Hepatitis C Virus Genotype 1a Research Articles

Efficacy of sofosbuvir in the treatment-naïve patients infected with 3a genotype of Hepatitis C.

Objectives: This study was conducted to test the efficacy of Sofosbuvir in patients of genotype 3a who are treatment-naïve which represents the most common setting in Pakistan. Study Design: Experimental study. Setting: Mayo Hospital, Lahore, Punjab, Pakistan. Period: August 2016 to September 2017. Material & Methods: We used an Open label and Quasi Experimental Study Design to test the efficacy of Sofosbuvir in 262 treatment-naïve patients. The duration of the therapy was 24 weeks. All patients were treated with Sofosbuvir 400mg once daily and Ribavirin 400 mg thrice daily. The end of treatment response i.e. ETR was noted at the end by determining the viral load by Polymerase Chain Reaction (PCR). Results: Of the 262 patients included in the study, 43 patients left the treatment either due to financial constraints barring them from following up or due to non-compliance. 11 patients left the treatment due to adverse events. 208 patients completed the 24-week therapy from which 201 (96.6 %) patients showed +Ve ETR. Two patients showed relapse both of whom had high viral load. Five patients were non-responders. The rate of discontinuation of Sofosbuvir due to adverse effects was low (4-5%). Conclusion: Patients with HCV genotype 3a have shown promising improvement in treatment response with Sofosbuvir as compared to the older treatment regimes. In contrast to the long duration of treatment and more disabling adverse effects profile of conventional regimes, Sofosbuvir, with its greater therapeutic efficacy and relatively well-tolerated adverse effects, is expected to provide a break-through in treating Hepatitis C and minimizing the incidence of its complications.

Required concentration index quantifies effective drug combinations against hepatitis C virus infection

Successful clinical drug development requires rational design of combination treatments based on preclinical data. Anti-hepatitis C virus (HCV) drugs exhibit significant diversity in antiviral effect. Dose-response assessments can be used to determine parameters profiling the diverse antiviral effect during combination treatment. In the current study, a combined experimental and mathematical approaches were used to compare and score different combinations of anti-HCV treatments. A “required concentration index” was generated and used to rank the antiviral profile of possible double- and triple-drug combinations against HCV genotype 1b and 2a. Rankings varied based on target HCV genotype. Interestingly, multidrug (double and triple) treatment not only augmented antiviral activity, but also reduced genotype-specific efficacy, suggesting another advantage of multidrug treatment. The current study provides a quantitative method for profiling drug combinations against viral genotypes, to better inform clinical drug development.

Changes in the Distribution Pattern of Hepatitis C Virus Genotypes Among Chronic Hepatitis Patients: a Cross-Sectional Study

Hepatitis C virus (HCV) is a major cause of liver diseases. It has been determined that HCV genotypes have a distinct geographical distribution, clinical outcome, and response to antiviral therapy. Over the past years, many studies have reported that HCV genotype 1a is the dominant genotype in Ahvaz city. In recent years, changes in the distribution pattern of HCV genotypes of different geographical regions have attracted a great deal of attention; hence, the aim of this study was to accurately evaluate such probable changes in Ahvaz in southwestern Iran. This is a cross-sectional study conducted from September 2017 to August 2020, including 262 patients suffering from chronic hepatitis C. HCV-RNA was extracted, and HCV genotyping was performed by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) method. To evaluate the association between HCV genotype, age, gender, and viral load, statistical analyses were done by SPSS software. HCV genotyping was done on 260 patients where genotype 3a had the highest prevalence over the period of 4 years with an average of 48.1%, followed by genotype 1a (46.5%). HCV genotype of two patients was not typeable. Although the difference between the two genotypes is currently small, the main result was finding an increasing trend in the prevalence of genotype 3a in recent years. The present study showed that the distribution pattern of HCV genotypes is gradually changing among chronic hepatitis C patients in Ahvaz city. The most important cause of such changes could be the alteration in HCV transmission routes and the increase in migration from areas where genotype 3 is dominant.

Prevalence and Genotype Distribution of Hepatitis C Virus from 1,668 Individuals of Sichuan Area in China.

Hepatitis C virus (HCV) is one of the main causes of liver fibrosis, chronic hepatitis, and liver cirrhosis. The aim of this study is to determine the prevalence of HCV, age-dependent prevalence and genotypes distribution in a large number of clinical samples in Sichuan area of China. In the past five years from 2014 to 2018, a total number of 4,508 individuals received the serum HCV-RNA analysis in the Sichuan Provincial People's Hospital. Viral nucleic acid was extracted from the serum samples and amplified using COBAS AmpliPre/COBAS TaqMan Detection Platform. Five HCV genotypes (1b, 2a, 3a, 3b, and 6a) of serum samples from 469 HCV positive individuals collected from 2016 to 2018 were analyzed using the PCR-fluorescence probe technique. A total of 1,668 individuals had positive results by high precision HCV-RNA quantitative technique, corresponding to a crude prevalence of 37.0% (95% confidence interval: 33.6 - 40.3%). The majority of HCV positive individuals were aged over 41 years, accounting for 80.7% (1,346/1,668, CI: 72.3 - 87.1%). Among the nine age groups, the 41 - 50-year age group had the highest HCV prevalence of 29.8% (497/1,668, CI: 25.6 - 32.3%). Of the 469 HCV-RNA positive serum samples collected in 2016 - 2018, genotype 1b was the most frequent type found in 357 individuals, corresponding to a prevalence of 76.1% (CI: 72.3 - 80.0%). Positive rates of HCV in the years of 2014 to 2018 showed a downward trend year by year, of which a majority of positive cases were aged over 41 years. HCV was distributed with multi-genotype features while genotype 1b yielded a very high prevalence in the Sichuan area. The results have potential for prevention and treatment of HCV infection, as well as epidemiological research.

Virucidal activity of oriental hornet Vespa orientalis venom against hepatitis C virus.

BackgroundHepatitis C virus (HCV) infection is a major worldwide health problem that can cause liver fibrosis and hepatocellular carcinoma (HCC). The clinical treatment of HCV infection mainly relies on the use of direct-acting antivirals (DAAs) that are usually expensive and have side effects. Therefore, achieving the discovery of more successful agents is always urgent. In this context, antiviral compounds that inhibit viral infections and disease progression with important therapeutic activities have been identified in animal venoms including arthropod toxins. This indicates that arthropod venoms represent a good natural source of promising candidates for new antivirals. MethodsThe antiviral activity of the wasp venom (WV), isolated from the Oriental hornet (Vespa orientalis), was assessed using cell culture technique with human hepatocellular carcinoma-derived cell line (Huh7it-1) and the recombinant strain of HCV genotype 2a (JFH1). ResultsThe results revealed that WV inhibited HCV infectivity with 50% inhibitory concentration (IC50) of 10 ng/mL, while the 50% cytotoxic concentration (CC50) was 11,000 ng/mL. Time of addition experiment showed that the WV blocked HCV attachment/entry to the cells probably through virucidal effect. On the other hand, the venom showed no inhibitory effect on HCV replication. ConclusionWV can inhibit the entry stage of HCV infection at non-cytotoxic concentrations. Therefore, it could be considered a potential candidate for characterization of natural anti-HCV agents targeting the entry step.

Hepatitis C virus genotype and its correlation with viral load in patients from Kathmandu, Nepal.

Knowledge about the distribution of hepatitis C virus (HCV) genotype and its correlation with viral load are important for the decision of treatment and the prediction of disease progression, however such information is very limited in Nepal. Here, we investigated the distribution of HCV genotypes and viral load for HCV-infected patients from Kathmandu, Nepal. Ninety-six patients with HCV infection and not on antiviral therapy were enrolled from three different medical centers in Kathmandu valley, Nepal. Demographics were recorded and blood samples were collected. Plasma was separated and HCV RNA was extracted. Reverse transcriptase PCR (RT-PCR) was performed to measure the viral load, and virus genotype was determined. Genotype 3a (n = 53, 55.2%) was the most prevalent, followed by 1b (n = 19, 19.8%), 1a (n = 18, 18.8%), 5a (n = 3, 3.1%), and mix types (n = 3, 3.1%). The median viral load for HCV genotype 1a was 770,942 IU/mL (IQR, 215,268-3,720,075), 1b was 700,000 IU/mL (IQR, 431,560-919,000), 3a was 1,060,000 IU/mL (IQR, 641,050-6,063,500), 5a was 673,400 IU/mL, and mixed was 6,428,000 IU/mL. A correlation between genotype and viral load was observed (p = 0.02), of which genotype 3a showed a high viral load. HCV genotypes 1a, 1b, 3a, and 5a were identified in Kathmandu, Nepal, and mixed genotype patients were observed in the patients studied. HCV genotype showed a correlation with viral load in patient plasma. This finding may contribute to the treatment and prevention of hepatitis C in Kathmandu, Nepal.

Current trends of Hepatitis C virus genotypes and associated risk factors in hemophilia patients in Pakistan.

Hemophilia is a rare bleeding disorder that needs plasma or clotting factor concentrate transfusion. Therefore chances of blood-borne pathogens like HCV transmission increase due to high prevalence in healthy donors. This study was aimed to determine the prevalence of HCV genotypes and associated risk factors in hemophilia patients of Khyber Pakhtunkhwa, Pakistan. Blood samples and data were collected from 672 hemophiliacs after proper consent obtained from each patient. Samples were analyzed for anti-HCV, HCV RNA and HCV genotype/s detection. Of the total, 22.32% (150) were anti-HCV positive, of which HCV RNA was detected in 18.45% (124) individuals. HCV genotype 3a was found with significantly higher prevalence (p<0.05) (19.35%) as compared to 2a (16.13%) and 1a (12.90%). HCV-3b and HCV-4 were found each in 3.22% samples. Dual infection of genotypes was found in 22.58% of individuals and 22.58% HCV RNA positive sampels were not typed. A total of 572 (85.12%) subjects had hemophilia A and 100 (14.88%) had hemophilia B. In hemophiliacs A the most dominant genotype was 3a (19.27%) while in hemophilia B, genotype 1a was prevalent (26.67%). Whole blood and plasma transfusion were observed as the main risk factors of HCV. It is concluded that HCV genotype 3a and 2a are prevalent in hemophilia patients of Khyber Pakhtunkhwa Pakistan and the main risk factor observed was an unscreened whole blood transfusion.

Investigation of Genotype Distribution in Hepatitis C Patients in Giresun Province

Introduction: HCV infections are an important public health problem due to their high chronicity, cirrhosis and advanced complications like hepatocellular carcinoma. In HCV infections, it is important and necessary to determine genotypes before treatment because treatment times and protocols vary according to genotypes. The aim of this study was to determine the distribution of HCV genotypes in HCV-RNA positive individuals in Giresun province and to investigate whether there was a statistically significant difference between genotypes and patient ages. Materials and Methods: HCV-RNA level and HCV genotype of 147 patients were included in the study. HCV RNA levels of the samples were studied by QIAsymphony SP (Qiagen) automated device, genotype determination by Rotor Gene Q (Qiagen) automated device by “real-time polymerase chain reaction (PCR)” method. Each sample was tested for HCV genotypes 1a, 1b, 2, 3, 4, 5a and 6. Results: Of the 147 patients genotyped; 128 (87%) genotype 1b, 9 (6%) genotype 1a, 8 (6%) genotype 3, 2 (1%) genotype 2 were detected. Genotypes 4, 5a and 6 were not detected. According to the HCV genotype distribution, median age and range (min.-max.) of the patients weren50 (30-83) for 1a, 70 (22-87) for 1b, 48.5 (36-61) for 2 and 33 (25-52) for 3. HCV RNA levels were between 37 and 12.630.170 IU/mL. Conclusion: The predominant genotype in the world and Turkey is genotype 1b. In our study, the most common genotype was also genotype 1b (87%), consistent with other studies in our country. This study contributed to HCV genotype distribution data in our region and country.

Seroprevalence of hepatitis B virus and hepatitis C virus infection among Malaysian population

Malaysia is a country with an intermediate endemicity for hepatitis B. As the country moves toward hepatitis B and C elimination, population-based estimates are necessary to understand the burden of hepatitis B and C for evidence-based policy-making. Hence, this study aims to estimate the prevalence of hepatitis B and C in Malaysia. A total of 1458 participants were randomly selected from The Malaysian Cohort (TMC) aged 35 to 70 years between 2006 and 2012. All blood samples were tested for hepatitis B and C markers including hepatitis B surface antigen (HBsAg), anti-hepatitis B core antibody (anti-HBc), antibodies against hepatitis C virus (anti-HCV). Those reactive for hepatitis C were further tested for HCV RNA genotyping. The sociodemographic characteristics and comorbidities were used to evaluate their associated risk factors. Descriptive analysis and multivariable analysis were done using Stata 14. From the samples tested, 4% were positive for HBsAg (95% CI 2.7–4.7), 20% were positive for anti-HBc (95% CI 17.6–21.9) and 0.3% were positive for anti-HCV (95% CI 0.1–0.7). Two of the five participants who were reactive for anti-HCV had the HCV genotype 1a and 3a. The seroprevalence of HBV and HCV infection in Malaysia is low and intermediate, respectively. This population-based study could facilitate the planning and evaluation of the hepatitis B and C control program in Malaysia.

Efficacy and safety of ledipasvir/sofosbuvir in 5,028 Mongolian patients infected with genotype 1 hepatitis C virus: A multicenter study.

Background/AimsLedipasvir/sofosbuvir (LDV/SOF) shows high efficacy and safety in patients with genotype 1-hepatitis C virus (HCV). We aimed to investigate the efficacy and safety of LDV/SOF in real-world Mongolian patients.MethodsBetween 2015 to 2019, 23 (0.5%) and 5,005 patients (99.5%) with genotype 1a and 1b HCV, respectively, were treated with a fixed-dose tablet containing 90 mg ledipasvir and 400 mg sofosbuvir for 12 weeks, and 81 patients (1.6%) with previous experience of interferon (IFN)-based treatment received additional 1,000 mg ribavirin. HCV RNA was measured at 4, 12, and 24 weeks after the first dose to determine rapid virologic response, end of treatment response (ETR), and sustained virologic response at 12 weeks after end of treatment (SVR12).ResultsMost patients (n=5,008; 99.6%) achieved ETR and SVR12 without virologic relapse. Patients with genotype 1a showed low rates of ETR and SVR12 in only 16 patients (69.6%). There was no significant difference in SVR12 rate between patients regardless of IFN experience (n=81; 1.6%), cirrhosis (n=1,151; 22.9%), HCV RNA >6×106 IU/mL (n=866; 17.2%), or liver stiffness >9.6 kPa (n=1,721; 34.2%) (100.0%, 99.3%, 99.4%, and 99.4%, respectively). No severe adverse events (AEs) were reported, and there was no dose reduction or interruption due to AE. The most common AEs were headache (n=472; 9.4%), fatigue (n=306; 6.2%), abdominal discomfort (n=295; 5.9%), and skin rash (n=141; 2.8%).ConclusionsLDV/SOF showed high efficacy and safety for patients with genotype 1, especially 1b HCV, in Mongolia. The real-world data might be applicable to patients in other Asian-Pacific countries.

Screening and identification of bioactive compounds from citrus against non-structural protein 3 protease of hepatitis C virus genotype 3a by fluorescence resonance energy transfer assay and mass spectrometry.

BACKGROUNDHepatitis C virus genotype 3a (HCV G3a) is highly prevalent in Pakistan. Due to the elevated cost of available Food and Drug Administration-approved drugs against HCV, medicinal natural products of potent antiviral activity should be screened for the cost-effective treatment of the disease. Furthermore, from natural products, active compounds against vital HCV proteins like non-structural protein 3 (NS3) protease could be identified to prevent viral proliferation in the host.AIMTo develop cost-effective HCV genotype 3a NS3 protease inhibitors from citrus fruit extracts.METHODSFull-length NS3 without co-factor non-structural protein 4A (NS4A) and codon optimized NS3 protease in fusion with NS4A were expressed in Escherichia coli. The expressed protein was purified by metal ion affinity chromatography and gel filtration. Citrus fruit extracts were screened using fluorescence resonance energy transfer (FRET) assay against the protease and polyphenols were identified as potential inhibitors using electrospray ionization-mass spectrometry (MS)/MS technique. Among different polyphenols, highly potent compounds were screened using molecular modeling approaches and consequently the most active compound was further evaluated against HCV NS4A-NS3 protease domain using FRET assay.RESULTSNS4A fused with NS3 protease domain gene was overexpressed and the purified protein yield was high in comparison to the lower yield of the full-length NS3 protein. Furthermore, in enzyme kinetic studies, NS4A fused with NS3 protease proved to be functionally active compared to full-length NS3. So it was concluded that co-factor NS4A fusion is essential for the purification of functionally active protease. FRET assay was developed and validated by the half maximal inhibitory concentration (IC50) values of commercially available inhibitors. Screening of citrus fruit extracts against the native purified fused NS4A-NS3 protease domain showed that the grapefruit mesocarp extract exhibits the highest percentage inhibition 91% of protease activity. Among the compounds identified by LCMS analysis, hesperidin showed strong binding affinity with the protease catalytic triad having S-score value of -10.98.CONCLUSIONFused NS4A-NS3 protease is functionally more active, which is effectively inhibited by hesperidin from the grapefruit mesocarp extract with an IC50 value of 23.32 µmol/L.

Molecular Characterization of Hepatitis C Virus for Developed Antiviral Agents Resistance Mutations and New Insights into in-silico Prediction Studies.

BackgroundIdentification and characterization of developed antiviral drug resistance mutations are key to the success of antiviral therapies against hepatitis C virus (HCV), which remains a worldwide highly prevalent pathogenic disease. Although most studies focus on HCV genotypes 1, 2 or 3, the investigation of drug resistance in HCV genotype 4, predominant in North Africa, is especially significant in Egypt.MethodsWe performed mutational and genotypic analysis of the untranslated region (UTR) and nonstructural protein 5B (NS5B) drug resistance-associated regions of HCV for patients in the surrounding villages of Mansoura city, who were not responding to different antiviral treatments (sofosbuvir (SOF), ribavirin, and interferon). Furthermore, molecular modelling approaches (homology modelling and docking studies) were used to investigate the significance of the identified NS5B mutations for SOF and ribavirin binding in the HCV genotype 4a NS5B active site.ResultsGenotypic analysis confirmed all samples to have genotype 4 with sub-genotype 4a predominant. Partial sequencing of the UTR and NS5B resistance-associated regions identified D258E, T282S and A307G mutations in all isolates of NS5B. The UTR mutation site at position 243 was associated with interferon resistance, whereas the NS5B T282S mutation was considered as significant for SOF and ribavirin resistance. Docking studies in the HCV genotype 4a homology model predict SOF and ribavirin to accommodate a nucleotide-like binding mode, in which the T282 residue does interfere with the binding as it would in HCV genotypes 1 and 2. Mutation energy calculations predict T282S to moderately destabilize the binding of SOF and ribavirin by 0.57 and 0.47 kcal/mol, respectively.ConclusionThe performed study identified and characterized several antiviral drug resistance mutations of HCV genotype 4a and proposed a mechanism by which the T282S mutation may contribute to SOF and ribavirin resistance.

Rapid visual detection of hepatitis C virus using a reverse transcription loop-mediated isothermal amplification assay

ObjectivesThe aim was to develop a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for the detection of hepatitis C virus (HCV) in a single closed tube. MethodsPlasma samples were collected from 200 HCV-infected patients. HCV-RNA was detected by one-step RT-LAMP processed at 65 °C for 60 min. The amplified products were detected by hydroxynaphthol blue (HNB)-dependent visual method and gel electrophoresis. Specificity was tested against other viruses. Sensitivity was determined using serial dilutions of extracted RNA. ResultsThe RT-LAMP assay detected 97.5% of HCV-RNA genotype 1, 91.1% of genotype 3, and 100% of genotype 6. The color change was evidenced with the naked eye. The assay demonstrated a clinical sensitivity of 95.5% and specificity of 100%, as well as no cross-reactivity with other viruses (i.e., hepatitis B virus, HIV). The limit of detection was as low as 10 ng per reaction for HCV genotypes 1a and 6, while it was 100 ng for genotype 3a. The assay showed a 100% detection threshold at a viral load of 5.00 log10 IU/mL in the clinical samples tested. ConclusionsThis study demonstrated the use of an RT-LAMP assay for the detection of HCV in a simple, rapid, and cost-effective manner, which will be useful in resource-limited settings to allow the identification of individuals in need of HCV treatment.

Body mass index (BMI) and alpha-fetoprotein (AFP) level correlate with the severity of HCV-induced fibrosis in a cohort of Egyptian patients with chronic HCV

BackgroundViral hepatitis is the seventh leading cause of mortality globally, and half of this mortality is attributed to hepatitis C virus (HCV). Egypt has the highest HCV prevalence worldwide, with an estimated 14.7% of the population being HCV-positive. HCV infection is the primary cause of liver fibrosis, cirrhosis, and hepatocellular carcinoma. Liver fibrosis varies in severity during chronic HCV infection, and 10–20% of chronic hepatitis C (CHC) patients with severe fibrosis develop cirrhosis. The goal of this work was to assess the clinico-demographic predictors of severity of HCV-induced fibrosis in a cohort of Egyptian patients.ResultsA cohort of Egyptian patients with chronic HCV genotype 4a infection showed significant association between severe fibrosis stages and obesity, represented by a higher body mass index (BMI), low albumin level, high alpha-fetoprotein (AFP) level, low thyroid-stimulating hormone (TSH) level, and high alkaline phosphatase (ALP) level. Multivariate analysis delineated BMI, TSH, and ALP as independent significant variables that could predict the risk of fibrosis severity in HCV infections.ConclusionThis study argues in favor of using the biomarker profile of CHC patients infected with HCV genotype 4a to identify patients at higher risk of developing severe fibrosis, which is a necessary first step towards precision medicine via patient stratification.

Primary HCV Drug Resistance Mutations in Patients with Newly Diagnosed HIV Infection

Objective of our work was to assess prevalence of the primary HCV drug resistance mutations in the NS5b gene in patients with newly diagnosed HIV infection.Materials and methods. The study material was 196 blood plasma samples from patients living in the North-Western Federal District with newly diagnosed HIV. Samples were examined for the anti-HCV antibodies and HCV RNA presence. If HCV RNA was detected, amplification was performed using three primers pairs that co-flanked the NS5b gene. After sequencing the indicated gene nucleotide sequence, the virus subtype was determined and drug resistance mutations were detected.Results and discussion. Antibodies to HCV were detected in 18.87 % of HIV-infected individuals. HCV RNA was detected in 18.36 % of the patients, including 89.18 % anti-HCV-positive and 1.88 % anti-HCV-negative. It was shown that co-infection is more common in men (77.8 %) compared to women (22.2 %) – χ2 = 3.996 at p = 0.0456, df = 2. The difference in the HIV viral load between the groups with HIV monoinfection and with HIV + HCV coinfection was demonstrated (χ2 = 6.284 at p = 0.0432, df = 2). A significant difference between the groups by the CD4 + lyphocytes number was shown. In the phylogenetic analysis, the HCV subtypes are distributed as follows: HCV 1b – 47.2 %, HCV 3a – 30.6 %, HCV 1a – 13.9 %, HCV 2a – 5.5 % and only one sample was defined as HCV 2k – 2.8 %, respectively. Nine samples (25 %) presented NS5b mutations in the positions related to the development of drug resistance of HCV, including two samples among HCV genotypes 1a and 3a (i.e., 5.6 % of the total HIV + HCV group), as well as five samples among HCV 1b (13.9 % of the total group). Mutations among HCV 1a were C316Y and N444D substitutions. Among HCV 1b, C316N, C451S, S556N/G substitutions were identified. Among patients with HCV 3a, 2 samples (5.6 %) with a D310N mutation associated with an unfavorable disease prognosis were found. The introduction of direct sequencing of HCV nucleotide sequences into the routine laboratory diagnostics will allow us to estimate the primary drug resistance mutations prevalence in risk groups to predict the HCV life-threatening complications development – fibrosis, cirrhosis, hepatocellular carcinoma, as well as the outcome of antiviral therapy prognosis. The data obtained can be rationally used to assess the dynamics of the HCV primary pharmacoresistance prevalence among HIV-infected individuals.

Impact of Interleukin 28B and ICAM-1 Genetic Polymorphisms on Response to Direct Antiviral Treatment Among HCV Infected Patients.

Single nucleotide polymorphisms (SNPs) of IL-28B and/or ICAM-1 could have a role in expecting a response from HCV infected patients to direct antiviral agents (DAAs). The aim of the current study was to investigate the impact of IL-28B rs12979860 and rs8099917, and, ICAM-1 rs281437 SNPs on response to treatment with sofosbuvir + Daclatsvir ± Ribavirin, among HCV-infected Egyptian patients. Whole blood genomic DNA was extracted from 120 participants (80 HCV-infected patients and 40 healthy volunteers). HCV-infected patients were subdivided into responders and nonresponders to DAAs. Liver function testing, anti-HCV antibodies, HCV-RNA viral load and HCV genotyping were performed. IL-28B and ICAM-1 SNPs were evaluated by real-time PCR. ALT and AST levels were significantly higher among non-responder HCV infected patients (P = 0.001*). 90% of the patients had HCV genotype 4a and the remaining 10% had 4l genotype. Allelic discrimination revealed that IL-28B rs12979860 T, IL-28B rs809917 T and ICAM-1 rs281437 C alleles were more frequent among HCV-infected patients (responders or non-responders) than controls. However, IL-28B rs8099917 G allele was more frequent among healthy controls. Regarding the response to DAAs treatment, HCV-infected patients with IL-28B rs8099917 GG genotype showed a significantly earlier viral response compared to those carrying TT alleles. ICAM-1 rs281437 CT alleles were non significantly more frequent among responders. However, IL-28B rs12979860 alleles did not show any difference. Genotyping of IL-28B rs8099917 is a useful independent tool for expecting a response of Egyptian HCV-infected patients to DAAs.

Potent virucidal activity of honeybee “Apis mellifera” venom against Hepatitis C Virus

Hepatitis C virus (HCV) is a global viral widespread without an available vaccine to prevent infection. HCV infection can cause serious liver diseases such as hepatocellular carcinoma (HCC). Current treatment of HCV infection depends on the FDA approved direct-acting antivirals (DAAs) which have side effects and expensive. Thus, development of a novel, more efficient, along with affordable pricing anti-HCV agents is still required. The purpose of the present study is to evaluate the antiviral effects of bee venom (BV) from the honeybee Apis mellifera on the HCV replication life cycle. The crude venom and its components were examined for their anti-HCV activities using Huh7it-1 cultured cells and the JFH1 strain of HCV genotype 2a. Results revealed that BV inhibited HCV infection with 50% inhibitory concentration (IC50) of 0.05 ng/ml, while the 50% cytotoxic concentration (CC50) being 20,000 ng/ml. The venom directly blocked HCV/cell entry by acting on virus particles in a dose dependent manner, whereas no interference on the host cells. Furthermore, venom showed no inhibitory effect on HCV replication and release. Interestingly, none of the main BV components including the mast cell degranulating peptide (MCD), mpamin, or the small peptides melittin (MLT) showed anti-HCV activity up to 5 μg/ml. In conclusion, these results suggest that BV has a direct virucidal activity against HCV and may exert its antiviral effect through a non-common peptide(s) or toxin complex within the crude venom. Therefore, the crude BV can be considered as a promising candidate for characterization and development of new and natural anti-HCV therapeutic agents.

S3511 Management of Complications After Liver Transplantation for Hepatitis C Negative Patients Receiving Hepatitis C Positive Organs

INTRODUCTION: More than 16,000 patients are awaiting a liver transplant with less than 6,700 successful liver transplants in the U.S. that occur each year. Using a hepatitis C virus (HCV) positive donor liver for transplantation increases the donor pool. When HCV negative patients receive an HCV positive liver, they are at risk of acquiring HCV infection. We report two cases of patients who were HCV negative and received HCV positive donor liver subsequently acquiring HCV infection and developing associated complications. CASE DESCRIPTION/METHODS: The first patient is a 71 year old male with a history of non-alcoholic steatohepatitis (NASH) cirrhosis, hepatocellular carcinoma, and hepatic encephalopathy. He developed HCV infection status-post orthotopic liver transplantation from HCV donor. Imaging before transplant and explant pathology showed hepatocellular carcinoma. He was found to have HCV genotype 2B infection 2 weeks post-transplant as part of protocol testing. He was treated with sofosbuvir/velpatasvir for 12 weeks and achieved sustained viral response (SVR). Imaging at 5 months post-op revealed 2 hypovascular masses diagnosed as epstein barr virus associated B-cell post-transplant lymphoproliferative disorder (PTLD). Treatment was initiated with rituximab and his hospital course was complicated by bacteremia and atrial fibrillation. The second patient is a 52 year old male with NASH cirrhosis status-post orthotopic HCV positive liver transplant. His post-transplant course was complicated by elevated liver enzymes and renal insufficiency. He was found to have HCV genotype 1a, 3 months after transplant, and was treated with sofosbuvir/velpatasvir for 12 weeks with achieving SVR. Liver tests subsequently returned to normal with treatment. DISCUSSION: Although using HCV positive donor liver increases the donor pool it is associated with increased risk of HCV transmission to the recipient. These recipients need to be closely monitored so they could be treated in a timely manner to prevent any associated complications.Figure 1.: CT scan showing two hypovascular hepatic masses in the right and left lobes, measuring up to 3 cm.

Hepatitis C Virus Transmission at a Long-Term Care Facility (LTCF) Providing Hemodialysis Services—Georgia, United States, 2019

Background: Hepatitis C virus (HCV) transmission at outpatient hemodialysis clinics is well documented, but little is known about HCV transmission risks in long-term care facilities (LTCFs) providing hemodialysis services. LTCFs can provide onsite hemodialysis for residents by contracting with a licensed hemodialysis clinic to either provide its staff to the LTCF or to train LTCF staff as caregivers. In August 2019, the Georgia Department of Public Health (DPH) was notified about an HCV seroconversion in patient A at a LTCF providing onsite hemodialysis. Methods: Three residents (including patient A) were receiving hemodialysis at the LTCF in August 2019; patients B and C had chronic HCV infection upon admission. Records were reviewed for medical history, behavioral risk factors, and healthcare exposures. We conducted onsite infection control assessments and interviewed staff. Serum specimens were collected for all 3 patients in August 2019 and HCV tested for genetic similarity using Global Hepatitis Outbreak Surveillance Technology (GHOST). Results: The facility reported initiating onsite hemodialysis in November 2018; facility staff were trained by a dialysis provider. Patient A, admitted in September 2018, was anti-HCV negative in June 2019 and both anti-HCV and HCV RNA positive in July 2019. Patient B was admitted in December 2018, discharged for 1 month in May 2019, and then readmitted. Patients A and B reported previous injection drug use, and they were not observed by staff to use during their stay and had limited mobility. Patient A was wheelchair confined and B was bed confined. Patient C was admitted in May 2019. HCV samples from patients A and B both had HCV genotype 1b and demonstrated 100% genetic relatedness, indicating that patient B was the likely source. Patient C had HCV genotype 1a. Hemodialysis was provided to residents simultaneously in a converted resident room with 4 hemodialysis stations, and the LTCF operated 2 shifts, 3 times per week. We observed multiple infection control gaps, such as preparation of IV medications and inadequate disinfection in the shared dialysis treatment area. Recommendations addressing gaps were issued, and a follow-up site visit was conducted to validate implementation. With the exception of May 2019, patients A and B received hemodialysis on the same shift and days from December 2018 to September 2019. Conclusions: Phylogenetic and epidemiological results indicate HCV transmission likely occurred during hemodialysis services provided by the LTCF. As the provision of dialysis expands to nontraditional settings such as LTCFs, it is essential that proper infection control procedures and oversight are in place.Funding: NoneDisclosures: None

S2713 Acute Kidney Injury Presenting as Hepatorenal Syndrome in the Setting of Glecaprevir/Pibrentasvir Treatment for Hepatitis C

INTRODUCTION: The regimen of glecaprevir and pibrentasvir is an effective treatment for hepatitis C (HCV), but FDA data suggests a risk of hepatobiliary toxicity. Here, we discuss the first description of hepatorenal syndrome secondary to hepatobiliary toxicity from glecaprevir/pibrentasvir. CASE DESCRIPTION/METHODS: A 65-year-old man with chronic HCV (genotype 1a), alcohol use disorder, and hepatocellular carcinoma (HCC), presented with abdominal distention and jaundice for one month. He was diagnosed with HCC in 2014 and treated with resection and adjuvant sorafenib without evidence of recurrence, and thus began HCV treatment with glecaprevir/pibrentasvir. At baseline he was Childs-Pugh class A with a total bilirubin of 0.9 mg/dL, INR of 0.95, and albumin of 3.2. Twenty-four days after initiation of glecaprevir/pibrentasvir he presented with fevers, fatigue, and dark urine. On exam he had jaundice, abdominal distension, and right upper quadrant tenderness. His labs showed a total bilirubin of 25.5 mg/dL, direct bilirubin of 16.1 mg/dL, INR of 1.64, and creatinine of 1.6 mg/dL (1.1 mg/dL two weeks prior). He was initially started on a three-day albumin challenge, but his renal function continued to decompensate, raising concern for a type 1 HRS, so he was transitioned to octreotide, midodrine, and albumin. Glecaprevir/pibrentasvir was also discontinued due to his acute liver decompensation after only 29 days of treatment. Eight days later, the patient’s creatinine had decreased from 2.0 to 1.3 mg/dL and his total bilirubin decreased from 25.6 to 16.4 mg/dL. Four months after discharge he has continued to improve with creatinine as low as 1.2mg/dL and a total bilirubin of 3.7 mg/dL. Notably, despite just four weeks of glecaprevir/pibrentasvir, his hepatitis C viral load has remained undetectable. DISCUSSION: In 2019, the FDA distributed a safety communication outlining liver injury in 46 individuals on glecaprevir/pibrentasvir and suggested avoidance in Child-Pugh class B and C patients. While research of the safety profile for glecaprevir/pibrentasvir in Child-Pugh class A is needed, this case reports highlights the importance of early and regular monitoring of liver and renal function in patients on this regimen. Current glecaprevir/pibrentasvir regimens are 12 weeks, yet a shortened four-week regimen still provided virus eradication in this case, raising the possibility of personalized treatment based on viral load. This could reduce potential side effects as well as the cost of antiviral therapy.