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Studying the agents of bovine viral diarrhea (BVD) is an important task given the high probability of new isolate introduction into the Russian Federation, as well as the need to take into account the genotype and subgenotype of the virus circulating in a herd when developing vaccines and diagnostic kits for the infection. During the work performed, 6 BVD virus isolates were recovered and identified. The recovery of these isolates in the lamb testicle cell subculture revealed that Bashkiria/2019, Kirov/2020 and Samara/2020 isolates belong to non-cytopathic bovine viral diarrhea virus biotypes, Chelyabinsk/2021 isolate demonstrated the characteristic cytopathic effect in the monolayer and was classified as a cytopathic variant of thevirus, the adaptation of Belgorod/2021 and Udmurtiya/2020 isolates to this cell system was not possible. The study also identified the species of the recovered isolates. Based on the analysis of the nucleotide sequence of genome 5’-untranslated region (5’-UTR) fragment, these isolates were classified as belonging to three genotypes of the virus. The phylogenetic analysis showed that Chelyabinsk/2021 and Udmurtiya/2020 isolates belong togenotype2 and demonstrate, respectively, 98% and99% homology with reference 890 strain of BVD virus. The recovered Bashkiria/2019, Samara/2020, Kirov/2020 isolates were classified as belonging to subtypes 1i, 1f and1b ofgenotype1, and Belgorod/2021 solate represents genotype 3 of the virus. The findings from the study confirm the presence of all three genotypes of bovine viral diarrhea virus in the Russian Federation and reiterate the need for the development of specific prevention and diagnosis tools for the disease.

Since the last century, the spread of the genotype 2 classical swine fever virus (CSFV) has caused significant issues for the pig breeding industries. Ideal strategies for controlling CSFV include vaccination and keeping farms free of CSFV. For vaccination, several attenuated CSFV viruses originating from genotype 1 are widely used; for the latter, accurate diagnosis is required for detection of the CSFV infection. Nucleic acid testing for CSFV usually uses tonsil samples, which requires an inconvenient sampling operation that injures pigs. Commercial serological tests for CSFV antibodies or antigens are unable to distinguish the genotype for originating virus. In this study, 20 mAbs were developed from the mice hybridoma cells. Four of the mAbs were identified to have the ability to only recognize the peptides derived from sub-genotype 2.1 strain, and two of them, MM1 and MM5, were further studied to identify critical binding sites (epitopes) on the E2 protein of CSFV. A total of 353 genotype 2 collections were made worldwide in GeneBank, 90.9% of which contained MM1 or MM5 epitopes. Moreover, 95.1% of sub-genotype 2.1 isolations contained MM5 epitope. Therefore, MM1 and MM5 have the potential to be developed as a diagnostic tool for detection of genotype 2 virus antigen by indirect ELISA or antibodies by competitive ELISA. [ABSTRACT FROM AUTHOR]

Enterovirus G belongs to the family Picornaviridae and are associated with a variety of animal diseases. We isolated and characterized a novel EV-G2 strain, CHN-SCMY2021, the first genotype 2 strain isolated in China. CHN-SCMY2021 is about 25 nm diameter with morphology typical of picornaviruses and its genome is 7341 nucleotides. Sequence alignment and phylogenetic analysis based on VP1 indicated that this isolate is a genotype 2 strain. The whole genome similarity between CHN-SCMY2021 and other EV-G genotype 2 strains is 78.3–86.4%, the greatest similarity is to EVG/Porcine/JPN/Iba26–506/2014/G2 (LC316792.1). Recombination analysis indicated that CHN-SCMY2021 resulted from recombination between 714,171/CaoLanh_VN (KT265894.2) and LP 54 (AF363455.1). Except for ST cells, CHN-SCMY2021 has a broad spectrum of cellular adaptations, which are susceptible to BHK-21, PK-15, IPEC-J2, LLC-PK and Vero cells. In piglets, CHN-SCMY2021 causes mild diarrhea and thinning of the intestinal wall. The virus was mainly distributed to intestinal tissue but was also found in heart, liver, spleen, lung, kidney, brain, and spinal cord. CHN-SCMY2021 is the first systematically characterized EV-G genotype 2 strain from China, our results enrich the information on the epidemiology, molecular evolution and pathogenicity associated with EV-G.

Histomonosis (syn. blackhead disease) is caused by the protozoan parasite Histomonas meleagridis and can result in high mortality in turkey flocks, a situation driven by the limitation of prophylactic and therapeutic interventions. Multi-locus sequence typing confirmed the existence of two genotypes, with the vast majority of reported histomonosis outbreaks being caused by genotype 1 in contrast to only a few detections of genotype 2. For the first time, genotype 2 of H. meleagridis was successfully isolated from an outbreak of histomonosis in a flock of 5-week-old turkeys and a clonal culture was established. Using this culture, an experimental infection was performed in naïve turkeys. The animal trial reflected the observations from the field outbreak and coincided with a previously reported case of histomonosis caused by genotype 2, albeit no mortality was observed in the infected birds whereas 17.1% mortality was noticed in the field outbreak from appearance of disease until slaughter. Post mortem investigations demonstrated that lesions were restricted to the caeca in the field outbreak and the experimental trial. In parallel with the experimental reproduction of pathological changes, an oral vaccination of day-old turkeys with a monoxenic genotype 1 vaccine was carried out to determine efficacy against a genotype 2 challenge. Successful vaccine uptake was characterized by the presence of the vaccine in the caeca determined by qPCR and immunohistochemistry (IHC). Excretion of the vaccine strain was confirmed prior challenge, with the majority of birds developing antibodies. The new monoxenic vaccine was able to minimize lesions in the caeca demonstrating heterologous protection. No parasites were detected in the liver by IHC in any of the vaccinated birds, compared to non-vaccinated animals. However, in 6 out of 17 birds of the vaccinated group a positive signal was obtained by real time PCR from liver samples with 2 positives being typeable by conventional PCR as genotype 2. Overall, H. meleagridis genotype 2 infection was successfully reproduced. Experimental vaccination with a genetically distantly related genotype 1 was able to reduce lesions, supporting protection by a recently developed vaccine candidate as an efficacious prophylactic strategy. [ABSTRACT FROM AUTHOR]

Abstract Chronic hepatitis C (CHC) is a major cause of cirrhosis, hepatocellular carcinoma (HCC), and mortality. Eliminating hepatitis C virus (HCV) can greatly improve long‐term outcomes. Several direct‐acting antiviral agents (DAAs), including sofosbuvir (SOF) plus different NS5A inhibitors, as well as non‐SOF‐based DAAs, including glecaprevir/pibrentasvir (GLE/PIB), have been approved for treating CHC genotype‐2 (GT‐2) patients in Taiwan. However, there is limited real‐world effectiveness data regarding these different regimens. Thus, we aimed to evaluate the real‐world efficacy in CHC GT‐2 patients who underwent these DAA regimens. We retrospectively enrolled CHC GT‐2 patients who were treated with SOF‐based DAAs or GLE/PIB at a single medical center. A total of 704 enrolled patients were treated with either SOF + ribavirin (RBV), SOF/daclatasvir (DCV) ± RBV, SOF/ledipasvir (LDV) ± RBV, SOF/velpatasvir (VEL) ± RBV, or with GLE/PIB. The overall sustained virological response (SVR) rate was 97.9%. The SVR rate was significantly lower in the SOF + RBV group (95.6%) than in the non‐SOF + RBV (98.9%) group, especially compared to the SOF/DCV (100%) and GLE/PIB groups (99.5%). Among patients treated with SOF + RBV, cirrhotic patients had significantly lower SVR rates than noncirrhotic patients (89.4% vs 98.2%). Multivariate analysis showed that patients with a younger age, hepatitis B virus coinfection, baseline cirrhosis, or those who received SOF + RBV were less likely to achieve SVR. In conclusion, for CHC GT‐2 patients, SOF in combination with DCV, LDV, or VEL, as well as GLE/PIB, achieved similar high efficacies, regardless of cirrhosis, treatment experience, or chronic kidney disease status. Therefore, the use of DAA therapy to eradicate HCV should not be delayed in these populations.

Background: Prototheca algaemia is a rare but life-threatening disease that occurs primarily in immunocompromised patients. We report a fatal case of Prototheca zopfii bloodstream infection in a 54-year-old woman receiving chemotherapy for relapsed acute lymphoblastic leukemia. Methods: The isolate was identified using an automated biochemical identification system (VITEK 2; bioMerieux) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (VITEK MS; bioMerieux). Partial 18S and 28S rDNA sequencing was performed for definitive identification and genotyping. Results: The patient had persistent neutropenic fever, and isolates from blood culture were identified as P. zopfii. Sequencing was performed and the isolate was confirmed to be P. zopfii genotype 2, which was newly named as P. bovis. The patient was treated with liposomal amphotericin B but died of septic shock. Conclusions: Prototheca spp. should be considered an emerging pathogen, especially in immunocompromised patients, due to its ubiquitous nature. [ABSTRACT FROM AUTHOR]

Background: Ropeginterferon alfa-2b is a novel mono-pegylated interferon that has only one major form as opposed to the 8 to 14 isomers of other on-market pegylated interferon products, allowing every-two-week injection with high tolerability. It received European Medicines Agency marketing authorization in 2019 and Taiwan Biologics License Applications Approval in 2020 for the treatment of polycythemia vera. This study aimed to evaluate the safety and efficacy of Ropeginterferon alfa-2b plus ribavirin in genotype 2 chronic hepatitis C (CHC) patients. Methods: Eighty-six treatment naive patients with genotype 2 CHC were randomized to weekly peginterferon alfa-2a (Peg–IFN–α2a) at 180 μg (n = 22), or every-two-week Ropeginterferon alfa-2b at 270 μg (n = 23), 360 μg (n = 21), 450 μg (n = 20), plus daily oral ribavirin 1000 mg (≤75 kg) or 1200 mg (>75 kg). Patients with rapid virologic response received 16-week regimen while those without RVR received 24-week regimen. The primary endpoint was sustained virologic response at 24 weeks post-treatment (SVR24). Results: SVR24 was achieved by 95.5%, 78.3%, 85.7%, and 60% of subjects in Peg–IFN–α2a 180 μg, Ropeginterferon alfa-2b 270 μg, 360 μg, and 450 μg groups, respectively. The safety profile was similar across 4 groups. The incidence rate of adverse event during the treatment period was 0.407, 0.252, 0.395, and 0.347 per patient-week, respectively. Conclusion: Ropeginterferon alfa-2b, although at only half the number of injections, is as safe and effective as Peg–IFN–α2a for genotype 2 CHC. A phase 3 study to confirm safety and efficacy of Ropeginterferon alfa-2b in genotype 2 CHC is ongoing.

Background/Aims: Sofosbuvir (SOF)-based therapy has been used in Korean patients with chronic hepatitis C virus (HCV) infection since January 2016. This study aimed to investigate the real-life effectiveness and safety of SOF-based therapy in genotype 2 HCV infection. Methods: From January to December 2016, 458 genotype 2 HCV-infected patients who received ≥1 dose of SOF-based therapy were consecutively enrolled in seven tertiary hospitals. Sustained virologic response (SVR) rates and safety were determined by intention- to-treat (ITT) and per-protocol (PP) analyses. Results: The mean age of the patients was 61.0 years; 183 (40%) were male, and 13.1% showed a high viral load (>6,000,000 IU/ mL). Among the 378 treatment-naïve patients, the SVR rates were 94.2% (ITT) and 96.7% (PP). Among the 80 treatmentexperienced patients, the SVR rates were 96.3% (ITT) and 98.7% (PP). Patients with a relatively high fibrosis-4 index score (>3.25) had similar SVR rates to those with a relatively low score (p=0.756). A total of 314 patients (68.6%) were treated with a reduced ribavirin dose at the prescriber’s discretion, but they showed similar SVR rates to those treated with the weight-based dose (ITT: 95.5% and 92.3%, PP: 97.4% and 96.3%, respectively). Adverse events were observed in 191 patients (41.7%), including 86 (18.8%) with anemia, but only one (0.2%) discontinued antiviral therapy due to nausea. Conclusions: SOF-based therapy showed high real-life efficacy and tolerability in Korean patients with genotype 2 chronic HCV infection, regardless of previous antiviral treatment experience and fibrosis score. A reduced ribavirin dose can be considered in this patient cohort.

Chronic hepatitis C (CHC) is a major cause of cirrhosis, hepatocellular carcinoma (HCC), and mortality. Eliminating hepatitis C virus (HCV) can greatly improve long‐term outcomes. Several direct‐acting antiviral agents (DAAs), including sofosbuvir (SOF) plus different NS5A inhibitors, as well as non‐SOF‐based DAAs, including glecaprevir/pibrentasvir (GLE/PIB), have been approved for treating CHC genotype‐2 (GT‐2) patients in Taiwan. However, there is limited real‐world effectiveness data regarding these different regimens. Thus, we aimed to evaluate the real‐world efficacy in CHC GT‐2 patients who underwent these DAA regimens. We retrospectively enrolled CHC GT‐2 patients who were treated with SOF‐based DAAs or GLE/PIB at a single medical center. A total of 704 enrolled patients were treated with either SOF + ribavirin (RBV), SOF/daclatasvir (DCV) ± RBV, SOF/ledipasvir (LDV) ± RBV, SOF/velpatasvir (VEL) ± RBV, or with GLE/PIB. The overall sustained virological response (SVR) rate was 97.9%. The SVR rate was significantly lower in the SOF + RBV group (95.6%) than in the non‐SOF + RBV (98.9%) group, especially compared to the SOF/DCV (100%) and GLE/PIB groups (99.5%). Among patients treated with SOF + RBV, cirrhotic patients had significantly lower SVR rates than noncirrhotic patients (89.4% vs 98.2%). Multivariate analysis showed that patients with a younger age, hepatitis B virus coinfection, baseline cirrhosis, or those who received SOF + RBV were less likely to achieve SVR. In conclusion, for CHC GT‐2 patients, SOF in combination with DCV, LDV, or VEL, as well as GLE/PIB, achieved similar high efficacies, regardless of cirrhosis, treatment experience, or chronic kidney disease status. Therefore, the use of DAA therapy to eradicate HCV should not be delayed in these populations. [ABSTRACT FROM AUTHOR]

Introduction: The real-world virological efficacy and safety of interferon-free direct-acting antiviral (DAA) therapy with ledipasvir (LDV) plus sofosbuvir (SOF) were assessed in patients who were chronically infected with hepatitis C virus (HCV) genotype 2. Methods: A total of 126 patients with chronic hepatitis C due to HCV genotype 2 infection who were treated with the LDV/SOF regimen were enrolled. The sustained virological response (SVR) rate and safety were analyzed. SVR was assessed in the intention-to-treat (ITT) population as well as in the modified intention-to-treat (mITT) population, which excluded patients with non-virological failure, including those who dropped out before the SVR assessment. Results: The overall SVR rates of the ITT and mITT populations were 87.3% (95% confidence interval [CI] 80.2–92.6) (110/126) and 97.3% (95% CI 92.4–99.4) (110/113), respectively. In the mITT population, the percentages of patients with undetectable HCV RNA at 4, 8, and 12 weeks after the start of therapy were 92.9% (95% CI 86.5–96.9) (105/113), 99.1% (95% CI 95.2–100.0) (112/113), and 100.0% (95% CI 97.4–100.0) (113/113), respectively. Subgroup analyses of the mITT population showed no significant differences in SVR rates according to age, sex, HCV genotype (subtype), history of interferon-based therapy, baseline FIB-4 index, or baseline estimated glomerular filtration rate. In all subpopulations, the SVR rates were > 90%. There were no severe adverse events associated with the treatment. Conclusion: The LDV/SOF regimen showed high virological efficacy and acceptable safety in patients with HCV genotype 2 infection. Trial Registration: UMIN registration no. 000038604. [ABSTRACT FROM AUTHOR]

Background: Ropeginterferon alfa-2b is a novel mono-pegylated interferon that has only one major form as opposed to the 8 to 14 isomers of other on-market pegylated interferon products, allowing every-two-week injection with high tolerability. It received European Medicines Agency marketing authorization in 2019 and Taiwan Biologics License Applications Approval in 2020 for the treatment of polycythemia vera. This study aimed to evaluate the safety and efficacy of Ropeginterferon alfa-2b plus ribavirin in genotype 2 chronic hepatitis C (CHC) patients.Methods: Eighty-six treatment naive patients with genotype 2 CHC were randomized to weekly peginterferon alfa-2a (Peg-IFN-α2a) at 180 μg (n = 22), or every-two-week Ropeginterferon alfa-2b at 270 μg (n = 23), 360 μg (n = 21), 450 μg (n = 20), plus daily oral ribavirin 1000 mg (≤75 kg) or 1200 mg (>75 kg). Patients with rapid virologic response received 16-week regimen while those without RVR received 24-week regimen. The primary endpoint was sustained virologic response at 24 weeks post-treatment (SVR24).Results: SVR24 was achieved by 95.5%, 78.3%, 85.7%, and 60% of subjects in Peg-IFN-α2a 180 μg, Ropeginterferon alfa-2b 270 μg, 360 μg, and 450 μg groups, respectively. The safety profile was similar across 4 groups. The incidence rate of adverse event during the treatment period was 0.407, 0.252, 0.395, and 0.347 per patient-week, respectively.Conclusion: Ropeginterferon alfa-2b, although at only half the number of injections, is as safe and effective as Peg-IFN-α2a for genotype 2 CHC. A phase 3 study to confirm safety and efficacy of Ropeginterferon alfa-2b in genotype 2 CHC is ongoing. [ABSTRACT FROM AUTHOR]

The demand for treatments for viral hepatitis using direct antiviral agents (DAAs) has increased; however, few real-world clinical studies are available. The objective of this study was to evaluate the efficacy and safety of sofosbuvir combined with ribavirin for patients with chronic hepatitis C (CHC) genotype 2 (GT2). A total of 106 consecutive CHC GT2 patients treated with sofosbuvir plus ribavirin between May 2016 and August 2018 (median age: 52.5 years, male: 51 [48.1%], treatment-naïve patients: 98 [92.5%]) were analyzed. The primary endpoint was sustained virologic response at 12 weeks (SVR12). The secondary endpoint was the occurrence of side effects during treatment. Of a total of 106 patients with CHC GT2, 103 were genotype 2a (97.2%), and 3 were 2b (2.8%). SVR12 was confirmed in 105 of 106 patients (99.1%). The one patient with treatment failure had combined liver cirrhosis and hepatocellular carcinoma. Twenty-five patients had liver cirrhosis in addition to hepatitis C virus (HCV) (Child-Turcotte-Pugh (CTP)-A, n = 24; C, n = 1), and SVR12 was confirmed in 24 of these patients (96.0%). The mean HCV RNA titer was 2,629,159 IU/ml. Reductions in haemoglobin levels occurred in 23 patients during treatment (3.0 mg/dL, mean), and consequently, ribavirin dose reduction was required (365.2 mg, mean). Sofosbuvir plus ribavirin was highly effective for the treatment of patients with CHC GT2 and had no serious, treatment-related adverse effects. [ABSTRACT FROM AUTHOR]

Classical swine fever (CSF) is an endemic disease in southeastern Asia and is one of the most important swine diseases in Vietnam. This study was conducted to characterize the pathology of natural cases of CSF in northern Vietnam in 2018 and their genetic prevalence. A total of 10 representative pigs were collected from four provinces (Hung Yen, Ha Noi, Quang Ninh and Thai Binh) during five outbreaks and examined pathologically. The gross and histopathological findings showed the disease was expressed as the acute or the subacute to chronic form of CSF, depending on the age of the animals. The most consistently observed lesions associated with infection by the classical swine fever virus (CSFV) included lymphoid depletions in tonsils, lymph node and spleen; histiocytic hyperplasia in spleen; cerebral haemorrhage; perivascular cuffing in the brain; renal erythrodiapedesis; urothelial vacuolation and degeneration and interstitial pneumonia. The immunohistochemical findings showed a ubiquitous CSFV antigen mainly in the monocytes/macrophages and in the epithelial and endothelial cells in various organs. CSFV neurotropism was also found in the small neurons of the cerebrum and the ganglia of the myenteric plexus. Analysis of the full‐length envelope protein (E2) genome sequence showed that all strains were genetically clustered into subgenotype 2.5, sharing a nucleotide identity of 94.0%–100.00%. Based on the results of this study, the strain was categorized as a moderately virulent CSFV. [ABSTRACT FROM AUTHOR]

Sofosbuvir plus daclatasvir with or without ribavirin has demonstrated a high efficacy and an acceptable safety profile in clinical trials of patients infected with genotype 2 hepatitis Cvirus (HCV); however, there are currently no real‐world data available for this regimen. To evaluate the real‐life safety and efficacy of sofosbuvir/daclatasvir with or without ribavirin in genotype 2 HCV patients in the French cohort ANRS CO22 HEPATHER(NCT01953458). In this ongoing, national, multicentre, prospective, observational study, we observed patients with HCV genotype 2 infection who initiated treatment with sofosbuvir (400 mg/d) plus daclatasvir with or without ribavirin (1‐1.2 g/d). Patients were divided into two treatment groups: sofosbuvir/daclatasvir with or without ribavirin (12 weeks/24 weeks). The primary end point was a sustained virological response at week 12 following the end of therapy. Overall, 88% and 91% of patients achieved a sustained virological response following 12 and 24 weeks of treatment with sofosbuvir/daclatasvir with or without ribavirin, respectively. The most common adverse events were asthenia (29%), headache (15%) and fatigue (20%), and ribavirin addition was associated with a higher rate of adverse events and treatment discontinuation. Sofosbuvir/daclatasvir with or without ribavirin was associated with lower rates of sustained virological response in the real‐life setting compared with the clinical setting and demonstrated suboptimal efficacy for the treatment of patients with genotype 2 chronic HCV. [ABSTRACT FROM AUTHOR]

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]

Aim: Hepatitis C virus genotype 2 is common in East Asia, sub‐Saharan Africa, and Latin America. However, many countries in these areas lag behind other areas of the world in government approval for new direct‐acting antivirals. The aim of this study was to evaluate the treatment outcome of ledipasvir/sofosbuvir (LDV/SOF) for patients with chronic hepatitis C virus genotype 2 infection. Methods: This is a two‐part multicenter, real‐world cohort study. Study 1 consisted of 58 consecutive patients who were treated with LDV/SOF for 12 weeks. Study 2 used propensity score matching for LDV/SOF (n = 58) and glecaprevir/pibrentasvir (n = 207) treatment groups (1:1) with a set of clinically important variables. Sustained viral response 12 weeks after the end of treatment (SVR12) and adverse events were evaluated in both studies. Results: In study 1, the overall SVR12 rates of the intention‐to‐treat and modified intention‐to‐treat populations were 94.8% (55/58) and 96.5% (55/57), respectively. High SVR12 rates were observed in almost all subgroups, including older age, compensated cirrhosis, and treatment experience. In study 2, propensity score matching of the entire study population yielded 52 matched pairs with similar baseline characteristics. There were no statistically significant differences between the LDV/SOF (96.1%) and glecaprevir/pibrentasvir (98.0%) groups in the overall SVR12 rates of the modified intention‐to‐treat populations, and their rates of treatment discontinuation and adverse events were similar. Conclusions: Treatment with LDV/SOF for hepatitis C virus genotype 2 resulted in a high rate of SVR12 and excellent tolerability. The outcomes of LDV/SOF were very similar to those of glecaprevir/pibrentasvir. [ABSTRACT FROM AUTHOR]

Aim. Study clinical outcomes in patients with, chronic hepatitis C depending on genotype of hepatitis C virus (HCV) and IL28B gene polymorphism. Materials and methods. 592 individuals were examined, 75 of those had HCV RNAgenotypes determined by PCR. Genotyping of single nucleotide polymorphisms (SNP) - rs 12979860 (C/T) and rs8099917 (T/G) in IL28B gene was carried out by real-time PCR. Results. HCV RNA was detected in 72 examined residents of Yakutia. HCV lb genotype was determined in 74.2% of cases, 3a - in 11.4%, la and 2 - 5.7% each. Frequency of polymorph variant rsl2979860 CC was 72.2%, CT - 27.8%, rs8099917 TT - 61.1%, TG - 23.2%. Conclusion. Combination of HCV lb with polymorphic variants of IL28B gene rs.l.2979860 CC and rs8099917 CT showed a less aggressive course of the disease. On the other hand, HCV infection of individuals with genotype 3a and polymorphism rsl2979860 CC or rs809917 TT of IL28B gene showed a more severe clinical presentation. The presence of polymorph variants rs8099917 T/G and rs 12979860 C/T showed more severe clinical outcomes of HCV infection (viral load up to 19035212 copies, cirrhosis with ascite, hepatocarcinoma).

Aims: Development of direct‐acting antivirals (DAAs) has made antihepatitis C virus (HCV) treatment highly safe and effective. However, the emergence of resistant‐associated variants (RAVs) after failure of DAA therapy affects retreatment outcomes. In particular, genotype 1 HCV with P32 deletion has been reported to be highly resistant to all approved non‐structural protein (NS)5A inhibitors. However, analysis of RAVs in genotype 2 HCV has been limited. Accordingly, in this study, we evaluated the roles of genotype 2 HCV variants in antiviral drug efficacy. Methods: We utilized HCV‐2b/2a (JFH‐1) chimeric virus (genotype 2a), which replicates more robustly than JFH‐1. We constructed various genotype 2a JFH‐1‐based HCV cell culture systems with NS3 (D168E), NS5A (F28S, F28S/M31I, P32 deletion, and Y93H), and NS5B (S282 T) RAVs and analyzed the replication ability and sensitivity to various anti‐HCV reagents. Results: Genotype 2a‐based HCV with NS5A–P32 deletion could not replicate even in long‐term cultures. Genotype 2a‐based HCV with NS5A‐F28S/M31I showed significantly higher replication ability than the wild‐type strain, and replication could not be suppressed, even with high concentrations of NS5A inhibitors, including pibrentasvir and velpatasvir (<1000–10 000 fold‐resistance compared with the wild‐type strain). However, genotype 2a‐based HCV with NA5A‐F28S/M31I was sensitive to HCV protease inhibitor, NS5B inhibitor, interferon‐α, and ribavirin. Genotype 2a‐based HCV with NS5B‐S282 T was resistant to sofosbuvir, but was highly sensitive to ribavirin compared with the control. Conclusions: When undertaking retreatment for genotype 2a HCV‐infected patients who fail to respond to DAAs, the optimized retreatment should be chosen according to the sensitivity of the emerging RAVs to anti‐HCV drugs. [ABSTRACT FROM AUTHOR]

Background and Aim: Data regarding the comparative effectiveness and safety of sofosbuvir (SOF) in combination with ribavirin (RBV), daclatasvir (DCV), or ledipasvir (LDV) for hepatitis C virus genotype 2 (HCV‐2) patients were limited. We aimed to evaluate the performance of these regimens in Taiwan. Methods: One hundred eighty‐seven HCV‐2 patients with compensated liver diseases receiving SOF in combination with RBV (n = 82), DCV (n = 66), or LDV (n = 39) for 12 weeks were retrospectively enrolled. The effectiveness was determined by sustained virologic response 12 weeks off therapy (SVR12). The patient characteristics potentially related to SVR12 were compared. The safety profiles and laboratory abnormalities were assessed. Results: The SVR12 rates were 93.9% (95% confidence interval [CI]: 86.5–97.4%), 98.5% (95% CI: 91.9–99.7%), and 100% (95% CI: 91.0–100%) in patients receiving SOF combined with RBV, DCV, and LDV, respectively. All patients tolerated treatment well. The stratified SVR12 rates were comparable regardless of baseline characteristics or week 4 viral decline among these regimens. Six (3.2%) patients had serious adverse events which were not related to treatment. The rates of fatigue, pruritus, and anemia tended to be higher in patients receiving RBV (22.0%, 19.5%, and 8.5%) combination than those receiving DCV (10.6%, 6.1%, and 1.5%) or LDV (10.3%, 5.1%, and 0%) combination. Conclusions: Sofosbuvir in combination with RBV, DCV, or LDV for 12 weeks is effective and well‐tolerated for HCV‐2 patients. Compared with DCV or LDV combination, the risks of fatigue, pruritus, and anemia are higher in patients receiving RBV combination. [ABSTRACT FROM AUTHOR]

Background: Until recently, interferon-free anti-hepatitis C virus (HCV) therapy for genotype 2 (GT2) HCV-infected hemodialysis patients was an unfulfilled medical need. Recent clinical trials of glecaprevir and pibrentasvir (G/P) for hemodialysis patients showed high efficacy and safety; however, the number of GT2 HCV-infected patients, especially Asian patients, was limited and most of them were treated with a 12-week regimen. In this prospective multicenter study, we aimed to investigate the efficacy and safety of G/P in Japanese hemodialysis patients with GT2 HCV infection.Methods: Twenty-seven Japanese hemodialysis patients with GT2 HCV infection who were started on with 8- or 12-week G/P regimen between November 2017 and June 2018 were included and followed up for around 12 weeks after treatment completion.Results: Among the 27 included patients, 13 non-liver cirrhosis (LC) and direct-acting antivirals (DAAs)-naïve patients were treated with 8 weeks of G/P and 14 patients with LC (n = 13) or history of failure of DAAs (n = 1) were treated with a 12-week regimen. The overall sustained virological response at 12 weeks after treatment completion (SVR 12) was 96.3% (26/27). All patients with 8 weeks of treatment achieved SVR12. Two patients discontinued the therapy at 2 and 11 weeks after treatment initiation. The patient who discontinued at 2 weeks due to pruritus alone failed to respond to G/P. No patients experienced lethal adverse events during the therapy, and the most common adverse event was pruritus.Conclusions: An 8- or 12-week G/P regimen is highly effective and safe in GT2 HCV-infected hemodialysis patients. [ABSTRACT FROM AUTHOR]

Background and Purpose: Sofosbuvir (SOF) and daclatasvir (DCV) treatment achieves excellent efficacy and safety in treating chronic hepatitis C (CHC) with various genotypes. Real world experience of SOF/DCV regimen to treat genotype 2 CHC was scanty in Asia. This study aimed to evaluate the effectiveness and safety of SOF/DCV with or without ribavirin to treat genotype 2 CHC patients in real world practice in Taiwan.Methods: Patients with genotype 2 CHC treated with 12-week of SOF/DCV or SOF/DCV/ribavirin were enrolled prospectively. Effectiveness was evaluated by sustained virological response (SVR) which was defined as undetectable hepatitis C virus (HCV) RNA at post-treatment week 12. Adverse events were recorded for safety analysis.Results: In total of 32 patients were enrolled from October 2016 to June 2017. All were infected with genotype 2 HCV. Sixteen patients (50%) exhibited cirrhosis including 6 patients with decompensation. Regimens of SOF/DCV and SOF/DCV/ribavirin were used to treat 14 and 18 patients, respectively. SVR was achieved in all 31 patients (100%) who completed follow-up. Significantly higher levels of cholesterol (p = 0.013) and higher low density lipoprotein-cholesterol (p = 0.015) were exhibited after successful viral clearance. SOF/DCV/ribavirin regimen resulted in more adverse events, significantly higher bilirubin levels, and decline of hemoglobin during treatment than SOF/DCV regimen. Four patients with chronic kidney disease maintained renal function during treatment. Overall, SOF/DCV or SOF/DCV/ribavirin treatment was well tolerated.Conclusion: SOF/DCV with or without ribavirin is highly effective and safe for patients with genotype 2 HCV infection in real-world experience in Taiwan. [ABSTRACT FROM AUTHOR]

Background and Aim: For genotype 2 chronic hepatitis C (CHC), the efficacy and safety of sofosbuvir plus ribavirin therapy (SOF + RBV) was better than pegylated interferon plus ribavirin therapy (PR) at a greater drug cost. This study investigated the cost‐effectiveness of SOF + RBV compared with PR for treatment‐naïve genotype 2 CHC in South Korea. Methods: Using a decision analytic Markov model, a cost‐effectiveness analysis comparing SOF + RBV with PR or no treatment for treatment‐naïve genotype 2 CHC was performed with probabilistic and deterministic sensitivity analyses from the payer's perspective in 2017. Three cohorts of patients aged 40–49, 50–59, and 60–69 years were simulated to progress through the fibrosis stages F0–F4 to end‐stage liver disease, hepatocellular carcinoma, or death. Published and calculated data on the clinical efficacy of the regimen, health‐related quality of life, costs, and transition probabilities were used. Results: While the incremental cost‐effectiveness ratio for PR was dominant over no treatment, the incremental cost‐effectiveness ratios for SOF + RBV were $20 058 for the patients in their 40s, $19 662 for those in their 50s, and $22 278 for those in their 60s compared with PR. Probabilistic sensitivity analysis indicated an 89.0% probability for the SOF + RBV to be cost‐effective at a willingness to pay of $29 754.4 (per‐capita gross domestic product in 2017) for the patients in their 40s and 94.1% and 89.1% for the patients in their 50s and 60s, respectively. Conclusions: The SOF + RBV is a cost‐effective option for genotype 2 treatment‐naïve CHC patients, especially for the patients with liver cirrhosis in Korea. [ABSTRACT FROM AUTHOR]

Bovine mastitis caused by Prototheca has been reported globally, and its incidence is increasing in dairy herds. The present study aimed to investigate the occurrence of Prototheca and persistence of Prototheca zopfii strains in Korean dairy herds. A total of 187 (7.5%) P. zopfii strains were isolated from 2,508 quarter milk samples collected from 50 dairy farms throughout Korea from 2015 to 2017. Prototheca zopfii was isolated from one farm among the 50 farms over the 3-yr period. The P. zopfii isolates belonged to genotype 2. Overall, Prototheca-positive quarter milk samples showed high somatic cell counts with an average value of log 6.48 ± 6.54 cells/mL. Prototheca zopfii was found to be persistent in an infected farm over a 2-yr period. To the best of our knowledge, this is the first report on the presence and persistence of protothecal mastitis caused by P. zopfii genotype 2 in a Korean dairy herd. This disease leads to a significant increase in somatic cell counts in milk, which persists for more than 1 yr in the affected cow udder. These results suggest that P. zopfii could pose a serious risk to dairy herds. Thus, strict surveillance for protothecal mastitis is urgently needed and sanitary conditions regarding the environment and milk collection are essential because of the lack of effective treatment options. [ABSTRACT FROM AUTHOR]

• We isolated and characterized a novel EV-G2 strain, CHN-SCMY2021, the first genotype 2 strain isolated in china. • Genetic characterization reveals recombination between EV-G genotype 2 strains in CHN-SCMY2021, with a whole genome similarity of 78.3%−86.4% to other EV-G genotype 2 strains. • Except for ST cells, CHN-SCMY2021 has a broad spectrum of cellular adaptations, which are susceptible to BHK-21, PK-15, IPEC-J2, LLC-PK and vero cells. • In piglets, CHN-SCMY2021 causes mild diarrhea and thinning of the intestinal wall. Enterovirus G belongs to the family Picornaviridae and are associated with a variety of animal diseases. We isolated and characterized a novel EV-G2 strain, CHN-SCMY2021, the first genotype 2 strain isolated in China. CHN-SCMY2021 is about 25 nm diameter with morphology typical of picornaviruses and its genome is 7341 nucleotides. Sequence alignment and phylogenetic analysis based on VP1 indicated that this isolate is a genotype 2 strain. The whole genome similarity between CHN-SCMY2021 and other EV-G genotype 2 strains is 78.3–86.4%, the greatest similarity is to EVG/Porcine/JPN/Iba26–506/2014/G2 (LC316792.1). Recombination analysis indicated that CHN-SCMY2021 resulted from recombination between 714,171/CaoLanh_VN (KT265894.2) and LP 54 (AF363455.1). Except for ST cells, CHN-SCMY2021 has a broad spectrum of cellular adaptations, which are susceptible to BHK-21, PK-15, IPEC-J2, LLC-PK and Vero cells. In piglets, CHN-SCMY2021 causes mild diarrhea and thinning of the intestinal wall. The virus was mainly distributed to intestinal tissue but was also found in heart, liver, spleen, lung, kidney, brain, and spinal cord. CHN-SCMY2021 is the first systematically characterized EV-G genotype 2 strain from China, our results enrich the information on the epidemiology, molecular evolution and pathogenicity associated with EV-G. [ABSTRACT FROM AUTHOR]

Aim: Combination therapy with sofosbuvir and ribavirin (SOF/RBV) has been recently available for chronic hepatitis C patients with genotype 2 (CHG2) in Japan. The domestic phase III clinical trial showed a high antiviral effect with a relatively safe adverse event (AE) profile. Our aim was to report an important AE detected during treatment. Methods: A prospective multi‐institutional study of 12‐week combination therapy with SOF/RBV for CHG2 was carried out to evaluate efficacy and safety. Results: The eligible subjects included 142 patients. Out of 50 assessable patients, 16% of the patients were diagnosed with hyperuricemia. The proportions of subjects with grade 1, grade 3, and grade 4 hyperuricemia were 12, 2, and 2%, respectively. Serum uric acid (UA) levels at week 1 of the therapy (W1) were numerically the highest during therapy in patients with hyperuricemia, and the ratio of W1/baseline serum UA levels was significantly higher than that of post‐treatment week 4 or 8/baseline serum UA levels in assessable patients. Serum UA levels at W1 were significantly correlated with body mass index. The difference between serum UA levels at W1 and baseline serum UA levels was significantly correlated with the difference between serum creatinine levels at W1 and baseline serum creatinine levels. Conclusions: Elevated serum UA level was a notable AE associated with SOF/RBV therapy for CHG2. However, because of the small number of subjects, the exact frequency of AEs should be re‐evaluated with larger cohorts. We need to remember that elevated serum UA level might develop during the therapy, especially at W1. [ABSTRACT FROM AUTHOR]

Treatment of HCV genotype (GT) 2-infected Japanese patients with paritaprevir (NS3/4A inhibitor boosted with ritonavir) and ombitasvir (NS5A inhibitor) without ribavirin for 12 weeks in the phase 2 study M12-536, and with ribavirin for 16 weeks in phase 3 study GIFT II resulted in SVR rates of 72.2% to 91.5%. Overall, 11 out of 125 patients with GT2a and 37 out of 79 patients with GT2b infection experienced virologic failure. The prevalence of baseline polymorphisms in NS3 and NS5A and their the impact on treatment outcome, as well as the development of viral resistance in GT2-infected patients experiencing virologic failure were evaluated by HCV NS3 and NS5A population and clonal sequence analyses. Baseline polymorphisms in NS3 that confer resistance to paritaprevir were rare in both GT2a- and GT2b-infected patients, while baseline polymorphisms in NS5A that confer resistance to ombitasvir were detected in 11.2% and 14.1% of the GT2a- and GT2b-infected patients, respectively. There was no significant impact of baseline polymorphisms on treatment outcome in Japanese patients. The most common treatment-emergent substitutions at the time of virologic failure occurred at amino acid positions 168 in NS3 and 28 in NS5A in both GT2a- and GT2b-infected patients. Although there was a higher rate of virologic failure in patients with GT2b infection, the resistance analyses presented in this report support the conclusion that testing for baseline resistance-associated polymorphisms is not warranted for HCV GT2-infected patients treated with a regimen of ombitasvir/paritaprevir/ritonavir + ribavirin for 16 weeks. [ABSTRACT FROM AUTHOR]

The aim of this study was to characterize the treatment response and tolerability of sofosbuvir plus ribavirin therapies in Japanese patients infected with hepatitis C virus (HCV) genotype (GT)-2. This retrospective study analyzed 114 Japanese HCV GT-2 patients treated for 12 weeks with 400 mg of sofosbuvir plus weight-based ribavirin daily. This treatment led to higher sustained virologic response at 12-weeks post-treatment (SVR12) rates in both treatment-naïve and treatment-experienced patients. The efficacy of this treatment in compensated cirrhotics was the same as that in patients with chronic hepatitis. HCV GT-2a infection and lower estimated glomerular filtration rates (eGFR) tended to be associated with SVR12. Of 114 patients, 113 completed the combination of sofosbuvir plus ribavirin for 12 weeks. Seven patients without SVR12 did not have HCV NS5B-S282 mutations. The overall SVR12 rate was 90.4% (103 of 114). More effective therapeutic optionswith less adverse events are desired to achieve higher SVR rates in HCV GT-2 Japanese patients. [ABSTRACT FROM AUTHOR]

Background & Aims Sofosbuvir (SOF) and weight-based ribarivin (RBV) represented until recently the standard of care in hepatitis C virus (HCV) genotype (GT)2 patients. In registration studies 12–16 weeks duration were associated with a 90% sustained virological response at 12 weeks (SVR12). Real life cohorts showed lower SVR12 rates. Methods SVR12 rates attained in an Italian real life cohort and possible benefits of a duration extended up to 20 weeks was investigated in HCV GT2 patients with cirrhosis. The role of 2k/1b chimeras as potential predictor of treatment failure was also analysed. Results Overall, 291 HCV GT2 infected patients with bridging fibrosis or cirrhosis were evaluated. Median age was 68 years (18–87); 163 were treatment naïve. Of 168 cirrhotic patients, 149 had Child-Pugh score A and 19 B, 50 platelets count <100,000/mm 3 and 62 albumin <3.5 g/dl. SVR12 were 95.53% overall, with 99.15% in non-cirrhotic patients and 93.06% in cirrhotic patients. In patients who completed treatment, SVR rates for cirrhotic patients resulted in 94.51%, and 94.94% after 16 or 20 weeks respectively. Predictors of SVR were low platelet count and esophageal varices (OR 7.2; 95% CI 1.67–31.25; p = 0.0022 and OR 0.1; 95% CI 0.01–0.72; p = 0.0079, respectively). Anemia was mild in 12.4%, moderate in 3.4%, and severe in 2.4% of cases. Anemia was slightly more frequent among longer duration but not associated with treatment discontinuations. No 2k/1b strains or genotypes different from those at baseline were identified at relapse. Conclusions In GT2 cirrhotic patients, SOF/RBV for 16 or 20 weeks is associated with real life SVR12 rates of 95%. Lay summary A duration of treatment of 16–20 weeks was recommended for treatment of HCV GT2 patients using the combination of sofosbuvir and ribavirin. Real life experiences, where patients received 12 weeks of treatment regardless of the severity of liver disease, suggested that response rates are lower than expected, in particular in patients with liver cirrhosis. A misleading genotyping of a 2k/1b strain as GT2 was also hypothesized as a further explanation for less effectiveness. We demonstrated that using the recommended extended duration in patients with more severe disease 95% of patients with severe liver disease including cirrhosis can be cured and that 2k/1b strain plays only a secondary role in specific countries like Germany. Although this combination has been recently replaced by sofosbuvir and velpatasvir fixed dose combination as the standard of care for treating HCV GT2 patients, our findings may inform physicians from countries where the new regimen is not yet available. [ABSTRACT FROM AUTHOR]

Background and Aims Hepatitis C virus ( HCV) infections with genotype 2 ( GT2) are generally considered as easy to treat. The current standard therapy is 12 weeks of sofosbuvir and ribavirin. However, sustained virological response ( SVR) rates varied substantially in distinct subgroups. Therefore, re-assessing the efficacy of interferon-free therapy in cohorts with larger patient numbers is warranted. Methods The German Hepatitis C registry is a national multicenter cohort. Patients are treated at the discretion of the physician. Data are collected by a web-based data system and confirmed by plausibility checks and on-site monitoring. Results A total of 265 (4.3%) of 6034 patients enrolled in the registry were infected with GT2, and 236 had initiated treatment (60% males, 98% Caucasian, median age 54 years). Treatment with sofosbuvir and ribavirin for 12 weeks achieved SVR at week 12 post-treatment ( SVR12) in 136/164 (83%) patients. SVR12 rates for this regimen were 80% (35/44) in treatment-experienced patients, 74% (20/27) in cirrhotics and 75% (21/28) in patients with HCV- RNA ≥6 million IU/mL. The overall SVR rate in patients treated with sofosbuvir/ribavirin 12 weeks per protocol ( PP), excluding therapy discontinuation or lost to follow-up, was 135/151 (89%). PP SVR12 rates were 91% for treatment naïve, 83% for cirrhotic and 80% for treatment-experienced patients respectively. Conclusions In this large GT2 cohort, sofosbuvir and ribavirin for 12 weeks achieved lower SVR rates compared to treatment outcomes expected from phase 3 trials. These findings highlight the need for establishing alternative treatment strategies for GT2 patients, especially in patients with unfavourable outcome factors. [ABSTRACT FROM AUTHOR]

Objective: Across Japan, around 2 million people are infected with hepatitis C virus (HCV) with long-term complications such as cirrhosis, hepatocellular carcinoma (HCC) and liver transplant (LT). Current treatment options have several limitations due to side effects, interferon intolerability and ineligibility, long treatment durations and low sustained virological responses (SVR) rates, especially for the most severe patients. Sofosbuvir (SOF) is the first nucleotide analog NS5B polymerase inhibitor with pan-genotypic activity. SOF, administered in combination with ribavirin (RBV) with or without pegylated interferon (PEGIFN) resulted in high SVR rates across genotype (GT) 1-6 patients. It is also the first available regimen for patients that are unsuitable for interferon. This analysis assessed the cost-utility ratio of sofosbuvir in GT2 patients in Japan.Research Design and Methods: A Markov model followed a cohort of 10,000 GT2 patients until patients reached 100 years of age. Approximately 20% of patients initiated treatment at the cirrhotic stage. Comparators were based on the current recommendations in Japan, including PEGIFN with ribavirin (RBV), telaprevir (TVR) in combination with PEGIFN + RBV and no treatment. Costs and outcomes were discounted at 2%.Results: Sofosbuvir was cost-effective across all the studied indications, especially in patients unsuitable for interferon, with incremental cost-effectiveness ratios (ICERs) lower than JPY 5,000,000. Compared to the other treatments included in the analysis, SOF + RBV resulted in improved clinical outcomes. Results were robust to sensitivity analyses.Conclusion: SOF combined with RBV was shown to be cost-effective in GT2 patients in Japan. Compared to PEGIFN + RBV, TVR + PEGIFN + RBV and no treatment SOF offers a more efficacious, shorter and better tolerated treatment option and extends treatment to reach HCV-infected patients who are ineligible for interferon-based regimens. Although adverse events were not included in the analyses, this would not make any changes to our conclusion. [ABSTRACT FROM AUTHOR]

Background: An interferon-free regimen including sofosbuvir and ribavirin (RBV) for patients with hepatitis C virus (HCV) genotype 2 (G2) infection leads to a drastic improvement of sustained virological response (SVR). However, the safety, tolerability, and efficacy in patients aged 75 or older have not been completely understood. Summary: Fifty-six patients with HCV G2 infection who were treated with sofosbuvir and weight-based dose of RBV were enrolled. Thirty-seven patients aged ≥75 and 19 patients aged ≤74 were classified as the aged and non-aged groups, respectively. The aged group was characterized by significantly more number of women, history of hepatocellular carcinoma, low serum albumin (ALB) level, low hemoglobin (Hb) concentration, low estimated glomerular filtration rate (eGFR), and high fibrosis-4 index (p = 0.0029). Forty-one patients were evaluated for SVR at 12 weeks after the end of therapy (SVR12); of them, all but one completed the treatment scheduled for 12 weeks. The aged group showed lower SVR12 rate than the nonaged group (81.3% for aged and 96.0% for non-aged groups). Although the Hb concentration and eGFR are significantly lower in the aged group throughout the clinical course, all patients in the aged group completed the 12-week treatment with a gradual increase of serum ALB level. Key Messages: The combination of sofosbuvir plus RBV is tolerable and beneficial in patients aged >75. However, intensive management of anemia by dose reduction of RBV is necessary, which could lead to a low SVR12 rate compared to that observed in patients younger than 75 years. [ABSTRACT FROM AUTHOR]

Although patients with congenital long QT syndrome (c-LQTS) are considered to be at high risk for anesthesia, few reports describe c-LQTS genotype-specific considerations for anesthesia. We describe a case of torsade de pointes (TdP) caused by sevoflurane in a patient with c-LQTS genotype 2 (LQT2). A 39-year-old woman diagnosed with c-LQTS was scheduled for an elective therapeutic abortion. Immediately after starting the operation, the patient developed TdP. Since pulseless ventricular tachycardia was sustained despite intravenous injection of lidocaine, defibrillation was performed. Analysis of the electrocardiogram revealed that the corrected QT interval before anesthesia was 530 ms and 2.0% sevoflurane markedly prolonged the corrected QT interval to 693 ms. Postoperative studies revealed a mutation in the KCNH2 gene. Anesthesiologists should note that patients with LQT2 could be more susceptible to volatile anesthetics than are those with other major genotypes. Genotype-specific management of anesthesia may reduce the risk of developing TdP during the perioperative period. [ABSTRACT FROM AUTHOR]

Background and purpose: Peginterferon Lambda was being developed as an alternative to alfa interferon for the treatment of chronic hepatitis C virus (HCV) infection. We compared peginterferon Lambda-1a plus ribavirin (Lambda/RBV) and Lambda/RBV plus daclatasvir (DCV; pangenotypic NS5A inhibitor) with peginterferon alfa-2a plus RBV (alfa/RBV) in treatment-naive patients with HCV genotype 2 or 3 infection. Methods: In this multicenter, double-blind, phase 3 randomized controlled trial, patients were assigned 2:2:1 to receive 24 weeks of Lambda/RBV, 12 weeks of Lambda/RBV + DCV, or 24 weeks of alfa/RBV. The primary outcome measure was sustained virologic response at post-treatment Week 12 (SVR12). Results: Overall, 874 patients were treated: Lambda/RBV, n = 353; Lambda/RBV + DCV, n = 349; alfa/RBV, n = 172. Patients were 65 % white and 33 % Asian, 57 % male, with a mean age of 47 years; 52 % were infected with genotype 2 (6 % cirrhotic) and 48 % with genotype 3 (9 % cirrhotic). In the Lambda/RBV + DCV group, 83 % (95 % confidence interval [CI] 78.5, 86.5) achieved SVR12 (90 % genotype 2, 75 % genotype 3) whereas SVR12 was achieved by 68 % (95 % CI 63.1, 72.9) with Lambda/RBV (72 % genotype 2, 64 % genotype 3) and 73 % (95 % CI 66.6, 79.9) with peginterferon alfa/RBV (74 % genotype 2, 73 % genotype 3). Lambda/RBV + DCV was associated with lower incidences of flu-like symptoms, hematological abnormalities, and discontinuations due to adverse events compared with alfa/RBV. Conclusion: The 12-week regimen of Lambda/RBV + DCV was superior to peginterferon alfa/RBV in the combined population of treatment-naive patients with genotype 2 or 3 infection, with an improved tolerability and safety profile compared with alfa/RBV. [ABSTRACT FROM AUTHOR]

Background & Aims In Taiwan, patients with chronic hepatitis C virus ( HCV) infection are currently treated with pegylated interferon-alpha plus ribavirin, but interferon-based regimens can be poorly tolerated, especially by those with advanced liver disease and the elderly. Sofosbuvir, an oral nucleotide analogue inhibitor of HCV NS5B polymerase, is approved in Europe, the USA and Japan for treating chronic HCV infection. This phase 3b study examined the efficacy and safety of sofosbuvir plus ribavirin in Taiwanese patients with chronic genotype 2 HCV infection ± compensated cirrhosis. Methods In this multicentre, open-label, phase 3b ( NCT02021643) study, 87 patients ( n = 43, treatment-naive; n = 44, treatment-experienced) received 12 weeks of treatment with sofosbuvir plus weight-based ribavirin. The primary efficacy endpoint was the proportion of patients with sustained virological response 12 weeks after treatment discontinuation ( SVR12). Safety and pharmacokinetic data were also collected. Results All 87 patients (100%; 95% confidence interval, 92-100%) achieved SVR12, including the 13 patients with compensated cirrhosis. The most common treatment-emergent adverse events ( AEs) were insomnia (16%, 14/87) and upper respiratory tract infection (16%, 14/87). No grade 3 or grade 4 AE was reported. There was one serious AE (biliary colic), which was deemed unrelated to study treatment. Laboratory abnormalities other than ribavirin-related reductions in haemoglobin were uncommon. Conclusions The results from this phase 3b study demonstrate that 12 weeks of treatment with the interferon-free regimen sofosbuvir plus ribavirin is effective and well tolerated in both treatment-naive and treatment-experienced Taiwanese patients with chronic genotype 2 HCV infection. [ABSTRACT FROM AUTHOR]

A novel strain of duck reovirus (DRV) associated with a high mortality in Pekin ducklings in China, 2013, was isolated and characterized. This strain (designated as HN5d) grew well in Vero cells and produced marked cytopathic effects. HN5d contains 10 dsRNA genome segments, a typical feature of avian orthoreovirus. Following cloning, sequencing, and sequence analysis of the genome segments, a unique deletion of 18 amino acids was found in the sigma C protein of HN5d when compared with that of the recent Chinese waterfowl reoviruses (e.g., DRV 091). Phylogenetic analysis of cDNA amplicons of segments encoding for the outer capsid proteins revealed that HN5d is a novel genotype 2 waterfowl reovirus isolate. Inoculation of Pekin ducklings with HN5d resulted in splenic necrosis, a typical feature of “Duck spleen necrosis disease” (DSND) discovered in China in 2006. Unlike the typical DSND, HN5d produced severer hemorrhagic and/or necrotic lesions in livers of experimentally infected ducklings. 20–30% of death was observed during the first 7 day in the experimentally exposed birds. These findings suggest that HN5d is a novel duck reovirus isolate with severer pathogenicity in Pekin ducklings. [ABSTRACT FROM AUTHOR]

Background & Aims HCV Council 2014, like its predecessor HCV Council 2011, assembled leading clinicians and researchers in the field of hepatitis C to critically evaluate current data regarding best practices for managing patients with chronic hepatitis C virus ( HCV). Methods Clinical practice statements were developed that reflect the areas of potential controversy with high clinical impact. Faculty members were responsible for reviewing the literature to support or reject these statements. After a review and comprehensive discussion of the data, the HCV Council faculty voted on the nature of the evidence and the level of support for each statement. Results The results of the detailed analysis with expert opinion are summarized in this article. Conclusion Numerous questions regarding optimal management of certain populations and clinical scenarios remain unanswered. The discussion in the article provides a summary of evidenced-based expert opinion that may help guide clinicians as additional information is developed. [ABSTRACT FROM AUTHOR]

Objective: Interferon-free therapy for hepatitis C virus (HCV) infection is costly, and therefore patients with advanced fibrosis are prioritized. Although coupled with considerable side effects, a large proportion of genotype 2/3 infected patients achieve a sustained virological response (SVR) following interferon-based therapy. The present study evaluates experimental clinical trial and verifying real-life data with the aim of identifying patients with a high likelihood of favorable outcome following short interferon-based treatment.Material and methods: The impact of established response predictors, e.g. age,ITPAandIL28Bgenetic variants, IP-10, liver histopathology and early viral kinetics on outcome was evaluated among HCV genotype 2/3 infected patients enrolled in the NORDynamIC trial. Similarly outcome was evaluated among Finnish and Swedish real-life genotype 2/3 infected patients treated for 12–16 weeks in accordance with national guidelines.Results: In the NORDynamIC trial, age <40 years or achieving HCV RNA <1000 IU/mL day 7 were highly predictive of favorable outcome following 12 weeks therapy. Among 255 Finnish real-life patients below the age of 40 years treated for 12 weeks with interferon and ribavirin, 87% of HCV genotype 2 and 79% of genotype 3 infected patients achieved SVR, and among 117 Swedish real-life patients treated for 12–16 weeks, 97% of HCV genotype 2 and 94% of genotype 3 infected achieved SVR.Conclusions: Short interferon-based therapy offers a high likelihood of achieving SVR for selected HCV genotype 2/3 infected patients, and is an acceptable option given that a thorough discussion of the side effects is provided prior to initiation. [ABSTRACT FROM PUBLISHER]

By screening a collection of fecal samples from young cats housed in three different shelters in South Italy, noroviruses (NoVs) were found in 3/48 (6.2%) specimens of animals with enteritis signs while they were not detected in samples collected from healthy cats (0/57). Upon sequence analysis of the short RNA-dependent RNA polymerase (RdRp) region, the three strains displayed the highest nucleotide (nt) and amino acid (aa) identities to the prototype GIV.2 strain lion/Pistoia/387/06/ITA (91.0–93.0% nt and 97.0–98.0% aa). The sequence of ~ 3.4-kb portion at the 3′ end of the genome of a NoV strain, TE/77-13/ITA, was determined. In the full-length ORF2, encoding the VP1 capsid protein, the virus was genetically closest to the canine GVI.2 NoV strains C33/Viseu/2007/PRT and FD53/2007/ITA (81.0–84.0% nt and 93.0–94.0% aa identities), suggesting a recombination nature, with the cross-over site being mapped to the ORF1-ORF2 junction. Based on the full-length VP1 amino acid sequence, we classified the novel feline NoV, together with the canine strains Viseu and FD53, as a genotype 2, within the genogroup GVI. These findings indicate that, as observed for GIV NoV, GVI strains may infect both the canine and feline host. Unrestricted circulation of NoV strains in small carnivores may provide the basis for quick genetic diversification of these viruses by recombination. Interspecies circulation of NoVs in pets must also be considered when facing outbreaks of enteric diseases in these animals. [ABSTRACT FROM AUTHOR]

Sofosbuvir is the first pan-genotypic direct acting antiviral agent to be approved. This article provides an overview of the pharmacology of sofosbuvir and ribavirin and a comprehensive summary of the phase 2 and 3 studies supporting dual sofosbuvir and ribavirin therapy for chronic hepatitis C infection. With the production of generic formulations of sofosbuvir, we anticipate this regimen leading the first wave for widespread, IFN-free treatment and becoming first line for all genotypes (including genotype 1) for much of the world—in particular in developing and middle income countries. We discuss the continued challenges with this regimen including among patients with decompensated liver disease and post-liver transplant, and renal failure. We address concerns of emerging resistance. We also discuss the future prospects including the global uptake of sofosbuvir and ribavirin for the treatment of all genotypes. [ABSTRACT FROM PUBLISHER]

Since optimization studies with Peginterferon (PegIFN) and Ribavirin (Rbv), antiviral treatment of hepatitis C virus (HCV) genotype 2 patients consisted in a 24-week course of dual therapy, resulting in 80-85 % sustained virological response (SVR) rates. PegIFN/Rbv combination was effective in most patients; however, it was burdened by side effects and was suboptimal in difficult-to-treat subgroups, like advanced fibrosis stages. Despite the attempts of treatment individualization according to baseline and on-treatment predictors to increase efficacy and tolerability, many patients had no access to treatment due to comorbidities contraindicating PegIFN administration. In this scenario, the development of new drugs directly targeting HCV replication cycle opened the way to IFN-free combination regimens that could not only increase efficacy but also, most of all, reduce side effects and expand treatment access. This review is focused on new treatment options in HCV-2 patients, from phase III studies to real-life data. [ABSTRACT FROM AUTHOR]

Aim This study assessed the efficacy and safety of telaprevir in combination with peginterferon-α-2b ( PEG IFN) and ribavirin ( RBV), for Japanese difficult-to-treat patients with hepatitis C virus ( HCV) genotype 2 who had not achieved sustained virological response ( SVR) during prior treatment. Methods In total, 108 relapsed (median age, 59.0 years) and 10 non-responding (median age, 59.0 years) patients with genotype 2 HCV participated. Patients received telaprevir (750 mg, every 8 h) for 12 weeks and PEG IFN/ RBV for 24 weeks. Results The SVR rates for relapsers and non-responders were 88.0% (95/108) and 50.0% (5/10), respectively. The SVR rates did not differ significantly between patients with rs8099917 TT and non- TT. The SVR rates for relapsers and non-responders with extended rapid viral response ( eRVR) were 97.6% (82/84) and 100% (5/5), respectively. On the other hand, the SVR rates for relapsers and non-responders completing the treatment protocol were 98.4% (61/62) and 100% (5/5), respectively. The overall safety profiles of telaprevir-based regimens were similar for Japanese patients with genotype 1 and 2 HCV infection who experienced treatment failure. Conclusion Telaprevir, in combination with PEG IFN/ RBV, provided a high SVR rate for genotype 2 HCV, difficult-to-treat patients who had not achieved SVR during prior IFN-based treatment. The eRVR had a strong influence on the cure rate of telaprevir-based therapy. In addition, the continuation of telaprevir-based treatment for up to 24 weeks was a significant predictor of SVR. [ABSTRACT FROM AUTHOR]

The efficacy of antiviral treatment depends on which of the seven genotypes (G1-G7) of hepatitis C virus (HCV) has infected the patient. Conventionally, clinicians regarded G2 and G3 infections as 'easy-to-treat': dual therapy with pegylated interferon and ribavirin produces a sustained virologic response in approximately 40-50% of patients with G1 infection, compared with 80% when analyses report combined data for G2 and G3 patients, which is standard practice in many clinical studies. However, sustained virologic response rates appear to be lower in certain subgroups of people infected with G3 compared with those with G2 or the general HCV-infected population. This review examines the growing evidence that factors related to the virus (e.g., baseline viral load and a rapid virologic response) and host characteristics (e.g., steatosis and fibrosis, metabolic syndrome, host polymorphisms and ethnicity) contribute to variations in therapeutic success in G3 HCV. [ABSTRACT FROM AUTHOR]

Background and Aim The single nucleotide polymorphism ( SNP) of interleukin 28 B ( IL28B) and the mutations in the NS5A region of hepatitis C virus ( HCV) genotype 1 have been associated with response to interferon ( IFN) therapy. However, these relationships in patients with HCV genotype 2 are not well understood. The aim of this study was to investigate whether the SNP of IL28B (rs8099917) and amino acid substitutions in the NS5A region in patients with HCV genotype 2 affect the response to IFN and ribavirin combination therapy. Methods The study enrolled 286 patients with chronic hepatitis C genotype 2. Patients received pegylated- IFN-alpha 2b once each week plus oral ribavirin daily for 24 weeks. Results Of the 286 patients, 215 (75.2%) achieved sustained virologic response ( SVR). Rate of SVR was similar in patients with IL28B TT allele (76%) and those with TG or GG alleles (72%). Patients with SVR were younger than those without SVR ( P < 0.001). SVR was achieved in 65.9% of patients with wild-type IFN sensitivity-determining region ( ISDR) and 83.5% of patients with mutant type ( P < 0.001). There were no significant differences in other factors, including sex, alanine aminotransferase, platelet count, HCV viral load, HCV genotype, and IL28B genotype. The factors related to SVR on multivariate analysis were age ( P = 0.019) and ISDR ( P = 0.003). Conclusions ISDR sequence variations are significantly associated with IFN responsiveness in patients with HCV genotype 2. The SNP of IL28B was not associated with SVR in patients with HCV genotype 2. [ABSTRACT FROM AUTHOR]