Direct-acting Antiviral Agent Treatment Research Articles

Angiopoietin-2 as a Predictor of Fibrosis Regression in Hepatitis C Virus-Patients after Direct Acting Antiviral Drugs

Abstract Background HCV infection is a major health concern. Disease progression to fibrosis, cirrhosis, and HCC is aided by the persistence of inflammatory reactions and cellular damage. Moreover, angiogenesis was found to have a substantial pathogenic role in disease progression. Serum Angiopoietin-2 appears to be correlated with liver stiffness in chronic HCV and its elevation is linked to disease progression from chronic hepatitis to cirrhosis. Aim of the Work The aim of this study was to evaluate the role of serum Angiopoietin-2 in the prediction of regression of fibrosis in chronic HCV patients receiving direct-acting antiviral agents. Patients and Methods Forty Egyptian chronic HCV patients for whom direct-acting antiviral agent (DAA) therapy was planned were included. All patients underwent assessment twice, at baseline and at SVR12, for standard laboratory tests, measurement of fibrosis using FibroScan, FIB-4 and APRI scores, and Angiopoietin-2 level. Results Among 40 patients; 26 (65%) are males and 14 (35%) are females. Their age is ranged between 35 and 60 years old with a mean age of 52.35 ± 6.08 and a median of 53.0 (50.0 – 57.0). The HCV-RNA titer is ranged from 3.60 to 7.20 log IU/mL with a mean titer of 5.99 ± 0.87 before treatment. The median is 6.20 (5.30 – 6.65). There was a significant improvement concerning the fibrosis stage after DAA treatment. Liver fibrosis indices were significantly associated with regression of liver fibrosis stage based on FibroScan data after DAA therapy. Liver size, spleen size and portal vein diameter were improved significantly after successful HCV eradication by DAAs. There was improvement in the Child-Pugh score after successful HCV eradication by DAAs but the difference was no statistically significant (p = 0.500). Baseline Ang-2 was statistically significant after successful HCV eradication by DAAs (p < 0.001). Overall, there was a positive significant correlation between Ang-2 and all the fibrosis stages (p = 0.001) and there was a statistically significant higher mean of Ang-2 in higher stages of liver fibrosis before treatment. Indeed Ang-2 increase significantly when the fibrosis stage increased and vice-versa before treatment. Ang-2 in higher stages of liver fibrosis after treatment. Indeed Ang-2 increase significantly when the fibrosis stage increased and vice-versa after treatment. The correlation between Ang-2 and fibrosis group (F0, F1, F2 & F3) were significant and the correlation between Ang-2 and the liver fibrosis stage (F4) were also significant before treatment. The correlations between Ang-2 levels and fibrosis group (F0, F1, F2 & F3) were significant as well as the advanced liver fibrosis (F4) after DAA therapy. Conclusion Angiopoietin-2 can be a useful predictor of fbrosis regression in chronic HCV patients receiving direct acting antiviral agents. Elevated baseline Angiopoietin-2 and advanced ibrosis stages may predict non-regression of liver fibrosis.

Natural History and Management of Hepatitis C in Children: 25 Years Experience of a Reference Center in Northern Italy.

Hepatitis C virus (HCV) infection natural history and management in the pediatric population are still debated. We retrospectively evaluated the outcome of a HCV pediatric population managed at the Pediatric Infectious Disease Unit of Luigi Sacco Hospital (Milan, Italy) from January 1997 to January 2022 (median follow-up 10 years) and we focused on the role of new drugs and transient elastography. Fifty-seven patients were enrolled: 8 (14%) had a spontaneous clearance, 33 were treated (58%), 7 (12%) were not treated because they were under 12 years old and 9 were lost at follow-up. HCV RNA was undetectable in all treated patients at the end of therapy, after 12 weeks (SVR12) and for the rest of their follow-up. All patients treated underwent elastography before and 1 year after therapy. Median stiffness pretherapy was 5.6 kPa, and 9 patients (16%) had abnormal transient elastography (>7 kPa, median 8.7 kPa). Median stiffness after treatment in the abnormal group was 6.8 kPa. Direct-acting antiviral agents are a safe and effective therapy for HCV chronic infection in the pediatric population. Liver elastography is normal in many vertically infected children before 12 years, but, when abnormal, it shows a significant improvement after direct-acting antiviral agent treatment. Further studies are needed to evaluate the role of elastography at diagnosis and follow-up in children.

Chimeric antigen receptor T-cell therapy after COVID-19 in refractory high-grade B-cell lymphoma

Although chimeric antigen receptor T-cell (CAR-T) therapies have dramatically improved the outcomes of relapsed/refractory B-cell malignancies, recipients suffer from severe humoral immunodeficiencies. Furthermore, patients with coronavirus disease 2019 (COVID-19) have a poor prognosis, as noted in several case reports of recipients who had COVID-19 before the infusion. We report the case of a 70-year-old woman who developed COVID-19 immediately before CAR-T therapy for high-grade B-cell lymphoma. She received Tixagevimab−Cilgavimab chemotherapy and radiation therapy but never achieved remission. She was transferred to our hospital for CAR-T therapy, but developed COVID-19. Her symptoms were mild and she was treated with long-term molnupiravir. On day 28 post-infection, lymphodepleting chemotherapy was restarted after a negative polymerase chain reaction (PCR) test was confirmed. The patient did not experience recurrence of COVID-19 symptoms or severe cytokine release syndrome. Based on the analysis and comparison of the previous reports with this case, we believe that CAR-T therapy should be postponed until a negative PCR test is confirmed. In addition, Tixagevimab−Cilgavimab and long term direct-acting antiviral agent treatment can be effective prophylaxis for severe COVID-19 and shortening the duration of infection.

Change in intraperitoneal shunt after DAA treatment for hepatitis C

Improvement and worsening of portal hypertension after direct acting antiviral agent (DAA) treatment for hepatitis C virus-related cirrhosis have been reported, and a consensus remains elusive. In this study, we underscored on the intraperitoneal shunt formed via portal hypertension and examined how the shunt system confirmed by computed tomography (CT) changes before and after treatment in cases in which sustained virological response (SVR) was attained with DAAs. Of the cases in which we achieved an SVR of 24 with DAA treatment for hepatitis C virus-related cirrhosis at our hospital, 83 cases in which CT images were taken before and after treatment were investigated. If the intraperitoneal shunt diameter changed by 20% or more, it was analyzed as an increase or decrease. In 29 patients, intraperitoneal shunt enlargement was noted. When examining factors related to the increase, multivariate analysis detected the FIB4 index at the end of the DAA treatment. Conversely, only four cases were observed in which the size decreased. At the end of treatment, the FIB4 index was the most important factor in increasing the intraperitoneal shunt after DAA treatment for hepatitis C virus-related cirrhosis, and fibrosis was believed to be an influencing factor.

Next-generation sequencing analysis of hepatitis C virus resistance-associated substitutions in direct-acting antiviral failure in South Korea.

We used next-generation sequencing (NGS) to analyze resistance-associated substitutions (RASs) and retreatment outcomes in patients with chronic hepatitis C virus (HCV) infection who failed direct-acting antiviral agent (DAA) treatment in South Korea. Using prospectively collected data from the Korean HCV cohort study, we recruited 36 patients who failed DAA treatment in 10 centers between 2007 and 2020; 29 blood samples were available from 24 patients. RASs were analyzed using NGS. RASs were analyzed for 13 patients with genotype 1b, 10 with genotype 2, and one with genotype 3a. The unsuccessful DAA regimens were daclatasvir+asunaprevir (n=11), sofosbuvir+ribavirin (n=9), ledipasvir/sofosbuvir (n=3), and glecaprevir/pibrentasvir (n=1). In the patients with genotype 1b, NS3, NS5A, and NS5B RASs were detected in eight, seven, and seven of 10 patients at baseline and in four, six, and two of six patients after DAA failure, respectively. Among the 10 patients with genotype 2, the only baseline RAS was NS3 Y56F, which was detected in one patient. NS5A F28C was detected after DAA failure in a patient with genotype 2 infection who was erroneously treated with daclatasvir+asunaprevir. After retreatment, 16 patients had a 100% sustained virological response rate. NS3 and NS5A RASs were commonly present at baseline, and there was an increasing trend of NS5A RASs after failed DAA treatment in genotype 1b. However, RASs were rarely present in patients with genotype 2 who were treated with sofosbuvir+ribavirin. Despite baseline or treatment-emergent RASs, retreatment with pan-genotypic DAA was highly successful in Korea, so we encourage active retreatment after unsuccessful DAA treatment.

Resistant-Associated Substitutions Do Not Affect HCV RNA and HCV Core Antigen Clearance During Direct-Acting Antiviral Agent Treatment in a Real-World Setting.

BackgroundSince oral direct-acting antiviral agents (DAAs) became available, the global hepatitis C treatment situation has undergone tremendous changes. However there are still many issues worthy of attention in treatment.MethodsWe selected 53 HCV-infected patients who were treated and followed up in the Peking University First Hospital from December 2017 to January 2021 to detect the RASs in HCV. Pearson correlation analysis was used to analyze HCV RNA and HCV cAg, the Fisher exact test and chi-square test was used to compare the effects of RASs on the rate of decline of HCV RNA and HCV core antigen (cAg) during DAA treatment.ResultsThe RASs and its prevalence on the NS3 are mainly Y56F 2.56% (1/39), Q80K 23.08% (9/39), S122G 71.79% (28/39), and V170I 38.46% (15/39). On the NS5A were R30Q 10.53% (4/38), P32A 5.26% (2/38), P58S 2.63% (1/39), and Y93H 21.05% (8/38). On NS5B were C316N 71.05% (27/38), C451H 2.63% (1/38), and I585C 2.63% (1/38). There was no significant correlation between the RASs (Y93H, V179I, Q80K, S122G, C316N) and HCV genotype (p > 0.05). The baseline serum HCV RNA and HCV cAg had a significant medium-degree correlation (r = 0.601, p = 0.002). After 1 week of DAA treatment was weak correlation (r = 0.413, p = 0.032). Q80K, S122G, V170I, Y93H, and C316N had no effect on the clearance of HCV RNA and HCV cAg within the first week of DAA treatment (p>0.05).ConclusionThe HCV genotype may have a limited impact on the presence of the five RASs (Y93H, V179I, Q80K, S122G, and C316N) as shown in this study. HCV RNA and HCV cAg have a correlation, especially at baseline is the highest; the appearance of some RASs has no effect on DAA treatment in most chronic hepatitis C patients.

Successful treatment of hepatitis C genotype 4 using sofosbuvir, daclatasvir, simeprevir and ribavirin in Egyptian patients with direct-acting antiviral agent treatment failure.

IntroductionIn chronic hepatitis C virus (HCV) patients in whom prior direct-acting antiviral agent (DAA) treatment had failed, outcomes after retreatment are optimal. Combination of sofosbuvir (SOF), daclatasvir (DCV), simeprevir (SIM), and ribavirin (RBV) in treatment experienced patients is recommended in current guidelines despite insufficient data. Our aim is to determine the efficacy and safety of SOF, DCV, SIM plus RBV in HCV infected patients who failed prior DAA treatment.Material and methodsOne hundred and seventeen patients who failed to respond to SOF containing regimens were randomized according to previous response to therapy to non-responders and relapsers. Duration of therapy depends on fibrosis stages. SOF, DCV, SIM and weight based RBV 12 weeks for F1 and F2 (group I) and 24 weeks for F3 and F4 (group II).ResultsIn the non-responder group, a sustained virologic response (SVR) occurred in 100% in group I (F1 and F2) and 97% in group II (F3 and F4). Relapse was 3% in group II (F3 and F4). No patients from either group had breakthrough or non-response. In relapsers SVR was 100% in group I (F1 and F2) and 96% in group II (F3 and F4). Breakthrough, relapse and non-response were 2%, 4%, 2% respectively only in group II (F3 and F4).ConclusionsCombining multiple DAAs with different viral targets may be effective treatment protocol in previous non-responders and relapsers with short durations of treatment.

Angiopoietin-2 as a predictor of fibrosis regression in chronic hepatitis C virus patients after direct-acting antiviral drugs

BackgroundHCV infection is a major health concern. Disease progression to fibrosis, cirrhosis, and HCC is aided by the persistence of inflammatory reactions and cellular damage. Moreover, angiogenesis was found to have a substantial pathogenic role in disease progression. Serum Angiopoietin-2 appears to be correlated with liver stiffness in chronic HCV and its elevation is linked to disease progression from chronic hepatitis to cirrhosis. The aim of this study was to evaluate the role of serum Angiopoietin-2 in the prediction of regression of fibrosis in chronic HCV patients receiving direct-acting antiviral agents. Forty Egyptian chronic HCV patients for whom direct-acting antiviral agent (DAA) therapy was planned were included. All patients underwent assessment twice, at baseline and at SVR12, for standard laboratory tests, measurement of fibrosis using FibroScan, FIB-4 and APRI scores, and Angiopoietin-2 level.ResultsStatistically significantly higher levels of baseline Ang-2 were detected with the progression of fibrosis stages with a p-value of <0.001. The best cutoff value of baseline Ang-2 in discrimination of liver cirrhosis (F4) from F0-F3 was > 630 pg/ml with 85.71% sensitivity and 84.85% specificity. A statistically significant decline of Ang-2 (from 464.3±237.2 pg/ml to 401.3±277.1 pg/ml) was noted after the achievement of SVR12 with a p-value < 0.001. Regression of liver fibrosis in this study is defined as a decrease of more than or equal to one stage in liver fibrosis. Lower baseline fibrosis stages and other non-invasive scoring systems (FIB-4 and APRI scores) were associated with regression of fibrosis following successful DAAs treatment. However, higher baseline Ang-2 levels were significantly associated with non-regression of fibrosis, and at a cutoff of >680 pg/ml, it might predict non-regression of fibrosis after successful eradication of HCV with DAAs with 93.33% sensitivity and 70% specificity.ConclusionsAngiopoietin-2 can be a useful predictor of fibrosis regression in chronic HCV patients receiving direct-acting antiviral agents. Elevated baseline Angiopoietin-2 and advanced fibrosis stages may predict non-regression of liver fibrosis.

A Novel Standard for Hepatocellular Carcinoma Screening Intensity After Hepatitis C Elimination.

PurposeTo investigate long-term incidence of hepatocellular carcinoma (HCC) and the factors associated with HCC occurrence after achieving sustained virological response (SVR) by direct-acting antiviral agent (DAA) treatment for hepatitis C virus (HCV).MethodsA total of 476 patients (male 227, female 249; median age 68) with chronic HCV infection who were treated with DAAs and achieved SVR were analyzed. The incidence of HCC and factors related to the development of HCC after HCV elimination were evaluated.ResultsThe median observation period was 46.4 months. During this period, 40 patients developed HCC. The incidence rates of HCC were 3.7%, 6.0%, 7.1%, 9.3%, and 10.6% at 1, 2, 3, 4, and 5 years post-SVR12, respectively. Multivariate analysis with pre-treatment factors revealed that platelet count, α-fetoprotein, fibrosis-4 (Fib-4) index, and previous HCC history were independent factors that contributed to development of HCC post-SVR following DAA treatment. Of these factors, previous HCC history was the most significant, followed by Fib-4 index. Using these two factors, a novel scoring system was established. The presence of previous HCC history was scored as 2, and then, the absence of previous HCC history was stratified by Fib-4 index (≥3.07, 1; <3.07, 0). The HCC occurrence rate at 5 years was 0.4% in the 0-point group, 6.8% in the 1-point group, and 55.6% in the 2-point group, respectively.ConclusionFib-4 index and previous HCC history were independent predictors for development of HCC after DAA treatment. Patients with these risk factors require careful observation.

A nurse-led, telehealth-driven hepatitis C management initiative in regional Victoria: Cascade of care from referral to cure

Introduction Elimination of hepatitis C virus stands as an unresolved World Health Organization target, and is associated with complications including cirrhosis and hepatocellular carcinoma. Hepatitis C virus management has been revolutionised following the widespread availability of direct-acting antiviral agents in Australia since 2016; however, large proportions of the population remain untreated. Telehealth-based service delivery is an accessible and effective alternative, and we aimed to assess qualitative and clinical outcomes in a clinical nurse consultant-led regional telehealth model. Methods A prospective cohort analysis of all patients referred to a Victorian regional hospital’s hepatitis C virus telehealth clinic between 1 April 2017 and 10 June 2020 was conducted. Data were collated from outpatient and electronic medical records. Results Fifty-five out of 71 referred patients were booked, with 44 patients (80%) attending at least one appointment. A history of alcohol use disorder and psychiatric comorbidity was seen in 25 (54%) and 24 (52%) patients, respectively. Twenty-one out of 24 (88%) eligible patients had direct-acting antiviral agent treatment and 14 out of 21 (67%) successfully completed the treatment. An average of 46.5 km, 54.6 min and $AUD30.70 was saved per patient for each visit. Observed benefits included: increased medical engagement, adherence to and completion of HCV treatment and cirrhosis monitoring. Telehealth-driven hepatocellular carcinoma surveillance was successful in the cirrhotic subgroup. Conclusion Clinical nurse consultant-led hepatitis C virus management via telehealth allows access to marginalised regional populations. Clinical outcomes were comparable to other cohorts with additional cost-benefit, efficiency gains and carbon footprint reduction amongst a previously unreported regional Victorian hepatitis C virus population.

Hypozincemia in Chronic Hepatitis C Is Improved with Viral Clearance by Direct-acting Antiviral Agents.

Objective Hypozincemia is a decrease in the serum zinc level of patients with hepatitis C and often requires zinc supplementation to improve the hepatic function. Our previous study showed the efficacy of direct-acting antiviral agent (DAA) treatment on serum zinc levels in patients with hepatitis C without zinc supplementation. In this study, we aimed to prospectively examine factors related to the improvement of serum zinc levels of patents with hepatitis C with DAA treatment. Methods Fifty-three patients with hepatitis C treated with DAAs between March 2018 and February 2019 at a university medical center were divided into two groups based on their initial serum level: the zinc deficiency group (n=43, <80 μg/dL) and the normal zinc group (n=10, ≥80 μg/dL). Their serum zinc levels and clinical parameters were measured before DAA treatment, at the end of treatment and 12 weeks post-treatment. Results All 53 patients achieved a sustained viral response to DAAs at the end of treatment and at follow-up. There was a significant increase in the serum zinc level from baseline to follow-up in the zinc deficiency group but not in the normal zinc group. The change in serum albumin was the only factor contributing to the observed increase in serum zinc levels by a multiple regression analysis. Conclusion DAA treatment in patients with hepatitis C improved hypozincemia due to the restored function of serum albumin, which binds to about 60% of serum zinc, upon the amelioration of the hepatitis C infection.

Survey of Clinician Opinions on Kidney Transplantation from Hepatitis C Virus Positive Donors: Identifying and Overcoming Barriers.

Transplant practices related to use of organs from Hepatitis C virus infected donors (DHCV+) is evolving rapidly. We surveyed U.S. kidney transplant programs by email and professional society listserv postings between 7/19-1/20 to assess attitudes, management strategies, and barriers related to use of viremic (nucleic acid testing (NAT)+) donor organs in HCV uninfected recipients. Staff at 112 unique programs responded, representing 54% of U.S. adult kidney transplant programs and 69% of adult deceased donor kidney transplant volume in 2019. Most survey respondents were transplant nephrologists (46%) or surgeons (43%). Among responding programs, 67% currently transplant DHCV antibody+/NAT- organs under a clinical protocol or as standard of care. By comparison, only 58% offer DHCV NAT+ kidney transplant to HCV- recipients, including 35% under clinical protocols, 14% as standard of care, and 9% under research protocols. Following transplant of DHCV NAT+ organs to uninfected recipients, 53% start direct acting antiviral agent (DAA) therapy after discharge and documented viremia. Viral monitoring protocols after DHCV NAT+ to HCV uninfected recipient kidney transplantation varied substantially. 56% of programs performing these transplants report having an institutional plan to provide DAA treatment if declined by the recipient's insurance. Respondents felt a mean decrease in waiting time of ≥18 months (range 0-60) justifies the practice. Program concerns related to use of DHCV NAT+ kidneys include insurance coverage concerns (72%), cost (60%), and perceived risk of transmitting resistant infection (44%). Addressing knowledge about safety and logistical/financial barriers related to use of DHCV NAT+ kidney transplantation for HCV uninfected recipients may help reduced discards and expand the organ supply.

Heart Transplant Using Hepatitis C-Seropositive and Viremic Organs in Seronegative Recipients.

BackgroundHepatitis C virus (HCV)-seropositive donor hearts are underutilized for orthotopic heart transplantation (OHT). The advancement of direct-acting antiviral agent (DAA) treatment for HCV makes utilizing HCV-seropositive and viremic donor organs in HCV-seronegative recipients a possibility.Material/MethodsFrom 1997 to 2019, adult patients who underwent OHT at our institution were retrospectively reviewed. Ten HCV-seronegative patients received HCV-seropositive donor hearts, 3 of which tested nucleic acid-positive. Kaplan-Meier curves were performed for survival analyses. This study was approved by the Institutional Review Board.ResultsRecipient median age was 57.5 years old, and 2 (20%) were female. Donor median age was 42 years old, and 3 (30%) were female. One donor was cured from HCV with DAA prior to OHT. Four recipients developed hepatitis C viremia immediately after OHT. DAA treatment was completed in 3 recipients who demonstrated cure. Thirty-day and 1-year survival rates were both 80%.ConclusionsWe describe 10 HCV-seronegative patients who received HCV-seropositive donor hearts at our institution, with excellent short-term outcomes, even in those who received nucleic acid testing positive organs. DAA can be effective in treating hepatitis C viremia before and after OHT, with excellent recipient survival. Large clinical studies are needed to further evaluate the long-term outcomes of DAA therapy in patients after heart transplantation.

Real-world effectiveness of glecaprevir/pibrentasvir and ledipasvir/sofosbuvir for mixed genotype hepatitis C infection: A multicenter pooled analysis in Taiwan.

Data on direct-acting antiviral agent (DAA) treatment for mixed genotype hepatitis C virus (HCV) infection are scant. This study examined the effectiveness of glecaprevir/pibrentasvir (GLE/PIB) and ledipasvir/sofosbuvir (LDV/SOF) for mixed HCV genotype infection in a real-world setting in Taiwan. We analysed the data from all patients with mixed HCV genotype infections treated with GLE/PIB or LDV/SOF from 2017 to 2019 in three Chang Gung Memorial Hospitals in Taiwan. The primary treatment outcome was sustained virologic response 12weeks after treatment cessation (SVR12). Adverse events (AEs) were also evaluated. A total of 5190 HCV patients received DAA treatment during this time period. Among them, 116 patients (2.2%) had mixed infections of any 2 or 3 genotypes of 1a, 1b, 2, 3 and 6. Fifty-four patients received GLE/PIB and 62 received LDV/SOF. SVR12 rates for LDV/SOF vs GLE/PIB therapy were 96.6% (56/58) vs 100% (51/51) by the per-protocol analysis and 90.3% (56/62) vs 94.4% (51/54) by the evaluable population analysis. Two patients with 1b+6 and 1b+2 genotype infections in the LDV/SOF group had relapse. Evaluating the GLE/PIB vs LDV/SOF groups for the most common AEs revealed pruritus (16.7% vs 4.8%), abdominal discomfort (5.6% vs 8%) and fatigue (5.6% vs 4.8%). One patient with AE-related treatment discontinuation presented with liver decompensation after 4-week GLE/PIB therapy. DAA-related significant laboratory abnormalities occurred in two patients with >3× elevated bilirubin level in the GLE/PIB group. GLE/PIB and LDV/SOF are well tolerated and achieve high SVR12 rates for patients with mixed HCV genotype infection.

Direct-acting antiviral agents do not increase the incidence of hepatocellular carcinoma development: a prospective, multicenter study

While achieving sustained virological response (SVR) following interferon-based or direct-acting antiviral agent (DAA) treatments reduces the incidence of hepatocellular carcinoma (HCC), an increase in unexpected early occurrence or recurrence of HCC after hepatitis C virus elimination by DAA treatments has been reported. We prospectively investigated the incidence and risk factors of HCC after DAA treatment in a large multicenter cohort in Japan. Patients with chronic hepatitis C with or without cirrhosis who were treated with DAAs and obtained SVR were enrolled. DAAs were administered for 3 or 6months. A total of 2552 patients were enrolled. Of these, 70 patients (2.7%) developed HCC. The 12-, 24-, and 36-month cumulative HCC incidences were 1.3%, 2.9%, and 4.9% in all patients; 2.5%, 5.2%, and 10.0% in those with cirrhosis; and 0.9%, 2.1%, and 2.9% in those without cirrhosis, respectively. Multivariate analysis revealed age, sex, gamma-glutamyl transpeptidase level, and fibrosis-4 index to be independent factors associated with HCC. Patients with these four factors had an approximately six-to-sevenfold increased risk for HCC development. Five patients with large and early tumor occurrence did not receive contrast imaging examinations before treatment. Although the results of our prospective study suggested that achieving SVR by DAA treatment reduces the incidence of HCC, HCC development still occurs. Careful follow-up is important in patients with risk factors.

Thailand practice guideline for management of chronic hepatitis C 2018

Chronic hepatitis C is one of the important cause of chronic liver diseases leading to cirrhosis and hepatocellular carcinoma worldwide. The prevalence of chronic hepatitis C in Thailand is about 1 - 5% where the prevalence is higher in the north and northeastern. Treatment of chronic hepatitis C has been developed and markedly improved in the last 3 decades. Since the advanced development of direct acting antiviral agent (DAA), treatment of chronic hepatitis C has been much improved not only in the efficacy but also tolerability and safety. IFN-free DAA treatment become a standard therapy in many country including Thailand. Due to fast development of HCV treatment strategies, Thailand Association for the Study of the Liver Disease has recurrently developed practice guideline for management of chronic hepatitis C in order to practically guide and to significantly improve HCV treatment in Thailand. The article reveals the detail of Thailand practice guideline for management of chronic hepatitis C 2018

Favouring modulation of circulating lipoproteins and lipid loading capacity by direct antiviral agents grazoprevir/elbasvir or ledipasvir/sofosbuvir treatment against chronic HCV infection

ObjectiveLipid homoeostasis is disturbed in patients with HCV infection. Direct-acting antiviral agent (DAA) treatment eradicates chronic HCV viraemia, but the dynamics of lipid components remain elusive. This study investigates the...

Factors Associated with Improved Glycemic Control by Direct-Acting Antiviral Agent Treatment in Egyptian Type 2 Diabetes Mellitus Patients with Chronic Hepatitis C Genotype 4.

BackgroundThe association of chronic hepatitis C virus (HCV) infection with type 2 diabetes mellitus (T2DM) was first reported in 1994. Little is known about the effect of direct-acting antiviral agents (DAAs) on glycemic control in T2DM patients. The aim of the present study was to evaluate the factors associated with improved glycemic control (IGC) by DAA treatment in Egyptian T2DM patients with chronic HCV genotype 4 infection.MethodsThis study included 460 T2DM patients with chronic HCV genotype 4 infection. Four hundred patients received DAAs and 60 patients did not receive DAAs. Patients with sustained virological response after 3 months of DAAs (378 patients) were allocated into two groups: first group included 292 patients (77.2%) with IGC and second group included 86 patients (22.8%) with non-improved glycemic control (NIGC).ResultsIn IGC group, 78 patients (26.7%) needed to decrease the dose of antidiabetic treatment. There were no significant differences between IGC and NIGC groups as regards age, sex, and body mass index. The percentage of patients with positive family history of T2DM, those with Child B class and duration of T2DM were significantly higher in NIGC group compared to IGC.ConclusionDiabetic patients receiving DAAs should be closely monitored for reduction of antidiabetic drugs especially insulin and sulfonylurea to avoid hypoglycemic events. Improvement of glycemic control with DAAs is more in patients without family history of T2DM, short duration of diabetes mellitus, and mild liver disease.

Second Generation Direct-Acting Antiviral Agents Eradicate Hepatitis C Virus (HCV) but Exacerbate Thrombocytopenia in a Patient with HCV-Associated Immune Thrombocytopenic Purpura (ITP): Case Report

BackgroundLymphotropism of HCV induces chronic immune stimulation, facilitating production of wide variety of autoantibodies, leading to HCV driven autoimmunity. Immune thrombocytopenic purpura (ITP) is one of extra hepatic manifestations of autoimmune diseases in HCV infection.The treatment landscape of hepatitis C virus infection has been dramatically altered in 2013 with the approvals of the second-generation protease inhibitor simeprevir and the nucleotide polymerase inhibitor sofosbuvir. In most patients treated with the direct-acting antiviral agent (DAA), HCV RNA became undetectable.However a little is known about how DAA therapy affects autoimmune diseases associated with HCV, especially in ITP. Cessation of immune stimulation by HCV following the treatment may alter immune responses and may modify autoimmune diseases.We report here a case of acute exacerbation of ITP following DAA treatment. DAA therapy appears to precipitate acute exacerbation of thrombocytopenia and ITP became refractory to all treatments including the measures that used to induce remission prior to DAA treatment.Case reportA 67-year-old man was diagnosed chronic HCV infection, genotype 1b, in 1997. He failed treatment with Interferons. Chronic active hepatitis subsequently progressed into cirrhosis with portal hypertension. His ITP required frequent treatments with Prednisone and IVIG. It became severe in early 2013. His platelet counts were low at 10,000. He responded well to high dose Prednisone but could not continue because of worsening diabetes. He also failed Rituxan. He received multiple treatments including eltrombopag and romiplostin which he did not respond well to. His ITP finally stabilized with monthly infusion of WinRho as maintenance therapy with platelet counts hovering around 40.000 for 6 months.In March 2014, he was started on HCV treatment with simeprevir, sofosbuvir and ribavirin. His baseline platelet count prior to the new treatment was in the 50000’s. It plummeted to below 10.000 two weeks into treatment. He developed multiple ecchymosis and blood blisters in the mouth. He completed his HCV treatment on June 3, 2014. His viral load was no longer detectable.However, ITP remained refractory and severe with platelet counts around 10,000. High dose Prednisone or WinRho which had been effective in raising platelet counts previously were no longer effective after DAA therapy. During this acute exacerbation of ITP, he was treated with IVIG 3 times a week and low dose Prednisone and NPlate weekly with increasing dosage. He developed frequent blood blisters in mouth and gum bleeding requiring emergency room visits and hospitalization where he received platelet transfusions along with IVIGG and high dose Prednisone. His hemoglobin was stable throughout. IVIGG was reduced to 2 times a week. At 8 weeks following completion of DAAs, his platelet count improved to 40.000s range without clinical sign of bleeding.DiscussionIt has been shown that the frequency of B-cell production of anti- GPIIb-IIIa antibody, an antibody against the major platelet surface autoantigen (BP IIb-IIIa) recognized by anti-platelet antibodies in patients with idiopathic thrombocytopenic purpura (ITP), was greater in HCV-ITP (9). An inverse correlation was found between platelet count and B-cell anti–GPIIb-IIIa Ab production in 51 patients with liver cirrhosis (73% with hepatitis C).In our patient, ITP was stable with maintenance infusion of WinRho for 6 months. Acute exacerbation of ITP 2 weeks into DAA therapy suggests that it was triggered by the DAAs. Thrombocytopenia is a well-recognized complication of interferon therapy for treatment of viral hepatitis. Simeprevir and sofosbuvir however, are not well known to affect the platelet count.A little is known on effect of DAAs on thrombocytopenia. Immune alteration following eradication of HCV and subsequent modification of autoimmunity could affect course of ITP associated with HCV infection. Meanwhile, it is important for physicians and patients to be aware of potentially dangerous complications of these second generation DAAs. DisclosuresNo relevant conflicts of interest to declare.