C/hepatitis G virus infection in an area endemic for hepatitis C virus

GB virus C/hepatitis G virus (GBV-C/HGV) is reported to be transmitted by blood products. This study reports infection with GBV-C/HGV from Area-O of town T, an area of high prevalence of antibody to hepatitis C virus (anti-HCV). Four hundred and thirty-five inhabitants of Area-O in town T were examined. Three hundred and forty-three inhabitants of Area-H in town T (where differences of age or sex are not markedly different to Area-O) were studied as controls. We investigated the virus markers and conducted a survey of life history in both areas. The seroprevalence of anti-HCV and GBV-C/HGV markers in Area-O was 17.7% and 11.7%, significantly higher than in Area-H (1.5% and 4.4%). The prevalence of GBV-C/HGV markers was significantly higher in the anti-HCV-positive group than in the sero-negative group. Anti-HCV- or GBV-C/HGV positive subjects tended to have a history of intravenous medications at hospital C in town T, suggesting iatrogenic infection through insufficient sterilization of needles and/or syringes.     

New treatments for chronic hepatitis C virus infection

The treatment of hepatitis C virus infection (HCV) by a combination of pegylated interferon and ribavirin, according to early viral kinetics, leads to a sustained virological response (SVR) in more than 50% of patients with chronic infection. This SVR is a complete recovery of the infection but more than 50% of genotype 1-infected patients do not achieve SVR. A better understanding of the viral cycle, and the characterization of viral enzymes which are potential targets, resulted in the development of new molecules, direct acting antivirals (DAA) targeted against HCV, either specific of genotype 1 (protease inhibitors NS3/NS4A and polymerase inhibitors NS5B) or with a wider spectrum (NS5A or entry inhibitors), and non-specific antivirals (new interferons, cyclophilin inhibitors). We describe the results of phase II and III trials which clearly demonstrated a 20 to 30% increase in the SVR rate of genotype 1-infected patients, either naïve or treatment experienced. These new drugs should be approved by the end of 2011, after a temporary approval for compassionate use in cirrhotic patients with previous relapse or partial response to the combination therapy. In the future, the main limitations of triple therapy will be safety (cutaneous rash or anemia which may be controlled), cost, compliance, viral resistance, and drug interactions that must be avoided by educating patients and physicians.     

T细胞应答在丙型肝炎病毒持续感染中的作用

HCV感染极易慢性化,已成为困扰全球人类健康的重要公共卫生问题。近年研究发现,T细胞应答可能在HCV感染慢性化中的发挥着重要作用,此文对T细胞应答与HCV持续感染的关系进行综述。     

丙型肝炎感染的实验模型研究进展

由于缺少稳定可靠的HCV感染细胞模型和廉价的动物模型,阻碍了对抗HCV病毒药物筛选和疫苗研究等的研究进程.因此寻找具有实际应用价值的HCV感染模型或HCV基因表达模型是国内外的研究热点.近年来的研究主要集中在动物模型、细胞模型方面.本文主要介绍这两方面的研究进展.     

Natural history of hepatitis C virus infection

The generally indolent, slow and protracted course of hepatitis C virus infection has limited the realisation of studies that evaluate its natural history. The aim of such studies has been the probability of death through hepatic disease, hepatic cirrhosis (compensated or decompensated), and/or hepatocarcinoma, or the development of a significant hepatic fibrosis (essential anatamopathological substrate for the development of the complications of hepatic cirrhosis). In spite of their possible limitations, the results of these studies show that chronic hepatitis C virus infection generally follows a benign evolutionary course, above all if this occurs in young patients (<50 years of age), without other aggravating factors of a possible hepatopathy (alcohol, coinfection by other viruses, immunosuppression) and if this is evaluated in the first 10-20 years of infection. At present, it is not possible to identify with precision those patients with HCV infection with a greater risk of developing a clinically relevant hepatic disease. However, it is likely that those subjects with high transaminases (> 2 times the normal value) and significant necroinflammatory activity (periportal necrosis) and fibrosis in the hepatic biopsy will show a more aggressive evolutionary course than those with normal transaminases and an almost normal hepatic biopsy.     

丙型肝炎病毒感染的研究

众多资料表明,慢性HCV感染与肝硬化和肝细胞癌相关.HCV感染已经逐渐成为全球健康的重大威胁,导致世界各地出现大量的慢性肝病患者.理解和掌握HCV感染的长期转归才能判断出患者发生HCV相关并发症的概率,此文就HCV感染的自然史作了综述.     

Treatment of chronic hepatitis C virus infection

At present the treatment of chronic hepatitis C virus infection is based on the combination of pegylated interferon (PEG-INF) and rivabirin (RBV) and basically attempts to eradicate the viral infection (sustained viral response). The pattern depends above all on the viral genotype, hence, patients with genotype 1, 4 and 5 require 48 weeks of treatment and high doses of RBV, while those with genotype 2 and 3 require 24 weeks of treatment and low doses of RBV. All patients with chronic C infection are possible candidates for antiviral therapy. However, given that the response to treatment is variable, that the treatment has secondary effects and supposes a high economic cost, it is recommendable in patients with hypertransaminasemia and moderate-severe chronic hepatitis in the histological study, as long as there are no counter-indications. This does not exclude other groups of patients who should be evaluated individually. In those patients with compensated hepatic cirrhosis, treatment can stabilise the disease and reduce the risk of complications appearing, although the rate of response is lower and some adverse effects are more frequent. In patients who have received previous antiviral treatment with standard interferon, alone or in association with RBV, without response to this or with response but later relapse, the decision on treatment must be individual. In patients with coinfection by human immunodeficiency virus (HIV), special attention must be paid to the degree of evolution of the disease due to HCV and to HIV, as well as the possible hepatoxicity of the antiretroviral treatment and the risk of secondary effects.     

Primary prevention of hepatitis C virus infection

Viral hepatitis type C is a worldwide public health problem of major concern. Waiting for a safe and effective vaccine able to confer protection to susceptible individuals, public health challenges for controlling hepatitis C require implementation of primary prevention measures that reduce risks of acquiring/transmitting HCV infection. Screening for safe blood and blood products, use of disposable syringes and needles and of universal precautions have dramatically reduced risk of infection in medical setting. Health education, counselling and testing of individuals at risk provide opportunities for controlling HCV infection.     

Sexual transmission of hepatitis C virus infection

The role of sexual transmission in the diffusion of HCV infection, was studied through the seroprevalence of anti-HCV antibodies in the heterosexual habitual partners of 83 anti-HCV positive subjects. The index cases were represented by 10 dialysed subjects, 31 patients with chronic liver disease and 42 healthy carriers. Seroprevalence of anti-HCV positivity reported in partners was 8.43%, with a higher rate in cohabitants of patients with chronic liver disease (16.12% vs 4.76% of carriers); no case was found among partners of dialysed subjects. Laboratory and ultrasonograph signs of chronic hepatitis were reported in 3 cases (3.61%). Control on 70% of the cohabitants' relatives, was negative for HCV infections. These data suggest a possible sexual transmission of HCV infection, even if its prevalence resulted modest, undoubtedly lower than in other disease sexually transmitted.     

丙型肝炎病毒感染及治疗转归中的NK细胞受体

NK细胞在HCV感染及治疗中起着至关重要的作用,其功能发挥受到表面受体的调节.该文对近年来NK细胞受体与HCV感染及治疗转归关系的研究进展作了综述.     

Toll样受体与丙型肝炎

Toll样受体(TLRs)系统是先天性免疫的重要组成部分,与HCV感染的免疫逃逸和发病机制有关.通过TLRs激动药治疗慢性丙型肝炎已获得初步疗效.文中对近年来有关TLRs在HCV感染发病和防治的研究进展作了综述.