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.

Rapid Response to Treatment of Autoimmune Hepatitis Associated With Remission at 6 and 12 Months.

BACKGROUND & AIMS: Changes in serum levels of transaminases immediately after initiation of treatment for autoimmune hepatitis (AIH) might be associated with biochemical markers of remission and liver-related events. We assessed the outcomes of patients with vs without rapid response to treatment of AIH in a large international cohort. METHODS: We performed a retrospective cohort study, collecting data from 2 independent cohorts of adults with AIH from 12 centers in 7 countries in Europe. We collected information on patient demographics; serologic, histologic, and biochemical analyses; and treatment. We used a receiver operating characteristic curve and Youden index to calculate the optimal percentage decrease in level of aspartate aminotransferase (AST) after 8 weeks of treatment that associated with normalization of transaminase levels after 26 weeks of treatment with predniso(lo)ne (primary outcome) in the first (discovery) cohort (n = 370). We evaluated the results in the second (validation) cohort (n = 370). Secondary outcomes were liver-related death or transplantation. We performed univariate and multivariable logistic and Cox regression with correction for confounders. RESULTS: A significant decrease in level of AST after 8 weeks of treatment was significantly associated with normalization of transaminase levels at 26 and 52 weeks (P < .001); a decrease of more than 80% in level of AST was associated with optimal normalization. In both cohorts, rapid responders (≥80% decrease in level of AST after 8 weeks) were more likely to achieve normalization of transaminases at 26 and 52 weeks when compared to non-rapid responders. Rapid responders in the discovery cohort had lower risk of liver-related death or transplantation (adjusted hazard ratio 0.18; 95% CI 0.05-0.63; P = .007), although this was not confirmed in the validation cohort. Results from measurement of alanine aminotransferase did not differ significantly from those of AST for the primary outcome. Slow responders (without normalization of transaminases after 1 year) had the highest risk of liver transplantation or liver-related death. CONCLUSIONS: In a retrospective study of patients with AIH, we found that a rapid response to treatment, based on level of AST after 8 weeks, associates with normalization of transaminase levels in the following year. Patients with a rapid response also have a lower risk of liver-related death or transplantation than patients without this rapid response.

High discontinuation rate of azathioprine in autoimmune hepatitis, independent of time of treatment initiation.

BACKGROUND: Guidelines regarding treatment for autoimmune hepatitis (AIH) favour two strategies for azathioprine (AZA) introduction: concurrent with steroids at induction or delayed by 2-4 weeks. The safety and efficacy of both strategies have been unexplored. METHODS: We established a cohort of 900 AIH patients from 12 centres in 7 European countries. There were 631 patients who used AZA as part of the therapeutic regimen. We distinguished two groups: patients with early AZA (<2 weeks) or delayed AZA initiation (≥2 weeks). Primary outcome was discontinuation of AZA in the first year of treatment. Cox regression and propensity score matching was performed to determine difference in outcomes between groups. RESULTS: Patients with early AZA initiation had significantly lower transaminases and bilirubin at baseline. Discontinuation rates of AZA did not differ between early and delayed starters (16.6% vs 14.2%), which did not reach statistical significance (hazard ratio 0.97, 95% confidence interval 0.61-1.55, P = .90). Stratification according to baseline disease activity or propensity score matching did not alter the results. Main reason for AZA discontinuation was intolerance to treatment (14.0% vs 13.2%, P = .78) with nausea and vomiting as main side effects. AIH remission rates were comparable among groups. CONCLUSION: The discontinuation rate of AZA in AIH treatment is ~15% in the first year of treatment. Early or delayed AZA initiation does not differ in remission and discontinuation rates in AIH induction therapy. Our data suggest that either strategy may be used as part of AIH treatment.

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.

Tacrolimus and Mycophenolate Mofetil as Second-Line Therapies for Pediatric Patients with Autoimmune Hepatitis.

BACKGROUND: We studied the efficacy and safety of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy in pediatric patients with autoimmune hepatitis (AIH) who were intolerant or non-responders to standard therapy (corticosteroid and azathioprine). PATIENTS AND METHODS: We performed a retrospective study of data from 13 centers in Europe, USA, and Canada. Thirty-eight patients (< 18 years old) who received second-line therapy (18 MMF and 20 tacrolimus), for a median of 72 months (range 8-182) were evaluated. Patients were categorized into two groups: Group 1 (n = 17) were intolerant to corticosteroid or azathioprine, and group 2 (n = 21) were non-responders to standard therapy. RESULTS: Overall complete response rates were similar in patients treated with MMF and tacrolimus (55.6 vs. 65%, p = 0.552). In group 1, MMF and tacrolimus maintained a biochemical remission in 88.9 and 87.5% of patients, respectively (p = 0.929). More patients in group 2 given tacrolimus compared to MMF had a complete response, but the difference was not statistically significant (50.0 vs. 22.2%, p = 0.195). Biochemical remission was achieved in 71.1% (27/38) of patients by tacrolimus and/or MMF. Decompensated cirrhosis was more commonly seen in MMF and/or tacrolimus non-responders than in responders (45.5 vs. 7.4%, p = 0.006). Five patients who received second-line therapy (2 MMF and 3 tacrolimus) developed side effects that led to therapy withdrawal. CONCLUSIONS: Long-term therapy with MMF or tacrolimus was generally well tolerated by pediatric patients with AIH. Both MMF and tacrolimus had excellent efficacy in patients intolerant to corticosteroid or azathioprine. Tacrolimus might be more effective than MMF in patients failing previous therapy.

Efficacy and Safety of Mycophenolate Mofetil and Tacrolimus as Second-line Therapy for Patients With Autoimmune Hepatitis.

BACKGROUND & AIMS: Predniso(lo)ne, alone or in combination with azathioprine, is the standard-of-care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy for patients with AIH. METHODS: We performed a retrospective study of data (from 19 centers in Europe, the United States, Canada, and China) from 201 patients with AIH who received second-line therapy (121 received MMF and 80 received tacrolimus), for a median of 62 months (range, 6-190 mo). Patients were categorized according to their response to SOC. Patients in group 1 (n = 108) had a complete response to the SOC, but were switched to second-line therapy as a result of side effects of predniso(lo)ne or azathioprine, whereas patients in group 2 (n = 93) had not responded to SOC. RESULTS: There was no significant difference in the proportion of patients with a complete response to MMF (69.4%) vs tacrolimus (72.5%) (P = .639). In group 1, MMF and tacrolimus maintained a biochemical remission in 91.9% and 94.1% of patients, respectively (P = .682). Significantly more group 2 patients given tacrolimus compared with MMF had a complete response (56.5% vs 34%, respectively; P = .029) There were similar proportions of liver-related deaths or liver transplantation among patients given MMF (13.2%) vs tacrolimus (10.3%) (log-rank, P = .472). Ten patients receiving MMF (8.3%) and 10 patients receiving tacrolimus (12.5%) developed side effects that required therapy withdrawal. CONCLUSIONS: Long-term therapy with MMF or tacrolimus generally was well tolerated by patients with AIH. The agents were equally effective in previous complete responders who did not tolerate SOC therapy. Tacrolimus led to a complete response in a greater proportion of previous nonresponder patients compared with MMF.

Treatment Response and Outcome with Two Different Prednisolone Regimens in Autoimmune Hepatitis.

BACKGROUND: Beyond available guidelines, therapy of autoimmune hepatitis (AIH) shows wide variation among physicians. We compared two regimens for treatment naive AIH: one recommended protocol with an initial prednisolone dose of 30 mg/day and our own 40 mg/day prednisolone with a slow dose tapering protocol. We analyzed the safety, response rates, and outcomes for two groups of treated patients. PATIENTS AND METHODS: We retrospectively evaluated data of 71 AIH patients including, group I (n = 32, prednisone 30 mg/day) and group II (n = 39, prednisone 40 mg/day). All patients also received azathioprine. RESULTS: The frequency of complete biochemical response was significantly higher in group II than in group I (69.2 vs. 43.8%, p = 0.031) after 3 months of therapy, but not after 6 and 12 months (79.5 vs. 59.4%, p = 0.065 and 89.5 vs. 80.6%, p = 0.30). In patients with severe interface hepatitis, the complete response rates were significantly higher in group II than in group I after 3 (63.6 vs. 23.1%, p = 0.02) and 6 months (72.7 vs. 38.5%, p = 0.046), but not after 12 months of therapy (86.4 vs. 69.2%, p = 0.221). Relapses were observed in 50% of group I and in 35.9% of group II during maintenance therapy (p = 0.23). Overall survival was significantly better in group II than in group I (100 vs. 87.5%, log-rank, p = 0.048). No severe steroid-related side effects were observed in either group. CONCLUSIONS: Our real-world experience suggests that an initial prednisolone dose of 40 mg/day with a slower tapering protocol induces earlier biochemical response, tends to result in less relapses during maintenance, and is associated with a better disease outcome.

Inflammation and chemerin in colorectal cancer.

Chemerin is expressed mainly in the adipose tissue. It is an agonist of chemokine-like receptor-1, which is expressed by the immune system cells. Chemerin stimulates the chemotaxis of the immune system cells, and this indicates the function of chemerin and chemokine-like receptor-1 in the immune response. The tumor microenvironment is very important for determining cancer cell growth and spreading. Therefore, we aimed to investigate the association between colorectal cancer, inflammation, and adipokines including chemerin, adiponectin, and vaspin. The study group consisted of patients with colon cancer, whereas the control subjects consisted of patients with benign conditions, diagnosed with colonoscopy. The two groups were compared in terms of the C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, adiponectin, chemerin, and vaspin. A total of 41 (28 men, 13 women) patients with confirmed colon cancer, and 27 (15 men, 12 women) controls without, confirmed by colonoscopy, were enrolled. The median chemerin levels were found significantly higher in the study group than the controls (390 vs. 340 ng/mL, p = 0.032), whereas the mean vaspin and adiponectin levels were not significantly different. The median values for the CRP, fibrinogen, and ESR were significantly higher in the patients with colon cancer, when compared to the control group (6.08 vs. 1.4 mg/L, p < 0.0001; 408 vs. 359 mg/dL, p = 0.002; and 30 vs. 8 mm/h, p < 0.0001, respectively). Our results show that higher levels of circulating chemerin, CRP, fibrinogen, and ESR are associated with an increased risk of developing colorectal cancer.

Nitric oxide is a potential mediator of hepatic inflammation and fibrogenesis in autoimmune hepatitis.

BACKGROUND: Despite advances in the understanding of the pathophysiological basis of autoimmune hepatitis (AIH), it is still difficult to delineate the mechanisms involved in progression from hepatic inflammation toward fibrosis. Our aim was to study serum concentrations of NO in AIH of different histological severity and possible effects of immunosuppressive therapy on NO production. MATERIALS AND METHODS: We studied serum NO metabolites (NOx) in 47 consecutive patients with AIH and in 28 age- and sex-matched controls. RESULTS: Serum NOx concentrations were higher in AIH patients than in controls (10.3 (4.5-27.3 µmol/L) vs. 4.3 (1.6-14.3 µmol/L), p < 0.001). According to liver histology, median NOx concentrations were significantly higher in patients with severe interface hepatitis compared to patients with mild-moderate interface hepatitis (12.3 (4.5-27.3 µmol/L) vs. 9.3 (4.6-20.3 µmol/L), p = 0.029). Similarly, serum NOx concentrations were significantly higher in patients with advanced fibrosis than in those with early fibrosis (12.2 (4.6-27.3 µmol/L) vs. 9.3 (6.6-12.8 µmol/L), p = 0.018). NOx concentrations decreased in 16 AIH patients who were tested also after biochemical remission was achieved (12.6 (4.5-22.8 µmol/L) at baseline and 5.9 (2.8-10.5 µmol/L) after remission, p = 0.001). CONCLUSION: This study shows that serum NOx levels are associated with the histological severity of AIH. Hepatocyte inflammation and injury may activate hepatic stellate cells and kupffer cells, and the consequences may include release of NO, which ultimately promotes hepatic fibrosis. Immunosuppressive therapy inhibits this process and the production of NO.

Acoustic Radiation Force Impulse (ARFI) for Fibrosis Staging in Patients with Autoimmune Hepatitis.

BACKGROUND/AIMS: The performance of non-invasive fibrosis markers has not been well studied in autoimmune hepatitis (AIH). Acoustic radiation force impulse imaging (ARFI) is a non-invasive radiological method for assessment of liver fibrosis. The aim of this study was to evaluate the accuracy of ARFI for fibrosis staging in patients with AIH. METHODOLOGY: AIH patients who undergone for control liver biopsy after at least two years of biochemical remission period were also assessed by ARFI. Liver fibrosis was staged according to the METAVIR scoring system. RESULTS: A total of 15 patients (13 women and 2 men) with mean age of 40.9 (18-59 years) were included in the study. Repeat liver biopsy was performed a mean of 4.9 (3-9 years) after AIH diagnosis. Nine patients had significant fibrosis scores (F ≥ 2) while, remain 6 patients had mild or no fibrosis. The mean (±SD) shear wave velocities for patients with fibrosis stage II-IV was significantly higher than those with fibrosis stage 0-I (2.28 ± 0.68 m/s and 1.20 ± 0.24, respectively, p = 0.002). CONCLUSIONS: ARFI is able to differentiate significant from non significant liver fibrosis in patients with AIH. Our study suggests that this non-invasive method can be used for monitoring fibrosis progression in AIH.

Factors associated with response to therapy and outcome of patients with primary biliary cirrhosis with features of autoimmune hepatitis.

BACKGROUND & AIMS: For patients with primary biliary cirrhosis (PBC) with features of autoimmune hepatitis (AIH), treatment with ursodeoxycholic acid (UDCA) alone or in combination with immunosuppression is controversial. Little is known about the factors associated with initial response to therapy or outcome. We performed a retrospective analysis of treatment strategies and factors associated with outcomes of patients with PBC-AIH. METHODS: We analyzed data from 88 patients who were diagnosed with PBC-AIH according to Paris criteria, from 7 centers in 5 countries. First-line therapies included UDCA alone (n = 30) or a combination of UDCA and immunosuppression (n = 58). RESULTS: Of patients who received UDCA alone as the first-line therapy, 37% did not respond to treatment. Severe interface hepatitis was independently associated with lack of response to treatment (P = .024; odds ratio, 0.05; 95% confidence interval, 0.004-0.68). The combination of UDCA and immunosuppression was effective in 73% of patients who had not been previously treated or had not responded to UDCA. The presence of advanced fibrosis was associated with lack of response to the combination of UDCA and immunosuppression (P = .003; odds ratio, 0.13; 95% confidence interval, 0.03-0.48). Second-line immunosuppressive agents (cyclosporine, tacrolimus, and mycophenolate mofetil) led to biochemical remission in 54% of patients who did not respond to initial immunosuppression. Liver transplants were given to 4 patients with PBC-AIH. Five patients died during follow-up (3 from liver-related causes). CONCLUSIONS: In a retrospective study of a large cohort of patients with PBC-AIH, UDCA alone did not produce a biochemical response in most patients with severe interface hepatitis; these patients require additional therapy with immunosuppression. Second-line immunosuppressive agents are effective in controlling disease activity in patients who do not respond to conventional immunosuppression.

The comparison of two different 5.5 fr sphincterotomes for selective cannulation of the common bile duct: a prospective, randomized study.

BACKGROUND AND AIM: There are scarce data regarding the impact of sphincterotome design on cannulation success. We aimed to compare two different 5.5 Fr standard sphincterotomes to determine initial cannulation success. METHODS: Adult patients with naive papillae were enrolled in a prospective, randomized, crossover study. Two different 5.5 Fr sphincterotomes preloaded with guidewire (GW) were used in two groups with 140 patients included per group. A total of five papillary attempts and two pancreatic channel entries were allowed as maximum targets. In a case of more than two pancreatic entries, a double GW technique was attempted before crossover. If choledochal cannulation was not achieved within ten papillary attempts or more than four pancreatic entries despite crossover, access papillotomy was performed. Successful biliary cannulation was the primary outcome. Secondary outcomes were incidence of early complications and overall cannulation success. RESULTS: Higher initial cannulation success was achieved in group I compared with group II (88.5 vs. 77.1%, p = 0.011). The crossover and double GW techniques reduced the need for precut from 11.7 to 5.3%. The overall cannulation success including precut for failed cases was 99.2% (group I) and 98.5% (group II). Sphincterotome type, presence of crossover, and number of cannulation attempts were predictors of successful cannulation in multivariate analysis. CONCLUSIONS: There was a significant difference in cannulation success between two different 5.5 Fr sphincterotomes. The cannulation success was mainly governed by sphincterotome design which serves a proper spatial orientation during the procedure. The combined use of crossover and double GW techniques may substantially decrease precut necessity.

Low serum vitamin D levels are associated with severe histological features and poor response to therapy in patients with autoimmune hepatitis.

BACKGROUND AND AIM: 25-Hydroxyvitamin D [25(OH)D] has an important role in fibrosis progression and inflammatory response in patients with various etiologies of chronic liver disease. However, its influence on autoimmune hepatitis (AIH) has not been investigated. We evaluated the association of serum 25(OH)D levels with clinical, biochemical and histological features and response to therapy in AIH. MATERIALS AND METHODS: Serum 25(OH)D levels were quantified in 68 therapy naïve AIH patients and 34 healthy controls. RESULTS: Mean serum 25(OH)D levels were significantly lower in AIH compared to healthy controls (16.8 ± 9.2 vs. 35.7 ± 13.6, p < 0.0001). Low levels of 25(OH)D (<30 µg/L) were independently associated with advance fibrosis and severe interface hepatitis in AIH patients [p = 0.014; odds ratio (OR) 0.12, 95% confidence interval (CI) 0.02-0.65 and p = 0.020; OR 0.17, 95% CI 0.04-0.76, respectively]. Severe 25(OH)D deficiency (<10 µg/L) was associated with advance fibrosis, severe interface hepatitis, low platelet counts and sampling time in a univariate analysis. Only interface hepatitis and fibrosis scores were independently associated with 25(OH)D deficiency in a multiple regression analysis (p = 0.005; OR 0.12, 95% CI 0.03-0.53 and p = 0.022; OR 0.15, 95% CI 0.03-0.75, respectively). Mean serum 25(OH)D levels were lower in non-responders compared to responders (9.2 ± 4.8 vs. 17.1 ± 9.4, p = 0.015), and 25(OH)D deficiency was more commonly observed in non-responders than the responders (80 vs. 43%, p = 0.036). CONCLUSIONS: Low 25(OH)D levels are associated with advance fibrosis and severe inflammation in AIH. Our study suggests that vitamin D may be a potential biomarker that predicts response to therapy and histological features in AIH.

Antibodies to soluble liver antigen in patients with various liver diseases: a multicentre study.

BACKGROUND: Antibodies to soluble liver antigen (anti-SLA) are specific serological markers of autoimmune hepatitis (AIH). The clinical significance and frequency of anti-SLA have never been reported among AIH patients from Italy and Turkey. To retrospectively assess the estimated prevalence, sensitivity, specificity and clinical significance of anti-SLA in AIH and various liver diseases. METHODS: A total of 986 patients who had been tested for serum anti-SLA were included in study. The presence of anti-SLA was detected using recombinant enzyme linked immunosorbent assay and immuno-blot. The general characteristics and outcome of patients were obtained from their medical records. RESULTS: Antibodies to SLA were found in 30 (3%) of 986 patients. Of these, 27 (90%) had AIH and its variants, whereas the remaining three (10%) had primary biliary cirrhosis. The prevalence of anti-SLA was 9% in AIH patients from Italy and 15% in patients from Turkey. The specificity of these antibodies was 99.5%, whereas sensitivity was 11%. The positive predictive and negative predictive values were 90% and 77.5% respectively (95% confidence interval). Biochemical remission was achieved in 90% of anti-SLA positive AIH patients, but relapse after immunosuppressive withdrawal or during maintenance therapy was observed in 53% of the patients. CONCLUSIONS: Seropositivity for anti-SLA occurs at similar frequencies in AIH patients from different geographical regions and ethnic groups. The sensitivity of anti-SLA is low, but it has high specificity for AIH. Additional studies are necessary to prove clinical significance of anti-SLA in AIH.

Diagnostic difficulties, therapeutic strategies, and performance of scoring systems in patients with autoimmune hepatitis and concurrent hepatitis B/C.

BACKGROUND: The diagnosis of autoimmune hepatitis (AIH) is already difficult, and that of AIH with chronic viral hepatitis including hepatitis B (HBV) or hepatitis C (HCV) is even more challenging. To date, only a few case-based studies have described this association. AIM: The aim was to retrospectively assess diagnostic difficulties, therapeutic approaches, and performance of the scoring systems in AIH patients with concurrent HBV and HCV. METHODS: A total of 25 patients from United States, Sweden, Italy, and Turkey were retrospectively evaluated. Both revised and simplified criteria suggested by the International Autoimmune Hepatitis Group were applied for each patient. All study data were obtained from medical records. RESULTS: Of the 25 patients, 20 (80%) had concomitant HCV and 5 (20%) had HBV. Based on the revised scoring system and simplified criteria, 18 (72%) and 12 (48%) patients were diagnosed as "probable" AIH. None of the patients were diagnosed as "definite" AIH according to both scoring systems. Patients with HCV initially were treated with immunosuppressive agents, and antiviral therapy was commenced when biochemical remission occurred. AIH patients with HBV were first treated with antiviral and thereafter, immunosuppressive therapy was started. CONCLUSIONS: This large case series describes concurrent AIH and chronic viral hepatitis. The revised scoring system for AIH had a better performance than the simplified scoring system. However, neither scoring system is optimal for diagnosing AIH alone. In these patients, a definitive diagnosis of AIH should be based on a combination of serological profiles, histological findings, scoring systems, treatment response, and outcomes.

The impact of sphincterotome design on selective cannulation of the common bile duct.

BACKGROUND AND AIM: There is a paucity of data regarding the impact of sphincterotome design on cannulation success. METHODS: We aimed to compare the 5.5 F standard sphincterotomes of two different manufacturers (sphincterotome 1: Endo-flex 5.5F [ENDO-FLEX GmbH, Voerde, Düsseldorf, Germany] vs sphincterotome 2: Ultratome 5.5F [Boston Scientific, Spencer, IN, USA]). Adult patients undergoing their first endoscopic retrograde cholangiopancreatography were included in two study groups. The sphincterotome preloaded with a guidewire was used for selective common bile duct cannulation in each group. Precut methods were applied in failed cases without crossover. Successful biliary cannulation in 10 attempts was the primary outcome. RESULTS: Baseline features and indications were similar between groups (n = 100, group I, sphincterotome 1, vs n = 100, group II, sphincterotome 2). A higher success in initial cannulation was obtained in group II compared to group I (92% vs 81%, P = 0.03). Moreover, number of cannulation attempts and time to cannulation differed. No statistical significance was noted in group I (8%) versus group II (3%) regarding pancreatitis rate. The overall cannulation success after precut in failed cases was 95% (group I) and 97% (group II). CONCLUSIONS: There was a significant difference in cannulation success between the two different sphincterotome. 5.5F Ultratome with guidewire was superior to 5.5F Endo-flex sphincterotome with guidewire in initial selective cannulation of common bile duct. The results may show the importance of sphincterotome features to overcome the obstacles during cannulation such as complex intrapapillary mucosal features.

Diagnosis and Treatment of Autoimmune Hepatitis: Questions, Answers, and Illustrative Cases: Endorsed by Autoimmune Liver Diseases Special Interest Group, Turkish Association for the Study of Liver.

Autoimmune hepatitis (AIH) is a rare, immune-mediated liver disease. It has a heterogeneous nature with varied clinical presentations. The management of patients with AIH is challenging in many ways. The main difficulties are inexperience due to the rarity of the disease, diagnostic confusion in controversial areas such as variant/overlap cases, acute presentations, the presence of non-alcoholic fatty liver disease or drug-induced liver injury features, and the long and complex course of treatment. Here, we provide a clear, concise, and visualized review regarding the diagnosis and treatment of AIH, including illustrative cases.