B-infected Patients Research Articles

HLA Gene Polymorphism in Patients with Chronic HBV Infection. Fundeni Clinical Institute Experience

Introduction: Hepatitis B virus (HBV) infection is a serious health problem for the public health systems in many countries worldwide. According to the European Society for the Liver Study, more than 350 million people are diagnosed with hepatitis B virus infection. Chronic viral HBV infection could be caused by the inability of both the cellular and humoral immune systems to eliminate HBV. HLA genes control cellular and humoral immune responses and present the viral antigens to CD8+ (cytotoxic T cells) and CD4+ T (T helper cells). Aim: To look at the HLA allele polymorphisms in chronic hepatitis B-infected patients to search for significant HLA allele associations. Methods: We have included 240 patients with HBV infection from the Gastroenterology and Hepatology ward, at Fundeni Clinical Institute. As a control group, 300 unrelated healthy people with no hepatitis B infection were also included. We have genotyped the HLA class I and class II genes for both patients and the control group with Next Generation Sequencing Illumina (Immucor, Mia Fora NGS Flex, Norcross, GA, USA). Results: Our preliminary data showed that HLA-DQA1*01:02:02 and HLADRB5*02:02:01 alleles are associated with the risk of HBV infection persistence. Conclusions: Our study showed that a specific HLA genotype profile is associated with chronic HBV infection in our Romanian patients.

Cloning and periplasmic soluble expression of hepatitis B surface antigen gene in Escherichia coli.

The objective of this study was to clone and express the hepatitis B surface antigen gene (HBsAg) in Escherichia coli (E. coli), thereby aiming to develop potential local therapeutics for combating Hepatitis B virus (HBV) infection in the Pakistani community by producing HBsAg in E. coli. Blood serum samples were collected from hepatitis B-infected patients, and their genomic DNA was extracted. Real-time and nested polymerase chain reaction (PCR) was performed to amplify the HBsAg gene. The gene of interest was cloned into the pET20b expression vector and transformed into E. coli BL21 (DE3) using Isopropyl β-D-1-thiogalactopyranoside (IPTG) induction. The gene's precise size was confirmed with gene-specific external and internal primers (681 bp and 400 bp, respectively). The HBsAg gene was successfully sequenced and submitted to GenBank, exhibiting 98% homology with targeted HBV sequences worldwide. The expression of HBsAg protein was confirmed through silver staining, Coomassie staining, western blot, and dot blot analysis. The expressed protein clones are now available for further development as a local recombinant DNA vaccine to prevent hepatitis B viral infection in the local community.

A CASE OF THYROTOXIC PERIODIC PARALYSIS AND MODERATE TO SE- VERE GRAVE’S OPHTHALMOPATHY REQUIRING INTRAVENOUS STEROID THERAPY WITH A COMORBIDITY OF CHRONIC HEPATITIS B INFECTION

Grave’s disease is an autoimmune thyroid disease with several characteristic symptoms and signs. Grave’s ophthalmopathy, an inflammatory disease in the orbital area, is the primary extrathyroid manifestation of Grave’s disease. About 5% of Grave’s ophthalmopathy patients have moderate to severe severity requiring high doses of systemic corticosteroid therapy. Grave’s disease also has a few complications, one of which is thyrotoxic periodic paralysis characterized by hypokalemia and muscle paralysis. Chronic hepatitis B virus infection has the potential to be co-incidence with other diseases (e.g., Grave’s ophthalmopathy). The need for a high dose of corticosteroid therapy in treating Grave’s ophthalmopathy is a risk of reactivation in hepatitis B-infected patients. This paper presented a Grave’s disease patient complicated with Grave’s ophthalmopathy who developed limb muscle weakness. The patient will receive high doses of corticosteroids and prophylactic lamivudine therapy to prevent hepatitis B virus reactivation.

Impact of HIV-1 subtypes on gross deletion in the nef gene after Korean Red Ginseng treatment

BackgroundThe number of primary human immunodeficiency virus (HIV)-1 non-B subtype infections (non-B) and that of reports regarding the differences in the pathogenesis of subtype B and non-B infections are increasing. However, to the best of our knowledge, there have been no reports on gross deletion in the nef gene (gΔnef) in non-B infections. MethodsTo determine whether there is a difference in the change in CD4+ T cells after treatment with Korean Red Ginseng (KRG) between patients with subtype B and non-B infections, we retrospectively analyzed and compared the annual decrease in CD4+ T cells (AD) and the proportion of gΔnef in 77 patients who were followed for more than 10 years in the absence of combination antiretroviral therapy. ResultsOverall, AD was significantly faster in patients with non-B infections than in those with subtype B infections. Survival analysis showed that the survival probability was significantly higher in subtype B than in non B-infected patients. These differences mainly resulted from significant differences in the amount of KRG and age. In the patients treated with KRG, there was a significant correlation between the amount of KRG and the AD in both subtypes. Interestingly, there was a significant correlation between the amount of KRG and the proportion of gΔnef in patients infected with subtype B, but not in those infected with non-B. The same phenomenon was observed when the KRG dose was adjusted. ConclusionOur results suggest that non-B may be biologically more stable than subtype B.

Genotype-specific versus pangenotypic regimens in patients infected with hepatitis C virus genotype 1b in real-world settings.

Introduction: The introduction of direct-acting antivirals (DAAs) has provided us with hope to eliminate hepatitis C virus (HCV) infection as a significant public health problem in the coming years. Objective: Our study aimed to compare the effectiveness and safety of genotype-specific and pangenotypic regimens in genotype 1b–infected patients treated in real-world settings. Patients and methods: Patients were selected from 990 HCV-infected individuals treated with DAAs in the Department of Infectious Diseases in Kielce, Poland, who had the therapy initiated between July 1, 2015 and December 31, 2020. Results: A total of 795 genotype 1b–infected patients with a median age of 51 years, female predominance (55%), and a 21.1% rate of cirrhosis were included in the analysis. A total of 69.9% of patients were treated with genotype-specific regimens. Those patients were significantly older, more often were treatment experienced, and had advanced liver fibrosis and cirrhosis compared with patients assigned to pangenotypic regimens. An overall sustained virologic response rate of 97.9% in the intention-to-treat (ITT) analysis and 99% after excluding nonvirologic nonresponders was achieved, with no significant difference between patients in the 2 treatment arms. Significantly higher proportions of men (P = 0.001) and DAA-experienced patients (P = 0.049) were documented among virologic nonresponders. Conclusions: We confirmed very high effectiveness and a good safety profile of both genotype-specific and pangenotypic regimens used in patients with genotype 1b HCV infection, and we found no differences between these 2 generations of medications. Male sex and previous treatment with DAAs were identified as negative predictors for therapy effectiveness.

Human respiratory syncytial virus diversity and epidemiology among patients hospitalized with severe respiratory illness in South Africa, 2012-2015.

BackgroundWe aimed to describe the prevalence of human respiratory syncytial virus (HRSV) and evaluate associations between HRSV subgroups and/or genotypes and epidemiologic characteristics and clinical outcomes in patients hospitalized with severe respiratory illness (SRI).MethodsBetween January 2012 and December 2015, we enrolled patients of all ages admitted to two South African hospitals with SRI in prospective hospital‐based syndromic surveillance. We collected respiratory specimens and clinical and epidemiological data. Unconditional random effect multivariable logistic regression was used to assess factors associated with HRSV infection.ResultsHRSV was detected in 11.2% (772/6908) of enrolled patients of which 47.0% (363/772) were under the age of 6 months. There were no differences in clinical outcomes of HRSV subgroup A‐infected patients compared with HRSV subgroup B‐infected patients but among patients aged <5 years, children with HRSV subgroup A were more likely be coinfected with Streptococcus pneumoniae (23/208, 11.0% vs. 2/90, 2.0%; adjusted odds ratio 5.7). No significant associations of HRSV A genotypes NA1 and ON1 with specific clinical outcomes were observed.ConclusionsWhile HRSV subgroup and genotype dominance shifted between seasons, we showed similar genotype diversity as noted worldwide. We found no association between clinical outcomes and HRSV subgroups or genotypes.

Profiling of Intestinal Microbiota in Patients Infected with Respiratory Influenza A and B Viruses.

Little is known about the association between respiratory viral infections and their impact on intestinal microbiota. Here, we compared the effect of influenza types, A and B, and influenza shedding in patients’ stools on the gut microbiota diversity and composition. Deep sequencing analysis was performed for the V4 region of the 16S rRNA gene. Fecal samples were collected from 38 adults with active respiratory influenza infection and 11 age-matched healthy controls. Influenza infection resulted in variations in intestinal bacterial community composition rather than in overall diversity. Overall, infected patients experienced an increased abundance of Bacteroidetes and a corresponding decrease in Firmicutes. Differential abundance testing illustrated that differences in gut microbiota composition were influenza type-dependent, identifying ten differentially abundant operational taxonomic units (OTUs) between influenza A- and influenza B-infected patients. Notably, virus shedding in fecal samples of some patients had significantly reduced gut bacterial diversity (p = 0.023). Further taxonomic analysis revealed that the abundance of Bacteroides fragilis was significantly higher among shedders compared to non-shedders (p = 0.037). These results provide fundamental evidence of the direct effect of influenza infection on gut microbiota diversity, as reported in patients shedding the virus.

The Use of Statin Is Associated With Better Disease-Free Survival In Patients with Hepatitis B-Related Hepatocellular Carcinoma after Curative Treatment

Background and aims: The association of use of statins and risk of hepatocellular carcinoma (HCC) hepatitis B-infected (HBV) patients has been reported. This study aimed to examine the effect of statin on survival after curative treatment for HCC in HBV population.

Serological markers and molecular analysis of hepatitis B infection in a tertiary care hospital at Kathmandu, Nepal.

To analyze the serology and molecular markers of the hepatitis B-infected patients from the tertiary care hospital at Kathmandu in Nepal. A total of 399 blood samples of patients from Sukraraj Tropical and Infectious Disease Hospital, Teku, Kathmandu, were collected. Samples were tested for HBsAg, HBeAg, and IgM anti-HBc using ELISA method. The samples were further categorized as acute and chronic. The genotyping was performed by real-time polymerase chain reaction (real-time PCR) and further validated by sequencing. Out of 399 samples that were collected, 271 and 128 samples were acute and chronic cases respectively. Fifty-six samples were genotyped by qPCR, out of which 40 samples belonged to genotype D, 4 to C/D recombinant, 5 to genotype C, 3 to genotype B, and 4 were genotype A respectively. From these, 15 samples were used for sequencing of P (polymerase) gene and S (surface) genes. Thus, obtained sequences were used to construct neighbor-joining tree using Tamura-Nei model evolution and further validated by Bayesian analysis. A total of four sub-genotypes namely A1, C1, D1, and D5 were detected. Hepatitis B virus infection is a global health problem affecting about 257 million people worldwide. In Nepal, there are few reports on the molecular and phylogenetic analysis of this virus. In this study, we report the circulation of seropositive occult hepatitis as well as CD-recombinant genotype in Nepalese population.

Real-world effectiveness and safety of OBT/PTV/r and dasabuvir for patients with chronic HCV genotype 1b infection in China: A multicenter prospective observational study

Background and aimReal-world data on the effectiveness and safety of treatment with the direct-acting antiviral agent-based regimen are limited on the Chinese mainland. The aim of this study was to conduct a multicenter, prospective, real-world study of ombitasvir/paritaprevir/ritonavir (OBT/PTV/r) combined with dasabuvir (DSV) in hepatitis C virus (HCV) genotype 1b-infected non-cirrhotic or compensated cirrhotic Chinese adult patients. Materials and methodsGenotype 1b-infected patients were enrolled at eight sites in China. Patients received 25/150/100 mg of OBT/PTV/r once daily combined with 250 mg of DSV twice daily for 8 weeks or 12 weeks. Sustained virological response at 12 weeks post-treatment (SVR12) and the incidence of adverse events were assessed. We have also evaluated the effect of intensive questioning of patients who were overdue for SVR12 testing. Intention-to-treat (ITT) and modified ITT (mITT) populations were used in the analysis. ResultsOne hundred forty patients were included, among whom 90.0% (126/140) were newly diagnosed, 9.3% (13/140) had compensated cirrhosis, 92.9% (130/140) received 12 weeks of treatment, and 7.1% (10/140) received 8 weeks of treatment. In the mITT population, the virological response rate at week 4 was 96.4% (108/112), and at the end of treatment was 100% (102/102). Among these patients, 139 patients completed 12 weeks of treatment, and 73 patients were followed-up. All followed-up patients achieved SVR12. There was no adverse event-related discontinuation. Serious adverse events during treatment were reported in two (1.4%) patients, and none were considered to be drug-related. Sixty-six (47.1%) patients did not return to receive the HCV RNA test at 12 weeks post-treatment. ConclusionsThe rate of SVR12 was consistent with Phase III clinical studies. OBT/PTV/r combined with DSV showed effectiveness in Chinese adult patients, and both tolerability and safety profile were favorable. However, patient compliance should be further improved in the real world.

T-cell responses following Natural Influenza Infection or Vaccination in Solid Organ Transplant Recipients

Little is known about cell-mediated immune responses to natural influenza infection in solid organ transplant (SOT) patients. The aim of our study was to evaluate the CD4+ and CD8+ responses to influenza A and B infection in a cohort of SOT patients. We collected peripheral blood mononuclear cells at influenza diagnosis and four weeks later from 31 SOT patients during the 2017–2018 influenza season. Infection-elicited influenza-specific CD4+ and CD8+ T-cell responses were measured using flow cytometry and intracellular cytokine staining and compared to responses following influenza vaccine in SOT patients. Natural infection was associated with a significant increase in CD4+ T-cell responses. For example, polyfunctional cells increased from 21 to 782 and from 193 to 1436 cells per 106 CD4+ T-cells among influenza A/H3N2 and B-infected patients (p = 0.006 and 0.004 respectively). Moreover, infection-elicited CD4+ responses were superior than vaccine-elicited responses for influenza A/H1N1 (931 vs 1; p = 0.026), A/H3N2 (647 vs 1; p = 0.041) and B (619 vs 1; p = 0.004). Natural influenza infection triggers a significant increase in CD4+ T-cell responses in SOT patients. Infection elicits significantly stronger CD4+ responses compared to the influenza vaccine and thereby likely elicits better protection against reinfection.

Comparative effectiveness of 8 versus 12 weeks of Ombitasvir/Paritaprevir/ritonavir and Dasabuvir in treatment-naïve patients infected with HCV genotype 1b with non-advanced hepatic fibrosis

PurposeSince 2017 treatment-naïve patients infected with genotype 1b of hepatitis C virus and minimal or moderate fibrosis can be treated with Ombitasvir/Paritaprevir/ritonavir + Dasabuvir (OPrD) for 8 weeks according to updated Summary of Product Characteristics. The aim of our study was to assess the comparative efficacy of 8 and 12-weeks therapy with OPrD in large cohort of patients eligible for 8 weeks regimen treated in real-world setting. Materials and methodsWe analysed data of 3067 HCV genotype 1b infected patients treated with OPrD between 2015 and 2017. Final analysis included patients with none, minimal or moderate fibrosis (F0–F2). ResultsA total of 771 patients were enrolled in the study, including 197 (26%) treated for 8-weeks and 574 patients fulfilling criteria for 8-weeks but assigned to 12-weeks regimen. Majority of patients had no or minimal fibrosis (F0–F1). Longer treatment duration was more often administered in patients with moderate fibrosis, comorbidities, concomitant medications. SVR was achieved in 186 (94%) patients treated for 8 weeks and 558 (97%) for 12 weeks (p = 0.07). After exclusion of lost to follow-up patients, sustained virological response (SVR) rate reached 95% and 99%, respectively (p = 0.01). We were not able to identify factors associated with non-response. ConclusionsThis real-word experience study confirmed similar, high effectiveness of 8 and 12-weeks regimens of OPrD in genotype 1b HCV infected patients with non-advanced fibrosis. Despite of reduced SVR rate after 8-weeks regimen, there is no need to extend therapy to 12-weeks in vast majority of such patients and no need to add ribavirin.

Baseline resistance associated substitutions in HCV genotype 1 infected cohort treated with Simeprevir, Daclatasvir and Sofosbuvir in Brazil

The World Health Organization estimates that 1% of the world population (71 million) is infected with hepatitis C virus (HCV). In 2015, three direct-acting antivirals (DAAs), simeprevir (SMV), sofosbuvir (SOF) and daclatasvir (DCV) were included in the Brazilian protocol for the treatment of chronic hepatitis C. Despite the fact that the use of these drugs is associated with higher treatment response rates and with lower incidence of side effects, studies have shown the association between the presence of viral resistance mutations and the failure of pharmacological treatment. This way, this study aimed to evaluate the safety and effectiveness of treatment for HCV genotypes 1a and 1b infected patients with these DAAs, also analyzing the occurrence and prevalence of baseline resistance associated substitutions (RAS), observing the impact of these mutations into the treatment success. Clinical data were collected from all the 262 HCV infected patients included for comparative analysis, while serum samples collected from 144 of these individuals, before treatment, were submitted to molecular biology approaches for mutation analysis into NS3, NS5A and NS5B regions. Regarding the treatment regimens, 49.6% of the patients received SOF+DCV±ribavirin and 50.4% used SOF+SMV±ribavirin. The sustained virological response at 12 weeks post-treatment (SVR12) rate was 92.7% (93.9% for SOF plus DCV and 91.7% for SOF plus SMV). No clinical or laboratorial factor was statistically associated with SVR. The most common adverse reactions were haematological events, nausea/vomiting, headache and asthenia. Out of 144 blood samples, 70 (48.6%) had detected RAS, 34.8% treated with SOF+DCV±ribavirin and 61.3% SOF+SMV±ribavirin. The resistance mutations against SMV were detected into NS3: substitutions G122S (28%), I170V (22.7%), Y56F (17.3%) and V132I (14.7%). The mutations against DCV R30Q (9.1%), P58H (6.1%) and Q62E (6.1%) were observed into NS5A, and for SOF the mutations A421V (10.6%), L159F (6.4%) and C316N (6.4%) were present inside NS5B viral protein. Four patients did not reach SVR, three of them presented viruses carrying RAS (1 treated with SOF+DCV and 2 with SOF+SMV). Some of these mutations, like R30Q (present in relapsing samples) and L159F, are well known by their influence on antiviral resistance, while others, like C316N, have a compensatory effect on viral fitness, maintaining these baseline RAS. The use of treatment regimens composed of SOF and DCV or SOF and SMV showed a high SVR rate, despite of a high rate of RAS, and a good tolerability profile in patients with HCV genotype 1. However, the high occurrence of baseline RAS observed in this casuistic is still a concern and studies like this show the necessity to understand how they are maintained in the population and to direct more efficiently the use of DAAs.

NS5A Gene Analysis by Next Generation Sequencing in HCV Nosocomial Transmission Clusters of HCV Genotype 1b Infected Patients.

Background: The aim of the study was to investigate the intra-host variability through next-generation-sequencing (NGS) of the NS5A-gene in nosocomial transmission-clusters observed in two Italian hospitals among hepatitis C virus (HCV)-genotype-1b infected patients. Methods: HCV-sequencing was performed by Sanger-sequencing (NS3 + NS5A + NS5B) and by NGS (NS5A, MiSeq-Illumina) in 15 HCV-1b infected patients [five acute with onco-hematologic-disease and 10 (4/6 acute/chronic) with β-thalassemia]. Resistance-associated-substitutions (RAS) were analysed by Geno2pheno-algorithm. Nucleotide-sequence-variability (NSV, at 1%, 2%, 5%, 10% and 15% NGS-cutoffs) and Shannon entropy were estimated. Phylogenetic analysis was performed by Mega6-software and Bayesian-analysis. Results: Phylogenetic analysis showed five transmission-clusters: one involving four HCV-acute onco-hematologic-patients; one involving three HCV-chronic β-thalassemia-patients and three involving both HCV-acute and chronic β-thalassemia-patients. The NS5A-RAS Y93H was found in seven patients, distributed differently among chronic/acute patients involved in the same transmission-clusters, independently from the host-genetic IL-28-polymorphism. The intra-host NSV was higher in chronic-patients versus acute-patients, at all cutoffs analyzed (p < 0.05). Even though Shannon-entropy was higher in chronic-patients, significantly higher values were observed only in chronic β-thalassemia-patients versus acute β-thalassemia-patients (p = 0.01). Conclusions: In nosocomial HCV transmission-clusters, the intra-host HCV quasispecies divergence in patients with acute-infection was very low in comparison to that in chronic-infection. The NS5A-RAS Y93H was often transmitted and distributed differently within the same transmission-clusters, independently from the IL-28-polymorphism.

Association of polymorphisms in inflammatory cytokines encoding genes with severe cases of influenza A/H1N1 and B in an Iranian population

BackgroundThe increased levels of blood cytokines is the main immunopathological process that were attributed to severe clinical outcomes in cases of influenza A, influenza B and people with influenza-like illness (ILI). Functional genetic polymorphisms caused by single nucleotide polymorphisms (SNPs) in inflammatory cytokines genes can influence their functions either qualitatively or quantitatively, which is associated with the possibility of severe influenza infections. The aim of the present case-control study was to investigate the association of polymorphisms in inflammatory cytokines genes with influenza patients and ILI group in an Iranian population.MethodsTotal number of 30 influenza B, 50 influenza A (H1N1) and 96 ILI inpatient individuals were confirmed by Real-time RT-PCR and HI assays. The genotype determination was assessed for defined SNPs in IL-1β, IL-17, IL-10 and IL-28 genes.ResultsThe frequencies of the IL-1β rs16944 (P = 0.007) and IL-17 rs2275913 (P = 0.006) genotypes were associated with severe influenza disease, while the frequencies of IL-10 rs1800872 and IL-28 rs8099917 were not associated with the disease (P > 0.05). Also, the absence of A allele in IL-17 rs2275913 SNP increased the risk of influenza A (H1N1) infection (P = 0.008).ConclusionsThis study demonstrated that influenza A- (H1N1) and B-infected patients and also ILI controls have different profiles of immune parameters, and individuals carrying the specific cytokine-derived polymorphisms may show different immune responses towards severe outcome.

NS5A gene analysis by next generation sequencing in HCV nosocomial transmission clusters of HCV genotype 1b infected patients

NS5A gene analysis by next generation sequencing in HCV nosocomial transmission clusters of HCV genotype 1b infected patients

Efficacy and safety of 12 weeks of daclatasvir, asunaprevir plus ribavirin for HCV genotype-1b infection without NS5A resistance-associated substitutions

Treatment with daclatasvir plus asunaprevir (DCV+ASV) for 24 weeks provided a sustained virologic response (SVR) rate of over 90% in hepatitis C virus genotype 1b (HCV-1b) infected patients without non-structural 5A (NS5A) resistance-associated substitutions (RASs) at the L31 and Y93 sites. In this study, we investigated whether adding ribavirin to the DCV+ASV combination could shorten the original treatment regimen to 12 weeks without compromising the treatment efficacy for HCV-1b patients without NS5A RASs. In the prospective, open-label, single-arm, nationwide multi-center phase III study, a total of 70 interferon-naïve or interferon-experienced HCV-1b patients without baseline L31/Y93 RASs received daclatasvir (60mg/day) and asunaprevir (100mg twice daily) plus weight-based ribavirin (1000-1200mg/day) for 12 weeks, with a 12-week post-treatment follow-up. The primary end-point was the rate of undetectable HCV RNA 12 weeks post-treatment (SVR12). The SVR12 rate was 97.1% (68/70) and 100% (68/68) in the full-analysis-set and the per-protocol population, respectively. None of the 68 patients who completed the 12-week treatment experienced relapse during post-treatment follow-up. Two patients withdrew from the study at treatment days 21 and 34 due to anorexia and fatigue, which were considered ribavirin-related and resolved post medication cessation. A total of 4 serious adverse events were reported and considered treatment-unrelated. No deaths or grade 4 adverse events requiring hospitalization was observed throughout the study. Truncated regimen of DCV+ASV plus ribavirin for 12 weeks was highly effective and safe in HCV-1b patients without NS5A L31/Y93 RAS.

Efficacy of direct-acting antiviral treatment in patients with compensated liver cirrhosis: A multicenter study.

Although the development of new direct-acting antivirals (DAAs) for the treatment of chronic hepatitis C virus (HCV) infection has markedly advanced, the effects of cirrhosis on DAA treatment remain unclear. We aimed to clarify the impact of cirrhosis on DAA treatment of patients infected with HCV. This large-scale, multicenter, retrospective study consisted of 2130 HCV genotype 1b-infected patients who were treated with one of the following DAA combination therapies: asunaprevir/daclatasvir (ASV/DCV), ledipasvir/sofosbuvir (LDV/SOF), or paritaprevir/ombitasvir/ritonavir (PTV/OBV/r). Ninety-two patients (4.3%) previously received DAA-based treatment. Seven hundred and forty-five patients (34.9%) had cirrhosis. Overall, the sustained virologic response (SVR) rate was 93.0%. The SVR rates in patients who received ASV/DCV, LDV/SOF, or PTV/OBV/r were 90.0%, 96.9%, and 97.6%, respectively. The SVR rate in patients with cirrhosis (89.1%) was significantly lower than that in patients without cirrhosis (95.1%, P = 6.94 × 10-7 ). In the multivariate analysis for the overall cohort, absence of cirrhosis (P = 1.26 × 10-3 ), no previous DAA-based treatment (P = 2.54 × 10-14 ), low HCV-RNA levels (P = 1.64 × 10-6 ), wild-type non-structural protein 5A L31/Y93 (P = 7.33 × 10-13 ), and DAA regimen (LDV/SOF or PTV/OBV/r) (P = 1.92 × 10-14 ) were independent factors contributing to SVR. Except for patients with DAA-based treatment history, absence of cirrhosis (P = 2.15 × 10-3 ; odds ratio, 2.51) was an independent factor contributing to SVR in 2038 DAA-naïve patients. This study suggests that the presence of cirrhosis reduces the SVR rate of DAA treatment, regardless of the type of DAA treatment.

Eight weeks of Paritaprevir/r/Ombitasvir + Dasabuvir in HCV genotype 1b with mild‐moderate fibrosis: Results from a real‐world cohort

The interferon-free regimen paritaprevir/ritonavir, ombitasvir + dasabuvir (PTV/r/OBV/DSV) has shown high efficacy in patients with hepatitis C virus (HCV) genotype 1b infection when administered for 8 or 12weeks, but data regarding the 8-week treatment are scarce. The aim of our study was to assess the efficacy and safety of the 8-week administration of PTV/r/OBV/DSV in a real-world cohort. We performed a multicentre observational study from Spanish Hepa-C database including patients receiving 8weeks of PTV/r/OBV/DSV (October 2016-November 2017). Those with advanced fibrosis, with non-genotype 1b or who were treatment-experienced were excluded. A total of 211 patients were registered from 23 Spanish centres; eleven were excluded. At baseline, 42.5% (n=85) were male, median (range) age was 57 (23-86), ALT was 45 (11-494)IU/mL, viral load was 6.1 (3.3-8.2) log10 IU/mL, and 74.5% had mild liver fibrosis (F0-F1) and 25.5% moderate fibrosis (F2). At the end of treatment (EOT), HCV viral load was undetectable in 100% (200/200). Seven patients relapsed after treatment discontinuation. Sustained virological response (SVR12) rates by intention-to-treat analysis were 96% (192/200). Regarding treatment safety, 2 patients developed ALT elevation >5x ULN, but there were no treatment discontinuations. One patient died 7weeks after EOT. Treatment with PTV/r/OBV/DSV in genotype 1b-infected treatment-naive patients with mild-moderate fibrosis shows excellent efficacy and safety in real life, similarly to clinical trials. Clinicaltrials.gov, number: NCT03122132.

Pre-Intervention Treatment, Screening, and Vaccination Rates in Hepatitis B-Infected Patients at an Urban Academic Center

Pre-Intervention Treatment, Screening, and Vaccination Rates in Hepatitis B-Infected Patients at an Urban Academic Center