Prevalence and Prognostic Importance of High Fibrosis-4 Index in COVID-19 Patients.

Introduction: The fibrosis 4 (FIB-4) index was developed to predict advanced fibrosis in patients with liver disease. We aimed to evaluate the association of FIB-4 with risk factors for progression to critical illness in middle-aged patients hospitalized for coronavirus disease 2019 (COVID-19). Method: We included patients aged 35-65 years who were hospitalized following a positive RT-PCR SARS-Cov-2 test in a tertiary hospital. All data were obtained from the medical records of the patients during the first admission to the hospital. The FIB-4 index was calculated according to the equation (age (years) x AST (IU/L)/platelet count (109/L)/√ALT (IU/L)). The FIB-4 index was divided into three categories according to the score categorisation: <1.3 = low risk, 1.3-2.67 = moderate risk, and >2.67 = high risk. Results: A total of 619 confirmed COVID-19 patients (mean age = 52 yrs.) were included in this study; 37 (6.0%) were admitted to the intensive care unit (ICU), of which 44% were intubated and eight (1.3%) patients died during follow-up. The results of patients with high FIB-4 scores were compared with those with low FIB-4 scores. In patients with high FIB-4 scores, male gender, and advanced age, decreased neutrophil, lymphocyte, thrombocyte, and albumin counts, elevated AST, LDH, CK, ferritin, CRP, and D-dimer, and low GFR were the high-risk factors for critical illness. Additionally, the number of patients referred to ICU with high FIB-4 who died had higher scores than from those with low scores. Conclusion: The FIB-4 index derived from baseline data obtained during hospitalisation can be used as a simple, inexpensive, and straightforward indicator to predict ICU requirement and/or death in middle-aged hospitalized COVID-19 patients.

Liver injury after SARS-CoV-2 vaccination: Features of immune-mediated hepatitis, role of corticosteroid therapy and outcome.

BACKGROUND AND AIMS: A few case reports of autoimmune hepatitis-like liver injury have been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. We evaluated clinical features, treatment response and outcomes of liver injury following SARS-CoV-2 vaccination in a large case series. APPROACH AND RESULTS: We collected data from cases in 18 countries. The type of liver injury was assessed with the R-value. The study population was categorized according to features of immune-mediated hepatitis (positive autoantibodies and elevated immunoglobulin G levels) and corticosteroid therapy for the liver injury. We identified 87 patients (63%, female), median age 48 (range: 18-79) years at presentation. Liver injury was diagnosed a median 15 (range: 3-65) days after vaccination. Fifty-one cases (59%) were attributed to the Pfizer-BioNTech (BNT162b2) vaccine, 20 (23%) cases to the Oxford-AstraZeneca (ChAdOX1 nCoV-19) vaccine and 16 (18%) cases to the Moderna (mRNA-1273) vaccine. The liver injury was predominantly hepatocellular (84%) and 57% of patients showed features of immune-mediated hepatitis. Corticosteroids were given to 46 (53%) patients, more often for grade 3-4 liver injury than for grade 1-2 liver injury (88.9% vs. 43.5%, p = 0.001) and more often for patients with than without immune-mediated hepatitis (71.1% vs. 38.2%, p = 0.003). All patients showed resolution of liver injury except for one man (1.1%) who developed liver failure and underwent liver transplantation. Steroid therapy was withdrawn during the observation period in 12 (26%) patients after complete biochemical resolution. None had a relapse during follow-up. CONCLUSIONS: SARS-CoV-2 vaccination can be associated with liver injury. Corticosteroid therapy may be beneficial in those with immune-mediated features or severe hepatitis. Outcome was generally favorable, but vaccine-associated liver injury led to fulminant liver failure in one patient.

Effects of immunosuppressive drugs on COVID-19 severity in patients with autoimmune hepatitis.

BACKGROUND: We investigated associations between baseline use of immunosuppressive drugs and severity of Coronavirus Disease 2019 (COVID-19) in autoimmune hepatitis (AIH). PATIENTS AND METHODS: Data of AIH patients with laboratory confirmed COVID-19 were retrospectively collected from 15 countries. The outcomes of AIH patients who were on immunosuppression at the time of COVID-19 were compared to patients who were not on AIH medication. The clinical courses of COVID-19 were classified as (i)-no hospitalization, (ii)-hospitalization without oxygen supplementation, (iii)-hospitalization with oxygen supplementation by nasal cannula or mask, (iv)-intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v)-ICU admission with invasive mechanical ventilation or (vi)-death and analysed using ordinal logistic regression. RESULTS: We included 254 AIH patients (79.5%, female) with a median age of 50 (range, 17-85) years. At the onset of COVID-19, 234 patients (92.1%) were on treatment with glucocorticoids (n = 156), thiopurines (n = 151), mycophenolate mofetil (n = 22) or tacrolimus (n = 16), alone or in combinations. Overall, 94 (37%) patients were hospitalized and 18 (7.1%) patients died. Use of systemic glucocorticoids (adjusted odds ratio [aOR] 4.73, 95% CI 1.12-25.89) and thiopurines (aOR 4.78, 95% CI 1.33-23.50) for AIH was associated with worse COVID-19 severity, after adjusting for age-sex, comorbidities and presence of cirrhosis. Baseline treatment with mycophenolate mofetil (aOR 3.56, 95% CI 0.76-20.56) and tacrolimus (aOR 4.09, 95% CI 0.69-27.00) were also associated with more severe COVID-19 courses in a smaller subset of treated patients. CONCLUSION: Baseline treatment with systemic glucocorticoids or thiopurines prior to the onset of COVID-19 was significantly associated with COVID-19 severity in patients with AIH.

Frequency, Predisposing Factors, and Clinical Outcome of Azathioprine-Induced Pancreatitis Among Patients With Inflammatory Bowel Disease: Results From a Tertiary Referral Center.

OBJECTIVE: The aim of the study was to identify the frequency of azathioprine-induced acute pancreatitis (AZA-AP) and related factors. METHODS: Seven hundred eighty-seven inflammatory bowel disease (IBD) patients on AZA therapy were retrospectively analyzed. Azathioprine-induced AP was diagnosed with positive imaging and/or an at least 3-fold increased amylase level, in presence of typical abdominal pain. The AZA-AP group was compared with patients on AZA therapy with no history of pancreatitis and 4 numerical adjacent cases with the same diagnosis were selected (group B). RESULTS: Fifty-four patients developed gastrointestinal symptoms (6.9%); however, only half of them (26 of 54) had pancreatitis, except 1, all within the first 2 months under AZA. When the AZA-AP group was compared with group B, only budesonide usage and active smoking were significantly more common in group A (46.2% vs 25%, P = 0.034, and 77% vs 51%, P = 0.017, respectively). Active smoking was the only independent risk factor for AZA-AP development (odds ratio, 3.208 [95% confidence interval, 1.192-8.632]). CONCLUSIONS: All IBD patients developed AZA-AP nearly all within the first 2 months. Azathioprine intolerance may be a hidden diagnosis in at least half of the patients with AZA-AP symptoms. All smoker IBD patients should be monitored closely for AZA-AP development.

Outcome of COVID-19 in Patients With Autoimmune Hepatitis: An International Multicenter Study.

BACKGROUND AND AIMS: Data regarding outcome of COVID-19 in patients with autoimmune hepatitis (AIH) are lacking. APPROACH AND RESULTS: We performed a retrospective study on patients with AIH and COVID-19 from 34 centers in Europe and the Americas. We analyzed factors associated with severe COVID-19 outcomes, defined as the need for mechanical ventilation, intensive care admission, and/or death. The outcomes of patients with AIH were compared to a propensity score-matched cohort of patients without AIH but with chronic liver diseases (CLD) and COVID-19. The frequency and clinical significance of new-onset liver injury (alanine aminotransferase > 2 × the upper limit of normal) during COVID-19 was also evaluated. We included 110 patients with AIH (80% female) with a median age of 49 (range, 18-85) years at COVID-19 diagnosis. New-onset liver injury was observed in 37.1% (33/89) of the patients. Use of antivirals was associated with liver injury (P = 0.041; OR, 3.36; 95% CI, 1.05-10.78), while continued immunosuppression during COVID-19 was associated with a lower rate of liver injury (P = 0.009; OR, 0.26; 95% CI, 0.09-0.71). The rates of severe COVID-19 (15.5% versus 20.2%, P = 0.231) and all-cause mortality (10% versus 11.5%, P = 0.852) were not different between AIH and non-AIH CLD. Cirrhosis was an independent predictor of severe COVID-19 in patients with AIH (P < 0.001; OR, 17.46; 95% CI, 4.22-72.13). Continuation of immunosuppression or presence of liver injury during COVID-19 was not associated with severe COVID-19. CONCLUSIONS: This international, multicenter study reveals that patients with AIH were not at risk for worse outcomes with COVID-19 than other causes of CLD. Cirrhosis was the strongest predictor for severe COVID-19 in patients with AIH. Maintenance of immunosuppression during COVID-19 was not associated with increased risk for severe COVID-19 but did lower the risk for new-onset liver injury during COVID-19.

Extrahepatic autoimmune diseases in primary biliary cholangitis: Prevalence and significance for clinical presentation and disease outcome.

BACKGROUND AND AIM: The prevalence and clinical significance of extrahepatic autoimmune diseases (EHAIDs) have not been evaluated in a large cohort of primary biliary cholangitis (PBC). METHODS: The medical records of 1554 patients with PBC from 20 international centers were retrospectively reviewed. Development of decompensated cirrhosis (ascites, variceal bleeding, and/or hepatic encephalopathy) and hepatocellular carcinoma were considered clinical endpoints. RESULTS: A total of 35 different EHAIDs were diagnosed in 440 (28.3%) patients with PBC. Patients with EHAIDs were more often female (92.5% vs 86.1%, P < 0.001) and seropositive for anti-mitochondrial antibodies (88% vs 84%, P = 0.05) and antinuclear antibodies and/or smooth muscle antibodies (53.8% vs 43.6%, P = 0.005). At presentation, patients with EHAIDs had significantly lower levels of alkaline phosphatase (1.76 vs 1.98 × upper limit of normal [ULN], P = 0.006), aspartate aminotransferase (1.29 vs 1.50 × ULN, P < 0.001), and total bilirubin (0.53 vs 0.58 × ULN, P = 0.002). Patients with EHAIDs and without EHAIDs had similar rates of GLOBE high-risk status (12.3% vs 16.1%, P = 0.07) and Paris II response (71.4% vs 69.4%, P = 0.59). Overall, event-free survival was not different in patients with and without EHAIDs (90.8% vs 90.7%, P = 0.53, log rank). Coexistence of each autoimmune thyroid diseases (10.6%), Sjögren disease (8.3%), systemic sclerosis (2.9%), rheumatoid arthritis (2.7%), systemic lupus erythematosus (1.7%), celiac disease (1.7%), psoriasis (1.5%), and inflammatory bowel diseases (1.3%) did not influence the outcome. CONCLUSIONS: Our study confirms that EHAIDs are frequently diagnosed in patients with PBC. The presence of EHAIDs may influence the clinical phenotype of PBC at presentation but has no impact on PBC outcome.

Anti-SLA and AMA-positive celiac disease: A report of two cases and evaluation of autoimmune liver serology.

Background and Aim: Antibodies to soluble liver antigen (anti-SLA) and anti-mitochondrial autoantibodies (AMA) are two specific serological markers of autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC). They are rarely detected in the sera of patients with non-liver autoimmune disorders. The biochemical, serological, and histological findings of two celiac disease (CD) patients who were seropositive for anti-SLA and/or AMA were evaluated. The data of two female patients who were 28 and 34 years old at the time of CD diagnosis were analyzed. The first patient presented with elevated liver function tests (LFTs) and immunoglobulin (Ig) G values. She was seropositive for both anti-SLA and AMA. A liver biopsy suggested features of AIH but no bile duct injury was noted. In addition to a gluten-free diet (GFD), immunosuppressive therapy was administered to normalize the LFTs. The second patient presented with elevated LFTs, a high IgG level, and a positive anti-SLA finding. A GFD was initiated, which resulted in an excellent clinical and biochemical response. Seropositivity for AMA in the first patient and anti-SLA in the second patient remained unchanged during follow-up but neither patient developed primary biliary cholangitis or AIH. Despite the high specificity of anti-SLA and AMA, these autoantibodies can be detected in CD without having any clinical relevance.

Two decades of research on autoimmune liver disease in Turkey.

BACKGROUND/AIMS: Autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) are the 3 main autoimmune liver diseases (AILDs). The epidemiology of AILD in Turkey is not known. To determine the scientific status, we performed a scientometric analysis of AILD-related original articles that originated from Turkey. MATERIALS AND METHODS: We searched the Web of Science database, the Science Citation Index Expanded (SCI-E), and the Social Sciences Citation Index (SSCI) by using the keywords "autoimmune hepatitis," "primary biliary cholangitis/primary biliary cirrhosis," and "primary sclerosing cholangitis" in conjunction with "Turkey." A scientometric analysis was done on the search results. RESULTS: We identified 117 AILD-related papers that were published in Turkey from 1997 to 2019. Among these, 70 case reports, letters, and reviews and 2 original articles that were not cited in SCI-E/SSCI were excluded. The remaining 45 original articles were further analyzed. These studies were related to AIH (n=22), PBC (n=7), PSC (n=9), PBC-AIH overlap (n=5), and others (n=2). Four of the publications originated in pediatric settings; 9 of 45 papers were published from 1997 to 2008 and 36 papers were published from 2009 to 2019. Most papers (75%) were reported from 5 centers; 9 papers (20%) were published in journals with an impact factor of 3 or higher. CONCLUSION: The overall number and quality of AILD-related papers in Turkey are unexpectedly low, although a number of papers have received considerable international recognition. More epidemiologic, prospective, and multicenter research projects are warranted to advance AILD knowledge and to produce high-quality research from Turkey.

The effect of concomitant ankylosing spondylitis on long-term outcome of patients with inflammatory bowel disease.

BACKGROUND/AIMS: The aim of the present study was to compare the demographic features and long-term outcomes of patients with inflammatory bowel disease (IBD) with or without ankylosing spondylitis (AS). MATERIALS AND METHODS: Among 1640 IBD (Crohn's disease and ulcerative colitis), 76 patients with IBD+AS were identified. The study group consisted of 76 patients with IBD with synchronous AS. The control group consisted of patients with only IBD, and those were selected according to their registry sequence number being the previous and next case to the diseased case with IBD+AS. The primary endpoint was to compare the rate of intestinal resections between both groups (IBD vs. IBD+AS). RESULTS: Among 76 patients with IBD+AS, 52 (68%) first presented with IBD, 11 (15%) with AS, and the remaining 13 (17%) had both diagnoses at the same time. The mean follow-up time was significantly longer in patients with IBD+AS (43.4 vs. 27.8 months; p=0.01). Twenty-two percent of patients with IBD and 14% of those with IBD+AS had an intestinal resection (p=NS). Biologic and systemic corticosteroid treatments were significantly more common among patients with IBD+AS (32% vs. 7% for biologics, p<0.0001 and 44% vs. 28% for corticosteroids, p=0.042). Age-sex-adjusted regression analysis for both groups disclosed IBD duration as the only independent predictor for resection (R2=0.178; p=0.016). CONCLUSION: The present study shows that up to 5% of patients with IBD may have AS. Patients with IBD+AS do not have a worse disease outcome than solo patients with IBD.

Validation of Risk Scoring Systems in Ursodeoxycholic Acid-Treated Patients With Primary Biliary Cholangitis.

INTRODUCTION: Risk stratification based on biochemical variables is a useful tool for monitoring ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC). Several UDCA response criteria and scoring systems have been proposed for risk prediction in PBC, but these have not been validated in large external cohorts. METHODS: We performed a study on data of 1746 UDCA-treated patients with PBC from 25 centers in Europe, United States, and Canada. The prognostic performance of the risk scoring systems (GLOBE and UK-PBC) and the UDCA response criteria (Barcelona, Paris I, Paris II, Rotterdam, and Toronto) were evaluated. We regarded cirrhosis-related complications (ascites, variceal bleeding, and/or hepatic encephalopathy) as clinical end points. RESULTS: A total of 171 patients reached a clinical end point during a median 7 years (range 1-16 years) of follow-up. The 5-, 10- and 15-year adverse outcome-free survivals were 95%, 85%, and 77%. The GLOBE and UK-PBC scores predicted cirrhosis-related complications better than the UDCA response criteria. The hazard ratio (HR) for a 1 standard deviation increase was HR 5.05 (95% confidence interval (CI): 4.43-5.74, P < 0.001) for the GLOBE score and HR 3.39 (95% CI: 3.10-3.72, P < 0.001) for the UK-PBC score. Overall, the GLOBE and UK-PBC risk scores showed similar and excellent prognostic performance (C-statistic, 0.93; 95% CI: 0.91%-95% vs 0.94; 95% CI: 0.91%-0.96%). DISCUSSION: In our international, multicenter PBC cohort, the GLOBE and UK-PBC risk scoring systems were good predictors of future cirrhosis-related complications.

Prevalence of fecal incontinence and associated risk factors in elderly outpatients: a cross-sectional study.

BACKGROUND: Data on the prevalence of fecal incontinence in elderly patients admitted to outpatient clinics in Turkey are scarce. AIMS: The aim of this study was to assess the prevalence of fecal incontinence and the associated risk factors in the elderly outpatients. METHODS: Patients 60 years and older admitted to a geriatrics outpatient clinic between October 2013 and March 2014 were included. Demographic characteristics, anthropometric measurements, marital status, educational status, parity (for females), fecal incontinence (FI), urinary incontinence (UI), constipation, comorbid conditions, and medications were recorded. FI assessment was based on the Fecal Incontinence Severity Index (FISI). RESULTS: A total of 364 patients (64.8% female, n = 236) with a mean age of 73.2 ± 8.1 years were enrolled in the study. The prevalence of FI was 9.9% (10.2% female, 9.4% male). UI was 42.6%. Co-occurrence of FI and UI was 7.4%. According to the FISI, the most frequent type of defecation was liquid stool (61.1%). While the predictive factors for FI were polypharmacy (standardized coefficient, [r] = 0.203, 95% confidence interval [CI] = 0.009-0.040, p = 0.002), UI (r = 0.134, 95% CI = 0.006-0.156, p = 0.035), and being married (r = 0.200, 95% CI = -0.088 to -0.020, p = 0.002) in females, those were UI (r = 0.306, 95% CI = 0.093-0.309, p < 0.001) and polypharmacy (r = 0.251, 95% CI = 0.009-0.043, p = 0.003) in males. CONCLUSIONS: In both genders, urinary incontinence and polypharmacy seem to be the most important risk factors for fecal incontinence. Fecal incontinence should be questioned in detail and evaluated using FISI in elderly outpatients.

Cardiac angiosarcoma: utility of [(18)F]fluorodeoxyglucose positron emission tomography-computed tomography in evaluation of residue, metastases, and treatment response.

Cardiac angiosarcomas are a rare form of malignancy. The majority of cases arise from the right atrium as mural masses. These tumors have extremely aggressive behavior, with early clinical symptoms that vary depending on location, size, and extent of the tumor. Most of these patients have a very short survival time. Surgical therapy is considered the best choice of therapy approach in cardiac angiosarcoma patients with nonmetastatic disease, even though the disease is rarely cured. Advanced diagnostic techniques facilitate accurate, noninvasive assessments of cardiac sarcomas. We report a case of a 62-year-old man with cardiac angiosarcoma who had multiple distant metastases that were revealed by [(18)F]fluorodeoxyglucose positron emission tomography-computed tomography imaging.