High Sustained Virological Response Research Articles

Addition of neutrophil-to-lymphocyte ratio to Pre-DAA FIB-4 does not increase prediction value for de novo liver complications in hepatitis C

Background and aimsDirect-acting antiviral agents (DAAs) achieve high sustained virologic response (SVR) in chronic hepatitis C patients; yet a proportion of patients still experience de novo liver complications after SVR. Identification of risk factors is clinically important. FIB-4 index is a useful noninvasive tool to assess fibrosis, while neutrophil-to-lymphocyte ratio (NLR) is a biomarker for systemic inflammation. Our study aimed to investigate whether the addition of NLR can increase the prediction power of pre-DAA FIB-4 for de novo liver complications after SVR. MethodsWe recruited patients via The Taiwan HCV Registry (TACR) and National Health Insurance Registry Database. The inclusion criteria were patients who achieved SVR12 after DAA and were followed for at least 24 months after SVR12. Liver complications included ascites, hepatic encephalopathy, variceal bleeding, and HCC. ResultsTotally 7657 patients were recruited from 2013 to 2018. Among them, 3674 patients (48.0%) had a FIB-4 value > 3.25 and 491 patients (6.4%) had a NLR >4 before DAA. After two-year of follow-up after SVR 12, 214 patients (2.8%) developed de novo liver complications. Factors associated with liver complications included male gender, diabetes mellitus, hyperlipidemia, chronic kidney disease, and pre-DAA FIB-4 >3.25 in multivariate analyses. Addition of NLR slightly did not increase the power of predicting liver complications. ConclusionsThe overall incidence of de novo liver complications after SVR is low during short-term follow-up. Elevated pre-DAA FIB-4 is associated with de novo liver complications after SVR, whereas the addition of pre-DAA NLR does not increase the prediction power.

Assessing the Efficacy of Novel Antiviral Therapies in Treating Hepatitis C.

Hepatitis C virus (HCV) infection is a major global health burden, with an estimated 58 million people chronically infected worldwide, according to the World Health Organization (WHO).While many people remain asymptomatic during the early stages of infection, chronic hepatitis C can cause long-term liver damage, significantly increasing the morbidity and mortality associated with the disease. The primary objective of this technical report is to find the efficacy of novel antiviral therapies in treating hepatitis C in a tertiary care hospital in Lahore. This technical report was done in Shalamar Hospital, Lahore, from June 2023 to June 2024. Data for the report were collected retrospectively from 500 patients through a review of patient medical records from the hospital. Medical and electronic health records provided the patient demographics (age, gender, ethnicity), hepatitis C genotype, liver disease stage (fibrosis or cirrhosis staging), previous treatment history, and type of antiviral therapy administered (direct-acting antivirals (DAA)).Out of 500, there were 280 (56%) male and 220 (44%) female patients. The mean age of the patients was 41.23±5.67 years. Patients were divided among mild, advanced, and post-liver transplant as 320 (64%), 150 (30%), and 30 (6%), respectively.Among the DAA regimens, sofosbuvir-based therapies had the highest sustained virologic response (SVR) rate of 95%, followed by glecaprevir/pibrentasvir at 93%. Ledipasvir/sofosbuvir and other DAAs showed slightly lower SVR rates, at 89% and 87%, respectively, indicating high overall efficacy across different therapies. This report concluded that DAAsare highly effective in treating hepatitis C, with an overall SVR rate of 92% and good tolerability across most patient groups. However, patients with genotype III, advanced liver disease, or post-liver transplant status may require personalized treatment approaches due to slightly lower efficacy.

Reduction of the Risk of Hepatocellular Carcinoma over Time Using Direct-Acting Antivirals: A Propensity Score Analysis of a Real-Life Cohort (PITER HCV).

The treatment of hepatitis C virus (HCV) with direct-acting antivirals (DAA) leads to high sustained virological response (SVR) rates, but hepatocellular carcinoma (HCC) risk persists in people with advanced liver disease even after SVR. We weighted the HCC risk in people with cirrhosis achieving HCV eradication through DAA treatment and compared it with untreated participants in the multicenter prospective Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. Propensity matching with inverse probability weighting was used to compare DAA-treated and untreated HCV-infected participants with liver cirrhosis. Kaplan-Meier analysis and competing risk regression analysis were performed. Within the first 36 months, 30 de novo HCC cases occurred in the untreated group (n = 307), with a weighted incidence rate of 0.34% (95%CI: 0.23-0.52%), compared to 63 cases among SVR patients (n = 1111), with an incidence rate of 0.20% (95%CI: 0.16-0.26%). The 12-, 24-, and 36-month HCC weighted cumulative incidence rates were 6.7%, 8.4%, and 10.0% in untreated cases and 2.3%, 4.5%, and 7.0% in the SVR group. Considering death or liver transplantation as competing events, the untreated group showed a 64% higher risk of HCC incidence compared to SVR patients (SubHR 1.64, 95%CI: 1.02-2.62). Other variables independently associated with the HCC occurrence were male sex, increasing age, current alcohol use, HCV genotype 3, platelet count ≤ 120,000/µL, and albumin ≤ 3.5 g/dL. In real-life practice, the high efficacy of DAA in achieving SVR is translated into high effectiveness in reducing the HCC incidence risk.

Effect of treatment periods on efficacy of glecaprevir and pibrentasvir in chronic hepatitis C: A nationwide, prospective, multicenter study.

In patients with chronic hepatitis C, 8 weeks of glecaprevir and pibrentasvir (GLE/PIB) treatment for chronic hepatitis (non-cirrhosis) and 12 weeks for cirrhosis have been approved in Japan. However, whether 8 weeks of treatment for cirrhosis may reduce treatment efficacy has not been adequately investigated. This prospective, nationwide, multicenter cohort study enrolled 1275 patients with chronic hepatitis C who received GLE/PIB therapy. The effect of liver fibrosis and treatment periods on the efficiency of GLE/PIB therapy was investigated. The primary endpoint was the sustained virological response (SVR) rate in patients with chronic hepatitis (non-cirrhosis) and cirrhosis. The association between treatment periods and liver fibrosis on the SVR after 12 weeks of treatment rate was investigated. The SVR rates in patients with chronic hepatitis with 8 weeks of treatment, chronic hepatitis with 12 weeks of treatment, cirrhosis with 8 weeks of treatment, and cirrhosis with 12 weeks of treatment were 98.9% (800/809), 100% (87/87), 100% (166/166), and 99.1% (211/213), respectively, and were was not different among these groups (P = 0.4). GLE/PIB therapy for chronic hepatitis C had high efficacy regardless of liver fibrosis status and treatment periods. Periods of GLE/PIB therapy could be chosen with available modalities, and high SVR rates could be achieved regardless of the decision.

Beyond genotype-4: Direct-acting antiviral agents in patients with chronic hepatitis C infection from the Eastern Province of Saudi Arabia.

Direct-acting antiviral agents (DAAs) have revolutionized the treatment of patients with chronic hepatitis C virus (HCV) infection, resulting in a high sustained virologic response (SVR) rate. However, the published data from the Eastern Province of Saudi Arabia are limited to small patient groups and specific DAAs used for patients with genotype-4.(GT-4). This study aimed to investigate the effectiveness and safety of DAAs for treating HCV infection in Saudi Arabia in a real-life setting. This retrospective study from January 2015 to December 2019 included all HCV-infected patients who received DAAs at a tertiary university hospital in Saudi Arabia. Baseline characteristics and laboratory data were collected from health records, including HCV RNA level, genotype, and presence of liver cirrhosis or steatosis. The primary outcome was undetectable HCV RNA at 12 weeks posttreatment (SVR12). Results were stratified based on different DAAs and HCV genotypes. Treatment-related adverse events were recorded. Statistical analyses were performed using SPSS version 25.0. Of the 117 patients included, 43.2% had advanced fibrosis or cirrhosis, and the majority (90.6%) were treatment-naïve. The mean age was 50.1 ± 15.5 years, with 57.3% females. The most common genotype was GT-4 (44.4%), followed by GT-1 (40.2%). Most patients (64.3%) received sofosbuvir and daclatasvir ± ribavirin, while the remaining patients received various DAAs. Overall, 98.3% of the patients achieved SVR12. The therapy was well tolerated, with fatigue and headache being the most common side effects. Treatment with DAAs is highly effective across different genotypes and various DDA regimens in the real world for treating HCV infection in the Eastern Province of Saudi Arabia, contributing to improved patient outcomes and the overall goal of HCV elimination.

The effect of direct-acting antivirals (DAA) on confirmed noninvasive fibrous parameters in chronic hepatitis C patients

Aims: Chronic hepatitis C (CHC) is an important public health problem in terms of the number of people it affects worldwide and the diseases it causes. The high sustained virological response (SVR) rates achieved by the use of direct-acting antiviral (DAA) drugs in the recent period have shown that a new era has begun in this disease. It was aimed to evaluate the effect of DAAs on confirmed noninvasive fibrous parameters together with their effectiveness.
 Methods: 75 patients who were started on DAA treatment for CHC were included in the study. In addition, laboratory parameters values at the beginning of the treatment, 12 and 24 weeks after the end of the treatment, hepatitis C virus ribonucleic acid (HCV RNA) results and Aminotransferase-to-Platelet Ratio Index (APRI), Fibrosis-4 (FIB-4) scores were compared.
 Results: The most common comorbidity in patients is hypertension (HT), and the most common source of transmission is surgical operations. Genotype 1b was the dominant genotype. The SVR rates of all patients 12 and 24 weeks after the end of treatment were 100%. The APRI and FIB-4 scores of the patients decreased significantly at the 12th and 24th weeks at the end of the treatment compared to the beginning of the treatment.
 Conclusion: The confirmed noninvasive fibrous parameters used in the treatment of CHC are useful in evaluating the results of the treatments applied.

ESTIMATION OF PREVALENCE OF HEPATITIS C VIRUS INFECTION BY SEROLOGICAL TEST AND REAL TIME RT-PCR TEST AMONG SUSPECTED VIRAL HEPATITIS CASES ATTENDING TERTIARY CARE HOSPITAL, KOLKATA

Objective: Hepatitis C virus (HCV) infection is a major public health problem in India and worldwide. Majority remain asymptomatic until they develop serious complications like liver cirrhosis or hepatocellular carcinoma with fatal outcome. Hence, early diagnosis of active HCV infection and prompt initiation of treatment is important. Treatment with directly acting antivirals (DAAs) resulted in high sustained virological response (SVR) rates of >95% globally. This study was done to estimate seroprevalence and prevalence of active HCV infection among study population. After initiation of treatment, SVR rates were estimated. Methods: This was hospital-based, cross-sectional, and observational study. Screening was done by third-generation Enzyme-linked immunosorbent assay to detect anti-HCV antibody, then confirmatory real-time reverse transcription-polymerase chain reaction (RT-PCR) test was done for detection of active cases and determining their viral load. Treatment of 12-week duration was initiated by DAAs and followed up to estimate SVR by doing real-time RT-PCR after 12 weeks of treatment completion. Result: Among 17,752 consecutive non-repetitive blood samples, seroprevalence was 1.78%. The prevalence of active cases was 1.52%. HCV active infection was prevalent more among male (64.21%) and among 40–60 years age group. History of multiple blood transfusion (58%) was the most common risk factor, followed by multiple sex partners (13.3%). Coinfections with Hepatitis B virus and Human immunodeficiency virus were seen in 13.65% of cases. About 92% of patients completed their treatment. SVR was 97.87%. Conclusion: High SVR of 97.87% is evidence-based data that support that proper treatment can eliminate HCV infection. Detection by real-time RT-PCR and highly effective DAA has made a paradigm shift to approach of HCV diagnosis and management in recent times

High sustained virologic response rates, regardless of race or socioeconomic class, in patients treated with chronic hepatitis C in community practice using a specialized pharmacy team.

Approved direct-acting antiviral (DAA) regimens against hepatitis C virus (HCV) can cure nearly all patients; however, socioeconomic disparities may impact access and outcome. This study assesses socioeconomic factors, differences in insurance coverage and the drug prior authorization process in HCV-infected patients managed in community practices partnered with a dedicated pharmacy team with expertise in liver disease. This Institutional Review Board-approved, ongoing study captures data on a cohort of 2480 patients from community practices. Patients had chronic hepatitis C and were treated with DAA regimens selected by their physician. The HCV Health Outcomes Centers Network provides comprehensive patient management including a dedicated pharmacy support team with expertise in the prior authorization process. In this cohort, 60.1% were male, 49% were Hispanic Whites (HW), 37% were Non-Hispanic Whites (NHW), and 14% were Black/African American (BAA). Eighty-seven percent of patients were treatment-naïve, 74% were infected with genotype 1 virus and 63% had advanced fibrosis/cirrhosis (F3/F4 = 68.2% HW, 65.6% BAA, 55.4% NHW). Forty percent of patients were on disability with the highest percentage in the BAA group and less than one-third were employed full time, regardless of race/ethnicity. Medicare covered 42% of BAA patients versus 32% of HW and NHW. The vast majority of HW (80%) and BAA (75%) had a median income below the median income of Texas residents. Additionally, 75% of HW and 71% of BAA had median income below the poverty level in Texas. Despite the above socioeconomic factors, 92% of all prior authorizations were approved upon first submission and patients received DAAs an average of 17 days from prescription. DAA therapy resulted in cure in 95.3% of patients (sustained virologic response = 94.8% HW, 94.0% BAA, 96.5% NHW). Despite having more advanced diseases and more negative socioeconomic factors, >94% of HW and BAA patients were cured. Continued patient education and communication with the healthcare team can lead to high adherence and > 94% HCV cure rates regardless of race/ethnicity or underlying socioeconomic factors in the community setting.

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.

Interventions for dialysis patients with hepatitis C virus (HCV) infection.

Interventions for dialysis patients with hepatitis C virus (HCV) infection.

Health Insurance and Initiation of Direct-Acting Antivirals for Hepatitis C in US Women With Human Immunodeficiency Virus.

Direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) is well tolerated, cost-effective, and yields high sustained virologic response rates, yet it has remained financially inaccessible to many patients. Participants of the Women's Interagency HIV Study (an observational US cohort) with human immunodeficiency virus (HIV) and HCV (RNA+) reporting no prior hepatitis C treatment were followed for DAA initiation (2015-2019). We estimated risk ratios (RRs) of the relationship between time-varying health insurance status and DAA initiation, adjusting for confounders with stabilized inverse probability weights. We also estimated weighted cumulative incidences of DAA initiation by health insurance status. A total of 139 women (74% Black) were included; at baseline, the median age was 55 years and 86% were insured. Most had annual household incomes ≤$18 000 (85%); advanced liver fibrosis (21%), alcohol use (45%), and recreational drug use (35%) were common. Across 439 subsequent semiannual visits, 88 women (63%) reported DAA initiation. Compared with no health insurance, health insurance increased the likelihood of reporting DAA initiation at a given visit (RR, 4.94; 95% confidence limit [CL], 1.92 to 12.8). At 2 years, the weighted cumulative incidence of DAA initiation was higher among the insured (51.2%; 95% CL, 43.3% to 60.6%) than the uninsured (3.5%; 95% CL, 0.8% to 14.6%). Accounting for clinical, behavioral, and sociodemographic factors over time, health insurance had a substantial positive effect on DAA initiation. Interventions to increase insurance coverage should be prioritized to increase HCV curative therapy uptake for persons with HIV.

Regression in hepatic fibrosis in elderly Chinese patients with hepatitis C receiving direct-acting antiviral treatment

BackgroundPatients infected with Hepatitis C virus (HCV) are recommended to receive treatment with direct-acting antiviral agents (DAAs), which have been certified to obtain a high sustained virological response (SVR). However, little is known about the benefits of successful anti-viral treatment to elderly patients with hepatic fibrosis. In this study, we aimed to assess degree of fibrosis in elderly patients with chronic hepatitis C (CHC) treated with DAAs, and to evaluate the correlations between identified factors associated with these changes.MethodsThis study retrospectively enrolled elderly patients with CHC who received DAAs in Tianjin Second People’s Hospital from April 2018 to April 2021. The degree of liver fibrosis was assessed using serum biomarkers and transient elastography (TE) expressed as the liver stiffness (LSM), while the hepatic steatosis was evaluated by controlled attenuated parameter (CAP). Changes in factors related to hepatic fibrosis were examined following treatment with DAAs, and associated prognostic factors were further evaluated.ResultsWe included 347 CHC patients in our analysis, where 127 of these were elderly patients. For the elderly group, the median LSM was 11.6 (7.9–19.9) kPa, and this value was significantly reduced to 9.7 (6.2–16.6) kPa following DAA treatment. Similarly, GPR, FIB-4 and APRI indices were significantly reduced from 0.445 (0.275–1.022), 3.072 (2.047–5.129) and 0.833 (0.430–1.540) to 0.231 (0.155–0.412), 2.100 (1.540–3.034) and 0.336 (0.235–0.528), respectively. While in younger patients, the median LSM reduced from 8.8 (6.1–16.8) kPa to 7.2 (5.3–12.4) kPa, and the trends of GPR, FIB-4 and APRI were also consistent. The CAP in younger patients increased with statistical significance, but we did not observe any significant change in CAP for the elderly group. Based on multivariate analysis, age, LSM, and CAP before baseline were identified as determinants for LSM improvement in the elderly.ConclusionIn this study, we found that elderly CHC patients treated with DAA had significantly lower LSM, GPR, FIB-4, and APRI values. DAA treatment did not significantly change CAP. Furthermore, we observed correlations between three noninvasive serological evaluation markers and LSM. Finally, age, LSM, and CAP were identified as independent predictors of fibrosis regression in elderly patients with CHC.

Efficacy and safety of ombitasvir/paritaprevir/ritonavir-based therapy in HCV patients with chronic kidney disease

Background and study aimsHepatitis C virus (HCV) prevalence inchronic kidney disease (CKD) patients is significantly higher than in the general population. This study evaluated the efficacy and safety of combined ombitasvir/paritaprevir/ritonavir-based therapy in HCV patients with renal impairment. Patients and methodsOur study included 829 patients with normal kidney functions (group 1) and 829 patients with CKD (group 2),which were subdivided into patients not requiring dialysis (group 2a) and those on hemodialysis (group2b). Patients received regimens of ombitasvir/paritaprevir/ritonavir with or without ribavirin or sofosbuvir/ombitasvir/paritaprevir/ritonavir with or without ribavirin for 12 weeks. Clinical and laboratory assessment was done before treatment, and patients were followed up for12 weeks after treatment. ResultsThe sustained virological response (SVR) at week 12 was significantly higher in group 1 than in the other three groups/subgroups, being 94.2% vs 90.2%, 90%, and 90.7%, respectively. The regimen with the highest SVR was ombitasvir/paritaprevir/ritonavir with ribavirin. The most common adverse event was anemia, which was more common in group 2. ConclusionOmbitasvir/paritaprevir/ritonavir-based therapy in chronic HCV patients with CKD is highly effective, with minimal side effects despite ribavirin-induced anemia.

Efficacy of generic sofosbuvir with daclatasvir compared to sofosbuvir/ledipasvir in genotype 4 hepatitis C virus: A prospective comparison with historical control.

Management of genotype 4 hepatitis C virus (HCV) has shifted to interferon-free regimens with a high sustained virological response (SVR-12), especially with NS5B/NS5A inhibitor combinations such as sofosbuvir and ledipasvir (Sof-Led). The guidelines have recommended the combination of sofosbuvir and another NS5A inhibitor, daclatasvir, to manage HCV genotypes 1-3. However, its use was extended to genotype 4 HCV based on extrapolating evidence. Our aim is to assess the efficacy of generic sofosbuvir + branded daclatasvir (Sof-Dac) compared to the Sof-Led combination in treating genotype 4 HCV. This study is an open-label, 2-period, noninferiority study that compared patients receiving a combination of generic sofosbuvir 400 mg and daclatasvir 60 mg orally daily (Group 2) prospectively to a historical control (Group 1) that included patients who received a combination of sofosbuvir/ledipasvir 400/90 mg orally daily. The primary endpoint is the proportion of patients who achieved SVR-12. The study included 111 patients in the (Sof-Led) Group 1 and 109 patients (Sof-Dac) Group 2. For the primary outcome, SVR-12 was achieved in 106 (95.5%) of the patients in Group 1 versus 108 (99.1%) in Group 2 (p = 0.2). In addition, all patients who achieved SVR-12 also achieved SVR-24. Generic sofosbuvir combined with branded daclatasvir was safe and effective for treating genotype 4 HCV compared to Sof-Led. This combination may significantly reduce the cost burden, enabling a larger pool of treated patients. Office of research affairs at KFSHRC RAC# 2171 036.

Sustained virological response (SVR) and safety of two direct acting anti-viral (DAA) combination therapies in Chronic Hepatitis-C infected patients of Lahore, Pakistan. A Randomized Controlled Trial

Chronic Hepatitis C (HCV) is a deadly infection affecting > 185 million people worldwide and led to liver cirrhosis, hepatocellular carcinoma, or liver failure. Recently, treatment regimens of chronic HCV have entered the era of direct acting anti-virals (DAAs). Sustained virological response (SVR) rate is one of the best available tools to evaluate the efficacy of DAA treatments. Objective: To compare SVR rate and safety of two combinations of DAA treatments (Sofosbuvir and Daclatasvir vs Sofosbuvir and Velpatasvir) in chronic HCV infected patients of Lahore, Pakistan. Methods: Present randomized controlled trial was conducted at Mayo Hospital, Lahore, Pakistan and recruited 76 chronic HCV infected patients according to Consort guidelines. Registered patients were allocated in two groups by lottery method. Group A received sofobuvir with daclatasvir (SOFO + DCV) while group B received sofobuvir with velpatasvir (SOFO + VEL) treatment for 12 weeks. Response to therapy was evaluated in terms of SVR after 24 weeks and safety profile of the drug. Results: Both treatment groups showed high SVR 24 weeks after the completion of therapy. Group A (SOFO + DCV) presented 92% SVR while group B showed 97% SVR rate. Both DAA combination therapies presented good efficacy and safety profile. Few contraindications noted during the treatment included fatigue, arthritis, headache, loss of appetite and anemia. Conclusions: The efficacy of both DAA combination therapies was comparably high with > 90% SVR rate. Group A proved safer as compared to group B. Studied DAA combinations are effective treatment options for chronic HCV treatment planning.

Prevalence and predictors of abnormal alanine aminotransferase in patients with HCV who have achieved SVR.

Chronic hepatitis C virus (HCV) is common. Treatment with direct acting antivirals (DAA) result in high sustained virologic response (SVR) associated with normalization of alanine aminotransferase (ALT). However, abnormal ALT after SVR has been observed. Since fatty liver disease can co-exist with HCV, its impact on abnormal ALT after SVR is unknown. This was a retrospective case-control analysis evaluating those with SVR and baseline fatty liver disease by transient elastography defined by controlled attenuated parameter (CAP) was performed. Abnormal ALT was defined as >1.5 ULN. The primary analysis compared abnormal ALT at SVR-12 and beyond in those with and without fatty liver disease. Six-hundred and ninety-three patients with SVR-12 were evaluated. Abnormal ALT at SVR-12 was present in 8.2% and was similar in those with and without fatty liver disease. Abnormal ALT at SVR-12 was associated with atrial fibrillation (p= .02), CAP (p= .047), age (p= .08), baseline ALT (p= .008), BMI (p= .002) and obesity (p= .02). On multivariate analysis, only BMI was associated with abnormal ALT at SVR-12 (p= .017). ALT at follow-up after SVR-12 was available in 264 patients. In those with initial normal ALT (n= 244), 11.5% had a delayed abnormal ALT and in those with initial abnormal ALT (n= 20), 47% remained abnormal while 53% normalized. Abnormal ALT after SVR following treatment with DAA is uncommon and related to increased BMI, but not related to underlying fatty liver disease assessed by CAP. The pattern of ALT can vary, and long-term follow-up is needed to assess the clinical impact of abnormal ALT after SVR.

Direct-Acting Antiviral Therapy for Hepatitis C Virus in Patients with BCLC Stage B/C Hepatocellular Carcinoma.

The benefits of hepatitis C virus (HCV)eradication for hepatocellular carcinoma (HCC) patients in Barcelona Clinic Liver Cancer (BCLC) stage B/C remain uncertain. In this hospital-based cohort study, all HCV-infected patients with BCLC stage B/C HCC during the period January 2017 to March 2021 were retrospectively screened, with 97 patients who had completed direct-acting antiviral (DAA) therapy being enrolled for final analysis. In total, the sustained virological response (SVR) rate was 90.7%. In logistic regression analysis, progressive disease (PD) to prior tumor treatments was significantly associated with SVR failure (odds ratio 5.59, 95% CI 1.30-24.06, p = 0.021). Furthermore, the overall survival (OS) rate was significantly higher in the SVR group than that in the non-SVR group (1-year OS: 87.5% vs. 57.1%, p = 0.001). SVR was found to be an independent factor related to OS (hazard ratio 8.42, 95% CI 2.93-24.19, p = 0.001). However, even upon achieving SVR, the OS rates in BCLC stage C or Child-Pugh stage B patients remained poor. In BCLC stage B/C HCC, DAA could achieve a high SVR rate except in those patients with PD to prior HCC treatments. SVR was related to improvements in OS; therefore, DAA therapy should be encouraged for patients diagnosed without a short life expectancy.

Hepatitis C Virus Infections in Patients with Hemophilia: Links, Risks and Management.

Haemophilia is a rare, hereditary bleeding disorder. Clotting factor concentrates were a revolutionary treatment which changed the life of people with haemophilia. However, early generation of clotting factor concentrates, without viral inactivation procedures in the manufacturing process, led to an increased risk of transmission of blood-borne viral infections, mainly due to hepatitis C virus and human immunodeficiency virus. As only 20% of HCV-infected patients clear the infection naturally, chronic HCV infection constitutes a serious health problem and a major cause of chronic liver disease in this group of patients. Fortunately, the use of viral inactivation procedures in the plasma-derived factor concentrates manufacturing process and the availability of alternative treatment options, led to a significant reduction of transfusion-associated viral infections. The advent of multiple, orally administrated, highly effective direct-acting antivirals (DAAs) is changing the natural history of HCV infection in patients with haemophilia as these drugs have an excellent safety profile and achieve very high sustained virological response rates, similar to the general population. Eradication of HCV-infection in patients with haemophilia is feasible via micro-elimination projects.

High sustained virologic response rate after 8 weeks of direct-acting antivirals in cancer patients with chronic hepatitis C virus.

There is no prospective data on 8 weeks of direct-acting antivirals (DAA) therapy with glecaprevir/pibrentasvir (GLE/PIB) or ledipasvir/sofosbuvir (LDV/SOF) in hepatitis C virus (HCV)-infected patients with different types of malignancies. This study evaluated the efficacy and safety with 8 weeks of DAA therapy in cancer patients with chronic HCV infection. Patients treated with DAAs at our center during 2014-2021 were included in a prospective observational study. Efficacy (sustained virologic response at 12 weeks; SVR12) and safety [adverse events and clinically significant drug-drug interactions (DDIs)] were assessed. We included 47 patients. Most were men (29; 62%), white (33; 70%), non-cirrhotic (45; 96%), and with HCV genotype 1 (38; 85%). None of the patients had HCC. The SVR12 rate was 96% (45/47; 95% CI: 86-99%) for the entire study cohort, 100% [17/17; 95% CI: 82-100%] for the patients treated with GLE/PIB and 93% [28/30; 95% CI: 79-98%] for the patients treated with LDV/SOF. Fisher's exact test showed no significant difference in SVR12 rates between the regimens (P = 0.53). No patients had serious adverse events (grade 3-4) or treatment discontinuation. Among the 17 patients who received concomitant cancer therapy, no DDIs occurred. Eight weeks of DAA therapy is highly effective and safe in HCV-infected patients with different types of malignancies and may grant access to investigational cancer therapy, broadening treatment options.

Hepatitis C treatment outcomes for Australian First Nations Peoples: equivalent SVR rate but higher rates of loss to follow-up

BackgroundFirst Nations Peoples of Australia are disproportionally affected by hepatitis C (HCV) infection. Through a prospective study we evaluated the outcome of direct-acting antiviral (DAA) therapy among First Nations Peoples with HCV infection.MethodsAdults who initiated DAA therapy at one of 26 hospitals across Australia, 2016–2019 were included in the study. Clinical data were obtained from medical records and the Pharmaceutical and Medicare Benefits Schemes. Outcomes included sustained virologic response (SVR) and loss to follow-up (LTFU). A multivariable analysis assessed factors associated with LTFU.ResultsCompared to non-Indigenous Australians (n = 3206), First Nations Peoples (n = 89) were younger (p < 0.001), morel likely to reside in most disadvantaged (p = 0.002) and in regional/remote areas (p < 0.001), and had similar liver disease severity. Medicines for mental health conditions were most commonly dispensed among First Nations Peoples (55.2% vs. 42.8%; p = 0.022). Of 2910 patients with follow-up data, both groups had high SVR rates (95.3% of First Nations Peoples vs. 93.2% of non-Indigenous patients; p = 0.51) and ‘good’ adherence (90.0% vs. 86.9%, respectively; p = 0.43). However, 28.1% of First Nations Peoples were LTFU vs. 11.2% of non-Indigenous patients (p < 0.001). Among First Nations Peoples, younger age (adj-OR = 0.93, 95% CI 0.87–0.99) and treatment initiation in 2018–2019 vs. 2016 (adj-OR = 5.14, 95% CI 1.23–21.36) predicted LTFU, while higher fibrosis score was associated with better engagement in HCV care (adj-OR = 0.71, 95% CI 0.50–0.99).ConclusionsOur data showed that First Nations Peoples have an equivalent HCV cure rate, but higher rates of LTFU. Better strategies to increase engagement of First Nations Peoples with HCV care are needed.