SVR12 Rates Research Articles

Effectiveness of Retreatment with ombitasvir/paritaprevir/ ritonavir, dasabuvir+sofosbuvir+ribavirin in Patients with Chronic Hepatitis C, Subtype 1b and Cirrhosis, Who Failed Previous with First- and Second-generation NS5A Inhibitors

The use of Direct�Acting Antiviral agents (DAAs) in patients with chronic HCV GenoType (GT) 1 infection results in Sustained Virologic Response (SVR) rates of 95%-97%, but 3%-5% of patients experience virologic failure. We observed 41 patients infected with HCV subtype 1b who failed previous treatment with DAAs, including 37 subjects (90.2%) with liver cirrhosis. In total, 30(73.2%) subjects previously received NS5A inhibitors of the first generation (ledipasvir, daclatasvir, or ombitasvir) and 11 subjects (26.8%) received NS5A inhibitors of the second generation (velpatasvir). All patients received retreatment with a combination of ombitasvir/paritaprevir/ritonavir and dasabuvir (3D) with Sofosbuvir (SOF) and Ribavirin (RBV). We compared SVR12 rates depending on fibrosis stage, presence of just single or double NS5A mutation (L31M/V/I and/or Y93H), and the generation of previously used NS5A inhibitors. Observed SVR12 rates were as follows: 97.6% (40/41 patients) overall; 100% in patients without cirrhosis (n=4) versus 97.3% in those with cirrhosis (n=37); 100% with single L31M/V/I or Y93H mutation (n=22) versus 94.4% with double mutations (n=18); 100% in patients who failed previous treatment with first�generation (n=30) versus 90.9% in those who failed previous treatment with second�generation NS5A inhibitors (n=11).

The comparison of two different direct acting antiviral regimens in treatment of chronic hepatitis C virus

Aim: Chronic hepatitis C virus (HCV) is considered a critical threat to the public health in the world. We compared treatment outcomes of Ombitasvir, Paritaprevir and Ritonavir with Dasabuvir (PrOD) and Ledipasvir (LDV) and Sofosbuvir (SOF) in real world patients with chronic HCV in treatment-naive and pre-treated patients with chronic HCV.MaterialS and Methods: 91 adult patients enrolled in our study and were divided in two groups. The first group; consisted of 53 patients, who orally received a fixed-dose combination tablet comprised of LDV and SOF once daily for 24 weeks. The second group; consisted of 38 patients, who orally received a fixed-dose combination tablet comprised of PrOD twice daily for 12 weeks without regard to fat or calorie content. Results: The results showed that sustained virologic response (SVR) rates were 100% in the both groups analyzed. 76 adverse events were occurred in total. 46 of overall adverse events were found on patients in the first group and 30 of those events were found on patients in the second group. Weakness (13.1%), pruritus (5.5%), myalgia (1.1%) nausea (5.5%), dry mouth (1.1%) and insomnia (1.1%) were observed among the patients. Twelve weeks after initiating treatment, virologic suppression was accomplished for all patients in the both groups. Additionally, laboratory analysis concluded that HCV-RNA levels of the overall patients were negative after 48 weeks of the onset of the treatment.Conclusion: The real world comparative analysis of two distinct treatment regimens concluded that administration of PrOD and LDV/SOF on the patients with chronic HCV has an extremely effective outcome. SVR12 rates of 100% were obtained in both treatment regimens for all treatment naive and treatment-experienced patients regardless of cirrhosis occurrence and of HCV genotype.

Response and safety of treatment of chronic hepatitis C by direct-acting antiviral drugs in patients with Child B-related cirrhosis

ObjectivesTo evaluate the response and safety of treatment of chronic hepatitis C virus (HCV) by direct-acting antiviral (DAAs) drugs in patients with Child B-related cirrhosis.BackgroundChronic HCV infection is considered to be one of the major public health diseases that affect most Egyptian population. The appearance of DAAs with its safety and high successful eradication rates has replaced the old treatment protocols, which used interferon.Patients and methodsThis was a cross-sectional study to collect data and outcome of chronic HCV-infected patients who were treated with DAAs. Treatment-naive patients without cirrhosis were treated without ribavirin, and those who had cirrhosis or were treatment experienced (interferon experienced or sofosbuvir experienced) received ribavirin. Efficacy and safety were assessed, and baseline factors associated with sustained virological response at post-treatment week 12 (SVR12) were explored.ResultsSVR at 12 weeks was more seen in Child grade A patients (98.5%) when compared with Child grade B patients (86.7%) and non-SVR was more seen in Child grade B patients (13.1%) when compared with Child grade A patients (1.5%).ConclusionTreatment of chronic HCV-infected patients with DAA drugs in patients has proved to be safe and associated with a high SVR12 rate, in patients with different stages of fibrosis.

Extended panel of biomarkers for long term monitoring of effectiveness of 3 direct antiviral regimen in HCV genotype 1b infection: results from a Romanian infectious disease hospital

Abstract Background: Hepatitis C virus can be eradicated with antiviral therapy, thus reducing the risk of disease progression and death associated with the final stage of liver disease. Methods: 241 patients received PrOD+RBV for 12 weeks. Clinical and laboratory data were assessed at baseline, week 4, 8, 12 (end of treatment, EOT), and 12 weeks after therapy (sustained virological response, SVR). Subsequently, biological and virological measurements were performed at least 48 weeks after obtaining SVR12 in responder patients. Results: Per protocol SVR12 rate was 97,6%. Severe adverse events were reported in 3 patients (1.24%) and led to treatment discontinuation (liver decompensation). One 58-year-old patient who completed the treatment died before SVR evaluation due to acute mesenteric ischemia (not related to antiviral therapy). Baseline total bilirubin above 2 mg/dl can be considered a predictive factor for non-response to PrOD+RBV treatment (p = 0.004). Of the 30 patients evaluated at least 48 weeks after SVR no one presented relapses, with no statistically significant differences in biological parameters changes and no adverse events were noted during the 48-week follow up period. Conclusion: Our study revealed the high effectiveness and good safety profile of PrOD +RBV in patients with genotype-1b HCV compensated cirrhosis (Child Pugh A) which were maintained during a 48-week period after treatment finalization.

Противовирусная терапия хронического гепатита С: многолетний опыт реальной клинической практики

Direct-acting antivirals (DAAs) have significantly changed the treatment of chronic hepatitis C (CHC) and the prognosis for patients since their introduction into clinical practice in 2014–2015. Objective. Study of the evolution and efficacy of antiviral therapy (AVT) for CHC based on the results of providing medical care to patients in Moscow in 2002–2020. Patients and methods. The study was conducted in the Center for the Treatment of Chronic Viral Hepatitis “Infectious Clinical Hospital No 1 of the Moscow City Health Department”. For quantitative variables, the mean and standard deviation were used, while for categorical variables, frequency and proportion were counted (%). Results. 69,745 patients were diagnosed with CHC among all the patients who were examined in the Center. The pooled SVR rate of various therapy regimens was as follows in the HCV genotype 1 (GT1) cohort: IFN + ribavirin – 41.7%; DAAs + PegIFN + ribavirin – 77.4%; IFN-free regimens – 94.0%. Age older than 40 years, diabetes mellitus (DM), history of AVT failure (retreatment), and liver cirrhosis (LC) adversely affected the achievement of SVR. In the patients with HCV GT2 and GT3, the IFN + ribavirin combination allowed SVR achievement in 68.5% of patients, while IFN-free regimens were effective in 95.2% of patients. The predictive factors for achieving SVR were similar to those in the GT1 subgroup, except that the effect of age and DM did not reach statistical significance. Conclusions. The efficacy of DAAs in real clinical practice significantly exceeds the efficacy of IFN-based regimens in patients with various HCV infection genotypes. Achievement of SVR as a result of AVT reduces the likelihood of LC and HCC development. Key words: viral hepatitis, chronic hepatitis, antiviral therapy, peginterferon, interferon-free, dual therapy, triple therapy

Directly Acting Antiviral-Based Treatment for HCV-Infected Persons Who Inject Drugs: A Multicenter Real-Life Study.

Background: We aimed to evaluate the factors associated with a virological response in a cohort of Hepatitis C virus (HCV)-infected people who inject drugs (PWID) treated with direct acting antivirals (DAAs). Methods: We conducted a multicenter retrospective cohort study enrolling HCV-infected PWID treated with DAAs. The primary outcome evaluated was the sustained virological response (SVR12) rate. Results: Five hundred and twenty HCV-infected PWID treated with all-oral DAA-based regimens were enrolled; a total of 168 (32.3%) patients presented genotype 1a, 109 (21.0%) genotype 1b, and 174 (33.5%) genotype 3; a total 152 of the 520 subjects (29.2%) were cirrhotics; a total 118 (22.7%) and 373 (71.7%) were treated with DAA regimens of second and third generation, respectively; a total 169 (33.6%) patients were receiving an opioid agonist at the start of antiviral therapy. Only 11 subjects (2.1%) did not show an SVR12. A significant correlation was found between treatment with opioid substitution therapy (p < 0.001), Human Immunodeficiency Virus (HIV) coinfection (p = 0.002), and treatment with first- or second-generation regimens (p = 0.0015) and HCV failure. Upon multivariate analysis, treatment with a first- or second-generation DAA was the only factor independently associated with failure (OR 10.4, 95% CI: 1.43 to 76.1, p = 0.02). Conclusions: Treatment with DAAs led to a high SVR12 rate (97.9%) in a large cohort of HCV-infected PWID. The only predictor of viral failure found in our analysis was treatment with first- and second-generation DAA.

Retrospective-prospective study of safety and efficacy of sofosbuvir-based direct-acting antivirals in HIV/HCV-coinfected participants with decompensated liver disease pre- or post-liver transplant.

Direct-acting antiviral (DAA) therapy has transformed the management of human immunodeficiency virus (HIV) and hepatitis C (HCV) coinfected patients with advanced liver disease. STOP-Coinfection was a multicenter prospective and retrospective, open-label study using sofosbuvir-based DAA therapy to treat HIV/HCV-coinfected participants pre- or post-liver transplant (LT). Sixty-eight participants with end-stage liver disease (Child-Turcotte-Pugh score ≥7 and Model for End-Stage Liver Disease score 6-29) were enrolled, 26 had hepatocellular carcinoma. Forty-two participants were treated pre-LT and 26 post-LT. All participants completed therapy without need for dose reduction or transfusion; eight required two or more courses of therapy. Ninety-three percent achieved a sustained virologic response and DAA therapy was well tolerated. Despite HCV cure, 12 end-stage liver disease participants required subsequent LT, 7 for decompensated liver disease. Thirteen participants died, 10 with decompensated liver disease pre-LT and three post-LT. Overall, transplant free survival was 42.8% at 4years and post-LT survival was 87.9% at 5years. We conclude that sofosbuvir-based DAA therapy is safe and highly effective in HCV-HIV patients with decompensated liver disease and post-LT, with post-LT survival rates comparable to other indications. This removes one of the last barriers to liver transplantation in this challenging cohort of recipients.

Feasibility and efficacy of 8 week Glecaprevir/Pibrentasvir to treat incarcerated viraemic HCV patients: A case-control study.

Inmates have higher HCV prevalence than general population, representing a fundamental step towards HCV eradication. Our aim was to compare 8-week glecaprevir/pibrentasvir treatment in a case-control study between incarcerated and free patients. Eleven Italian prisons and six outpatient clinics were involved. Patients were matched for sex, risk factors, METAVIR grade, HIV and HBV co-infections. About 131 incarcerated (Group A) and 131 free patients (Group B) were included. Mean age was 43.0±9.6years and 42.8±9.9 in Group A and B, respectively (P=.74). SVR rates were 96.2% and 99.2% in Group A and Group B respectively (P=.21). Five drop-outs occurred in Group A, one in Group B. Incarceration, being PWIDs and OST were not associated with SVR reductions (CI 95%). In conclusion, imprisonment does not influence unplanned interruptions or SVR rates when receiving short-term therapies. Short schedules with pangenotypic regimens could be a good approach to hard-to-reach populations, such as incarcerated patients.

Treatment of hepatitis C in HIV/HCV co-infected with direct-acting antiviral (DAA) regimens in a single clinic in Tripoli/Libya

Background: HIV/HCV co-infection is common in Libya, as the main risk factor is IVDU. Liver cirrhosis can be prevented by HCV eradication. Worldwide, high efficacy of direct acting antivirals (DAA) in the treatment of hepatitis C (HCV) in HIV-1 co-infected patients was reported, however no data available in Libya. We aimed to evaluate the efficacy of DDA in a cohort of HIV co-infected patients. Methods and materials: With intention to treat, we conducted a single center observational study that enrolled all HIV co-infected patients who were presented for HCV treatment from November 2016 to May 2019, we evaluated HIV status, HCV viral load and genotype, and liver status. Treatment success (SVR12) was defined by undetectable HCV-RNA 12 weeks after cessation. Results: A total of 80 HIV/HCV co-infected patients were started treatment of hepatitis C, age ranged from 27 to 69 years (mean 45years), 72 (90%) were males, triple infection reported in 3 (4%). Most of the patients were on antiretroviral therapy, and only 5 (9%) were not on ART drugs. CD4 count was not available in 26patients, >500 in 24 (30%), between 300 to 500 in 13 (16%), and <300 in 17 (21%). HCV genotype 1 found in 44 (55%) patients, genotype 4 &3 found in 20 (25%), and 16 (20%) patients respectively. Naïve patients to HCV treatment were 57 (81%), non-responder and relapse to previous treatment were 7 (9%), and 8 (10%) respectively. Liver cirrhosis by ultrasound abdomen was documented in 21 (26%) patients, APRI score was <.7 in 42 (52.5%), and >.7 in 17 (21%). 6 patients received Interferon in combination with Sofosbuvir and Ribavirin. Interferon free based treatment started in 74 patients (56 received Ledipasvir/Sofosbuvir), 17 received Daclatasvir plus Sofosbuvir, 1 received Sofosbuvir plus Ribavirin), Sustained virological response (SVR) was available in 51 patients, it was achieved in 49/51 (96%). Conclusion: All DAA regimens were well-tolerated and yielded high SVR12 rates in HIV/HCV-co-infected patients, including patients with advanced liver disease and previously non-responder or relapser to interferon and Ribavirin therapy. Treatment of hepatitis C should be offered to all HIV co-infected patients to prevent progression of liver disease to liver cirrhosis and its com.

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

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

Incidence and Impact of Persistent Viremia on SVR Rates in Patients Receiving Direct-Acting Antiviral Therapy.

Rates of persistent viremia (PV) while on direct-acting antiviral therapy were low (5.7%) in a real-world cohort of 983 patients. High sustained virologic response rates were achieved both in patients with PV (92.9%) and those with rapid virologic response (96.5%), without significant differences.

Real-world efficacy and safety of 12-week sofosbuvir/velpatasvir treatment for patients with decompensated liver cirrhosis caused by hepatitis C virus infection.

This study aimed to evaluate the real-world efficacy and safety of 12-week sofosbuvir/velpatasvir (SOF/VEL) treatment for patients with decompensated liver cirrhosis caused by hepatitis C virus (HCV) infection. A total 72 of patients with Child-Pugh (CP) class B or C were enrolled. We evaluated the sustained virologic response at 12weeks after the end of treatment (SVR12), adverse events (AEs), and changes in the liver function. All participants had genotype 1 or 2 HCV infection. At baseline, the numbers of patients with CP class B and C were 59 and 13, respectively. The overall SVR12 rate was 95.8% (69/72); 94.9% (56/59) in CP class B and 100% (13/13) in CP class C. The serum albumin level, prothrombin time and ascites were significantly improved (P < 0.01); however, the serum bilirubin level and encephalopathy did not improve. Among patients who achieved SVR12, 75.0% showed an improvement in their CP score, while 5.9% showed a worsening. The presence of large portosystemic shunt (diameter ≥6mm) and hyperbilirubinemia (≥2.0mg/dL) were independent factors that interfered with the improvement in the CP score (P < 0.05). The most common AEs were encephalopathy (15.3%) and skin symptoms (7.9%). Two patients discontinued SOF/VEL due to AEs. Treatment with SOF/VEL for 12weeks was relatively safe and effective for patients with decompensated cirrhosis. An SVR provided an improvement of the liver function in the majority of patients. However, large portosystemic shunt and hyperbilirubinemia were independent factors that interfered with the improvement in the CP score.

Treatment of Hepatitis C Cirrhotic Patients With Directly Acting Antivirals: A Multicenter Study.

With the introduction of sofosbuvir-based regimens, high cure rates and decreased duration has been achieved. Several studies showed variances in SVR rates between different genotypes, with lower rates of SVR among cirrhotic patients. The aim of our study was to assess the safety and effectiveness of sofosbuvir-based antiviral regimens for the treatment of HCVinfected Egyptian cirrhotic patients. This was a retrospective, observational, and comparative study. A total of nine hundred and forty-six cirrhotic patients with chronic HCV genotype 4 infection, who were eligible for direct acting drugs (DAAs) therapy, were enrolled. The primary outcome measures were the number of patients with successful eradication of the virus evidenced by SVR at 12 weeks after discontinuation of therapy (SVR12), and the secondary outcome measures were the incidence of adverse effects associated with the tested HCV therapy. Among the 946 patients enrolled in the study, 527 patients (55.7%) were males and 419 patients (44.3%) were females with a mean age of 54.00±8.88 years. 20.2% were diabetics and 19.1% were hypertensive. Patients were classified according to Child-Pugh classifications; 818 patients (86.46%) were Child-Pugh class A cirrhosis, while 28 patients (13.53%) were Child-Pugh class B cirrhosis. The SVR12 rate was 96.93% (917 /946). Treatment response in the Child-Pugh class A cirrhosis was 794 (97%) after 12 weeks, while treatment response in the Child-Pugh class B cirrhosis was 123 (96%). Mild side effects were observed in 76 patients. Sofosbuvir based regimens were effective and safe in the treatment of cirrhotic patients with chronic hepatitis C genotype 4.

Real-world safety and effectiveness of ledipasvir/sofosbuvir for the treatment of chronic hepatitis C virus genotype 1 in Japan.

As patients with chronic hepatitis C virus (HCV) tend to be older and/or have advanced liver disease in Japan, real-world data are needed to evaluate safe and effective treatment options. The study aim was to assess safety and effectiveness of ledipasvir/sofosbuvir (LDV/SOF) in a real-world cohort of Japanese patients with HCV genotype (GT) 1 infection overall and by patient subgroups: elderly, compensated cirrhotic, advanced fibrotic and those with hepatocellular carcinoma (HCC). A large prospective observational study was conducted, enrolling adult patients treated for HCV GT1 infection with LDV/SOF at clinical sites across Japan. Patients were observed for safety outcomes during and 4weeks after treatment, and for sustained virologic response at 12-weeks post-treatment (SVR12). Incidence rates (IRs) of adverse drug reactions (ADRs) and serious ADRs (SADRs) and SVR12 rates were assessed overall and by subgroups. ADR and SADR IRs were low (2.26 and 0.17 per 100 person-months, respectively) and did not significantly differ in elderly patients or those with presence of compensated cirrhosis, worsening fibrosis or HCC. SVR12 rates were high overall (98.5%) and across subgroups investigated (≥94%), including patients who were elderly (98.2%), treatment-experienced (97.6%), advanced fibrotic (≥95.8%), had existing NS5A resistance-associated substitutions reported pre-treatment (95.0%), compensated cirrhosis (95.7%), HCC (94.0%) and other chronic liver diseases (96.1%). In this large, real-world observational study of Japanese patients with HCV GT1 infection, LDV/SOF treatment resulted in low incidence of adverse events, with high real-world effectiveness, even among patients with potentially higher risks of adverse safety outcomes and treatment failure.

Telemedicine HCV treatment in department of corrections results in high SVR in era of direct-acting antivirals.

Chronic hepatitis C virus (HCV) is common in the Department of Corrections (DOC). Telemedicine is an effective way to treat HCV. The goal of this report was to demonstrate high SVR rate in DOC patients using telemedicine irrespective of the HCV genotype (GT) and DAAs used. Demographic, clinical and laboratory data were prospectively collected. A total of 870 DOC patients were evaluated and completed HCV therapy June 2015-December 2019 with SVR data were included. The mean age was 50years, 90% were male, 63% were Caucasian, the majority (79%) had GT 1, 92% were treatment naive, and 80% had advanced fibrosis (FIB-4≥3.25 and/or transient elastography≥9.5kPa). The overall SVR was 97% and was similar among all DAAs irrespective of age, sex, race, HIV status, fibrosis level, GT, ribavirin use, prior treatment experience or DAA duration. We conclude that HCV treatment in the DOC through telemedicine is achievable and highly effective with overall SVR 97%, irrespective of the underlying GT or DAA regimen used and can eliminate HCV in this microenvironment and reduce the overall burden of HCV.

Efficacy and Safety of All-oral Emitasvir and Sofosbuvir in Patients with Genotype 1b HCV Infections without Cirrhosis

Background and Aims: Emitasvir is a new type of hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor, and the data of phase 2 trial has shown emitasvir-sofosbuvir to have good safety and tolerance. We conducted this phase 3 trial to further verify the efficacy and safety.Methods: We evaluated the antiviral activity and safety of a 12-week regimen of emitasvir phosphate (100 mg) combined with sofosbuvir (400 mg) once daily in non-cirrhotic patients with genotype 1 HCV infection. The primary endpoint was a sustained virological response at 12 weeks (SVR12) after the end of treatment.Results: Of the 362 patients enrolled in the trial, 39.8% were male, 99.2% had HCV genotype 1b, 0.8% had genotype 1a and 79.8% were treatment-naïve. The average age was 47.2 years. All patients completed the treatment and follow-up. All 3 patients with genotype 1a achieved SVR. Two genotype 1b treatment-naïve patients experienced virologic relapse. The rate of SVR12 was 99.7% (358/359), and SVR24 was 99.4% (357/359) in genotype 1b. Overall, 36.2% had resistance-associated substitutions (RASs) in NS5A and 98.3% had RASs in NS5B at baseline. The RASs at baseline had no effect on the rates of response. Serious adverse events were reported in 16 patients and were not related to emitasvir-sofosbuvir. Most adverse events did not require therapy.Conclusions: The 12 weeks of treatment with emitasvir-sofosbuvir was a highly efficient and safe treatment for a wide range of patients with HCV genotype 1b infection without cirrhosis, who had not been treated or who had been treated with interferon-based regimen previously.

Real‐world efficacy of sofosbuvir plus velpatasvir therapy for patients with hepatitis C virus‐related decompensated cirrhosis

Combination therapy with sofosbuvir (SOF) plus velpatasvir (VEL) is approved for patients with hepatitis C virus (HCV)-related decompensated cirrhosis. We analyzed the real-world efficacy of SOF/VEL therapy. Thirty-three patients with HCV-related decompensated cirrhosis (25 and eight patients with Child B and C, respectively) were treated with SOF/VEL for 12weeks. The HCV non-structural protein (NS)5A and NS5B drug resistance-associated substitutions (RASs) were determined by direct sequencing. Thirty-two of 33 patients completed the treatment, but the remaining patient discontinued the therapy during third week of the treatment due to aggravation of hepatic encephalopathy. Serum HCV-RNA became negative during the treatment in all patients but relapsed after the end of therapy in five patients. In total, 28 out of 33 patients (85%) achieved sustained virological response 12weeks following completion of treatment (SVR12). The SVR12 rate was 96% in patients with Child B, but significantly lower, at 50%, in patients with Child C (P < 0.05). In genotype 1b HCV-infected patients, all eight patients without baseline NS5A RASs, but only three of seven patients with RASs, achieved SVR12. Multivariate analysis identified Child B (odds ratio, 35.8 for Child C; P = 0.045) as an independent predictor of SVR12. Median serum albumin levels significantly increased only in patients who achieved SVR12. Child-Pugh scores improved in 16 of 28 patients (57%) following achievement of SVR12. The effect of SOF/VEL therapy is lower for patients with Child C. Improvement of hepatic function is expected after viral eradication with SOF/VEL therapy in patients with decompensated cirrhosis.

Independent Risk Factors for Hepatocellular Carcinoma Recurrence after Direct-Acting Antiviral Therapy in Patients with Chronic Hepatitis C

Background/AimsThis study was performed to evaluate the efficacy of direct-acting antivirals (DAAs) in Korean patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) and to investigate the risk factors associated with HCC recurrence.MethodsA total of 100 patients with HCV-related HCC, who were treated with DAAs between May 2015 and December 2016, were recruited from seven university hospitals in Korea. Claim data of 526 patients with HCC obtained from the Health Insurance Review and Assessment Service in South Korea were used for external validation of the results.ResultsAmong the 100 patients, 88% achieved a sustained virological response (SVR) 12 weeks after the end of DAA therapy (SVR12), and 37% experienced HCC recurrence after DAA therapy. Short last HCC treatment durability (<12 months) before DAA commencement was independently associated with HCC recurrence (hazard ratio [HR], 2.89; p=0.011). In the nationwide validation cohort, 20.3% of the patients experienced HCC recurrence. The last HCC treatment with a noncurative method, a short last HCC treatment durability (<12 months), and a longer total duration of HCC treatment (≥18 months) were independently related with HCC recurrence (HR 3.73, p<0.001; HR 3.34, p<0.001; and HR 1.74, p=0.006; respectively).ConclusionsDAA therapy showed an acceptable SVR12 rate in patients with HCV-related HCC. Short last HCC treatment durability (<12 months) was associated with HCC recurrence after DAA therapy. This finding suggests that the last HCC treatment durability is an important predictor of HCC recurrence after DAA therapy. (Gut Liver 2021;15-419)

Real-World Clinical Application of 12-Week Sofosbuvir/Velpatasvir Treatment for Decompensated Cirrhotic Patients with Genotype 1 and 2: A Prospective, Multicenter Study.

IntroductionClinical trials of direct-acting antivirals for patients with decompensated cirrhosis have been conducted, but there is limited information on the medicinal applications in clinical settings. We aimed to evaluate the safety and efficacy of sofosbuvir/velpatasvir for decompensated cirrhotic patients with genotypes 1 and 2 in real-world clinical practice.MethodsA prospective, multicenter study of 12-week sofosbuvir/velpatasvir was conducted for patients with decompensated cirrhosis at 33 institutions.ResultsThe cohort included 71 patients (52 genotype 1, 19 genotype 2): 7 with Child–Pugh class A, 47 with class B, and 17 with class C (median score 8; range 5–13). The albumin–bilirubin (ALBI) score ranged from − 3.01 to − 0.45 (median − 1.58). Sixty-nine patients (97.2%) completed treatment as scheduled. The overall rate of sustained virologic response at 12 weeks post-treatment (SVR12) was 94.4% (67/71). SVR12 rates in the patients with Child–Pugh classes A, B, and C were 85.7%, 97.9%, and 88.2%, respectively. Among 22 patients with a history of hepatocellular carcinoma treatment, 20 (90.9%) achieved SVR12. The Child–Pugh score and ALBI grade significantly improved after achieving SVR12 (p = 7.19 × 10−4 and 2.42 × 10−4, respectively). Notably, the use of diuretics and branched-chain amino acid preparations significantly reduced after achieving SVR12. Adverse events were observed in 19.7% of the patients, leading to treatment discontinuation in two patients with cholecystitis and esophageal varices rupture, respectively.ConclusionTwelve weeks of sofosbuvir/velpatasvir in real-world clinical practice yielded high SVR rates and acceptable safety profiles in decompensated cirrhotic patients with genotypes 1 and 2. Achievement of SVR not only restored the liver functional reserve but also reduced or spared the administration of drugs for related complications.Trial RegistrationUMIN registration no, 000038587.Electronic supplementary materialThe online version of this article (10.1007/s40121-020-00329-y) contains supplementary material, which is available to authorized users.

Effectiveness and safety of glecaprevir/pibrentasvir in chronic hepatitis C patients: Results of the Italian cohort of a post-marketing observational study

Background and AimsThe MARS post-marketing, observational study evaluates glecaprevir/pibrentasvir in a large population of Italian patients who are infected with HCV. Patients and MethodsAchievement of SVR12 was the primary endpoint in the overall population and by subpopulations of interest (treatment-naïve and treatment-experienced patients, subjects infected with different HCV genotype/sub-genotype, cirrhotic and non-cirrhotic patients, patients with different severity of fibrosis, patients with an APRI score ≥1, subjects with comorbidities, HIV-coinfected patients, elderly patients and people who use drugs). Safety and quality of life (assessed by SF-36 and Work Productivity and Activity Impairment) were also evaluated. ResultsThe SVR12 rate was 99.4% (319/321; 95% CI: 97.8–99.8%) in the core population with sufficient follow-up (n = 321), 99.7% (289/290) in 8-week treated patients, and high (>96%) across subgroups. Only three patients (0.9%) had treatment-related adverse events that led to treatment discontinuation. In total, 30.1% of patients showed an improvement of ≥2.5 points in the Physical Component Summary of the SF-36 from baseline to the end of treatment, and this figure raised to 37.5% with the achievement of SVR12. Corresponding values for MCS were 42.2% and 42.8%, respectively. ConclusionGlecaprevir/pibrentasvir is safe and effective across subpopulations who are underserved in clinical trials.