Received Direct-acting Antiviral Treatment Research Articles

Differences in the course of hepatocellular carcinoma depending on the DAA treatment

Background and aims: 58 million people live with chronic hepatitis C virus (HCV) infection which can lead to liver cirrhosis and hepatocellular carcinoma (HCC). Currently, a non-interferon therapy based on direct-acting antivirals (DAA) is the standard treatment of HCV infection. This study aimed to assess the occurrence of HCC after treatment with DAA and evaluate whether the course of the disease and liver function is different in patients treated with DAA compared to those who did not receive such therapy. Materials and methods: We studied the population of adult patients from the 2015-2021 period and analyzed the demographic and clinical data, including alcohol abuse, liver enzymes, Child-Pugh and model for end-stage liver disease scores, imaging tests, liver biopsy and elastography, if performed. The Mann-Whitney U and the McNemar’s tests were used. The p-value was set at 0.05. Results: The study included n=34 patients with HCC. In this group n=22 patients (61%) were diagnosed with a chronic HCV infection and n=11 (50%) were receiving DAA treatment. Patients who were receiving DAA developed multiple HCC significantly less often compared to patients not treated with DAA (45.5% vs. 69.6%). We also observed a significantly less common occurrence of portal vein thrombosis (8.7% vs. 18.2%) and distant metastases (0.0% vs. 13.0%) in patients with HCC receiving DAA. Patients with HCC who underwent DAA therapy had significantly lower levels of serum liver enzymes in comparison with patients diagnosed with HCC and not receiving DAA. Conclusions: HCC occurring in patients treated with DAA was more often associated with lymphadenopathy, multiple tumors, portal vein thrombosis and distant metastases probably due to restricted treatment qualification criteria. DAA treatment led to a decrease in the inflammatory activity in the liver. It is important to adjust qualification protocols so that all patients suffering from chronic HCV infection could receive the treatment as soon as possible.

Treatment Outcomes of HCV Infection in People Living with HIV: A Case Series from a Single Center in Korea.

Limited information is available on the clinical course and treatment outcomes of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection in Korea. A retrospective case series was conducted of patients with HIV-HCV coinfection who received interferon (IFN)-based or direct-acting antiviral (DAA) treatment for HCV at a tertiary care hospital between 2000 and 2023. Early virological response (EVR) was defined as a 2-log reduction in HCV RNA levels or undetectable HCV RNA levels at treatment week 12. A sustained virologic response (SVR) was defined as undetectable HCV RNA at 12 weeks after treatment completion. Of the 33 patients with HIV-HCV coinfection, 19 received anti-HCV treatment, of whom 12 received IFN-based treatment and 10 received DAA treatment. The median age at the time of anti-HCV treatment was 49 years (interquartile range, 42-57 years) and 15 patients (79%) were male. Of the 12 patients who received IFN-based anti-HCV treatment, 10 showed EVR and 8 achieved SVR. However, 2 patients who achieved SVR experienced recurrence of HCV infection during follow-up; therefore, the overall success rate of IFN-based treatment was 50% (6/12). All 10 patients (including 3 in whom IFN-based treatment failed) who received DAA treatment (5 with previous anti-HCV treatment and 5 treatment-naïve), achieved SVR and did not experience recurrence of HCV infection during follow-up; therefore, the overall success rate of DAA treatment was 100%. In Korean patients with HIV-HCV coinfection, treatment outcomes were better with DAA treatment than with IFN-based treatment.

Characteristics and Treatment Rate of Patients With Hepatitis C Virus Infection in the Direct-Acting Antiviral Era and During the COVID-19 Pandemic in the United States

Clinical data on hepatitis C virus (HCV) treatment rates in the United States are sparse. To evaluate HCV treatment rates in the era of direct-acting antivirals (DAAs). This retrospective cohort study used data from the deidentified Optum Cliniformatics Data Mart Database (2014-2021) on patients with HCV in the DAA and COVID-19 eras. The database includes patients with private health insurance in the US. The treatment rate and changes over time were assessed with adjusted log-binomial regression, and factors associated with treatment were examined using multivariable logistic regression. A total of 133 348 patients with HCV (79 567 [59.7%] men; mean [SD] age, 59.7 [12.3] years; 4448 [3.3%] Asian, 24 662 [18.5%] Black, and 74 750 [56.1%] White individuals) were included; 38 180 (26.8%) had HCV RNA data, and of those, 20 277 (53.1%) had positive HCV RNA. Overall, 13 214 patients with positive HCV RNA tests (65.2%) received DAA treatment; 6456 of 6634 patients treated with DAAs (97.3%) achieved sustained virologic response. After adjusting for age, sex, and race and ethnicity, the treatment rate in 2018 was 0.5 times greater than the rate in 2014 (adjusted prevalence ratio, 1.50; 95% CI, 1.42-1.59) but declined after 2018, decreasing from 64.8% to 61.2%, and especially after 2019, when it decreased to less than 60% (P < .001). The number of patients with viremic HCV identified in between April 2020 and March 2021 also decreased to 496 from 2761 and 3258 in the preceding 2 years. Receiving care from a gastroenterologist or infectious disease specialist with advanced care practitioner (ie, nurse practitioner, physician assistant, or clinical nurse specialist) was independently associated with greater odds of DAA treatment (adjusted odds ratio [aOR], 1.64; 95% CI, 1.07-1.50). Patients with decompensated cirrhosis and/or hepatocellular carcinoma (HCC) were 31% less likely to receive treatment compared with those without (aOR, 0.69; 95% CI, 0.54-0.90). In this cohort study, less than two-thirds of insured patients with viremic HCV received DAA treatment, with declines in both the treatment rate and the number of viremic HCV diagnoses since 2019 and especially during the COVID-19 pandemic. Further efforts are needed to increase HCV diagnosis and treatment, especially for those with cirrhosis and HCC. An urgent call for nationwide actions to improve access to DAA treatment, community outreach programs, and specialists through referral pipelines is needed in the United States to stay on track to meet the World Health Organization goal of reducing the burden of viral hepatitis with the eventual goal to eliminate viral hepatitis.

Sustained virological response after treatment with direct antiviral agents in individuals with HIV and hepatitis C co-infection.

Randomized trials and observational studies have consistently reported rates of sustained virological response (SVR), equivalent to hepatitis C virus (HCV) cure, as high as 95% following treatment with direct-acting antiviral (DAA) treatment in individuals with HIV and HCV co-infection. However, large studies assessing whether SVR rates differ according to demographic and clinical strata are lacking. Additionally, the SVR rates reported in the literature were typically computed in non-random samples of individuals with available post-DAA HCV-RNA measures. Here, we aimed to estimate the probability of SVR after DAA treatment initiation in persons with HIV and HCV co-infection overall and by demographic and clinical characteristics with and without adjustment for missing HCV-RNA testing. We included adults with HIV-HCV co-infection who received DAA treatment between 2014 and 2020 in HepCAUSAL, an international collaboration of cohorts from Europe and North America. We estimated the proportions of DAA recipients who had documented SVR (defined as an undetectable HCV-RNA at least 12 weeks after the end of DAA treatment) overall and by strata defined by age, sex, presence of cirrhosis, calendar period, mode of HIV acquisition, CD4 cell count and HCV genotype at DAA treatment. We then compared these rates with those obtained using the parametric g-formula to impute SVR status for individuals with no SVR assessment. A total of 4527 individuals who initiated DAA treatment (88% males, median [IQR] age 56 [50, 62] years) were included. Of the total of 642 (14%) individuals had no HCV-RNA test on or after 12 weeks after the end of treatment. The overall observed and g-formula imputed SVR rates were 93% (95% CI 93, 94) and 94% (95% CI 92, 95), respectively. SVR estimates were similarly high across all strata. A substantial proportion of individuals who received DAA treatment were never assessed for SVR post-DAA and strategies for more systematic routine HCV-RNA testing should be considered. Our estimates with and without adjustment for missing HCV-RNA testing indicate SVR rates of approximately 95%, like those reported in clinical trials.

Disparities in Access to Hepatitis C Treatment Among Arizona Medicaid Beneficiaries With Chronic Hepatitis C.

High costs of direct-acting antivirals (DAAs) have led to their restricted access for patients with hepatitis C virus (HCV). The aim was to assess how HCV treatment access and predictors of HCV treatment changed in the post-DAA period compared with pre-DAA period. A retrospective cohort study using Arizona Medicaid data was conducted for patients with HCV to compare treatment initiation rates between pre-DAA (January 2008-October 2013) and post-DAA (November 2013-December 2018) periods. Multivariable logistic regression was used, controlling for demographic and clinical variables. Twenty-four thousand and ninety and 28,756 patients during the pre-DAA and post-DAA periods were identified. Overall, 12.6% were treated in the post-DAA period compared with 7.8% in the pre-DAA period ( P <0.001). The relative increase in the HCV treatment initiation rate from the pre-DAA to the post-DAA period was significant greater for Black beneficiaries compared with White beneficiaries ( P =0.002). Hispanic beneficiaries were less likely to be treated in the post-DAA period [adjusted odds ratios (aOR): 0.88; CI: 0.79-0.98] compared with White beneficiaries. Those with mental illness (aOR: 0.71; 95% CI: 0.63-0.80) and substance use disorders (aOR: 0.63; 95% CI: 0.58-0.68) were less likely to be treated in the post-DAA period. Although treatment initiation increased and disparities for Black beneficiaries compared with White beneficiaries attenuated in the post-DAA period, only 13% of Arizona Medicaid patients with HCV received DAA treatment. Disparities in DAA access remained among Hispanic patients and those with mental illness and substance use disorders.

The utility of HCV core antigen for evaluation of viremia at 48 weeks posttreatment with direct‐acting antivirals

AbstractThe hepatitis C virus core antigen (HCV‐cAg) assay is a cheap and rapid alternative to HCV‐RNA detection, while the results were limited to 12 weeks following direct‐acting antiviral (DAA) treatment. In this study we aimed to investigate the role of the HCV‐cAg assay up to 48 weeks after DAA treatment. We enrolled 98 patients with chronic HCV infection who received DAA treatment in this study. Plasma samples were assessed for HCV‐RNA (AmpliPrep/COBAS TaqMan assay, Roche) and HCV‐cAg (Abbott ARCHITECT HCV‐cAg assay) levels at baseline, 12 weeks (P12) and 48 weeks (P48) after DAA treatment. The sensitivity and specificity of HCV‐cAg were compared with those of HCV‐RNA. A total of 284 samples from 98 enrolled participants were analyzed. HCV‐cAg levels changed in parallel with HCV‐RNA levels in HCV‐infected patients during and after DAA therapy. HCV‐cAg levels showed excellent correlation with HCV viral load (R = 0.951, R2 = 0.905, β = 0.951, and P &lt; .001). The overall sensitivity and specificity for HCV‐cAg in detecting quantifiable HCV‐RNA thresholds were 96.9% and 100%, respectively. Three patients with baseline HCV viremia had nonreactive HCV‐cAg (false‐negative rate was 1.02%); none of the patients were HCV‐cAg positive and HCV‐RNA negative. At 48 weeks after DAA treatment, the HCV‐cAg assay detected all patients with viremia, demonstrating 100% sensitivity and specificity. In conclusions, the HCV‐cAg assay has high sensitivity and specificity for the detection of pre‐ and post‐DAA treatment viremia and may be a useful tool to confirm viremia at P12 and P48.

Hepatic fibrosis changes in patients with chronic hepatitis C infection who respond to direct-acting antivirals.

BACKGROUND: Clearance of hepatitis C virus (HCV) can potentially slow or reverse liver fibrosis and cirrhosis. Studies of fibrosis changes after treatment with direct-acting antivirals (DAAs) are limited.OBJECTIVES: We aimed to assess the impact of DAAs on fibrosis in HCV treatment responders.DESIGN: Retrospective cohort study.SETTING: Tertiary care centers.PATIENTS AND METHODS: This study included adult patients who received DAA treatment for HCV (naïve and experienced) from June 2015 to January 2019 who were treatment responders. Biochemical and hematological data and noninvasive fibrosis markers were recorded at baseline and follow-up.MAIN OUTCOME MEASURES: Aspartate aminotransferase/platelet ratio index (APRI), fibrosis-4 score (FIB-4) and liver stiffness measurements (LSM) at baseline and follow-up.SAMPLE SIZE AND CHARACTERISTICS: 172 HCV treatment responders, mean (SD) age 54.1 (14.1) and body mass index 28.8 (6.5) kg/m2 at baseline; 96 (55.8%) were females.RESULTS: Fifty-eight (33.7%) patients were HCV treatment-experienced. Most patients were genotype 4 (n=125, 73%) and the mean follow-up was 141 (57.9) weeks. Compared with baseline, changes in alanine aminotransferase (P<.001), aspartate aminotransferase (P<.001), and albumin (P=.01) were statistically significant. Changes in LSM (15.09 kPa [11.4] vs. 10.19 kPa [7.4], P<.001), APRI (0.81 [0.7] vs. 0.34 [0.2], P<.001), and FIB-4 (1.99 [1.4) vs.1.35 [0.9], P<.001), and AST/ALT ratio (0.86 [0.32] vs. 0.95 [0.41], P=.015) were statistically significant. Differences in many of the same parameters were statistically significant between patients with low fibrosis (F0-F1) (n=59, 34.3%) and significant fibrosis (≥F2) (n=113, 65.7%).CONCLUSIONS: Our findings confirm that clearance of HCV with DAAs is associated with significant improvement in fibrosis as assessed by noninvasive liver fibrosis measures, which supports the concept of post-treatment fibrosis regression. Long follow-up studies are needed to assess the impact on morbidity and mortality.LIMITATIONS: Absence of histological correlation with these noninvasive scores. No assessment of fibrosis changes based on HCV geno-type or treatment regimen.CONFLICT OF INTEREST: None.

Hepatitis B Reactivation in Patients Treated with Direct-Acting Antivirals for Hepatitis C

Introduction: There is limited research about HBV reactivation (HBVr) due to direct-acting antivirals (DAA) for HCV and most are limited by short duration of follow-up, small sample size, and absence of baseline HBV DNA. We aimed to determine the incidence and clinical course of HBVr in HBsAg and/or anti-HBcIgG positive patients treated with DAA for HCV. Methods: Seven centers retrospectively analyzed their database on HCV patients treated with DAA between 2015 and 2019. Patients with HBV coinfection or resolved HBV infection were enrolled. Serum transaminases, HBsAg, HBeAg, and HBV DNA were followed every 4 weeks during DAA treatment and every 12 weeks 1 year after treatment. Entecavir or tenofovir disoproxil fumarate was started in case of HBVr. The development of HBVr, HBV flare, liver failure, and mortality were determined. Results: 852 patients received DAA treatment for HCV. Among them, 35 (4.1%) had HBV coinfection and 246 (28.9%) had resolved HBV infection. 257 patients (53.3% male, mean age: 63 ± 9) constituted the study group (29 with coinfection and 228 with resolved infection). Three patients with coinfection were HBV DNA positive. HBVr developed in 10 (34.5%) HBsAg positive patients, either during (n = 3) or 12–48 weeks after finishing DAA treatment. HBV flare and acute liver failure developed in 1 patient (3.4%), each. Two patients with resolved infection developed HBVr (0.87%) and one (0.44%) had HBV flare. Overall, none of the patients died or underwent liver transplantation due to HBVr. Conclusion: Patients with HBV/HCV coinfection have a high risk of HBVr after DAA treatment and should receive antiviral prophylaxis. Patients with resolved infection have a low risk of HBVr and can be monitored by serial ALT measurements.

Hepatitis C Virus Treatment Response to Direct-acting Antivirals Among Adolescents With HIV/HCV Coinfection: Real-world Data From Ukraine.

Direct-acting antivirals (DAAs) have been approved for treating chronic hepatitis C virus (HCV) in children and adolescents. Although DAAs have been used in real-world settings for the treatment of HCV monoinfected adolescents, few reports of real-world use of DAAs in children and adolescents who are coinfected with human immunodeficiency virus (HIV) are available. We evaluated the real-world safety and effectiveness of DAAs in HIV/HCV coinfected adolescents from the Ukraine Paediatric HIV Cohort Study including all those for whom treatment outcomes were available by April 2021. Overall, 6 coinfected adolescents had received DAA treatment; 4 with sofosbuvir/ledipasvir (SOF/LDV), 1 with SOF/LDV+ribavirin, and 1 with SOF/daclatasvir. No patient discontinued treatment due to adverse events and no serious adverse events were reported. All 6 patients achieved sustained virologic response by 12 weeks after the end of therapy. DAA treatment was well tolerated and effective in adolescents with HIV/HCV coinfection in a real-world setting.

Brief Report: HCV Universal Test-and-Treat With Direct Acting Antivirals for Prisoners With or Without HIV: A Prison Health Care Workers-Led Model for HCV Microelimination in Thailand.

This study investigated the sustained virologic responses (SVRs) among prisoners with hepatitis C virus (HCV) using universal test-and-treat approach by prison health care workers in a central male prison in Thailand. A universal HCV screening was conducted in a maximum-security central prison (Klong Prem Central Prison) in Thailand. HCV RNA-confirmed prisoners were treated with generic sofosbuvir/velpatasvir by prison health care workers, regardless of their HCV genotypes and duration of prison sentences. We evaluated the SVR rates at 12 weeks after completing direct acting antivirals (DAA) treatment. A total of 68 prisoners with detectable HCV RNA received DAA treatment. The median age and duration of prison sentences were 44 years (interquartile range, 41-53) and 25 (interquartile range, 19-33) years, respectively. Twenty-five percentage of the participants was coinfected with HIV, and 6% of the participants was coinfected with hepatitis B virus. Among all prisoners who received DAA treatment, 20 (29%) had genotype (GT)-1a, 3 (4%) had GT-1b, 22 (32%) had GT-3a, 3 (4%) had GT-3b, and 7 (10%) had GT-6. Overall, improvements in liver biomarkers were seen after HCV treatment, and SVR was achieved in 97% of the participants with per-protocol analysis and in 90% of the participants with intention-to-treat analysis. HCV treatment using DAA among prisoners through universal test-and-treat approach led by prison health care workers is highly effective and safe, and such model can potentially help to facilitate the goals of HCV microelimination among prisoners in Thailand.

Role of PNPLA3 in the Assessment and Monitoring of Hepatic Steatosis and Fibrosis in Patients with Chronic Hepatitis C Infection Who Achieved a Sustained Virologic Response.

Background and Objectives: Hepatic diseases are an important public health problem. All patients with chronic hepatitis C virus (HCV) infection receive treatment, regardless of hepatic fibrosis severity. However, evaluation of hepatic fibrosis and steatosis is still useful in assessing evolution, prognosis and monitoring of hepatic disease, especially after treatment with direct-acting antivirals (DAAs). The aim of this study was to assess the link between patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphism and the degree of hepatic steatosis and fibrosis in patients with chronic HCV infection, as well as changes in steatosis and fibrosis three monthsafter obtaining a sustained viral response (SVR). Materials and Methods:Ourstudy included 100 patients with chronic hepatitis C (CHC) infection and compensated cirrhosis who received DAA treatment and who were evaluated using Fibromax prior to and 3 months after SVR. The influence of PNPLA3 (CC, CG, GG) genotype among these patients on the degree of post-treatment regression of steatosis and fibrosis was assessed. Results: Regression was noticed in the degree of both hepatic steatosis and hepatic fibrosis post-DAA treatment (three months after SVR). Analysis of the correlation between PNPLA3 genotype and fibrosis indicated that the average level of fibrosis (F) before DAA treatment was higher in patients with the GG genotype than in patients with the CC or CG genotype. Three months after SVR, the average level of fibrosis decreased; however, it remained significantly increased in GG subjects compared to that in CC or CG patients. The degree of hepatic steatosis before treatment was not significantly different among patients with different PNPLA3 genotypes, and no significant correlations were observed three months after SVR. Conclusions: The genetic variants of PNPLA3 influence the evolution of hepatic fibrosis. The GG subtype plays an important role in the degree of hepatic fibrosis both before and after treatment (three months after SVR)and could be a prognostic marker for assessment of post-SVR evolution.

Clinical and Financial Implications of 2 Treatment Strategies for Donor-derived Hepatitis C Infections.

Background.Transplanting hepatitis C viremic donor organs into hepatitis C virus (HCV)-negative recipients is becoming increasingly common; however, practices for posttransplant direct-acting antiviral (DAA) treatment vary widely. Protracted insurance authorization processes for DAA therapy often lead to treatment delays.Methods.At our institution, 2 strategies for providing DAA therapy to HCV– recipients of HCV+ transplants have been used. For thoracic organ recipients, an institution-subsidized course of initial therapy was provided to ensure an early treatment initiation date. For abdominal organ recipients, insurance approval for DAA coverage was sought once viremia developed, and treatment was initiated only once the insurance-authorized supply of drug was received. To evaluate the clinical impact of these 2 strategies, we retrospectively collected data pertaining to the timing of DAA initiation, duration of recipient viremia, and monetary costs incurred by patients and the institution for patients managed under these 2 DAA coverage strategies.Results.One hundred fifty-two transplants were performed using HCV viremic donor organs. Eighty-nine patients received DAA treatment without subsidy, and 62 received DAA treatment with subsidy. One patient who never developed viremia posttransplant received no treatment. Subsidizing the initial course enabled earlier treatment initiation (median, 4 d [interquartile range (IQR), 2–7] vs 10 [IQR, 8–13]; P < 0.001) and shorter duration of viremia (median, 16 d [IQR, 12–29] vs 36 [IQR, 30–47]; P < 0.001). Institutional costs averaged $9173 per subsidized patient and $168 per nonsubsidized patient. Three needlestick exposures occurred in caregivers of viremic patients.Conclusions.Recipients and their caregivers stand to benefit from earlier DAA treatment initiation; however, institutional costs to subsidize DAA therapy before insurance authorization are substantial. Insurance authorization processes for DAAs should be revised to accommodate this unique patient group.

Hepatitis C treatment outcomes among patients treated in co-located primary care and addiction treatment settings

BackgroundPersons with substance use disorders face major barriers to hepatitis C virus (HCV) treatment. Co-location of addiction and HCV treatment is appealing, yet there are limited data on outcomes using this model. This study evaluated HCV outcomes of patients treated with direct-acting antivirals (DAAs) by primary care providers in two sites of co-located addiction/HCV care. MethodsThe study conducted a retrospective chart review for all patients receiving DAA treatment from 2016 to 2018 at 1) a hospital-based primary care clinic with an office-based buprenorphine program, and 2) a primary care clinic within an opioid treatment program (i.e. methadone clinic). The study classified patients into 3 groups according to treatment status: buprenorphine maintenance, methadone maintenance, or neither. Descriptive analyses compared patient demographics, clinical characteristics, adherence to monitoring and treatment, and the primary outcome of sustained virologic response at 12 weeks (SVR12), defined as an undetectable HCV viral load at least 12 weeks after completing treatment. ResultsThis study included 50 patients who initiated DAA treatment. The majority of patients were unemployed (74.0%), did not smoke tobacco (54.0%), and had psychiatric comorbidities (80.0%). Many also experienced homelessness during treatment (22.0%) and experienced previous incarceration (36.0%). Only a few had recently injected drugs (4.0%). Seven of 7 (100%) patients were treated with buprenorphine, 21 of 24 (87.5%) patients were treated with methadone, and 17 of 19 (89.5%) patients receiving no opioid addiction treatment fully completed HCV DAA treatment. When including patients with missing SVR12 data with the cohort that did not achieve cure, we observe that 44 of 50 patients (88.0%) achieved SVR12. Excluding patients missing SVR12 data, we observed that 44 of 46 patients (95.7%) achieved SVR12. ConclusionPersons with substance use disorders treated with DAAs in co-located primary care and addiction treatment settings can achieve high rates of cure despite significant comorbidities and barriers. DAA treatment should be expanded to co-located HCV and addiction settings.

Clinical impact of direct-acting antiviral treatment on patients with hepatitis C virus–related oral lichen planus

<h3>Objectives</h3> Oral lichen planus (OLP) is a chronic inflammatory mucocutaneous disease. It has been related to hepatitis C virus (HCV) infection as one of the extrahepatic pathologic manifestations. The current treatment for HCV infection with direct-acting antivirals (DAAs) is highly effective and safe. This study aimed to evaluate the impact of HCV eradication on OLP clinical manifestations. <h3>Methods</h3> Patients with a histologic diagnosis of OLP and HCV chronic infection were recruited from the oral medicine and internal medicine units of the University of Campania "Luigi Vanvitelli." All patients received DAA treatment and were monitored at baseline and during and after treatment for liver function and antiviral response. Patients underwent an oral clinical examination before receiving DAAs (T0) and 8 weeks after the end of treatment (T1), and they were observed periodically in follow-up (FU). Statistical analysis was performed using Mann-Whitney and Wilcoxon tests, chi-square tests, and Fisher exact tests. <h3>Results</h3> Eighteen patients (13 females and 5 males; median age, 75 years) with chronic HCV infection of different genotypes were enrolled. All patients cleared HCV RNA with a sustained virologic response at FU. No adverse events were reported. The median FU was 92 weeks at T2. At T0, 5 patients presented with reticular and bilateral white lesions; 7 patients presented with erosive OLP; and 6 patients presented with a mixed form. The mean percentages of oral sites involved were 30% (±13.9) at T0, 20.8% (±12.9) at T1, and 16.2% (±15.2) at T2, showing improvement from T0 to T1 (<i>P</i> = .007) and T2 (<i>P</i> = .005). One patient developed oral cancer during the treatment and was excluded. Oral lesions have improved in 9 cases (52.9%) at T1 and in 10 cases (55.6%) at FU (T2); among these, 6 (60%) showed complete remission. However, statistical analysis did not reveal a significant correlation between oral improvement and HCV genotype (<i>P</i> = .64), viral load (<i>P</i> = .27), liver status (<i>P</i> = .60), isolated HBcAb positivity (<i>P</i> = .633), and type of DAA received (<i>P</i> = .103). <h3>Conclusions</h3> DAA treatment leading to HCV eradication can improve OLP symptoms. However, a causative relationship between HCV infection and OLP pathogenesis is difficult to establish. Further studies are necessary.

Clinical course of hepatitis C virus-positive patients with decompensated liver cirrhosis in the era of direct-acting antiviral treatment.

The aim of the present study was to investigate the clinical course in hepatitis C virus (HCV)-positive patients with decompensated liver cirrhosis after direct-acting antivirals (DAAs) have been used for HCV infection. This multicenter study prospectively analyzed a registered cohort composed of 73 HCV-positive patients with decompensated cirrhosis who attended our 11 institutions between January 2018 and July 2018. Prognoses, including changes in the liver reserve, hepatocellular carcinoma (HCC), decompensation events, and survival, were analyzed up to July 2020, as was the initiation of DAA treatment. Sixty-four (87.7%) and nine (12.3%) patients had Child-Pugh class (C-P) B and C at baseline, respectively. Within 2years after enrollment, 17 patients (23.3%) received treatment with DAAs, and 31 patients (42.5%) developed uncontrolled HCC, switched to palliative care, or died. Patients who received DAA treatment were significantly younger and had significantly higher alanine aminotransferase levels and lower platelet counts than the patients who did not receive DAA treatment. The rates of overall survival, cumulative HCC occurrence, and cumulative hospitalization for any hepatic decompensation event at 2years were 64.8%, 13.1%, and 65.6%, respectively. Overall survival was significantly shorter and the HCC occurrence and hospitalization rates were significantly higher in C-P C patients than in C-P B patients. Among HCV-positive patients with decompensated cirrhosis, approximately one-fourth received DAA treatment, but more than 40% of the patients lost the opportunity for treatment with DAAs.

Screening for hepatitis C in an outpatient endoscopy unit.

The Canadian Liver Foundation recommends routine hepatitis C (HCV) screening for Canadians born between 1945 and 1975. This study aimed to determine the feasibility and outcomes of targeted birth cohort HCV screening during routine outpatient endoscopic procedures in a tertiary care hospital. We conducted a prospective cohort study of individuals born between 1945 and 1975 who attended outpatient endoscopy procedures at Kingston Health Sciences Centre from 2017 to 2019. Patients who consented received the HCV OraSure point-of-care test for the HCV antibody (HCV Ab). If positive, serum for HCV RNA was sent, and patients were linked to care with a hepatologist. 2,179 patients met birth cohort criteria for HCV screening. Of those, 1,079 (49.5%) were approached for study inclusion, and 160 (15.0%) declined participation, leaving 912 patients who provided consent. The median age was 62 years (IQR 55-67). Overall, 6/912 (0.7%) of participants were HCV Ab positive and 5/912 (0.6%) were HCV RNA positive. Four were linked to care for consideration of direct-acting antiviral (DAA) therapy, 3 received DAA treatment, and all 3 achieved sustained virologic response (SVR). Birth cohort screening for HCV in an outpatient endoscopy unit identified an HCV prevalence similar to population estimates. In this model, however, 50% of eligible patients were not approached for screening. Linkage to care for assessment of treatment was high at 80%, and of those who received therapy, all achieved SVR. These results suggest this cohort is a suitable population for HCV screening; however, we need strategies to increase recruitment of all eligible individuals.

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.

S3266 Treatment of Hepatitis C Virus Infection in Patients With Cancer in the Era of Direct Acting Antivirals: An Indonesian National Cancer Center Experience

INTRODUCTION: The decision to start direct-acting antivirals (DAA) treatment in HCV infected patients with cancer has been largely influenced by the cancer treatment plan and clinical judgment. The aim of this current study was to explore the practice of HCV treatment with DAA in “Dharmais” hospital, the Indonesian National Cancer Center. METHODS: Medical records of HCV infected patients with cancer who received DAA treatment between January 2016 and April 2020, were retrospectively analyzed. RESULTS: A total of 15 HCV infected patients with cancer that were treated with DAA, were included in this study. Of 15 patients, 1 had HCC, 13 had solid cancer other than HCC, and 1 had hematological cancer. HCV was diagnosed before chemotherapy in 14 patients with non-HCC malignancy. Liver cirrhosis was diagnosed in six patients. Two patients received ledipasvir and sofosbuvir, while thirteen patients received daclatasvir and sofosbuvir. Undetectable viral load at 12-week follow-up (SVR12) was achieved in seven patients. Of 8 patients who did not achieve SVR, six patients died due to progression of primary cancer, two patients died due to deterioration of liver function before the end of DAA treatment. One patient, who achieved SVR 12, died one year after DAA treatment due to primary cancer. CONCLUSION: Prognosis of primary cancer and patients’ life expectancy should be determined before starting DAA treatment. Further study should be done to explore the benefits of DAA in HCV patients with cancer.

Persistent augmentation of central arterial stiffness following viral clearance by direct-acting antivirals in chronic hepatitis C.

Chronic hepatitis C virus (HCV) infection is associated with risk of cardiovascular diseases. Although direct-acting antivirals (DAA) result in rapid eradication of HCV, their long-term impact on arterial stiffness remains unclear. This study aimed to evaluate changes in parameters of central arterial stiffness from pretreatment, through sustained virological response, to one year after viral clearance. Patients with chronic HCV receiving DAA treatment were enrolled prospectively. Medical history and comorbidities of all patients were collected. Lipid profiles, liver stiffness by transient elastography and central blood pressures using pulse wave analysis of the brachial artery by cuff sphygmomanometry were measured before treatment, at viral clearance and at one year following viral clearance. Augmentation index (AIx), a parameter of aortic stiffness, was calculated as the ratio of augmentation pressure to central pulse pressure. After DAA treatment, all included patients with chronic HCV (n=102) had achieved viral clearance. Cholesterol, low-density lipoprotein (LDL) and triglyceride/high-density lipoprotein (TG/HDL) increased significantly at viral clearance and persisted at one year (all P<.001). AIx was also elevated significantly at viral clearance and persisted one year later (P<.001). Changes in AIx remained significant only in patients with increased values from baseline in either LDL (P<.01) or TG/HDL (P<.001). Central arterial stiffness and lipid profiles in patients with chronic HCV worsen immediately after viral eradication by DAA treatment and persist at one year. Worsening of lipid profiles after DAA treatment contributes to central arterial stiffness in this patient population and persists long term.

Lipid profile changes after direct acting antiviral treatment in different genotypes of chronic hepatitis C virus‐infected patients

AbstractThe fact that chronic hepatitis C (CHC) virus interacts with serum lipid metabolism is well‐known, and previous studies have demonstrated that hepatitis C virus (HCV) eradication using direct acting antivirals (DAAs) or interferon‐based therapy, can cause lipid levels to increase during treatment. The current study focused on HCV patients with different genotypes who had a sustained virological response (SVR); their lipid levels and metabolism changes after DAA treatment were investigated. The current study retrospectively included 394 patients who received DAAs treatment for CHC with SVR in Liouying Chi‐Mei Medical Center. Patients who accepted lipid‐lowering therapy within 6 months prior to the start of DAA treatment were excluded. The patient's lipid profiles and homeostasis model assessment‐insulin resistance (HOMA‐IR) index were measured and evaluated at baseline and after 12 weeks of treatment. The SVR rate was 96.2% across all patients. The mean triglyceride level was not significantly increased after SVR. The mean total cholesterol level was significantly increased from baseline 165.2 ± 33.6 mg/dL to after SVR 184.5 ± 36.0 mg/dL (P &lt; .0001). The mean high‐density lipoprotein cholesterol (HDLC) was significantly increased from baseline level 45.9 ± 12.3 mg/dL to after SVR 49.0 ± 12.4 mg/dL (P &lt; .0001). The mean low‐density lipoprotein cholesterol (LDLC) was significantly increased from baseline 95.2 ± 28.3 mg/dL to after SVR 111.7 ± 31.3 (P &lt; .0001). The HOMA‐IR had no significant change in the 294 patients without diabetes. The subgroups analysis of genotypes 1a, 1b, 2, and 6 revealed a significant increase in total cholesterol and LDLC levels following treatment. In conclusion, it was found that lipid profiles, including total cholesterol, HDLC, and LDLC levels, were significantly increased after DAA treatment for CHC patients who achieved SVR 12 with genotypes 1a, 1b, 2, and 6.