病毒性肝炎干扰素治疗的临床分析

目的探讨干扰素治疗慢性乙型病毒性肝炎和同时合并其他类型病毒性肝炎的疗效．方法自1996／1998年，被诊断为慢性乙型肝炎和同时合并其他类型病毒性肝炎共85例，应用干扰素治疗55例，其中单纯慢性乙型肝炎44例，混合感染11例，对照30例建立在异常的ALT水平（大于正常1．5倍）至少6mo和阳性的乙肝病毒标记物（HBsAg和HBeAg）和阳性的HBVDNA．用a干扰素300万单位／次，3次／wk，肌肉注射，疗程6mo．结果应用干扰素治疗的55例病例中，23例阳性，HBeAg阴转（占41．8％），对照组5例（占16．7％，P＜0．01），18例HBVDNA阴转（占32．7％），对照组1例（占3％，P＜0．01）；14例HBsAg阴转（占25．5％），对照组3例（占1％，P＜0．01），上述结果均有高度显著性差异；在44例慢性乙肝患者中，23例阳性HBeAg阴转（占51％），对照组0（P＜0．01），该结果有高度显著性差异；治疗前ALT水平127．9u／L±10．2u／L；用药后短时期内20例出现ALT升高，水平为207．9u／L±10．2u／L（占36．4％）；停药后6mo8例阴转的HBeAg阳转（占14．5％），5例阴转的HBVDNA阳转（占9．1％）．结论干扰素对慢性乙型肝炎的治疗可提高治愈率（HBeAg阴转率41．8％，HBVDNA阴转率32．7％）；a-干扰素对单纯慢性乙型肝炎的治疗同对混合感染?

肝胆平口服液治疗病毒性肝炎500例

目的观察肝胆平口服液治疗病毒性肝炎的效果．方法应用肝胆平口服液（主要由大黄、胆草等组成）治疗病毒性肝炎500例．男350例，女150例，急性肝炎420例，慢性活动型肝炎10例，慢性迁延型肝炎8例，瘀胆型肝炎62例．所有患者口服肝胆平20mL，2次／d，5d为一疗程．重症者连用2～3个疗程对照组采用菌桅黄、门冬氨酸钾镁等国内常用保肝退黄药物治疗．通过1mo治疗对比两组治疗效果．结果服用肝胆平口服液组，用药15d后，退黄显效率75％．对照组显效率22％（P＜0．01）．用药20d后，治疗组和对照组降酶率分别为75％和23％（P＜0．01）．治疗组和对照组降浊分别为54％和20％（P＜0．01）用药40d，治疗组和对照组转阴率（HBsAg）分别为42％和20％．结论经非煎煮方法制备纯中药制剂（肝胆平口服液）对各种类型肝炎的治疗，可起到意想不到的疗效．可明显减轻症状，减少并发症发生率，提高HBsAg转阴率，尤其对于顽固性高胆红素血症患者，疗效独特，具有速效、高效、长效的作用．与相同药物经煎煮所得之药液相比，临床疗效更佳．

病毒性肝炎新动向推测

目的推测细胞凋亡在病毒性肝炎发病中的新认识．方法细胞凋亡是细胞生命的基本特征之一，并且有着广泛的生理学和病理学意义，这对理解生命个体的正常发育、疾病过程及其影响等具重要意义．就细胞凋亡在病毒性肝炎发病机制中的作用，学者们早已观察到并且早有认识，研究发现，肝病患者普遍都发生细胞凋亡，凋亡细胞主要散布在肝小叶中，在小叶内坏死灶及小叶周边碎屑坏死处，可见凋亡细胞呈灶状甚至成群分布，重症肝炎肝细胞死亡也以凋亡为主，肝细胞凋亡与肝组织的炎症也有关系，组织炎症活动度较高者细胞凋亡也较多，第八次全国病毒性肝炎学术会议上，有人报告用检测不同型的慢性乙肝患者的肝组织发现Fas表达，细胞凋亡和细胞DNA损伤程度与慢性肝炎严重性呈正相关，有人也专门就慢性肝病患者末梢血单个核细胞（PBMC）的Fasl表达状况作过调查，结果提示，不论乙型或丙型肝炎，不论慢性肝炎或肝硬变，都可见到末梢血单个核细胞中Fasl表达的增多，这可能是机体清除病毒的作用之一．结果病毒性肝炎是人类易感的传染性疾病，他对机体的健康状况影响极大，很大程度的降低本人的日常劳动强度，部分患者也过早衰亡．因此我们有必要重新对病毒性肝炎经典的发病机制作出更新、更具体、更完整的理论认识，其最终?

健脾护肝丸开创扶正为主治急肝之路

目的以扶正为主治急性黄疸型肝炎的中医疗法探讨．方法急性黄疸型肝炎20例，用健脾护肝丸（核桃仁、大枣肉、春砂仁等七味药组成），并配合陈溪黄虎汤对症加减治疗．其中男17例，女3例，非乙型肝炎11例，乙型肝炎9例，最高ALT2655V／L，最低ALT538V／L，平均ALT1340V／L．TBILI568．4μmol／L．治疗期为1mo～3mo．结果13例治疗1mo肝功恢复正常（占65％），3例治疗2mo肝功恢复正常（占15％），1例治疗3mo肝功恢复正常（占5％），2例明显好转后缺最后检验单（因门诊治疗不便索取）．文中列举非乙肝例1，男，39岁，ALT2655，TBILI63．2μmol／L，治疗1mo痊愈．例2，男，55岁，ALT：1425V／L，TBILI446．9μmol／L，A／G0．72，治疗2mo肝功恢复正常，临床症状痊愈．乙肝例1，男，27岁，肝功检查ALT538V／L，TBILI568．4μmol／L，HBsAg两对半为大三阳，治疗3mo肝功正常，乙肝大三阳转阴．例2，男，24岁，ALT2488V／L，HBsAg阳性，治疗1mo肝功正常，HBsAg转阴．结论健脾护肝丸，结合对症加减用法，其治疗急肝疗效显著，有望实现早治无重肝的预想．

Hepatocellular carcinoma prevention:A worldwide emergence between the opulence of developed countries and the economic constraints of developing nations

Hepatocellular carcinoma (HCC) is the fifth most common neoplasm, the major cause of death in patients with liver cirrhosis, and the third most common cause of cancer-related death in the world. The geographic distribution of HCC varies significantly and 80% of cases occur in developing countries (Far East and South Asia) where the prevalence of viral hepatitis is higher. The treatment of HCC is difficult because most patients are diagnosed when the tumour is in an advanced stage and is not amenable to potential curative therapy, thus prevention is the key to reducing HCC and its related morbidity and mortality. HCC is unique among cancers, occurring mostly in patients with a known risk factor. Ninety percent of HCCs develop in the context of chronic liver diseases and mainly in patients with cirrhosis. Viral hepatitis is the most common cause of HCC worldwide, followed by alcoholic liver disease (ALD) and other causes such as non-alcoholic fatty liver disease (NAFLD), genetic haemocromatosis (GH) and primary biliary cirrhosis in an advanced stage (Ⅲ- Ⅴ). In certain areas of the People’s Republic of China, exposure to aflatoxin and HBV infection are thought to be responsible for the extraordinary high risk of HCC. Substantial progresses in the prevention of virusl-related hepatitis (screening of blood units, use of disposable sanitary tools, HBV vaccination) have been achieved in developed countries, but in the same areas, alcohol- and dysmetabolism-related HCCs are emerging problems which require specific interventions in terms of public health measures. In developing countries, economic constraints limit the development of any program for the prevention of viral hepatitis transmission (including health education campaigns, healthcare politics, primary prevention and the improvement of hygienic and sanitary conditions). When viral liver disease is established, only a minority of patients are treated worldwide and benefit a possible preventive effect of medical treatment onHCC development. Thus the real contribution of medical treatment to HCC prevention in patients with chronic viral hepatitis is small. Great efforts are needed to identify more effective medical measures for primary and secondary prevention of HCC.

Chronic Epstein-Barr virus-related hepatitis in immunocompetent patients

AIM: To investigate reactivated Epstein-Barr virus (EBV) infection as a cause for chronic hepatitis. METHODS: Patients with occasionally established elevated serum aminotransferases were studied. HIV, HBV and HCV-infections were excluded as well as any other immunosuppressive factors, metabolic or toxic disorders. EBV viral capsid antigen (VCA) IgG and IgM, EA-R and EA-D IgG and Epstein-Barr nuclear antigen (EBNA) were measured using IFA kits. Immunophenotyping of whole blood was performed by multicolor flow cytometry. CD8+ T cell responses to EBV and PHA were determined according to the intracellular expression of IFN-γ. RESULTS: The mean alanine aminotransferase (ALT) and gamma glutamyl transpeptidase (GGTP) values exceeded twice the upper normal limit, AST/ALT ratio < 1. Serology tests showed reactivated EBV infection in all patients. Absolute number and percentages of T, B and NK cells were within the reference ranges. Fine subset analysis, in comparison to EBV+ healthy carriers, revealed a significant decrease of naive T cells (P < 0.001), accompanied by increased percentage of CD45RA- (P < 0.0001), and terminally differentiated CD28-CD27- CD8+ T cells (P < 0.01). Moderately elevated numbers of CD38 molecules on CD8+ T cells (P < 0.05) proposed a low viral burden. A significantly increased percentage of CD8+ T cells expressing IFN-γ in response to EBV and PHA stimulation was registered in patients, as compared to controls (P < 0.05). Liver biopsy specimens from 5 patients revealed nonspecific features of low-grade hepatitis.CONCLUSION: Chronic hepatitis might be a manifestation of chronic EBV infection in the lack of detectable immune deficiency; the expansion of CD28- CD27- and increase of functional EBV-specific CD8+ T cells being the only surrogate markers of viral activity.

Hepatitis B virus prevalence and transmission risk factors in inflammatory bowel disease patients at Clementino Fraga Filho university hospital

AIM: To evaluate the prevalence of hepatitis B virus (HBV) infection in inflammatory bowel disease (IBD) patients that followed up in our hospital and try to identify the possible risk factors involved in this infection transmission. METHODS: This was a cross-sectional study for which 176 patients were selected according to their arrival for the medical interview. All these patients had already IBD diagnosis. The patient was interviewed and a questionnaire was filled out. RESULTS: In the group of 176 patients whom we examined, we found that 17% (30) were anti-HBc positive. Out of 30 patients with positive anti-HBc, 2.3% (4) had positive HBsAg and negative HBV-DNA. In an attempt to identify the possible HBV infection transmission risk factors in IBD patients, it was observed that 117 patients had been submitted to some kind of surgical procedure, but only 24 patients had positive anti-HBc (P = 0.085). It was also observed that surgery to treat IBD complications was not a risk factor for HBV infection transmission, since we did not get a statically significant P value. However, IBDpatients that have been submitted to surgery to treat IBD complications received more blood transfusions then patients submitted to other surgical interventions (P = 0.015). CONCLUSION: There was a high incidence of positive anti-HBc (17%) and positive HBsAg (2.3%) in IBD patient when compared with the overall population (7.9%).

Mechanisms and significance of liver steatosis in hepatitis C virus infection

The pathogenesis of liver damage associated with chronic hepatitis C virus （HCV） infection is thought to be largely immunomediated. However, some frequent histoo pathological features, such as steatosis, suggest a direct cytopathic effect of HCV. The direct responsibility of HCV in the pathogenesis of steatosis is shown by： （1） the association with HCV genotype 3 infection, suggesting that some viral sequences are involved in the intracellular aco cumulation of lipids; （2） the correlation between severity of steatosis and HCV replication levels; （3） association between response to treatment and disappearance of steatosis. Experimental studies have shown that the nuo cleocapsid protein of HCV （core protein） is capable and sufficient to induce lipid accumulation in hepatocytes. Moreover, the observation that chronic hepatitis C pao tients have reduced serum levels of ApoB suggests an interference with the very-low density lipoprotein （VLDL） assembly, although other mechanisms are possible. In patients with sustained virological response induced by antiviral therapy, such levels are normalized. Other obo servations suggest that the pathogenesis of steatosis in chronic hepatitis C is not solely due to HCV. The origin of the mild steatosis observed in most patients may be metabolic, since its severity correlates with body mass index and insulin resistance. Most studies have shown a correlation between presence and/or severity of steatosis and fibrosis stage, but it is unclear whether this effect is direct or mediated by the associated insulin resistance, increased susceptibility to apoptosis, or by inflammao tory cytokines. Finally, steatosis negatively influences the rate of response to antiviral treatment, as confirmed by large clinical trials. Management of steatosis in chronic hepatitis C requires knowledge of its pathogenesis and may involve both life-style changes and pharmacological interventions, although the latter remain largely experio mental.

Current treatment indications and strategies in chronic hepatitis B virus infection

The optimal approach to the management of several marginal cases with chronic hepatitis B virus (HBV) infection is controversial. Serum HBV DNA and ami-notransferase levels, and the degree of necroinflammation and fibrosis determine the therapeutic decisions. All patients with elevated aminotransferase (> twice the upper limit of normal) and serum HBV DNA above 20 000 IU/mL should be treated. Liver biopsy is important for therapeutic decisions in cases with mild aminotransferase elevations and serum HBV DNA below 20 000 IU/mL. Chronic HBV patients who do not receive treatment should be followed for life. There are seven agents licensed for chronic hepatitis B: standard and pegylated interferon-alpha, lamivudine, adefovir, entecavir, telbivudine and tenofovir. One-year courses with pegylated interferon-alpha induce sustained off-therapy remission in 30%-32% of patients with HBeAg-positive chronic hepatitis B and in a smaller proportion of patients with HBeAg-negative chronic hepatitis B. Oral antivirals achieve initial on-therapy responses in the majority of patients, but are intended as long-term therapies. Viral suppression has favourable effects on patients' outcome and modifies the natural course of the disease. Viral resistance, however, is the major drawback of long-term oral antiviral therapy. Lamivudine monotherapy is associated with the highest and ente-cavir monotherapy with the lowest resistance rate so far. There has been no resistance to tenofovir, but afteronly 18 mo of treatment to date. The optimal first-line anti-HBV therapy with the best long-term cost/benefit ratio remains unclear. If oral antiviral agents are used, compliance should always be ascertained and HBV DNA levels should be regularly tested.

FibroSURE^(TM) and FibroScan~ in relation to treatment response in chronic hepatitis C virus

AIM:To compare histological endpoint assessment using noninvasive alternatives to biopsy during treatment in a chronic hepatitis C virus(HCV)cohort.METHODS:Patients with chronic HCV were randomized to receive interferon-based therapy for 24(genotypes 2/3)or 48(genotype 1)wk.FibroSURE～TM(FS)was assessed at baseline and at week-12 post-treatment follow-up.Baseline biopsy for METAVIR was assessed by a single pathologist.FibroScan～ transient elastogra-phy(TE)was performed during treatment in a patient subset.RESULTS:Two thousand and sixty patients(n = 253 in Asia)were classif ied as METAVIR F0-1(n = 1682)or F2-4(n = 378).For F2-4,FS(n = 2055)had sensitiv-ity and specif icity of 0.87 and 0.61,respectively,with area under the receiver-operating curve of 0.82;corre-sponding values for TE(n = 214)and combined FS/TE(n = 209)were 0.77,0.88 and 0.88,and 0.93,0.68 and 0.88.Overall FS/TE agreement for F2-4 was 71%(κ = 0.41)and higher in Asians vs non-Asians(κ = 0.86 vs 0.35;P < 0.001).Combined FS/TE had 97% accuracy in Asians(n = 33).Baseline FS(0.38 vs 0.51,P < 0.001)and TE(8.0 kPa vs 11.9 kPa,P = 0.006)scores were lower in patients with sustained virological response than in nonresponders,and were maintained through follow-up.CONCLUSION:FS and TE may reliably differentiate mild from moderate-advanced disease,with a potential for high diagnostic accuracy in Asians with chronic HCV.

Psychological impact of chronic hepatitis C:Comparison with other stressful life events and chronic diseases

AIM： To examine the psychological impact of chronic hepatitis C （CHC） diagnosis in a large cohort of CHC patients as compared with other stressful life events and chronic diseases carrying a risk of life-threatening complications. METHODS： One hundred and eighty-five outpatients with compensated CHC were asked to self-grade, using a 100-mm visual analogue scale （VAS）, the degree of stress caused by the learning of CHC diagnosis and the perceived severity of their disease. Diagnosis-related stress was compared to four other stressful life events and perceived CHC severity was compared to four other common chronic diseases. RESULTS： Learning of CHC diagnosis was considered a major stressful event （mean ± SD scores： 72±25）, significantly less than death of a loved-one （89±13, P〈0.0001） and divorce （78 ± 23, P〈0.007）, but more than job dismissal （68 ± 30, P〈 0.04） and home removal （26±24, P〈 0.0001）. CHC was considered a severe disease （74± 19）, after AIDS （94±08, P〈 0.001） and cancer （91± 11, P〈 0.001）, but before diabetes （66±23, P〈0.001） and hypertension （62±20, P〈0.001）. Perceived CHC severity was not related to the actual severity of liver disease, assessed according to Metavir fibrosis score. In multivariate analysis, diagnosisrelated stress was related to perceived disease severity （P〈0.001）, trait anxiety （P〈 0.001） and infection through blood transfusion （P〈 0.001）. CONCLUSION： Our results show the considerable psychological and emotional burden that a diagnosis of CHC represents, even in the absence of significant liver disease. They should be taken into account when announcing a diagnosis of CHC in order to reduce its negative effects.

Aptamers Against Viral Hepatitis:from Rational Design to Practical Application

Aptamers are short nucleic acids or peptides that strongly bind to a protein of interest and functionally inhibit a given target protein at the intracellular level. Besides high affinity and specificity, aptamers have several advantages over traditional antibodies. Hence, they have been broadly selected to develop antiviral agents for therapeutic applications against hepatitis B and C viruses (HBV, HCV). This review provides a summary of in vitro selection and characterization of aptamers against viral hepatitis, which is of practical significance in drug discovery.

Current progress in the treatment of chronic hepatitis C

Over the last decade, the standard of care for the treat- ment of chronic hepatitis C has been the combination of pegylated-interferon-alfa （PEG-IFN） and ribavirin （RBV） which results in sustained virological response （SVR） rates of 75%-85% in patients with genotypes 2 or 3 but only of 40%-50% in patients with genotype 1. Cur- rently, there are rapid and continuous developments of numerous new agents against hepatitis C virus （HCV）, which are the focus of this review. Boceprevir and tela- previr, two first-generation NS3/4A HCV protease inhibi- tors, have been recently licensed in several countries around the world to be used in combination with PEG- IFN and RBV for the treatment of genotype 1 patients. Boceprevir or telaprevir based triple regimens, com- pared with the PEG-IFN/RBV combination, improve the SVR rates by 25%-31% in treatment-naTve genotype 1 patients, by 40%-64% in prior relapsers, by 33%-45% in prior partial responders and by 24%-28% in prior null responders. At the same time, the application of response-guided treatment algorithms according to the on-treatment virological response results in shortening of the total therapy duration to only 24 wk in 45%-55% of treatment-na＇ive patients. There are, however, several challenges with the use of the new triple combinations in genotype 1 patients, such as the need for immediate results of HCV RNA testing using sensitive quantitative assays, new and more frequent adverse events （anemia and dysgeusia for boceprevir; pruritus, rash and anemia for telaprevir）, new drug interactions and increasing dif- ficulties in compliance. Moreover, the SVR rates are still poor in very difficult to treat subgroups of genotype 1 patients, such as null responders with cirrhosis, while there is no benefit for patients who cannot tolerate PEG- IFN/RBV or who are infected with non-1 HCV genotype. Many newer anti-HCV agents of different classes and numerous combinations are currently under evaluation with encouraging results. Preliminary data suggest that the treatment of chronic HCV patients with well toler- ated combinations of oral agents without PEG-IFN is feasible and may lead to a universal HCV cure over the next 5-10 years.

Survival and prognostic factors in hepatitis B virus-related acute-on-chronic liver failure

AIM:To investigate the survival rates and prognostic factors in patients with hepatitis B virus-related acuteon-chronic liver failure(HBV-ACLF).METHODS:Clinical data in hospitalized patients with HBV-ACLF admitted from 2006 to 2009 were retrospectively analyzed.Their general conditions and survival were analyzed by survival analysis and Cox regression analysis.RESULTS:A total of 190 patients were included in this study.The overall 1-year survival rate was 57.6%.Patients not treated with antiviral drugs had a significantly higher mortality[relative risk(RR)=0.609,P=0.014].The highest risk of death in patients with ACLF was associated with hepatorenal syndrome(HRS)(RR=2.084,P=0.026),while other significant factors were electrolyte disturbances(RR=2.062,P=0.010),and hepatic encephalopathy(HE)(RR=1.879,P<0.001).CONCLUSION:Antiviral therapy has a strong effect on the prognosis of the patients with HBV-ACLF by improving their 1-year survival rate.HRS,electrolyte disturbances,and HE also affect patient survival.

Treatment of hepatitis C virus infection

Acute and chronic hepatitis C virus (HCV) infection remains a serious health problem worldwide, however, there has been advancement in the treatment of HCV infection due to standard treatment using pegylated interferon and ribavirin. The literature indicates that therapy for HCV is becoming more individualized. In addition to considering genotype and viral RNA levels before treatment, achievement of an early virologic response (EVR) and a rapid virologic response (RVR) is now possible during therapy. Moreover, problem patients, such as non-responders, relapsers, HIV or HBV co- infected patients, patients with liver cirrhosis, and pre- or post-liver transplantation patients are an increasing fraction of the patients requiring treatment. This article reviews the literature regarding standard treatments and problem patients with acute and chronic HCV infection. It also includes discussion on contraindications and side effects of treatment with interferon and ribavirin, as well as new drug development.

New therapeutic vaccination strategies for the treatment of chronic hepatitis B

Chronic hepatitis B virus(CHB) is currently treated with either interferon-based or nucleot(s)idebased antiviral therapies.However,treatment with pegylated interferon alpha results in a durable antiviral response in only about 30%patients and is associated with side effects.Most patients receiving nucleot(s)ide analogue treatment do not establish long-term,durable control of Infection and have rebounding viremia after cessation of therapy.Thus,novel therapy strategies are necessary to achieve the induction of potent and durable antiviral immune responses of the patients which can maintain long-term control of viral replication.Therapeutic vaccination of HBV carriers is a promising strategy for the control of hepatitis B.Here the authors review new therapeutic vaccination strategies to treat chronic hepatitis B which may be introduced for patient treatment in the future.

Genetic diversity of the hepatitis C virus: Impact and issues inthe antiviral therapy

The hepatitis C Virus (HCV) presents a high degree of genetic variability which is explained by the combination of a lack of proof reading by the RNA dependant RNA polymerase and a high level of viral replication. The re- sulting genetic polymorphism defines a classification in clades, genotypes, subtypes, isolates and quasispecies. This diversity is known to reflect the range of responses to Interferon therapy. The genotype is one of the pre- dictive parameters currently used to define the antiviral treatment strategy and the chance of therapeutic suc- cess. Studies have also reported the potential impact of the viral genetic polymorphism in the outcome of antivi- ral therapy in patients infected by the same HCV geno- type. Both structural and non structural genomic regions of HCV have been suggested to be involved in the Inter- feron pathway and the resistance to antiviral therapy. In this review, we first detail the viral basis of HCV diversity. Then, the HCV genetic regions that may be implicated in resistance to therapy are described, with a focus on the structural region encoded by the E2 gene and the non- structural genes NS3, NS5A and NS5B. Both mechanisms of the Interferon resistance and of the new antiviral drugs are described in this review.

Hepatitis C virus genotypes in Serbia and Montenegro: The prevalence and clinical signifi cance

AIM： To investigate the prevalence of hepatitis C virus （HCV） genotypes in Serbia and Montenegro and their influence on some clinical characteristics in patients with chronic HCV infection. METHODS： A total of 164 patients was investigated. Complete history, route of infection, assessment of alcohol consumption, an abdominal ultrasound, standard biochemical tests and liver biopsy were done. Gene sequencing of 5＇ NTR type-specific PCR or commercial kits was performed for HCV genotyping and subtyping. The SPSS for Windows （version 10.0） was used for univariate regression analysis with further multivariate analysis. RESULTS： The genotypes 1, 2, 3, 4, 1b3a and 1b4 were present in 57.9%, 3.7%, 23.2%, 6.7%, 6.7% and 1.8% of the patients, respectively. The genotype 1 （mainly the subtype 1b） was found to be independent of age in subjects older than 40 years, high viral load, more severe necro-inflammatory activity, advanced stage of fibrosis, and absence of intravenous drug abuse. The genotype 3a was associated with intravenous drug abuse and the age below 40. Multivariate analysis demonstrated age over 40 and intravenous drug abuse as the positive predictive factors for the genotypes lb and 3a, respectively.CONCLUSION： In Serbia and Montenegro, the genotypes 1b and 3a predominate in patients with chronic HCV infection. The subtype lb is characteristic of older patients, while the genotype 3a is common in drug abusers. Association of the subtype lb with advanced liver disease, higher viral load and histological activity suggests earlier infection with this genotype and eventually its increased pathogenicity.

Current treatment options and response rates in children with chronic hepatitis C

Vertical transmission has become the most common mode of transmission of hepatitis C virus (HCV) in children.The rate of perinatal transmission from an HCVinfected mother to her child ranges from 2% to 5% and the prevalence of HCV in children in developed countries ranges between 0.1% and 0.4%.Spontaneous viral clearance seems to be dependent on the genotype and has been reported between 2.4%-25%.For chronically infected patients,treatment with recombinant polyethylene glycol (PEG)-interferon α-2b and daily ribavirin has now been approved as standard treatment for children 2-17 years of age.In five large prospective studies,a total of 318 children and adolescents aged 3-17 years were treated either with subcutaneous PEG-interferon α-2b at a dose of 1-1.5 μg/kg or 60 μg/m2 once a week in combination with oral ribavirin (15 mg/kg per day) or PEG-interferon α-2a with ribavirin.Subjects with genotype 1 and 4 received the medication for 48 wk and individuals with genotype 2 and 3 mainly for 24 wk.Overall sustained viral response (SVR) was achieved in 193/318 (60.7%) of treated patients.Stratified for genotype;120/234 (51%) with genotype 1,68/73 (93%) with genotype 2/3,and 6/11 (55%) with genotype 4 showed SVR.Relapse rate was between 7.7% and 17%.Overall,treatment was well tolerated;how-ever,notable side effects were present in approximately 20%.According to recent experiences in the treatment of chronic hepatitis C in children and adolescents,a combination of PEG-interferon α with ribavirin has been found to be well tolerated and highly efficacious,particularly in individuals with genotype 2/3.Thus,this treatment can be recommended as standard of care until more effective treatment options will become available for genotype 1 patients.

Long-term outcomes of chronic hepatitis C patients with sustained virological response at 6 months after the end of treatment

AIM: To assess the clinical, biochemical, and virological outcome during long-term follow-up of chronic hepatitis C patients with sustained virological response following effective antiviral therapy.METHODS: This study was a retrospective cohort study including 171 sustained responders defi ned as HCV RNA PCR negative at 6 mo after the end of effective antiviral treatment (SVR-6). Clinical signs and symptoms, bio- chemical hepatic parameters, ultrasonography and HCV RNA PCR were followed.RESULTS: Mean follow-up period was 35.38 ± 22.2 mo after the end of treatment. Twenty-seven (15.8%) responders had evidence of cirrhosis before treatment. Forty-eight (28.1%), 107 (62.6%) and 6 (3.5%) patients were genotype 1, 3, and 6 respectively, while 10 patients (5.8%) were unclassifi ed. There were no virological and biochemical relapses during the period of follow-up. None of the patients showed evidence of hepatic decom- pensation. However, there were 3 patients (1.8%) de- veloping hepatocellular carcinoma at 14, 18, 29 mo after treatment discontinuation, two of whom had evidence of cirrhosis prior to therapy.CONCLUSION: The study shows that during a follow- up interval for about 3 years in 171 chronic hepatitis C patients with sustained viral response after effective antiviral treatment there were no evident signs of either biochemical or clinical relapse of liver disease in all but three patients who developed hepatocellular carcinoma.