Association of chronic hepatitis C and lichen planus--in two patients

Relationship between hepatitis C virus (HCV) infection and lichen planus (LP) is well known but controversial in the literature. AIM: Two patients with lichen planus and chronic hepatitis C are presented. One of them suffered with disseminated LP and the other had cutaneous and oral erosive symptoms. METHODS: The chronic hepatitis of the patients was proved by elevated ALT and AST level, anti HCV (ELISA) and HCV-PCR serological examinations and liver biopsy. The diagnosis of lichen planus established on he typical clinical symptoms and the histological examination. RESULTS: HCV RNA in the skin specimen from the biopsy of the skin lesion was detected by RT-PCR method, but the non affected skin specimen from the first patient was HCV RNA negative. Treatment of the chronic hepatitis C with specific therapy (interferon-alpha + ribavirin) in the second patient led to the regression of lichen planus symptoms. CONCLUSIONS: The authors supposed that the lichen planus is one of the extrahepatic manifestations of HCV infection and there is a real correlation between the two diseases in these cases.     

Viral co-infections in hepatitis C: HBV, HBV-C/HGV and TTV studies

BACKGROUND/AIMS: The prevalence of co-infections with hepatitis B virus (HBV) and novel hepatitis viruses GBV-C (Hepatitis G virus, HGV) and TT virus (TTV) in chronic hepatitis C (HCV) infection has been studied. In patients with chronic hepatitis C and in asymptomatic healthy HCV carriers, the influence of these agents on the course of HCV infection was assessed. METHODS: a total of 110 HCV-positive individuals, among them 77 patients with chronic hepatitis C--50 of them treated with interferon (IFN)--and 33 HCV carriers with normal alanine aminotransferase have been investigated. HBV-DNA, HGV RNA and TTV DNA were detected by PCR, to determine HBsAg and anti-HBc ELISA technic has been used. RESULTS: In the healthy population, the prevalence of anti-HCV was 0.3%, HBsAg 0.09%, anti-HBc 2.5%, HGV RNA 8.0% and TTV DNA 18.5%, respectively. In chronic hepatitis C HBsAg (accompanied with HBV-DNA) occurred in 1.29%, anti-HBc 25.97%, HGV RNA in 9.09% and TTV DNA in 40.25% of cases. In IFN-treated patients with sustained remission, the frequency of TTV was 20% vs. 45.7% found in non-responders. Among asymptomatic HCV-carriers, the prevalence of anti-HBc was 27.27%, HGV RNA 9.09% and TTV DNA 75.7% respectively. CONCLUSIONS: Neither previous HBV infection, nor HGV RNA and TTV DNA had apparent effect on the course of chronic HCV infection. TTV was detected with the lowest frequency in persons with sustained remission due to IFN, suggesting antiviral effect of IFN on TTV.     

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.     

Examination of hepatitis c virus antibody seropositive blood donors and their relatives

INTRODUCTION: 239 anti-HCV seropositive blood donors (132 male, 107 female, age: 19-61, mean: 40.59 y.) and 174 family members of them (74 male, 100 female, age: 4-65, mean: 23.67 y.) were studied for chronic hepatitis C virus infection and chronic liver disease. Detailed virus serology, ultrasonography, and 6 months follow-up and--in patients with HCV RNA--liver biopsy were made. RESULTS: HCV RNA was determined in 165 patients. 70% of them were HCV RNA positive. The ALT level was normal in 95 cases (57%), and lower, than twice of the normal was in 34 cases (20%) among them. Liver biopsy was made in 79 patients; chronic C hepatitis was proven in 75 cases (steatosis in 3 cases, alcoholic liver disease in 1 case was observed). Inflammatory activity was minimal (HAI < 3) in 17, mild (HAI: 3-6) in 41, moderate (HAI: 7-9) in 7, and severe (HAI > 9) in 10 cases. There was no correlation between the serum ALT levels and the severity of the histological activity of chronic C hepatitis. Authors stress the importance of the fact, that 2 patients had normal ALT and 5 patients ALT levels were lower, than the twice of the normal of the 17 patients with significant inflammatory activity (HAI < 6). Chronic C hepatitis need for antiviral therapy was occurred in 45% of patients who known themselves previously healthy. CONCLUSIONS: The necessity of the systematic examination of anti-HCV seropositive patients and of the importance of the liver biopsy in patients with HCV RNA positivity is stressed. 3 anti-HCV seropositive cases of 174 family members of the blood donors were observed, but none of them was HCV RNA positive. It seems to be, family members of the HCV infected patients have no increased risk for HCV infection.     

乙型肝炎患者重叠感染丙型肝炎、庚型肝炎病毒的研究

[目的 ]了解乙型肝炎患者重叠感染丙型肝炎病毒 (HCV)、庚型肝炎病毒 (HGV)的情况。 [方法 ]应用 EL ISA法分别对 86 8例乙肝患者、5 17例乙肝病毒携带者检测血清抗 - HCV和抗 - HGV,应用逆转录聚合酶链反应法分别对HCV、HGV感染者进行血清 HCV- RNA、HGV- RNA检测 ,并与乙肝病毒携带者比较。 [结果 ]乙肝患者与乙肝病毒携带者 HCV感染率分别为 14.5 %、2 .3% ,HGV感染率分别为 15 .6 %、3.9% ,HCV和 HGV的重叠感染率分别为 2 .3%、0 .2 % ,两组间 HCV、HGV合并感染率均有非常显著性差异 (P<0 .0 1)。乙肝患者中 HCV感染者 HCV- RNA阳性率14.3% ,HGV感染者 HGV- RNA阳性率 11.9%。 [结论 ]乙型肝炎、丙型肝炎、庚型肝炎可以重叠感染。急慢性乙型肝炎患者的 HCV、HGV重叠感染率不同。     

我国部分地区丙型肝炎病毒基因分型研究

目的：研究中国丙型肝炎病毒（HCV）基因型分布。方法：应用AmplicorPCR试剂盒检测北京、青岛、固安和周口等地27例抗－HCV阳性的单采浆供血员和36例慢性丙型肝炎病人血清HCV RNA,并对其中36例HCV RNA阳性者用INNO－LiPA^TMHCV II试剂进行HCV基因分型。结果：抗－HCV阳性的单采浆供血员和慢性丙型肝炎病人HCV RNA检出率0分别为48.15％（13／27）和69.44%(25／36）,平均为60.32％（38／63）。对13例HCV RNA阳性的单采浆供血员和23例慢性丙型肝炎病人HCV基因分型结果表明,29例（80.55％）为1b型,5例（13.89％）为2型,另2例（5.56％）不能被分型。结论：上述调查地区流行的HCV基因型以1b型占优势。     

Non-invasive fibrosis assessment in chronic hepatitis C: aspartate-aminotransferase to platelet ratio index (APRI) and transient elastography (FibroScan)

Although liver biopsy is the gold standard for the diagnosis of liver disease, non-invasive tests may also play a role in the evaluation of liver fibrosis. Authors studied two fibrosis markers, aspartate-aminotransferase / platelet ratio index (APRI) and liver stiffness (LS) measurement to assess fibrosis in different forms of chronic hepatitis C virus (HCV) infection. Patients and methods: out of 119 HCV-infected patients 75 had biopsy-proven chronic hepatitis C, 24 had HCV-cirrhosis, 20 individuals were symptom-free HCV-carriers with persistently normal alanine-aminotransferase and 30 healthy blood donors served as controls. Wai's APRI score was calculated from aspartate-aminotransferase and platelet number. For LS measurement transient elastography (FibroScan) was applied. METAVIR fibrosis score was determined by liver biopsy. Results: In patients with chronic hepatitis C infection both fibrosis markers were significantly elevated comparing to normal controls and the markers were the highest in HCV-associated cirrhosis. Values of symptom-free HCV-carriers corresponded to those obtained from healthy controls. Both APRI and LS results correlated with the METAVIR score. LS identified fibrosis better than APRI. Using a novel sequential algorithm that comprises APRI and LS for assessment of fibrosis, 47.8% of HCV patients did not need biopsy for diagnosing significant (F≥2) fibrosis. Conclusion: both fibrosis markers, particularly in combination, may represent a useful option in the noninvasive assessment of fibrosis in HCV infection.     

The hepatitis C virus--principal causative agent in non-A, non-B hepatitis

The diagnosis of non-A, non-B (NANB) hepatitis was based on the exclusion of hepatitis A and B infection and other known causes of hepatitis, such as other viruses, alcohol and toxic effects. More recently, an RNA has been isolated from a NANB-infected chimpanzee serum and with its aid a polypeptide antigen was produced by molecular biological methods. Antibodies to this antigen--as part of the infectious agent, called hepatitis C virus (HCV)--were detected in the sera of infected patients. Studies with this antigen/antibody system proved, the HCV is responsible for the majority of posttransfusion and sporadic NANB hepatitis cases worldwide. The antibody appears late, in the serum up to 6 months after the infection. The occurrence of the infection is high among hemophiliacs and drug abusers. Anti-HCV antibody was detected also in certain liver disease with "unknown etiology" (chronic active hepatitis, primary biliary cirrhosis). This newly developed test provides the possibility to prove HCV infection in different groups of patients by detecting an antibody to a component of HCV.     

乙型、丙型、庚型肝炎病毒多重感染研究

目的探讨庚型肝炎感染患者是否存在双重感染和多重感染。方法应用庚型肝炎病毒（ＨＧＶ）ＮＳ３区逆转录聚合酶链反应技术检测了ＨＧＶ系列稀释的质控血清及ＡｂｂｏｔＧＢＶ－Ｃ参比样品中ＨＧＶＲＮＡ，并对９０例丙型肝炎病毒（ＨＣＶ）ＲＮＡ阳性和１２例乙型肝炎、丙型肝炎双重感染献血员进行了ＨＧＶＲＮＡ的检测。结果ＨＧＶ系列稀释质控血清１０－１～１０－５均为阳性；１０－６为阴性。２份ＡｂｂｏｔＧＢＶ－Ｃ样品均为ＨＧＶＲＮＡ阳性。９０例ＨＣＶＲＮＡ阳性样品中，８例ＨＧＶＲＮＡ阳性（１７．８％）；１２例乙、丙双重感染者中４例（４／１２）ＨＧＶＲＮＡ阳性。结论不仅存在ＨＣＶ及ＨＧＶ双重感染，也存在多重感染。     

Peripheral neuropathy without cryoglobulinemia in patients with hepatitis C virus infection

BACKGROUND: An association between essential mixed cryoglobulinemia and hepatitis C virus infection has been documented by many reports. Some clinical manifestations such as purpura, arthralgia, vascular lesions and peripheral neuropathies are also connected with the presence of detectable cryoglobulins. The association between HCV infection, the presence of mixed cryoglobulinemia and peripheral neuropathy is well documented. The aim of this study was to define the possible presence of peripheral neuropathy in HCV patients without detectable cryoglobulins and the possible association with the different genotypes. METHODS: Twenty patients (11 females, 9 males) with chronic HCV hepatitis and without detectable cryoglobulins were submitted to neurological and electrophysiological studies to detect a possible peripheral neurological involvement. In all patients the HCV infection was assumed by the presence of antibodies to HCV with ELISA assay and then confirmed with recombinant immunoblot assay. HCV genotyping was obtained by INNO LIPA in 15 out of 20 patients. In 4 patients a sural nerve biopsy was possible. RESULTS: Genotype 1b was present in 80% of patients, while 1a in 13.3% and 4 in 6.6%. Thirteen patients had positive neurological anamnesis (65%), while neurological examination was positive in 40% of the cases. Electromyographic study was positive in 50% of subjects. The sural nerve biopsies agreed with axonal degeneration in amyelinated fibres. CONCLUSIONS: Our results suggest a possible peripheral neurological system involvement in patients with HCV infection without cryoglobulins.     

Prevalence and clinical features of skin diseases in chronic HCV infection. A prospective study in 96 patients

BACKGROUND: Between extra-hepatic manifestations of hepatitis C virus (HCV) infection particular interest is focused on some dermatological diseases such as: leukocytoclastic vasculitis, oral lichen planus, pruritus-urticaria, psoriasis, etc. The aim of this study was to determine the prevalence of some dermatoses in our population of patients with HCV infection and describe the more characteristics clinical pictures. METHODS: Ninety-six patients (36 men and 60 women) aged from 35 to 74 years with HCV documented by 3rd generation ELISA and RIBA tests were prospectively examined for 3 years to determine the prevalence of some skin disorders, reported as associated with HCV infection. All patients were also studied for presence and quantification of HCV-RNA by polymerase chain reaction and genotyping when possible. Eighty-one underwent a liver biopsy. Routine laboratory tests and some immunological investigations (ANA, AMA, SMA, LKM, ANCA, ICC, crioglobulins) were performed using standard procedures and indirect immunofluorescence, nephelometric, RIA methods. RESULTS: Twelve of 96 patients (12.5%) presented skin disorders in progress of chronic virus C hepatitis: 5 cases of leukocytoclastic vasculitis (LCV) by mixed cryoglobulinemia, 1 case of pruritus, 2 cases of oral lichen planus (OLP), 2 cases of alopecia areata, 1 case of urticaria, 1 case of psoriasis. CONCLUSIONS: Our findings show a calculated prevalence of clinical dermatoses in HCV infected patients around 12.5%. These findings confirm however the importance of liver examination in presence of skin diseases not related to other pathogenetic mechanisms.     

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     

血液透析及丙肝病毒感染者F蛋白抗体分析

目的探讨丙型肝炎病毒(hepatitis C virus,HCV)F蛋白抗体在血液透析人群HCV感染者中的分布特点及其影响因素。方法利用pEGX-4T-2/HCV-F融合载体表达蛋白HCV-F/GST作为抗原,包被酶联反应板,间接ELISA法检测128例血液透析HCV感染者血清中的HCV-F抗体;Logistic回归分析患者特征与HCV-F抗体是否阳性的关系。结果 128例HCV感染者中F抗体阳性率为45.3%;单因素分析显示,血透时间、HBcAb、HCV RNA与F抗体是否阳性的差异有统计学意义(分别P=0.038、P=0.012和P=0.002);多因素分析显示,血透时间>10年(OR=4.153,95%CI=1.435～12.023)、HCV RNA阳性(OR=3.6979,5%CI=1.498～9.123)是HCV-F抗体阳性的影响因素。结论血液透析人群HCV感染者中可检出F抗体;F蛋白的表达可能与HCV复制有关。     

Hepatitis C virus transmission in family members of Egyptian patients with HCV related chronic liver disease

Hepatitis C virus (HCV) infection in Egypt has become a major public health problem. In the present study, sexual and intrafamilial transmission of HCV infection were assessed in the family members of 200 Egyptian patients (index patients) with HCV-RNA positive and biopsy ascertained chronic hepatitis C. Index patients were 139 men (mean age 55+/-11 years) and 61 women (mean age 48+/-8 years). Family members consisted of 200 spouses; 139 women (mean age 45+/-12 years) and 61 men (mean age 58+/-9 years); and 355 children (183 males and 172 females, mean age 11.8+/-10 years). All the family members were tested for the presence of antibodies to HCV in their sera. Thereafter, HCV-RNA detection by PCR and HCV serotype determination were performed in antibody positive contacts. Hepatitis C virus antibodies were detected in 28 (14%) spouses, all of them were also positive for HCV-RNA. Hepatitis C virus serotypes were identical in HCV seropositive patient-spouse pairs (Serotype 4). None of the 355 children involved in this study showed HCV antibodies in their sera. No significant difference was found between the prevalence of male-to-female and female-to-male transmission of HCV. A highly significant association was found between both the age of the spouse and the duration of marriage to index patient and HCV seropositivity in spouses. Moreover, HCV seropositivity in spouses was significantly related to increased serum ALT and HCV-RNA levels, histological severity of chronic hepatitis C and to a history of dental care, as a risk factor for HCV acquisition, in index patients. It was concluded that spouses of patients with HCV viremia and chronic liver disease have an increased risk for acquiring HCV, while intrafamilial acquisition of HCV in non sexual contacts seems to be rare. The authors suggest that spouses of HCV viraemic patients should be followed routinely for markers of HCV infection and liver disease.     

丙型肝炎病毒感染与情感认知障碍

越来越多的研究证据表明,慢性HCV感染者存在情感认知障碍。通过磁共振质子波谱等技术能检测到HCV感染与中枢神经系统代谢异常密切相关。其发生机制可能是,HCV能够通过复制侵犯神经系统,引起中枢或周围神经系统病变,情感认知障碍为其表现之一。此文就HCV感染与情感认知障碍的相关研究进行了综述。     

Possible role of angiotensin-converting enzyme polymorphism on progression of hepatic fibrosis in chronic hepatitis C virus infection

Many functional polymorphisms in the rennin-angiotensin system (RAS) have been described; these polymorphisms have been postulated to contribute to fibrosis in several diseases. Our aim was to study the frequency of ACE I/D polymorphism in chronic hepatitis C virus (HCV) infection and its association with liver fibrosis and response to treatment. This study included 90 patients with chronic hepatitis C. All patients received antiviral therapy in the form of pegylated interferon and ribavirin. Patients were grouped according to the stage of liver fibrosis by biopsy into: group 1 (fibrosis: 0 or 1); group 2 (fibrosis: 2 or 3) and group 3 (fibrosis: 4 or 5). The study included also 170 healthy subjects, as a control group. Polymerase chain reaction was carried out to detect the different ACE genotypes. The D/D genotype was significantly more prevalent among HCV patients compared to controls (65.6% vs 48.2%, P = 0.006). Degree of necroinflammation was significantly higher among patients with I/I genotype when compared to patients with D/D genotype (P = 0.04). No significant difference in the distribution of the ACE I/D genotypes between the fibrosis groups and between responders and non responders to interferon therapy. The D/D genotype may increase the susceptibility to infection with hepatitis C.     

Clinical course and outcome of a nosocomial outbreak of hepatitis C in a urology ward

This paper describes a prospective study of the clinical course and outcome of a nosocomial outbreak of hepatitis C virus (HCV) infection in six male urology patients at a hospital in Stara Zagora, Bulgaria. These patients had been previously hospitalised in the urology ward, during which all had received intravenous therapy. Approximately three weeks later, all six were admitted to the infectious diseases unit with acute hepatitis, shown to be caused by HCV genotype 1b. The diagnosis was confirmed by polymerase chain reaction during the first week of their hospital stay. Infected patients were followed up for 30 months following diagnosis and 54 potential contacts for 6 months post-exposure. Four patients recovered completely; one developed chronic HCV infection and one died. The latter already had cirrhosis due to co-infection with hepatitis B virus. The investigation established the index case as a patient with chronic hepatitis C, who had been an in-patient on the same ward at the same time. The most likely route of transmission was intravenous heparin flushes administered with a common syringe. Contrary to the common assumption that acute HCV infection often leads to chronic disease, only one chronic case was observed during the 30-month period of investigation.     

Treatment of recurrent hepatitis C virus infection after liver transplantation

The main indication of liver transplantation is the final stage of liver cirrhosis developed in hepatitis C virus (HCV) infection. The recurrence of HCV infection after transplantation is a common situation. The recurrent hepatitis C is a progressive disease, in 20 percent of patients it produces liver cirrhosis without treatment beside immunosuppression within 5 years. The treatment of recurrent HCV infection is the most important factor of the survival in patients with transplantation. The authors review the factors influencing the progression of recurrent HCV infection on the basis of literary data and also on their observation. They discuss in details the effect of immunosuppressive treatment, the importance in the selection of corresponding immunosuppressive drugs. They review the main keypoints in the diagnosis of recurrent hepatitis C, underline the important role of liver biopsy carried out according to the protocol in the diagnosis, furthermore the hard consultation among pathologist, hepatologist and surgeon. They demonstrate the observations with the treatment of patients on the waiting list, the results in the early, preemptive treatment of recurrent chronic hepatitis, furthermore the treatment modalities and the results in patients with chronic hepatitis C histologically proved. The drug of choice of chronic hepatitis C after transplantation is the combined therapy with pegylated interferon and ribavirin. This therapy is able to assure virus-free stage in 20-50 percent of patients. In the virus-free patients the inflammatory activity in the liver significantly decreases, the histologic activity index improves. There are data showing the effect of treatment for inhibiting the fibrosis, but multicenter studies are necessary for the confirmation of these data. The advantage of early antiviral therapy without histologic alteration has not been confirmed by most of the trials. The anaemia and the neutropenia are frequent side effects in this patient group, that is why the applications of erythropoietin and granulocyte stimulating factor are recommended. Further trials and clinical studies are necessary for the optimal treatment of patients with recurrent hepatitis C, and to determine the dosage of pegylated interferon and ribavirin, to decrease the duration of therapy and the side effects, finally to achieve a healing phase of higher degree.     

北京市4 055名健康儿童丙型肝炎血清流行病学调查

目的 了解北京市城区儿童中丙型肝炎的发病情况。方法 对北京市４个城区４０５５名健康儿童用ＥＬＩＳＡ法进行丙型肝炎病毒抗体（抗－ＨＣＶ）检测。结果 抗－ＨＣＶ阳性１４人,同时伴丙型肝炎病毒核糖核酸阳性４人,ＨＣＶ感染率为０．３５％。各城区、各年龄组、男女性儿童间ＨＣＶ感染率比较差异无显性。但有输血、注射人血球蛋白等史与无上述历史组对比,ＨＣＶ感染率差异有极显性。１４例抗－ＨＣＶ阳性儿童的父母检     

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.