Features Of Hepatitis C Virus Infection Research Articles

Person-Centred Hepatitis C Virus Treatment In Community Settings

The World Health Organization (WHO) has set a target to eliminate the Hepatitis C virus (HCV) as a public health threat by 2030. To achieve this, HCV treatment needs to be accessible through primary health care providers in community settings. In Australia, general practitioners and nurse practitioners can prescribe nearly free direct-acting antiviral (DAA) medication. However, there are still many barriers to the provision of HCV treatment in community settings. Considering the characteristics of HCV infection, people with HCV, and the Australian primary health system, person-centred HCV treatment is suggested to improve treatment uptake and adherence. Although the provision of person-centred HCV treatment in community settings is emphasised, the characteristics of these models are not well described. This short report describes the characteristics of person-centred HCV treatment in community settings to inform policy and practices in supporting HCV elimination. The characteristics were developed based on the analysis of findings of studies conducted by the author using person-centred care framework. The studies included a mixed methods systematic literature review, a Delphi study, and a mixed methods case study on a community-based model of care for treating HCV.

Natural history and clinical features of hepatitisC virus infection during childhood: A nationwide, observational survey in Japan.

Few data on spontaneous clearance rates of cases of mother-to-child transmission of hepatitisC viral (HCV) infection are available in Japan. Furthermore, the treatment courses of interferon-based and direct-acting antiviral agent (DAA) therapies for children are also unclear. Our aim was thus to clarify the long-term natural progression of HCV infection and the treatment outcomes of children in Japan. We conducted a combined multicenter, observational survey involving 65 pediatric institutions in Japan. Pediatric HCV infection cases with patients born between 1973 and 2021 were collected over the 11-year period from 2012 to 2022. A total of 563 patients were enrolled, with 190 excluded for having insufficient laboratory data or treatment information, resulting in 373 eligible cases. Of 328 cases of mother-to-child infection, 34 (10.4%) had spontaneous clearance, with a median time to spontaneous clearance of 3.1years (range 0.9-7.2years). Of the total 373 eligible cases, 190 received antiviral therapy (interferon-based therapy, 158; DAA therapy, 32). Sustained virologic response rates after first-line treatment were 75.3% (119/158) and 100% (32/32) for interferon-based therapy and DAA therapy, respectively, with the DAA group showing a shorter time from therapy initiation to viral negativity (2.7 vs. 1.0months; p=0.0031). Approximately 10% of Japanese children infected by mother-to-child transmission achieve spontaneous resolution of HCV infection. Our findings indicate that DAA therapy is safe and highly effective in Japanese children, achieving higher sustained virologic response rates and shorter time to clearance of the virus compared with interferon-based therapy.

Prevalence and characteristics of hepatitis C virus infection detected by extended screening of working-age adults in Madrid (Spain).

Hepatitis C virus (HCV) infection is a leading cause of liver-related morbidities and mortality. Antiviral treatment is highly successful but only a fraction of infected subjects are aware of their HCV status; therefore, prevalence studies are essential to identify HCV-infected individuals. Our aim was to analyze the prevalence and characteristics of HCV infection among working-age adults in Madrid (Spain). Extended screening for HCV infection was performed by measuring HCV antibodies in blood collected preoperatively from individuals requiring surgical treatment of work-related injuries or at baseline from subjects suffering occupational exposures to biological fluids. HCV RNA was measured in HCV antibody-positive subjects unaware of their HCV status. Serum aminotransferases were measured in all participants. During a six-year period (2013-2018), 16,734 consecutive patients were studied. Two hundred and twenty-eight (1.4%) were HCV antibody-positive [191 (83.8%) males; 37 (16.2%) females; median (SD) age: 49.2 (7.5) years], 94 (41.2%) were unaware of their HCV status, and 41 (17.9%) had detectable HCV RNA [mean (SD) log10 UI/mL: 5.6 (1.1)]. Most HCV antibody-positive subjects were born during the 1945-1965 period (birth cohort group), and the prevalence of active HCV infection was higher in this group (56.1% vs 43.9%; p = 0.194). Overall, 62 (27.8%) participants had elevated serum aminotransferases, including 22 (57.9%) with active HCV infection (p < 0.001). Screening for HCV infection in working-age adults detected a significant proportion of HCV-infected individuals with viremia and normal transaminase levels, who were unaware of their infection status. Extended screening for HCV infection is warranted.

Use of an Outbred Rat Hepacivirus Challenge Model for Design and Evaluation of Efficacy of Different Immunization Strategies for Hepatitis C Virus.

Background and AimsThe lack of immunocompetent small animal models for hepatitis C virus (HCV) has greatly hindered the development of effective vaccines. Using rodent hepacivirus (RHV), a homolog of HCV that shares many characteristics of HCV infection, we report the development and application of an RHV outbred rat model for HCV vaccine development.Approach and ResultsSimian adenovirus (ChAdOx1) encoding a genetic immune enhancer (truncated shark class II invariant chain) fused to the nonstructural (NS) proteins NS3‐NS5B from RHV (ChAd‐NS) was used to vaccinate Sprague‐Dawley rats, resulting in high levels of cluster of differentiation 8–positive (CD8+) T‐cell responses. Following RHV challenge (using 10 or 100 times the minimum infectious dose), 42% of vaccinated rats cleared infection within 6‐8 weeks, while all mock vaccinated controls became infected with high‐level viremia postchallenge. A single, 7‐fold higher dose of ChAd‐NS increased efficacy to 67%. Boosting with ChAd‐NS or with a plasmid encoding the same NS3‐NS5B antigens increased efficacy to 100% and 83%, respectively. A ChAdOx1 vector encoding structural antigens (ChAd‐S) was also constructed. ChAd‐S alone showed no efficacy. Strikingly, when combined with ChAd‐NS, ChAD‐S produced 83% efficacy. Protection was associated with a strong CD8+ interferon gamma–positive recall response against NS4. Next‐generation sequencing of a putative RHV escape mutant in a vaccinated rat identified mutations in both identified immunodominant CD8+ T‐cell epitopes.ConclusionsA simian adenovirus vector vaccine strategy is effective at inducing complete protective immunity in the rat RHV model. The RHV Sprague‐Dawley rat challenge model enables comparative testing of vaccine platforms and antigens and identification of correlates of protection and thereby provides a small animal experimental framework to guide the development of an effective vaccine for HCV in humans.

The preoperative management of Hepatitis C may improve the outcome after total knee arthroplasty

With an ageing population of patients who are infected with hepatitis C virus (HCV), the demand for total knee arthroplasty (TKA) in this high-risk group continues to grow. It has previously been shown that HCV infection predisposes to poor outcomes following TKA. However, there is little information about the outcome of TKA in patients with HCV who have been treated successfully. The purpose of this study was to compare the outcomes of TKA in untreated HCV patients and those with HCV who have been successfully treated and have a serologically confirmed remission. A retrospective review of all patients diagnosed with HCV who underwent primary TKA between November 2011 and April 2018 was conducted. HCV patients were divided into two groups: 1) those whose HCV was cured (HCV-C); and 2) those in whom it was untreated (HCV-UT). All variables including demographics, HCV infection characteristics, surgical details, and postoperative medical and surgical outcomes were evaluated. There were 64 patients (70 TKAs) in the HCV-C group and 63 patients (71 TKAs) in the HCV-UT cohort. The mean age at the time of surgery was 63.0 years (sd 7.5; 44 to 79) in the HCV-C group and 61.7 years (sd 6.9; 47 to 88) in the HCV-UT group. HCV-UT patients had a significantly longer mean hospital stay (3.4 days vs 2.9 days; p = 0.04), were more likely to be transferred to the intensive care unit (14.1% vs 4.3%; p = 0.04), and were significantly more often discharged to a post-acute care facility (39.4% vs 14.3%; p < 0.01). HCV-UT patients had significantly more postoperative infections (15.5% vs 4.3%; p = 0.03), surgical complications (21.1% vs 7.1%; p = 0.02), and revision TKA (12.7% vs 1.4%; p < 0.01) than HCV-C patients. The preoperative treatment of HCV can reduce the risk of complications, including prosthetic joint infection and revision TKA. We recommend that HCV treatment regimens should be integrated into the preoperative optimization protocol for this high-risk group of patients. Cite this article: Bone Joint J 2019;101-B:667-674.

Hepatitis C virus, alcohol and lipid droplets

Hepatitis C virus (HCV) persistence drives the progression of HCV infection. This progression is usually asymptomatic in HCV-infected patients. For many years, clinical manifestations of HCV persistence are restricted to fatty liver followed by slow development of fibrosis, cirrhosis and hepatocellular carcinoma [1, 2]. Thus, HCV persistence is a “first hit” triggering HCV pathogenesis. There are “second hits” that stabilize the infection and cause faster progression, exacerbation of pathological features of HCV infection and poor response to anti-viral therapy. One of these “second hits” known to affect HCV pathogenesis is alcohol. Liver steatosis is common for both HCV infection and alcohol and is considered as a cofactor in development and progression of fibrosis. Hepatitis C virus is an RNA virus packaged into an enveloped virus particle. HCV polyprotein has 3000 amino acids and is co-translational and posttranslational processed by cellular and viral proteases to form three structural proteins (core, E1 and E2), an ion channel protein (p7) and six non-structural proteins (NS2, NS3, NS4A, NS4B, NS5A, NS5B) [3]. Viral RNA replication requires the formation of a membrane-associated replication complex composed on HCV non-structural proteins, RNA and cellular membranes. Enveloped HCV virions carrying a newly synthesized viral genome are formed by budding into the endoplasmic reticulum lumen and leave the cells through the secretory transGolgi pathway [4].

Hepatitis C virus infection among drug addicts in Italy

There is a lack of updated nationwide records regarding hepatitis C virus (HCV) infection among drug addicts in Italy. The prevalence and characteristics of HCV infection in a national sample of drug addicts in Italy were determined. Five hundred forty-three drug addicts (mean age 35.3 years, 85.1% males), selected from 25 Italian Centers for Substance Dependence were enrolled to be evaluated for anti-HCV, HCV-RNA, HCV genotype, HBV markers, anti-HDV, and anti-HIV during the period of April-November 2009. Anti-HCV prevalence was 63.9%. HCV-RNA was detected in 68.3% of patients positive for anti-HCV. Genotypes 1 and 3 prevailed (49.3% and 39.7%, respectively). However, 9.3% of the subjects had genotype 4, a rate over threefold higher than the one observed in 1996 among drug addicts in central Italy. Needle sharing was the strongest independent predictor of the likelihood to contract an HCV infection (OR 8.9; 95% CI: 5.0-16.0). Only 19.3% of subjects received antiviral treatment for HCV. The prevalence of HBsAg and HIV positivity was 2.8% and 3.1%, respectively. The pattern of HBV markers showed that nearly one-third of subjects had been vaccinated, while 42.3% were negative for any marker of HCV. The prevalence of HCV infection is high among drug addicts in Italy. The incidence of Genotype 4 is increasing and this may lead to the spreading of the disease to the general population in the near future. Efforts should be made to improve the rate of antiviral treatment for drug addicts with HCV infection and vaccination against hepatitis B.

Gaining Greater Insight into HCV Emergence in HIV-Infected Men Who Have Sex with Men: The HEPAIG Study

ObjectivesThe HEPAIG study was conducted to better understand Hepatitis C virus (HCV) transmission among human immuno-deficiency (HIV)-infected men who have sex with men (MSM) and assess incidence of HCV infection among this population in France.Methods and ResultsAcute HCV infection defined by anti-HCV or HCV ribonucleic acid (RNA) positivity within one year of documented anti-HCV negativity was notified among HIV-infected MSM followed up in HIV/AIDS clinics from a nationwide sampling frame. HIV and HCV infection characteristics, HCV potential exposures and sexual behaviour were collected by the physicians and via self-administered questionnaires. Phylogenetic analysis of the HCV-NS5B region was conducted.HCV incidence was 48/10 000 [95% Confidence Interval (CI):43–54] and 36/10 000 [95% CI: 30–42] in 2006 and 2007, respectively. Among the 80 men enrolled (median age: 40 years), 55% were HIV-diagnosed before 2000, 56% had at least one sexually transmitted infection in the year before HCV diagnosis; 55% were HCV-infected with genotype 4 (15 men in one 4d-cluster), 32.5% with genotype 1 (three 1a-clusters); five men were HCV re-infected; in the six-month preceding HCV diagnosis, 92% reported having casual sexual partners sought online (75.5%) and at sex venues (79%), unprotected anal sex (90%) and fisting (65%); using recreational drugs (62%) and bleeding during sex (55%).ConclusionsThis study emphasizes the role of multiple unprotected sexual practices and recreational drugs use during sex in the HCV emergence in HIV-infected MSM. It becomes essential to adapt prevention strategies and inform HIV-infected MSM with recent acute HCV infection on risk of re-infection and on risk-reduction strategies.

Reply to the correspondence letter by Dr. Giuseppe Indolfi “Spontaneous clearance of hepatitis C virus in vertically infected children. Any clue for treatment?”

We thank Giuseppe Indolfi for adding information on factors affecting the overall prognosis of vertical hepatitis C virus (HCV) infection. We fully agree that their work [1], which we refer to twice in our publication, as well as other studies provide valuable information on the course of HCV infections in children. However, neither of the published studies is population based. Therefore, cases with high liver function test (LFT) values are probably overrepresented, since they are discovered more easily, and the rate of clearance may be overestimated. Accordingly, the chance of spontaneous HCV clearance and hence the benefit of early treatment remains somewhat uncertain in the individual young child [2]. In our six patients, the combination of the longitudinal course of LFTs plus HCV gene copy number appeared to aid in predicting the chance of viral resolution. As mentioned in our paper, we concur that other features of HCV infection, such as viral genotype and IL28B polymorphisms, contribute to viral resolution in children [1, 3, 4]. Therefore, information on IL28B polymorphisms in our patients would have been interesting. Yet, given the small number of cases, it would not have allowed for sound conclusions on its role in clearance. Currently, the decision for early versus delayed treatment remains an individual one. Whereas treatment can be delayed until the age of 5 years in most patients, some children with HCV genotype 1a and persistently elevated LFTs without signs of viral clearance may benefit from earlier treatment, as suggested by the work of Bortolotti et al. [1]. Better treatment algorithms can only be developed in multicenter interventional studies of highest quality.

The prevalence of GB virus C/hepatitis G virus RNA among healthy and HCV-infected Catalan children

GB virus C (GBV-C) is a blood-borne flavivirus. The prevalence of GBV-C viremia among healthy adults is 0.5% to 4% and, to date, no disease has been definitely associated with GBV-C infection. We conducted a cross-sectional study to evaluate GBV-C viremia prevalence in a group of 327 healthy children with normal alanine amino transferase (ALT) levels (Group A) and elevated ALT levels (Group B) of unknown origin, and among 38 pediatric patients with mother-to-child-transmitted hepatitis C virus (HCV) infection (Group C). No statistically significant differences were observed between prevalences in Groups A and B (2.2% vs 6.7%, p = 0.06). None of the children in Groups A or B who tested positive for GBV-C RNA showed any clinical symptoms. The prevalence of GBV-C viremia in Group A was lower than for patients in Group C (2.2% vs 13.2%, p = 0.007); no differences were observed in HCV infection characteristics between those patients who were co-infected with GBV-C and those who were not. In conclusion, while GBV-C viremia is more frequent among HCV-infected pediatric patients, it is neither associated with liver disease nor has any influence on HCV-related chronic hepatitis.

Risk Factors for Hepatitis C on the Texas-Mexico Border

Our clinical experience suggested that hepatitis C virus (HCV) infection in this Texas-Mexico border area might have features, especially risk factors, that differ from some other areas of the United States. Therefore, we conducted a prospective analysis to investigate the epidemiology, risk factors, and certain other characteristics of HCV infection in the El Paso region. During a 2-yr period, individuals with a positive HCV serology were considered as "patients" and those with a negative hepatitis serology panel were "controls." A questionnaire survey was conducted in person or by telephone with individuals (patients and controls) who agreed to participate in the interview process. We identified and interviewed 320 patients and 307 controls. All of the contacted patients and controls agreed to be interviewed. Many established and potential risk factors for HCV transmission were documented in the patients. Furthermore, multiple potential risk factors were often present in individual patients. However, on multivariate analysis only injection drug use, blood transfusion, and tattooing were found to be significant independent risk factors for HCV infection. In the great majority of patients, tattoos were applied by friends (including gang members), inmates in jail/prison, or self, rather than commercial parlors. Tattooing is an independent risk factor for HCV infection in this United States-Mexico border area. The role of nonsterile tattooing practices in HCV transmission merits additional examination in regard to precise risk settings, frequency, and mechanisms of infection.

Production of interleukin-18 and interleukin-12 in patients suffering from chronic hepatitis C virus infection before antiviral therapy.

Interleukin-12 and -18 (IL-12 and IL-18) are known to enhance the cytotoxic T-lymphocyte response synergistically, but their precise involvement in hepatitis C virus (HCV) infection is not well known, especially for IL-18. Enzyme-linked immunosorbent assay (ELISA) was used to study the production of these cytokines in plasma and peripheral blood mononuclear cells (PBMCs) stimulated by lipopolysaccharide (LPS) of patients infected chronically with HCV before initiation of antiviral therapy. Fifty-six patients and 40 healthy controls were evaluated. Patients infected with genotype 1 or with genotype other than genotype 1 HCV had significantly a high production of plasma IL-12 compared with controls (P < 0.05). However, patients infected with genotype 1 HCV had lower levels of PBMC IL-18 than were founded in the controls (P < 0.05); plasma IL-18 also tended to be lower in this group of patients than in the controls, although nonsignificantly. Plasma IL-18 was related to hepatic histological activity (P < 0.05). The data suggest a relationship between these two cytokines and some features of HCV infection, so that their respective production in relation to the outcome of the infection deserves further study.

Lower expression of CD81 B-cell receptor in lymphoproliferative diseases associated with hepatitis C virus infection.

Chronic hepatitis C virus (HCV) infection is frequently associated with type II mixed cryoglobulinaemia (MC), a benign lymphoproliferative disease (LPD). More recently, HCV has been implicated as a possible aetiologic factor of B-cell non-Hodgkin lymphoma (B-NHL). CD81, a B-cell surface receptor, has been proposed as a receptor for HCV binding and entry in circulating B cells. The stimulation of CD81 complex enables B cells to respond to lower concentrations of antigen and finally induces B-cell proliferation. We studied the phenotypic expression of CD81, CD19 and CD5 on circulating B cells in HCV patients LPD-positive or LPD-negative. Sixty-two patients were anti-HCV antibody positive. Among HCV positive patients, 44 were HCV RNA positive with an histologically proven chronic active hepatitis of whom 10 had a B-NHL, 14 an MC and 24 no extrahepatic manifestation. Eighteen patients were HCV RNA negative with evidence of resolved infection. A control group included 40 healthy subjects. Peripheral blood mononuclear cells (PBMC) were stained for surface expression of CD81, CD19 and CD5 using monoclonal antibodies, and were analyzed by flow cytometry. The percentage of PBMC expressing CD81, CD19 and CD5 receptors were compared between the groups by univariate analysis. Logistic regression model variables were then evaluated to correlate the presence of an LPD with HCV infection characteristics (i.e. age, gender, genotype, duration of infection, HCV RNA positivity, liver histological lesions), or phenotypic expression of CD81, CD19 and CD5 receptors on PBMC. HCV antibody-positive compared with HCV-negative subjects had a higher expression of CD19 receptor (23 +/- 13 vs 13 +/- 1%, P = 0.003). Among HCV RNA positive-patients, LPD+ compared with LPD- patients had a lower expression of CD81 (58 +/- 28 vs 82 +/- 18%, P = 0.001) and CD5 receptor (66 +/- 16 vs 74 +/- 13%, P = 0.04). In multivariate analysis, the expression of CD81 receptor was a negative (OR = 0.15, 95% CI = 0.04-0.64, P = 0.01) and CD19 receptor a positive (OR = 4.81, 95% CI =1.29-17.88, P = 0.02) predictive factor for an LPD. We found two negative predictive factors for HCV RNA positivity, i.e. age (OR = 0.23, 95% CI. = 0.08-0.62, P = 0.003) and the expression of CD81 receptor (OR = 0.34, 95% CI = 0.13-0.89, P = 0.02). In patients with a chronic active HCV infection, the presence of a lymphoproliferative disease, either MC or B-NHL, is associated with lower expression of CD81 and higher expression of CD19 receptor on peripheral B cells.

Impact of hepatitis C virus duration and hepatitis C virus genotypes on renal transplant patients: correlation with clinicopathological features.

The aim of this study was to evaluate the long-term impact of chronic hepatitis C virus (HCV) infection on the liver in renal transplant patients. We studied 78 patients for whom at least one posttransplant liver biopsy (LB) was available and for whom the duration of HCV infection was precisely defined. The LB were graded according to a histological activity index, i.e., the Knodell score, divided into the activity score and the fibrosis score. They were also classified as either normal or showing evidence of chronic persistent hepatitis, chronic active hepatitis (CAH), or cirrhosis. The study comprised 7 HCV-positive/hepatitis B surface antigen-positive patients (group 1); 4 HCV-positive/RNA-negative patients (group 2); and 67 HCV-positive/RNA-positive patients (group 3). The three groups were comparable according to demographic data and baseline immunosuppression. The median time from transplantation to LB was 38 months (range, 10-306 months). At that time, alanine aminotransferase (ALT) levels had increased in 71.4%, 0%, and 42% of patients from groups 1, 2, and 3, respectively (P=0.07). The total Knodell score showed significantly more severe lesions in group 1 patients (6.2+/-3.2) than in group 2 (1+/-1.2) or in group 3 (4.6+/-2.4) patients (P=0.007). The Knodell score also showed that the fibrosis score was significantly higher in group 1 (2.3+/-1.6) than in group 2 (0) or in group 3 (0.9+/-1.1) patients (P=0.007). Overall, there were 28 cases of CAH (36%) and 4 cases of cirrhosis (5%). We did not observe any correlation between liver histology and characteristics of HCV infection or the type of chronic immunosuppression (double-drug versus triple-drug therapy). However, liver histology (total Knodell score) and the activity score were significantly correlated with ALT levels. Multivariate analysis did identify (i) four independent variables that could explain the degree of liver fibrosis-the sex of the patient, the number of blood units received before transplantation, increased ALT levels at the time of LB, and the occurrence of at least one acute rejection episode (thus the receipt of methylprednisolone pulses); and (ii) two independent variables associated with the occurrence of CAH-the number of blood units before transplantation and increased ALT levels at the time of LB. This study showed that renal transplant patients infected by HCV for more than 10 years, with a mean posttransplant follow-up of more than 5 years, showed more severe liver lesions when coinfected by hepatitis B virus. Overall, we observed only four cases of cirrhosis (5%) and evidence of histological CAH lesions in 36% of the patients.

A prospective study of hepatitis C virus infection after needlestick accidents.

There have been few prospective studies of hepatitis C virus (HCV) infection after needlestick accidents in hospital employees. In the present study, the prevalence and features of HCV infection after needlestick accidents were evaluated prospectively measuring serum HCV-RNA. Subjects were 56 employees who had HCV needlestick accidents. To monitor the development of hepatitis, the serum ALT levels and HCV-related seromarkers, such as first generation anti-HCV (RIA), second generation anti-HCV (PHA) and HCV-RNA (RT-PCR) were measured every month for at least 12 months after the accidents. Three of 56 (5.4%) recipients developed HCV infection. HCV-RNA was detected in all three recipients within 4 months after the exposure, and second-generation HCV antibody was detected in two of three recipients. The detection of HCV-RNA was earlier than that of HCV antibody. Two of three HCV-infected recipients developed type C acute hepatitis and one of two received interferon therapy; however, the other case received no medication. The detection of HCV-related seromarkers and the elevation of ALT levels were transient in these three recipients: thus, none developed chronic hepatitis. In conclusion, HCV infection developed in 5.4% of recipients within 4 months after HCV accidents. All of these HCV-infected recipients showed fair prognosis. HCV-RNA was a beneficial parameter for early detection of HCV infection.