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Background: Hepatitis C virus (HCV) infection is a major public health concern. Persons living with HCV infection are at risk of developing liver cirrhosis and progressing to end-stage liver disease and liver cancer (hepatocellular carcinoma). The present study was undertaken to assess the prevalence of HCV infection in patients admitted as well as outpatient department services of a Zonal Hospital. Methods: The present study was cross-sectional, observational study, conducted in patients >18 years of age, clinically suspected acute infectious hepatitis or admitted to the intensive care unit, and willing to participate in the study. Results: In the present study, 472 patients were studied for hepatitis C infection. Majority of cases were from 51 to 60 years age group (34.5%), followed by 61–70 years age group (26.7%). Female cases were (51.3%) slightly more than male (48.7%). Rapid method and enzyme-linked immunosorbent assay (ELISA) methods detected HCV prevalence as 5.7% and 12.5%, respectively. After HCV genotype testing, the prevalence was 12.1%. Majority had 3A genotype (69.49%), followed by 1A genotype (16.95%), 1B genotype (8.47%), 3B genotype (3.39%), and 4 genotypes (1.69%). ELISA testing was significantly correlated with HCV genotype testing (P = 0.017) while the rapid method was not correlated with HCV genotype testing (P = 0.937). Conclusion: There is a high prevalence of HCV among the suspected, genotype 3 being the most common.

Hepatitis E virus (HEV) is the main cause of acute hepatitis in humans worldwide and is responsible for a large number of outbreaks especially in Africa. Human infections are mainly caused by genotypes 1 and 2 of the genus Paslahepevirus, which are exclusively associated with humans. In contrast, viruses of genotypes 3 and 4 are zoonotic and have their main reservoir in domestic and wild pigs, from which they can be transmitted to humans primarily through the consumption of meat products. Both genotypes 3 and 4 are widespread in Europe, Asia, and North America and lead to sporadic cases of hepatitis E. However, there is little information available on the prevalence of these genotypes and possible transmission routes from animal reservoirs to humans in African countries. We therefore analysed 1086 pig sera collected in 2016/2017 in four districts in Sierra Leone for antibodies against HEV using a newly designed in-house ELISA. In addition, the samples were also analysed for HEV RNA by quantitative real-time RT-PCR. The overall seroprevalence in Sierra Leone was low with only 44 positive sera and a prevalence of 4.0%. Two serum pools were RT-PCR-positive and recovered partial sequences clustered into the genotype 3 (HEV-3) of the order Paslahepevirus, species Paslahepevirus balayani. The results are the first evidence of HEV-3 infection in pigs from Sierra Leone and demonstrate a low circulation of the virus in these animals to date. Further studies should include an examination of humans, especially those with close contact with pigs and porcine products, as well as environmental sampling to evaluate public health effects within the framework of a One Health approach. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is a major cause of acute viral hepatitis worldwide. Up to now, no approved treatment nor a globally licensed vaccine is available. Several recombinant HEV vaccines have been developed to protect against HEV infection in humans, including the commercially available Hecolin vaccine, which are mainly based on HEV genotype 1. However, the efficacy of these vaccines against other HEV genotypes, especially genotype 3 is unknown. In this study, we evaluated the protective efficacy of Hecolin® and a novel genotype 3-based vaccine p239(gt3) against HEV-3 in a pig infection model. Pigs were divided into three groups: one group was vaccinated with Hecolin®, the second group was vaccinated with p239(gt3), and the control group received no vaccine. All pigs were subsequently challenged with HEV genotype 3 to assess the effectiveness of the vaccines. Although all immunised animals developed a high titer of neutralizing antibodies, the results showed that both vaccine applications could not provide complete protection against HEV (gt3) infection: Two out of four animals of the Hecolin® group displayed even virus shedding, and viral RNA could be detected in bile and/or liver of three out of four animals in both vaccination groups. Only one out of four animals in each group was fully protected. Neither Hecolin® nor the novel p239(gt3) vaccine provided sufficient protection against genotype 3 infection. While Hecolin® only partial protected pigs from HEV shedding, the novel p239(gt3) vaccine was at least able to prevent infected pigs from virus shedding. The results highlight the need for further development of HEV vaccines that exhibit broad protection against multiple HEV genotypes and the use of appropriate animal infection models.

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. Among its 8 genotypes (GT), GT3 has a relatively lower sustained virological response to highly effective direct‐acting antiviral agents (DAA). Sofosbuvir (SOF), an anti‐NS5B polymerase inhibitor, is a core component of many anti‐HCV DAA cocktail regimens, and its resistant mutations are rare in clinics because these mutations usually severely impair the NS5B polymerase activity, including a mutation S282T in NS5B, the most frequently reported SOF‐resistant mutation. In this study, we selected SOF‐resistant variants of a previously developed GT3 subgenomic replicon (PR87A7). Two mutations were identified in the viral genome of SOF‐resistant PR87A7 variants, Q606R in nontargeted NS3 and S282T in targeted N5SB. We demonstrated that Q606R could rescue the replication defect of S282T in PR87A7, and the resulting double mutant confers the SOF resistance. Finally, we showed that NS3‐606R could not compensate for the replication defect of S282T in other GTs. In conclusion, we identified a novel GT3‐specific combination of two mutations that confers SOF resistance. Our result calls for attention to potential mutations that may arise in nontargeted viral proteins during the SOF‐based DAA treatment of chronic HCV. [ABSTRACT FROM AUTHOR]

Hepatitis E caused by hepatitis E virus (HEV) is considered an emerging foodborne zoonosis in industrialized, non-endemic countries. Domestic pigs and wild boars are considered the main reservoir of HEV. However, HEV can also infect an ever-expanding host range of animals, but they exact role in transmitting the virus to other species or humans is mostly unknown. In this work, we investigated the spread of HEV in free-living and captive spotted deer (Axis axis) from Uruguay in a 2-year period (2020–2022) and examined the role of this invasive species as a new potential reservoir of the virus. In addition, with the aim to gain new insights into viral ecology in the context of One Health, by using camera trapping, we identified and quantified temporal and spatial coexistence of spotted deer, wild boars, and cattle. In free-living animals, we detected an anti-HEV seropositivity of 11.1% (6/54). HEV infection and viral excretion in feces were assessed by RT-PCR. Thirteen of 19 samples (68.4%) had HEV RNA. Six samples were amplified using a broadly reactive RT-PCR and sequenced. No captive animal showed evidence of HEV infection. Additionally, HEV RNA was detected in a freshwater pond shared by these species. Phylogenetic and p-distance analysis revealed that zoonotic HEV genotype 3 strains circulate together with unclassified variants related to moose HEV whose potential risk of transmission to humans and other domestic and wild animals is unknown. The data presented here suggest that spotted deer (A. axis) may be a novel host for zoonotic HEV strains. [ABSTRACT FROM AUTHOR]

Objective　To investigate the efficacy and safety of Sofosbuvir/Velpatasvir ± ribavirin (SOF/VEL±RBV) in the treatment of genotype 3 chronic hepatitis C cirrhotic patients. Methods　Patients diagnosed with genotype 3 (GT3) HCV infection and treated at the Third People's Hospital of Kunming City from June 2018 to February 2023 were retrospectively included. All patients had liver cirrhosis and were treated with SOF/VEL ＋RBV for 12 weeks, SOF/VEL therapy for 12 or 24 weeks if favorable ribavirin contrainminated or ribavirin intolerant. The virologic indexes, liver and kidney function indexes and adverse reactions of the patients were analyzed before treatment, 4 weeks, 12 weeks and 12 weeks after drug withdrawal. Results　A total of 319 patients were included, including 308 cases in SOF/VEL+RBV group and 11 cases in SOF/VEL group. After 12 weeks off-treatment, the sustained virological response ( SVR12) rate in SOF/VEL+ RBV group was 98.37% ( 303/308), and the levels of APRI score and FIB-4 index were decreased compared with baseline (P < 0.05) . The levels of total bilirubin, aspartate aminotransferase and alanine aminotransferase were all decreased, and the differences were statistically significant ( all P < 0.05) . The SVR12 rate of SOF/VEL group was 72.73% (8/11) . The adverse reactions were mild hemolytic anemia (15.26%), fatigue (8.12%) and rash (8.77%) in SOF/VEL+RBV group, and fatigue ( 9.09%) in 1 case in SOF/VEL group. Conclusion　SOF/VEL+RBV could achieve higher SVR12 and well tolerated for GT3 HCV-infected patients either with compensated cirrhosis or decompensated cirrhosis patients. Liver function, renal function and liver fibrosis could also be improved after treatment. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C (HCV) is a primary cause of hepatocellular carcinoma (HCC). Although antiviral treatment reduces risk of HCC, few studies quantify the impact of treatment on long‐term risk in the era of direct‐acting antivirals (DAA). Using data from the Chronic Hepatitis Cohort Study, we evaluated the impact of treatment type (DAA, interferon‐based [IFN], or none) and outcome (sustained virological response [SVR] or treatment failure [TF]) on risk of HCC. We then developed and validated a predictive risk model. 17186 HCV patients were followed until HCC, death or last follow‐up. We used extended landmark modelling, with time‐varying covariates and propensity score justification and generalized estimating equations with a link function for discrete time‐to‐event data. Death was considered a competing risk. We observed 586 HCC cases across 104,000 interval‐years of follow‐up. SVR from DAA or IFN‐based treatment reduced risk of HCC (aHR 0.13, 95% CI 0.08–0.20; and aHR 0.45, 95% CI 0.31–0.65); DAA SVR reduced risk more than IFN SVR (aHR 0.29, 95% CI 0.17–0.48). Independent of treatment, cirrhosis was the strongest risk factor for HCC (aHR 3.94, 95% CI 3.17–4.89 vs. no cirrhosis). Other risk factors included male sex, White race and genotype 3. Our six‐variable predictive model had 'excellent' accuracy (AUROC 0.94) in independent validation. Our novel landmark interval‐based model identified HCC risk factors across antiviral treatment status and interactions with cirrhosis. This model demonstrated excellent predictive accuracy in a large, racially diverse cohort of patients and could be adapted for 'real world' HCC monitoring. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is the main cause of acute hepatitis in humans worldwide and is responsible for a large number of outbreaks especially in Africa. Human infections are mainly caused by genotypes 1 and 2 of the genus Paslahepevirus, which are exclusively associated with humans. In contrast, viruses of genotypes 3 and 4 are zoonotic and have their main reservoir in domestic and wild pigs, from which they can be transmitted to humans primarily through the consumption of meat products. Both genotypes 3 and 4 are widespread in Europe, Asia, and North America and lead to sporadic cases of hepatitis E. However, there is little information available on the prevalence of these genotypes and possible transmission routes from animal reservoirs to humans in African countries. We therefore analysed 1086 pig sera collected in 2016/2017 in four districts in Sierra Leone for antibodies against HEV using a newly designed in-house ELISA. In addition, the samples were also analysed for HEV RNA by quantitative real-time RT-PCR. The overall seroprevalence in Sierra Leone was low with only 44 positive sera and a prevalence of 4.0%. Two serum pools were RT-PCR-positive and recovered partial sequences clustered into the genotype 3 (HEV-3) of the order Paslahepevirus, species Paslahepevirus balayani. The results are the first evidence of HEV-3 infection in pigs from Sierra Leone and demonstrate a low circulation of the virus in these animals to date. Further studies should include an examination of humans, especially those with close contact with pigs and porcine products, as well as environmental sampling to evaluate public health effects within the framework of a One Health approach.

Yilihamu Abulitifu,1 Jiangshan Lian,2 Munire Adilijiang,1 Lan Liu,1 Fengcong Zhao,1 Wen Qian,1 Yongping Zhang1 1Department of Infectious Diseases, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 2Department of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Yongping Zhang, Department of Infectious Diseases, People’s Hospital of Xinjiang Uygur Autonomous Region, No. 91, Tianchi Road, Urumqi, Xinjiang, 830001, People’s Republic of China, Tel +86 13999233386, Fax +86 991 8563585, Email zhangyongping2@126.comPurpose: Patients with cirrhosis from genotype 3 (GT3) hepatitis C virus (HCV) infection are difficult to cure. This study investigated the effectiveness and safety of sofosbuvir-velpatasvir (SOF/VEL) with and without ribavirin (RBV) in patients with GT3 HCV-infection-related cirrhosis from Xinjiang, China.Patients and Methods: This study included 33 patients with GT3 HCV infected cirrhosis, who were treated with either SOF/VEL+RBV for 12 weeks (n = 27) or SOF/VEL alone for 24 weeks (n = 6) between January 2019 and June 2021. The primary endpoint was a sustained virological response at 12 weeks (SVR12), post-treatment. Secondary endpoints included changes from baseline in Child-Pugh-Turcotte scores, clinical results, hepatic-encephalopathy status, ascites, and gastrointestinal bleeding at 12 weeks, post-treatment.Results: Out of the 33 patients, 18 (54.6%) were diagnosed with GT3a, 15 (45.4%) with GT3b, 16 (48.5%) with compensated cirrhosis, and 17 (51.5%) with decompensated cirrhosis. SVR12 was 87.9% (compensated cirrhosis: 93.8%, decompensated cirrhosis: 82.4%). The Child-Pugh-Turcotte scores improved at 12 weeks (p < 0.05). Total bilirubin, albumin, and alanine transaminase levels, as well as hepatic-encephalopathy were significantly improved among patients with compensated and decompensated cirrhosis (p < 0.05). The blood cell count and serum creatinine levels did not deteriorate.Conclusion: SOF/VEL, with and without RBV, was effective, safe, and well-tolerated as a treatment for GT3 HCV associated cirrhosis.Keywords: hepatitis C, genotype 3, cirrhosis, sofosbuvir-velpatasvir, ribavirin

Hepatitis E virus (HEV) is an emerging zoonotic pathogen associated with relevant public health issues. The aim of this study was to investigate HEV presence in free-living capybaras inhabiting urban parks in São Paulo state, Brazil. Molecular characterization of HEV positive samples was undertaken to elucidate the genetic diversity of the virus in these animals. A total of 337 fecal samples were screened for HEV using RT-qPCR and further confirmed by conventional nested RT-PCR. HEV genotype and subtype were determined using Sanger and next-generation sequencing. HEV was detected in one specimen (0.3%) and assigned as HEV-3f. The IAL-HEV_921 HEV-3f strain showed a close relationship to European swine, wild boar and human strains (90.7–93.2% nt), suggesting an interspecies transmission. Molecular epidemiology of HEV is poorly investigated in Brazil; subtype 3f has been reported in swine. This is the first report of HEV detected in capybara stool samples worldwide. [ABSTRACT FROM AUTHOR]

Objective: Substance use is a gradually increasing public health problem. Viruses such as hepatitis B, hepatitis C, and HIV can be transmitted with intravenous substance use and cause significant morbidity and mortality. Therefore, we aimed to evaluate the hepatitis B, hepatitis C, HIV, and syphilis test results of patients followed at the Şanlıurfa Alcohol and Drug Addiction Research Treatment and Training Center (AMATEM) clinic. Methods: The age, gender, background, information about type of substance addiction of the patients and HBsAg, anti-HBs, anti-HCV, anti-HIV, and venereal disease research laboratory (VDRL) test results were evaluated. Results: A total of 427 patients over 18 who were followed at the AMATEM clinic between 2021 and 2022 were included in the study. Of these, 408 (95.6%) were male, and 19 (4.4%) were female. The mean age of the participants was 27.03±5.5 years. Three hundred fifteen (73.8%) patients had intravenous substance use, and all these patients (100%) used opioids. HBsAg positivity was detected in 3 (0.71%), and Anti-HCV positivity was detected in 52 (12%) patients. While only 20 (38.46%) of these patients had applied to the relevant clinics for further testing and treatment, HCV-RNA positivity was detected in 12 (60%) of the patients. In addition, the frequency of genotype 3 was higher in HCV RNA-positive patients (66.67%). Conclusion: Opioid use was at the forefront both in the whole patient population and in patients with anti-HCV positivity. Although anti-HCV positivity was detected at a high rate compared to the general population, only one out of every three patients had applied to the relevant clinics for further testing and treatment. Thanks to the new treatment options Hepatitis C is a curable disease. Screening programs are extremely important to ensure both personal and community viral eradication by providing patients with suitable treatments. [ABSTRACT FROM AUTHOR]

The hepatitis E virus (HEV) is the main cause of viral acute hepatitis in the world, affecting more than 20 million people annually. During the acute phase of infection, HEV can be detected in various body fluids, which has a significant impact in terms of transmission, diagnosis or extrahepatic manifestations. Several studies have isolated HEV in the genitourinary tract of humans and animals, which could have important clinical and epidemiological implications. So, our main objective was to evaluate the presence of HEV in testis of naturally infected wild boars (Sus scrofa). For it, blood, liver, hepatic lymph node and testicle samples were collected from 191 male wild boars. The presence of HEV was evaluated in serum by PCR, as well as in tissues by PCR and immunohistochemistry. Four animals (2.09%; 95%CI: 0.82–5.26) showed detectable HEV RNA in serum, being confirmed the presence of HEV‐3f genotype in three of them by phylogenetic analysis. HEV was also detected in liver and/or hepatic lymph nodes of the four animals by RT‐PCR, as well as by immunohistochemistry analysis. Only one of these wild boars also showed detectable viral load in testis, observing HEV‐specific labelling in a small number of fibroblasts and some Sertoli cells. Our results confirm the presence of HEV genotype 3 in naturally infected wild boar testis, although no associated tissue damage was evidenced. This study does not allow us to discard semen as a possible source of HEV transmission in suids. Future experimental studies are necessary to evaluate the impact of HEV genotype 3 on fertility and the possibility of transmission through sexual contact in this specie. [ABSTRACT FROM AUTHOR]

Objective To study the efficacy and safety of real-world sofosbuvir/velpatasvir (SOF/VEL) in combination with or without ribavirin (RBV) in the treatment of patients with chronic hepatitis C (CHC) genotype 3 in Yunnan. Methods A total of 219 patients with genotype 3 CHC between January 2018 and March 2022 were selected and treated with SOF/VEL in combination with or without RBV for 12 weeks or 24 weeks with a 12-week follow-up after discontinuation of the drug. General demographic data, HCV RNA quantification, liver function, and liver stiffness measurements were collected from patients. Results Among 219 patients with genotype 3 CHC, abnormal biochemical parameters and liver hardness values were significantly lower than baseline at 12 weeks of discontinuation, with a sustained viral response rate of 95.4% (209/219). 60 cases reported mild adverse effects, mainly anemia, malaise and headache, and no serious adverse effects were observed. Conclusions SOF/VEL in combination with or without RBV regimen can result in high response rates in patients with hepatitis C genotype 3 without cirrhosis or combined with compensated cirrhosis, but lower response rates in patients with hepatitis C genotype 3 in combination with chronic liver failure. Patients may have mild adverse effects and an acceptable safety profile with this regimen. [ABSTRACT FROM AUTHOR]

Introduction Delhi is hyperendemic for dengue virus (DENV) where all the four DENV have previously been reported. A constant vigilance of circulating DENV serotypes is important in surveillance, since the introduction of a new variant to areas affected by preexisting serotypes constitutes a risk factor for dengue hemorrhagic fever and dengue shock syndrome. Objectives This retrospective study was performed with an objective to determine the circulating serotype and genotype of DENV in acute phase blood samples of patients who have reported to a tertiary liver care hospital in New Delhi during the last 2 years (2017–2018). Methods The data of clinician-initiated testing for dengue nonstructural protein 1 (NS1) antigen (Ag) was searched in the institutional hospital information system. The serum sample of dengue NS1 Ag-positive cases confirmed by enzyme-linked immunosorbent assay (ELISA; PANBIO, Gyeonggi-do, ROK) and a fever duration of less than 5 days were retrieved from the laboratory archive. The DENV serotyping on these sample was performed by reverse transcriptase polymerase chain reaction (RT-PCR). Sequencing and phylogenetic analysis was done for the capsid premembrane (CprM) region to determine the genotype. Results A total of 440 acute-phase samples were received. Twenty one (4.77%) were positive for dengue NS1 Ag with a mean age of 35.1 years and male-to-female ratio of 1.1:1. Eight cases (38.09%) were positive by dengue RT-PCR and all belonged to DENV-3 serotypes. Phylogenetic tree analysis revealed DENV-3 clustered to genotype III with 100% homology with 2008 Indian subcontinent strain. Conclusion This study revealed circulation of DENV-3, genotype III in Delhi from 2017 to 2018, similar to the 2008 viral type. Virological surveillance is an important exercise to be done for viral infections with public threat and outbreak potential.

Hepatitis C virus (HCV) is an important contributor to chronic morbidity and mortality in developing countries. The study’s objective was to determine the genotype distribution and risk factors associated with the transmission of HCV infections in pediatric patients. Rapid screening and confirmation by the enzyme-linked immunosorbent assay (ELISA) were used to analyze 585 pediatric blood specimens hospitalized and visited the outpatient department of the largest tertiary care hospital in Pakistan. Detection and genotyping of HCV RNA were performed using a real-time polymerase chain reaction (RT-PCR). Demographic data and a history of risk factors were gathered through a survey questionnaire. HCV RNA was detected in 323 (72.4%) cases which showed viral load ranging from Log10 IU/mL < 3 to > 6 IU/mL. HCV genotype 3a was detected in 256 (79.3%) cases while type 3b and 1a was observed in 36 (11.1%) and 31 (9.6%) patients, respectively. HCV positivity was significantly associated with the cases from rural areas [p = 0.005; odds ratio (OR) 1.65; 95% CI 1.16-2.23] and also significantly associated with low-income group [p < 0.001; OR 5.75; 95% CI 3.90-8.40]. The primary risk factors associated with HCV transmission in children were family history (p = 0.002), blood transfusion (p = 0.03), surgical procedures (p = 0.02), and history of injections (p = 0.05). HCV genotype 3a is the most common genotype in children. The main risk factors for HCV transmission in children are blood transfusion, surgical procedures, and injection practices by informal health care providers.

The shortage of livers has led most transplant centers to use extended criteria donors. Hepatitis C virus (HCV) RNA-positive donor organs are typically not given to patients who have cleared HCV. A 64-year-old male with chronic hepatitis C, genotype 1b was listed for LT with hepatocellular carcinoma. While on the waiting list, the patient was treated with sofosbuvir, ledipasvir, and ribavirin and achieved an HCV RNA

Background: The hepatitis C virus has a high mutation rate, which results in the emergence of resistance-associated substitutions (RASs). Despite direct-acting antivirals (DAAs) efforts to treat chronically infected HCV genotype 3 (GT3) patients, there are concerns about the emergence and persistence of RASs in DAA failures. The objective of this study was to determine the prevalence of clinically relevant RASs in HCV NS5A and NS5B regions before and after treatment to better understand the role of RASs in treatment failures. Methods: Viral RNA was extracted before and after treatment from serum samples. NS5A and NS5B regions of HCV were amplified by nested PCR, followed by Sanger sequencing. The nucleotide sequences were aligned against HCV GT3 reference sequences, and amino acid substitutions were analyzed using the geno2pheno [hcv] webserver. Results: A total of 76 patients failing DAA therapy were stratified from the cohort of 1388. RASs were detected at the baseline in 15/76 patients and at relapse in 20/76 patients with cirrhosis and previously treated with interferons. The most prevalent NS5A RAS was Y93H found in all treatment-failing patients (14/54 in DCV vs. 6/22 in VEL), followed by A62S/T and A30K. No RASs were identified in NS5B. RASs that were present at the baseline persisted through the 24-week follow-up period and were enriched with emerging RASs during the treatment. The presence of RASs may be one of the causes of treatment failures in 26.3% of patients. Amino acid substitutions were present at the baseline in most of the patients with RASs against NS5A inhibitors. Patients with the baseline Y93H and/or A30K relapse more frequently than patients harboring A62S/T. Conclusion: Treatment-failing patients harbored NS5A RASs, and the most frequent were A30K (5/20), A62S/T (20/20), and Y93H (20/20). Direct resistance testing is recommended for optimizing re-treatment strategies in treatment-failing patients. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is an important contributor to chronic morbidity and mortality in developing countries. The study's objective was to determine the genotype distribution and risk factors associated with the transmission of HCV infections in pediatric patients. Rapid screening and confirmation by the enzyme-linked immunosorbent assay (ELISA) were used to analyze 585 pediatric blood specimens hospitalized and visited the outpatient department of the largest tertiary care hospital in Pakistan. Detection and genotyping of HCV RNA were performed using a real-time polymerase chain reaction (RT-PCR). Demographic data and a history of risk factors were gathered through a survey questionnaire. HCV RNA was detected in 323 (72.4%) cases which showed viral load ranging from Log10 IU/mL < 3 to > 6 IU/mL. HCV genotype 3a was detected in 256 (79.3%) cases while type 3b and 1a was observed in 36 (11.1%) and 31 (9.6%) patients, respectively. HCV positivity was significantly associated with the cases from rural areas [p = 0.005; odds ratio (OR) 1.65; 95% CI 1.16-2.23] and also significantly associated with low-income group [p < 0.001; OR 5.75; 95% CI 3.90-8.40]. The primary risk factors associated with HCV transmission in children were family history (p = 0.002), blood transfusion (p = 0.03), surgical procedures (p = 0.02), and history of injections (p = 0.05). HCV genotype 3a is the most common genotype in children. The main risk factors for HCV transmission in children are blood transfusion, surgical procedures, and injection practices by informal health care providers. [ABSTRACT FROM AUTHOR]

While evidence suggests presence of HEV infection in humans in Zambia, currently, there is no information on its occurrence in domestic pigs. Here, we investigated the presence of HEV antibodies and genome in domestic pigs in Zambia. Sera (n = 484) from domestic pigs were screened for antibodies against HEV by ELISA while genome detection in fecal (n = 25) and liver (n = 100) samples from slaughter pigs was conducted using nested RT–PCR assay. Overall, seroprevalence was 47.7% (231/484) while zoonotic genotype 3 HEV RNA was detected in 16.0% (20/125) of slaughtered pigs. This is the first report to highlight occurrence of HEV infection in domestic pigs in Zambia. This finding suggests possible contamination of the pork supply chain. Moreover, there is a potential risk of zoonotic transmission of HEV to abattoir workers, pig farmers and handlers.

Background: The hepatitis C virus has a high mutation rate, which results in the emergence of resistance-associated substitutions (RASs). Despite direct-acting antivirals (DAAs) efforts to treat chronically infected HCV genotype 3 (GT3) patients, there are concerns about the emergence and persistence of RASs in DAA failures. The objective of this study was to determine the prevalence of clinically relevant RASs in HCV NS5A and NS5B regions before and after treatment to better understand the role of RASs in treatment failures.Methods: Viral RNA was extracted before and after treatment from serum samples. NS5A and NS5B regions of HCV were amplified by nested PCR, followed by Sanger sequencing. The nucleotide sequences were aligned against HCV GT3 reference sequences, and amino acid substitutions were analyzed using the geno2pheno [hcv] webserver.Results: A total of 76 patients failing DAA therapy were stratified from the cohort of 1388. RASs were detected at the baseline in 15/76 patients and at relapse in 20/76 patients with cirrhosis and previously treated with interferons. The most prevalent NS5A RAS was Y93H found in all treatment-failing patients (14/54 in DCV vs. 6/22 in VEL), followed by A62S/T and A30K. No RASs were identified in NS5B. RASs that were present at the baseline persisted through the 24-week follow-up period and were enriched with emerging RASs during the treatment. The presence of RASs may be one of the causes of treatment failures in 26.3% of patients. Amino acid substitutions were present at the baseline in most of the patients with RASs against NS5A inhibitors. Patients with the baseline Y93H and/or A30K relapse more frequently than patients harboring A62S/T.Conclusion: Treatment-failing patients harbored NS5A RASs, and the most frequent were A30K (5/20), A62S/T (20/20), and Y93H (20/20). Direct resistance testing is recommended for optimizing re-treatment strategies in treatment-failing patients.

Introduction Delhi is hyperendemic for dengue virus (DENV) where all the four DENV have previously been reported. A constant vigilance of circulating DENV serotypes is important in surveillance, since the introduction of a new variant to areas affected by preexisting serotypes constitutes a risk factor for dengue hemorrhagic fever and dengue shock syndrome. Objectives This retrospective study was performed with an objective to determine the circulating serotype and genotype of DENV in acute phase blood samples of patients who have reported to a tertiary liver care hospital in New Delhi during the last 2 years (2017-2018). Methods The data of clinician-initiated testing for dengue nonstructural protein 1 (NS1) antigen (Ag) was searched in the institutional hospital information system. The serum sample of dengue NS1 Ag-positive cases confirmed by enzyme-linked immunosorbent assay (ELISA; PANBIO, Gyeonggi-do, ROK) and a fever duration of less than 5 days were retrieved from the laboratory archive. The DENV serotyping on these sample was performed by reverse transcriptase polymerase chain reaction (RT-PCR). Sequencing and phylogenetic analysis was done for the capsid premembrane (CprM) region to determine the genotype. Results A total of 440 acute-phase samples were received. Twenty one (4.77%) were positive for dengue NS1 Ag with a mean age of 35.1 years and male-to-female ratio of 1.1:1. Eight cases (38.09%) were positive by dengue RT-PCR and all belonged to DENV-3 serotypes. Phylogenetic tree analysis revealed DENV-3 clustered to genotype III with 100% homology with 2008 Indian subcontinent strain. Conclusion This study revealed circulation of DENV-3, genotype III in Delhi from 2017 to 2018, similar to the 2008 viral type. Virological surveillance is an important exercise to be done for viral infections with public threat and outbreak potential. [ABSTRACT FROM AUTHOR]

Background Few studies about the evolutionary history of the hepatitis E virus (HEV) have been conducted. The aim of our work was to investigate and make inferences about the origin and routes of dispersion of HEV-3 in Argentina. Methods Phylogenetic, coalescent and phylogeographic analyses were performed using a 322-bp ORF2 genomic fragment of all HEV-3 sequences with known date and place of isolation published at GenBank until May 2018 (n=926), including 16 Argentinian sequences (isolated from pigs, water and humans). Results Phylogenetic analysis revealed two clades within HEV-3: abchij and efg. All Argentinian samples were grouped intermingled within clade 3abchij. The coalescent analysis showed that the most recent common ancestor for the clade 3abchij would have existed around the year 1967 (95% highest posterior density (HPD): 1963–1970). The estimated substitution rate was 1.01×10−2 (95%HPD: 9.3×10ˉ3–1.09×10ˉ 2 ) substitutions/site/y, comparable with the rate previously described. The phylogeographic approach revealed a correspondence between phylogeny and place of origin for Argentinian samples, suggesting many HEV introductions in the country, probably from Europe and Japan. Conclusions This is the first evolutionary inference of HEV-3 that includes Argentinian strains, showing the circulation of many HEV-3 subtypes, obtained from different sources and places, with recent diversification processes. Accession numbers [ KX812460], [KX812461], [KX812462], [KX812465], [KX812466], [KX812467], [KX812468], [KX812469]. [ABSTRACT FROM AUTHOR]

Background In clinical trials, hepatitis C virus (HCV) salvage treatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) achieved an SVR12 rate of >95% in NS5A-experienced participants. Lower SVR12 rates have been reported in real-world studies, particularly for genotype (GT)3 infection and cirrhosis. We determined the efficacy and safety of SOF/VEL/VOX in a large real-world cohort. Methods We assessed the efficacy of salvage SOF/VEL/VOX for HCV infection in NS5A-inhibitor experienced participants with cirrhosis and portal hypertension, prior liver transplantation (LT) or severe extra-hepatic manifestations. SOF/VEL/VOX was available via an early access program. The primary outcome was SVR12. Secondary outcome was frequency of adverse events (AE). Findings Ninety-seven participants were included. Median age was 58, 82% were male, 78% had cirrhosis, most with portal hypertension (61%, n = 46/76), and 18% had prior-LT. Of the cirrhotic participants, 96% were Child-Turcotte-Pugh class A, and 4% were class B. Of the 72% with GT3, 76% were also cirrhotic. By intention-to-treat analysis, SVR12 rate was 85% (n = 82/97). Per protocol, the SVR12 rate was 90%, including 91% in GT1 (GT1a n = 18/18, GT1b n = 2/4), 89% in GT3 (n = 59/66) and 100% in GT6 (n = 3/3). SVR12 in participants with GT3 and cirrhosis was 90%. No predictors of non-SVR12 were identified. There were 4 serious AEs including 1 death and 3 hepatic decompensation events. NS5A resistance-associated substitutions detected at baseline did not affect SVR12. Conclusions This real-world study confirms high efficacy of SOF/VEL/VOX for the treatment of difficult-to-cure NS5A-inhibitor experienced patients, including those with GT3 and cirrhosis. Treatment was well tolerated in most; however, serious AEs can occur in those with advanced liver disease. [ABSTRACT FROM AUTHOR]

Information on hepatitis E virus (HEV) strains circulating in animal reservoirs in Bulgaria is currently lacking. Herein, by screening HEV seropositive sera obtained from Bulgarian swine and wild boars, viral RNA was detected at high prevalence rate (28.2%) in industrial pigs. Sequence analysis of the partial polymerase (RdRp) region revealed the highest genetic correlation with HEVs of genotype (Gt) 3 identified in French and Dutch patients. For three such strains, a 700-bp fragment of the open reading frame 2 gene was generated. On phylogenetic analysis, the Bulgarian strains clustered tightly (93.8–98.3% nt) with human and animal HEVs classified within the Gt3 subtype c. [ABSTRACT FROM AUTHOR]

Abstract Objective In 2015, Georgia launched HCV elimination program. Initially, patients with advanced liver disease were treated with sofosbuvir-based regimen—the only DAA available for all genotypes. Purpose of the study was assessing real-world data of treatment outcome among patients with HCV GEN3 and advanced liver fibrosis with sofosbuvir-based regimens. Results Totally 1525 genotype 3 patients were eligible for analysis; most (72.6%) were aged > 45 years, majority were males (95.1%), and all (100%) had advanced liver disease (F3 or F4 by METAVIR score based on elastography). Of those who received sofosbuvir/ribavirin (SOF/RBV) for 24 weeks, 79.3% achieved SVR, while 96.5% who received sofosbuvir/pegylated interferon/ribavirin (SOF/PEG/RBV) for 12 weeks achieved SVR (p

Objective: To evaluate the efficacy of sofosbuvir with daclatasvir and its promising effects on liver functions especially in respect to earlier treatment failure patients to frame an appropriate regimen for them. Study Design: A prospective, observational cohort study. Place and Duration of Study: Pak Emirates Military Hospital Rawalpindi, Army Medical College Rawalpindi, from Jan 2018 to Dec 2018. Methodology: A total of 114 patients infected with genotype 3 were segregated into two groups according to their treatment status with 57 patients in each group. They received treatment according to the World Health Organization guidelines to assess the efficacy in terms of sustained virological response upon 12 weeks of completion of treatment (SVR 12) and to evaluate changes in serum alanine aminotransferase (ALT), total bilirubin, albumin and prothrombin time (PT). The results were comparatively analyzed between the groups. Results: The percentage of patients attaining SVR 12 was nearly same in both the groups (94.7% vs 93%). Improvement in ALT, total bilirubin, serum albumin and prothrombin time was highly significant (p

BACKGROUND & OBJECTIVE: The role of Velpatasvir/Sofosbuvir in the treatment of hepatitis C virus type 3 infection is evaluated in terms of virologic responses. i.e Rapid Virological Response (RVR) End of treatment response (ETR) and Sustained virological response (SVR 12). METHODOLOGY: This was a descriptive case study conducted in Liver OPD of Benazir Bhutto Hospital during 01 November 2018 to 30 April 2019 , in which 100 patients of HCV were enrolled, all of them had HCV genotype 3 infection. Every patient was treated with combination of Velpatasvir/Sofosbuvir 100mg/400 mg Once Daily as part of treatment regimen of HCV infection for 12 weeks. Pre-treatment HCV RNA QUANTITATIVE PCR was done, which was repeated on 4, 12 weeks of treatment and then 12 weeks post treatment. RESULTS: Among 100 patients, 51 (51%) were male and 49 (49%) were females. Mean age of patients was 43.2 ± 10.4 years (mean ± SD). Mean BMI of enrolled patients was 21.34 ± 2.40 kg/m2. 33% patients were cirrhotic while 67% were non cirrhotic. 53% patients were treatment experienced while 47% were treatment naïve. Rapid Virological Response (RVR) was achieved in 92%, End of treatment response (ETR) was achieved in 96%, while Sustained Virological response (SVR12) was achieved in 99% patients. The results were stratified according to age, gender and BMI. There was no effect of these parameters on the final results.

Hepatitis E virus (HEV) is an emerging zoonotic pathogen associated with relevant public health issues. The aim of this study was to investigate HEV presence in free-living capybaras inhabiting urban parks in São Paulo state, Brazil. Molecular characterization of HEV positive samples was undertaken to elucidate the genetic diversity of the virus in these animals. A total of 337 fecal samples were screened for HEV using RT-qPCR and further confirmed by conventional nested RT-PCR. HEV genotype and subtype were determined using Sanger and next-generation sequencing. HEV was detected in one specimen (0.3%) and assigned as HEV-3f. The IAL-HEV_921 HEV-3f strain showed a close relationship to European swine, wild boar and human strains (90.7–93.2% nt), suggesting an interspecies transmission. Molecular epidemiology of HEV is poorly investigated in Brazil; subtype 3f has been reported in swine. This is the first report of HEV detected in capybara stool samples worldwide.

Abstract Background There is paucity of data using direct anti-viral agents (DAA) in patients on maintenance hemodialysis (MHD) infected with HCV-genotype 1 & 3. Aim of the study was to evaluate DAA therapy in patients infected with HCV-genotype 1 & 3 on MHD. Methods A prospective open label, parallel, non-randomized interventional trial was conducted in patients with Hepatitis-C on maintenance hemodialysis. Total of Sixty two (62) patients with hepatitis-C on maintenance hemodialysis were screened and 36 patients were enrolled and then equally allocated in 1:1 ratio to group 1 who received 400 mg daily sofosbuvir/ 60 mg daily daclatasvir and group 2 who received thrice a week 400 mg Sofosbuvir and daily 60 mg daclatasvir for 12 weeks. Patients with compensated cirrhosis received therapy for 24 weeks. Relevant data was obtained before, during and after therapy. HCV viral load was assessed at week 4, 8, at end of therapy and 12 weeks after treatment. Results Eighteen (18) patients were allocated in each group. Three patients in group 1 withdrawn from the study after 2 weeks due to refusal to participate, while one withdrawn in group 2 due to development of adverse effect. Mean age of patients was 47.22 + 14.17 in group 1 and 53.89 + 14.11 in group 2. Genotype 3 was most common in group 1 patients, n = 12 (66.6%), and n = 11 (61.1%) in group 2. All patients in both groups achieved undetectable viral load at 12th week. As per intention to treat analysis overall 29/36 (80.55%) patients achieved SVR (group 1 = 15/18; group 2 = 14/18) and as per-protocol analysis overall 29/32 (90.62%) patients achieved SVR (group 1 = 15/15; group 2 = 14/17). Conclusion Direct acting antiviral therapy using sofosbuvir and declatsavir is highly effective and tolerable in patients with HCV genotype 1 & 3 undergoing maintenance hemodialysis, especially when given daily. Trial registration This trial is registered in WHO, International Clinical Trial Registry Platform, through Iranian Registry of Clinical Trials (IRCT) having IRCT ID: IRCT20170614034526N3, registered retrospectively on 2019-03-08.

In the last decade, the number of reported hepatitis E virus (HEV) infections in Germany, including Bavaria, has continued to rise. In order to identify risk factors associated with HEV infection, we investigated notified hepatitis E cases from Bavaria during 2017. The project "Intensified Hepatitis E Surveillance in Bavaria" included interviews with questionnaires, collection and genotyping of stool, serum and food samples. In addition, certain risk factors were examined in a sample comparison with healthy population using univariable analysis and logistic regression. In total, 135 hepatitis E cases from Bavaria were included in the analysis. Mean age for women was 46 (range 20–74) years and 47.5 (range 20–85) for men. 56 of the cases (41.5%) were asymptomatic. Among the symptomatic cases, both men and women were equally affected with symptoms like fever (16.3%), jaundice (18.8%) and upper abdominal pain (28.2%). 145 human samples (serum, stool) and 6 food samples were collected. 15.9% of the human samples (n = 23) were positive for HEV RNA by reverse-transcription quantitative real-time PCR (RT-qPCR). Identified risk factors significantly associated with hepatitis E were sausage consumption with odds ratio 9.6 (CI 1.3–70.1), fish with OR 2.2 (CI 1.1–4.4) and cat ownership with OR 1.9 (CI 1.3–3.0) in multivariable analyses. Further investigation is needed to confirm the role of fish in HEV transmission. Autochthonous HEV genotype 3 is prevalent in Bavaria and there could be more transmission routes contributing to the spread of HEV than previously known. Undercooked meat, offal, sausages, fish, shellfish and contact with animals and pets are possible sources for infection. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to investigate the role of resistance‐associated substitutions (RASs) to direct‐acting‐antivirals (DAAs) in HCV genotype 3 (GT3). Methods: Within the Italian VIRONET‐C network, a total of 539 GT3‐infected patients (417 DAA‐naïve and 135 DAA‐failures, of them, 13 at both baseline and failure) were analysed. Sanger sequencing of NS3/NS5A/NS5B was performed following home‐made protocols. Results: The majority of patients were male (79.4%), 91.4% were injection drug users, 49.3% were cirrhotic and 13.9% were HIV co‐infected. Phylogenetic analysis classified sequences as GT3a‐b‐g‐h (98%‐0.4%‐0.2%‐1.2%) respectively. Overall, 135 patients failed a DAA regimen: sofosbuvir (SOF)/daclatasvir (DCV) or velpatasvir (VEL)±ribavirin (RBV) (N = 91/15) and glecaprevir (G)/pibrentasvir (P) (N = 9). Moreover, 14.8% of patients were treated with suboptimal regimens for GT3: 3D ± RBV (Paritaprevir/r + Ombitasvir+Dasabuvir, N = 15), SOF + Simeprevir (SIM) (N = 1) or SOF/Ledipasvir (LDV) ± RBV (N = 4). RAS prevalence was 15.8% in DAA‐naïve patients. At failure, 81.5% patients showed at least one RAS: 11/25 (44.0%) in NS3, 109/135 (80.7%) in NS5A, 7/111 (6.3%) in NS5B SOF‐failures. In NS5A‐failures, Y93H RAS was the most prevalent (68.5% vs 5.1% DAA‐naïve, P <.001) followed by A30K (12.7% vs 2.8% in DAA‐naïve, P <.001). Analysing baseline samples, a higher prevalence of NS5A‐RASs was observed before treatment in DAA‐failures (5/13, 38.5%) vs DAA‐naïves (61/393, 15.5%, P =.04). Regarding 228 DAA‐naïve patients with an available outcome, 93.9% achieved a SVR. Interestingly, patients with baseline Y93H and/or A30K had SVR rate of 72.2% vs 95.7% for patients without NS5A‐RASs (P =.002). Conclusions: In this real‐life GT3 cohort, the majority of failures harboured resistant variants carrying NS5A‐RASs, the most frequent being Y93H. The presence of natural NS5A‐RASs before treatment was associated with failure. Further analyses are needed to confirm this observation, particularly for the new current regimens. [ABSTRACT FROM AUTHOR]

Background: Combination of pegylated interferon α-2a or α-2b has been considered to be the standard for treating HCV infection among children. Many new agents inhibiting HCV during various steps while replicating is under study around the world. This study was aimed to note the efficacy of sofosbuvir and ribavirin among children having HCV infection. Methods: This was an open label experimental trail done at Department of Gastroenterology, Children Hospital and The Institute of Child Health, Multan. The study duration was from July to December 2019. A total of 89 HCV treatment naïve children aged 6–16 years of age, having HCV PCR as positive were enrolled. Sofosbuvir as 400 mg once a day along with ribavirin 10–15 mg per kg per day in the form of once or twice as divided doses were given in all the cases. After starting the treatment, along with side effects, rapid virological response (RVR) as PCR at 4 weeks, early virological response (EVR) at 12 weeks and post treatment 12 weeks HCV PCR as sustained virological response (SVR) was noted. Results: Out of a total of 89 children, there were 53 (59.6%) boys and 36 (40.4%) girls. Mean age was noted to be 12.42±2.57 years. Majority of the children, 72 (80.9%) had genotype 3 while genotype 1 was noted in 11 (12.4%) and un-typable in remaining 6 (6.7%). History of blood or blood products transfusion was seen to be the commonest mode of HCV transmission, found in 41 (46.1%) children, perinatal transmission in 20 (22.5%) and history of previous surgery in 9 (10.1%). Rapid virological response was noted in 73 (83.1%) children, all 89 (100%) children achieved EVR whereas SVR was noted in 86 (96.7%). Headache was the commonest side effect, reported by 24 (27.0%) followed by nausea in 15 (16.9%). Conclusion: Regardless of the genotype, sofosbuvir and ribavirin combination therapy was noted to have excellent efficacy amongst children with HCV infection. History of blood and blood product transfusion was the commonest risk factor found. [ABSTRACT FROM AUTHOR]

Background and Aim The prohibitively high cost of direct‐acting antivirals (DAA) for hepatitis C virus (HCV) infection remains a barrier to treatment access in Singapore. We aimed to evaluate whether DAA as first‐line therapy would be cost‐effective for genotype 3 (GT3) HCV patients compared with pegylated interferon and ribavirin (PR). Methods A decision tree analysis was used to compare the costs and outcomes of DAA and PR as first‐line therapy. Treatment effectiveness, defined as sustained virological response, was assessed using a retrospective cohort of treated GT3 HCV patients. Direct medical costs were estimated from the payer’s perspective using billing information. We obtained health utilities from published literature. We performed extensive one‐way sensitivity analyses and probabilistic sensitivity analyses to account for uncertainties regarding the model parameters. Results In base case analysis, first‐line therapy with DAA and PR yielded quality‐adjusted life years (QALYs) of 0.69 and 0.62 at a cost of USD 54 634 and USD 23 857, respectively. The resultant incremental cost‐effectiveness ratio (ICER) (USD 449 232/QALY) exceeded the willingness‐to‐pay threshold (USD 53 302/QALY). The ICER was robust for uncertainties regarding the model parameters. The cost of DAA is the key factor influencing the cost‐effectiveness of HCV treatment. At current price, DAA as first‐line therapy is not cost‐effective compared with PR, with or without consideration of retreatment. Threshold analysis suggested that DAA can be cost‐effective if it costs less than USD 17 002 for a 12‐week treatment course. Conclusion At current price, DAA as first‐line therapy is not cost‐effective compared with PR in GT3 HCV patients in Singapore.

Abstract Background Patients with hepatitis C virus (HCV) genotype 3 infection remain a difficult-to-cure population. This study evaluated the efficacy and safety of sofosbuvir-based regimen in genotype 3 patients in a real-world setting. Methods HCV genotype 3a-infected adults with compensated liver disease were treated with sofosbuvir (SOF)/velpatasvir (VEL) or SOF/daclatasvir (DCV) with or without ribavirin (RBV) for 12 or 24 weeks, respectively. Efficacy was measured by sustained virologic response at post-treatment week 12 (SVR12). Adverse events were evaluated throughout the treatment and follow-up course. Results A total of 41 genotype 3a-infected patients were included. Of them, 10 patients (24%) had cirrhosis, 3 (7%) had renal impairment, and 2 (5%) failed previous treatment. Nine patients (22%) were treated with SOF/VEL and 32 (78%) with SOF/DCV with or without RBV. SVR 12 was achieved in 100% (9/9) of patients treated with SOF/VEL for 12 weeks and in 97% (31/32) of those treated with SOF/DCV for 12 or 24 weeks. RBV addition and extension of treatment duration did not improve the SVR of SOF/DCV (RR: 1.04; P = 0.99 and RR: 1.09; P = 0.375, respectively). Ten patients with cirrhosis, 1 on hemodialysis and 2 with treatment-experience achieved SVR12. One treatment-naïve non-cirrhotic patient on hemodialysis treated with SOF/DCV for 24 weeks relapsed at week 8 post-treatment. No serious adverse events and relevant laboratory abnormalities were observed. Conclusion SOF/VEL and SOF/DCV are highly efficacious and well tolerated in genotype 3a-infected patients with or without cirrhosis. RBV coadministration and extension of SOF/DCV treatment appear to add no improvement for efficacy.

Nowadays, the retreatment of patients with Hepatitis C virus (HCV) genotype 3 (GT3) especially cirrhotic, who have already been treated with regimens containing a NS5A inhibitor represents a challenge. Use a novel retreatment option for patients with a difficult approach. We present three case reports of retreatment with a new combination of Direct-acting antivirals (DAAs), Sofosbuvir, Elbasvir/Grazoprevir in patients with GT3 with a previous failure with Sofosbuvir/Ledipasvir. All the cases achieved sustained virologic response (SVR) at week +12 without adverse effects. In our experience, this combo may represent an effective and safe option for these patients.

Sofosbuvir/ledipasvir (SOF/LED) is recommended for treatment of genotypes 1, 4, 5 and 6. Despite some preliminary data from the ELECTRON-2 trial regarding use of SOF/LED combination in chronic hepatitis C genotype 3, there are no guidelines recommending this combination in such patients. We conducted this study to evaluate the efficacy of the overall sustained virologic response at 12 weeks (SVR 12) and safety of SOF/LED in chronic hepatitis C genotype 3 infection in our population. It was a prospective, hospital-based observational study. All patients with chronic hepatitis C genotype 3 treated with SOF/LED were divided into two groups: patients with cirrhosis and without cirrhosis. Patients without cirrhosis received SOF/LED (90/400 mg) for 12 weeks; however, patients with cirrhosis received treatment for 24 weeks. We enrolled 104 patients with chronic hepatitis C over a period of 24 months. Of the total, 66 were women (63.5%) and 38 were men (36.5%). The average age was 40 years (range: 18–76 years). Of 104 patients, 86 (82.7%) were of genotype 3, 15 (14.9%) were of genotype 1 and 3 (2.9%) were of genotype 4. Ninety-two (88%) were noncirrhotic and 12 (11.5%) were cirrhotic. Ninety-five (95.2%) were treatment naïve. Among genotype 1 and 4, all patients achieved rapid virologic response and SVR 12. Of 86 genotype 3 patients, 78 (90.6%) were noncirrhotic and 8 (9.3%) were cirrhotic. Among genotype 3 patients without cirrhosis, 75 (96%) achieved SVR 12 while 6 (75%) with cirrhosis achieved SVR 12. All patients tolerated the combination well; however, some patients experienced nausea (26%), headache (25%) and fatigue (21%). No patient had to discontinue therapy due to adverse drug reactions. Single tablet LED and SOF combination is safe and effective in genotype 3 patients without cirrhosis even without ribavirin. Being effective in genotype 3, the combination can be used as a pangenotypic drug in patients without cirrhosis. [ABSTRACT FROM AUTHOR]

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Background: Hepatitis C virus (HCV) is a blood-borne virus which globally affects around 79 million people and is associated with high morbidity and mortality. Chronic infection leads to cirrhosis in a large proportion of patients and often causes hepatocellular carcinoma (HCC) in people with cirrhosis. Of the 6 HCV genotypes (G1-G6), genotype-3 accounts for 17.9% of infections. HCV genotype-3 responds least well to directly-acting antivirals and patients with genotype-3 infection are at increased risk of HCC even if they do not have cirrhosis., Aim: To systematically review and critically appraise all risk factors for HCC secondary to HCV-G3 in all settings. Consequently, we studied possible risk factors for HCC due to HCV-G3 in the literature from 1946 to 2023., Methods: This systematic review aimed to synthesise existing and published studies of risk factors for HCC secondary to HCV genotype-3 and evaluate their strengths and limitations. We searched Web of Science, Medline, EMBASE, and CENTRAL for publications reporting risk factors for HCC due to HCV genotype-3 in all settings, 1946-2023., Results: Four thousand one hundred and forty-four records were identified from the four databases with 260 records removed as duplicates. Three thousand eight hundred and eighty-four records were screened with 3514 excluded. Three hundred and seventy-one full-texts were assessed for eligibility with seven studies included for analysis. Of the seven studies, three studies were retrospective case-control trials, two retrospective cohort studies, one a prospective cohort study and one a cross-sectional study design. All were based in hospital settings with four in Pakistan, two in South Korea and one in the United States. The total number of participants were 9621 of which 167 developed HCC (1.7%). All seven studies found cirrhosis to be a risk factor for HCC secondary to HCV genotype-3 followed by higher age (five-studies), with two studies each showing male sex, high alpha feto-protein, directly-acting antivirals treatment and achievement of sustained virologic response as risk factors for developing HCC., Conclusion: Although, studies have shown that HCV genotype-3 infection is an independent risk factor for end-stage liver disease, HCC, and liver-related death, there is a lack of evidence for specific risk factors for HCC secondary to HCV genotype-3. Only cirrhosis and age have demonstrated an association; however, the number of studies is very small, and more research is required to investigate risk factors for HCC secondary to HCV genotype-3., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

This study aims to evaluate the clinical effectiveness in terms of sustained virological response (SVR), predictors of SVR and safety of available second‐generation generic direct‐acting antivirals in Pakistani chronic hepatitis C patients. This is a retrospective study conducted in multiple centers of Pakistan from January 2015 to January 2019. The samples include patients infected with chronic hepatitis C virus, regardless of virus genotype, cirrhosis, or prior treatment. A total of 993 patients were included in the present study, with the majority receiving sofosbuvir with daclatasvir (95%), sofosbuvir with daclatasvir and ribavirin (4%), and sofosbuvir with ribavirin (1%). There were 96% cases of chronic hepatitis, 3% cases compensated cirrhosis, and 1% cases of decompensated cirrhosis. Genotype 3 (99.6%) was the most common genotype. Overall SVR after 12 weeks was 98% for all treatment regimens. High SVR12 was observed with sofosbuvir in combination with daclatasvir (98.5%), then sofosbuvir in combination with daclatasvir and ribavirin (90.2%) and sofosbuvir in combination with ribavirin (75%). SVR rates were high in chronic hepatitis C patients (98.2%) as compared with cirrhotic patients (92.1%) and it was high in treatment‐naive (98.8%) then interferon experienced patients (90.1%). In multivariate binary logistic regression analysis, patients' education status, treatment strategy, viral load, and alanine aminotransferase had a statistically significant association with SVR at 12 weeks. No major adverse events occurred which required treatment discontinuation. Generic oral direct acting antiviralss (sofosbuvir with daclatasvir) achieved higher SVR12 rates and were well tolerated in this large real‐world cohort of genotype 3 infected patients. Highlights: In this study we have analyzed the clinical effectiveness, predictors and safety profile of available second generation generic direct‐acting antivirals in Pakistani chronic Hepatitis C patients.Generic sofosbuvir with daclatasvir achieved 98% SVR rate after 12 weeks in this large real‐world cohort of genotype 3 infected patients.The predictors of low SVR12 were poor education status, high viral load and elevated level of ALT. [ABSTRACT FROM AUTHOR]

Abstract Background Chronic hepatitis C virus (HCV) genotype (GT) 3 infection with advanced liver disease has emerged as a challenging to treat by direct-acting antivirals (DAAs), but the efficacy of DAAs in Chinese HCV-GT3 patients is rarely reported. This study aimed to analyze the efficacy of sofosbuvir (SOF)-based regimens in Chinese patients with HCV-GT3 and compensated liver disease. Methods This was a registered retrospective study. All patients had completed at least 12 weeks SOF-based regimens therapy (with or without RBV), and were followed up for at least 24 weeks after therapy discontinuation. The primary endpoint was sustained virological response 24 weeks after end of therapy (SVR24). Results A total of 102 patients who completed at least 12 weeks therapy were finally included, with 57 in SOF + Daclatasvir (SOF + DCV), 24 in SOF + DCV + ribavirin (RBV) and 21 in SOF/Velpatasvir (SOF/VEL). The total SVR24 rate was achieved in 90.20% (92/102), with 85.96% (49/57) in SOF + DCV, 91.67% (22/24) in SOF + DCV + RBV and 100.00% (21/21) in SOF/VEL. Among 10 relapsed patients (8 in SOF + DCV and 2 in SOF + DCV + RBV), the short course (12 weeks) of therapy and no RBV addition may be the leading cause. In this cohort, the SVR24 rate was not statistically different between patients with and without cirrhosis (81.82% [27/33] vs. 94.20% [65/69], P = 0.073). Additionally, both FIB-4 (4.03 vs. 2.08, P

Hepatitis E virus (HEV) infection is a major health problem worldwide. In developed countries, zoonotic transmission of HEV genotypes (Gt) 3 and 4 is caused by the ingestion of raw or undercooked meat of infected pigs and wild boars, the main reservoirs of HEV. However, additional animals may harbour HEV or HEV-related strains, including carnivores. In this study, we investigated the molecular epidemiology of orthohepeviruses in wild canids by screening a total of 136 archival faecal samples, collected from wolves (42) and red foxes (94) in Northwestern Italy. Orthohepevirus RNA was identified in a faecal specimen, collected from a wolf carcass in the province of La Spezia (Liguria Region, Italy). The nearly full-length (7212 nucleotides) genome of the strain HEV/81236/Wolf/2019/ITA (GenBank accession no. MZ463196) was determined by combining a sequence-independent single-primer amplification (SISPA) approach with the Oxford Nanopore Technologies sequencing platform. Upon phylogenetic analysis, the HEV detected in wolf was segregated into clade HEV-3.1, displaying the highest nucleotide (nt) identity (89.0–93.3%) to Gt3 strains belonging to subtype c. Interestingly, the wolf faecal sample also contained porcine astrovirus sequences, endorsing the hypothesis of a dietary origin of the HEV strain due to preying habits.

Information on hepatitis E virus (HEV) strains circulating in animal reservoirs in Bulgaria is currently lacking. Herein, by screening HEV seropositive sera obtained from Bulgarian swine and wild boars, viral RNA was detected at high prevalence rate (28.2%) in industrial pigs. Sequence analysis of the partial polymerase (RdRp) region revealed the highest genetic correlation with HEVs of genotype (Gt) 3 identified in French and Dutch patients. For three such strains, a 700-bp fragment of the open reading frame 2 gene was generated. On phylogenetic analysis, the Bulgarian strains clustered tightly (93.8–98.3% nt) with human and animal HEVs classified within the Gt3 subtype c.

Aim: Few studies have evaluated real-world clinical experience with sofosbuvir (SOF) plus ribavirin (RBV) in hepatitis C virus (HCV) genotypes 2 and 3 infections from Turkey. Thus, this study aimed to investigate the results of sofosbuvir plus ribavirin therapy in genotype 2 and 3 cases followed in an infectious disease clinic at a university hospital in Hatay, southern Turkey. Material and Methods: In this single-centre, retrospective, observational study, 58 eligible patients treated with SOF/RBV (400 mg of SOF plus weight-based RBV) therapy between October 2016 and February 2019 were examined. Forty-three patients who had completed the duration of treatment and had known virological response status were evaluated for treatment outcomes. Results: SOF/RBV achieves a sustained virological response (SVR) rate of 96.3% and 100% in the HCV genotype 2 and 3 groups, respectively, with treatment duration of 12-24 weeks. No patient experienced a virologic breakthrough while only one experienced virologic relapse after the completion of therapy. The incidence of adverse events was 25.5% (11/43) while the most common (11.6%) adverse event was ribavirin-related hemolytic anemia. Conclusion: The current study revealed that the SOF/RBV therapy achieved excellent response rates with a good safety profile in non-cirrhotic Turkish patients infected with HCV genotype 2 or 3. [ABSTRACT FROM AUTHOR]

Objective: In 2015, Georgia launched HCV elimination program. Initially, patients with advanced liver disease were treated with sofosbuvir-based regimen—the only DAA available for all genotypes. Purpose of the study was assessing real-world data of treatment outcome among patients with HCV GEN3 and advanced liver fibrosis with sofosbuvir-based regimens. Results: Totally 1525 genotype 3 patients were eligible for analysis; most (72.6%) were aged > 45 years, majority were males (95.1%), and all (100%) had advanced liver disease (F3 or F4 by METAVIR score based on elastography). Of those who received sofosbuvir/ribavirin (SOF/RBV) for 24 weeks, 79.3% achieved SVR, while 96.5% who received sofosbuvir/pegylated interferon/ribavirin (SOF/PEG/RBV) for 12 weeks achieved SVR (p < 0.01). Among patients with liver cirrhosis (defined as F4) overall cure rate was 85.7% as opposed to 96.4% for those with F3. Females were more likely to be cured (98.7% vs 89.7%; OR = 8.54). Patients aged 31–45 years had higher likelihood of achieving SVR compared to patients aged 46-60 years (95.7% vs 87.4%; OR = 0.32,). Independent predictors of SVR were treatment with SOF/PEG/RBV (aOR = 6.72) and lower fibrosis stage (F3) (aOR = 4.18). Real-world experience among HCV GEN3 patients with advanced liver fibrosis and treated by sofosbuvir regimen w/o PEGIFN, demonstrated overall high SVR rate. [ABSTRACT FROM AUTHOR]

Background & Aims: In the direct‐acting antiviral era, treatment of genotype‐3 HCV (HCV‐GT3) is still challenging. Real‐life comparisons between recommended regimens, sofosbuvir (SOF)+daclatasvir (DAC), SOF/velpatasvir (VEL), glecaprevir/pibrentasvir (GLE/PIB), are scarce. We aimed at filling this data gap. Methods: Sustained virological response 12 weeks after treatment completion (SVR12) was assessed for all HCV‐GT3 patients consecutively treated within the Lombardia web‐based Navigatore HCV‐Network; differences in SVR12 across regimens were evaluated by logistic regression. Results: Of the 2082 subjects with HCV‐GT3, 1544 were evaluable for comparisons between regimens: SOF + DAC (1023, 66.2%), SOF/VEL (369, 23.9%), GLE/PIB (152, 9.8%). Patients treated with former regimens were more frequently male, cirrhotic, HIV‐positive, pretreated, used ribavirin in their regimen, and had lower baseline HCV‐RNA. SVR12 was similar across groups: 94.8% in SOF + DAC, 97.6% in SOF/VEL, 96.7% in GLE/PIB (P =.065). At univariate analysis, SVR12 was associated with female gender (97.9% vs 94.8%, P =.007) and lower median pretreatment Log10HCV‐RNA (5.87 vs 6.20, P =.001). At multivariate logistic regression analysis, treatment with SOF/VEL was associated with a higher likelihood of SVR12 than SOF + DAC, but only in the absence of ribavirin (98% vs 90.3%). Female gender and lower pretreatment HCV‐RNA were independently associated with SVR12. Conclusions: In a large real‐life setting of HCV‐GT3‐infected patients with a high proportion of cirrhosis, the success rate was remarkable. The slight advantage of SOF/VEL on SOF + DAC was significant only without ribavirin. The current prescription shift towards novel regimens (ie SOF/VEL and GLE/PIB) in easier‐to‐treat patients allows ribavirin‐free and shorter schedules without mining SVR12 in this <> genotype. [ABSTRACT FROM AUTHOR]

Summary: Twelve weeks sofosbuvir/velpatasvir (SOF/VEL) is a highly effective pan‐genotypic regimen for hepatitis C. Phase 2 data suggest 8 weeks of treatment may be sufficient for previously untreated noncirrhotic patients with genotype 3 (GT3) infection. To maximize the number of patients potentially cured within a fixed treatment budget, we elected to treat such patients locally eligible for treatment (F2/3), with 8 weeks of SOF/VEL. By local protocol, treatment‐naive patients with F2 (LSM > 6.9kPa < 9.5kPa) or F3 fibrosis (≥9.5kPa < 12.5kPa) were eligible for 8‐week SOF/VEL treatment. Patients commencing treatment before 1 Oct 2017 were identified from the Scottish HCV database. Baseline and treatment outcome data obtained. Ninety patients were included for analysis (72 (80%) male, mean age 45 (IQR ± 8.4), 28 (31.1%) F3 fibrosis). Opioid agonist therapy (OAT) was prescribed in 82 (91.1%) patients. Of 49 patients attending Glasgow city Alcohol and Drug Services, 27 (55.1%) had evidence of recent drug use (< 3 months) including 8 (16.3%) with self‐reported intravenous drug use. On an intention‐to‐treat basis, SVR rates were 86/90 (95.6%, 95% CI 89.0‐98.8). Excluding those who prematurely discontinued treatment (n = 4), died prior to SVR testing (n = 1) or whom experienced reinfection (n = 1), per‐protocol SVR rate was 84/84 (100%, 95% CI 95.7‐100.0). In conclusion, eight‐week SOF/VEL is highly effective in treatment‐naive GT3 patients with significant fibrosis. This offers a non‐protease inhibitor‐based 8‐week regimen which may be useful for complex drug interactions or where time‐limited opportunity for treatment. In limited resource settings, reduction in drug acquisition costs may help achieve progress towards the goal of HCV elimination. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy of sofosbuvir with daclatasvir and its promising effects on liver functions especially in respect to earlier treatment failure patients to frame an appropriate regimen for them. Study Design: A prospective, observational cohort study. Place and Duration of Study: Pak Emirates Military Hospital Rawalpindi, Army Medical College Rawalpindi, from Jan 2018 to Dec 2018. Methodology: A total of 114 patients infected with genotype 3 were segregated into two groups according to their treatment status with 57 patients in each group. They received treatment according to the World Health Organization guidelines to assess the efficacy in terms of sustained virological response upon 12 weeks of completion of treatment (SVR 12) and to evaluate changes in serum alanine aminotransferase (ALT), total bilirubin, albumin and prothrombin time (PT). The results were comparatively analyzed between the groups. Results: The percentage of patients attaining SVR 12 was nearly same in both the groups (94.7% vs 93%). Improvement in ALT, total bilirubin, serum albumin and prothrombin time was highly significant (p<0.001). When all the parameters were statistically compared, no substantial difference in the results was obtained. Conclusion: This study exhibited that the regimen consisting of sofosbuvir and daclatasvir is equally effective and beneficial for newly diagnosed and earlier treatment failure patients by eradicating the virus and improving liver function parameters which ultimately result in improved quality of life. [ABSTRACT FROM AUTHOR]

BACKGROUND & OBJECTIVE: The role of Velpatasvir/Sofosbuvir in the treatment of hepatitis C virus type 3 infection is evaluated in terms of virologic responses. i.e Rapid Virological Response (RVR) End of treatment response (ETR) and Sustained virological response (SVR 12). METHODOLOGY: This was a descriptive case study conducted in Liver OPD of Benazir Bhutto Hospital during 01 November 2018 to 30 April 2019, in which 100 patients of HCV were enrolled, all of them had HCV genotype 3 infection. Every patient was treated with combination of Velpatasvir/Sofosbuvir 100mg/400 mg Once Daily as part of treatment regimen of HCV infection for 12 weeks. Pre-treatment HCV RNA QUANTITATIVE PCR was done, which was repeated on 4, 12 weeks of treatment and then 12 weeks post treatment. RESULTS: Among 100 patients, 51 (51%) were male and 49 (49%) were females. Mean age of patients was 43.2 ± 10.4 years (mean ± SD). Mean BMI of enrolled patients was 21.34 ± 2.40 kg/m2. 33% patients were cirrhotic while 67% were non cirrhotic. 53% patients were treatment experienced while 47% were treatment naïve. Rapid Virological Response (RVR) was achieved in 92%, End of treatment response (ETR) was achieved in 96%, while Sustained Virological response (SVR12) was achieved in 99% patients. The results were stratified according to age, gender and BMI. There was no effect of these parameters on the final results. CONCLUSION: Virological response (RVR, ETR, SVR12) of Velpatsvir/Sofosbuvir and Ribavirin is encouraging. [ABSTRACT FROM AUTHOR]

Abstract Background Six distinct genetic variants (genotypes 1 − 6) of hepatitis C virus (HCV) exist globally. Certain genotypes are more prevalent in particular countries or regions than in others but, globally, genotype 3 (GT3) is the second most common. Patients infected with HCV GT1, 2, 4, 5 or 6 recover to a greater extent, as measured by sustained virological response (SVR), following treatment with regimens based on direct-acting antivirals (DAAs) than after treatment with older regimens based on pegylated interferon (Peg-IFN). GT3, however, is regarded as being more difficult to treat as it is a relatively aggressive genotype, associated with greater liver damage and cancer risk; some subgroups of patients with GT3 infection are less responsive to current licensed DAA treatments. Newer DAAs have become available or are in development. Methods According to PRISMA guidance, we conducted a systematic review (and descriptive statistical analysis) of data in the public domain from relevant clinical trial or observational (real-world) study publications within a 5-year period (February 2011 to May 2016) identified by PubMed, Medline In-Process, and Embase searches. This was supplemented with a search of five non-indexed literature sources, comprising annual conferences of the AASLD, APASL, CROI, EASL, and WHO, restricted to a 1-year period (April 2015 to May 2016). Results Of the all-oral regimens, the efficacy (SVR12 ≥ 90%) of sofosbuvir plus daclatasvir- and velpatasvir-based regimens in clinical trials supports and reinforces their recommendation by guidelines. Other promising regimens comprise grazoprevir + elbasvir + sofosbuvir, and ombitasvir + paritaprevir/ribavirin + sofosbuvir. Newer regimens incorporating pibrentasvir + glecaprevir or grazoprevir + ruzasvir + MK-3682 (uprifosbuvir), offer all-oral, ribavirin-free SVR12 rates consistently greater than 95%. Observational studies report slightly lower overall SVR rates but reflect corresponding clinical trial data in terms of treatments most likely to achieve good responses. Conclusions On the basis of SVR12, we established that for treating GT3 infections (i) regimens incorporating newer DAAs are more effective than those comprising older DAAs, and (ii) ribavirin may be of less benefit in newer DAA regimens than in older DAA regimens. The analysis provides evidence that DAA regimens can replace Peg-IFN-based regimens for GT3 infection.