Children with hepatitis C

Hepatitis C affects thousands of children throughout the world. Most children acquire the virus through vertical transmission, although parenteral routes of acquisition are also common. Hepatitis C progresses slowly, with mild biopsy findings and no symptoms in most children and in many adults. However, significant liver inflammation and fibrosis can occur in childhood. Trials of antiviral therapy with interferon and ribavirin have shown these drugs to be effective in almost half of the children treated. Children tend to tolerate therapy well. Further research on the natural history and treatment of hepatitis C in children is needed because the infection can have serious long-term consequences, including end-stage liver disease and hepatocellular carcinoma.     

慢性丙型肝炎患者HCV基因型分析

目的研究慢性丙型肝炎患者HCV基因型概况。方法采用基因芯片法检测HCV基因分型;采用PCR法测定HCV RNA定量。结果在570例患者中,HCV RNA阳性552例（95%）,其中1b型400例（72.4%）,2a型63例（11.4%）,3a型20例（3.6%）,3b型20例（3.6%）,1b＋2a型12例（2.1%）,1a型2例（0.4%）,6型7例（1.26%）,1b＋3a型1例（0.18%）,2a＋1b型3例（0.5%）,未定型24例（4.3%）;不同HCV基因型感染者血清HCVRNA水平无统计学差异（P〉0.05）。结论本组患者HCV基因型以1b型为主,2a型次之,多种混合型的出现提示HCV基因型呈现多样化趋势。     

Hiv coinfection with hepatitis C and hepatitis B

HIV, hepatitis C virus, and hepatitis B virus are global health concerns. Due to shared routes of transmission, coinfection is common. The incidence of liver-related mortality in coinfected patients has risen significantly since the inception of highly active antiretroviral therapy, a treatment that has helped decreased mortality rates from AIDS and opportunistic infections. This trend has led to increased research into the evaluation and management of the coinfected patient. This article details the principles of successful management of this challenging patient population.     

Genotypes of hepatitis C virus in Italian patients with chronic hepatitis C

To assess the prevalence of different hepatitis C virus genotypes in an European population of patients with chronic hepatitis C, 79 consecutive Italian patients were studied. After having cloned and sequenced part of the 5′ untranslated region of the virus in 21 patients, oligonucleotide probes were synthesized to be used in a more rapid dot-blot hydridization test. Using this method, 42% of patients were found infected by HCV type 1, 45% by HCV type 2 and 4% by HCV type 3, while seven patients remained unclassified. Patients infected by HCV type 3 were significantly younger and had a milder form of liver disease, compared to those infected by HCV type 1 or HCV type 2. Patients with HCV type 2 or HCV type 3 responded to interferon therapy much better than those with HCV type 1. These results provide information on the prevalence of different HCV genotypes in our region, and indicate the usefulness of the dot-blot hybridization procedure for rapid screening of HCV genotypes.     

Counselling patients with hepatitis C

Hepatitis C virus (HCV) is usually but not exclusively transmitted by the parenteral route. Some precautions are recommended for infected patients as well as his/her close contacts and family members. The risk of sexual transmission and from household contacts is very low. Use of condoms is only recommended in cases of multiple partners and for those at high risk of transmission. Some personal objects should not be shared, i.e. razors, toothbrushes and nail clippers, but it is not necessary to avoid sharing eating utensils. Sexual partners may be tested for anti-HCV HCV-positive individuals should refrain from donating blood, organs and tissue. Clear and evidenced-based information should be provided to patients as to the means of prevention with special attention to individual risk groups such as IV drug abusers. The risk of HCV transmission after needlestick injury, although low, justifies universal precaution measurements for health-care workers. Nosocomial transmission has been described after medical procedures, especially haemodialysis and endoscopy. Thus, disinfection procedures as well as universal precautions are essential for all health-care workers. It is also important for HCV patients to inform health-care workers beforehand about their HCV status. Perinatal transmission is rare and is usually related to the degree of maternal viral load. Pregnancy is not contra-indicated in HCV. infected individuals and breast-feeding is allowed. Finally, HCV patients with active disease should be advised to refrain from alcohol intake, especially during antiviral therapy. After HCV infection it is necessary to consider not only diagnostic and therapeutic steps but also the risk of transmission in the patient's circle and consequences for the patient.     

Risks associated with hepatitis A and hepatitis B in patients with hepatitis C.

Individuals with hepatitis C virus (HCV) are at risk for acquiring hepatitis A virus (HAV) or hepatitis B virus (HBV) because of shared risk factors. A number of organizations recommend vaccination against HAV and HBV for patients with HCV. The rationale for vaccinating these patients is to prevent hepatic superinfections. Acute HAV superinfection causes more severe disease, acute hepatic failure, and higher fatality rates in patients with underlying chronic liver disease, specifically chronic HBV infection and chronic HCV infection. Available data, although limited, suggest that HBV coinfection with HAV and HCV causes more severe hepatic injury than infection with HAV or HCV alone. At standard doses, hepatitis A and hepatitis B vaccines are safe and immunogenic in patients with mild-to-moderate hepatitis C or chronic liver disease. Regardless of disease severity, vaccination should be routinely administered to patients upon diagnosis of HCV infection. Early vaccination is important because response to vaccination is reduced as liver disease progresses. Prevaccination and postvaccination serology testing is recommended in specific populations. A new combination hepatitis A and hepatitis B vaccine has been shown to be as safe and effective as monovalent hepatitis A and B vaccines and is currently under review by the United States Food and Drug Administration. A combination vaccine would offer ease of administration and convenience and could increase compliance in patients with hepatitis C or other chronic liver disease: two groups that should be more aggressively targeted by healthcare professionals.     

Fulminant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis C

There have been conflicting reports of the clinical outcome of acute hepatitis A virus (HAV) infection in patients with chronic hepatitis C virus (HCV) infection. A prospective study evaluated 432 patients with chronic hepatitis C (183 with cirrhosis) over a 7-year period. Of the 17 patients with concurrent HAV infection, seven developed fulminant hepatitis and six died. None of these patients had cirrhosis; however, the HLA phenotype (A1; B8:DR3) appeared to be a significant factor in the development of fulminant hepatitis. Patients with this phenotype had high titres of antinuclear antibodies, antismooth muscle antibodies and antiasialoglycoprotein-receptor antibodies, possibly reflecting the induction of autoimmune hepatitis in this group. The high frequency of fulminant hepatitis in patients with HAV/HCV coinfection contrasts with other surveys, although a large Centers for Disease Control and Prevention (CDC) survey demonstrated that HAV infection in patients with pre-existing chronic liver disease (CLD) is associated with increased mortality. It is likely that CLD has some importance as an underlying factor in the development of fulminant hepatitis following HAV infection. Further prospective studies are needed to clarify this issue.     

Adefovir combined with hepatitis C virus treatment may prevent hepatitis B reactivation after hepatitis C virus eradication in hepatitis B and C virus carriers

This observation reports that a hepatitis B virus (HBV) reactivation, as the result of hepatitis C virus (HCV) eradication on a dominant HCV coinfected HBV/HCV patient, was subsequently prevented by treating both viral infections together. This finding raises the question as to whether preemptive HBV treatment should be prescribed along with HCV treatment to prevent HBV from being reactive after HCV eradication in coinfected HBV/HCV patients.     

Hyperlipasemia associated with hepatitis C virus

Extrahepatic manifestations of chronic hepatitis C virus (HCV) infection have been well described. However, hyperlipasemia and/or pancreatitis have not been reported. Following the observation that several HCV patients had elevated lipase levels, this retrospective study was conducted to assess the association between hyperlipasemia and/or pancreatitis with hepatitis C infection. Of 204 subjects who underwent evaluation for hepatitis C, 103 had lipase levels determined at baseline. The control group consisted of 41 nonHCV subjects with a variety of gastrointestinal diseases including 18 with nonalcoholic liver disease. Twenty-five percent of HCV patients had elevated lipase at baseline as compared to 10% of controls (P = 0.04; OR = 3.1; 95% CI: 1.02–9.60). Mean lipase levels were 253 ± 72 units/liter (normal range 114–286 units/liter and 210 ± 42 units/liter for the HCV and control groups, respectively (P = 0.002). No significant difference in amylase was found between the groups. There was a significant association between ALT (>1.5 times the upper limit of normal) and lipase (P = 0.02; OR = 3.0; 95% CI: 1.1–7.5). Among 30 patients who received interferon-based therapy ± ribavirin, 11 had elevated lipase at baseline. Six of these patients responded to therapy and demonstrated normalization of lipase levels. In contrast, allnonresponders with baseline hyperlipasemia continued to have high lipase levels (P = 0.17; OR = 4.0; 95% CI: 0.6–28.4). Furthermore, only 3 of 8 (37.5%) patients with normal lipase responded to treatment as compared to 6 of 10 (60%) of hyperlipasemic patients (P = 0.36; OR = 2.5; 95% CI: 0.4–16.9). In conclusion, hyperlipasemia and/or subclinical pancreatitis may represent extrahepatic manifestations of HCV infection and should not preclude treatment.     

New infection with heterotypic hepatitis C virus in a patient with long-term hepatitis C virus eradication

BACKGROUND: Experimental hepatitis C virus infection in chimpanzees has shown that natural hepatitis C virus infection does not induce protective immunity and reinfection can occur in seroconverted animals. AIM: To study the clinical, virological and histological outcome of a new infection sustained by a different hepatitis C virus strain after a primary infection with eradication of the original virus. PATIENTS AND METHODS: A young Italian man with chronic hepatitis C virus type 4 hepatitis was treated with Interferon therapy and achieved a sustained biochemical and virological response. After long follow-up, an asymptomatic flare-up of alanine transaminase occurred. This alanine transaminase increase was associated with serum hepatitis C virus RNA positivity and a low viral load, and the infecting hepatitis C virus genotype was type 3. The clinical and virological course of this new infection is described. RESULTS AND CONCLUSIONS: This report shows that there is no protective immunity against hepatitis C virus type 3 after infection by hepatitis C virus type 4 strain.     

重型丙型肝炎患者肝外脏器病毒感染和复制状态

目的 探讨丙型肝炎患者肝外脏器丙型肝炎病毒（HCV）感染和复制状态。方法 采用逆转录-聚合酶链反应（RT-PCR）、原位杂交（ISH）和免疫组织化学法,对9例重型丙型肝炎患者肝外8种脏器内HCV基因、HCV复制中间体和HCV抗原表达进行了研究。结果 采用RT-PCR,9例患者肝外脏器均可检出HCV基因,6例（66.7%）检出HCV复制中间体及HCV抗原;采用ISH和免疫组化法,5例（55.6%）检出HCV基因。除脾脏外,心脏、肾脏、胰腺、肾上腺、肠道、胆囊和淋巴结等脏器细胞内有HCV基因和HCV抗原表达。结论 肝外多种脏器细胞可能支持HCV复制;肝外HCV感染程度低,复制水平低。     

Distribution of different hepatitis C virus genotypes in patients with hepatitis C virus infection

AIM:To investigate the presence of mixed infection and discrepancy between hepatitis C virus(HCV) genotypes in plasma,peripheral blood mononuclear cells(PBMCs),and liver biopsy specimens.METHODS:From September 2008 up to April 2009,133 patients with chronic hepatitis C referred to Firouzgar Hospital for initiation of an antiviral therapy were recruited in the study.Five milliliters of peripheral blood was collected from each patient and liver biopsy was performed in those who gave consent or had indications...     

Immunization with hepatitis C virus-like particles protects mice from recombinant hepatitis C virus-vaccinia infection

We have recently demonstrated that immunization with hepatitis C virus-like particles (HCV-LPs) generated in insect cells can elicit both humoral and cellular immune responses in BALB/c mice. Here, we evaluate the immunogenicity of HCV-LPs in HLA2.1 transgenic (AAD) mice in comparison to DNA immunization. HCV-LP immunization elicited a significantly stronger humoral immune response than DNA immunization. HCV-LP-immunized mice also developed stronger HCV-specific cellular immune responses than DNA-immunized mice as determined by using quantitative enzyme-linked immunospot (ELISpot) assay and intracellular cytokine staining. In BALB/c mice, immunization with HCV-LPs resulted in a >5 log10 reduction in vaccinia titer when challenged with a recombinant vaccinia expressing the HCV structural proteins (vvHCV.S), as compared to 1 log10 decrease in DNA immunization. In HLA2.1 transgenic mice, a 1-2 log10 reduction resulted from HCV-LP immunization, whereas no reduction was seen from DNA immunization. Adoptive transfer of lymphocytes from HCV-LP-immunized mice to naive mice provided protection against vvHCV.S challenge, and this transferred immunity can be abrogated by either CD4 or CD8 depletion. Our results suggest that HCV-LPs can induce humoral and cellular immune responses that are protective in a surrogate HCV challenge model and that a strong cellular immunity provided by both CD4 and CD8 effector lymphocytes may be important for protection from HCV infection.     

Nucleotide sequence diversity of hypervariable region 1 of hepatitis C virus in Japanese hemophiliacs with chronic hepatitis C and patients with chronic posttransfusion hepatitis C

Hemophiliac patients with chronic hepatitis C might be exposed to and become infected with multiple hepatitis C virus (HCV) strains by means of frequent use of blood products, even if they are infected with a single subtype of HCV. To test this hypothesis, we analyzed the genetic diversity of hypervariable region 1 (HVR1) of HCV in chronically infected hemophiliacs and in patients with chronic posttransfusion hepatitis with a single HCV inoculation. The diversity of nucleotide sequences in HVR1 of serum HCV RNA was compared between 21 hemophiliacs infected with a single HCV subtype and 16 patients with posttransfusion HCV infection. The number of HCV quasispecies was determined by fluorescence single-strand conformation polymorphism (SSCP) analysis. Direct sequencing was performed to determine the diversity in HVR1. The number of HCV quasispecies in the blood was 5.2 +/- 2.0 clones in hemophiliacs and 4.0 +/- 2.3 clones in posttransfusion patients, a nonsignificant difference (P = .0943). The number of sites at which the nucleotide was not homogenous in all quasispecies was significantly higher in hemophiliacs (13.0% +/- 7.4%) than in posttransfusion hepatitis patients (2.7% +/- 2.8%; P < .0001). In conclusion, there was a high degree of genetic variation in HVR1 of HCV specimens isolated from hemophiliacs compared with posttransfusion patients. These findings indicate the possibility that multiple infections of a single HCV subtype may occur among patients frequently exposed to blood products; single HCV subtypes may therefore derive from multiple origins.     

Persistent acute hepatitis in a patient with chronic hepatitis C

We describe the case of a patient with chronic hepatitis C (CHC) who showed a progressive increase in aminotransferase level, reaching values of aspartate aminotransferase 1723 UI/L, alanine aminotransferase 1519 UI/L and gamma-glutamyl-transpeptidase 296 with a bilirubin level of 6 mg/dL and direct bilirubin level of 4.6 mg/dL. One year previously, the patient had been diagnosed with CHC, genotype 1, and had an initial hepatitis C virus RNA load of 249,000 UI/mL. All the specific blood tests performed were negative except for antisoluble liver antigen (anti-SLA) antibodies, which were positive in two different determinations. A diagnosis of overlap syndrome CHC and autoimmune hepatitis was made. Steroid and azathioprine treatment was started with good response. The relationship between CHC and anti-SLA is not well characterized but has been described in these patients. We found no prior reports in the literature of CHC associated with positive anti-SLA in a patient with persistent acute hepatitis.