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LINKED CONTENT: This article is linked to Armandi et al papers. To view these articles, visit https://doi.org/10.1111/apt.17941 and https://doi.org/10.1111/apt.18025. [ABSTRACT FROM AUTHOR]

Background Therapeutic options for hospitalized patients with severe coronavirus disease 2019 (sCOVID-19) are limited. Preliminary data have shown promising results with baricitinib, but real-life experience is lacking. We assessed the safety and effectiveness of add-on baricitinib to standard-of-care (SOC) including dexamethasone in hospitalized patients with sCOVID-19. Methods This study is a 2-center, observational, retrospective cohort study of patients with sCOVID-19, comparing outcomes and serious events between patients treated with SOC versus those treated with SOC and baricitinib combination. Results We included 369 patients with sCOVID-19 (males 66.1%; mean age 65.2 years; median symptom duration 6 days). The SOC was administered in 47.7% and combination in 52.3%. Patients treated with the combination reached the composite outcome (intensive care unit [ICU] admission or death) less frequently compared with SOC (22.3% vs 36.9%, P  = .002). Mortality rate was lower with the combination in the total cohort (14.7% vs 26.6%, P  = .005), and ICU admission was lower in patients with severe acute respiratory distress syndrome (29.7% vs 44.8%, P  = .03). By multivariable analysis, age (odds ratio [OR] = 1.82, 95% confidence interval [CI] = 1.36–2.44, per 10-year increase), partial pressure of oxygen/fraction of inspired oxygen ratio (OR = 0.60, 95% CI = .52–0.68, per 10 units increase), and use of high-flow nasal cannula (OR = 0.34; 95% CI,.16–0.74) were associated with the composite outcome, whereas baricitinib use was marginally not associated with the composite outcome (OR = 0.52; 95% CI,.26–1.03). However, baricitinib use was found to be significant after inverse-probability weighted regression (OR = 0.93; 95% CI,.87–0.99). No difference in serious events was noted between treatment groups. Conclusions In real-life settings, addition of baricitinib to SOC in patients hospitalized with sCOVID-19 is associated with decreased mortality without concerning safety signals. [ABSTRACT FROM AUTHOR]

Background & Aims: Discontinuation of nucleos(t)ide analogues (NA) remains a debatable issue in HBeAg‐negative chronic hepatitis B (CHB). This study aimed to address the outcome of HBeAg‐negative CHB patients who discontinued NA therapy. Methods: This prospective study included 57 non‐cirrhotic HBeAg‐negative Caucasian CHB patients who discontinued NA therapy after median virological remission of 6 years. All patients had regular blood tests. Virological relapse was defined as HBV DNA > 2000 IU/mL or >20 000 IU/mL and biochemical relapse as ALT > ULN (40 IU/mL) or >2xULN. All patients with retreatment predefined criteria restarted entecavir or tenofovir. Results: Of the 57 patients, 29 remained without retreatment after median follow‐up of 65 months (range: 36‐87) following treatment discontinuation. At 3, 6, 12, 24, 36 and 48 months, cumulative rates of retreatment were 16%, 20%, 32%, 35%, 46% and 50%, while the proportion of patients with HBV DNA < 2000 IU/mL and ALT < ULN were 73%, 60%, 52%, 52%, 47% and 37% respectively. All patients had virological and biochemical response after retreatment. No patient developed liver failure, hepatocellular carcinoma or death. Cumulative rates of HBsAg loss were 2%, 4%, 7%, 10% and 20% at 3, 6, 12, 24 and 36 months. HBsAg levels < 100 IU/mL at the end of NA treatment could predict HBsAg loss (P =.001). Conclusions: Our study supports that NA therapy can be safely stopped in non‐cirrhotic patients with HBeAg‐negative CHB. Over a median follow‐up of more than 5 years, half of the patients remained without retreatment with a substantial proportion of them achieving functional cure. [ABSTRACT FROM AUTHOR]

Background Long-term monotherapy with nucleos(t)ide analogs (NAs) represents the treatment option for the majority of patients with chronic hepatitis B (CHB), an aging population with a greater likelihood of comorbidities. We assessed the prevalence of concurrent non-hepatic diseases and the safety monitoring in a large cohort of CHB patients receiving NAs and their potential impact on disease outcomes. Methods We included 500 consecutive CHB patients from 5 major tertiary Greek centers, under long-term therapy with an NA. Epidemiological/clinical characteristics and data on concomitant disease, drug use and investigations ordered were collected. Results The mean age was 58 years and 66% were male. Most patients were receiving tenofovir disoproxil fumarate (TDF, 60%) or entecavir (ETV, 37%) monotherapy. Decompensated cirrhosis at baseline was present in 10%, while hepatocellular carcinoma (HCC) under therapy developed in 21 patients. The median duration of total NA therapy was 56 and of latest therapy 42 months. The most common (prevalence >10%) comorbidities were hypertension (28%), non-HCC cancer(s) (12%), and diabetes (11%). Patients with a longer duration of latest therapy (≥4 vs. <4 years) were older (mean age: 58 vs. 56 years, P=0.004), had more frequent history of prior use of NA(s) (53% vs. 35%, P<0.001), and less frequent liver decompensation (5% vs. 13%, P=0.008) and non-HCC cancers (8% vs. 15%, P=0.020). HCC developed more frequently in patients with than in those without diabetes (11% vs. 3%, P=0.022). Conclusion Greek CHB patients currently treated with NAs, almost exclusively ETV or TDF, are often older than 60 years, have several comorbidities, and thus require careful management. [ABSTRACT FROM AUTHOR]

Background Direct-acting antivirals (DAAs) offer high cure rates in people who inject drugs (PWID) with hepatitis C virus (HCV) infection. There are concerns regarding lower response rates among PWID in real life. We evaluated the outcome of DAA therapy in PWID in a real-world setting and the factors that affect it. Methods We performed a retrospective analysis of 174 PWID with chronic hepatitis C who started DAAs in a Greek liver clinic in collaboration with an addiction program. Patients who did not return for reassessment were considered as lost to follow up (LTFU). A logistic regression model was used to assess factors associated with a sustained virological response 12 weeks after treatment completion (SVR12) and LTFU. Results Patients' mean age was 48±9.2 years and 91/174 (52.3%) were attending opioid substitution treatment programs. Overall, 144/174 (82.8%) patients completed therapy and presented for SVR12 testing, 8/174 (4.6%) did not complete treatment and 22/174 (12.6%) were LTFU. Overall SVR12 was 79.9% (139/174). For those with an available SVR12 test the response rate reached 96.5% (139/144). Regression analysis did not indicate any significant association between patient characteristics and SVR12. Age <45 years and genotype 3 were independent predictors of LTFU. Parallel use was found to have a trend towards LTFU. Conclusions HCV treatment by hepatologists and addiction specialists is feasible, effective and safe in a real-world setting. However, as 12% of patients appear to be LTFU, more emphasis should be placed on interventions guaranteeing follow up for SVR testing and general care. [ABSTRACT FROM AUTHOR]

Summary: The optimal duration of treatment with nucleos(t)ide analogues (NAs) for patients with HBeAg‐negative chronic hepatitis B (CHB) is unknown. The aim of this study was to identify an immune signature associated with off‐treatment remission to NA therapy. We performed microarray analysis of peripheral blood mononuclear cell (PBMCs) from six patients with chronic hepatitis B who stopped NA therapy (three with off‐treatment remission, three with relapse) and five patients with chronic HBV infection (previously termed 'inactive carriers') served as controls. Results were validated using qRT‐PCR on a second group of 21 individuals (17 patients who stopped treatment and four controls). PBMCs from 38 patients on long‐term NA treatment were analysed for potential to stop treatment. Microarray analysis indicated that patients with off‐treatment remission segregated as a distinct out‐group. Twenty‐one genes were selected for subsequent validation. Ten of these were expressed at significantly lower levels in the patients with off‐treatment remission compared to the patients with relapse and predicted remission with AUC of 0.78‐0.92. IFNγ, IL‐8, FASLG and CCL4 were the most significant by logistic regression. Twelve (31.6%) of 38 patients on long‐term NA therapy had expression levels of all these four genes below cut‐off values and hence were candidates for stopping treatment. Our data suggest that patients with HBeAg‐negative CHB who remain in off‐treatment remission 3 years after NA cessation have a distinct immune signature and that PBMC RNA levels of IFNγ, IL‐8, FASLG and CCL4 may serve as potential biomarkers for stopping NA therapy. [ABSTRACT FROM AUTHOR]

Background Only limited data concerning hepatitis B (HBV) and C viruses (HCV) coinfection are available. Direct-acting antivirals (DAAs) may be more effective for HCV clearance than interferon (IFN)-based regimens with a risk of HBV reactivation. Methods We retrospectively enrolled 40 HBV/HCV-coinfected patients to evaluate their clinical profile and treatment outcomes. Results Chronic dual infection was present in 25/40 (62.5%) patients, acute HCV superinfection in 5/40 (12.5%) patients and acute HBV superinfection in 10/40 (25%). Twenty-five patients (62.5%) were treated: 16/25 (64%) with IFN, 4/25 (16%) with nucleot(s)ide analogs (NUCs) and 5/25 (20%) with DAAs. Of the 16 patients treated with IFN-based therapy, 6 (37.5%) achieved both sustained virological response (SVR) and HBsAg clearance. Of the 4 patients treated with NUCs, one (25%) achieved both SVR and HBsAg clearance. All five patients treated with DAAs (100%) achieved SVR, while one case of HBV reactivation was recorded. Fifteen of the 40 patients (37.5%) did not receive any treatment. Eight of them (53.5%) presented with acute HBV superinfection: spontaneous HCV clearance was recorded in 5/8 (62.5%), while HBsAg clearance occurred in 6/8 (75%). Three of them (20%) presented with acute HCV superinfection; spontaneous HCV clearance was recorded in one of the three (33.5%). The other four patients (26.5%) presented with dual HBV/HCV infection. Conclusions A significant proportion of patients presented with active HBV replication. Treatment with DAAs seems to be efficacious for HCV eradication. However, clinicians should be aware of HBV reactivation. HBV superinfection may lead to both HBsAg and HCV clearance. [ABSTRACT FROM AUTHOR]

Background The diagnosis of bacterial infection in cirrhotic patients may be difficult, because of the absence of classical signs such as fever and raised white blood cell count. The role of C-reactive protein (CRP) in this context has not been clearly defined. Methods Clinical and laboratory characteristics of 210 consecutive cirrhotic patients with (n=100) or without (n=110) bacterial infection were compared with a control group of non-cirrhotic patients with infection (n=106). Results Significantly fewer patients with cirrhosis had a body temperature ≥37°C when presenting with bacterial infection (56% cirrhotic vs. 85.5% non-cirrhotic patients, P=0.01). Mean leukocyte count was 6.92 x 10³/mm³ in patients with cirrhosis and infection, 5.75 x 10³/mm³ (P=0.02) in cirrhotic patients without infection, and 11.28 x 10³/mm³ in non-cirrhotic patients with infection (P<0.001). Multivariate analysis revealed that CRP level and model for end-stage liver disease score were significantly associated with the presence of infection in patients with cirrhosis. A cutoff level of CRP>10 mg/L indicated the presence of infection with a sensitivity of 68%, a specificity of 84.5% and an area under the receiver operating characteristic curve of 0.8197. CRP cutoff level differed according to the severity of the liver disease: Child-Pugh score (CPS) A: 21.3 mg/L, B: 17 mg/L, and C: 5.78 mg/L. Conclusions CRP at admission could help diagnose infection in cirrhotic patients. Since the severity of liver disease seems to affect the CRP values, lower CRP levels might indicate infection. Clinical suspicion is necessary to avoid delay in diagnosis and initiate antibiotic treatment. [ABSTRACT FROM AUTHOR]

here is also increasing evidence that vaccination for SARS-CoV-2 may induce autoimmunity.3,4 Here, we present a case of histologically confirmed AIH after mRNA vaccination against SARS-CoV-2. A typical autoimmune hepatitis (AIH) case following Covid-19 mRNA vaccination. Autoimmune hepatitis following COVID-19 vaccination: true causality or mere association?. [Extracted from the article]