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Background & Aims: The sofosbuvir (SOF) / velpatasvir (VEL) / voxilaprevir (VOX) combination has been evaluated in more than 800 patients enrolled in phase II and phase III studies, where it demonstrated excellent safety and efficacy, achieving overall sustained viral response (SVR) rates of more than 95%. We aimed to assess the efficacy and safety of SOF/VEL/VOX in a real-world study, including patients previously treated for genotype 1b hepatitis C virus (HCV) infection that did not obtain a sustained viral response with previous direct-acting antivirals (DAAs) therapy. Methods: In Romania, through a nationwide government-funded program in 2019-2020, 213 patients with chronic hepatitis C non-responders to previous DAAs therapy, received treatment with SOF/VEL/VOX 400/100/100 mg/day for 12 weeks. We performed a retrospective longitudinal study that included 143 individuals who were treated in Bucharest, Iași, Craiova and Constanța clinics, all with genotype 1b HCV infection. Efficacy was assessed by the percentage of patients achieving SVR 12 weeks post-treatment (SVR12). Serious adverse events (SAE) were registered. Results: Our cohort comprised 53% males with a median age of 60 years (27÷77); 47% were pre-treated with ombitasvir/paritaprevir/ritonavir+dasabuvir ± ribavirin, 40% with ledipasvir/SOF, 13% with elbasvir/grazoprevir. 42% of patients associated co-morbidities, 45% had compensated liver cirrhosis, 2% had treated hepatocellular carcinoma (HCC) and 1% had hepatitis B virus co-infection. SVR by intention to treat was reported in 139/143 (97.2%) and per protocol in 141/143 (98.6%). No predictive factors for SVR were identified. Rate of liver decompensation in patients with cirrhosis was 6% and was statistically associated in multivariate analysis with Child-Pugh score (p<0.01) and with severe steatosis (p=0.004). Occurrence of new HCC was reported in 3.6% of all patients with cirrhosis and was associated with poor liver function [higher Child-Pugh score (p=0.001) and low albumin levels (p=0.02)]. Serious adverse events related to therapy were reported in 1/143(0.7%). Conclusions: SOF/VEL/VOX was highly efficient in our population of patients with a 97.2% SVR. Liver decompensation occurred in 6% of cirrhotic patients at SVR, related to hepatic dysfunction. [ABSTRACT FROM AUTHOR]

Background and Aims: We assessed the clinical and economic impact of direct‐acting antiviral (DAA) therapy for hepatitis C virus (HCV) in England, Italy, Romania and Spain. Methods: An HCV progression Markov model was developed considering DAA eligibility and population data during the years 2015‐2019. The period of time to recover the investment in DAAs was calculated as the cost saved by avoiding estimated clinical events for 1000 standardized treated patients. A delayed treatment scenario because of coronavirus disease (COVID‐19) was also developed. Results: The estimated number of avoided hepatocellular carcinoma, decompensated cirrhosis and liver transplantations over a 20‐year time horizon was: 1,057 in England; 1,221 in Italy; 1,211 in Romania; and 1,103 in Spain for patients treated during 2015‐2016 and 640 in England; 626 in Italy; 739 in Romania; and 643 in Spain for patients treated during 2017‐2019. The cost‐savings ranged from € 45 to € 275 million. The investment needed to expand access to DAAs in 2015‐2019 is estimated to be recovered in 6.5 years in England; 5.4 years in Italy; 6.7 years in Romania; and 4.5 years in Spain. A delay in treatment because of COVID‐19 will increase liver mortality in all countries. Conclusion: Direct‐acting antivirals have significant clinical benefits and can bring substantial cost‐savings over the next 20 years, reaching a Break‐even point in a short period of time. When pursuing an exit strategy from strict lockdown measures for COVID‐19, providing DAAs should remain high on the list of priorities in order to maintain HCV elimination efforts. [ABSTRACT FROM AUTHOR]

A case study is presented on the prevalence of hepatitis B and C virus infections in the Roma population in Romania, highlighting higher infection rates in this group compared to the general population and the importance of screening. However, itraises concerns about the limited sample size and lack of a clear methodology in the study, questioning its representativeness for the broader Roma population.

Background & Aims: Elimination of hepatitis C worldwide is more feasible if micro-elimination screening strategies are adopted. We aimed to screen hepatitis C virus (HCV) in specific high-risk populations in certain sub-regions of Romania and link them to antiviral treatment. Methods: A multicenter prospective study was conducted among the hospitalized or ambulatory adult patients from March 2019 to March 2020 in more than 20 medical institutions from 4 Romanian cities (Bucharest, Iasi, Timisoara, Cluj-Napoca). A rapid diagnostic test for HCV diagnosis was performed to all admitted patients and the positive ones were sent to gastroenterology departments for confirming the active infection, staging and treatment prescription. Results: In total, 25,141 subjects signed the informed consent and were consequently enrolled into the study. The prevalence of anti-HCV antibodies was 1.39% (95%CI: 1.25-1.54) and increased with the number of risk factors presented by one subject. There was a positive association between the presence of anti-HCV antibodies and female gender (p<0.001), rural area of residence (p<0.001), advanced age (p<0.001), as well as a negative association with the education level (p<0.001). Conclusions: In a hospital-based screening micro-elimination program in Romania, HCV prevalence was lower than previously reported. This is a first step towards a cost-effective screening in a well-defined group of persons at risk and provides sufficient capacity to deliver access to HCV treatment and linkage to care in Romania. [ABSTRACT FROM AUTHOR]

Abstract: Background: Direct antiviral agents (DAA) showed very good results in terms of efficacy and safety in clinical trials, but real‐life data are still needed in order to confirm this profile. Material and methods: In Romania, through a nationwide government‐funded programme in 2015‐2016, approx.5800 patients with virus C cirrhosis received fully reimbursed DAA therapy with OBV/PTV/r+DSV+RBV for 12 weeks. We analysed a national prospective cohort enrolling the first 2070 patients, all with genotype 1b. The only key inclusion criteria was advanced fibrosis (Metavir stage F4) confirmed by Fibromax testing (or liver biopsy/Fibroscan). Efficacy was assessed by the percentage of patients achieving SVR 12 weeks post‐treatment (SVR12). Results: Forty patients stopped the treatment because of hepatic decompensation (1.9%), 21 stopped because of other adverse events and one was lost to follow‐up. This cohort was 51% females, mean age 60 years (25÷82), 67% pretreated, 70% associated NASH, 67% with severe necro‐inflammation (severity score 3‐Fibromax), 37% with comorbidities, 10.4% with Child Pugh A6, 0.5% B7. The median MELD score was 8.09 (6 ÷ 22). SVR by intention‐to‐treat was reported in 1999/2070(96.6%), 55/2070 failed to respond. Liver decompensation was statistically associated in multivariate analysis with platelets< 105/mm3(P = .03), increased total bilirubin (P < .001), prolonged INR (P = .02), and albumin<3.5 g/dL (P = .03). Conclusions: OBV/PTV/r+DSV+RBV proved to be highly efficient in our population of cirrhotics with a 96.6% SVR. Serious adverse events related to therapy were reported in 61/2070(2.9%), most of them liver decompensation (1.9%), related to hepatic dysfunction, and lower platelet count. [ABSTRACT FROM AUTHOR]

Background & Aims: Hepatitis C virus (HCV) infection is a common condition with endemic prevalence in some areas of the world. In Romania, the mean prevalence is about 3%. New treatments have become available on the market in recent years and new drugs are in the pipeline. A re-evaluation of HCV therapy was considered mandatory. The Romanian Society of Gastroenterology and Hepatology undertook this task for the practitioners of this country. Methodology: A group of recognized experts was created who screened the available literature and the major available guidelines. A list of items requiring attention was created and these were discussed and rated. Decisions were taken by consensus. Recommendations: We present here the second part of the Society's recommendations for chronic HCV infection treatment. An agreement between experts was reached regarding the therapy of the special categories of patients infected with HCV, complications and monitoring of the therapy, follow-up of the patients who reached sustained virologic response and re-treatment of the patients with therapy failure. Conclusions: This Position Paper represents a guide for the assessment and the therapy of HCV infection. The recommendations are in concordance with other guidelines but are applied to real-life conditions in Romania. [ABSTRACT FROM AUTHOR]

Background & Aims: Hepatitis C Virus (HCV) infection is a common condition with endemic prevalence in some areas of the world. In Romania, the mean prevalence is about 3%. New treatments became available on the market in recent years and new drugs are in the pipeline. A re-evaluation of HCV therapy was considered mandatory. The Romanian Society of Gastroenterology and Hepatology undertook this task for the practitioners of this country. Methodology: A group of recognized experts was created who screened the available literature and the major available guidelines. A list of items requiring attention has been created. These items were discussed and rated. Decisions were taken by consensus. Recommendations: We present here the first of the two parts of our Society's recommendations for chronic HCV infection treatment. An agreement was reached regarding the diagnostic tools, the assessment of severity and the up-dated therapy schedules. Conclusions: This Position Paper represents a guide for the assessment and the therapy of HCV infection. The recommendations are in concordance with other guidelines but are applied to the real-life conditions in this country. [ABSTRACT FROM AUTHOR]

Aims: This study was aimed at determining the seroprevalence of hepatitis C virus (HCV) infection in Romania and the possible risk factors and modality of HCV transmission. Methods: A nationwide cross-sectional survey among the adult population was conducted between 2006-2008 in Romania through a population multicenter stratified random cluster sampling. Serum samples from 13,460 subjects were tested with a 3rd generation ELISA and a standardized questionnaire concerning the socio-demographic characteristics and potential risk factors was used. Results: The prevalence rate of HCV infection in Romanian adult population was 3.23% with significant differences between the main geographical regions (Moldavia 4.25%, Wallachia & Dobrogea 3.35% and Transylvania & Banat 2.63%), as well as between different counties (maximum 7.19%, minimum 0.56%). Overall participation rate to the survey of the selected subjects was 74.69%. Risk factors for HCV infection were: blood/blood products transfusions (p=0.0001), previous surgery (elective and emergency, p=0.0001 and p=0.043, respectively), frequent hospitalizations (p=0.0001), injections at home (p=0.0001), accidents/trauma (p=0.0001), occupational hazard related to blood exposure (p=0.025), intravenous drug administration (p=0.002), a partner chronically infected with HCV/hepatitis B virus (HBV) (p=0.046), first sexual intercourse <18 years (p=0.019), familial exposure to HCV/HBV infection (p=0.001) or to chronic HBV/HCV liver disease (p=0.001), personal history of chronic HBV infection (p=0.001). HCV RNA positivity was detected in 91% of the anti HCV positive subjects. Conclusions: Overall HCV prevalence in Romania is 3.23%. Both nosocomial and non-nosocomial routes are implicated as risk factors for HCV infection. [ABSTRACT FROM AUTHOR]

Pegylated interferon-alpha in combination with ribavirin currently represents the therapeutic standard for the hepatitis C virus infection. Interferon based therapy may be responsible for many cutaneous side effects. We report a case of drug-induced Sweet's syndrome secondary to hepatitis C antiviral therapy. To our knowledge, this is the first reported case of Sweet's syndrome in association with pegylated interferon-alpha therapy. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 66 year-old male patient who had a history of orthotopic liver transplantation for hepatitis C virus (HCV) liver cirrhosis. Topics discussed include the early detection of advanced pancreatic cancer in the patient, the abdominal computed tomography (CT) scan performed on the patient, and the recurrence of HCV in the patient.

Background & Aims: Literature data suggest that HCV genotype-1b is present in 93-99% of the Romanian patients infected with hepatitis C virus (HCV). We present the genotyping tests recently performed on patients with HCV and advanced fibrosis eligible for the Direct-Acting Antiviral (DAA) therapy, as well as the prevalence of these cases across Romania. Methods: The genotyping method was performed on 7,421 HCV patients with advanced fibrosis. The detection method was automatic real time PCR platform M2000 (Abbott). Every subject was introduced into a database including age, sex, county and address. Results: Genotype 1b was almost exclusively present: 7,392/7,421 (99.6%). Genotype 1b patients were 19.6% from Bucharest, 49% were males, with a median age of 60 years. Genotype non-1b was encountered in 29/7,421 subjects (0.4%), 62% were males, 69% from Bucharest and the median age was 52 years. Most of the subjects (75%) were in the 6th and 7th age decade. The prevalence of these cases varied significantly across Romanian counties: the highest was in Bucharest (61.3/105), Bihor (47/105), Iasi (46/105) and Constanţa (43/105), and the lowest in Ilfov (2.8/105), Harghita (3.7/105), Covasna (5.4/105) and Maramureş, Romania (8.8/105) (p<0.001). Conclusions: Genotype 1b is encountered in 99.6% of patients with chronic hepatitis C and advanced fibrosis from Romania. The presence of genotypes non-1b is more common in Bucharest, in males and at a younger age. There are significant differences regarding the distribution of these cases across Romania: the highest rates are in Bucharest, Bihor, Iasi and Constanta. [ABSTRACT FROM AUTHOR]

Objectives: The current study aimed at evaluating the association between metabolic syndrome (MeS) in patients with hepatitis C virus (HCV) liver cirrhosis (compensated, genotype, 1b) and changes after sustained viral response (SVR) following a 12-week therapy with paritaprevir, ritonavir, ombitasvir, dasabuvir, and ribavirin (PrOD+R). Methods: The current multicenter retrospective study included 809 patients diagnosed with compensated HCV cirrhosis (child class A), all 1b genotype treated for 12 weeks with direct acting antiviral agents - PrOD+R - regimen (according to the protocol practiced in Romania) and achieved SVR. The parameters of MeS (according to the definition of the International Diabetes Federation) were collected from medical records before and 12 weeks after the treatment. The results were collected in a central database and analyzed with SPSS 18.0. Statistical analysis used both descriptive and analytical methods with a significance level of 95% (CI 95%). Results: Out of the 809 patients, 105 (13%) demonstrated 3 out of the 5 criteria for MeS. Based on the MeS criteria, the commonest parameters were abnormal glycaemia (54.1%), followed by visceral obesity (38.6%), raised triglycerides (26.1%), high blood pressure (12.1%), and a low high-density lipoprotein (HDL)-cholesterol (4.6%). The re-assessment of MeS parameters after SVR showed favourable changes, which were statistically significant: a siginficanttly lower serum triglyeride level (182.32 vs. 153.50 mg/dL, P = 0.001), lower systolic arterial blood pressure (130.57 vs. 124.85 mmHg; P = 0.001), lower diastolic arterial blood pressure (80.26 vs. 78.42 mmHg; P = 0.001) and lower glyceamic levels (130.06 vs. 120.71 mg/dL; P = 0.001), as well as a significant rise in HDL-cholesterol levels (48.61 vs. 50.50 mg/dL; P = 0.003). Abdominal circumference was the only parameter, which did not change after SVR. Following the changes sustained after SVR, 26.7% of the patients no longer fulfilled the minimum 3 criteria for MeS. No correlation was observed between the presence of MeS and the risk of severe adverse events, but it was noted that 37.5% of the patients who decompensated, 66.7% of the ones who developed hepatocarcinoma and 100% of the ones that died of abnormal glycaemic levels. Conclusions: Hyperglycemia, and not MeS, is associated with HCV compensated liver cirrhosis genotype 1b, and is a risk factor for severe adverse events. The attainment of SVR through PrOD+R regimen results in short-term improvements in MeS parameters. [ABSTRACT FROM AUTHOR]

Background & Aims: Liver stiffness (LS) measurement by Transient Elastography (TE) has been widely accepted as a tool for fibrosis assessment. The aim of this study was to assess LS dynamics in a group of patients with HCV liver cirrhosis after interferon free treatment (IFT). Methods: This two-center clinical trial included 225 patients with compensated HCV cirrhosis (all genotype 1b), who received IFT for 12 weeks. All patients were evaluated by means of TE at the beginning and at the end of treatment (EOT), and a subgroup (170 patients) also 12 weeks after EOT; all of them had sustained viral response (SVR). Reliable LS measurements (LSM) were defined as a median value of 10 valid LSM, with IQR <30% and SR ≥60%. Both M and XL probes were used. For diagnosing cirrhosis we used a cut-off value of 12kPa as proposed by the Tsochatzis meta-analysis. We considered a decrease or increase of more than 10% in LSM as being significant. Results: Out of 225 subjects, reliable measurements were obtained in 93.7%, so that the final analysis included 211 patients. The mean LS values decreased significantly after IFT: 26.4±11.7 vs. 23.5±13.3 kPa (p=0.01). Most patients, 59.2% (125/211) presented more than 10% decrease in LS values, 24.1% (51/211) had stable LS values, while in 16.4% (35/211) cases, the LS values increased. In the subgroup of 170 patients with LSM also performed 12 weeks after EOT (SVR), the mean LS values were significantly lower as compared to baseline: 21.3±11 kPa vs. 27.4±11.9 kPa (p<0.0001) and also as compared to EOT: 21.3±11 kPa vs. 23.7±13.3 kPa (p<0.0001). Conclusion: In our patients with HCV liver cirrhosis, the mean LS values evaluated by TE significantly decreased after antiviral treatment at EOT and also 12 weeks after EOT as compared to baseline. Overall, about 60% of patients had LS values at EOT lower than at baseline, while 12 weeks after EOT about 75% of patients had LS values lower than at baseline. [ABSTRACT FROM AUTHOR]

Background and aim: The current standard of care in chronic HCV genotype 1 hepatitis is the combination of pegylated interferon (PegIFN) with ribavirin for 48 weeks. The aim of our paper was to verify if there are significant differences regarding the sustained virologic response (SVR) in patients treated with PegIFN alfa-2a vs. those treated PegIFN alfa-2b, both in combination with ribavirin. Method: We performed a retrospective study on 507 patients with chronic viral C hepatitis treated with PegIFN alpha-2a 180 μg/kg/week or PegIFN alpha-2b 1.5 μg/kg/week plus ribavirin in the recommended doses according to weight, following the current treatment guidelines. We evaluated the SVR defined as PCR RNA-HCV undetectable 24 weeks after the end of treatment. Results: There were no differences regarding the baseline characteristics among the subgroups of patients treated with PegIFN alpha-2a or PegIFN alpha-2b concerning the pretreatment viral load (p=0.2445), the severity of fibrosis (p=0.2403), the mean age of the patients (p=0.9597) and the women/men ratio (p=0.2087). The SVR rates in patients treated with PegIFN alpha-2a were similar to those in patients treated with PegIFN alpha-2b: 208/338 (61.5%) vs. 94/169 (55.6%) (p=0.2129). Conclusion: Sustained virologic response rates were similar in HCV genotype 1 patients treated with PegIFN alpha-2a and with Peg-IFN alpha-2b. [ABSTRACT FROM AUTHOR]