Natural Course Of Hepatitis C Virus Infection Research Articles

Hepatitis C virus: A critical approach to who really needs treatment.

Introduction of effective drugs in the treatment of hepatitis C virus (HCV) infection has prompted the World Health Organization to declare a global eradication target by 2030. Propositions have been made to screen the general population and treat all HCV carriers irrespective of the disease status. A year ago the new severe acute respiratory syndrome coronavirus 2 virus appeared causing a worldwide pandemic of coronavirus disease 2019 disease. Huge financial resources were redirected, and the pandemic became the first priority in every country. In this review, we examined the feasibility of the World Health Organization elimination program and the actual natural course of HCV infection. We also identified and analyzed certain comorbidity factors that may aggravate the progress of HCV and some marginalized subpopulations with characteristics favoring HCV dissemination. Alcohol consumption, HIV coinfection and the presence of components of metabolic syndrome including obesity, hyperuricemia and overt diabetes were comorbidities mostly responsible for increased liver-related morbidity and mortality of HCV. We also examined the significance of special subpopulations like people who inject drugs and males having sex with males. Finally, we proposed a different micro-elimination screening and treatment program that can be implemented in all countries irrespective of income. We suggest that screening and treatment of HCV carriers should be limited only in these particular groups.

Hepatitis C awareness among therapists and general practitioners. Survey results

In order to improve the diagnosis and treatment of chronic hepatitis C in the framework of this study was the awareness among general practitioner (GPs) and physicians in various districts of Chelyabinsk Oblast was assessed. A continuous study of hepatitis C virus (HCV) awareness among therapists and GPs was conducted within the framework of the regional research-to-practice conference Multidisciplinary Issues of Family Medicine on May 19, 2018. 78 questionnaires have been distributed. Thus, 78 therapists from different districts of Chelyabinsk Oblast took part in the study. For these purposes, a questionnaire of 12 questions developed by Olga I. Sagalova was used. The study involved 78 therapists from different districts of Chelyabinsk Oblast. 20.52% (n=16) of respondents were from the healthcare institutions (HCI) of urban districts of Chelyabinsk Oblast, 39.74% (n=31) were from the HCIs of municipal districts of Chelyabinsk Oblast, and 39.74% (n=31) from the HCIs of the city of Chelyabinsk. The survey revealed certain gaps in therapists awareness of the natural course of the disease, diagnosis, routing, the natural course of HCV infection, as well as its extrahepatic manifestations. The survey results indicate a lack of understanding among physicians and therapists of tactics for managing patients with HCV infection and emphasize the need to improve interdisciplinary interaction between infectious disease specialists, primary care doctors and doctors of other specialties including the development and implementation of an educational strategy for non-infectious disease doctors. The results indicate the needs to increase the level of education among doctors in the diagnosis and management of patients with HCV in accordance with guidelines and to include screening for HCV infection in the guidelines for selected chronic non-communicable diseases as part of the initial examination.

Heterologous Immunity between Adenoviruses and Hepatitis C Virus (HCV): Recombinant Adenovirus Vaccine Vectors Containing Antigens from Unrelated Pathogens Induce Cross-Reactive Immunity Against HCV Antigens.

Host immune responses play an important role in the outcome of infection with hepatitis C virus (HCV). They can lead to viral clearance and a positive outcome, or progression and severity of chronic disease. Extensive research in the past >25 years into understanding the immune responses against HCV have still resulted in many unanswered questions implicating a role for unknown factors and events. In our earlier studies, we made a surprising discovery that peptides derived from structural and non-structural proteins of HCV have substantial amino acid sequence homologies with various proteins of adenoviruses and that immunizing mice with a non-replicating, non-recombinant adenovirus vector leads to induction of a robust cross-reactive cellular and humoral response against various HCV antigens. In this work, we further demonstrate antibody cross-reactivity between Ad and HCV in vivo. We also extend this observation to show that recombinant adenoviruses containing antigens from unrelated pathogens also possess the ability to induce cross-reactive immune responses against HCV antigens along with the induction of transgene antigen-specific immunity. This cross-reactive immunity can (a) accommodate the making of dual-pathogen vaccines, (b) play an important role in the natural course of HCV infection and (c) provide a plausible answer to many unexplained questions regarding immunity to HCV.

Prevalence of chronic hepatitis C virus infection among childhood cancer survivors in Stockholm, Sweden

Background: Childhood cancer survivors treated before 1992, when blood donor screening for hepatitis C virus (HCV) infection was introduced, are at risk of transfusion-transmitted HCV infection. A national HCV screening campaign targeting blood transfusion recipients was launched in Sweden in 2007–2010. The aims of this study were to, among adult childhood cancer survivors in Stockholm County, investigate the prevalence of HCV infection, the natural course of infection, treatment outcome and anti-HCV testing frequency before, during and after the screening campaign and finally to actively screen the untested ones.Material and Methods: This was a combined retrospective register based and prospective screening study of adult childhood cancer survivors (n = 686) treated for malignancy in Stockholm before 1992. In the first part, we investigated the prevalence of HCV infection and previous anti-HCV testing, and in the second part, we actively traced and HCV-screened the remaining untested cohort living in Stockholm. Analysis of previous documented anti-HCV tests in medical records, laboratory records, and the national communicable disease registry was performed. In the second part, 231 presumably untested individuals were contacted by mail and offered an anti-HCV test. The natural course of HCV infection and treatment outcome was analyzed for those found to be chronically infected.Results: In total, 235 patients were tested and 11 were HCV-RNA positive. The overall prevalence of chronic HCV infection among the tested childhood cancer survivors was thus 4.7% (95% CI = 2.6–8.2%), which is almost 10 times higher than the national prevalence of 0.5%. Only 12% of the Stockholm cohort were tested during the screening campaign in 2007–2010, while the test uptake using active tracing screening within this study was 40% (p < .001).Conclusion: With today’s effective treatment options, active tracing and HCV screening of childhood cancer survivors are recommended.

Alterations of the NK cell pool in HIV/HCV co-infection.

BackgroundA relevant proportion of human immunodeficiency virus (HIV) infected patients is co-infected with the hepatitis C virus (HCV). HCV co-infection in HIV-positive patients is associated with faster progression of liver disease in comparison to HCV mono-infection. Natural killer (NK) cells critically modulate the natural course of HCV infection. Both HIV and HCV mono-infection are associated with alterations of the NK cell pool. However, little data is available concerning phenotype and function of NK cells in HIV/HCV co-infection.MethodsA total of 34 HIV/HCV co-infected, 35 HIV and 39 HCV mono-infected patients and 43 healthy control persons were enrolled into this study. All HIV-positive patients were under effective antiretroviral therapy. NK cell phenotype, IFN-γ production and degranulation were studied by flow cytometry.ResultsNK cell frequency in HIV/HCV co-infection was significantly lower than in healthy individuals but did not differ from HIV and HCV mono-infection. HIV/HCV co-infection was associated with significantly decreased expression of the maturation/differentiation markers CD27/62L/127 on NK cells but increased expression of CD57 compared to healthy controls. Of note, expression also differed significantly from HCV mono-infection but was similar to HIV mono-infection, suggesting a pronounced impact of HIV on these alterations. Similar findings were made with regard to the NK cell receptors NKG2A/C and NKp30. More importantly, NK cells in co-infection displayed a highly impaired functional activity with significantly lower IFN-γ production and degranulation than in healthy donors as well as HIV and HCV mono-infection, suggesting a synergistic effect of both viruses.ConclusionsOur data indicate that HIV/HCV co-infection is associated with significant alterations of the NK cell pool, which might be involved in the rapid progression of liver disease in co-infected patients and which mainly reflect alterations observed in HIV mono-infection.

Liver disease progression in hepatitis C virus carriers with normal alanine aminotransferase levels

We read with great enthusiasm the article of Wiese et al.1 that, in our opinion, has a paramount relevance to understanding the natural history of hepatitis C virus (HCV) infection. In particular, this article does greatly in helping us to evaluate the progression to more severe liver damage of the so-called healthy HCV carriers (i.e., viremic persons with normal alanine aminotransferase [ALT] levels and liver histology). It is known that up to 30%-40% of patients with chronic HCV infection have persistently normal ALT levels,2 with many of them showing normal liver histology or minimal fibrosis. The natural course of HCV infection in these patients is not well known. Whereas some studies showed that HCV carriers with normal ALT have mild and stable disease, others reported a significant progression of fibrosis in approximately 20%-30% of such patients.3 In their first study4 describing the 20-year follow-up of over 1,000 women infected in East Germany in January 1979 by contaminated anti-D immune globulin, the researchers reported that 26 patients should be considered as true healthy carriers (i.e., normal liver, normal ALT, and persistent HCV viremia). At 25-year follow-up,5 only 11 women had remained in a healthy state, whereas the others had progressed to chronic hepatitis C (CHC). However, in this third evaluation after 35-year follow-up,1 no mention has been made about the histological and clinical status of these otherwise healthy, HCV-infected women. Thus, we wonder how many of these carriers had remained in a true healthy state 35 years after contamination and how many further carriers had progressed to CHC. Furthermore, the degree of liver damage was more or less severe in the carriers progressing to CHC with respect to other patients; were differences observed in virological response between the two groups of patients? Indeed, whether healthy HCV carriers should be offered antiviral treatment in clinical practice has been the subject of an ongoing debate.6 Introduction of the combination therapy of pegylated interferon plus ribavirin results in higher response rates,7 with a favorable risk/benefit ratio also in patients with mild or no fibrosis.8, 9 The important data of the East Germany HCV Study Group might give an answer to this unmet issue: What should we treat, the infection or the disease?10 Claudio Puoti, M.D.1 Lia Bellis, M.D.1 Olga Mitidieri Costanza, M.D.2 Maria Giuseppa Elmo, M.D.3 1Department of Internal Medicine and Liver Unit Marino General Hospital Rome, Italy 2Molecular Biology Unit Marino General Hospital Rome, Italy 3Department of Mental Health, Local Health Center Rome, Italy

End‐stage renal disease and African American race are independent predictors of mild liver fibrosis in patients with chronic hepatitis C infection

Recipients of haemodialysis for end-stage renal disease (ESRD) have a higher prevalence of hepatitis C virus (HCV) infection relative to the general US population. However, the natural course of HCV infection in patients with renal failure, including African Americans (AAs) and Caucasian Americans (CAs), is not well known. We compared the degree of liver inflammation and fibrosis in AA and CA patients with HCV infection, with and without ESRD. This was a cross-sectional study of 156 HCV patients with ESRD (130 AAs and 26 CAs) with a liver biopsy between 1992 and 2005. The control group consisted of 138 patients (50 AAs; 88 CAs) with HCV infections and a serum creatinine <1.5 mg/dL with a liver biopsy between 1995 and 1998. Specimens were graded for inflammation and fibrosis using Knodell histological activity index. Compared to patients without renal impairment, HCV patients with renal failure were older and more likely to be AA. Patients with renal impairment had lower mean serum transaminases, a higher mean serum alkaline phosphatase levels (all P < 0.0001) and less hepatic necro-inflammation (Knodell histological activity index -I, II and III; P < 0.05) and fibrosis (Knodell histological activity index -IV; P < 0.0001). There were no racial differences in serum liver chemistry and histology scores among patients with renal failure. In a multivariate analysis, younger age, ESRD, AA race and a lower serum alkaline phosphatase were associated with lower odds for advanced liver fibrosis. Thus, HCV patients with ESRD had a lower degree of hepatic inflammation and fibrosis compared to those without renal disease, independent of race.

Spontaneous viral clearance of chronic HCV infection in Upper Egypt: A community-based study with a 10 year follow-up

Background and study aims Hepatitis C virus (HCV) infection is a global blood-borne disease with the highest prevalence in Egypt. The natural course of HCV infection is highly variable. The reason why the infection persists in some patients and resolves spontaneously in others is not known. The aim of this study was to detect the frequency of spontaneous clearance of chronic HCV infection in Upper Egypt and to determine the predictors of persistence of HCV infection. Patients and methods In 1997, a community-based study was performed in Sallam village in Upper Egypt. Out of the 329 patients who had positive HCV-RNA, 200 patients were included in this study, after excluding cirrhotic patients at the start of the study and those who had received specific treatment for HCV infection. These patients were followed up every six months prospectively starting from 2004 till 2007 by clinical, ultrasonographic, and laboratory examinations (liver functions, complete blood count, prothrombin time and concentration). Serum HCV-RNA was tested for at the end of the follow up period. Results After a 10-year follow-up, spontaneous clearance of chronic HCV infection was detected in 35 (17.5%) out of 200 patients. Most of clinical and laboratory abnormalities were detected in patients with HCV-RNA persistence than those who had cleared HCV-RNA. By ultrasonographic examination, normal liver echopattern was found in 30 (85.7%) cases with HCV-RNA clearance and in 75 (45.5%) patients who had HCV-RNA persistence. Evidence of liver cirrhosis was found only in 9 cases with HCV-RNA persistence (5.5%). Old age (>60 years) was the strongest predictor of persistence of HCV infection followed by obesity and history of blood transfusion. Conclusions Spontaneous clearance of chronic HCV infection could occur without any specific antiviral therapy in 17.5% of patients. Older age was the strongest predictor of persistence of HCV infection followed by obesity and infection by blood transfusion.

Protective effect of human leukocyte antigen B27 in hepatitis C virus infection requires the presence of a genotype-specific immunodominant CD8+ T-cell epitope

Human leukocyte antigen B27 (HLA-B27) is associated with protection in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection. This protective role is linked to single immunodominant HLA-B27-restricted CD8+ T-cell epitopes in both infections. In order to define the relative contribution of a specific HLA-B27-restricted epitope to the natural course of HCV infection, we compared the biological impact of the highly conserved HCV genotype 1 epitope, for which the protective role has been described, with the corresponding region in genotype 3 that differs in its sequence by three amino acid residues. The genotype 3a peptide was not recognized by CD8+ T cells specific for the genotype 1 peptide. Furthermore, patients with acute or chronic infection with HCV genotype 3a did not mount T-cell responses to this epitope region, and their autologous viral sequences showed no evidence of T-cell pressure. Finally, we found a significantly higher frequency of HLA-B27 positivity in patients with chronic HCV genotype 3a infection compared to genotype 1 infection, indicating that there is no protection by HLA-B27 in HCV genotype 3 infection. Our data indicate that the protective effect of HLA-B27 is limited to HCV genotype 1 infection and does not expand to other genotypes such as genotype 3a. This can most likely be explained by intergenotype sequence diversity leading to the loss of the immunodominant HLA-B27 epitope in viral strains other than genotype 1. Our results underline the central role of a single HLA-B27-restricted epitope-specific CD8+ T-cell response in mediating protection in HCV genotype 1 infection.

The hepatitis C virus enigma

Hepatitis C virus (HCV) has a high propensity to establish chronic infection with end-stage liver disease. The high turnover of virus particles and high transcription error rates due to lack of proof-reading function of the viral polymerase imply that HCV exists as quasispecies, thus enabling the virus to evade the host immune response. Clearance of the virus is characterized by a multispecific, vigorous and persistent T-cell response, whereas T-cell responses are weak, narrow and transient in patients who develop chronic infection. At present, standard treatment is a combination of pegylated interferon-alpha and ribavirin, with a sustained viral response rate of 40-80%, depending on genotype. The mechanisms for the observed synergistic effects of the two drugs are still not known in detail, but in addition to direct antiviral mechanisms, the immunomodulatory effects of both drugs seem to be important, with a shift from Th2- to Th1-cytokine profiles in successfully treated patients. This article describes virus-host relations in the natural course of HCV infection and during treatment.

The hepatitis C virus-associated dysmetabolic syndrome

We did appreciate the formidable effort by Drs. Sheikh, Sanyal, and colleagues to provide a succinct and yet complete overview of the molecular mechansims involved in the development of insulin resistance in those with hepatitis C virus (HCV) infection.1 The reading of this article raises two major comments. First, the authors correctly point out HCV to be now viewed “to cause a metabolic syndrome”. Indeed it is not the same metabolic syndrome (MS) as seen in HCV-negative individuals encompassing insulin resistance associated with altered body fat distribution, arterial hypertension, and disturbed glucose and lipid metabolism. In particular, although data are still preliminary, it would appear HCV features a specific HCV-associated dysmetabolic syndrome (HCADS) consisting of the triad of insulin resistance, hypocholesterolemia, and hepatic steatosis.2 At variance with the “true” MS, HCADS might therefore not feature obesity, atherogenic dyslipidemia, and arterial hypertension.2 The second comment, also strictly connected to the former, is that insufficient information is so far available on whether HCADS follows the same course as the MS. For instance, available data appear to support the theory that, similar to the true MS, HCADS is also associated with hepatic steatosis3, 4 and an increased risk of developing type 2 diabetes.5 However, literature data on the risk of premature atherosclerosis in those individuals with HCADS are scant, somewhat contradictory, and more important, available studies are not comparable in terms of experimental design and population studied,2 so that this question remains open. While basic research discloses exciting new therapeutic strategies against HCV infection, clinical observations may well provide additional clues to highlight similarities and differences between the MS and HCADS. Such clinical observations may, in turn, indicate or contraindicate the use of drugs such as hydroxymethyl-glutaryl-coenzyme A inhibitors (statins). Statins, as the most popular cholesterol-lowering agents, are widely used in the MS and display in vitro anti-HCV properties.6 However, results from an in vivo pilot study with atorvastatin have been disappointing.7 Moreover, statins are familiar to the diabetologist but perhaps may still raise concern among those caring for (HCV) liver patients.8 In conclusion, we feel the combined efforts of the basic scientist together with clinical judgement will result in the generation of new ideas eventually conducive to the altered natural course of HCV infection, not only from a virological, but also from a metabolic point of view. Amedeo Lonardo*, Paola Loria*, * University of Modena and Reggio Emilia, Department of Internal Medicine, Endocrinology, Metabolism and Geriatrics, Modena, Italy.

Expression of alternate reading frame protein (F1) of hepatitis C virus in Escherichia coli and detection of antibodies for F1 in Indian patients

Apart from the core (21 kD), a novel hepatitis C virus (HCV) frame shift protein (F1) is synthesized from the initiation codon of the polyprotein sequence followed by ribosomal frame shift into the −2/+1 reading frame. To date, no information is available on F1 protein of Indian isolates, and hence detection of antibodies for F1 protein in Indian patients assumes great relevance. Specific primers have been designed to amplify sequence coding for 120aa of truncated F1 (tF1). The amplified tF1 has been cloned in bacterial expression vector, pET21b for expression in Escherichia coli. Partially purified expressed protein has been subjected to western blot analysis using patients’ sera. Three HCV positive sera employed in western analysis showed positive signals to tF1, while sera from uninfected individuals failed to give any signals. Further, results of western blots, carried out with patients sera titrated with purified core protein, confirmed the presence of antibodies specific to F1. The positive signal observed for F1 in western analysis with HCV infected sera suggests that F1 protein is synthesized in the natural course of HCV infection in Indian patients as well. Presence of antibodies against F1 protein of subtype 1c has been demonstrated, for the first time, in Indian patients.

Does Cyclosporine Have a Beneficial Effect on the Course of Chronic Hepatitis C Infection After Renal Transplantation?

The aim of our study was to assess the long-term liver histology in renal transplant patients infected with hepatitis C virus (HCV) who were treated with a cyclosporine-based regimen. Among 55 anti-HCV(+)/RNA(+) patients, liver biopsies (LB) were requested every 3 to 4 years after transplantation: two LBs ( n = 55); three LBs ( n = 44); four LBs ( n = 10). Overall, the rate of liver fibrosis progression was 0.07 ± 0.03 Metavir U/y. Only three patients out of 55 (5.4%) developed cirrhosis. Liver fibrosis remained stable throughout follow-up in 21 patients; increased in 21 patients; and improved in the remaining 13 patients. The incidence of posttransplant diabetes mellitus was low (9%). We concluded that HCV infection is not harmful to liver histology in more than 50% of renal transplant patients with grafts functioning more than 6 years. Cyclosporine might have beneficial effects on the natural course of HCV infection after renal transplantation.

Hepatitis C and steatosis: a reappraisal

The overall prevalence of steatosis in patients with Hepatitis C virus (HCV) chronic infection is 55.5% (range 34.8-81.2%). This is a two to threefold increase compared with the prevalence of steatosis in chronic hepatitides because of other aetiologies and of the figures expected on the grounds of a steatosis-HCV chance association. HCV genotype 3 (HCV-3) has specific epidemiological features; furthermore, as compared with HCV-non-3 genotypes, it is associated with a higher prevalence (74.1%vs 47.9%, P < 0.01) and with more severe grades of steatosis (prevalence of grade 3 steatosis 29.6 vs 5.5 P < 0.01). Host and viral factors play a role, although to a variable extent, in the pathogenesis of HCV-3 and non-3 steatosis. HCV load and body mass index are associated with steatosis in HCV-3 and in HCV-non-3 patients respectively. Serum cholesterol levels and liver steatosis at baseline follow an inverse relationship in HCV infection. As hypocholesterolaemia corrects only in those sustained responders to antiviral treatment both in genotype 3 and in non-3 genotypes, the occurrence of a virally induced, acquired and reversible hypobetalipoproteinaemia seems plausible. Steatosis affects the natural course of HCV infection: it is associated with fibrosis, a possible mediator of increased risk to develop type 2 diabetes, it impairs the response to antiviral treatment in HCV-3 patients and might constitute a risk factor for the development of hepatocellular carcinoma. These observations indicate the need to evaluate the efficacy of combined antiviral and 'metabolic' approaches vs standard antiviral regimes in patients with steatosis and HCV chronic infection.

Nonstructural 5A gene variability of hepatitis C virus (HCV) during a 10-year follow up

Seven patients with chronic hepatitis C virus (HCV) infection were followed up for 10 years in order to analyze the molecular evolution of the HCV nonstructural 5A (NS5A) gene. Serum samples were obtained from seven patients with anti-HCV who were HCV-RNA positive. The HCV NS5A region, including the interferon sensitivity-determining region (ISDR), protein kinase R binding domain (PKR-BD), and V3 was amplified and cloned, and then sequenced. The nucleotide sequences of the region at the beginning and at the end of the 10 years were aligned with the CLUSTAL W program, version 1.8, and the corresponding amino-acid sequences were deduced. The three serine residues at positions 2197, 2201, and 2204, suggested to be important for hyperphosphorylation of NS5A, were highly conserved in different patients and were within the quasispecies of each patient. The wild-type ISDR or minimally mutated strain was dominant in all the patients and the number of quasispecies decreased over time. Our findings showed that the functional domains of NS5A were generally conserved over an interval of 10 years. Quasispecies distribution was variable and distinctly clustered over time during the natural course of HCV infection. These results may contribute to better understanding of HCV natural infection.

Association of TNF-beta polymorphism with disease severity among patients infected with hepatitis C virus.

The pathogenesis of chronic hepatitis C virus (HCV) infection remains unclear. Tumour necrosis factor alpha (TNF-alpha) is alleged to contribute in the pathogenesis of chronic HCV infection. Single nucleotide polymorphism in TNF-alpha and -beta genes could influence the outcome of HCV infection. The aim was to study single nucleotide polymorphism in TNF-alpha promoter region and Nco I polymorphisms in the TNF-beta gene in patients with chronic hepatitis C. Fifty-two patients with histologically proven chronic hepatitis, who had raised ALT levels (>1.5 x ULN) and were HCV RNA positive, were studied. Genotyping of -308 promoter variant of TNF-alpha was performed by PCR with primers that incorporated an Nco I restriction site. For PCR typing of the TNF-beta Nco I restriction fragment length polymorphism, sequence specific primers were used. Polymorphism in the TNF-alpha G/G, G/A and A/A allele was not different between HCV patients and healthy controls. TNF-beta A/A allele was significantly more common (P = 0.02) in patients (28.8%) as compared to controls (12.8%), whereas no significant difference was observed for TNF-beta G/A and G/G alleles [corrected]. Nco I TNF-beta A/A was strongly associated with -308 TNF-alpha G/G (RR of HCV persistence = 4.9), indicating possible linkage between TNF-beta A/A and TNF-alpha G/G allele. Patients with severe hepatic fibrosis more frequently had the TNF-beta A/A allele as compared to patients with mild disease (P = 0.04). Immunogenetic factors, such as single nucleotide polymorphisms in TNF-beta (A/A allele), may affect the natural course of HCV infection, in particular, the disease progression. Larger studies including cytokine expression profiles are needed to fully understand the contribution of the polymorphisms described in the pathogenesis of chronic hepatitis C.

Infection rate and spontaneous seroreversion of anti-hepatitis C virus during the natural course of hepatitis C virus infection in the general population.

Hepatitis C virus (HCV) infection is common worldwide but there are different prevalence rates in different countries. Data on the incidence of HCV in the general population are scarce. Spontaneous viral clearance occurs in 10-25% of infected individuals after acute infection yet controversy exists regarding the frequency of spontaneous clearance during the natural course of HCV infection in the general population. Anti-HCV prevalence, HCV infection rate, and the kinetics of anti-HCV were studied in a cross section of the general population of central Italy. Anti-HCV prevalence (EIA-3 Ortho, RIBA-3 Ortho Chiron) was estimated in 3884 randomly selected individuals. Infection rate and antibody kinetics were estimated in 2032 participants for whom a second blood sample was taken after a median follow up of seven years. HCV-RNA determination by polymerase chain reaction was performed on follow up sera. The overall confirmed anti-HCV prevalence was 2.4%. Two participants seroconverted for anti-HCV, giving an overall infection rate of 1.4 cases per 10 000 person years (95% confidence interval 0.2-5.2 per 10 000 person years). Of the 36 individuals confirmed as anti-HCV positive at enrollment, seven (19.4%) showed complete seroreversion. Seven (87%) of the eight individuals with indeterminate results at enrollment were serologically non-reactive at the end of follow up. Of the 25 participants confirmed to be anti-HCV positive at both enrollment and follow up, 23 (92.0%) with stable serological profiles tested positive for HCV-RNA at the end of follow up. There is still a permanent risk, although low, of HCV spread in the general population in an area of low level endemicity. In this setting, a wide spectrum of modifications of viral and antibody patterns can be observed in HCV infected patients.

Treatment of chronic hepatitis C virus infection in children

Hepatitis C virus (HCV) infection may occur in infants and children, although it is much less common than it is in adults. The main transmission routes include mother-to-infant transmission, use of HCV infected blood products, unsterile needles or syringes and other invasive procedures.The natural course of HCV infection in children is variable: some (20–40%) develop an acute resolving infection and spontaneous regression occurs in approximately one-third of infants of HCV infected mothers before 2 years of age. Approximately 60–80% of HCV infected children develop a chronic infection with varying degrees of activity and fibrosis, mostly mild during childhood. However, the potential risks of liver cirrhosis and hepatoma during later life are obvious.Interferon is the main agent used to treat HCV infection in children. The response to interferon at the end of 4–12 months of therapy ranges from 25–90%. A sustained response was found in 36–56% of children 6–36 months after the end of therapy. The duration of therapy is recommended to be 12 months. At the end of 3 months, an evaluation of the response is indicated in the majority of children, except those with thalassemia, in whom evaluation of response should be conducted at the end of 6 months of therapy.The benefit of other therapies, such as combination therapy with interferon and ribavirin in children with hepatitis C is currently under investigation.

The natural course of hepatitis C virus infection 18 years after an epidemic outbreak of non-A, non-B hepatitis in a plasmapheresis centre

BACKGROUNDThe natural history of hepatitis C virus (HCV) infection is variable and factors determining the course of the illness are unclear. AIMSTo determine the natural course of HCV infection in...

Hepatitis C virus infection and liver disease: peculiar epidemiological and clinicopathological features.

Hepatitis C virus (HCV) infection is associated with a wide spectrum of liver disease ranging from asymptomatic carriage to severe forms of chronic hepatitis. HCV is not invariably pathogenic and genetic heterogeneity of HCV could be a major cause of such a variability. In clinical practice this means that presence and replication of the virus do not invariably imply a virus-induced liver damage. IgM antibodies that are the best diagnostic tools for the other forms of viral hepatitis are not sensitive and specific enough for hepatitis C, therefore we have to look for alternatives. Detection of anti-HCV does not help to distinguish past from present infections and only anti-HCV seroconversion in previously negative patients can indicate a recent HCV infection. However, the significant association between serum anti-C100-3 and HCV-RNA suggests that anti-HCV can be considered an indirect marker of HCV infectivity. In anti-HCV-negative infections and early acute hepatitis cases HCV-RNA detection will represent a valid diagnostic alternative. In patients undergoing antiviral therapy monitoring anti-HCV by immunoblotting assays and HCV-RNA by quantitative assays represent a valid tool to predict response that invariably has occurred in patients who had undetectable serum HCV-RNA and/or decreasing anti-HCV titres. Assays that detect multiple anti-HCV antibodies all together appear unsuitable for monitoring because they miss the disappearance of single antibodies. Anti-C22 appears the most frequent and earliest to be detected and usually it has the highest titre. Anti-C100 titres decrease earlier than anti-C33 and anti-C22 in patients with chronic HCV hepatitis who respond to antiviral therapy. The natural course of HCV infection appears to be characterized by three consecutive phases: disease, asymptomatic carrier and recovery. If transition from the first to the last occurs very slowly or the disease phase persists for years it may warrant in susceptible hosts severe forms of liver disease.