Early Virological Response Research Articles

High Cure Rates for Hepatitis C Virus Genotype 6 in Advanced Liver Fibrosis With 12 Weeks Sofosbuvir and Daclatasvir: The Vietnam SEARCH Study.

BackgroundGenotype 6 is the most genetically diverse lineage of hepatitis C virus, and it predominates in Vietnam. It can be treated with sofosbuvir with daclatasvir (SOF/DCV), the least expensive treatment combination globally. In regional guidelines, longer treatment durations of SOF/DCV (24 weeks) are recommended for cirrhotic individuals, compared with other pangenotypic regimens (12 weeks), based on sparse data. Early on-treatment virological response may offer means of reducing length and cost of therapy in patients with liver fibrosis.MethodsIn this prospective trial in Vietnam, genotype 6-infected adults with advanced liver fibrosis or compensated cirrhosis were treated with SOF/DCV. Day 14 viral load was used to guide duration of therapy: participants with viral load <500 IU/mL at day 14 were treated with 12 weeks of SOF/DCV and those ≥500 IU/mL received 24 weeks. Primary endpoint was sustained virological response (SVR).ResultsOf 41 individuals with advanced fibrosis or compensated cirrhosis who commenced treatment, 51% had genotype 6a and 34% had 6e. The remainder had 6h, 6k, 6l, or 6o. One hundred percent had viral load <500 IU/mL by day 14, meaning that all received 12 weeks of SOF/DCV. One hundred percent achieved SVR12 despite a high frequency of putative NS5A inhibitor resistance-associated substitutions at baseline.ConclusionsPrescribing 12 weeks of SOF/DCV results in excellent cure rates in this population. These data support the removal of costly genotyping in countries where genotype 3 prevalence is <5%, in keeping with World Health Organization guidelines. NS5A resistance-associated mutations in isolation do not affect efficacy of SOF/DCV therapy. Wider evaluation of response-guided therapy is warranted.

Early virological response in six patients with hepatitis D virus infection and compensated cirrhosis treated with Bulevirtide in real-life.

Hepatitis delta virus (HDV) infection is the most severe form of viral hepatitis. Bulevirtide (BLV, Hepcludex® ) is an HDV/HBV entry inhibitor approved in June 2020 in the European Union for adult patients with chronic hepatitis delta (CHD) and compensated liver disease and positive HDV RNA viral load. This real-life preliminary report described early virological efficacy and safety of BLV in six patients with CHD and compensated liver disease: four patients were treated with the combination of BLV (2mg/d in subcutaneous injection) and pegylated interferon (PEG-IFN) and two patients with BLV monotherapy. Four patients treated with combined therapy had a decline of a minimum of 1log10 and 3/3 of 2log10 of HDV-VL at 12 and 24 weeks, respectively. One patient among four had stopped the treatment at 12 weeks because of thrombocytopenia and an HDV-VL relapse was notified 24weeks after treatment cessation. Three patients among four (3/4) had undetectable HDV-VL during the therapy (<100IU/ml). One patient (1/2) treated with BLV monotherapy had a decline of HDV-VL by 1log10 at 8 weeks and 1/1 by 2log10 at 28 week on-treatment. Two patients among four (2/4) with combined therapy had normal ALT reached at 4 and 56 weeks. One patient (1/2) with BLV monotherapy achieves ALT normalization at​ 4 weeks on treatment. Hepatitis B surface antigen (HBsAg) levels remain unchanged. Three among six (3/6) patients had an elevation of total biliary acids without pruritus. These early data generated confirm the interest in this new treatment. Final results will be important to demonstrate long-term clinical benefit (fibrosis reversibility and reduction in hepato-cellular carcinoma [HCC]).

IgE antibodies to hepatitis C virus core and nonstructural antigens in chronic hepatitis C patients before and after antiviral treatment

Few studies on the immunoglobulin E (IgE) immune response in chronic hepatitis C have been reported. In this study, we tested the antigenicity of commercial recombinant hepatitis C virus (HCV) core and nonstructural protein NS3, NS4, and NS5 antigens and the IgE immune response to these antigens in chronic hepatitis C patients before and after antiviral treatment with pegylated interferon (IFN)-α plus ribavirin for 12 weeks. The effects of antiviral treatment were investigated in 20 out of 35 participants. We developed amplified immunoassays using these antigens and IgG-depleted patient sera. Seropositivity for IgE antibodies was determined, and serum IgE and cytokine levels were measured. Anti-core, anti-NS3, and anti-NS4 IgE antibodies were observed in most patients, whereas anti-NS5 antibodies were less prevalent. Antiviral treatment decreased the production of anti-core, anti-NS3, and anti-NS4 IgE antibodies, but not anti-NS5 IgE antibodies. A significant decrease in the anti-NS3 and anti-NS4 IgE antibody levels was observed in patients who presented with an early sustained virological response, but no effects on anti-core and anti-NS5 IgE antibodies was observed. The serum levels of IFN-γ, interleukin (IL)-2, IL-6, tumor necrosis factor-α, and IL-10, but not IL-4, were similar between patients before and after antiviral therapy. Thus, the immune response of IgE antibodies to HCV antigens was comparable to that of anti-HCV IgG antibodies. The usefulness of anti-NS3 IgE antibodies in diagnosing occult hepatitis C and monitoring antiviral treatment with directly acting antiviral medication must be investigated in future studies.

Pegylated interferon and ribavirin gone but not forgotten in the era of direct-acting antivirals.

Therapy with pegylated interferon and ribavirin (PEG-IFN+RBV) for chronic hepatitis C (CHC) remains the only option available for children in many Eurasian and European countries. Our aim was to evaluate the influence of host and viral factors on response to IFN-based therapy to optimize it for those in whom directly acting antivirals (DAA) are currently unavailable. Seventeen vertically infected, treatment naive children (10 male and 7 female) aged 5-16 years with CHC underwent a course of PEG-IFN+RBV. The end point was sustained virologic response (SVR). Host and virus factors were divided into pre- and on-treatment predictors of response to therapy. Eleven patients obtained SVR (64%), 4 were non-responders (23%), and 2 were relapsers (12%). Significant relationship was found between HCV RNA elimination and following variables: virus genotype and early virologic response (EVR) (P<0.037, P<0.029 respectively). Higher eradication rate was observed in patients infected with genotype 3 HCV (100% vs. 65% with genotype 1 or 4), and in those with undetectable HCV RNA by week 12 (88% vs. 66% with viremia). EVR was associated with SVR (83% vs. 0% in nonresponders; P<0.004). C allele of IL28B rs12979860 was a predictor of EVR (P<0.043). The SVR rates among CC, CT, and TT carriers were as follows: 75%, 67%, and 33%. Detection of favorable HCV and IL28B genotype prior to commencement of PEG-IFN+RBV and continuing it in patients with EVR is of major importance for those in whom DAA are still unavailable.

The association of the heterogeneity of HBV reverse transcriptase quasispecies with antiviral efficacy after treatment with nucleos(t)ide analogues for 10years.

To assess the heterogeneity of HBV reverse transcriptase (RT) quasispecies during 10years of antiviral therapy and their association with antiviral efficacy. Nineteen patients with chronic hepatitis B (CHB) infection receiving nucleos(t)ide analogues (NAs) were enrolled. Based on the antiviral efficacy after 1year of treatment, 5 patients were grouped into an early virologic response (EVR) group, while 8 patients were grouped into a late virologic response (LVR) group. Furthermore, 6 CHB patients that had undergone antiviral treatment for 10years were grouped into a virologic breakthrough (VBT) group. The HBV RT from each patient were amplified, cloned, and sequenced. The complexity of the RT gene in the EVR group was significantly higher than that in the LVR (P=0.0393) and VBT groups (P=0.0141). Phylogenetic tree analysis showed that the average branch length of the EVR and LVR groups were significantly greater than that of VBT group (P<0.001). The complexity (at the nucleotide level) of the RT quasispecies was negatively correlated with the corresponding HBV DNA load (P=0.0163) at one year post-antiviral treatment. Moreover, both the LVR and VBT groups accumulated more deleterious mutations than the EVR group. After 1year of NAs treatment, the increased HBV quasispecies complexity and evolutionary topologies, coupled with less deleterious mutations, are likely associated with a favorable efficacy during long-term antiviral treatment.

Pegylated interferon and ribavirin gone but not forgotten in the era of direct-acting antivirals

BACKGROUND Therapy with pegylated interferon and ribavirin (PEG-IFN+RBV) for chronic hepatitis C (CHC) still remains the only option available for children in many Eurasian and European countries. Our aim was to evaluate the influence of host and viral factors on response to IFN-based therapy to optimize it for those in whom directly acting antivirals (DAA) are currently unavailable. METHODS Seventeen vertically infected, treatment naive children (10 male and 7 female) aged 5-16 years with CHC underwent a course of PEG-IFN+RBV. The end point was sustained virologic response (SVR). Host and virus factors were divided into pre- and ontreatment predictors of response to therapy. RESULTS Eleven patients obtained SVR (64%), 4 were nonresponders (23%), and 2 were relapsers (12%). Significant relationship was found between HCV RNA elimination and following variables: virus genotype and early virologic response (EVR) (p< .037, p< .029 respectively). Higher eradication rate was observed in patients infected with genotype 3 HCV (100% vs. 65% with genotype 1 or 4), and in those with undetectable HCV RNA by week 12 (88% vs. 66% with viremia). EVR was associated with SVR (83% vs. 0% in nonresponders; p< .004). C allele of IL28B rs12979860 was a predictor of EVR (p < .043). The SVR rates among CC, CT, and TT carriers were as follows: 75%, 67%, and 33%. CONCLUSIONS Detection of favourable HCV and IL28B genotype prior to commencement of PEG-IFN+RBV, and continuing it in patients with EVR is of major importance for those in whom DAA are still unavailable.

Efficacy of peg-interferon-nucleoside analog sequential optimization therapy in HBeAg-positive patients with CHB.

This study aimed to evaluate the efficacy of Peg-interferon (Peg-IFN)-nucleoside analog (NA) sequential optimization therapy (SOT) in HBeAg-positive patients with chronic hepatitis B (CHB). In this prospective two-center study, 132 CHB patients were assigned to receive Peg-IFN standard therapy for 48weeks (65 patients) or Peg-IFN monotherapy for 12-24weeks and NA add-on for those without early virological response (EVR) (67 patients). Both patient groups were monitored and followed for 24weeks after treatments stop. At week 24 after treatments stop, the Peg-IFN-NA SOT group achieved more HBsAg levels drop (- 1.35 vs - 0.67 log10 IU/mL, p = 0.016), higher HBsAg ≤ 100IU/mL (32.8% vs 9.2%, p = 0.001), HBV DNA undetectable (79.1% vs 49.2%, p < 0.001), and ALT normalization (80.6% vs 38.5%, p < 0.001) rates compared with Peg-IFN monotherapy. At week 24 after treatments stop, nosignificantdifference was found in HBeAg seroconversion (35.8% vs 27.7%, p = 0.316), HBsAg loss (8.9% vs 4.6%, p = 0.323) and HBsAg seroconversion rates (4.5% vs 1.5%, p = 0.325) between Peg-IFN monotherapy group and Peg-IFN-NA SOT group. Starting with Peg-IFN followed by addition of NA achieved more HBsAg levels drop, and higher HBsAg ≤ 100IU/mL, HBV DNA undetectable, and ALT normalization rates compared with Peg-IFN monotherapy.

Modulation of Immune Cell Subsets by Hepatitis C Virus and Antiviral Therapy in Early Virological Response HCV Genotype 4-Infected Patients with Compensated Liver Disease

Background: Resolution of chronic hepatitis C virus (HCV) infection requires a complicated interaction between immune cell subsets. The effect of antiviral therapy on immune cell subsets remains to be defined. This study aimed to investigate the absolute count of certain immune cell subsets during therapy with pegylated interferon-α and ribavirin (PegIFN/RBV). Materials and Methods: Sixty HCV genotype 4-infected patients with compensated liver disease were treated with PegIFN/RBV therapy for 52 weeks. Efficacy was measured by studying the early virological response (EVR) at post-therapy week 12. Absolute counts of mature T cells, T helper cells, T cytotoxic cells, activated T cells, natural killer cells, natural killer/T (NKT) cells, B cells, and T regulatory cells (Treg), and the ratio of T helper to T cytotoxic cells were longitudinally analyzed by flow cytometry throughout the treatment and follow-up course. Results: Of the 60 genotype 4-infected subjects, 39 (65%) had EVR and 21 (35%) were non-EVR patients. In the first part of this study, there were significantly lower mean absolute count values of mature T, T cytotoxic, B, and NKT cells. Also, we detected statistically significantly lower mean values for the percentages of T cytotoxic, NKT, Treg, and activated T cells of HCV-infected patients at baseline values when compared with healthy subjects. After the initiation of PegIFN/RBV therapy, frequencies of T helper cells, activated T cells, Treg cells, B cells, and T helper:T cytotoxic ratio were found to be significantly lower in EVR patients than in non-EVR patients (p < 0.05). In contrast, frequencies of T cytotoxic and NKT cells were significantly increased in EVR patients when compared to non-EVR patients (p < 0.05). Conclusion: These results suggest a pattern of higher levels of T cytotoxic and NKT cells, and lower levels of T helper, activated T, Treg, and B cell populations in patients who respond favorably to PegIFN/RBV therapy.

Comparison of 48‐week efficacy of tenofovir vs entecavir for patients with chronic hepatitis B: A network meta‐analysis

Both tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are accepted as first-line treatments for chronic hepatitis B (CHB). However, there are few randomized studies comparing their efficacy. The primary aim of this study was to compare the efficacy of TDF and ETV using a network meta-analysis of randomized trials. The secondary aim was to additionally include propensity-matched cohort studies in a conventional meta-analysis. We systematically searched PubMed, EMBASE, Cochrane Library and Web of Science for published English-language randomized and propensity-matched studies between 1/1/2000 and 4/2/2020. Outcomes included undetectable HBV DNA, ALT normalization and HBeAg seroconversion at 48weeks. We excluded patients who had co-infection or significant prior treatment with antivirals. 13517 participants from 16 studies (11 RCTs, n=2675; five propensity-matched cohort studies, n=10842) were included. Virological response at 48weeks was higher in patients receiving TDF compared to ETV using both the network meta-analytic approach (OR 1.69, P<.001) and the conventional meta-analysis including propensity-matched cohort studies (OR 1.40, P<.001). On subgroup analysis, this difference was only significant in HBeAg-positive patients (OR 1.81, P=.037). There was limited evidence to suggest a higher rate of ALT normalization with ETV (OR 0.74, P=.07). There was no difference in rates of HBeAg seroconversion between the two antivirals. TDF is more likely than ETV to induce virological response at 48weeks in treatment-naïve CHB patients. Future studies should focus on elucidating associations between early and sustained virological response with adverse patient outcomes including development of HCC or cirrhosis.

Hepatitis C infection at a tertiary hospital in South Africa: Clinical presentation, non-invasive assessment of liver fibrosis, and response to therapy.

Hepatitis C is a viral infection that leads to chronic liver disease, resulting in significant morbidity and mortality. To describe the demographic characteristics and clinical presentation of patients with chronic hepatitis C infection. The aspartate aminotransferase-to-platelet ratio index (APRI) and the fibrosis index based on 4 factors (FIB-4) were assessed for prediction of liver fibrosis. We retrospectively reviewed 87 records of patients who presented to the liver clinic at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa, from January 2007 to December 2016. Patients' records were reviewed and analysed using SPSS statistical software version 24. Convenience sampling was used. The patients' mean (standard deviation (SD)) age was 52.6 (12.3) years. Fifty-four percent were female. Hepatitis C virus genotype 5 was exclusively found in blacks (p&lt;0.001), constituting 60.3% of infections in this ethnic group and 48.7% in the cohort, followed by genotype 1 (21.8%), genotype 3 (15.4%), genotype 4 (10.3%) and mixed-genotype infections (3.8%). Genotype 5 patients were older (mean (SD) age 56.7 (9.8) years) than genotype 1 (46.3 (11.4) years) and genotype 3 (42 (9.8) years) (p=0.002 and p&lt;0.001, respectively). The receiver operating characteristic curve for METAVIR F0 v. APRI (cut-off &lt;0.7) showed a moderate correlation, with an area under the curve (AUC) of 0.349 (p=0.002), sensitivity of 78.8%, specificity of 70.6% and a negative predictive value (NPV) of 63.2%. METAVIR F4 v. APRI (cut-off ≥1.5) showed an AUC of 0.881 (p=0.001) with sensitivity of 85.7%, specificity of 93% and a positive predictive value (PPV) of 67%. METAVIR F0 v. FIB-4 (cut-off &lt;1.45) showed a moderate correlation, with an AUC of 0.332 (p=0.021), sensitivity of 78.3%, specificity of 53.8% and an NPV of 73.7%. METAVIR F4 v. FIB-4 (cut-off &gt;3.25) had a strong correlation, with an AUC of 0.952 (p&lt;0.001), sensitivity of 63.6%, specificity of 100% and a PPV of 100%. Early virological response (EVR) was found to predict sustained virological response (SVR) to therapy (odds ratio 27.8; 95% confidence interval 2.8 - 274.3; p=0.004). Compared with other genotypes, genotype 5 was predominant in our cohort, particularly in older age groups. Moreover, APRI and FIB-4 scores correlated significantly with advanced fibrosis in HCV patients. Finally, EVR during therapy was found to determine SVR.

Viral Hepatitis C (HCV) in Hemodialysis

The aim of the study is to show the prevalence and risk factors of HCV at our hemodialysis (HD) center , in a study carried out on chronic hemodialysis patients during the year 2019, we identified eight cases out of 87 patients infected with HCV, or 9%. The average age in this population is 48 years, dialysed for an average of 15 years. Viral infection was discovered on average 12.5 years after the start of hemodialysis, during a routine screening examination. In this series, the genotype 1b was found in 2 cases (25%). Seven patients were treated out of the eight HCV hemodialysis patients, received dual therapy with sofosbuvir 400mg and daclar 60 mg for three months, with an early virologic response. A study done during a previous period, between 2015 and 2018, in the same center, looking at the risk factors for HCV transmission: 11 cases out of 134 hemodialysis patients infected with HCV. Among these cases, we noted the following factors; Blood transfusion: 3 cases (27.2%), surgery: 4 cases (45.4%), dental care: 2 cases (18%), no obvious cause: 2 cases (9%). Serologically ; HCV antibodies positive: 11/134, i.e. an 8.2% seroprevalence, PCR-viral RNA was positive in 10 out of 11 patients, i.e. a prevalence of 7.4% by PCR, number of copies: Above 1.03x 1, 000,000 (100%), number of Logs: Sup to 3.32 (100%), negative PCR: 01 patient.

Entecavir add-on Peg-interferon therapy plays a positive role in reversing hepatic fibrosis in treatment-naïve chronic hepatitis B patients: a prospective and randomized controlled trial.

BackgroundThe efficacy of entecavir (ETV) add-on peg-interferon therapy compared with ETV monotherapy in treatment-naïve hepatitis B virus (HBV) patients remains controversial. We investigated whether adding peg-interferon to ongoing ETV treatment leads to a better curative effect or not.MethodsAll patients have been recruited between August 2013 and January 2015 from the Shanghai Public Health Clinical Center and Zhongshan Hospital (China). Eligible HBV patients (n = 144) were randomly divided (1:1) to receive either ETV monotherapy (n = 70) or peg-interferon add-on therapy from week 26 to 52 (n = 74). Patients were followed-up for at least 2 years. Indexes including hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) seroconversion rate, sustained virologic response, transient elastography value, and histological scores were evaluated every 3 months until the end of the study. The rate of patients with HBsAg loss was defined as the primary endpoint criteria.ResultsAt week 26, no patient achieved HBsAg seroconversion in either group. At week 52, one patient in the monotherapy group was HBsAg-negative but there was none in the combination therapy group. The monotherapy group showed significantly better liver function recovery results than the combination therapy group. At week 78, one patient in the combination group had HBsAg seroconverted. At week 104, only three patients in the combination therapy group were HBsAg-negative compared with one patient in monotherapy. The mean alanine aminotransferase and aspartate aminotransferase levels and transient elastography values decreased significantly compared with baseline. Both groups showed a favorable decrease in alpha-fetoprotein (monotherapy: 4.5 [2.8, 7.1] vs. 2.2 [1.8, 3.1] ng/mL, P < 0.001; combination therapy: 5.7 [3.0, 18.8] vs. 3.2 [2.0, 4.3] ng/mL, P < 0.001) and an improved result of liver biopsy examination scores. The combination group showed a better improvement in histology compared with the monotherapy group (mean transient elastography value 6.6 [4.9, 9.8] vs. 7.8 [5.4, 11.1] kPa, P = 0.028). But there was no significant difference in HBsAg conversion rate (1.8% [1/56] vs. 4.1% [3/73], P = 0.809) and HBeAg conversion rate (12.5% [7/56] vs. 11.0% [8/73], P = 0.787), as well as HBV-DNA, sustained virologic response (93.2% vs. 98.5%, P = 0.150) between the two groups.ConclusionsBoth therapies supported liver function recovery and histology improvement. Combination therapy did not show better anti-viral efficacy in HBsAg or HBeAg seroconversion compared with monotherapy. However, combination therapy played a more positive role in reversing hepatic fibrosis compared with monotherapy.Trial registrationClinicalTrials.gov: NCT02849132; https://clinicaltrials.gov/ct2/show/NCT02849132

Relevance of T helper Type 1, 2 and 17 Cytokine Profiles to the Outcome of Therapy in Hepatitis C Patients

Background: This study aimed to investigate the relationship of T helper type (Th)1/Th2/Th17 type cytokines produced by chronically hepatitis C virus (HCV)-infected patients in response to pegylated interferon-α plus ribavirin (Peg-IFN/RBV) therapy. These finding will help us to identify the type of cytokines which participate in restoring functional antiviral T cell responses resulting in improved viral clearance. Methods and results: Sixty genotype-4 HCV-infected patients received Peg-IFN/RBV therapy for 12 weeks. Levels of Th1 cytokines (IL-2, IL-8, IL-12, TNFα, IFNγ), Th2 cytokines (IL-4, IL-6, IL-10) and Th17 cytokines (IL-17A, IL-17F) were estimated by ELISA. In post-treatment samples, mean levels of Th1 cytokines IL-12 and IFNγ were significantly higher in patients with an early virologic response (EVR) when compared to non-EVR. In contrast, mean levels of IL-17A and IL-17F in post-treatment samples were significantly higher in non-EVR patients compared to EVR patients. Interestingly, in post-treatment samples the anti-inflammatory Th2 cytokines IL-4 and IL-6 were produced at significantly higher levels in non-EVR patients than in EVR patients. Also, after treatment, the ratios of pro-inflammatory to anti-inflammatory cytokines were higher in EVR as compared to non-EVR patients. Conclusion: A pattern of stronger Th1- and weak Th17 reactivity in HCV-infected patients supports a favorable response to Peg-IFN/RBV therapy.

Effectiveness and safety of narlaprevir in real clinical practice of chronic hepatitis C

Objective: to analyze the efficacy and safety of using direct antiviral action drug narlaprevir/ritonavir in combination with the prolonged alpha-interferon and ribavirin drugs in the conditions of day-time hospitals of St. Petersburg and. Novgorod. Materials and methods : The study included. 35 patients with CHC of the 1st genotype. For treating these patients, a three-component regimen was used, which included the use of narlaprevir/ritonavir in combination, with peg-interferon and ribavirin. Results: among all patients included, in the study, a sustained, virological response was noted, in 85,7%. Early virological response was observed, in 91,3% cases. The recurrence rate was observed, in 10% patients. In 3 patients, therapy was interrupted, for the following reasons: due to inefficiency, the development of serious adverse events, and on its own initiative. Conclusion: the data obtained, demonstrate high, virological and. clinical efficacy and. safety of narlaprevir in combination with peg-interferon and ribavirin, in the treatment of chronic viral hepatitis C.

Ultra-short duration direct acting antiviral prophylaxis to prevent virus transmission from hepatitis C viremic donors to hepatitis C negative kidney transplant recipients.

We conducted an adaptive design single-center pilot trial between October 2017 and November 2018 to determine the safety and efficacy of ultra-short-term perioperative pangenotypic direct acting antiviral (DAA) prophylaxis for deceased hepatitis C virus (HCV)-nucleic acid test (NAT) positive donors to HCV negative kidney recipients (D+/R-). In Group 1, 10 patients received one dose of SOF/VEL (sofusbuvir/velpatasvir) pretransplant and one dose on posttransplant Day 1. In Group 2A (N=15) and the posttrial validation (Group 2B; N=25) phase, patients received two additional SOF/VEL doses (total 4) on Days 2 and 3 posttransplant. Development of posttransplant HCV transmission triggered 12-week DAA therapy. For available donor samples (N=27), median donor viral load was 1.37E+06IU/mL (genotype [GT]1a: 70%; GT2: 7%; GT3: 23%). Overall viral transmission rate was 12% (6/50; Group 1:30% [3/10]; Group 2A:13% [2/15]; Group 2B:4% [1/25]). For the 6 viremic patients, 5 (83%) achieved sustained virologic response (3 with first-line DAA therapy; and two after retreatment with second-line DAA). At a median follow-up of 8months posttransplant, overall patient and allograft survivals were 98%, respectively. The 4-day strategy reduced viral transmission to 7.5% (3/40; 95% confidence interval [CI]: 1.8%-20.5%) and could result in avoidance of prolonged posttransplant DAA therapy for most D+/R-transplants.

Outcome of sofosbuvir based regimen in chronic hepatitis C patients with chronic kidney diseases on maintenance hemodialysis from western India

Introduction: The introduction of direct-acting antiviral (DAA)-based therapies for hepatitis C virus (HCV) has revolutionized the approach to HCV treatment. The data of sofosubvir based regimen in HCV infected Chronic Kidney Diseases (CKD) Patients on maintenance hemodialys (MHD) is not widely available. Our study was aimed to evaluate the effect of sofosbuvir–Ledipasvircombinationregimen in HCV positive CKD patient on MHD. Materials and Methods: Patients aged more than 12 years with HCV RNA positive and on MHD were included. Patients having liver cirrhosis and already started DAAs were excluded. Before starting treatment genotype, viral load routine clinical and laboratory data (CBC, SGPT, S.Albumin, S.Fetoprotein) were collected at baseline and also at 4, 12, and 24weeks during the treatment. All patients irrespective of genotypes were started sofosbuvir 400mg plus Ledipasvir 90 mg combination alternate day for 12 weeks. HCV RNA viral load was assessed at the end of 4, 12 and 24wks.We evaluated early virological response (EVR) at end of 4th weeks, end of treatment response (ETR) at the end of 12 weeks and sustained virological response (SVR) at the end of 24 weeks after initiation of therapy. Results: We had enrolled 210 HCV RNA patients with male (n=166) predominance with mean age of 31.6±10 years. Genotype 1 in 179 (85.2%) and genotype 3 in 31(14.8%) were found. 208 patients (99.03%) had achieved complete response at 12 wks (SVR12). 2 patients (1b,3) did not respond even at 24 wks. None of patient discontinued therapy because of side effects. No significant change in hemoglobin, platelet count and bilirubin. Conclusions: Sofosbuvir-Ledipasvir therapy on alternate day for 12 weeks was found effective therapy for HCV?infected CKD patients on MHD. Keywords: Sofosbuvir, Ledipasvir, HCV treatment, Haemodialysis, Western India.

Hepatitis C virus genotype 3a: Predictive factors associated with treatment response in patients of Peshawar.

Hepatitis C Virus (HCV) is a flavivirus responsible for causing chronic liver diseases including cirrhosis and hepatocellular carcinoma. Identification of various patient and virus-related factors that can help predict response to antiviral therapy is extremely important in formulating the best therapeutic strategy for each patient either to continue or stop the therapy. The present study aimed to determine Sustained Virological Response (SVR) in HCV genotype 3a infected patients that received combination therapy of Sofosbuvir and Ribavirin and to investigate various factors that can help predict SVR. Study Design: Longitudinal Study Settings: Institute of basic Medical Sciences, Khyber Medical University, Peshawar (IBMS, KMU). Period: July 2016 to September 2017. Materials and Methods: Treatment response was evaluated among 100 HCV genotype 3a infected patients that received Sofosbuvir and Ribavirin therapy for 24 weeks. Various baseline parameters including hematological, biochemical and viral profiles of were recorded. HCV genotype determination was carried out by type specific nested PCR based genotyping assay. Viral load was determined at baseline, at 12 weeks for Early Virological Response (EVR) and at 24 weeks of treatment for SVR. Viral RNA quantification was carried out by Real Time PCR. Results: Out of 100 patients, SVR was observed in 83% of patients; while 17% of the chronic HCV 3a infected patients were Non-Responders (NR). Mean age of patients was low 34 ± 9.8 among patients who achieved SVR as compared to patients with non-response (41 ± 10). The 24 weeks Alanine aminotransferase (ALT) levels were significantly lower among patients with SVR (p-value ≤ 0.05). Although statistically not significant, baseline viral load was higher in NR group (p-value ≥ 0.05), than those with SVR. Association of EVR with SVR was found statistically significant (OR= 2.8, 95% CI 1.2-6.4, p-value ≤ 0.05). Conclusions: The current study indicated that pre and on-treatment monitoring of patients receiving anti-viral therapy is important for the management of patients with chronic HCV infection.

Immunomodulation of CXCL10 Secretion by Hepatitis C Virus: Could CXCL10 Be a Prognostic Marker of Chronic Hepatitis C?

Chemokine (C-X-C motif) ligand (CXCL)10 and other CXCR3 chemokines are involved in the pathogenesis of acute and “chronic hepatitis C virus (HCV) infection” (CHC). Here, we review the scientific literature about HCV and CXCL10. The combination of circulating CXCL10 and single nucleotide polymorphisms (SNPs) in IL-28B can identify patients with acute HCV infection most likely to undergo spontaneous HCV clearance and those in need of early antiviral therapy. In CHC, the HCV and intrahepatic interferon- (IFN-) γ drive a raised CXCL10 expression by sinusoidal endothelium and hepatocytes, thereby inducing the recruitment of CXCR3-expressing T cells into the liver; thus, CXCL10 plays an important role in the development of necroinflammation and fibrosis. Increased CXCL10 was significantly associated with the presence of active vasculitis in HCV-associated cryoglobulinemia, or with autoimmune thyroiditis in CHC. Pretreatment CXCL10 levels are predictive of early virological response and sustained virological response (SVR) to IFN-α and ribavirin and may be useful in the evaluation of candidates for therapy. The occurrence of SNPs adjacent to IL-28B (rs12979860, rs12980275, and rs8099917), and CXCL10 below 150 pg/mL, independently predicted the first phase viral decline and rapid virological response, which in turn independently predicted SVR. Directly acting antiviral agents-mediated clearance of HCV is associated with the loss of intrahepatic immune activation by IFN-α, associated by decreased levels of CXCL10. In conclusion, CXCL10 is an important marker of HCV clearance and successful therapy in CHC patients. Whether CXCL10 is a novel therapeutic target in CHC will be evaluated.

HCV core antigen is a useful predictor during pegylated-interferon/ribavirin therapy in patients with hepatitis C virus genotype 1b

Enzyme immunoassays for quantifying hepatitis C virus (HCV) core antigen (Ag) have been proposed as an alternative to HCV RNA detection. The present study aimed to investigate the early kinetics of serum HCVcAg and its usefulness in predicting virological responses.The clinical data of 135 patients with chronic hepatitis C treated with pegylated interferon alpha (PEG-IFN-α) and ribavirin was retrospectively collected. The patients were grouped according to their treatment outcomes as follows: sustained virological response (SVR), nonsustained virological response (N-SVR), and relapse.Higher HCVcAg and HCV RNA levels were observed in patients in the N-SVR group than in the other groups at baseline. HCVcAg better predicted rapid virological response (RVR) compared with HCV RNA and had a predictive value similar to that of HCV RNA for SVR and early virological response. In the relapse group, HCV RNA decreased to 0 after 48 weeks, whereas HCVcAg was still detectable, indicating that HCVcAg more sensitively predicted relapse in antiviral therapy than HCV RNA.For patients treated with PEG-INF-α and ribavirin, HCVcAg may more sensitively predict relapse than HCV RNA.

Daclatasvir plus Sofosbuvir with or without ribavirin in patients with chronic Hepatitis C genotype 3a in Pakistani population - A real world experience.

Background and Objectives:Pakistan is among leading countries of world in prevalence of chronic hepatitis C Daclatasvir plus sofosbuvir is recommended for treatment of CHC. The purpose of study was to determine the sustained virological response in patients with chronic viral hepatitis C genotype 3a irrespective of previous treatment experience or presence of liver cirrhosis.Methods:Open label observational study was conducted at ABSTH Gujrat from January 2017 to April 2018 using non-probability purposive sampling. Patients chronically infected with hepatitis C virus having genotype 3a irrespective of presence of cirrhosis or previous treatment experience were included. Treatment naive patients without cirrhosis were given 12 weeks regimen of daily daclatasvir 60mg along with daily sofosbuvir 400mg. Patients with either compensated cirrhosis or treatment experienced were given 24 weeks regimen of daily daclatasvir 60mg along with daily sofosbuvir 400mg with weight based ribavirin. Data analysis was done using SPSS 20.0Results:Total 125 patients were included in study out of which 42 (33.6%) were male and 83 (66.4%) were female. Early virological response and end treatment response was achieved by 124 (99.2%) patients. Twenty four patients were lost to further follow-up and SVR24 was available for 101(80.8%) patients out of which 48 were having cirrhosis and 53 were without cirrhosis. SVR24 was achieved by 96 patients (95%). Virological response was better in treatment naive patients and without cirrhosis compared to treatment experienced and those with cirrhosis.Conclusion:Daclatasvir plus sofosbuvir is an effective combination in patients with chronic hepatitis C genotype 3a infection.