Sustained Virological Response After Early Discontinuation of Hepatitis C Treatment.

To date, the effectiveness of direct-acting antivirals (DAAs) discontinued before 4 weeks has not been analysed in routine clinical practice. The study aimed to determine whether such a short therapy will enable achieving a sustained virological response under real-world experience. The study population of 97 patients who discontinued DAA therapy and had data enabling analysis of patient and disease characteristics, and assessment of treatment effectiveness was selected from 16,815 patients registered in the EpiTer-2 database. The most common reason for discontinuation was hepatic decompensation (20.6%) or the patient's personal decision (18.6%). Patients who discontinued treatment were significantly older, more frequently therapy-experienced, more likely to have cirrhosis, a history of decompensation and a Child-Pugh B or C classification than those who completed treatment. SVR was achieved by 93.5% of patients who discontinued treatment after 4 weeks, 60.9% if discontinued at 3 or 4 week and 33.3% at Week 1 or 2. Patients receiving pangenotypic but not genotype-specific treatment who discontinued after 4 weeks were as likely to achieve SVR as those who completed therapy. Patients who responded to treatment that lasted no longer than 2 weeks had a low baseline viral load (<400,000 IU/mL). Despite discontinuation of therapy after Week 4, the chances of SVR are high. Very early discontinuation does not preclude therapeutic success, especially in patients with low baseline viral load.

Real-world effectiveness and safety of direct-acting antivirals in patients with cirrhosis and history of hepatic decompensation: Epi-Ter2 Study.

BACKGROUND AND AIMS: The aim of this study was to assess the real-life effectiveness and safety of direct acting antivirals (DAAs) in patients with cirrhosis and history of hepatic decompensation compared to those with compensated cirrhosis. METHOD: Data of patients treated with DAAs and included in the EpiTer-2 database (N = 10 152) were collected retrospectively. The primary endpoint was sustained viral response (SVR) at 12 weeks posttreatment. Patients were also evaluated in terms of liver-related adverse events and treatment modification/discontinuation. RESULTS: The overall SVR rate was 91.4% in the intent to treat (ITT) analysis and 95.2% in the per-protocol (PP) analysis (P < .001). Patients with decompensated cirrhosis had lower SVR rates compared to those with compensated cirrhosis in ITT analysis (86.4% vs 92.0%, P < .001), while not in PP analysis (92.9% vs 95.5%, P > .05). Adverse events (AE) occurred 45.6% and 29.3% of patients with decompensated and compensated cirrhosis (P < .001). Patients with decompensated cirrhosis were at higher risk of death (5.4% vs 0.9%; P < .0001) or liver decompensation (21.5% vs 1.3%; P < .0001). Treatment with protease inhibitors was not associated with hepatic decompensation (P = .3). Only 82.6% of patients with decompensated cirrhosis completed DAA treatment (vs 92.8% in compensated cirrhotics; P < .0001). CONCLUSION: Despite higher frequency of AE and treatment modifications, once completed, DAAs yield comparable results for patients with decompensated and compensated cirrhosis. High rate of serious adverse events in patients with advanced liver disease treated with PI may not be related to the detrimental effect of the medications, but rather to the disease itself.

Is an 8-week regimen of glecaprevir/pibrentasvir sufficient for all hepatitis C virus infected patients in the real-world experience?

BACKGROUND AND AIMS: The revolution of the antiviral treatment of hepatitis C virus (HCV) infection resulting in higher effectiveness came with the introduction of direct-acting antivirals with pangenotypic regimens as a final touch. Among them, the combination of glecaprevir (GLE) and pibrentasvir (PIB) provides the opportunity for shortening therapy to 8 weeks in the majority of patients. Because of still insufficient evaluation of this regimen in the real-world experience, our study aimed to assess the efficacy and safety of 8-week GLE/PIB in chronic hepatitis C patients depending on liver fibrosis and genotype (GT). METHODS: The analysis included patients who received GLE/PIB for 8 weeks selected from the EpiTer-2 database, large retrospective national real-world study evaluating antiviral treatment in 12 584 individuals in 22 Polish hepatology centers. RESULTS: A total of 1034 patients with female predominance (52%) were enrolled in the analysis. The majority of them were treatment naïve (94%), presented liver fibrosis (F) of F0-F3 (92%), with the most common GT1b, followed by GT3. The overall sustained virologic response after exclusion of nonvirologic failures was achieved in 95.8% and 98%, respectively (P = 0.19). In multivariate logistic regression HCV GT-3 (beta = 0.07, P = 0.02) and HIV infection (beta = -0.14, P < 0.001) were independent predictors of nonresponse. CONCLUSIONS: We demonstrated high effectiveness of 8-week GLE/PIB treatment in a non-GT3 population irrespective of liver fibrosis stage. Comparable efficacy was achieved in non-cirrhotic patients regardless of the genotype, including GT3 HCV.

Real-world experience with Grazoprevir/Elbasvir in the treatment of previously "difficult to treat" patients infected with hepatitis C virus genotype 1 and 4.

BACKGROUND AND AIM: Grazoprevir/elbasvir (GZR/EBR) was approved for the treatment of chronic hepatitis C virus (HCV) genotype 1 and 4 infected patients with or without compensated liver cirrhosis. The aim of this study was to assess GZR/EBR regimen in the real-world experience, particularly in previously "difficult-to-treat" patients with chronic kidney diseases, human immunodeficiency virus-coinfected, cirrhotics, and treatment-experienced. METHODS: The analysis included patients treated with GZR/EBR selected from 10 152 individuals from the EpiTer-2 database, large national real-world study evaluating antiviral treatment in 22 Polish hepatology centers between 2015 and 2018. Data were completed retrospectively and submitted online. RESULTS: A total of 1615 patients who started GZR/EBR therapy in 2017 and 2018 with a female predominance (54%) and median age of 54 years were analyzed. The majority were infected with GT1b (89%) and treatment naïve (81%). Liver cirrhosis was diagnosed in 19%, and 70% of patients had comorbidities, of which chronic renal disease was present in 7% and HIV-coinfection in 4%. Overall, a sustained virologic response (SVR) was achieved by 95% according to intent-to-treat (ITT) and 98% after exclusion of lost to follow up (modified ITT). No differences were found in cure rate between all included patients and subpopulations previously considered as difficult-to-treat. Majority of patients completed the treatment course as scheduled, adverse events were mostly mild and did not lead to therapy discontinuation. CONCLUSIONS: GZR/EBR treatment carried-out in patients infected with HCV genotype 1 and 4 demonstrated good tolerability and an excellent SVR rate with no effectiveness reduction in so called difficult-to-treat populations.

The efficacy of paritaprevir/ritonavir/ombitasvir+dasabuvir and ledipasvir/sofosbuvir is comparable in patients who failed interferon-based treatment with first generation protease inhibitors - a multicenter cohort study.

BACKGROUND: According to the EASL and AASLD guidelines, the recommended treatment for patients who failed to achieve a sustained virologic response (SVR) on prior interferon-based triple therapy with protease inhibitors (PI), is a combination of sofosbuvir and NS5A inhibitors. Polish national recommendations also allow the use of paritaprevir/ritonavir/ombitasvir+dasasbuvir±ribavirin (PrODR) in this group of patients. The aim of the study was to evaluate the efficacy and safety of PrODR vs. ledipasvir/sofosbuvir±RBV (LSR) in PI-experienced patients in real-life setting. METHODS: Our analysis included patients registered in the nationwide, investigators initiated, multicentre EpiTer-2 database. Among 4530 patients registered, 335 with genotype 1 (93% 1b) were previously treated with IFN-based regimens with PIs: 127 with boceprevir (BOC), 208 with telaprevir (TVR). Patients with advanced fibrosis (F3/F4) were significantly predominant (BOC 28.4%/61.4%, TVR 18.8%/64.4%, respectively). Subjects were assigned to IFN-free retreatment as follows: BOC - 64 (50.4%) PrODR and 63 (49.6%) LSR; TVR- 103 (49.5%) PrODR and 105 (50.5%) LSR. RESULTS: SVR rates were comparable for particular groups: BOC → PrODR- 100%; BOC → LSR - 98%; TVR → PrODR - 97%; TVR → LSR - 96% (intent-to treat analysis-ITT) and BOC → PrODR→100%; BOC → LSR - 99%; TVR → PrODR - 99%; TVR → LSR - 98% (modified intent-to treat analysis-mITT). Both treatment regimens had a favourable safety profile. Adverse events (AEs) were generally mild or moderate in severity. Three deaths were reported. The treatment was stopped due to AEs in five patients (three treated with PrODR and two with LSR). CONCLUSION: Efficacy and safety of treatment with PrODR and LSR is comparable in BOC or TVR-experienced patients.

The Real-World Efficacy and Safety of Direct-Acting Antivirals for Chronic Hepatitis C in Patients Active Malignancies.

BACKGROUND: Over the past years, the introduction of direct-acting antivirals (DAAs) revolutionized chronic hepatitis C treatment. We aimed to characterize and assess treatment efficacy in three specific groups of patients treated with DAAs: those with active solid malignant tumors (SMTs), hematological diseases (HDs) and hepatocellular carcinomas (HCCs). METHODS: A total of 203 patients with active oncological disease (SMT n = 61, HD = 67, HCC n = 74) during DAA treatment in 2015-2020 selected from the EpiTer-2 database were analyzed retrospectively and compared to 12,983 patients without any active malignancy. RESULTS: Extrahepatic symptoms were more frequent in HD patients (17.2% vs. SMT = 10.3%, HCC = 8.2%, without = 7.8%, p = 0.004). HCC patients characterized with the highest ALT activity (81 IU/L vs. SMT = 59.5 IU/L, HD = 52 IU/L, without = 58 IU/L, p = 0.001) more often had F4 fibrosis as well (86.11% vs. SMT = 23.3%, HD = 28.8%, controls = 24.4%, p = 0.001). A significant majority of subjects in HCC, HD and SMT populations completed the full treatment plan (HCC = 91%; n = 67, HD = 97%; n = 65, SMT = 100%; n = 62). Concerning the treatment efficacy, the overall sustained virologic response, excluding non-virologic failures, was reported in 93.6% HD, 90.16% SMT and 80.6% in HCC patients. CONCLUSIONS: As presented in our study, DAA therapy has proven to be highly effective and safe in patients with active SMTs and HDs. However, therapy discontinuations resulting from liver disease progression remain to be the major concern in HCC patients.

Real-life effectiveness of antiviral therapy for HCV infection with pangenotypic regimens in HIV coinfected patients.

BACKGROUND: The aim of this study was to evaluate the real-life efficacy of pangenotypic antivirals in HIV-HCV-positive patients. RESEARCH DESIGN AND METHODS: The analysis included 5650 subjects who were treated with pangenotypic anti-HCV drugs: 5142 were HCV-positive and 508 were HIV-HCV-positive. RESULTS: Patients with HCV-monoinfection were older (p < 0.0001), however patients with HCV-monoinfection had a higher proportion of advanced fibrosis F4 (p < 0.0001). There were no differences between the study groups in the rate of SVR12 in ITT-analysis (87,6% versus 93,9% in coinfection and monoinfection group, respectively; p > 0.05). However, there was a difference between study groups in PP-analysis, HIV/HCV and HCV, respectively 95.9% vs 97.9%, p = 0.0323. Additionally, there were a higher rate of patients who did not apply for follow-up (SVR12) in coinfected patients (7,9% vs 3,6% respectively p = 0.0001). In multivariante analysis, factors associated with worse response to the pangenotypic anti-HCV therapy included male sex, HCV genotype 3, stage of fibrosis and decompensation of liver function and HIV coinfection. CONCLUSIONS: The real-life results of pangenotypic anti-HCV treatment are veryeffective in the group of HIV-HCV-coinfected patients. However, the finaleffectiveness is slightly lower than that obtained in HCV monoinfectedpatients.

Real-world effectiveness of genotype-specific and pangenotypic direct-acting antivirals in HCV-infected patients with renal failure.

Aim of the study: The aim is to summarize the effectiveness and safety of genotype-specific and pangenotypic hepatitis C virus (HCV) treatments in patients with renal failure. Material and methods: In the EpiTer-2 database, which includes data from 22 hepatology centers in Poland, 593 patients with HCV infection and kidney failure were identified. According to KDIGO 2022, they fulfilled the criteria of chronic kidney disease. Patients were divided into two groups: treated with genotype-specific regimens (n = 428) and pangenotypic options (n = 165), in relation to the stage of kidney disease determined using the glomerular filtration rate (GFR) (Cockcroft and Gault equation). Two separate groups were created for hemodialyzed patients (n = 134) and patients after kidney transplantation (n = 89). Results: In a total of 593 patients, 78.7% were treatment-naïve and 23.9% had liver cirrhosis, in 27.5% of cases decompensated. In both groups, the dominant genotype was GT1b. Among patients treated with genotype-specific regimens, LDV/SOF ± RBV, OBV/PTV/r + DSV ± RBV, and GZR/EBR ± RBV treatments were given to 31.5%, 31.5%, and 34.8% of patients respectively. In pangenotypic regimens, GLE/PIB was chosen in 50.3%. Ninety-six percent and 98.8% of patients in the genotype-specific regimen and 88.5% and 94.8% in the pangenotypic regimen achieved a sustained virologic response at 12 weeks (SVR12) in the intention-to-treat and per protocol population respectively. Liver cirrhosis was identified as a risk factor for virological failure. During the study, 14 patients died, 7 in each of the two groups, none related to the antiviral treatment. Conclusions: Both types of treatment regimens are equally effective and safe in patients with renal failure. The stage of renal failure or transplant does not influence the antiviral response.

Efficacy of 8- versus 12-week treatment with ledipasvir/sofosbuvir in chronic hepatitis C patients eligible for 8-week regimen in a real-world setting.

Introduction: Non-cirrhotic treatment-naive hepatitis C patients infected with genotype 1 can be treated with ledipasvir/sofosbuvir (LDV/SOF) for 8 weeks, but in practice this regimen is frequently extended up to 12 weeks at least in part due to insufficient real-world data supporting shortening of treatment. The aim of our study was to compare 8- and 12-week regimens' efficacy in patients eligible for 8-week therapy in a real-world setting. Material and methods: Data of HCV genotype 1 infected patients treated with LDV/SOF between 2015 and 2018 included in the EpiTer-2 database were analyzed with respect to patients' characteristics and length of treatment. Results: Among a total of 1718 patients treated with LDV/SOF, 679 were included in the analysis, 238 (35%) received 8-week regimen, whereas 441 were treated for 12 weeks although they fulfilled the criteria for a shorter course. The majority of patients were infected with genotype 1b (89%) and demonstrated minimal fibrosis (55%). The 12-week regimen was assigned significantly more frequently to patients with comorbidities, concomitant medications and advanced liver fibrosis. The sustained virologic response rate was similar after 8 (98%) and 12 (97%) weeks of therapy according to intent-to-treat analysis and reached 99% in both groups after exclusion of patients lost to follow-up. Conclusions: We confirmed high effectiveness regardless of treatment duration with LDV/SOF in non-cirrhotics infected with HCV genotype 1 eligible for the 8-week regimen according to the current label. This real-world study also demonstrated no need for addition of ribavirin (RBV) in this population and showed that shortening of treatment significantly improves the safety profile of LDV/SOF medication.

HCV Genotype Has No Influence on the Incidence of Diabetes-EpiTer Multicentre Study.

HCV infection is one of the main reasons for liver cirrhosis and hepatocellular carcinoma. In recent years, one finds more and more extrahepatic manifestations of HCV infection, including its possible influence on the development of diabetes. In the presented work, one finds the frequency analysis of the incidence of diabetes among 2898 HCV infected patients treated in Poland, and the assessment of their relevance to the HCV genotype and the progression of fibrosis. The results indicate that the hepatitis C infection seems to be a risk factor for diabetes in persons with more advanced liver fibrosis, for older people, and for the male gender. Thus, one found no differences regarding the frequency of its incidence depending on HCV genotype, including genotype 3.

Hepatitis C Infection as a Risk Factor for Hypertension and Cardiovascular Diseases: An EpiTer Multicenter Study.

Hepatitis C infection is one of the main reasons for liver cirrhosis and hepatocellular carcinoma. In recent years, more and more is being heard about extrahepatic manifestations of the hepatitis C infection including its possible influence on the development of hypertension and cardiovascular diseases. In the given work, the frequency analysis of the incidence of hypertension and cardiovascular diseases among 2898 HCV-infected patients treated in Poland and the assessment of their relevance to the HCV genotype and the progression of liver fibrosis can be found. The prevalence of hypertension in the group of analyzed patients was 39% and was significantly associated with old age (OR = 1.08 (1.07-1.08)) and female sex, as well as the progression of liver fibrosis (OR = 1.54 (1.29-1.85)). Hypertension was found in 47.6% of patients with F4 fibrosis, 42.1% of patients with F3 fibrosis, and 25% of patients with F1 fibrosis. The incidence of cardiovascular disease in the studied group of patients was as follows: all incidents, 131 (4.52%); including ischemic heart disease 104, (3.95%); stroke, 2 (0.07%); atherosclerosis, 21 (0.72%); and aneurysms, 4 (0.14%). The obtained results prove that the prevalence of cardiovascular diseases is significantly associated with the advanced age of patients and the progression of liver fibrosis. The relevance of sex and the HCV genotype to the prevalence frequency of cardiovascular diseases in the study group has not been proven. This being the case, no differences in the frequency of their incidence depending on the HCV genotype, including genotype 3, was found. Hepatitis C infection as a non-classical risk factor for cardiovascular disease and hypertension does require further studying.

HCV resistance-associated substitutions following direct-acting antiviral therapy failure - Real-life data from Poland.

BACKGROUND: This study analysed the NS3 and NS5A mutation frequencies, persistence and drug susceptibility in a cohort of real-life patients, with failed hepatitis C virus (HCV) therapy following directly acting antiviral (DAA) treatment. METHODS: NS3/NS5A Sanger sequences from 105 patients infected with HCV genotype (G) 1a (6,5.7%), G1b (94,89.5%), G3a (4,3.8%), and G4 (1,1.0%) post DAA treatment failure were analysed. NS3 and NS5A resistance-associated substitutions (RASs) were identified using the geno2pheno algorithm and associated with clinical variables. Time trends were examined using logistic regression. RESULTS: NS5A RAS were found in 87.9% of sequences derived from patients exposed to this class of agents, whereas NS3 RAS was found in 59.1% of HCV protease-exposed subjects. The frequency of the NS3 RAS increased with fibrosis stage, from 40.0% among F0/F1 individuals to 81.8% among patients with liver cirrhosis (F4, p = 0.094). NS5A mutation frequencies were 7.6% for 28A/V/M, 10.6% for 30 K/Q/R, 42.4% for 31I/F/M/V, and 75.8% for 93H. For NS3, the most common RASs were 56F-23.7%, 168A/E/I/Y/T/V-14.0%, and 117H-5.4%. Susceptibility to glecaprevir/pibrentasvir, velpatasvir/voxlaprevir, and elbasvir/grazoprevir was retained in 92.9%, 43.4%, and, 25.3% of patients, respectively. The frequency of NS3 RAS decreased with time elapsed from failure to sampling (p = 0.034 for trend). NS5A RAS frequency remained stable over the 24-months. CONCLUSIONS: Following DAA treatment failure, NS5A and NS3 RASs were common with increasing frequency among patients with advanced liver disease. In most cases, despite the presence of RASs, susceptibility to DAA combinations with higher genetic barrier was retained.

Hepatotropic Properties of SARS-CoV-2-Preliminary Results of Cross-Sectional Observational Study from the First Wave COVID-19 Pandemic.

Liver injury-expressed as elevated liver enzymes-is common in patients with COVID-19. Little is known about the potential mechanisms of liver damage by SARS-CoV-2. A direct cytopathic effect on hepatocytes as well as injury related to hypoxia or hepatotoxicity are being considered. The aim of the study was to compare the clinical characteristic of COVID-19 disease in patients with normal and abnormal liver enzymes activity. A group of 150 patients with COVID-19, hospitalized in our center, was analyzed. Patients with the known liver comorbidities were excluded (n = 15). Clinical features and laboratory parameters were compared between patients with normal and abnormal aminotransferase values. Liver injury expressed as any alanine aminotransferase (ALT) elevation was noted in 45.6% of patients hospitalized due to COVID-19. The frequencies of aspartate aminotransferase (AST) elevation were lower. It was noted that elevated ALT/AST unfavorably affected other parameters related to liver function such as albumin level; gamma-glutamyl transpeptidase (GGTP); and partly, ALP activity and influenced inflammation-related parameters. The most probable cause of mild hepatitis during COVID-19 was anoxia and immune-mediated damage due to the inflammatory response following SARS-CoV-2 infection. A direct cytopathic effect of SARS-CoV-2 on hepatocytes, albeit less probable, can be considered as well. The use of potentially hepatotoxic drugs may contribute to liver damage.

Effectiveness and Safety of Pangenotypic Regimens in the Most Difficult to Treat Population of Genotype 3 HCV Infected Cirrhotics.

There is still limited data available from real-world experience studies on the pangenotypic regimens in patients with genotype (GT) 3 hepatitis C virus (HCV) infection and liver cirrhosis. The current study aimed to evaluate the efficacy and safety of pangenotypic regimens in this difficult-to-treat population. A total of 236 patients with mean age 52.3 ± 11.3 years and male predominance (72%) selected from EpiTer-2 database were included in the analysis; 72% of them were treatment-naïve. The majority of patients (55%) received the combination of sofosbuvir/velpatasvir (SOF/VEL), 71 without and 58 with ribavirin (RBV), whereas the remaining 107 individuals were assigned to glecaprevir/pibrentasvir (GLE/PIB). The effectiveness of the treatment following GLE/PIB and SOF/VEL regimens (96% and 93%) was higher compared to SOF/VEL + RBV option (79%). The univariate analysis demonstrated the significantly lower sustained virologic response in males, in patients with baseline HCV RNA ≥ 1,000,000 IU/mL, and among those who failed previous DAA-based therapy. The multivariate logistic regression analysis recognized only the male gender and presence of ascites at baseline as the independent factors of non-response to treatment. It should be emphasized that despite the availability of pangenotypic, strong therapeutic options, GT3 infected patients with cirrhosis still remain difficult-to-treat, especially those with hepatic impairment and DAA-experienced.

Factors influencing the failure of interferon-free therapy for chronic hepatitis C: Data from the Polish EpiTer-2 cohort study.

BACKGROUND: The introduction of direct-acting antiviral drugs into clinical practice has revolutionized the treatment of chronic hepatitis C, making it highly effective and safe for patients. However, few researchers have analyzed the factors causing therapy failure in some patients. AIM: To analyze factors influencing the failure of direct antiviral drugs in the large, multicenter EpiTer-2 cohort in a real-world setting. METHODS: The study cohort consisted of patients with chronic hepatitis C treated at 22 Polish centers from 2016-2020. Data collected from the online EpiTer-2 database included the following: hepatitis C virus (HCV) genotype, stage of fibrosis, hematology and liver function parameters, Child-Turcotte-Pugh and Model for End-stage Liver Disease scores, prior antiviral therapy, concomitant diseases, and drugs used in relation to hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV) coinfections. Adverse events observed during the treatment and follow-up period were reported. Both standard and machine learning methods were used for statistical analysis. RESULTS: During analysis, 12614 patients with chronic hepatitis C were registered, of which 11938 (mean age: 52 years) had available sustained virologic response (SVR) data [11629 (97%) achieved SVR and 309 (3%) did not]. Most patients (78.1%) were infected with HCV genotype 1b. Liver cirrhosis was diagnosed in 2974 patients, while advanced fibrosis (F3) was diagnosed in 1717 patients. We included patients with features of hepatic failure at baseline [ascites in 142 (1.2%) and encephalopathy in 68 (0.6%) patients]. The most important host factors negatively influencing treatment efficacy were liver cirrhosis, clinical and laboratory features of liver failure, history of hepatocellular carcinoma, and higher body mass index. Among viral factors, genotype 3 and viral load also exerted an influence on treatment efficacy. Classical statistical analysis revealed that treatment ineffectiveness seemed to be influenced by the male sex, which was not confirmed by the multivariate analysis using the machine learning algorithm (random forest). Coinfection with HBV (including patients with on-treatment reactivation of HBV infection) or HIV, extrahepatic manifestations, and renal failure did not significantly affect the treatment efficacy. CONCLUSION: In patients with advanced liver disease, individualized therapy (testing for resistance-associated variants and response-guided treatment) should be considered to maximize the chance of achieving SVR.

Nosocomial COVID-19 Infection and Severe COVID-19 Pneumonia in Patients Hospitalized for Alcoholic Liver Disease: A Case Report.

BACKGROUND COVID-19 is an infectious disease caused by SARS-CoV-2. It has spread rapidly through the world, endangering human life. The main target of COVID-19 is the lungs; however, it can involve other organs, including the liver. Patients with severe COVID-19 have an increased incidence of abnormal liver function, and patients with liver disorders are considered to be at a higher risk of severe COVID-19 infection. The mechanism of liver injury reported in 14% to 53% of COVID-19 patients is poorly recognized and several possibilities need to be considered (cytokine storm, direct viral action, hypoxia). The incidence of underlying liver comorbidities in patients with a COVID-19 infection ranges from 1% to 11%. CASE REPORT This is a report of 2 nosocomial COVID-19 infections and severe COVID-19 pneumonia in 2 patients who were hospitalized during treatment for alcoholic liver disease (ALD). Case 1 and case 2 were a 31-year-old woman and a 40-year-old woman, respectively, with decompensated ALD and symptoms of the COVID-19 infection. Both patients were transferred from another hospital to our hospital after confirmation of COVID-19 during their hospitalization. The course of the infection progressed rapidly in both patients with the development of multiple-organ failure and death over a short period. CONCLUSIONS There are no clear recommendations on the management of ALD in the COVID-19 pandemic. Alcoholic hepatitis may be a risk factor for severe COVID-19 and a poor outcome. A high percentage of nosocomial COVID-19 infections are observed; therefore, special precautions should be taken to minimize the risk of COVID-19 exposure.

Low risk of HBV reactivation in a large European cohort of HCV/HBV coinfected patients treated with DAA.

OBJECTIVES: The aim of the study was to analyze the prevalence and clinical characteristics of HCV/HBV coinfection and to evaluate the rate of HBV-reactivation during anti-HCV therapy in a large real-world study. METHODS: Analyzed population consisted of 10,152 chronic hepatitis C patients treated with DAA between 2015 and 2019 in a nationwide study. Prior to the DAA all subjects had HBsAg and 60% anti-HBc testing. RESULTS: 111 of 10,152 patients (1.1%) had detectable HBsAg and 1239 of 6139 (20.2%) anti-HBcAb. The prevalence of occult hepatitis B was 0.48%. HCV/HBV patients were younger with a higher proportion of males, HIV-coinfected, and advanced fibrosis. They were less often diagnosed with diabetes but more often with chronic kidney disease. In HBsAg(+) subjects with baseline HBV-DNA available 6/102 (5.9%) HBV-reactivations during or after DAA therapy were observed, and in two (1.9%) significant hepatic flares were noted. In HBsAg(-)/anti-HBc(+) group 2 (0.16%) reactivations were observed only in patients undergoing immunosuppressive therapy. DISCUSSION: Data from a large European cohort suggest a relatively low risk of HBV-reactivation during DAA-therapy for HCV infection in HBsAg(+) patients. In HBsAg(-)/anti-HBc(+) HBV-reactivation seems to be limited to subjects with immunodeficiency. Importantly, previous exposure to HBV and occult hepatitis B is present in a significant proportion of HCV-infected.

Real World Experience of Chronic Hepatitis C Retreatment with Genotype Specific Regimens in Nonresponders to Previous Interferon-Free Therapy.

Background and Aim: The development of interferon- (IFN-) free regimens substantially improved efficacy of treatment for HCV, but despite excellent effectiveness the failures still occur. The aim of our study was to evaluate the efficacy of retreatment with genotype specific direct acting antivirals- (DAA-) based regimens in nonresponders to previous IFN-free therapy. Materials and Methods: Analysed population consisted of 31 nonresponders to IFN-free regimen, which received second IFN-free rescue therapy, selected from 6228 patients included in a national database EpiTer-2. Results: Age and gender distribution were similar, whereas proportion of genotype 1b was slightly higher and genotype 4 lower in the whole population compared to studied one. Patients included in the study demonstrated much more advanced fibrosis. Primary therapy was discontinued in 12 patients, which were recognized as failures due to nonvirologic reason, whereas virologic reason of therapeutic failure was recognized in 19 patients which completed therapy. Overall sustained virologic response (SVR) rate was 81% and 86% in intent-to-treat (ITT) and modified ITT analysis, respectively (74% and 78% in virologic failures, 92% and 100% in nonvirologic failures). Resistance-associated substitutions (RAS) testing was carried out in 8 patients from the group of completed primary therapy and three of them had potential risk for failure of rescue therapy due to NS5A association, while two of them achieved SVR. Conclusions: We demonstrated moderate effectiveness of genotype specific rescue therapy in failures due to virologic reason and high in those who discontinued primary therapy. Therefore rescue therapy with genotype specific regimens should be considered always if more potent regimens are not available.

Is Interferon-Based Treatment of Viral Hepatitis C Genotype 3 Infection Still of Value in the Era of Direct-Acting Antivirals?

The aim of the study is to analyze treatments available for patients infected with genotype (G) 3 hepatitis C virus (HCV) in Poland at the beginning of the interferon (IFN)-free era and evaluate the efficacy and safety of different therapeutic options administered in a real-world setting. We analyzed data of 198 patients who started antiviral therapy after July 1, 2015, and completed it before December 31, 2016; 57.6% of them had liver cirrhosis and 46% were treatment experienced. Fifty percent of patients were assigned to sofosbuvir (SOF)+pegylated IFN alfa (PegIFNa)+ribavirin (RBV), 9% to PegIFNa+RBV, 36% received SOF+RBV, and 5% SOF+daclatasvir (DCV)±RBV. Cirrhotic patients were assigned more frequently to IFN-free regimens. Overall, a sustained virological response was achieved by 84.3% of patients in intent-to-treat (ITT) analysis and 87% in modified ITT analysis. For SOF+PegIFNa+RBV and SOF+DCV±RBV regimens, the sustained virologic response (SVR) rate reached at least 90%, whereas the two other therapeutic options demonstrated efficacy <80%. The SVR rate in noncirrhotics was higher than in cirrhotics, irrespective of regimen. Adverse events were documented in 52.5%, with the most common being weakness/fatigue and anemia. We confirmed effectiveness and safety of the SOF-based treatment in a real-world cohort of patients with chronic HCV G3 infection. Most notably, we demonstrated good tolerability and high efficacy of the SOF+PegIFNa+RBV regimen.