Direct-acting Antivirals In Patients Research Articles

Efficacy and safety of direct-acting antiviral regimen for patients with hepatitis C virus genotype 2: a systematic review and meta-analysis.

Direct-acting antivirals (DAAs) show high cure rates in treating chronic hepatitis C virus (HCV). However, the effect of DAAs on patients infected with genotype 2 (GT2) is difficult to determine despite the availability of several DAA regimens. A systematic search of six databases (PubMed, Embase, Cochrane Library, Web of Science, CNKI, and Clinicaltrial.gov) was conducted through April 20, 2022. We considered the sustained virological response 12 weeks after treatment (SVR12) as the efficacy outcome, and adverse events (AEs) as the safety outcome. By calculating the mean SVR12 and the proportion of AEs among patients, we considered the intervention effect for each DAA regimen. The random effect model was then used in all meta-analyses. This systematic review and meta-analysis aimed to summarize the evidence on efficacy and safety of DAAs in patients infected with HCV GT2. The Bayesian Markov Chain Monte Carlo (MCMC) network metanalysis was used to indirectly compare regimen in GT2 patients. Among 31 articles included (2,968 participants), consisting of 1,387 treatment-naive patients and 354 patients with cirrhosis. The overall pooled SVR12 rate was 94.62% (95% CI: 92.43-96.52%) among the participants who received all doses of treatment. Meta-analysis results of AEs revealed that fatigue was the most common AE (14.0%, 95% CI: 6.4-21.6%), followed by headache (13.1%, 95% CI: 9.2-17.1%), whereas death and serious adverse events were uncommon. We compared DAA-based treatments indirectly using meta-analysis and found the combination of Sofosbuvir plus Velpatasvir and Glecaprevir plus Pibrentasvir, each administered over a 12-week period, were identified as the most effective and relatively safe in managing chronic hepatitis C virus genotype 2 (HCV GT2) infection. Both treatments achieved a SVR12 of 100% (95% CI 99-100%).

The Impact of the G6PD Gene Mutations in Patients with Chronic Hepatitis C Infection Treated with Direct-Acting Antivirals: A Multicenter Observational Study.

Following the advent of direct-acting antivirals (DAAs), the treatment of hepatitis C virus (HCV) infection is now rarely challenging. However, data are still limited concerning DAA use in patients affected by glucose-6-phosphate dehydrogenase deficiency (G6PDd). Based on these considerations, the goal of this study was to evaluate the effectiveness and safety of DAAs in this subpopulation. A retrospective multicenter observational study (2015-2023) was conducted on all 2754 consecutive HCV-positive patients treated with first- and second-generation all-oral DAAs, and with a G6PDd diagnosis confirmed by quantitative testing (n = 38). At the treating clinician's discretion, an enhanced clinical and laboratory follow-up was performed, generally on a monthly basis both during treatment and up to six months after the end of it. Concerning hematochemical parameters, no significant differences were found between any considered time point. In all cases, no treatment-related adverse events were reported, and virologic response rates were as expected without G6PDd. In conclusion, in a large experience which, to the best of our knowledge, is unprecedented in the literature, the treatment of HCV hepatitis with nearly all available DAAs in patients with G6PDd as a comorbidity-a common occurrence in countries such as Italy-proved to be highly effective and safe.

Skeletal muscle mass increases after viral eradication with direct-acting antivirals in patients with chronic hepatitis C: A longitudinal study.

Results of studies evaluating the effect of viral eradication following direct-acting antiviral (DDA) therapy on skeletal muscle mass of patients with chronic hepatitis C (CHC) are scarce. To assess the components of sarcopenia (low muscle mass, low muscle strength and low physical performance) in a cohort of CHC individuals before and after DAA therapy. We performed a longitudinal study of patients with CHC who underwent body composition assessment before (T0), and at 12 (T1) and 48 (T2) weeks after DDA therapy. Bioelectrical Impedance Analysis was used to assess skeletal mass muscle (SM) and phase angle (PhA). SM index (SMI) was calculated by dividing the SM by squared height. Muscle function was evaluated by hand grip strength (HGS) and timed up-and-go (TUG) test. Mixed-effects linear regression models were fitted to SMI, HGS and physical performance and were used to test the effect of HCV eradication by DAA. 62 outpatients (mean age, 58.6 ± 10.8 years; 58% with compensated cirrhosis) were included. Significant decreases in liver fibrosis markers and an increase of 0.20 and 0.22 kg/m2 in the SMI were observed at T1 and T2. Following DAA therapy, an increase of one unit of PhA was associated with a reduction of 0.38 min in TUG. HCV eradication with DAA therapy was associated with a dynamic reduction of non-invasive markers of liver fibrosis and increased muscle mass in 62 patients with CHC who had an undetectable HCV load at 12 weeks after completion of antiviral treatment.

Clinical outcomes and prognostic factors after HCV clearance with DAA in HIV/HCV-coinfected patients with advanced fibrosis/cirrhosis.

We assessed long-term clinical outcomes and prognostic factors for liver disease progression after sustained viral response with direct-acting antivirals in patients coinfected with HIV/HCV with advanced fibrosis or cirrhosis. A total of 1300 patients who achieved sustained viral response with direct-acting antivirals from 2014 to 2017 in Spain were included: 1145 with compensated advanced chronic liver disease (384 advanced fibrosis and 761 compensated cirrhosis) and 155 with decompensated cirrhosis. The median follow-up was 40.9 months. Overall, 85 deaths occurred, 61 due to non-liver non-AIDS-related causes that were the leading cause of death across all stages of liver disease. The incidence (95% CI) of decompensation per 100 person-years (py) was 0 in patients with advanced fibrosis, 1.01 (0.68-1.51) in patients with compensated cirrhosis, and 8.35 (6.05-11.53) in patients with decompensated cirrhosis. The incidence (95% CI) of HCC per 100 py was 0.34 (0.13-0.91) in patients with advanced fibrosis, 0.73 (0.45-1.18) in patients with compensated cirrhosis, and 1.92 (1.00-3.70) per 100 py in patients with decompensated cirrhosis. Prognostic factors for decompensation in patients with compensated advanced chronic liver disease included serum albumin, liver stiffness measurement (LSM), and fibrosis 4. In this population, LSM and LSM-based posttreatment risk stratification models showed their predictive ability for decompensation and HCC. Non-liver non-AIDS-related events were the leading causes of morbidity and mortality after direct-acting antiviral cure among coinfected patients with advanced fibrosis/cirrhosis. Among those with compensated advanced chronic liver disease, baseline LSM and posttreatment LSM-based models helped to assess decompensation and HCC risk.

Outcomes of direct-acting antivirals in patients with HCV decompensated cirrhosis: a systematic review and meta-analysis

BackgroundDirect-acting antivirals (DAA) are effective for chronic hepatitis C virus (HCV) treatment. However, their impact on overall survival (OS), hepatocellular carcinoma (HCC) occurrence, HCC-free survival, and liver function in patients with HCV decompensated cirrhosis remains uncertain. This study aimed to evaluate the effects of DAA treatment on this population.MethodsStudies were identified by searching the MEDLINE, SCOPUS, and CENTRAL databases. OS and HCC-free survival probabilities and time data were extracted from Kaplan-Meier curves. A one-stage meta-analysis using parametric Weibull regression was conducted to estimate the relative treatment effects of DAA vs. no DAA. The primary outcome was the OS rate. The secondary outcomes were HCC-free survival, HCC occurrence rate, and improvement in the Model for End-stage Liver Disease (MELD) score.ResultsEight cohorts comprising 3,430 participants (2,603 in the DAA group and 1,999 in the no-DAA group) were included. The OS probabilities at 12 and 24 months were 95 and 90% for the DAA group, respectively, compared with 89 and 80% in the no-DAA group, respectively. Hazard ratio (HR) was 0.48 (95% confidence interval (CI): 0.39, 0.60; p < 0.001). The HCC-free survival probabilities at 12 and 24 months were 96 and 90%, respectively, in the former, and 94 and 85%, respectively, in the latter. The HR of HCC occurrence was 0.72 (95% CI: 0.52, 1.00; p = 0.05), which suggests that DAA treatment in decompensated cirrhosis may lead to a 28% lower risk of HCC occurrence. The mean MELD score difference was −7.75 (95% CI: −14.52, −0.98; p = 0.02).ConclusionImprovement in OS and MELD score is a long-term benefit of DAA treatment in patients with HCV decompensated cirrhosis, with a marginal effect of the treatment on HCC development.

Real-World Effectiveness and Safety of Direct-Acting Antivirals in Patients with Chronic Hepatitis C and Epilepsy: An Epi-Ter-2 Study in Poland.

In Poland, active HCV infection affects between 0.4 and 0.5% of the population, i.e., about 150,000 people, while the number of patients with epilepsy is estimated to be 350,000-400,000. Currently available antiviral therapies show little interaction with neurological drugs. The aim of our study was to evaluate the effectiveness and safety of the treatment of chronic HCV infection in patients with coexisting epilepsy. A total of 184 epilepsy patients were selected from the group of 10,152 HCV-infected patients treated for HCV infection within the Epiter-2 database from 2015 to 2018. Comparing the effectiveness and safety of anti-HCV regimens between the patients with comorbid epilepsy and 3573 patients without comorbidities was our study's objective. The effectiveness of anti-HCV treatment was high in both the sample and the control group. No statistically significant SVR difference was observed between the sample group, with ITT = 93.5% and mITT = 95.5%, and the control group, with ITT = 95.2% and mITT = 97.5%, regardless of the genotype and the stage of liver disease at the start of therapy. The treatment was safe in patients with epilepsy. The effectiveness and safety of HCV treatment in patients with epilepsy are comparable to those of patients with no significant comorbidities.

Outcome of direct-acting antiviral treatment in patients with hepatitis C virus/hepatitis B virus coinfection

BackgroundOral direct-acting antiviral (DAA) regimens for chronic hepatitis C virus (HCV) infection have greatly improved treatment efficacy, with sustained virological response (SVR) rates of > 95% for HCV monoinfected patients. However, hepatitis B virus (HBV)/HCV coinfection is more complex than monoinfection with HBV or HCV alone. We evaluated the SVR rate at 12 weeks post-treatment with DAAs in patients with HCV/HBV and evaluated the rate of HBV reactivation during and 6 months after treatment.ResultsAmong the included patients, 191 (95.5%) achieved SVR. Older age, low platelet count, high serum creatinine, and higher liver stiffness value measured by fibroscan were predictors of failure to achieve SVR. The 16 patients (8%) with HBV reactivation patients had significantly higher ALT and serum creatinine and a high HCV RNA viral load at baseline compared with that of those without HBV reactivation.ConclusionPatients who received DAAs to treat HCV/HBV coinfection showed a high SVR. However, it is important to be aware of the potential risk for HBV reactivation during and after treatment with DAAs.

THU-221 - Efficacy of direct-acting antivirals in patients with hepatitis C virus-associated cryoglobulinemia and monoclonal gammopathy

THU-221 - Efficacy of direct-acting antivirals in patients with hepatitis C virus-associated cryoglobulinemia and monoclonal gammopathy

Efficacy of direct-acting antivirals in patients with HCV-associated cryoglobulinemia and monoclonal gammapathy

Efficacy of direct-acting antivirals in patients with HCV-associated cryoglobulinemia and monoclonal gammapathy

Real-world Safety and Effectiveness of 24-week Sofosbuvir and Ribavirin Treatment in Patients Infected with Rare Chronic Hepatitis C Virus Genotypes 3, 4, 5, or 6 in Japan.

Objectives Real-world evidence on the safety and effectiveness of direct-acting antivirals in patients infected with chronic hepatitis C virus (HCV) genotypes (GTs) 3, 4, 5, or 6 in Japan is limited. This prospective observational study assesses the real-world safety profile and treatment effectiveness among patients prescribed sofosbuvir with ribavirin (SOF+RBV) for HCV GT3-6 infection in Japan. Methods Adults receiving 24-week SOF+RBV treatment for HCV GT3-6 infection were prospectively enrolled and observed through 24 weeks post-treatment for treatment-emergent adverse events (AEs) considered related to SOF and/or RBV by treating physicians and for a sustained virologic response at 12 and 24 weeks post-treatment (SVR12, SVR24). Incidence rates of related AEs and serious AEs (SAEs) were calculated. Proportions of patients experiencing related AEs/SAEs and those achieving SVR12 and SVR24 were assessed overall and by baseline characteristics, including treatment experience and cirrhosis status. Results Among the 50 patients included in the safety analysis, 92% had GT3 infection. The incidence rates of related AEs and SAEs were low overall (1.52 and 0.25 per 100 person-weeks, respectively), with 6.0% and 14.0% patients experiencing AEs related to SOF or RBV, respectively. There were no marked differences in the occurrence of related AEs/SAEs by patient baseline characteristics. SVR12 and SVR24 were achieved in 83.7% (41/49) and 82.2% (37/45) of patients, respectively. Lower effectiveness was observed among treatment-experienced patients and patients with cirrhosis at baseline. Conclusions This study demonstrated that SOF+RBV treatment for HCV GT3-6 infection was safe, effective, and an important treatment option for this difficult-to-treat patient population in Japan.

Efficacy of direct-acting antivirals in patients with hepatitis C virus-associated cryoglobulinemic vasculitis: Results of a long-term follow-up

Objective – to evaluate the long-term outcomes of HCV eradication with direct-acting antivirals (DAAs) in patients with hepatitis C-associated cryoglobulinemic vasculitis (HCV-CV)Materials and methods. We retrospectively assessed 48 patients with HCV-CV treated with DAAs. The activity of HCV-CV was assessed by using Birmingham Vasculitis Activity Score version 3 (BVAS v. 3). In patients with HCV-CV the rate of sustained virologic (defined as undetectable HCV-RNA levels 12 weeks after treatment cessation) and immunological (defined as absence of circulating cryoglobulins, rheumatoid factor and normal C4 level) response; and the rate of complete (defined by a BVAS v. 3 score of 0) and partial (defined as BVAS v. 3 score <50% of the baseline score) clinical response were evaluated. Immunosupressants were given before or after DAAs therapy if clinically needed.Results. Median time of follow-up from treatment cessation were 26,5 (11,5–62,3) months. All 48 (100%) patients achieved sustained virologic response. Elimination of cryoglobulins were reported in 20 (41,7%) patients, complete immunological response-in 4 (8,3%) cases. Complete and partial clinical responses were observed in 13 (27,1%) and 19 (39,6%) patients, respectively. BVAS v. 3 score <4 at baseline was independently associated with complete clinical response (ОR=7,58; 95% CI: 1,42–40,48; р=0,018). 3 (6,3%) patients demonstrated HCV-CV relapse.Conclusion. Patients with HCV-CV require a long-term follow-up period even after reaching the SVR. The use of BVAS v. 3 score before the DAAs therapy can facilitate the planning of therapeutic approach, particularly, when identifying the patients in whom the immunosupressive therapy should be considered after viral eradication.

Frequency of De Novo Hepatocellular Carcinoma after Direct-acting Antiviral Therapy for Chronic Hepatitis C: A Prospective Follow-up.

Chronic hepatitis C (CHC) management has changed tremendously after direct-acting antivirals (DAAs) availability. Sustained virological response (SVR) has improved significantly, but one of the major concerns is the chances of de novo hepatocellular carcinoma (HCC) development after DAAs. The objective of the study is to calculate the frequency of newly diagnosed cases of HCC after antiviral therapy for CHC in Pakistan. This prospective, interventional research was conducted from June 2017 to September 2020. All patients after antiviral therapy for CHC were followed with an ultrasound abdomen and α-fetoprotein, six monthly. Multiphasic computed tomography (CT) of the abdomen was performed in suspected cases. For quantitative variables, the mean and standard deviations were calculated, whereas the qualitative variables were analyzed by frequencies and percentages. Among 180 patients, 110 were men and 70 were women with a mean age of 45.52 ± 11.71 years. One hundred and twenty-six patients were noncirrhotic, 38 had compensated cirrhosis while 16 had decompensated cirrhosis. One hundred and sixty-four (91.11%) patients achieved SVR, of which 22 (12.22%) patients developed new HCC during follow-up. Compensated cirrhosis group had 10 patients, the decompensated group had 12 patients, and the noncirrhotic group had no new HCC cases. Among patients with the new HCC, 12 achieved SVR. The risk of the development of HCC after antiviral treatment is highly significant among patients with liver cirrhosis. So, a strict surveillance strategy should be adopted in every cirrhotic patient following treatment with DAA agents even if they achieve SVR. Chances of developing HCC are still significantly high even after achieving SVR with DAAs in patients with liver cirrhosis.Patients with liver cirrhosis should be under surveillance for HCC even after achieving SVR after DAAs treatment. Rasool S, Hanif S, Ahmad A, et al. Frequency of De Novo Hepatocellular Carcinoma after Direct-acting Antiviral Therapy for Chronic Hepatitis C: A Prospective Follow-up. Euroasian J Hepato-Gastroenterol 2022;12(2):73-76.

Short-term hepatocyte function and portal hypertension outcomes of sofosbuvir/velpatasvir for decompensated hepatitis C-related cirrhosis

BackgroundIt is unclear whether hepatocyte function and/or portal hypertension improves if a sustained virologic response (SVR) is achieved with direct-acting antivirals in patients with decompensated hepatitis C-related cirrhosis.MethodsWe examined the safety and efficacy of a 12-week course of sofosbuvir/velpatasvir (SOF/VEL) in 20 patients with decompensated hepatitis C-related cirrhosis. We also investigated changes in the hepatocyte receptor index (LHL15) and blood clearance index (HH15) by Tc-99 m-galactosyl human serum albumin scintigraphy, liver stiffness measurement (LSM) by transient elastography, and hepatic venous pressure gradient (HVPG) in patients who achieved an SVR at 24 weeks after treatment (SVR24).ResultsOne patient discontinued treatment because of rectal variceal hemorrhage, and 19 patients completed treatment. SVR24 was achieved in 17 patients (89%). Median LHL15 increased from 0.72 pre-treatment to 0.82 after SVR24 (p = 0.012), and median HH15 decreased from 0.82 pre-treatment to 0.76 after SVR24 (p = 0.010). The percentage of patients with LSM ≥ 20 kPa was 90% before treatment and remained at 90% after SVR24. However, the percentage with severe portal hypertension (defined as HVPG ≥ 12 mmHg) decreased from 92% pre-treatment to 58% after SVR24 (p = 0.046). Patients with a decreased HVPG from pre-treatment to after SVR24 had a smaller pre-treatment spleen volume than those with an increased HVPG (median, 252 vs. 537 mL, p = 0.028).ConclusionAchieving SVR24 with SOF/VEL treatment in patients with decompensated hepatitis C-related cirrhosis can be expected to improve hepatocyte function and portal hypertension on short-term follow-up.

Cardiometabolic effects of direct-acting antivirals in patients with hepatitis C

Cardiometabolic effects of direct-acting antivirals in patients with hepatitis C

Safety and effectiveness of direct-acting antivirals in patients with chronic hepatitis C and chronic kidney disease.

Background/AimsTo evaluate the effectiveness and safety of direct acting antivirals (DAAs) available in chronic kidney disease (CKD) patients with hepatitis C virus (HCV) infection in Korea.MethodsIn a retrospective, multicenter cohort study, 362 patients were enrolled from 2015 to 2019. The effectiveness and safety of DAAs including glecaprevir/pibrentasvir, sofosubvir/ribavirin, ledipasvir/sofosbuvir, and daclatasvir/asunaprevir were analyzed for patients according to CKD stage. We evaluated sustained virologic response at week 12 after treatment (SVR12) as primary endpoint. The effectiveness and safety were also evaluated according to CKD stage.ResultsAmong 362 patients, 307 patients completed DAAs treatment and follow-up period after end of treatment. The subjects comprised 87 patients (62 with CKD stage 3 and 25 with CKD stage (4–5), of whom 22 were undergoing hemodialysis). HCV patients with CKD stage 1 and 2 (estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m2) showed SVR12 of 97.2% and 95.4% respectively. SVR12 of CKD stage 3 and 4–5 (eGFR < 60 mL/min/1.73 m2) patients was 91.9% and 91.6% respectively. Patients undergoing hemodialysis achieved SVR12 (90.9%). Treatment failure of DAAs in stage 1, 2, 3, and 4–5 was 2.8%, 2.7%, 1.6%, and 4%. DAAs showed good safety profile and did not affect deterioration of renal function.ConclusionsDAAs shows comparable SVR12 and safety in CKD patients (stage 3, 4, and 5) with HCV compared with patients with stage 1 and 2. The effectiveness and safety of DAAs may be related to the treatment duration. Therefore, it is important to select adequate regimens of DAAs and to increase treatment adherence.

RESIST-HCV Criteria to Monitor Progression of Low-Risk Esophageal Varices in Patients With Compensated Cirrhosis After HCV Eradication: The SIMPLE Study: SIMPLE: Scoring Index to Monitor Progression of Low-risk Esophageal varices.

Noninvasive criteria to predict the progression of low-risk esophageal varices (EV) in patients with compensated hepatitis C virus (HCV) cirrhosis after sustained virological response (SVR) by direct-acting antivirals (DAAs) are lacking. Our aim was to assess the diagnostic performance of Rete Sicilia Selezione Terapia-HCV (RESIST-HCV) criteria for EV progression compared with elastography-based criteria (Baveno VI, Expanded Baveno VI, and Baveno VII-HCV criteria). All consecutive patients observed at 3 referral centers with compensated HCV cirrhosis with or without F1 EV who achieved sustained virological response by DAAs were classified at last esophagogastroduodenoscopy (EGDS) as RESIST-HCV low risk (i.e., low probability of high-risk varices [HRV]) if platelets were >120 × 10 9 /L and serum albumin >3.6 g/dL or RESIST-HCV high risk (i.e., high probability of HRV) if platelets were <120 × 10 9 /L or serum albumin <3.6 g/dL. The primary outcome was the progression to HRV. The area under the receiver operating characteristic curve and decision curve analysis of noninvasive criteria were calculated. The cohort consisted of 353 patients in Child-Pugh class A (mean age 67.2 years, 53.8% males). During a mean follow-up of 44.2 months, 34 patients (9.6%, 95% CI 6.7%-13.5%) developed HRV. At the last EGDS, 178 patients (50.4%) were RESIST-low risk, and 175 (49.6%) were RESIST-high risk. RESIST-HCV criteria showed the highest area under the receiver operating characteristic curve (0.70, 95% confidence interval 0.65-0.75), correctly sparing the highest number of EGDS (54.3%), with the lowest false-positive rate (45.7%), compared with elastography-based criteria. Decision curve analysis showed that RESIST-HCV had higher clinical utility than elastography-based criteria. Biochemical-based RESIST-HCV criteria are useful to easily predict HRV development after HCV eradication by DAAs in patients with compensated cirrhosis and low-risk EV.

The clinical impact of direct-acting antiviral treatment on patients affected by hepatitis C virus-related oral lichen planus: a cohort study

ObjectivesOral lichen planus (OLP) is a chronic inflammatory mucocutaneous disease. Literature supports an association between OLP and Hepatitis C virus (HCV) infection. The current treatment for HCV infection with direct-acting antivirals (DAAs) is highly effective and safe. The aim of this study is to evaluate the clinical impact of viral eradication with DAAs in patients with HCV and OLP.Materials and methodsFor this cohort observational study, 18 patients with HCV and OLP were recruited; all patients received DAAs. Nineteen patients with OLP without HCV were recruited as controls. Both groups received an oral clinical examination, taking photographs of the oral mucosa, at three time points. Size and type of lesions, clinical and efficacy scores, were evaluated at each time point with ImageJ software. Changes were assessed by a general linear model repeated measures analysis. Kruskal–Wallis H and Mann–Whitney U tests were used to evaluate the differences between subgroups.ResultsAll patients of the study group reached a sustained virological response. The study group showed a correlation between viral load and clinical status (p < 0.05), higher clinical scores at baseline (p = 0.001) and higher efficacy index than controls (p < 0.001), improving over time (p < 0.001); controls did not show significant changes (p = 0.196). One patient of the experimental group developed oral squamous cell carcinoma (OSCC) of the tongue during the DAAs treatment.ConclusionsIn this study, patients with HCV and OLP showed a worst clinical oral status than controls at baseline. However, treatment for virus eradication can improve the oral lichen planus clinical course.Clinical relevanceHCV eradication can improve the clinical course of patients with HCV-related OLP.

Long-term prediction of hepatocellular carcinoma using serum autotaxin levels after antiviral therapy for hepatitis C

Introduction and objectivesContinuous monitoring for hepatocellular carcinoma is necessary following treatment with direct-acting antivirals in patients with hepatitis C virus infection. We investigated whether the long-term follow-up of serum autotaxin levels could predict the development of hepatocellular carcinoma. Patients and MethodsThis prospective observational study enrolled adult patients with chronic hepatitis C virus infection who presented to the study center from January 2016 to March 2021. Among the patients who achieved a sustained viral response, the relationship between the development of hepatocellular carcinoma and serum autotaxin levels was assessed before treatment with direct-acting antivirals; at the end of therapy; at 12 and 24 weeks; and at 12, 24, 36, and 48 months after treatment. ResultsData were analyzed for 139 patients. Thirteen patients developed hepatocellular carcinoma 48 months after treatment. The cut-off serum autotaxin values that predicted hepatocellular carcinoma after 24 weeks were 1.22 (men) and 1.92 (women) mg/L. The area under the curve for serum autotaxin was 0.83 (95% confidence interval [CI]:0.71–0.95) in men and 0.90 (95% CI: 0.82–0.99) in women. The positive predictive value of serum autotaxin was 0.208 (95% CI: 0.139–0.248), and the negative predictive value was 0.971 (95% CI: 0.939–0.990). The cumulative incidence of hepatocellular carcinoma was significantly higher when serum autotaxin levels were above the cut-off value after 24 weeks (p < 0.0001). ConclusionsSerum autotaxin is a candidate biomarker for predicting hepatocellular carcinoma during the long-term follow-up of patients with a sustained viral response following treatment with direct-acting antivirals.

Long-term hepatic function of patients with compensated cirrhosis following successful direct-acting antiviral treatment for hepatitis C virus infection.

Direct-acting antivirals (DAAs) have contributed to the improvement of outcomes for all patients with chronic hepatitis C. The aim of this study was to evaluate the long-term hepatic benefits of hepatitis C virus (HCV) cure by DAAs in patients with compensated cirrhosis. This multicenter cohort study consisted of consecutive patients with compensated cirrhosis who initiated interferon-free DAA treatment before September 2016. The impact of treatment on long-term hepatic function was followed for at least 4years after the end of treatment, and the progression to decompensation was evaluated. The data of 394 patients were available for study. The median age was 70, and 41% had modified albumin-bilirubin (ALBI) grade 2b. During a short-term follow-up 1year after the end of treatment, FIB-4 index and ALBI score significantly improved. The achievement rates of FIB-4<3.25 (40%) and ALBI grade 1 (70%) reached their plateau in the first year; however, there were significant further improvements in platelet count and α-fetoprotein level after the first year. The annual incidence of decompensation was 1.30 (95% confidence interval 0.83-2.02) per 100 person-years. In multivariable analysis, male sex and modified ALBI grade 2b at baseline were associated with decompensation. In a large real-world cohort of patients with compensated cirrhosis treated with a DAA, remarkable improvement in hepatic function was seen after HCV cure, especially during the first year after the end of treatment. Treatment in the early stage of cirrhosis would be of great benefit for preventing liver deterioration to decompensation.

Health care utilization and costs associated with direct-acting antivirals for patients with substance use disorders and chronic hepatitis C.

BACKGROUND: Patients with substance use disorders (SUD) and chronic hepatitis C virus infection (HCV) have limited access to direct-acting antivirals (DAAs) due to multilevel issues related to providers (eg, concern about reinfection); patients (eg, refusal); payers (eg, prior authorization); and health system structure, although clinical guidelines recommend timely DAA treatment for patients with SUD and HCV. Effects of DAAs on real-world health care utilization and costs among these patients is unknown. OBJECTIVE: To compare changes in medical service utilization and costs related to liver, SUD, and all-cause morbidity in patients with SUD and HCV treated with DAAs (DAA group) vs not treated with DAAs (non-DAA group). METHODS: We conducted a retrospective cohort study using MarketScan Commercial and Medicare Supplemental Claims databases (2012-2018) for newly diagnosed HCV treatment-naive adults with SUD. We used difference-in-differences analyses, stratified by cirrhosis status, to determine the adjusted ratio of rate ratio (RoRR) to assess the difference in the relative changes from the pre- to posttreatment periods between the 2 groups. RESULTS: 6,266 patients with SUD and HCV were identified. Of these patients who also had cirrhosis (n = 607), 49% (n = 298) initiated DAA therapy for HCV, whereas of those without cirrhosis (n = 5,659), 22% (n = 1,219) initiated DAAs. For patients with cirrhosis (n = 607), the liver-related costs decreased by $6,213 (95% CI = -$8,571, -$3,856) for the DAA group and $1,585 (95% CI = -$4,659, $1,490) for the non-DAA group. The relative decreases in the rate of liver-related costs were larger for the DAA group than for the non-DAA group, and the relative changes between groups were significantly different (RoRR = 0.37, 95% CI = 0.19-0.73). There was no difference in the relative changes after DAAs in the rate of SUD-related visits/costs or all-cause costs between the 2 groups. For patients without cirrhosis (n = 5,659), a similar association was observed. Besides, the relative decreases in the rate of SUD-related emergency department (ED) visits (RoRR = 0.54, 95% CI = 0.38-0.77); SUD-related long-term care visits (RoRR = 0.30, 95% CI = 0.13-0.73); all-cause ED visits (RoRR = 0.75, 95% CI = 0.64-0.88); and all-cause long term-care visits (RoRR = 0.36, 95% CI = 0.18-0.72) were larger in the DAA group than in the non-DAA group. CONCLUSIONS: DAAs are associated with a significant decrease in the rate of SUD-related ED visits and liver-related costs without increasing the rate of all-cause costs among patients with SUD and HCV, suggesting that the benefits of DAAs extended beyond liver-related outcomes, especially in this disadvantaged population. DISCLOSURES: Research reported in this publication was supported in part by the National Institute on Drug Abuse of the National Institutes of Health (K01DA045618). The funder did not have a role in the design, the execution, the analyses, the interpretation of the data, or the decision to submit the results of this study. The authors have no potential conflicts of interest.