Clinical and patient-reported outcome profile of patients with hepatitis B viral infection from the Global Liver Registry™.

Chronic hepatitis B (CHB) infection is one of the most common causes of cirrhosis and liver cancer worldwide. Our aim was to assess clinical and patient-reported outcome (PRO) profile of CHB patients from different regions of the world using the Global Liver Registry. The CHB patients seen in real-world practices are being enrolled in the Global Liver Registry. Clinical and PRO (FACIT-F, CLDQ, WPAI) data were collected and compared to baseline data from CHB controls from clinical trials. The study included 1818 HBV subjects (48 ± 13 years, 58% male, 14% advanced fibrosis, 7% cirrhosis) from 15 countries in 6/7 Global Burden of Disease super-regions. The rates of advanced fibrosis varied (3-24%). The lowest PRO scores across multiple domains were in HBV subjects from the Middle East/North Africa (MENA), the highest - Southeast/East and South Asia. Subjects with advanced fibrosis had PRO impairment in 3 CLDQ domains, Activity of WPAI (p < 0.05). HBV subjects with superimposed fatty liver had more PRO impairments. In multivariate analysis adjusted for location, predictors of PRO impairment in CHB included female sex, advanced fibrosis, and non-hepatic comorbidities (p < 0.05). In comparison to Global Liver Registry patients, 242 controls from clinical trials had better PRO scores (Abdominal, Emotional, and Systemic scores of CLDQ, all domains of WPAI) (p < 0.05). In multivariate analysis with adjustment for location and clinicodemographic parameters, the associations of PROs with the enrollment setting (real-life Global Liver Registry vs. clinical trials) were no longer significant (all p > 0.10). The clinico-demographic portrait of CHB patients varies across regions of the world and enrollment settings. Advanced fibrosis and non-hepatic comorbidities are independently associated with PRO impairment in CHB patients.

Clinical and Patient-Reported Outcomes From Patients With Nonalcoholic Fatty Liver Disease Across the World: Data From the Global Non-Alcoholic Steatohepatitis (NASH)/ Non-Alcoholic Fatty Liver Disease (NAFLD) Registry.

BACKGROUND & AIMS: Globally, nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease. We assessed the clinical presentation and patient-reported outcomes (PROs) among NAFLD patients from different countries. METHODS: Clinical, laboratory, and PRO data (Chronic Liver Disease Questionnaire-nonalcoholic steatohepatitis [NASH], Functional Assessment of Chronic Illness Therapy-Fatigue, and the Work Productivity and Activity Index) were collected from NAFLD patients seen in real-world practices and enrolled in the Global NAFLD/NASH Registry encompassing 18 countries in 6 global burden of disease super-regions. RESULTS: Across the global burden of disease super-regions, NAFLD patients (n = 5691) were oldest in Latin America and Eastern Europe and youngest in South Asia. Most men were enrolled at the Southeast and South Asia sites. Latin America and South Asia had the highest employment rates (>60%). Rates of cirrhosis varied (12%-21%), and were highest in North Africa/Middle East and Eastern Europe. Rates of metabolic syndrome components varied: 20% to 25% in South Asia and 60% to 80% in Eastern Europe. Chronic Liver Disease Questionnaire-NASH and Functional Assessment of Chronic Illness Therapy-Fatigue PRO scores were lower in NAFLD patients than general population norms (all P < .001). Across the super-regions, the lowest PRO scores were seen in Eastern Europe and North Africa/Middle East. In multivariate analysis adjusted for enrollment region, independent predictors of lower PRO scores included younger age, women, and nonhepatic comorbidities including fatigue (P < .01). Patients whose fatigue scores improved over time experienced a substantial PRO improvement. Nearly 8% of Global NAFLD/NASH Registry patients had a lean body mass index, with fewer metabolic syndrome components, fewer comorbidities, less cirrhosis, and significantly better PRO scores (P < .01). CONCLUSIONS: NAFLD patients seen in real-world practices in different countries experience a high comorbidity burden and impaired quality of life. Future research using global data will enable more precise management and treatment strategies for these patients.

Severe impairment of patient-reported outcomes in patients with chronic hepatitis C virus infection seen in real-world practices across the world: Data from the global liver registry.

Cure of chronic hepatitis C (CHC) can lead to improvement of health-related quality of life and other patient-reported outcomes (PROs). While extensive PRO data for CHC patients who were enrolled in clinical trials are available, similar data for patients seen in real-world practices are scarce. Our aim was to assess PROs of CHC patients enrolled from real-world practices from different regions and to compare them with those enrolled in clinical trials. CHC patients seen in clinical practices and not receiving treatment were enrolled in the Global Liver Registry (GLR). Clinical and PRO (FACIT-F, CLDQ-HCV, WPAI) data were collected and compared with the baseline data from CHC patients enrolled in clinical trials. N = 12,171 CHC patients were included (GLR n = 3146, clinical trial subjects n = 9025). Patients were from 30 countries from 6 out of 7 Global Burden of Disease (GBD) super-regions. Compared with clinical trial enrollees, patients from GLR were less commonly enrolled from High-Income GBD super-region, older, more commonly female, less employed, had more type 2 diabetes, anxiety and clinically overt fatigue but less cirrhosis (all p < 0.001). Out of 15 PRO domain and summary scores, 12 were lower in GLR patients than in subjects enrolled in clinical trials (p < 0.001). In multiple regression models, anxiety, depression, and fatigue were associated with significant PRO impairment in CHC patients (p < 0.05). After adjustment for the clinico-demographic confounders, the association of PRO scores of CHC patients with enrolment settings was no longer significant (all p > 0.05). In conclusion, hepatitis C patients seen in the real-world practices have PRO impairment driven by fatigue and psychiatric comorbidities.

Helicobacter pylori infection prevalence in ambulatory settings in 2017-2019 in RUSSIA: The data of real-world national multicenter trial.

BACKGROUND: The recent data on the prevalence of Helicobacter pylori (H. pylori) infection in Russia are limited. The aim of the study was to compare Helicobacter pylori infection prevalence in ambulatory settings in Russia in 2017 and 2019 years. MATERIALS AND METHODS: Subjects visiting primary care centers were invited to take part in the study. H. pylori status was assessed by 13 C-urea breath test (UBT). Data on subjects' demography, previous treatment exposure, and place of residence were collected in all federal districts of Russia in 2017 and in 2019 calendar years and processed centrally. RESULTS: The data of 19,875 subjects were available for analysis. The prevalence of H. pylori infection assessed by positive UBT in treatment-naive subjects was highest in the Southern (54.9%) and the North Caucasian (45.1%) federal districts. A significant difference (p < 0.05) in H. pylori prevalence between two testing periods was found only in a half of federal districts: the Central (46.2% in 2017 vs. 36.2% in 2019), the Northwestern (38.6% vs. 35.5% accordingly), the Volga (40.6% vs. 33.0%, accordingly), and the Ural (40.4% vs. 32.7%, accordingly). The lowest prevalence of H. pylori infection was revealed in the age group <18 years old (20.2%), while the highest in the age group of 41-50 years old (43.9%). In 2017, the prevalence of H. pylori was significantly (p < 0.05) higher than in 2019 in all age groups but younger than 18 and older than 70 y.o., where similar rates were found during both study periods. CONCLUSIONS: The prevalence of H. pylori according to 13 C-UBT testing of primary care visitors in Russia is lower than expected (38.8%). The highest prevalence of H. pylori infection found in the Southern and the North Caucasian federal districts of Russia and in the age group of 41-50 years old. This study was registered at clinicaltrials.gov (NCT04892238).

Is elimination of hepatitis C virus realistic by 2030: Eastern Europe.

The WHO elimination goals (diagnosis of 90% of the cases of hepatitis C virus (HCV), treatment coverage in 80% and a 65% reduction in deaths from HCV) are set to be reached by 2030. Although these elimination programmes are extremely important in the Eastern European countries (Russia, Ukraine, Belarus and Moldova) with a high prevalence of HCV, limited economic resources prevent their development and implementation. Regardless of the decrease in the incidence HCV in all Eastern European countries, low diagnosis and treatment access, especially in high-risk populations, will not allow to achieve HCV elimination or even to control the infection by 2030.

Alcohol-Related Liver Disease Is Rarely Detected at Early Stages Compared With Liver Diseases of Other Etiologies Worldwide.

BACKGROUND & AIMS: Despite recent advances in treatment of viral hepatitis, liver-related mortality is high, possibly owing to the large burden of advanced alcohol-related liver disease (ALD). We investigated whether patients with ALD are initially seen at later stages of disease development than patients with hepatitis C virus (HCV) infection or other etiologies. METHODS: We performed a cross-sectional study of 3453 consecutive patients with either early or advanced liver disease (1699 patients with early and 1754 with advanced liver disease) seen at 17 tertiary care liver or gastrointestinal units worldwide, from August 2015 through March 2017. We collected anthropometric, etiology, and clinical information, as well as and model for end-stage liver disease scores. We used unconditional logistic regression to estimate the odds ratios for evaluation at late stages of the disease progression. RESULTS: Of the patients analyzed, 81% had 1 etiology of liver disease and 17% had 2 etiologies of liver disease. Of patients seen at early stages for a single etiology, 31% had HCV infection, 21% had hepatitis B virus infection, and 17% had nonalcoholic fatty liver disease, whereas only 3.8% had ALD. In contrast, 29% of patients seen for advanced disease had ALD. Patients with ALD were more likely to be seen at specialized centers, with advanced-stage disease, compared with patients with HCV-associated liver disease (odds ratio, 14.1; 95% CI, 10.5-18.9; P < .001). Of patients with 2 etiologies of liver disease, excess alcohol use was associated with 50% of cases. These patients had significantly more visits to health care providers, with more advanced disease, compared with patients without excess alcohol use. The mean model for end-stage liver disease score for patients with advanced ALD (score, 16) was higher than for patients with advanced liver disease not associated with excess alcohol use (score, 13) (P < .01). CONCLUSIONS: In a cross-sectional analysis of patients with liver disease worldwide, we found that patients with ALD are seen with more advanced-stage disease than patients with HCV-associated liver disease. Of patients with 2 etiologies of liver disease, excess alcohol use was associated with 50% of cases. Early detection and referral programs are needed for patients with ALD worldwide.

Efficacy and safety of elbasvir/grazoprevir in participants with hepatitis C virus genotype 1, 4, or 6 infection from the Asia-Pacific region and Russia: Final results from the randomized C-CORAL study.

BACKGROUND AND AIM: Although treatment with direct-acting antivirals has dramatically improved morbidity and mortality attributable to chronic hepatitis C virus infection, universal access to these medicines has been slow in the Asia-Pacific region and Russia. This study evaluated efficacy and safety of elbasvir/grazoprevir in participants with hepatitis C virus infection from Asia-Pacific countries and Russia (C-CORAL). METHODS: C-CORAL was a phase 3, randomized, placebo-controlled study (NCT02251990). Treatment-naive, HIV-negative, cirrhotic and non-cirrhotic participants with chronic hepatitis C genotype 1, 4, or 6 infection were randomized to elbasvir 50 mg/grazoprevir 100 mg once daily for 12 weeks (immediate-treatment group) or placebo followed by deferred treatment with elbasvir/grazoprevir (deferred-treatment group). The primary efficacy outcome was sustained virologic response at 12 weeks, and the primary safety outcome was a comparison between the immediate-treatment group and placebo phase of the deferred-treatment group. RESULTS: A total of 489 participants were randomized (immediate-treatment group, n = 366; deferred-treatment group, n = 123). Sustained virologic response at 12 weeks in the combined immediate/deferred-treatment groups was 94.4% (459/486; 95% confidence interval = 92.4-96.5%). Sustained virologic response at 12 weeks was 98.2% in participants with genotype 1b, 91.9% with genotype 1a, and 66.7% with genotype 6 infection. Similar rates of adverse events and drug-related adverse events were seen in the immediate-treatment group versus placebo phase of the deferred-treatment group (51.0% vs 50.4% and 21.4% vs 21.1%). CONCLUSIONS: Elbasvir/grazoprevir for 12 weeks represents an effective and well-tolerated treatment option for treatment-naive people with genotype 1 infection from Asia-Pacific countries and Russia.

Late Relapse Versus Hepatitis C Virus Reinfection in Patients With Sustained Virologic Response After Sofosbuvir-Based Therapies.

BACKGROUND: The development of direct-acting antivirals in recent years has dramatically enhanced rates of viral eradication to >90% in patients with chronic hepatitis C virus (HCV) infection. To determine true treatment efficacy and define the most appropriate retreatment, it is important to distinguish virologic relapse from reinfection when patients in whom HCV is eradicated during treatment become infected with a new HCV strain after treatment. METHODS: We investigated the prevalence of late recurrent viremia (patients with sustained virologic response 12 weeks after the end of treatment but detectable HCV RNA at follow-up week 24) and used refined phylogenetic analysis of multiple HCV genes to distinguish virologic relapse from reinfection. RESULTS: Across 11 phase 3 clinical trials of ledipasvir-sofosbuvir (SOF) and SOF, only 12 of 3004 patients had detectable HCV RNA following sustained virologic response 12 weeks after the end of treatment. Of these 12 patients with late recurrent viremia, 11 had the same HCV genotype/subtype at baseline and at recurrence. Phylogenetic analysis demonstrated that 58% (7 of 12) of these patients were successfully treated with the SOF-based regimen, with HCV eradication achieved, but became reinfected with a different HCV strain after treatment. The remaining 5 patients with late recurrent viremia had virologic relapse in which the HCV present at baseline persisted in the liver or another compartment and reemerged in the blood 24 weeks after treatment. CONCLUSIONS: The incidence of late recurrent viremia was low. Distinguishing reinfection from virologic relapse has implications for determining true treatment efficiency and selecting optimal retreatment strategies.

Daclatasvir/asunaprevir/beclabuvir, all-oral, fixed-dose combination for patients with chronic hepatitis C virus genotype 1.

BACKGROUND AND AIM: This multinational (Taiwan, South Korea, Russia) phase 3 study evaluated the all-oral, ribavirin-free, fixed-dose combination (DCV-TRIO) of daclatasvir (NS5A inhibitor) 30 mg, asunaprevir (NS3 inhibitor) 200 mg, and beclabuvir (NS5B inhibitor) 75 mg, in patients with chronic hepatitis C virus genotype-1 infection, with or without compensated cirrhosis. METHODS: UNITY-4 (NCT02170727) was an open-label, two-cohort study in which 169 patients, treatment-naive (n = 138) or treatment-experienced (n = 31), received twice-daily DCV-TRIO for 12 weeks with 24 weeks of post-treatment follow-up. The primary efficacy end point was sustained virologic response at post-treatment week 12 (SVR12) in treatment-naive patients. RESULTS: Eighty-eight (52%) patients were men, 81 (48%) Taiwanese, 78 (46%) Korean, and 10 (6%) Russian; 23 (14%) had compensated cirrhosis, and 52 (31%) were IL28B (rs1297860) non-CC genotype. Baseline resistance-associated NS5A polymorphisms (L31 and/or Y93) were detected in 25/165 (15%) patients with available genotype-1 sequencing data. SVR12 was achieved by 98.6% (136/138; 95% confidence interval: 94.9-99.8%) of treatment-naive and 100% (31/31; 95% confidence interval: 88.8-100%) of treatment-experienced patients. Both virologic failures were found to be infected with hepatitis C virus genotype-6g; 100% SVR12 was observed for genotype-1a (n = 8) and genotype-1b (n = 157). Two patients experienced serious adverse events. Eight (5%) patients experienced reversible grade 3/4 alanine aminotransferase or aspartate aminotransferase elevations, leading to discontinuation in four (2%); all achieved SVR12. There were no grade 3/4 total bilirubin increases and no deaths. CONCLUSIONS: Twelve weeks of DCV-TRIO was well tolerated and provided 100% SVR12 in treatment-naive and treatment-experienced patients with genotype-1 infection, with or without cirrhosis, including those with baseline NS5A-L31 or NS5A-Y93 resistance-associated substitutions.

Autoimmune gastritis studies and gastric cancer: True renaissance or bibliometric illusion.

A bibliometric analysis of studies dedicated to autoimmune gastritis (AIG) recently published demonstrated a noteworthy surge in publications over the last three years. This can be explained by numerous publications from different regions of the world reporting the results of several studies that stimulated reassessment of our view of AIG as a precancerous condition. Follow-up studies and retrospective analyses showed that the risk of gastric cancer (GC) in AIG patients is much lower than expected if the patients ever being infected with Helicobacter pylori (H. pylori) were excluded. The low prevalence of precancerous lesions, such as the incomplete type of intestinal metaplasia, may explain the low risk of GC in AIG patients because the spasmolytic polypeptide-expressing metaplasia commonly observed in AIG does not involve clonal reprogramming of the gastric gland and can be considered as an adaptive change rather than a true precancerous lesion. However, changes in gastric secretion due to the progression of gastric atrophy during the course of AIG cause changes in the gastric mic-robiome, stimulating the growth of bacterial species such as streptococci, which may promote the development of precancerous lesions and GC. Thus, Streptococcus anginosus exhibited a robust proinflammatory response and induced the gastritis-atrophy-metaplasia-dysplasia sequence in mice, reproducing the well-established process for carcinogenesis associated with H. pylori. Prospective studies in H. pylori-naïve patients evaluating gastric microbiome changes during the long-term course of AIG might provide an explanation for the enigmatic increase in GC incidence in the last decades in younger cohorts, which has been reported in economically developed countries.

Nonalcoholic Fatty Liver Disease: Disease Burden and Disease Awareness.

Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide and has been implying an unprecedented burden to health care systems. The prevalence of NAFLD has exceeded 30% in developed countries. Considering the asymptomatic nature of undiagnosed NAFLD, high suspicion and noninvasive diagnosis have utmost importance especially in primary care level. At this point, patient and provider awareness should be optimal for early diagnosis and risk stratification for patients at risk of progression.

Evaluation of the Efficacy of Kombucha-Based Drink Enriched with Inulin and Vitamins for the Management of Constipation-Predominant Irritable Bowel Syndrome in Females: A Randomized Pilot Study.

Background: Constipation-predominant irritable bowel syndrome (IBS-C) mainly affects females, and dietary interventions for symptom relief often yield poor results because of low patient adherence. The development of functional food products enriched with dietary fibers may increase patients' adherence to a healthy diet and relieve IBS-С symptoms. Objective: This proof-of-concept, open-label, randomized controlled pilot study is aimed to evaluate the efficacy of kombucha enriched with inulin and vitamins in females with IBS-C. Methods: Forty females with IBS-C were randomly assigned to receive either 220 mL of kombucha enriched with inulin (2.53 g/220 mL) and vitamins (B1 - 0.59 mg, B2 - 0.55 mg, B3 - 5.9 mg, B6 - 0.7 mg, and folic acid - 81.4 µg/220 mL) or water for 10 d. Stool frequency, Bristol stool scale score (BSSS), and abdominal symptoms were evaluated using a 5-point Likert scale on days 5, 9 and 14 of the study. The palatability of the drink was assessed using a visual analog scale. Results: After 10 d, the kombucha group showed a significant increase in stool frequency (0.60 ± 0.31-0.85 ± 0.19 times/d; P = 0.004) compared with the control (0.63 ± 0.33 compared with 0.72 ± 0.28; P = 0.6). The mean values of the BSSS increased in the kombucha group (3.0 ± 1.2-4.4 ± 1.0; P = 0.001), whereas they remained unchanged in the control (2.9 ± 1.2 compared with 3.4 ± 1.2; P = 0.6). The kombucha group also experienced a significant decrease in the feeling of incomplete bowel emptying (1.88 ± 0.78 compared with 1.41 ± 0.56 points; P = 0.015), which was not observed in the control group. Conclusions: Short-term consumption of kombucha enriched with inulin and vitamins was associated with an increase in stool frequency, an improvement in the BSSS, and a reduction in the feeling of incomplete bowel emptying in females with IBS-C. Further large-scale clinical trials investigating the efficacy of kombucha enriched with inulin and vitamins in patients with IBS-C are warranted to prove the observed effects. Trial registration number: This trial was registered at clinicaltrials.gov as NCT05164861 (==https://clinicaltrials.gov/study/NCT05164861?term=NCT05164861&rank=1; registered on 18 December, 2021).

Elimination of HCV in Russia: Barriers and Perspective.

Hepatitis C virus (HCV) is highly prevalent in Russia, representing the largest pool of hepatitis C patients in Europe. Effective treatment regimens with direct-acting antivirals can achieve HCV cure in all patients; therefore, in 2016 the World Health Organization proposed eliminating hepatitis C as a public health threat by 2030. However, only a small number of countries are on track to meet the WHO's hepatitis C elimination targets by 2030 due to many barriers in healthcare systems. This review focuses on a discussion about the epidemiology of HCV in Russia, the economic burden of HCV-related diseases, and treatment access with particular reference to the barriers for the elimination of HCV.

Prevalence of resistance-associated substitutions and phylogenetic analysis of hepatitis C virus infection in Russia.

OBJECTIVES: Due to limited hepatitis C virus (HCV) sequence availability from patients in Russia, the relationship between subtypes and baseline resistance-associated substitutions (RAS) to direct antiretroviral treatment outcome is not fully understood. METHODS: Deep sequencing of HCV NS3, NS5A, and NS5B sequences was performed on plasma HCV samples from 412 direct-acting antiviral (DAA)-naïve patients from Russia. Phylogenetic analysis was performed to investigate sequence similarities between HCV strains from Russia, Asia, Europe, and North America. Pretreatment HCV RAS was assessed with a 15% cutoff. RESULTS: HCV genotype GT1b and GT3a sequences in Russia were related to strains in Europe and Asia. The prevalence of GT1a and GT2a was low in Russia. In GT1b, the prevalence of NS5A Y93H was lower in Russia (6%) compared with Asia (15%). The prevalence of NS5B L159F was similar between Russia and Europe (26-39%). GT3a RAS prevalence was similar between Russia and Asia, Europe, and North America. The 2k/1b recombinant strain in Russia was related to strains from Europe. A higher prevalence of the NS5A RAS L31M (10%) was observed in 2k/1b sequences compared to GT1b (1-6%). CONCLUSIONS: The prevalence of RASs and the phylogenetic analysis showed similarities in HCV strains between Russia, Europe, and North America. This information may be useful for HCV regimens in Russia.

Elbasvir/Grazoprevir for HCV Infection in Russia: A Randomized Trial.

PURPOSE: Hepatitis C virus (HCV) infection is a major healthcare concern in Russia, where almost 5 million individuals are viremic. Elbasvir/grazoprevir is a fixed-dose combination therapy for the treatment of HCV genotype 1 and genotype 4 infection. The present analysis aimed to assess the safety and efficacy of elbasvir/grazoprevir in individuals with HCV infection enrolled at Russian study sites in the C-CORAL study. PATIENTS AND METHODS: C-CORAL (Protocol PN-5172-067; NCT02251990) was a Phase 3, placebo-controlled, double-blind study conducted throughout Asia and Russia. Treatment-naive participants with chronic HCV infection were randomly assigned to receive immediate or deferred treatment with elbasvir 50 mg/grazoprevir 100 mg once daily for 12 weeks. Participants in the immediate-treatment group received elbasvir/grazoprevir for 12 weeks, and those in the deferred-treatment group received placebo for 12 weeks, followed by open-label elbasvir/grazoprevir for 12 weeks. The primary endpoint was sustained virologic response at 12 weeks after completion of therapy (SVR12). RESULTS: One hundred and nineteen Russian participants were randomized (immediate-treatment group, n=88; deferred-treatment group, n=31). Most participants were white (99%) with HCV genotype 1b infection (97%) and mild-to-moderate (F0-F2) fibrosis (70%). SVR12 was achieved by 98.9% participants in the immediate-treatment group and by 100% of those receiving deferred elbasvir/grazoprevir in the deferred-treatment group. One participant relapsed with nonstructural protein 5A (NS5A) L28M and Y93H resistance-associated substitutions at baseline and at time of failure. Drug-related adverse events were reported by 19% of participants receiving elbasvir/grazoprevir in the immediate-treatment group and by 16% of those receiving placebo in the deferred-treatment group. No serious adverse event or deaths occurred, and no participant discontinued treatment owing to an adverse event. CONCLUSION: Elbasvir/grazoprevir for 12 weeks was highly effective in treatment-naive Russian individuals with HCV genotype 1b infection.

Sofosbuvir/velpatasvir for the treatment of HCV: excellent results from a phase-3, open-label study in Russia and Sweden.

BACKGROUND: In both Russia and Sweden, the dominant hepatitis C virus (HCV) is genotype 1, but around one-third of patients have genotype 3 infection. For such countries, HCV genotype testing is recommended prior to therapy. An effective pangenotypic therapy may potentially eliminate the need for genotyping. In this study, we evaluated the efficacy and safety of sofosbuvir/velpatasvir for 12 weeks in patients from Russia and Sweden. METHODS: In an open-label, single-arm phase-3 study, patients could have HCV genotype 1-6 infection and were treatment-naïve or interferon treatment-experienced. All patients received sofosbuvir/velpatasvir, once daily for 12 weeks. The primary endpoint was sustained virologic response 12 weeks post-treatment (SVR12). RESULTS: Of 122 patients screened, 119 were enrolled and treated. Overall, half (50%) were male, 18% had cirrhosis, and 24% had failed prior interferon-based therapy. In total, 66% of patients were infected with HCV genotype 1 (59% 1b and 7% 1a), 6% with genotype 2, and 29% with genotype 3. The overall SVR12 rate was 99% (118/119, 95% confidence interval 95-100%). One treatment-experienced patient infected with HCV genotype 3 experienced virologic relapse after completing treatment. The most common adverse events were headache (16%) and fatigue (7%). Serious adverse events were observed in four patients, but none were related to treatment. No patients discontinued treatment due to adverse events. CONCLUSION: Sofosbuvir/velpatasvir as a pangenotypic treatment for 12 weeks was highly effective in patients from Russia and Sweden infected with HCV genotypes 1, 2, or 3. Sofosbuvir/velpatasvir was safe and well-tolerated. Clinical trial number: ClinicalTrials.gov NCT02722837.