Hepatitis C Virus Subtypes 1a Research Articles

Distribution pattern, molecular transmission networks, and phylodynamic of hepatitis C virus in China.

In China, few molecular epidemiological data on hepatitis C virus (HCV) are available and all previous studies were limited by small sample sizes or specific population characteristics. Here, we report characterization of the epidemic history and transmission dynamics of HCV strains in China. We included HCV sequences of individuals belonging to three HCV surveillance programs: 1) patients diagnosed with HIV infection at the Beijing HIV laboratory network, most of whom were people who inject drugs and former paid blood donors, 2) men who have sex with men, and 3) the general population. We also used publicly available HCV sequences sampled in China in our study. In total, we obtained 1,603 Ns5b and 865 C/E2 sequences from 1,811 individuals. The most common HCV strains were subtypes 1b (29.1%), 3b (25.5%) and 3a (15.1%). In transmission network analysis, factors independently associated with clustering included the region (OR: 0.37, 95% CI: 0.19-0.71), infection subtype (OR: 0.23, 95% CI: 0.1-0.52), and sampling period (OR: 0.43, 95% CI: 0.27-0.68). The history of the major HCV subtypes was complex, which coincided with some important sociomedical events in China. Of note, five of eight HCV subtype (1a, 1b, 2a, 3a, and 3b), which constituted 81.8% HCV strains genotyped in our study, showed a tendency towards decline in the effective population size during the past decade until present, which is a good omen for the goal of eliminating HCV by 2030 in China.

Epidemiological and molecular characterization of HBV and HCV infections in HIV-1-infected inmate population in Italy: a 2017–2019 multicenter cross-sectional study

HBV/HCV co-infection is common in HIV-1-infected prisoners. To investigate the characteristics of HIV co-infections, and to evaluate the molecular heterogeneity of HIV, HBV and HCV in prisoners, we carried-out a multicenter cross-sectional study, including 65 HIV-1-infected inmates enrolled in 5 Italian detention centers during the period 2017–2019. HIV-1 subtyping showed that 77.1% of inmates were infected with B subtype and 22.9% with non-B subtypes. Italian nationals were all infected with subtype B (93.1%), except two individuals, one infected with the recombinant form CRF72_BF1, and the other with the HIV-1 sub-subtype A6, both previously not identified in inmates of Italian nationality. Non-Italian nationals were infected with subtype B (52.6%), CRFs (36.8%) and sub-subtypes A1 and A3 (5.2%). HIV variants carrying resistance mutations to NRTI, NNRTI, PI and InSTI were found in 7 inmates, 4 of which were never exposed to the relevant classes of drugs associated with these mutations. HBV and/or HCV co-infections markers were found in 49/65 (75.4%) inmates, while 27/65 (41.5%) showed markers of both HBV and HCV coinfection. Further, Italian nationals showed a significant higher presence of HCV markers as compared to non-Italian nationals (p = 0.0001). Finally, HCV phylogenetic analysis performed in 18 inmates revealed the presence of HCV subtypes 1a, 3a, 4d (66.6%, 16.7% and 16.7%, respectively). Our data suggest the need to monitor HIV, HBV and HCV infections in prisons in order to prevent spreading of these viruses both in jails and in the general population, and to implement effective public health programs that limit the circulation of different genetic forms as well as of viral variants with mutations conferring resistance to treatment.

Retreatment of patients with chronic hepatitis C, subtype 3a, and cirrhosis, who previously failed a regimen containing NS5A inhibitors with sofosbuvir/velpatasvir plus ribavirin for 24 weeks

Background & Aims The use of direct acting antiviral agents (DAAs) in patients with chronic HCV genotype (GT) 3a infection results in sustained virologic response (SVR) rates of 93–98%, but 5–8% of patients experience virologic failure. Methods. We observed 48 patients infected with HCV subtype 3a who failed previous treatment with DAAs, including 43 subjects (89.6%) with liver cirrhosis. Thirty-seven (77%) subjects previously received NS5A inhibitors of the first generation (daclatasvir) and 11 subjects (23%) – of the second generation (velpatasvir). All patients received retreatment with sofosbuvir (SOF)/ velpatasvir (VEL) and ribavirin (RBV) for 24 weeks. We compared SVR12 rates depending on fibrosis stage, presence of NS5A mutation (L31M or A30K and Y93H), and on the generation of previously used NS5A inhibitors. Results. Observed SVR12 rate were: 83,3% (40/48 patients) overall; 100% in patients without cirrhosis (n=5) vs 81,4% (n=35) in those with cirrhosis (n=43) (P=0,01); 86,7% (n=13) with single L31M or A30K(n=15) vs 77,8% (n=21) with Y93H mutation (n=27) (P=0,46), 86,5% (n=32) in patients who previously failed first generation (n=37) vs 72,7% (n=8) in those who failed second generation NS5A inhibitors (n=11) (P=0,35). Conclusions. Retreatment with SOF/VEL+RBV was highly effective and safe in patients with chronic HCV GT3a infection, including those with liver cirrhosis, who previously failed DAA containing NS5A inhibitors. Presence of NS5A RASs L31M, A30K, and Y93H at the baseline, as well as the generation of previously used NS5A inhibitors did not impact SVR12 rates.

Phylogenetic tree of NS5A gene of hepatitis C virus from infected Iraqi patients

Hepatitis C is a liver illness caused by the hepatitis C virus (HCV). Acute and chronic hepatitis can be caused by the virus. Hepatitis C infection affects an estimated 71 million people worldwide. Two hundred blood samples were collected (128 males and 72 females), ranged in age from 4 to 80 years and diagnosed through a rapid test and the real time-PCR from the teaching medical city hospital in Baghdad from October 2018 until April 2019. The results showed that 89 samples were positive for HCV by serological tests, and other samples are not. Also, the most frequent age of infection of HCV was between 51 and 80 years. In all samples, the partial region of the NS5A gene was successfully amplified and sequenced. PCR-sequencing revealed three subtyping were; subtype 1a, 1b, and 4a. Phylogenetic analysis revealed subtype concordance of 99 % with a bootstrap hepatitis C virus subtype 1b isolate AASN1 Iraq (ID:MT554101.1). The clusters including HCV subtype 1a isolate AASN20 Iraq (ID:MT554100.1) the identical 96 %, and the clusters including HCV subtype 4a isolate AASN35 Iraq (ID:MT554099.1) the identical 99%.

Molecular and spatial epidemiology of HCV among people who inject drugs in Boston, Massachusetts.

Integration of genetic, social network, and spatial data has the potential to improve understanding of transmission dynamics in established HCV epidemics. Sequence data were analyzed from 63 viremic people who inject drugs recruited in the Boston area through chain referral or time-location sampling. HCV subtype 1a was most prevalent (57.1%), followed by subtype 3a (33.9%). The phylogenetic distances between sequences were no shorter comparing individuals within versus across networks, nor by location or time of first injection. Social and spatial networks, while interesting, may be too ephemeral to inform transmission dynamics when the date and location of infection are indeterminate.

Patterns and correlates of hepatitis C virus phylogenetic clustering among people living with HIV in Australia in the direct-acting antiviral era: A molecular epidemiology study among participants in the CEASE cohort.

Background and AimsIn moving towards the elimination of hepatitis C virus (HCV) infection among people living with HIV, understanding HCV transmission patterns may provide insights to guide and evaluate interventions. In this study, we evaluated patterns of, and factors associated with HCV phylogenetic clustering among people living with HIV/HCV co‐infection in Australia in the direct‐acting antiviral era.MethodsHCV RNA was extracted from dried blood spot (DBS) samples collected between 2014 and 2018 in the CEASE cohort study. The HCV Core‐E2 region was amplified by a polymerase chain reaction and Sanger sequenced. Maximum likelihood phylogenetic trees (1000 bootstrap replicates) were used to identify patterns of clustering (3% genetic distance threshold). Mixed‐effects logistic regression was used to determine correlates of phylogenetic clustering. Factors assessed were sexual risk behavior, education, injecting drug use, housing, employment, HIV viral load, age, sex, and sexuality.ResultsPhylogenetic trees were reconstructed for HCV subtype 1a (n = 139) and 3a (n = 63) sequences, with 29% (58/202) in a pair or cluster. Overall (n = 202), phylogenetic clustering was positively associated with younger age (under 40; adjusted odds ratio [aOR] 2.52, 95% confidence interval [CI] 1.20–5.29), and among gay and bisexual men (n = 168), was positively associated with younger age (aOR 2.61, 95% CI 1.10–6.19), higher education (aOR 2.58, 95% CI 1.09–6.13), and reporting high‐risk sexual behavior (aOR 3.94, 95% CI 1.31–11.84). During follow‐up, five reinfections were observed, but none were in phylogenetic clusters.ConclusionThis study found a high proportion of phylogenetic relatedness, predominantly among younger people and gay and bisexual men reporting high‐risk sexual behavior. Despite this, few reinfections were observed, and reinfections demonstrated little relationship with known clusters. These findings highlight the importance of rapid HCV treatment initiation, together with monitoring of the phylogeny.

Molecular Epidemiology and Baseline Resistance of Hepatitis C Virus to Direct Acting Antivirals in Croatia.

Molecular epidemiology of hepatitis C virus (HCV) is exceptionally complex due to the highly diverse HCV genome. Genetic diversity, transmission dynamics, and epidemic history of the most common HCV genotypes were inferred by population sequencing of the HCV NS3, NS5A, and NS5B region followed by phylogenetic and phylodynamic analysis. The results of this research suggest high overall prevalence of baseline NS3 resistance associate substitutions (RAS) (33.0%), moderate prevalence of NS5A RAS (13.7%), and low prevalence of nucleoside inhibitor NS5B RAS (8.3%). Prevalence of RAS significantly differed according to HCV genotype, with the highest prevalence of baseline resistance to NS3 inhibitors and NS5A inhibitors observed in HCV subtype 1a (68.8%) and subtype 1b (21.3%), respectively. Phylogenetic tree reconstructions showed two distinct clades within the subtype 1a, clade I (62.4%) and clade II (37.6%). NS3 RAS were preferentially associated with clade I. Phylogenetic analysis demonstrated that 27 (9.0%) HCV sequences had a presumed epidemiological link with another sequence and classified into 13 transmission pairs or clusters which were predominantly comprised of subtype 3a viruses and commonly detected among intravenous drug users (IDU). Phylodynamic analyses highlighted an exponential increase in subtype 1a and 3a effective population size in the late 20th century, which is a period associated with an explosive increase in the number of IDU in Croatia.

The Transmission Route and Selection Pressure in HCV Subtype 3a and 3b Chinese Infections: Evolutionary Kinetics and Selective Force Analysis.

Hepatitis C virus (HCV) genotype 3 (GT-3) represents 22–30% of all infections and is the second most common genotype among all HCV genotypes. It has two main subtypes, GT-3a and GT-3b, that present epidemiological differences in transmission groups. This report generated 56 GT-3a and 64 GT-3b whole-genome sequences to conduct an evolutionary kinetics and selective force analysis with reference sequences from various countries. Evolutionary analysis showed that HCV GT-3a worldwide might have been transmitted from the Indian subcontinent to South Asia, Europe, North America and then become endemic in China. In China, GT-3a may have been transmitted by intravenous drug users (IDUs) and become endemic in the general population, while GT-3b may have originated from IDUs and then underwent mutual transmission between blood donors (BDs) and IDUs, ultimately becoming independently endemic in IDUs. Furthermore, the spread of GT-3a and GT-3b sequences from BD and IDU populations exhibit different selective pressures: the proportion of positively selected sites (PPSs) in E1 and E2 from IDUs was higher than in BDs. The number of positive selection sites was higher in GT-3b and IDUs. These results indicate that different selective constraints act along with the GT-3a and GT-3b genomes from IDUs and BDs. In addition, GT-3a and GT-3b have different transmission routes in China, which allows us to formulate specific HCV prevention and control strategies in China.

Evolutionary modeling reveals enhanced mutational flexibility of HCV subtype 1b compared with 1a

SummaryHepatitis C virus (HCV) is a leading cause of liver-associated disease and liver cancer. Of the major HCV subtypes, patients infected with subtype 1b have been associated with having a higher risk of developing chronic infection and hepatocellular carcinoma. However, underlying reasons for this increased disease severity remain unknown. Here, we provide an evolutionary rationale, based on a comparative study of fitness landscape and in-host evolutionary models of the E2 glycoprotein of HCV subtypes 1a and 1b. Our analysis demonstrates that a higher chronicity rate of 1b may be attributed to lower fitness constraints, enabling 1b viruses to more easily escape antibody responses. More generally, our results suggest that differences in evolutionary constraints between HCV subtypes may be an important factor in mediating distinct disease outcomes. Our analysis also identifies antibodies that appear escape-resistant against both subtypes 1a and 1b, providing directions for designing HCV vaccines having cross-subtype protection.

Viral genome wide association study identifies novel hepatitis C virus polymorphisms associated with sofosbuvir treatment failure

Persistent hepatitis C virus (HCV) infection is a major cause of chronic liver disease, worldwide. With the development of direct-acting antivirals, treatment of chronically infected patients has become highly effective, although a subset of patients responds less well to therapy. Sofosbuvir is a common component of current de novo or salvage combination therapies, that targets the HCV NS5B polymerase. We use pre-treatment whole-genome sequences of HCV from 507 patients infected with HCV subtype 3a and treated with sofosbuvir containing regimens to detect viral polymorphisms associated with response to treatment. We find three common polymorphisms in non-targeted HCV NS2 and NS3 proteins are associated with reduced treatment response. These polymorphisms are enriched in post-treatment HCV sequences of patients unresponsive to treatment. They are also associated with lower reductions in viral load in the first week of therapy. Using in vitro short-term dose-response assays, these polymorphisms do not cause any reduction in sofosbuvir potency, suggesting an indirect mechanism of action in decreasing sofosbuvir efficacy. The identification of polymorphisms in NS2 and NS3 proteins associated with poor treatment outcomes emphasises the value of systematic genome-wide analyses of viruses in uncovering clinically relevant polymorphisms that impact treatment.

Consistency of spatial dynamics of HIV-1 and HCV among HIV-1/HCV coinfected drug users in China

BackgroundAs the transmission routes of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) are similar, previous studies based on separate research on HIV-1 and HCV assumed a similar transmission pattern. However, few studies have focused on the possible correlation of the spatial dynamics of HIV-1 and HCV among HIV-1/HCV coinfected patients.MethodsA total of 310 HIV-1/HCV coinfected drug users were recruited in Yingjiang and Kaiyuan prefectures, Yunnan Province, China. HIV-1 env, p17, pol and HCV C/E2, NS5B fragments were amplified and sequenced from serum samples. The genetic characteristics and spatial dynamics of HIV-1 and HCV were explored by phylogenetic, bootscanning, and phylogeographic analyses.ResultsAmong HIV-1/HCV coinfected drug users, eight HCV subtypes (1a, 1b, 3a, 3b, 6a, 6n, 6v, and 6u) and two HIV-1 subtypes (subtype B and subtype C), three HIV-1 circulating recombinant forms (CRF01_AE, CRF07_BC and CRF08_BC), and four unique recombinant forms (URF_BC, URF_01B, URF_01C and URF_01BC) were identified. HCV subtype 3b was the most predominant subtype in both Yingjiang and Kaiyuan prefectures. The dominant circulating HIV-1 subtypes for drug users among the two areas were CRF08_BC and URF_BC. Maximum clade credibility trees revealed that both HIV-1 and HCV were transmitted from Yingjiang to Kaiyuan.ConclusionsThe spatial dynamics of HIV-1 and HCV among HIV-1/HCV coinfected drug users seem to have high consistency, providing theoretical evidence for the prevention of HIV-1 and HCV simultaneously.

Prevalence of occult hepatitis C virus infection in beta-thalassemia major patients in Ahvaz, Iran.

Occult hepatitis C virus infection (OCI) is defined by the presence of HCV RNA in peripheral blood mononuclear cells (PBMCs) and liver tissue cells despite the absence of HCV RNA in plasma. Currently, OCI is classified into two types: seropositive OCI (anti-HCV positive and serum HCV RNA negative) and seronegative OCI (anti-HCV and serum HCV RNA negative). Beta-thalassemia is described as a blood disorder that decreases the synthesis of hemoglobin. Repeated blood transfusion is the standard treatment for patients with beta-thalassemia major (BTM), and this increases the risk of exposure to infectious agents. The aim of this study was to investigate the prevalence of OCI among BTM patients. Plasma and PBMCs were collected from 90 BTM patients who were referred to Shafa Hospital in the city of Ahvaz and were screened for HCV antibody using a commercial ELISA kit as the first step. Next, nested RT-PCR was performed on extracts of plasma and PBMCs. HCV RNA from positive PBMCs was sequenced, the sequences were aligned, and a phylogenetic tree was constructed to determine their relationship to reference sequences retrieved from the GenBank database. Seventy-nine out of 90 patients (87.8%) were negative for HCV Ab (seronegative), while 11 patients (12.2%) were seropositive. HCV RNA was found in PBMCs of four patients (66.7%) who were negative for HCV Ab (seronegative) and two patients (33.3%) who were positive for HCV Ab (seropositive). HCV RNA was not detected in plasma samples from these six patients. Six out of 90 BTM patients (6.7%) had OCI. HCV genotyping revealed that all six patients were infected with HCV subtype 3a. We found a high frequency of OCI in BTM patients, which warrants more attention, considering the importance of this infection. Further studies are needed to determine the actual prevalence of OCI in BTM patients in Iran.

Using host genetics to infer the global spread and evolutionary history of HCV subtype 3a.

Studies have shown that hepatitis C virus subtype 3a (HCV-3a) is likely to have been circulating in South Asia before its global spread. However, the time and route of this dissemination remain unclear. For the first time, we generated host and virus genome-wide data for more than 500 patients infected with HCV-3a from the UK, North America, Australia, and New Zealand. We used the host genomic data to infer the ancestry of the patients and used this information to investigate the epidemic history of HCV-3a. We observed that viruses from hosts of South Asian ancestry clustered together near the root of the tree, irrespective of the sampling country, and that they were more diverse than viruses from other host ancestries. We hypothesized that South Asian hosts are more likely to have been infected in South Asia and used the inferred host ancestries to distinguish between the location where the infection was acquired and where the sample was taken. Next, we inferred that three independent transmission events resulted in the spread of the virus from South Asia to the UK, North America, and Oceania. This initial spread happened during or soon after the end of World War II. This was subsequently followed by many independent transmissions between the UK, North America, and Oceania. Using both host and virus genomic information can be highly informative in studying the virus epidemic history, especially in the context of chronic infections where migration histories need to be accounted for.

Detection rate of specific antibodies to the HCV CORE+1 protein in “naive” cronically HCV-infected patients in depends on the stage of liver fibrosis and the HCV subtype

Objective: The goal of this study was to examine the prevalence of anti-core+1 in “naive” patients with chronic hepatitis C and different stages of liver fibrosis infected by HCV subtypes 1b and 3a.Materials and methods: A total of 86 “naive” patients (37 men and 49 women) with CHC observed in the Botkin infectious disease hospital in 2017, were included in this study. The average age was 50,7±2,7. Laboratory tests included ALT and bilirubin. In 53 patients, the fibrosis stage in the liver tissue was evaluated by the TE method using Fibroscan (Echosens, France). The presence of antibodies to the core+1 protein in blood serum samples was determined by the “inhouse” indirect ELISA method using synthetic peptides F10 and F13, which amino acid sequences correspond to the antigenic determinants of core+1 protein of the HCV subtypes 1b and 3a, respectively.Results: In total, anti-core + 1 were detected in 27 (31,4%) subjects. It has been shown that the detection rate of anticore+1 does not depend on the HCV subtype. The study has indicated no statistically significant dependence between the presence of anti-core+1 and biochemical activity es of the infectious process (ALT, bilirubin). Anti-core+1 were detected in patients with all stages of fibrosis, however, the detection rate of anti-core+1 was statistically higher in patients with stage F4 fibrosis than in patients without liver fibrosis.Conclusion: The obtained results suggest a possible role of the core+1 protein in the development of fibrosis. In the natural course of HCV infection, the detection of anti-core+1 can be considered as a prognostic marker for the progression of fibrosis in the liver tissue.

Effect of Baseline Resistance-Associated Substitutions on Thalassemia Patients with Chronic HCV Infection: A Two-Year Follow-Up.

BACKGROUND Direct-acting antivirals (DAAs) against hepatitis C virus (HCV) infection showed the presence of resistant-associated substitutions (RASs). The aim of the present study was to carry out a follow-up of patients with baseline RASs to report the impact of RASs on DAA therapy outcome.METHODS In a cohort study, we analyzed NS5A and NS5B RASs among nine thalassemia cases by baseline RASs. In a 2-year follow-up, we analyzed viral markers and biochemical and hematological parameters of the participants and their sustained virologic response (SVR). Statistical analyses were performed using SPSS software version 22.RESULTS RASs for HCV subtype 1a included M28V, L31M, and H58P. For subtype 1b: L28M, R30Q, S24F, and C316N. And for subtype 3a: C316S, and S24F. In patients with cirrhosis (n = 5), ALT (p = 0.001) and AST (p = 0.007) levels were significantly reduced after treatment, and creatinine level slightly increased (p = 0.025). However, no significant data was observed in non-cirrhotic patients following the treatment. CONCLUSION The present study did not show any adverse effects of DAA therapy among patients with thalassemia suffering from chronic HCV infection with baseline RASs. Furthermore, reduction in ferritin and liver stiffness levels after DAA therapy could show the efficacy of DAA in such patients.

The incidence of resistance-associated variants to NS5A in HCV subtypes 1a and 1b in Taiwan

BackgroundResistance-associated variants (RAVs) to direct-antiviral agents (DAAs) may hamper treatment. There was a lack of data on the natural prevalence of RAVs in Taiwanese HCV-infected patients. We investigated the real-life presence of RAVs in the nonstructural 5A (NS5A) region in HCV genotype 1a and 1b in chronically infected individuals in Taiwan. MethodsIn this single-center cohort study, nested polymerase chain reaction and direct sequencing analysis was used to determine the frequency of RAVs in the HCV NS5A region in patients with HCV genotype 1a (n = 55) and 1b (n = 525). ResultsIn genotype 1a strains, the incidence of RAVs was 16.4% (9/55) in the NS5A region (M28V/T, n = 6, 10.9%; Q30L, n = 1, 1.8%; Y93N/H, n = 3, 5.5%). In genotype 1b, the incidence of RAVs was 17.5% (92/525) in the NS5A region (L31I/M/V, n = 7, 1.3%; Y93 H/S, n = 87, 16.5%). Patients with RAVs had significantly higher HCV RNA levels (6.1 ± 0.7 vs 5.9 ± 0.8 log IU/mL, p = 0.001) and lower rGT levels (28.9 ± 18.9 vs. 42.9 ± 57.0 U/L, p = 0.001) compared to those without RAVs. Multivariate analysis identified HCV RNA levels (odds ratio = 1.145, 95% CI: 1.060–1.237, p = 0.001) and rGT (OR = 0.989, 95% CI: 0.978–0.999, p = 0.035) as risk factors that are associated with the presence of RAVs. Importantly, there is no association between the presence of RAVs and no SVR (3.8% in patients with RAVs, 15.9% in patients without RAVs, p = 0.32). ConclusionRAVs, especially M28V and Y93H in the NS5A region, were highly prevalent in patients with genotype 1a and 1b HCV, respectively, in Taiwan, and they were linked to high HCV RNA levels and low rGT levels. Before using the NS5A inhibitors, the presence of mutated HCV variants should be taken into consideration.

Resistance-associated substitutions (RASs) to HCV direct-acting antivirals (DAAs) at baseline of treatment in thalassemia patients: a referral center study.

Patients with thalassemia major are at high risk of hepatitis C through blood transfusion from donors infected by hepatitis C virus (HCV). The use of direct-acting antiviral (DAA) therapy against such HCV infections has increased in different populations. However, resistant viral variants can affect treatment outcomes, and therefore improved surveillance strategies are needed. Accordingly, we aimed to evaluate resistance-associated substitutions (RASs) to HCV DAAs at the baseline of treatment in thalassemia patients in a referral center. Out of 89 thalassemia patients who suffered from HCV infection and were referred to our center between 2016 and 2017, 43 underwent further analysis of the HCV nonstructural proteins NS5A and NS5B using polymerase chain reaction (PCR) sequencing methods. Unique primers were designed using bioinformatics software for separate detection of HCV subtypes 1a, 3a, and 1b. Detection of RASs was performed based on previously published literature. Statistical analysis was carried out using SPSS version 19. The participants, 60.4% (26/43) of whom were male, had a mean age ± standard deviation (SD) of 33.0 ± 5.0years. HCV subtype 1a was found in 27 cases, 3a in 13, and 1b in three. In HCV subtype 1a there were 163 mutations in NS5A and 212 mutations in NS5B. The frequency of RASs was 20.9% (8 RASs in 9 patients), including M28V and H58P in subtype 1a, L28M, R30Q, C316N, and C316S in subtype 1b, and S24F in subtype 3a. Statistically, the subtype 1b and a higher mutation rate in NS5A were associated with RASs (p-value < 0.05). The emergence of natural RASs to HCV DAAs serves as a warning of the risk of drug resistance in response to the broad usage of antivirals. However, relapses in these DAA-treated HCV-infected thalassemia patients are rarely reported. Our findings indicate that the prevalence of RASs prevalence at baseline was 20.9% in these patients, and this calls for extrapolation to a larger population study, as highlighted in other studies, with larger sample sizes, high-throughput methods, and follow-up in order to fully evaluate treatment outcomes in RASs-detected individuals. Optimized therapeutic strategies, particularly in complex, difficult-to-cure patients, can effectively prevent DAA treatment failure as a result of selection for RASs.

Impact of hepatitis C virus genotype 3 on liver disease progression in a Chinese national cohort.

Hepatitis C virus (HCV) genotype 3, particularly subtype 3b, is increasing in prevalence and distribution in China. This study evaluated the prevalence, regional distribution, clinical characteristics, host factors, treatment outcomes, and disease progression of patients with HCV genotype 3 in China. A 5-year follow-up was preceded by a cross-sectional study. Treatment choices were at the discretion of treating physicians. Estimated infection time to overall-disease-progression (defined by ≥1 of: newly diagnosed cirrhosis; cirrhosis at baseline, Child-Turcotte-Pugh score increased 2 points or more; progression from compensated cirrhosis to decompensated cirrhosis; hepatocellular carcinoma; liver transplantation; or death) was calculated using the Kaplan-Meier method. Cox regression analyses were conducted to evaluate the risk factors for disease progression. The cross-sectional study enrolled 997 patients, including 91 with HCV genotype 3 infection. Among them, subtype 3b (57.1%) was more dominant than subtype 3a (38.5%). Five hundred and twelve patients were included into the follow-up phase. Among patients analyzed for estimated infection time to overall-disease-progression, 52/304 (17.1%) patients with HCV genotype 1 and 4/41 (9.8%) with HCV genotype 3 (4/26 with genotype 3b, 0/13 with genotype 3a, and 0/2 with undefined subtype of genotype 3) experienced overall-disease-progression. Patients with HCV genotype 3 were younger than those with genotype 1 (mean age: 39.5 ± 8.7 vs. 46.9 ± 13.6 years) and demonstrated more rapid disease progression (mean estimated infection time to overall-disease-progression 27.1 vs. 35.6 years). HCV genotype 3, specifically subtype 3b, is associated with more rapid progression of liver disease. Further analysis to compare HCV subtype 3a and 3b is needed in high prevalence regions. NCT01293279, https://clinicaltrials.gov/ct2/show/NCT01293279; NCT01594554, https://clinicaltrials.gov/ct2/show/NCT01594554.

From the Editor’s Desk…: December 2019

From the Editor’s Desk…: December 2019

Distribution of hepatitis C virus genotypes and subtypes in a group of patients with chronic hepatitis C from Canton Sarajevo, 2012-2018

Background: Hepatitis C virus (HCV) genotypes and subtypes exhibit significant geographic variations.Aim: To analyse the distribution of genotypes/subtypes of HCV in a group of patients with chronic hepatitis C from Canton Sarajevo during 2012-2018.Material and methods:The study enrolled 247 human plasma samples of HCV-RNA positive patients with available results of HCV genotyping test.Results: During 2012-2018, the domination of subtypes 1a (34.01%), 1b (28.34%) and genotype 3 (23.89%) was registered. In 2012 and 2013, HCV subtype 1a was the most common (27/63; 42.86% and 17/40; 42.50%, respectively). In 2014, the leading HCV genotype/subtype were 3 and 1b (17/57; 29.82%). In 2015, the dominance of HCV genotype 3 (14/39; 35.90%) continued, while in 2016, the same number of HCV subtypes 1a and 1b (11/30; 36.67%) was recorded. Although in a small number of tested, during 2017, HCV subtype 1b was the most prevalent (7/14; 50.00%), and in 2018, it was replaced by a HCV subtype 1a (3/4; 75.00%). Distribution of HCV genotypes/subtypes by age group of patients varied significantly (p=0.000). The largest number of patients (71/247; 28.74%) belonged to the age category 30-39 years and HCV genotypes/subtypes 1, 3, 4, 1a and 1b were identified. Except in 2017, male gender significantly dominated (p=0.000). In males, HCV subtype 1a (68/170; 40.00%) was the most common, while in women it was HCV subtype 1b (44/77; 57.14%).Conclusion: This six-year retrospective study showed the time variations of the circulating HCV genotypes/subtypes among patients with chronic hepatitis C in Canton Sarajevo. Genotyping of the HCV has an important implications for diagnosis and treatment of the patients.