Course Of Hepatitis C Virus Infection Research Articles

Hepatitis-C during Pregnancy: Antenatal period challenges, management and the way forward.

Pregnant women and the general public are both directly impacted by cirrhosis which is a chronic liver disease. It is also widely known that women who have a history of injectable drug use and cirrhosis are more prone to experience unfavorable consequences that have a negative impact on the health of both the mother and the unborn child. Higher maternal Hepatitis-C Virus (HCV) in pregnancy viral load, length of labor, use of amniocentesis or fetal scalp monitoring and protracted membrane rupture are all the risk of perinatal transmission of HCV in newborns. Globally, a large number of childbearing-age women become affected by HCV every year and vertical transmission of HCV is still a serious public health concern. Pregnancy-related immune alterations have a significant impact on the course of HCV infection throughout the third trimester and provide favorable circumstances for the spread of the virus. The exacerbation of hepatic damage during pregnancy and the postpartum period is mostly responsible for HCV-specific cell-mediated immune responses. An extensive literature search done via electronic search engine including Cochrane library databases, PubMed, Google Scholar, Science Direct and HCV in pregnancy articles were included.

Hepatitis C and Human Pegivirus Coinfection in Patients with Chronic Hepatitis C from the Brazilian Amazon Region: Prevalence, Genotypes and Clinical Data.

Coinfection of HPgV-1 with hepatitis C virus (HCV) is common due to shared modes of transmission, with a prevalence of HPgV-1 viremia of approximately 20% among individuals with chronic HCV infection. The aim of the present study was to estimate the prevalence of HPgV-1 RNA and circulating genotypes in patients with hepatitis C from a health service located in the city of Belém, in the state of Pará, Northern Brazil. A total of 147 samples were included in the study from February to December 2019. Among the participants, 72.1% (106/147) were monoinfected with HCV, with detectable HCV viral RNA, and 27.9% (41/147) were coinfected with HCV/HPgV-1. The most frequently found genotypes were HPgV-1 genotypes 1 and 2 (36.6% and 63.4%), respectively. While for HCV there was a predominance of genotypes 1 and 3 (58.5% and 41.5%). No significant differences were found when comparing any risk, sociodemographic, or clinical factors between groups. Also, there was no statistically significant difference when relating the viral genotypes of both agents. This study indicated that the prevalence of infection by HPgV-1 is high in HCV carriers in Belém, Pará, and probably does not change the clinical course of HCV infection, however, further studies are still needed.

Prevalence of hepatitis C virus infection among men who have sex with men with human immunodeficiency virus-1 infection between 2010 and 2020 in Japan: A single-center retrospective cohort study

IntroductionThe high prevalence of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) is an important health issue. The purpose of this study is to investigate the actual prevalence of HCV infection among HIV-positive MSM in Japan. MethodsThis study is a single-center retrospective cohort study. We collected data of HIV-infected MSM who visited our hospital from January 2010 to December 2020, and evaluated HCV prevalence, course of HCV infection, and direct-acting antiviral (DAA) treatment efficacy in HIV-infected MSM. ResultsOverall, 1135 HIV-infected MSM had HCV antibody (Ab) tests during the observation period. The first anti-HCV Ab positive rate in HIV-infected MSM was 4% (45/1135), and the seroconversion rate of HCV antibody was 3.6% (39/1090). Treponema pallidum hemagglutination antigen positivity (odds ratio [OR], 5.28; 95% confidence interval [CI], 2.9 to 10.5) and intravenous drug injection (OR, 19; 95% CI, 3.4 to 149) were identified as factors associated with HCV Ab positivity. Spontaneous elimination of HCV infection was observed in 17.9% (7/39) of patients. DAA treatment was performed in 43 cases, and the overall sustained virologic response 12 (SVR12) rate for DAA treatment was 93% (40/43). ConclusionA high HCV infection rate among HIV-infected MSM was observed in Japan. The DAA treatment response rate in patients with HIV/HCV co-infection was the high response rate.

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.

Biomarkers in HCV-related mixed cryoglobulinemia patients withnon-Hodgkin lymphoma.

Chronic Hepatitis C virus (HCV) infection can cause severe extrahepatic manifestations, such as mixed cryoglobulins (MC), up to the development of B cell nonHodgkin's lymphoma (B-NHL). Mechanisms transforming of HCV infection into lymphoproliferative and/or autoimmune disorders are still poorly understood. In course of HCV infection, the sustained virus-driven antigenic stimulation may probably induce a B-cell clonal expansion. Measurements of serum free light chains (FLCs) levels, considered as a direct marker of B cell activity, are analyzed with increasing interest in clinical practice, for diagnosis, monitoring and follow-up of plasma cell dyscrasia. Syndecan-1 (CD138) is a transmembrane heparan sulfate proteoglycan expressed and actively shed by most myeloma cells. Membrane CD138 represents the major receptor protein for HCV attachment to the hepatocyte surface and high levels of circulating sCD138 levels are detected in patients at early stage of B-cell chronic lymphocytic leukemia. This study is aimed to evaluate sCD138 and FLC levels as diagnostic biomarkers of HCV-related MC with B-NHL. We enrolled 35 HCV-MC-NHL patients, characterized for the specific type of cryoglobulins, and 25 healthy blood donors (HBD) as negative control. Serum sCD138 levels were determined using ELISA kits specific for human sCD138. Serum FLCs were assessed by means of the turbidimetric assay. We found that serum levels of sCD138, as well as FLCs, were significantly higher in patients than in HBD (p<0.001). In agreement with the definition of HCV-driven lymphoproliferative disorders as the consequence of a multifactorial and multistep pathogenetic process, we suggest that sCD138 and FLCs could be considered putative independent markers of worsening progression of the disease.

Determination of HCV genotypes and viral loads in chronic hepatic Sudanese infected patients

Background. Knowledge of Hepatitis C virus (HCV) genotypes is significant for arranging treatment regimes. Quantitative HCV RNA testing provides prognostic data useful in monitoring the efficacy of antiviral therapy.&#x0D; Methods. A total of 1203 serum samples were collected from individuals attending out-patients units at Khartoum State and Gezera State. The study population comprises two groups. Blood donors study groups (n= 600) and chronic hepatic patients during the course of HCV infection (n= 603). Serum samples were screened using enzyme linked immune-sorbent assay (ELISA) (Biokit, A.S. Spain®).HCV positive samples (n=100) were quantified by HCV Real-TM Quant SC (Sacace Biotechnologies Italy®).&#x0D; Results: Hundred HCV seropositive samples were subjected to genotyping and quantitative analysis of these samples using RT- PCR, HCV genotype 4 was the predominant genotype (92%) followed by genotype 2 (4%), Genotype 1 (2%) and 3 (2%) in different groups. The average viral load of the patients infected with genotype 4 was higher than an average viral load of the patients infected with genotypes 1,2 and 3.&#x0D; Conclusions: The present study highlighted that genotype 4 is the predominant genotype in Sudanese hepatic patients followed by genotype 2. The severity of liver disease was more among genotype 4 patients as assessed by a higher viral load.

The course of elderly patients with persistent hepatitis C virus infection without hepatocellular carcinoma.

Little is known about the course of elderly patients with persistent hepatitis C virus (HCV) infection. We investigated the course of HCV infection in this patient population. Among 9,126 HCV antibody-positive patients who visited our hospital between 1995 and 2015, there were 453 patients with continuous follow-up who survived to age 80. They were included in the study following the inclusion criteria: confirmed persistent detection of HCV RNA, no HCV eradication if anti-HCV therapy occurred before enrollment, and no development of hepatocellular carcinoma (HCC) before enrollment. For all study patients, baseline was defined as the date when they turned 80. Mortality rates after the age of 80years and cause of death were analyzed. During the study period, 155 patients (34.2%) died. Median survival time (MST) after age 80 was 8.8years, which was comparable to that of the general population (10.1years). Among 155 deceased patients, the majority (115 patients, 74.2%) died due to non-liver-related disease, followed by HCC (28 patients, 18.1%) and liver-related disease other than HCC (12 patients, 7.7%). Patients with advanced liver fibrosis (FIB-4 index > 3.25, n = 245) had shorter MST than patients with mild liver fibrosis (FIB-4 index ≤ 3.25, n = 208) (7.1 vs. 10.2years; p = 0.020) due to a higher mortality rate from liver-related complications, including HCC. Most elderly HCV patients die from non-liver-related disease, especially those with less advanced liver fibrosis.

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.

Determination of HCV Genotypes and Viral Loads in Chronic Hepatic Sudanese infected Patients

Background. Knowledge of Hepatitis C virus (HCV) genotypes is significant for arranging treatment regimes. Quantitative HCV RNA testing provides prognostic data useful in monitoring the efficacy of antiviral therapy. Methods. A total of 1203 serum samples were collected from individuals attending out-patients units at Khartoum State and Gezera State. The study population comprises two groups. Blood donors study groups (n= 600) and chronic hepatic patients during the course of HCV infection (n= 603). Serum samples were screened using enzyme linked immune-sorbent assay (ELISA) (Biokit, A.S. Spain®).HCV positive samples (n=100) were quantified by HCV Real-TM Quant SC (Sacace Biotechnologies Italy®). Results: Hundred HCV seropositive samples were subjected to genotyping and quantitative analysis of these samples using RT- PCR, HCV genotype 4 was the predominant genotype (92%) followed by genotype 2 (4%), Genotype 1 (2%) and 3 (2%) in different groups. The average viral load of the patients infected with genotype 4 was higher than an average viral load of the patients infected with genotypes 1,2 and 3. Conclusions: The present study highlighted that genotype 4 is the predominant genotype in Sudanese hepatic patients followed by genotype 2. The severity of liver disease was more among genotype 4 patients as assessed by a higher viral load.

Hepatitis C in Pregnant Women and Their Children.

Hepatitis C virus (HCV) infection presents unique challenges in the setting of pregnancy. HCV can contribute to pregnancy-related morbidity and pregnancy can influence the course of HCV infection. There is a significant risk of transmission to the fetus and newborn infant. Identification of HCV infection in women of childbearing potential and those who are currently pregnant offers important opportunities for the woman and for past, present and future children.

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.

METHODS OF TRANSMISSION AND FEATURES OF THE COURSE OF HEPATITIS C VIRUS INFECTION IN CHILDREN: MEDICAL AND SOCIAL ASPECTS

Introduction: Hepatitis C virus (HCV) infection is a major global problem. According to WHO, 150-200 million people globally have hepatitis C infection. Even though HCV infection morbidity rate in children is relatively low in comparison with the adult population, approximately 5 million children in the world have active HCV. There is a number of differences between HCV infection in adults and in children. However, the data pertaining to this issue is controversial. The aim: Research, analysis and synthesis of information from contemporary literature on transmission of infection and characteristics of the course of HCV infection in children. Materials and methods: Analysis and synthesis of information from contemporary literature on transmission of infection and characteristics of the course of HCV infection in children were conducted. Conclusions: Information from literature of the latest years on peculiarities of infection, disease course and complications of HCV infection in children was analyzed and summarized in this article.

Serological profile of asymptomatic HCV positive patients with low level of cryoglobulins.

Clinical spectrum of hepatitis C virus (HCV)-related cryoglobulinemia varies from an asymptomatic presentation to severe vasculitis and lymphoma. A recent study in HCV-negative patients suggests that low cryoglobulins (CGs) levels are responsible for severe renal and neurological complications. The aim of this study was to identify a panel of serological biomarkers associated with low levels of CGs in HCV-positive patients. We studied a population of 79 untreated patients with chronic HCV infection: 13 naïve patients without CGs; 28 patients with asymptomatic mixed cryoglobulinemia (MC) and low levels of CGs (16/28 with polyclonal type III and 12/28 with microheterogeneous type III CGs); 38 patients with symptomatic MC and high levels of type II CGs. Serum samples were collected and examined for rheumatoid factor (RF) IgG and IgM, free light chains (FLCs) and C3 and C4 complement components. We found that RF-IgG and IgM, free k chains and k+λ were increased while C4 component was reduced, both in symptomatic and asymptomatic patients. Our results suggest that, even in absence of MC symptoms, the low levels of CGs may represent a trigger of activation for immune system in course of HCV infection. The identification of a correlated biomarkers panel could improve the clinical management of these patients and pave the way for target treatment strategies. © 2018 BioFactors, 45(3):318-325, 2019.

Relationship between antibodies to hepatitis C virus core+1 protein and treatment outcome.

BackgroundIt has been suggested that hepatitis C virus (HCV) core+1 protein plays a crucial role in the viral life cycle, potentially affecting liver cirrhosis and the development of hepatocellular carcinoma.MethodsTo investigate its relationship with the outcome of HCV standard combination therapy with peginterferon-α plus ribavirin, we screened 139 consecutive HCV patients (119 with chronic HCV infection and 20 who spontaneously cleared HCV) for the presence of anti-core+1 antibodies (Abs). In addition, liver fibrosis was determined by FibroScan in all but one patients.ResultsTwenty-nine patients were cirrhotic (stiffness >12.5 kPa, F4 METAVIR), all of them with mild liver cirrhosis (Child-Pugh score A). Eighty-six of 139 patients were treatment-experienced with standard combination therapy. Fifty of them had achieved a sustained virological response, while 36 were non-responders. The prevalence of anti-core+1 Abs in patients with chronic HCV infection was 22.69% (27/119 patients): 18% (9/50 patients) in responders and 36.11% (13/36 patients) in non-responders (P=0.050). Five (17.24%) of the 29 cirrhotic patients and 22 (24.72%) of the 89 non-cirrhotic patients were positive for anti-core+1 Abs (P=0.405). Furthermore, the presence of anti-core+1 Abs correlated with the poor response interleukin (IL) 28B genotype TT (P=0.040). No correlation between spontaneous clearance and anti-core+1 Abs was observed (P=0.088).ConclusionThe presence of anti-core+1 Abs might be correlated with the poor response IL28B TT genotype and may negatively affect the outcome of standard combination treatments in HCV patients, suggesting that core+1 may play a biological role in the course of HCV infection.

Negative Correlation Between Hepatitis C Virus (HCV) and Let-7 MicroRNA Family in Transplanted Livers: The Role of rs868 Single-Nucleotide Polymorphism

BackgroundGenetic alterations of TGF-β pathway members, including its transmembrane receptor, TGFBR1, may influence the course of HCV infection. Rs868 is a single-nucleotide polymorphism of the 3′UTR region of TGFBR1, located in a binding site for the conserved let-7/miR98 microRNA family. Previously, we demonstrated a favorable course of hepatitis C recurrence after liver transplantation in rs868 AG genotype of the transplanted liver when compared to rs868 AA. The aim of the present study was to confirm the biological effect of rs868.Material/MethodsHepG2 cell line was transfected with luciferase vectors cloned with 3′UTR of TGFBR1 gene encompassing different rs868 alleles. Post-transplant liver biopsies from 61 patients with HCV-related end-stage liver disease were evaluated histopathologically and analyzed for the expression of TGFBR1 mRNA, let-7/miR98 microRNAs, HCV RNA load, and rs868 genotype.ResultsLuciferase expression was significantly lower in the A allele-containing vector. TGFBR1 mRNA and HCV RNA load were correlated negatively with let-7/miR98 microRNAs and this correlation was significantly stronger for rs868 AG compared to AA genotype. A strong positive correlation was demonstrated between TGFBR1 and HCV in both genotypes. In AG heterozygotes, let-7/miR98 microRNAs showed a strong negative correlation with periportal or periseptal interface hepatitis (Ishak A score).ConclusionsThere is a negative correlation between let-7/miR98 microRNAs and HCV viral load and TGFBR1 mRNA after liver transplantation. In the rs868 AG heterozygotes, this correlation was stronger and there was a negative correlation between let-7/miR98 and Ishak A score, which is in concordance with the previously demonstrated protective role of this genotype in post-transplant hepatitis C recurrence.

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.

Scavenger receptor class B member 1 (SCARB1) variants modulate hepatitis C virus replication cycle and viral load

There are numerous coding and non-coding variants in the SCARB1 gene that encodes scavenger receptor class B member 1 (SR-BI), a key receptor for both high density lipoproteins and hepatitis C virus (HCV). Many have been linked to clinical phenotypes, yet their impact on the HCV replication cycle is incompletely understood. The aim of this study was to analyze the impact of these variants on the molecular biology and clinical course of HCV. We analyzed key coding non-synonymous as well as non-coding SCARB1 variants using virological in vitro and human genetics approaches. Non-synonymous variants: S112F and T175A have greatly reduced HCV receptor function. When present on the cell surface, these variants are impaired in their ability to interact with HCV E2. Non-coding variants: The G allele in rs3782287 is associated with decreased viral load. Haplotype analysis confirmed these findings and identified haplotype rs3782287 A/rs5888 C as a risk allele associated with increased viral load. We also detected a trend towards lower hepatic SR-BI expression in individuals with the rs3782287 GG genotype associated with low viral load suggesting a potential underlying mechanism. Coding and non-coding genetic SCARB1 variants modulate the HCV replication cycle and possibly clinical features of hepatitis C. These findings underscore the relevance of SR-BI as an HCV receptor and contribute to our understanding of inter-individual variation in HCV infection. The cell surface receptor SR-BI (scavenger receptor class B member 1), is essential for hepatitis C virus (HCV) entry into hepatocytes. Variations in the gene coding this receptor influence infectivity and viral load. We analyzed these variations to gain a better understanding of inter-individual differences over the course of HCV infection.

The impact of the recipient and donor interferon lambda-3 polymorphism on the course of HCV infection following liver transplantation.

Aim of the studyAim of the study was to assess the impact of the recipient and donor interferon lambda-3 (IFNL3) single-nucleotide polymorphisms (SNPs) rs12979860 and rs8099917 on the course of hepatitis C virus (HCV) reinfection following liver transplantation.Material and methodsThe study involved 141 subjects after liver transplantation for HCV-induced cirrhosis, performed between 2000 and 2015. It assessed the impact of both SNPs on the outcomes of interferon/ribavirin (IFN/RBV) treatment following transplantation, HCV viral load, laboratory test results, histological lesions in the liver graft, the risk of acute rejection, and the development of hepatocellular carcinoma (HCC) in patient’s own liver.ResultsIn the case of rs12979860, SVR was achieved in 58.8% of recipients with the CC genotype, and only 12% of recipients with the TT genotype (p = 0.016). Recipients with the rs12979860 CC variant had lower viral load and lower alanine transaminase (ALT) activity than recipients with a non-CC variant. Opposite effects were demonstrated in the analysis of the donors’ genotype. Recipients with the unfavorable variants (rs12979860 TT and rs8099917 GG) had a lower risk of graft rejection and tended to have a higher risk of developing HCC in their own liver.ConclusionsThe IFNL3 rs12979860 polymorphism may be considered a predictor for IFN/RBV effectiveness following liver transplantation. The course of HCV reinfection following liver transplantation may be more aggressive if an unfavorable variant in the recipient coexists with a promising variant in the donor. Particularly careful monitoring for HCC in recipients with unfavorable IFNL3 variants is warranted.

Impact of HIV infection in patients infected with chronic HCV (genotypes 1a and 3a): virological and clinical changes

Background: Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection has become a serious public health problem. The influence of HIV/HCV coinfection on plasma HCV RNA loads and clinical criteria which are usually regarded as a predictor of the progress of liver disease have not been reliably evaluated.Objectives: This study investigated the impact of HIV infection on HCV RNA load and clinical indexes in Yazd and Tehran.Materials and methods: HCV/HIV-coinfected patients and HCV-monoinfected controls were examined and compared for plasma HCV RNA and related risk factors such as HCV genotypes, liver enzymes, and transmission routes.Results: A total of 54 HCV/HIV-coinfected patients and 88 HCV-monoinfected controls were studied. The HCV RNA load mean was significantly higher in HCV/HIV-coinfected patients than in HCV-monoinfected patients (p < 0.001). HCV RNA load mean in patients infected with HCV without anti-HCV therapy was lower than HIV/HCV patients with and without highly active antiretroviral therapy that this difference was significant (p < 0.001). The HCV RNA levels were significantly higher in HIV/HCV genotype 3a coinfected patients than in genotype 3a monoinfected patients (p < 0.001). HIV RNA levels were lower in genotype 1a infected patients than in genotype 3a infected patients, but this difference was not significant statistically. The ALT mean levels were significantly higher in genotype 3a HIV/HCV-coinfected patients than in genotype 3a HCV-monoinfected patients (p < 0.001).Conclusions: HIV/HCV coinfection leads to a significant increase in plasma HCV RNA. Further evaluations of the effects of ART and HIV infection on the course of HCV infection and the response to treatment against HCV infection in other and different genotypes are also needed. Moreover, HIV-infected patients should be screened regularly for HCV coinfection, particularly if they are in high-risk groups such as IDUs and recipients of blood transfusions.