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Hepatitis C virus (HCV) infection is more prevalent in people living with HIV-AIDS (PLHA) and portends a poorer prognosis. Pharmacokinetic studies suggest the absence of significant interaction between velpatasvir and dolutegravir which has been recently recommended as part of preferred first-line antiretroviral therapy (ART) regimens by WHO. However, clinical data on the use of velpatasvir-based regimen in PLHA taking dolutegavir is lacking. Hence, we aimed to assess the efficacy and safety of sofosbuvir and velpatasvir (SOF + VEL) in HCV and HIV coinfected patients on dolutegravir-based ART. Forty-five consecutive PLHA with HCV coinfection on dolutegravir-based ART were prospectively enrolled. All patients were treated SOF + VEL for 12 weeks. Complete haemogram, liver and renal function tests were assessed at baseline, 4 weeks and at end of treatment. Sustained virological response (SVR) was assessed at 12 weeks after end of treatment. The majority were males (95.5%) with a mean age of 32.8 ± 12.3 years. Cirrhosis was present in 6 (13.3%) patients. All patients completed 12 weeks of therapy with SOF + VEL, but SVR could not be assessed in two patients. Forty-two (97.7%) of the remaining 43 patients attained SVR-12. SVR-12 rate was 97.7% and 93.3% by per protocol and intention to treat analysis, respectively. No grade III/IV adverse events were reported, and there was no worsening of blood counts, liver or renal function test parameters. The pan-genotypic regimen of SOF + VEL is safe and effective in PLHA with HCV coinfection who are on dolutegravir-based ART., (© 2023 John Wiley & Sons Ltd.)

Effective management of HIV and hepatitis C virus (HCV) coinfection warrants special emphasis on interactions between direct acting antivirals (DAAs) and antiretroviral therapy (ART) along with maintenance of treatment compliance. All HIV-HCV coinfected adult patients (2015-2020) were included in this real-life retrospective study. Prevalence of coinfection, proportion of coinfected patients treated, compliance rate, sustained virological response at week 12 (SVR12) after the end of therapy, and adverse events were assessed. Among 4578 HIV patients, 232 (5.1%) had HCV coinfection. Ninety-two (39.7%) were intravenous drug users. One hundred twenty-eight (55.1%) patients presented to the liver clinic. Seventy-six (32.8%) patients [mean age: 36.6 ± 10.4 years; 65 (85.5%) males; mean CD4 count: 396 ± 246 cells/mL] completed DAA therapy, whereas 52 (22.4%) patients defaulted and 75 (32.3%) were lost to follow-up. Sixty-seven (82.2%) patients had chronic hepatitis and 9 (11.8%) had compensated cirrhosis. Median (range) HCV-RNA was 5.9 × 10 6 IU/mL (2.4 × 10 5- 9.9 × 10 5 ). Among 15 (19.5%) treatment experienced patients, 14 were pegylated interferon experienced and one was NS5A-inhibitor experienced. ART regimens comprised a combination of tenofovir (T), lamivudine (L), efavirenz (E), nevirapine (N), and/or zidovudine (Z) at dosage and modifications as applicable [TLE: 63 (82.9%), ZLN:11 (14.5%), and ZLE: 2 (2.6%)]. Overall, 74 (97.4%) out of 76 patients who completed DAA therapy achieved SVR12. Adverse events were minor and well-tolerated. HIV-HCV-coinfected patients demonstrate excellent SVR12 and tolerability with available DAAs, with no major adverse events.

Chronic hepatitis C virus (HCV) infection is associated with neuropsychiatric changes. Also, patients with cirrhosis may develop overt or minimal hepatic encephalopathy. Sustained virological response (SVR) with direct-acting antiviral agents (DAAs) may improve the neuropsychiatric manifestations and quality of life (QoL). Consecutive patients (with and without cirrhosis, all genders and aged 18-65 years) with hepatitis C were assessed at enrolment and at 12 weeks after therapy completion for mood (Beck's Depression Inventory [BDI]), anxiety (generalized anxiety disorder [GAD-7]), QoL (SF-36 ver.2) and computer-based tests for number connection (NCT), visual memory, Stroop test and reaction times. We recruited 385 viraemic chronic HCV patients (76.1% male, 21.0% cirrhotic, mean age 39.4 ± 14.2 years, 59.3% genotype 3, mean HCV RNA load 5.8 log). Overall SVR-12 rates were 90.6%, with cure rates 87.6% and 91.4% in patients with and without cirrhosis, respectively. Patients who achieved SVR-12 had mean percentage reduction in BDI (11.3%, p = .000), GAD (8.6%, p = .001) and Stroop test (58.4%, p = .001), with improved NCT (1.7%, p = .001), visual memory (13.7%, p = .001) and digit span (23.8%, p = .002). On multivariate logistic regression, adherence (OR, 17.5 [95% CI 2.80-110.50], p = .000), high ALT (OR 1.02 [95% CI 1.00-1.05]), and BDI score (OR 1.73 [95% CI 1.42-3.26] p = .039) predicted cure. SVR-12 was associated with improved visual memory ≥5.5 (AUC-0.708; sensitivity 62.5%, specificity 63%, p = .000) and % correct Stroop test responses >26.6% (AUC-0.918, sensitivity 94.4% specificity 80.4%, p = .000). In conclusion, given the cumulative evidence of the safety of DAAs and efficacy of improving cognitive and neuropsychological and quality-of-life outcomes irrespective of age and gender, as shown in our study, future recommendations should focus on integrated universal HCV care to enable HCV elimination., (© 2022 John Wiley & Sons Ltd.)

Hepatitis C virus infection among kidney transplant recipients (KTRs) is an important public health concern worldwide. Evidence on available treatments given shows a greater variability for safety and efficacy, thus we performed this large analysis to present the pooled findings. PubMed/Medline, ScienceDirect, and Google Scholar were searched to identify observational studies of both interferon‑based conventional treatment (CT) and recently approved direct‑acting antivirals (DAAs), published before November 2020. Meta‑analysis of effectiveness outcome (sustained virological response [SVR12]) and safety data (adverse events and discontinuation rate) was performed using a random‑effect model. Subgroup analysis based on ± ribavirin with both treatments was performed to assess its relevance in clinical practice. Chi‑square and I2 tests were used to assess heterogeneity between the studies. Twenty‑five and 9 observational records reporting on treatment with DAAs (n = 943) and CT (n = 125), respectively, are analyzed. The overall pooled estimate of SVR12 rate was found as 95.3%, (range: 92.6%–97%) with DAAs in comparison to 46.4% (range: 33.7%–59.6%) with CT. The pooled prevalence of adverse drug reactions (ADRs) in CT was higher as 47.8% than in DAAs as 23.8%, consequently showing a high discontinuation rate of 31.7% in CT as compared to 6.5% with DAAs. Subgroup analyses of both DAAs and interferon‑based treatment ± ribavirin showed decreased effectiveness and increased ADR rates on adding ribavirin. The effectiveness of DDAs was found significantly higher than CT with a better safety profile in KTRs. Ribavirin did not provide any additional benefits while given in combination with either of the treatments available. [ABSTRACT FROM AUTHOR]

Introduction: Sofosbuvir (SOF) and velpatasvir (VEL) is a pan‐genotypic regimen for the treatment of Hepatitis C virus (HCV) infection. The data on the efficacy and safety of this regimen is end‐stage renal disease (ESRD) is scanty. This systematic review and meta‐analysis was done to ascertain the efficacy and safety of SOF and VEL in patients with chronic Hepatitis C (CHC) and ESRD on renal replacement therapy (RRT). Methods: Systematic search of Pubmed, Embase, Scopus, and Google Scholar was conducted using the search term (end‐stage renal disease OR renal replacement therapy OR chronic kidney failure OR severe renal impairment OR chronic kidney disease OR haemodialysis OR dialysis OR peritoneal dialysis) AND (sofosbuvir OR velpatasvir OR NS5A inhibitors OR directly acting antivirals). Pooled sustained virologic response (SVR) and adverse event rates with 95% confidence intervals were estimated. Results: Seven studies (410 patients with CHC and ESRD on RRT) fulfilled our eligibility criteria. The overall pooled SVR rate of SOF and VEL in patients with HCV on RRT was 97.69% (95% CI: 95.71 to 98.92). There was no significant heterogeneity (I2: 39.3%, p‐value of Cochran's Q = 0.13) among the studies. The pooled estimate of efficacy of SOF‐VEL combination among patients with cirrhosis was 91.94% (95% CI 77.03–98.52). Pooled SVR rates in genotype 3 infection [94.6%, (95%: CI 81.3–99.4)] was comparable to that in those with documented non‐genotype 3 infection [94.63%, (95% CI 87.12–98.44)]. No serious adverse event attributable to SOF and VEL was reported in the included studies. Conclusion: The fixed‐dose combination of SOF and VEL is effective and safe in CHC patients with ESRD on RRT. SUMMARY AT A GLANCE: This systematic review/meta‐analysis revealed collective evidence that the sofosbuvir/velpatasvir combination is efficacious and safe for HCV eradication in patients on kidney replacement therapy. [ABSTRACT FROM AUTHOR]

ABSTRACT: Aims: The data regarding the treatment of chronic hepatitis C (CHC) in renal transplant recipients is lacking from the Asia‐Pacific region. The aim of the present study was to assess the safety and efficacy of directly acting antivirals (DAAs) in the treatment of CHC infection in renal transplant recipients. Methods: A total of 47 CHC infected renal transplant recipients were enrolled in this real life observational cohort analysis between March 2015 and September 2016. Presence of hepatic fibrosis/cirrhosis was assessed on transient elastography (Fibroscan). Fourteen patients were treated with Sofosbuvir and Ribavirin for 24 weeks. Twenty‐two patients received Sofosbuvir and Ledipasvir and 12 patients received Sofosbuvir and Daclatasvir with (n = 3) or without (n = 31) Ribavirin for 12 or 24 weeks depending on genotype and underlying cirrhosis. Data were analyzed for safety and treatment efficacy [sustained virological response at 12 weeks (SVR12)]. Results: The median baseline HCV RNA concentration in the whole group was 7.38 × 106 IU/mL (1.23 × 104–6.36 × 107). The SVR12 rates were 100% in all groups except in the Sofosbuvir and Ribavirin group (86%). Transient Elastography revealed minimal or no fibrosis (F0‐F1) in 31 (65.96%) patients, moderate fibrosis (F2) in 11 (23.4%) patients and cirrhosis in five (10.64%) patients. The only serious adverse effect was anaemia observed in eight (57%) patients in the Sofosbuvir and Ribavirin group. Conclusion: DAAs including Sofosbuvir, Daclatasvir and Ledipasvir with or without ribavirin are safe and effective for the treatment of chronic hepatitis C in renal transplant recipients. [ABSTRACT FROM AUTHOR]

There is no "gold standard" tool for the assessment of frailty in cirrhosis. This study compares Liver Frailty Index (LFI), Short Physical Performance Battery (SPPB), Fried Frailty Criteria (FFC), and Clinical Frailty Scale (CFS) for frailty assessment and ascertains its impact on predicting mortality and hospitalizations in a cohort of outpatients with cirrhosis. 116 patients were enrolled in this prospective observational cohort study. Frailty assessment was done using LFI, SPPB, FFC, and CFS. All patients were followed up for 6 months. The primary outcome was the first of either all-cause unplanned hospitalization or all-cause mortality occurring within 6 months of the study period. 100 (86.2%) males and 16 (13.8%) females with a mean age of 50.2 (48.4–51.9, 95% CI) years were included. The most common cause of cirrhosis was alcoholic liver disease (47.4%) followed by hepatitis C (12.9%) and Nonalcoholic steatohepatitis (NASH) (10.3%). There was no significant difference in prevalence of frailty based on LFI (43.1%), FFC (36.2%), CFS (44%), and SPPB (47.4%) (P > 0.05). Frail patients had worse outcomes compared to the Not frail group. At 6 months, the mortality rate in Frail patients was 42% versus 1.5% for the Not frail; hospitalization in Frail patients occurred in 92% versus 6% in the Not frail. On multivariable analysis, independent predictors of mortality were Frailty [OR 14 (1.4–54.2)], alcohol-related cirrhosis [OR 4.2 (1.1–16.3)], Child-Turcotte-Pugh (CTP) [OR 2.1 (1.4–2.9)] and Chronic liver disease questionnaire (CLDQ) [OR 0.1 (0.1–0.4)] scores. LFI, SPPB, FFC, and CFS are comparable in frailty assessment in patients with cirrhosis. Importantly, comparability of the commonly used scores for frailty assessment and prediction of hospitalization and mortality allows flexibility for clinical application. [ABSTRACT FROM AUTHOR]