Hepatitis C Virus RNA Positive Individuals Research Articles

Successes and challenges of best practice alerts to identify and engage individuals living with hepatitis C virus

IntroductionMany individuals living with hepatitis C virus (HCV) are unaware of their diagnosis and/or have not been linked to programs providing HCV care. The use of electronic medical record (EMR) systems may assist with HCV infection identification and linkage to care.MethodsIn October 2021, we implemented HCV serology-focused best practice alerts (BPAs) at The Ottawa Hospital (TOH) via our EMR (EPIC). Our BPAs were programmed to identify previously tested HCV seropositive individuals. Physicians were prompted to conduct HCV RNA testing and submit consultation requests to the TOH Viral Hepatitis Program. We evaluated data post-BPA implementation to assess the design and related outcomes.ResultsFrom 1 September 2022 to 15 December 2022, a total of 2,029 BPAs were triggered for 139 individuals. As a consequence of the BPA prompts, nine HCV seropositive and nine HCV RNA-positive individuals were linked to care. The proportion of total consultations coming from TOH physicians increased post-BPA implementation. The BPA alerts were frequently declined, and physician engagement with our BPAs varied across specialty groups. Programming issues led to unnecessary BPA prompts (e.g., no hard stop to the prompts even though the individual was treated and cured and individuals linked to care without first undergoing HCV RNA testing). A fixed 6-month lookback period for test results limited our ability to identify many individuals.ConclusionAn EMR-based BPA can assist with the identification and engagement of HCV-infected individuals in care. However, challenges including issues with programming, time commitment toward BPA configuration, productive communication between healthcare providers and the programming team, and physician responsiveness to the BPAs require attention to optimize the impact of BPAs.

Chronic hepatitis C elimination prison initiative: HCV-intensive test and treat, a whole prisoner population HCV test-and-treat program in England.

Prison residents are at high risk for hepatitis C virus (HCV) infection. HCV test-and-treat initiatives within prisons provide an opportunity to engage with prison residents and achieve HCV micro-elimination. The aim of the prison HCV-intensive test and treat initiative was to screen over 95% of all prison residents for HCV infection within a defined number of days determined by the size of the prison population and to initiate treatment within 7-14 days of a positive HCV RNA diagnosis. An HCV-intensive test and treat toolkit was developed based on learnings from pilot HCV-intensive test and treat events. From January 2020 to September 2021, 13 HCV-intensive test and treat events took place at prisons in England selected based on high levels of reception blood-borne virus testing and good access to peers from The Hepatitis C Trust. Among a total of 8487 residents, 8139 (95.9%) underwent testing for HCV. Across the 13 prisons included, HCV antibody and RNA prevalence was 8.2% and 1.5%, respectively. The treatment initiation rate among HCV RNA-positive individuals (n = 124) was 79.0%. The HCV-intensive test and treat initiative presented here provides a feasible and rapid test-and-treat process to achieve HCV elimination within individual prisons. The HCV-intensive test and treat toolkit can be adapted for rapid HCV testing and treatment events at other prisons in the United Kingdom and worldwide.

Opportunistic Treatment of Hepatitis C Infection Among Hospitalized People Who Inject Drugs (OPPORTUNI-C): A Stepped Wedge Cluster Randomized Trial.

We aimed to evaluate the efficacy of opportunistic treatment of hepatitis C virus (HCV) infection among hospitalized people who inject drugs (PWID). We performed a pragmatic, stepped wedge cluster randomized trial recruiting HCV RNA positive individuals admitted for inpatient care in departments of internal medicine, addiction medicine, and psychiatry at three hospitals in Oslo, Norway. Seven departments were sequentially randomized to change from control conditions (standard of care referral to outpatient care) to intervention conditions (immediate treatment initiation). The primary outcome was treatment completion, defined as dispensing the final package of the prescribed treatment within six months after enrolment. A total of 200 HCV RNA positive individuals were enrolled between 1 October 2019 and 31 December 2021 (mean age 47.4 years, 72.5% male, 60.5% injected past 3 months, 20.4% cirrhosis). Treatment completion was accomplished by 67 of 98 (68.4% [95% confidence interval {CI}: 58.2-77.4]) during intervention conditions and by 36 of 102 (35.3% [95% CI: 26.1-45.4]) during control conditions (risk difference 33.1% [95% CI: 20.0-46.2]; risk ratio 1.9 [95% CI: 1.4-2.6]). The intervention was superior in terms of treatment completion (adjusted odds ratio [aOR] 4.8 [95% CI: 1.8-12.8]; P = .002) and time to treatment initiation (adjusted hazard ratio [aHR] 4.0 [95% CI: 2.5-6.3]; P < .001). Sustained virologic response was documented in 60 of 98 (61.2% [95% CI: 50.8-70.9]) during intervention and in 66 of 102 (64.7% [95% CI: 54.6-73.9]) during control conditions. An opportunistic test-and-treat approach to HCV infection was superior to standard of care among hospitalized PWID. The model of care should be considered for broader implementation. Clinical Trials Registration. NCT04220645.

Ten years countdown to hepatitis C elimination in Belgium: a mathematical modeling approach

BackgroundChronic infection with the hepatitis C virus (HCV) remains a worldwide health problem. As a result, the World Health Organization (WHO) has set elimination targets by 2030. This study aims to examine the position of Belgium in meeting the WHO's targets by 2030.MethodsA Markov disease progression model, constructed in Microsoft Excel, was utilized to quantify the size of the HCV-infected population, by the liver disease stages, from 2015 to 2030. Two scenarios were developed to (1) forecast the disease burden in Belgium under the 2019 Base and (2) see what is needed to achieve the WHO targets.ResultsIt was estimated that the number of HCV RNA-positive individuals in Belgium in 2015 was 18,800. To achieve the WHO goals, Belgium needs to treat at least 1200 patients per year. This will only be feasible if the number of screening tests increases.ConclusionsBelgium is on target to reach the WHO targets by 2030 but will have to make sustained efforts. However, eradicating HCV requires policy changes to significantly increase prevention, screening, and treatment, alongside public health promotion, to raise awareness among high-risk populations and health care providers.

Low hepatitis C virus-viremia prevalence yet continued barriers to direct-acting antiviral treatment in people living with HIV in the Netherlands.

To describe hepatitis C virus (HCV)-viremia prevalence and barriers to direct-acting antiviral (DAA) treatment during unrestricted access to DAA in a nationwide cohort of people with HIV (PWH). Retrospective analysis of prospectively collected data. We calculated yearly HCV-viremia prevalence as proportion of HCV RNA-positive individuals ever HCV-tested. We then included HCV-viremic individuals with ≥1 visit during the era of universal DAA-access (database lock = December 31, 2018). Based on their last visit, individuals were grouped as DAA-treated or -untreated. Variables associated with lack of DAA-treatment were assessed using targeted maximum likelihood estimation. In November 2020, physicians of DAA-untreated individuals completed a questionnaire on barriers to DAA-uptake and onward HCV-transmission risk. Among 25 196 PWH, HCV-viremia decreased from 4% to 5% between 2000 and 2014 to 0.6% in 2019. Being DAA-untreated was associated with HIV-transmission route other than men who have sex with men, older age, infrequent follow-up, severe alcohol use, detectable HIV-RNA, HCV-genotype 3, and larger hospital size. With universal DAA-access, 72 of 979 HCV-viremic individuals remained DAA-untreated at their last visit. Of these, 39 were no longer in care, 27 remained DAA-untreated in care, and six initiated DAA since database lock. Most common physician-reported barriers to DAA-uptake were patient refusal (20/72, 28%) and infrequent visit attendance (19/72, 26%). Only one DAA-untreated individual in care was engaging in activities associated with onward HCV-transmission. Prevalence of HCV-viremic PWH is low in the Netherlands, coinciding with widespread DAA-uptake. Barriers to DAA-uptake appear mostly patient-related, while HCV-transmission seems unlikely from the few DAA-untreated in care.

Epidemiology and Clinical Characteristics of Individuals with Hepatitis C Virus Infection in the United States, 2017-2019.

IntroductionHepatitis C virus (HCV) is the most common bloodborne chronic infection in the US. Following approval of highly effective, direct-acting antivirals in 2014, the diagnostic and treatment rates for HCV infection in the US have evolved. This study assessed the number of individuals with HCV screening or diagnostic testing and the clinical characteristics and treatment of HCV-infected individuals between 2017 and 2019.MethodsIndividuals screened for HCV antibody and/or tested for HCV ribonucleic acid (RNA) from 2017 to 2019 by two large US laboratory companies were included in this analysis. Clinical characteristics, such as HCV genotype, fibrosis stage, HIV coinfection and demographics, were assessed in HCV RNA-positive individuals. HCV treatment and subsequent achievement of sustained virologic response were imputed using data-driven algorithms based on successive viral load decline and negativity.ResultsFrom 2017 to 2019, the number of individuals tested for HCV antibody increased by 5.7%, from 7,580,303 in 2017 to 8,009,081 in 2019. The percentage of individuals tested who were HCV antibody positive was stable, ranging from 5.0% in 2017 to 4.9% in 2018 and 2019. The number of HCV RNA-positive individuals decreased by 5.0% from 382,500 in 2017 to 363,532 in 2019. Of HCV RNA-positive individuals, the proportions with genotype (GT) 3 and minimal fibrosis increased over time; proportions of individuals aged < 40 years increased, while the proportion aged 50 to 59 years decreased. Treatment rates increased from 23.4% in 2017 to 26.8% in 2019.ConclusionsThe percentage of HCV antibody-positive individuals remained stable from 2017 to 2019. The number of individuals tested HCV RNA positive decreased over the years. Demographics shifted toward a younger population with less fibrosis and higher rates of GT3. More than 70% of diagnosed individuals were not treated during this interval, highlighting a need for unfettered access to treatment.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01928-y.

A Feasibility Study to Increase Chronic Hepatitis C Virus RNA Testing and Linkage to Care among Clients Attending Homeless Services in Amsterdam, The Netherlands.

People who inject drugs (PWID) are disproportionately affected by hepatitis C virus (HCV) infections and are frequently homeless. To improve HCV case finding in these individuals, we examined the feasibility of rapid HCV RNA testing in homeless services in Amsterdam. In 2020, we provided a comprehensive service to homeless facilities, which included workshops on HCV for personnel, a “hepatitis ambassador” at each facility, a rapid, onsite HCV RNA fingerstick test service, and assistance with linkage to care. Risk factors for HCV RNA-positive status were examined using Bayesian logistic regression. Of the 152 participants enrolled, 150 (87% men; median age: 47 years) accepted rapid HCV testing. Seven tested HCV RNA positive (4.7%, 95%CrI = 1.31–8.09; 7/150). Of these, five (71%) were linked to care, of whom four (57%, 4/7) initiated treatment and one (14%, 1/7) delayed treatment due to a drug–drug interaction. Of these four people, two completed treatment (50%), of whom one (25%) achieved sustained virologic response after 12 weeks. HCV RNA-positive individuals were more likely to originate from Eastern Europe (posterior-odds ratio (OR) = 3.59 (95% credible interval (CrI) = 1.27–10.04)) and to inject drugs (ever: posterior-OR = 3.89 (95% CrI = 1.37–11.09); recent: posterior-OR = 3.94 (95% CrI = 1.29–11.71)). We identified HCV RNA-positive individuals and linkage to care was relatively high. Screening in homeless services with rapid testing is feasible and could improve HCV case finding for PWID who do not regularly attend primary care or other harm reduction services for people who use drugs.

Hepatitis C virus cascade of care in the general population, in people with diabetes, and in substance use disorder patients

BackgroundThe aim was to evaluate the hepatitis C virus (HCV) cascade of care in the general population (GP) and in two high-risk populations: patients with diabetes mellitus (DM) and substance users (AS) in treatment in Reggio Emilia Province, Italy.MethodsA population-based cross-sectional study was conducted that included 534,476 residents of the Reggio Emilia Province, of whom 32,800 were DM patients and 2726 AS patients. Age-adjusted prevalence was calculated using the direct method of adjustment based on the age-specific structure of EU population.ResultsThe prevalence of HCV testing was 11.5%, 13.8%, and 47.8% in GP, DM, and AS patients respectively, while HCV prevalence was 6.5/1000, 12.6/1000, and 167/1000, respectively. The prevalence of HCV RNA positivity was 4.4/1000, 8.7/1000, and 114/1000 in the three populations, respectively. The rates of HCV RNA-positive individuals not linked to care were 27.9%, 27.3%, and 26% in GP, DM, and AS patients, respectively, while the rates of those cured or cleared were 70.9%, 71%, and 69.9%, respectively. The prevalence of HCV testing was higher for females of reproductive age than for males the same age: 218.4/1000 vs. 74.0/1000, respectively. While more foreigners than Italians underwent the HCV test and were HCV positive, fewer foreigners than Italians received HCV treatment and were cured.ConclusionsThe low HCV testing and linkage to care rates remain an important gap in the HCV cascade of care in Northern Italy. The prevalence of cured/cleared residents remains lower among foreigners than among Italians.

Opportunistic treatment of hepatitis C virus infection (OPPORTUNI-C): study protocol for a pragmatic stepped wedge cluster randomized trial of immediate versus outpatient treatment initiation among hospitalized people who inject drugs

BackgroundScaled-up direct-acting antiviral (DAA) treatment of hepatitis C virus (HCV) infection among people who inject drugs (PWID) is crucial to reach the World Health Organization HCV elimination targets within 2030. One of the critical obstacles to HCV care in this population is the lack of treatment models within specialist healthcare adapted to marginalized individuals.MethodsOPPORTUNI-C is a pragmatic stepped wedge cluster randomized trial comparing the efficacy of immediate initiation of HCV treatment with the current standard of care among PWID admitted for inpatient care. Screening for HCV RNA will be performed as soon as possible after admission. The intervention includes immediate non-invasive liver disease assessment, counseling, and initiation of pan-genotypic DAA treatment with individualized follow-up. Standard of care is a referral to outpatient care at discharge. To mimic usual clinical practice as closely as possible, we will use a pragmatic clinical trial approach utilizing clinical infrastructure, broad eligibility criteria, flexible intervention delivery, clinically relevant outcomes, and collection of data readily available from the electronic patient files. The stepped wedge design involves a sequential rollout of the intervention over 16 months, in which seven participating clusters will be randomized from standard of care to intervention in a stepwise manner. Randomization will be stratified according to cluster size to keep high prevalence clusters separated. The trial will include approximately 220 HCV RNA positive individuals recruited from departments of internal medicine, addiction medicine, and psychiatry at Akershus University Hospital, Oslo University Hospital, and Lovisenberg Diaconal Hospital, Oslo, Norway. Individuals not able or willing to give informed consent and those with ongoing HCV assessment or treatment will be excluded. The primary outcome is treatment completion, defined as dispensing of the final prescribed DAA package from the pharmacy within 6 months after inclusion. Secondary outcomes include treatment uptake, virologic response, reinfection incidence, and resistance-associated substitutions.DiscussionRepresenting a novel model of care suited to reach and engage marginalized PWID in HCV care, this study will inform HCV elimination efforts locally and internationally. If the model proves efficacious and feasible, it should be considered for broader implementation, replacing the current standard of care.Trial registrationClinicalTrials.gov, NCT04220645. Registered on 7 January 2020.

Screening for hepatitis C in a general adult population in a low-prevalence area: the Troms\xf8 study

BackgroundChronic hepatitis C virus (HCV) infection can progress to cirrhosis and end-stage liver disease in a substantial proportion of patients. The infection is frequently asymptomatic, leaving many infected individuals unaware of the diagnosis until complications occur. This advocates the screening of healthy individuals. The aim of this study was to estimate the prevalence of HCV infection in the general adult population of the municipality of Tromsø, Norway, and to evaluate the efficiency of such an approach in a presumed low-prevalence area.MethodsThe study was part of the seventh survey of the Tromsø Study (Tromsø 7) in 2015–2016. Sera from 20,946 individuals aged 40 years and older were analysed for antibodies to HCV (anti-HCV). A positive anti-HCV test was followed up with a new blood test for HCV RNA, and the result of any previous laboratory HCV data were recorded. Samples positive for anti-HCV and negative for HCV RNA were tested with a recombinant immunoblot assay. All HCV RNA positive individuals were offered clinical evaluation.ResultsAmong 20,946 participants, HCV RNA was detected in 33 (0.2%; 95% CI: 0.1–0.3), of whom 13 (39.4%; 95% CI: 22.7–56.1) were unaware of their infection. The anti-HCV test was confirmed positive in 134 individuals (0.6%; 95% CI: 0.5–0.7) with the highest prevalence in the age group 50–59 years. Current or treatment-recovered chronic HCV-infection was found in 85 individuals (0.4%; 95% CI: 0.3–0.5) and was associated with an unfavorable psychosocial profile.ConclusionIn this population-based study, the prevalence of viraemic HCV infection was 0.2%. A substantial proportion (39%) of persons with viraemic disease was not aware of their infectious status, which suggests that the current screening strategy of individuals with high risk of infection may be an inadequate approach to identify chronic HCV infection hidden in the general population.

Management of hepatitis C in decentralised versus centralised drug substitution programmes and minimally invasive point-of-care tests to close gaps in the HCV cascade.

In Switzerland, intravenous drug use accounts for the majority of hepatitis C virus (HCV) infections. Early HCV treatment prevents further transmissions and reduces morbidity and mortality due to decompensated liver cirrhosis and hepatocellular carcinoma. Nevertheless, patients in drug substitution programmes are often insufficiently screened and treated. The aim was to compare the current state of HCV management in centralised and decentralised drug substitution programmes of the canton Aargau. Objectives were human immunodeficiency virus (HIV) and HCV prevalence, compliance with guidelines and gaps in the HCV cascade, as well as feasibility/acceptance/validity of HIV/HCV rapid tests on finger-prick blood and noninvasive liver fibrosis assessment with Fibroscan®. For the cross-sectional study, in June 2013, questionnaires and free rapid tests for HIV (Determine®) and HCV (OraQuick®) that used capillary blood (finger-stick) were sent to 161 physicians providing drug substitution treatment for 631 patients. Free liver fibrosis assessment with Fibroscan® by a member of the study team was offered to all patients. Additionally, patients were directly recruited by the study team in the heroin substitution programme and several addiction clinics visited every 4-6 months, as well as in the Infectious Diseases Outpatient Clinic (questionnaire, rapid tests and Fibroscan® in the same session). Between July 2013 and July 2015, 205 (32.5%) of the 631 patients receiving opioid substitution in the canton Aargau were enrolled, 192 (93.7%) with HIV/HCV rapid tests and 167 (81.5%) with Fibroscan®. Acceptance of Fibroscan® was higher when offered in the same session (94.1 vs 69.2%). Overall, 77.8% had ever used intravenous drugs. HCV seroprevalence was 53.7% (109/203), HCV RNA prevalence 27.8%. Overall, 7.4% (15/202) were HIV infected, all of whom were HCV co-infected and under antiretroviral treatment. Of the 205 patients included, 104 (50.7%) were recruited in a decentralised setting (family practice / pharmacy) and 101 (49.3%) in a centralised setting (heroin programme, addiction clinic, Infectious Diseases Outpatient Clinic). Compliance with guidelines (regular HIV/HCV screening, workup of HCV-positive patients, availability of HAV/HBV serology) was consistently lower in the decentralised setting, characterised by a higher proportion of females, longer median time in the programme, lower percentage of daily attendance, ever-use of intravenous drugs and HIV and HCV infections. We identified several gaps in the HCV cascade: 23.9% (49/205) had never been HCV screened; 18.9% (18/95) of the HCV positive patients had no HCV RNA test. Of the 61 patients developing chronic HCV infection, 19.7% (12) were not HCV genotyped, 52.5% (32) had no liver fibrosis assessment (liver biopsy) and 54.1% (33) never received treatment; 25.0% (7/28) did not achieve a sustained virological response with interferon-based treatment. The 192 HCV rapid tests showed a sensitivity of 90.4% (94/104; 95% confidence interval 84.7-96.1%) and a specificity of 100% (88/88), and provided 14 new HCV diagnoses. Eight of ten patients with a false-negative HCV rapid test were HCV RNA negative (2 unknown). Among the 88.6% (39/44) currently HCV RNA-positive individuals with valid Fibroscan® results, 24 (61.5%) had a liver stiffness <7.5 kPa. Both HIV co-infection and alcohol overconsumption doubled the risk of severe fibrosis/cirrhosis in HCV positive patients. In contrast to HIV, HCV transmission among intravenous drug users is still ongoing. The management of hepatitis C in drug substitution patients needs improvement, especially in family practices. Minimally invasive "point-of-care" diagnostics such as the HCV antibody rapid test using capillary blood and mobile Fibroscan® can close some of the gaps in the HCV cascade. HCV RNA determination in capillary blood is still an unmet need. A "one-stop strategy" might improve linkage to care. Restricting the new, highly efficient (90-100% sustained virological response for all genotypes) direct-acting antivirals to patients with at least stage F2 fibrosis withholds treatment from two thirds of the chronically infected and prevents us from reaching the WHO goal of 80% treatment uptake necessary to eliminate hepatitis C by 2030.

Prevalence and Genotypic Distribution of Hepatitis C Virus in Peshawar KPK, Pakistan

This present study was planned to obtain an up-to-date picture of Hepatitis C virus (HCV) infection and its genotypes distribution in Peshawar, Khyber Pakhtunkhwa, Pakistan, as well as of the relationship between HCV genotypes and demographic and clinical parameters, and the risk factors in patients with an HCV subtype. Samples (blood) from 1978 individuals were collected and were tested using a strip-based method called the immunochromatographic test (ICT) for the existence of antibodies against HCV. It was observed that 158 of the 1978 individuals (7.9%) harbored antibodies in their blood against HCV, among which the female percentage (53.2%) was higher than that of the male (46.8%). Among the different age groups, the highest number of incidences of HCV antibodies was found in the age group of 31–40 years (26.6%). ICT positive samples were further screened by polymerase chain reaction (PCR) to determine the existence of active HCV-RNA, and it was found that 6.21% (123) of the total population (1978) tested, was positive, among which the female rate (56.91%) was observed to be higher than that of the male (43.09%). The highest incidence recorded was in the age group of 41–50 years (33.3%). HCV RNA positive individuals were genotyped: genotype 3a (45.5%) was dominant among the other detected genotypes, followed by 1a (11.4%), 3b (4.9%), and 2a (4.1%). It was concluded that the highest prevalence of HCV was found in females, and that the dominant genotype of the screened individuals was 3a genotype.

Prevalence of HCV genotypes in district Mardan

BackgroundApproximately 170 million people are infected with Hepatitis C virus (HCV) worldwide. The prevalence of chronic HCV infections in Pakistan is about 5%, with most individuals being infected with HCV genotype 3a. Data on HCV genotypes distribution across various districts of the country are scarce. One example is district Mardan from where such data is available only from 17 individuals. Accordingly, the present study aimed at determining HCV genotypes distribution among 177 HCV RNA positive individuals from district Mardan.FindingsSerum samples (n = 215) from patients suspected of hepatitis C were collected and processed for Nested PCR based detection and subsequent genotyping. Gender-wise and age-wise differences in HCV prevalence and HCV genotypes distribution were determined by χ2 test. Out of the total 215 serum samples, 177 were found to be positive for HCV RNA. The genotype 3a was the most predominant genotype among HCV RNA positive samples with a prevalence of 90.3%, followed by genotype 1a (5.6%), mixed genotypes (2.8%), genotype 3b (0.6%) and genotype 4 (0.6%). The HCV prevalence was higher in young individuals than old people and was indicative of reduced survival rate beyond 40 years.ConclusionHCV genotype 3a is the most predominant genotype in district Mardan. The state of the art preventive and therapeutic strategies should be implemented to control the spread of HCV infections. Further temporal studies involving different geographical areas of Pakistan, are required to improve the control measures for HCV infection.

Molecular Epidemiology and Interferon Susceptibility of the Natural Recombinant Hepatitis C Virus Strain RF1_2k/1b

Hepatitis C virus (HCV) genotype is an important determinant of virological response to antiviral therapies. Currently, there are no data available on the molecular epidemiology and interferon susceptibility of the natural intergenotypic recombinant RF1_2k/1b (RF1) strain. Genotyping and RF1-PCR screening were performed on samples from 604 HCV RNA-positive individuals from 7 countries. uPA/SCID mice carrying human hepatocytes (chimeric mice) were infected with the RF1_2k/1b strain, and the susceptibility of the strain to interferon and ribavirin was compared with the susceptibilities of 2 different strains of genotype B, used as references. Six new RF1 cases were identified in this study; 5 (2%) of 281 in Russia and 1 (1%) of 90 in Uzbekistan. Phylogenetic analyses based on Core/E1 and NS5b indicated that all RF1 representatives share a common evolutionary ancestor. Infection with RF1 was established in chimeric mice. Reduction of RF1 viral load was observed in response to 3 injections of 3 microg/kg pegylated-interferon alpha-2a alone or in combination with 50 mg/kg of ribavirin (0.5 or 1.4 log-copies/mL). All identified RF1-type strains appear to be introduced from a single source, suggesting that intergenotypic recombination in HCV is sporadic and not associated with cocirculation of different genotypes in a population. The RF1 strain in this study was responsive to interferon in vivo.

Interleukin-10 or tumor necrosis factor-α polymorphisms and the natural course of hepatitis C virus infection in a hyperendemic area of Japan

We investigated the effects of polymorphisms in interleukin (IL)-10 and tumor necrosis factor (TNF)-α on the natural course of hepatitis C virus (HCV) infection in a community-based population in Japan. A total of 460 anti-HCV antibody seropositive individuals were classified into two groups, those who were positive or negative for HCV RNA. In HCV RNA-positive individuals with at least four annual alanine aminotransferase (ALT) measurements taken between 1993 and 2003, 74 exhibited persistently normal ALT levels, while 211 had one or more elevated ALT level tests. We examined the relationships between polymorphisms in the genes encoding IL-10 (−1082, −819, −592) or TNF-α (−308, −238) and HCV clearance, ALT abnormalities, or serum level of type IV collagen 7S, a marker of hepatic fibrosis. These polymorphisms were equally distributed among the patient subgroups with differential HCV RNA clearances or ALT abnormalities. Serum levels of type IV collagen 7S, however, were significantly higher in individuals with an A at position −238 or −308 in the TNF-α gene promoter than in individuals lacking these polymorphisms. We conclude that, while the relationships between inherited variations in IL-10 or TNF-α expression are not associated with alterations in HCV clearance or ALT levels, TNF-α polymorphisms may be associated with hepatic fibrosis.

Undiagnosed hepatitis C virus infection in hemodialysis patients: Value of HCV RNA and liver enzyme levels

At present, routine screening for hepatitis C virus (HCV) infection is based on the detection of antiviral antibodies. Underdiagnosis of HCV infection by using HCV antibody tests, however, still occurs. Additional diagnostic means are provided by the polymerase chain reaction (PCR). The measurement of aminotransferase (ASAT and ALAT) has served as an auxiliary, less specific test. The present research aimed to design practical and low cost strategies to diminish underdiagnosis of HCV infection in dialysis patients. With this purpose in mind, we examined whether aminotransferases values in HCV antibody-negative patients could be related to undiagnosed HCV infection, by using HCV RNA testing by PCR as the gold standard. In 112 hemodialysis patients, we found 78 negative and 34 positive for HCV antibodies. A major finding was that 222 (28.2%) out of the 78 HCV antibodies-negative patients had positive HCV RNA by PCR. In repeated samples taken at six months follow-up from 19 out of these 22 patients, only one of them was positive for anti-HCV antibodies; moreover, a positive HCV RNA by PCR was confirmed in 13 (68.5%) of them. Within the HCV antibody-negative group, the mean values of ASAT, ALAT and gammaglutamiltransferase were higher (P < 0.001, P < 0.001 and P < 0.02, respectively) in the HCV PCR-positive versus the HCV PCR-negative patients. No significant differences were found in the liver enzyme values between the HCV antibody-negative, HCV RNA positive and the HCV antibody positive, HCV RNA positive individuals. Histological samples from two HCV RNA positive, HCV antibody-negative patients disclosed the presence of a mild liver disease. In conclusion, the present study demonstrates the critical importance of HCV RNA determination by PCR in hemodialysis patients who have no detectable circulating antibodies against the HCV. Furthermore, in conditions in which PCR technology is not readily available, we have established that the existence of a moderate increase of aminotransferases is a helpful clue to detect patients with absent HCV antibodies, and might represent an useful, low cost tool for HCV screening in dialysis patients.