Serum hepcidin levels in chronic liver disease: a systematic review and meta-analysis.

OBJECTIVES: Dysregulation of hepcidin-iron axis is presumed to account for abnormal iron status in patients with chronic liver disease (CLD). Our aim is to determine the effect of specific etiologies of CLD and of cirrhosis on serum hepcidin levels. METHODS: PubMed, Embase, Web of Science were searched for studies comparing serum hepcidin levels in patients with CLD to that in controls using enzyme-linked immunosorbent assay. The study was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Guidelines. Statistical analysis was carried out with STATA using random effects model to calculate the mean difference (MD) between two groups. RESULTS: Hepcidin levels were significantly lower in subjects with hepatitis C virus (16 studies) [MD -1.6 (95 % CI: -2.66 to -0.54), p<0.01] and alcoholic liver disease (3 studies) [MD -0.84 (95 % CI: -1.6 to -0.07), p=0.03] than controls. Serum hepcidin was significantly higher in subjects with non-alcoholic fatty liver disease (12 studies) [MD 0.62 (95 % CI: 0.21 to 1.03), p<0.01], but did not differ in subjects with hepatitis B and controls (eight studies) [MD -0.65 (95 % CI: -1.47 to 0.16), p=0.12]. Hepcidin levels were significantly lower in patients with cirrhosis of any etiology (four studies) [MD -1.02 (CI: -1.59 to -0.45), p<0.01] vs. controls (CI: confidence interval). CONCLUSIONS: Serum hepcidin levels are altered in common forms of CLD albeit not in a consistent direction. Additional study is needed to determine how changes in hepcidin levels are related to dysregulation of iron metabolism in CLD.

Effectiveness and Safety of EUS Rendezvous After Failed Biliary Cannulation With ERCP: A Systematic Review and Proportion Meta-analysis.

BACKGROUND: Endoscopic ultrasound-guided rendezvous (EUS-RV) endoscopic retrograde cholangiopancreatography (ERCP) is an alternative to interventional radiology-guided rendezvous ERCP in patients who failed biliary cannulation with conventional ERCP. However, there is significant variation in reported rates of success and adverse events associated with EUS-RV-assisted ERCP. We performed a systematic review and a proportion meta-analysis to reliably assess the effectiveness and safety of the EUS-RV-assisted ERCP. MATERIALS AND METHODS: We conducted a comprehensive search of multiple electronic databases and conference proceedings (from inception through August 2020) to identify studies reporting EUS-RV-assisted ERCP in patients who failed biliary cannulation with conventional ERCP techniques. Using the random-effects model described by DerSimonian and Laird, we calculated the pooled rates of technical success, clinical success, and adverse events of EUS-RV-assisted ERCP. RESULTS: Twelve studies reporting a total of 342 patients were included in the meta-analysis. The pooled rate of technical success (12 studies reporting a total of 342 patients) was 86.1% [95% confidence interval (CI): 78.4-91.3]. The pooled rate of clinical success (4 studies reporting a total of 94 patients) was 80.8% (95% CI: 64.1-90.8). The pooled rate of overall adverse events (12 studies; 42 events in 342 patients) was 14% (95% CI: 10.5-18.4). Low to moderate heterogeneity was noted in the analyses. CONCLUSIONS: EUS-RV-assisted ERCP appears to be effective and safe in patients who failed biliary cannulation with conventional ERCP. Given the risk of adverse events, it should be performed in centers with expertise in therapeutic endoscopic ultrasound.

Biliary Sphincterotomy Alone versus Biliary Stent with or without Biliary Sphincterotomy for the Management of Post-Cholecystectomy Bile Leak: A Systematic Review and Meta-Analysis.

BACKGROUND: Endoscopic therapy with endoscopic retrograde cholangiopancreatography is considered the first-line treatment in the management of post-cholecystectomy bile leak (PCBL). Currently, there is no consensus on the most effective endoscopic intervention for PCBL. Hence, we performed a systematic review and meta-analysis to compare the effectiveness and safety of the two interventional groups (biliary sphincterotomy [BS] alone vs. biliary stent ± BS) in management of PCBL. METHODS: We conducted a comprehensive search of multiple electronic databases and conference proceedings (from inception through January 2021). The primary outcome was to compare the pooled rate of clinical success between the 2 groups. The secondary outcome was to estimate the pooled rate of adverse events. RESULTS: The pooled rate of clinical success with BS alone (5 studies, 299 patients) was 88% (95% confidence interval (CI): 84-92%, I2: 0%) and for biliary stent ± BS (5 studies, 864 patients) was 97% (CI: 93-100%, I2: 79%). The rate of clinical success in biliary stent ± BS group was significantly higher than BS alone group (OR: 3.91 95% CI: 2.29-6.69, p < 0.001, I2: 13%). The rate of adverse events was numerically lower in biliary stent ± BS group compared to BS alone (3 studies; OR: 0.65 95% CI: 0.41-1.03, p = 0.07) without statistical significance. Low heterogeneity was noted in the analysis. CONCLUSIONS: Biliary stent ± BS is more effective in endoscopic management of PCBL compared to BS alone. This may be related to inter-endoscopist variation in completeness of sphincterotomy and post-sphincterotomy edema, which can influence the preferential trans-papillary flow of bile.

Ursodeoxycholic Acid Decreases Incidence of Primary Biliary Cholangitis and Biliary Complications After Liver Transplantation: A Meta-Analysis.

After liver transplantation (LT), the role of ursodeoxycholic acid (UDCA) is not well characterized. We examine the effect of UDCA after LT in the prophylaxis of biliary complications (BCs) in all-comers for LT and the prevention of recurrent primary biliary cholangitis (rPBC) in patients transplanted for PBC. Two authors searched PubMed/MEDLINE and Embase from January 1990 through December 2018 to identify all studies that evaluate the effectiveness of UDCA prophylaxis after LT for BCs in all LT recipients and rPBC after LT in patients transplanted for PBC. Odds ratios (ORs) were calculated for endpoints of the BC study. Pooled recurrence rates were calculated for rPBC. The study was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. A total of 15 studies were included, comprising 530 patients in the analysis for BCs and 1727 patients in the analysis for rPBC. UDCA was associated with decreased odds of BCs (OR, 0.70; 95% confidence interval [CI], 0.52-0.93; P = 0.01) and biliary stones and sludge (OR, 0.49; 95% CI, 0.24-0.77; P = 0.004). Prophylactic use of UDCA did not affect the odds of biliary stricture. For patients transplanted for PBC, the rate of rPBC was lower with the prophylactic use of UDCA (IR 16.7%; 95% CI, 0.114%-22.0%; I2 = 36.1%) compared with not using prophylactic UDCA (IR 23.1%; 95% CI, 16.9%-29.3%; I2 = 86.7%). UDCA after LT reduces the odds of BC and bile stones and sludge in all-comer LT recipients and reduces or delays the incidence of rPBC in patients transplanted for PBC. UDCA use after LT could be considered in all LT recipients to reduce the odds of BC and may be particularly beneficial for patients transplanted for PBC by reducing the incidence of rPBC.

Randomized controlled trial comparing the Franseen needle with the Fork-tip needle for EUS-guided fine-needle biopsy.

BACKGROUND AND AIMS: EUS-guided FNA primarily provides cytologic samples. EUS-guided fine-needle biopsy (FNB) with needles that provide histologic specimens may enhance diagnostic yield and facilitate accessory tissue staining. Several different needle designs are currently available and design superiority is unknown. We designed a randomized controlled trial to compare 2 commonly used EUS-FNB needles in their ability to provide histologic tissue samples (primary endpoint) and to reach an accurate diagnosis (secondary endpoint). METHODS: A total of 150 lesions from 134 patients (November 2018 to June 2019) were randomized 1:1 between biopsy with a Franseen needle and a Fork-tip needle. The groups were compared regarding the quality of the tissue samples and diagnostic accuracy. RESULTS: Of 150 lesions, 75 were pancreatic and 75 were other solid lesions in and around the GI tract. There was no statistically significant difference between the Franseen needle and the Fork-tip needle in the yield of adequate histologic samples, 71 of 75 (94.7%) versus 72 of 75 (96%), (P = 1.00), an absolute difference of -1.3% (95% confidence interval [CI], -8.1% to 5.4%). The 2 groups were similar in the diagnostic accuracy of histologic analysis, 64 of 75 (85.3%) versus 68 of 75 (90.7%) (P = .45), absolute difference -5.4% (95% CI, -15.7% to 5%); and in the diagnostic accuracy of combined cytologic and histologic analysis, 65 of 75 (86.7%) versus 69 of 75 (92%) (P = .43), absolute difference -5.3% (95% CI, -15.2% to 4.5%). CONCLUSIONS: There was no significant difference in the performance of the Franseen needle versus the Fork-tip needle. Both needles achieved a high yield of histologic tissue samples and high diagnostic accuracy. (Clinical trial registration number: NCT03672032.).

Outcomes of Radiofrequency Ablation versus Endoscopic Surveillance for Barrett's Esophagus with Low-Grade Dysplasia: A Systematic Review and Meta-Analysis.

BACKGROUND: Endoscopic therapy using radiofrequency ablation (RFA) is a recommended treatment for Barrett's esophagus with high-grade dysplasia (BE-HGD) without a visible lesion which is managed by resection. However, currently, there is no consensus on the management of BE with low-grade dysplasia (BE-LGD) - RFA versus endoscopic surveillance. Hence, we performed a systematic review and meta-analysis of these comparative studies to compare the risk of progression to HGD or esophageal adenocarcinoma (EAC) among patients with BE-LGD treated with RFA versus endoscopic surveillance. METHODS: The primary outcome was to compare the risk of progression to HGD or EAC among patients with BE-LGD treated with RFA versus endoscopic surveillance. RESULTS: Four comparative studies reporting a total of 543 patients with BE-LGD were included in the meta-analysis (234 in RFA and 309 in endoscopic surveillance). The progression of BE-LGD to either HGD or EAC was significantly lower in patients treated with RFA compared to endoscopic surveillance (OR: 0.17, 95% confidence interval [CI]: 0.04-0.65, p = 0.01). The progression to HGD alone was significantly lower in patients treated with RFA versus endoscopic surveillance (OR: 0.23, 95% CI: 0.08-0.61, p = 0.003). The progression to EAC alone was numerically lower in RFA than endoscopic surveillance without statistical significance (OR: 0.44, 95% CI: 0.17-1.16, p = 0.09). Moderate heterogeneity was noted in the analysis. CONCLUSIONS: Based on our meta-analysis, there was a significant reduction in the risk of progression to HGD or EAC among patients with BE-LGD treated with RFA compared with those undergoing endoscopic surveillance. Endoscopic eradication therapy with RFA should be the preferred management approach for BE-LGD.

A Novel Score to Predict Esophageal Varices in Patients with Compensated Advanced Chronic Liver Disease.

BACKGROUND AND AIMS: Several criteria have been described to noninvasively predict the presence of high-risk esophageal varices in patients with compensated advanced chronic liver disease (cACLD). However, a recent study showed that treatment with ß blockers could increase decompensation-free survival in patients with clinically significant portal hypertension, thereby making it important to predict the presence of any esophageal varices. We aimed to develop a simple scoring system to predict any esophageal varices. METHODS: We retrospectively reviewed patients who had vibration-controlled transient elastography (VCTE) at Cook County Hospital, Chicago, USA. Patients with cACLD and liver stiffness measurement (LSM) ≥ 10 kPa with esophagogastroduodenoscopy performed within one year of VCTE were analyzed. We generated a novel score to predict esophageal varices, using the beta coefficient of predictive variables. The score was validated in an external cohort at the University of Iowa Hospital, USA. RESULTS: There were 372 patients in the development cohort and 200 patients in the validation cohort. LSM, platelet count, and albumin were identified as predictors of esophageal varices and were included for generating the Cook County score as "platelet count * - 0.0155872 + VCTE score * 0.0387052 + albumin * - 0.8549209." The area under receiver operating curve for our score was 0.86 for any varices and 0.85 for high risk varices and avoided more endoscopies than the expanded Baveno VI criteria while maintaining a very low miss rate (negative predictive value > 99%). CONCLUSION: We propose a new, highly accurate, and easy-to-use scoring system to predict the presence of not only high-risk but any esophageal varices in patients with cACLD.

Multimedia based education on bowel preparation improves adenoma detection rate: Systematic review & meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Colorectal cancer (CRC) is the third most common cause of cancer worldwide. Studies have shown a strong association between screening colonoscopy and a reduced risk of death from colorectal cancers. The incidence of poor bowel preparation has been reported in up to 25% cases. We conducted a systematic review and comprehensive meta-analysis to evaluate the effect of patient education using multimedia platforms on adenoma detection rate and adequacy of bowel preparation. METHODS: Multiple databases were searched through May 2020 for studies that reported the efficacy of multimedia education (smartphone app and online audio-visual aids) in improving quality of bowel preparation and its effect on adenoma detection rate (ADR). Meta-analysis was performed to determine whether multimedia based patient education (MM) helps improve ADR and bowel preparation quality as compared to controls (CT). RESULTS: We included 13 randomized controlled trials with a total of 3754 patients. Eight studies reported outcomes on ADR and 12 reported on adequacy of bowel preparation. Overall ADR was higher in patients receiving multimedia based education as compared to CT (risk ratio (RR) 1.25, confidence interval (CI) 1.01-1.56, P = 0.04). A higher proportion of patients receiving multimedia based education achieved adequate bowel preparation (RR 1.2, CI 1.1-1.3, P = 0.001). In patients with mean age over 50 years, ADR was better in MM cohort as compared to controls (RR 1.3, CI 1.1-1.6, P = 0.001). CONCLUSION: Pre-colonoscopy patient education using multimedia based platforms seems to improve ADR and the adequacy of bowel preparation.

Predictive Factors and Time to Development of Hepatic Decompensation in Patients with Non-alcoholic Fatty Liver Disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of cirrhosis in the USA. OBJECTIVES: We aimed to determine the time to develop hepatic events in patients with NAFLD and develop a simple model to identify patients at risk for hepatic decompensation. DESIGN: Retrospective cohort study. PATIENTS: Seven hundred patients with NAFLD met inclusion criteria for the study. Patients were divided into model construction (n = 450) and validation (n = 250) cohorts. MAIN MEASURES: Demographic, clinical, and laboratory variables were gathered at the time of diagnosis of NAFLD. Kaplan-Meier analysis determined the time to development of hepatic events from initial diagnosis. A time-to-event prediction model was established in the model construction cohort using the multivariate Cox proportional hazards model and was then internally validated. KEY RESULTS: Forty-nine (7%) patients developed hepatic events at a mean duration of 6.2 ± 4.2 years from initial diagnosis. Kaplan-Meier probability of developing a hepatic event at 5-, 10-, and 12-year intervals was 4.8%, 10.6%, and 11.3%, respectively. Age, presence of diabetes, and platelet count were identified as significant variables to predict hepatic events. NAFLD decompensation risk score was developed as "age × 0.06335 + presence of diabetes (yes = 1, no = 0) × 0.92221 - platelet count × 0.01522" to predict the probability of hepatic decompensation. Risk score model had an area under the curve of 0.89 (95% CI = 0.92, 0.86) and it performed well in both the validation (0.91, 0.87-0.94) and the overall cohort (0.89, 0.87-0.91). CONCLUSIONS: A significant proportion of patients with NAFLD developed hepatic decompensation. We have provided a simple, objective model to help identify "at-risk" patients.

ERCP with overtube-assisted enteroscopy in patients with Roux-en-Y gastric bypass anatomy: a systematic review and meta-analysis.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) in patients with Roux-en-Y gastric bypass (RYGB) anatomy is challenging. Overtube-assisted enteroscopy (OAE) is usually needed to perform ERCP in these patients. There is significant variation in the reported rates of success and adverse events across published studies. We performed a systematic review and meta-analysis to reliably estimate the pooled rates of success and adverse events. METHODS: We performed a systematic search of multiple electronic databases through February 2020 to identify studies reporting outcomes of OAE-ERCP in post-RYGB patients. The pooled rates of enteroscopy success, technical success, and adverse events were estimated for OAE-ERCP. The pooled rates of success and adverse events were also estimated for ERCP using double-balloon enteroscopes (DBE) alone. RESULTS: 10 studies reporting a total of 398 procedures were included in the meta-analysis. The pooled rates of enteroscopy and technical success of OAE-ERCP were 75.3 % (95 % confidence interval [CI] 64.5 - 83.6) and 64.8 % (95 %CI 53.1 - 74.9) respectively. The pooled rate of adverse events was 8.0 % (95 %CI 5.2 - 12.2). The pooled rates of enteroscopy and technical success of DBE-ERCP (four studies) were 83.5 % (95 %CI 68.3 - 92.2) and 72.5 % (95 %CI 52.3 - 86.4), respectively. The pooled rate of adverse events with DBE-ERCP was 9.0 % (95 %CI 5.4 - 14.5). Substantial heterogeneity was noted. CONCLUSIONS: OAE-ERCP appears to be effective and safe in post-RYGB patients. Among the currently available techniques, OAE-ERCP is the least invasive approach in this challenging group of patients. Future studies comparing the effectiveness and safety of alternative novel techniques, such as endosonography-directed transgastric ERCP, with OAE-ERCP are needed.

Serrated polyp detection rate and advanced adenoma detection rate from a US multicenter cohort.

BACKGROUND: Interval colorectal cancers may be associated with a low serrated polyp detection rate (SDR) and advanced adenoma detection rate (AADR). We aimed to determine the SDR and AADR for endoscopists in a United States multicenter cohort. METHODS: We included average-risk screening colonoscopies from five medical centers in the United States. Endoscopists with data on at least 100 average-risk screening colonoscopies were included. We calculated median SDR and AADR for endoscopists with adequate adenoma detection rates (ADRs) > 25 %. We analyzed the relationship between ADR and SDR, and between ADR and AADR using nonparametric Spearman correlation coefficients, scatter plots, and linear regression. RESULTS: We included 3513 screening colonoscopies performed by 26 gastroenterologists. The mean age of patients was 56.8 years (SD 7.4) and 1585 (45 %) were male. All but one endoscopist had an ADR above 25 %. There was a significant positive but modest correlation between ADR and SDR (rho = 0.67, P < 0.01), and between ADR and AADR (rho = 0.56, P < 0.01). For endoscopists with an adequate ADR, median (interquartile range) ADR was 43 % (32.0 % - 48.6 %), median SDR was 8.4 % (7.3 % - 11.4 %), and median AADR was 9.3 % (6.4 % - 12.6 %). CONCLUSION: A significant percentage of endoscopists have either a low SDR or low AADR despite an adequate ADR, justifying the need for separate SDR and AADR benchmarks. Based on our multicenter cohort, endoscopists with adequate ADRs had a median SDR and median AADR of about 8 % and 9 %, respectively.

Diagnostic Yield of Colonoscopy in Young Adults with Lower Gastrointestinal Symptoms in a Multicenter Midwest Cohort.

BACKGROUND/AIMS: Serious gastrointestinal (GI) pathologies are common in older adults compared to young adults (≤40 years). Data on the diagnostic yield (DY) of colonoscopy in young adults with lower GI symptoms are lacking. We aimed to evaluate the overall DY of colonoscopy; and the DY stratified by the presence or absence of bright red blood per rectum (BRBPR) in young adults ≤40 years. METHODS: We reviewed diagnostic colonoscopies performed in young adults by 18 gastroenterologists at 2 different institutions from -October 2016 to April 2019. Patients with familial colorectal cancer (CRC) syndromes were excluded. DY was calculated based on the proportion of abnormal colonoscopy defined as having inflammatory bowel disease (IBD), microscopic colitis (MC), advanced adenoma, or CRC. RESULTS: We included 454 patients, mean (SD) age was 31 (3) years, 162 (36%) were males and mean (SD) BMI was 30 (8.5). BRBPR was the indication for colonoscopy in 194 (43%) patients, 260 (57%) patients had colonoscopy for other lower GI symptoms (abdominal pain, chronic diarrhea, constipation) but without BRBPR. Overall DY of colonoscopy in young adults with lower GI symptoms was 15%; IBD was seen in 43 (10%) patients, MC 10 (2%), and advanced neoplasia/CRC 20 (4%). Overall DY in patients with BRBPR was significantly higher than in patients without BRBPR (22 vs. 11%, p = 0.001). The DY for IBD was also higher in young adults with BRBPR versus without BRBPR (15 vs. 6%, p = 0.003). The DY of patients with both BRBPR and abdominal pain was 34%, for BRBPR and diarrhea was 40%, and for all 3 symptoms of BRBPR, diarrhea, and abdominal pain was 52%. CONCLUSIONS: Significant proportion of young adults with BRBPR have abnormal pathology (22%) justifying evaluation by colonoscopy. For other lower GI symptoms without BRBPR, the necessity of endoscopic evaluation should be determined clinically on a case-to-case basis due to the low overall DY.

Comparison of Biliary Stent versus Biliary Sphincterotomy Alone in the Treatment of Bile Leak.

BACKGROUND AND AIMS: Bile leaks are uncommon but are a painful postoperative complication of hepatobiliary interventions. Many authors advocate treating them with biliary stenting. We compared the outcomes in patients treated with endoscopic biliary sphincterotomy (EBS) alone versus EBS with biliary stenting. METHODS: We reviewed charts of patients treated endoscopically for bile leak from 2009 to 2015 at our tertiary care center. Based on endoscopists' practice preference, patients underwent EBS alone or with a biliary stent. Clinical resolution of bile leak and total number of endoscopic and nonendoscopic interventions were compared between patients treated with EBS alone versus EBS with a biliary stent. RESULTS: Fifty-eight patients were included; etiology was cholecystectomy (52), hepatic resection (5), and liver trauma (1). The leak was from the cystic duct (22), duct of Luschka (23), common bile, or hepatic duct (2), and intrahepatic duct (11). Thirty-seven patients had EBS alone (EBS group), and 21 had stents (stent group). Single intervention resolved the bile leak in 34 (92%) patients in EBS group and 19 (90%) in the stent group (p = 0.85). Resolution was slower (p = 0.02) and more patients required second intervention (p < 0.01) in the stent group. CONCLUSION: EBS with or without a biliary stent is highly effective in the management of bile leak. Clinical resolution of the bile leak is quicker with EBS alone, requires fewer interventions, and may cost less.

Unusual Etiology for Transaminitis.

An infection with Enterobius vermicularis (pinworm) commonly affects the gastrointestinal (GI) tract. The ectopic localization of an enterobius infectious is rare, especially in the liver. We report the case of a 37-year-old man who presented to the gastroenterology clinic with abdominal pain and was found to have elevated transaminases. Workup for acute/chronic liver disease was unrevealing. He underwent endoscopic evaluation showing a live pinworm in the colon. He was treated with albendazole with improvement in GI symptoms and resolution of his transaminitis. There are scarce reports in the literature describing pathognomonic, clinical, imaging, and laboratory findings for pinworm infection. Here, we attempt to review the literature for hepatic involvement with an enterobius infection and discuss the findings via this case.

Systematic review and meta-analysis to determine the impact of iron depletion in dysmetabolic iron overload syndrome and non-alcoholic fatty liver disease.

AIMS: Iron reduction has been proposed as treatment for dysmetabolic iron overload syndrome (DIOS) and non-alcoholic fatty liver disease (NAFLD), but results of published trials are conflicting. We undertook a systematic review and meta-analysis to determine the impact of phlebotomy in DIOS and NAFLD. METHODS: We searched multiple databases systematically for studies evaluating the impact of phlebotomy in DIOS and NAFLD. We calculated weighted summary estimates using the inverse variance method. Study quality was assessed using the Cochrane collaboration tool. RESULTS: We identified nine studies with 820 patients (427 had phlebotomy, 393 lifestyle changes alone). Iron depletion did not improve the Homeostasis Model Assessment (HOMA) index (mean difference [MD] -0.6; confidence interval (CI), -1.7, 0.5; P = 0.3), insulin level (MD -0.8 mU/L; CI, -5.3, 3.7; P = 0.73), or aspartate aminotransferase (AST) (MD -0.7 IU/L; CI, -3.2, 1.8; P = 0.6) in DIOS and/or NAFLD patients as compared to lifestyle changes alone (five studies, 626 patients). There was mild improvement in alanine aminotransferase (ALT) (MD -6.6 IU/L; CI, -11, -2.1); P < 0.01), but the effect size was very small (Cohen's d, 0.15; r statistic, 0.07). Even in the subgroup of patients with NAFLD and hyperferritinemia, phlebotomy did not improve the HOMA index, insulin level, ALT, or AST. Additionally, no study showed significant improvement in liver inflammation or fibrosis with iron reduction. CONCLUSIONS: Phlebotomy does not bring about significant improvement in indices of insulin resistance, liver enzymes, or liver histology in patients with DIOS and/or NAFLD compared to lifestyle changes alone. Current evidence does not support the use of phlebotomy in patients with DIOS or NAFLD.

Topical steroids in eosinophilic esophagitis: Systematic review and meta-analysis of placebo-controlled randomized clinical trials.

BACKGROUND AND AIMS: Eosinophilic esophagitis (EoE) is a clinicopathologic condition characterized by symptoms of esophageal dysfunction in the presence of eosinophil-predominant inflammation of esophageal mucosa. Topical steroids are recommended as first line pharmacologic therapy in EoE. We aimed to determine the efficacy of topical steroids in inducing histologic and clinical remission in children and adults with EoE. METHODS: We performed a systematic search of the MEDLINE, EMBASE, Scopus, and Cochrane library databases for studies investigating the efficacy of topical steroids in EoE. We collected data on the number of patients, dose and duration of therapy, complete and partial histological response, and clinical improvement. We performed meta-analysis of placebo-controlled randomized clinical trials using Review Manager version 5.2. We used funnel plots to evaluate for publication bias. RESULTS: Five studies that included 174 patients with EoE were included in the meta-analysis. Topical fluticasone was administered in three studies involving 114 patients, and topical budesonide in two studies involving 60 patients. Patients treated with topical steroids, as compared with placebo, had higher complete histological remission (odds ratio [OR] 20.81, 95% confidence interval [CI] 7.03, 61.63) and partial histological remission (OR 32.20, 95% CI 6.82, 152.04). There was a trend towards improvement in clinical symptoms with topical steroids as compared with placebo but it did not reach statistical significance (OR 2.72, 95 %CI 0.90, 8.23). CONCLUSIONS: Topical corticosteroids seem to be effective in inducing histological remission but may not have similar significant impact in improving clinical symptoms of EoE. Studies with large sample size are needed to uniformly validate symptom improvement in EoE.

Utility of Platelet Count for Predicting Cirrhosis in Alcoholic Liver Disease: Model for Identifying Cirrhosis in a US Population.

BACKGROUND: Thrombocytopenia has been shown to be the single most useful laboratory investigation for identifying subclinical cirrhosis of varying etiologies. However, alcohol per se can result in thrombocytopenia, and hence it is unclear whether platelet count can identify cirrhosis in patients who are alcoholic. OBJECTIVES: To characterize the utility of clinical predictors, especially platelet count, for identifying the presence of cirrhosis in alcoholics. To develop a simple, objective model for identifying cirrhosis in alcoholics. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 2,471 consecutive hospitalized patients with abnormal liver enzyme levels were screened, from which 272 patients with a history of recent and ongoing alcohol intake, negative diagnostic studies for alternative etiologies of chronic liver disease, and recent liver imaging with ultrasound or CT scan were included. MAIN MEASURES: Results of liver imaging and admission laboratory studies including liver enzymes, coagulation studies, and blood counts. KEY RESULTS: One hundred twenty-nine patients (47%) had cirrhosis based on imaging; 143 patients (53%) had no cirrhosis. A pre-sobriety platelet count (during ongoing alcohol intake) of less than 70*10(3) cells/mm(3) was effective for ruling in cirrhosis (positive likelihood ratio [LR] 6.8, 95% CI: 3.4, 14); platelet count greater than 200*10(3) was useful for ruling out cirrhosis in alcoholics (negative LR 0.18, 95% CI: 0.10, 0.35). Multivariate logistic regression analysis identified international normalized ratio (INR) (p < 0.01) and pre-sobriety platelet count (p < 0.01) as independent predictors of cirrhosis. A Model for identifying Cirrhosis in Alcoholic Liver Disease (MCALD) was developed using the INR and pre-sobriety platelet count; it had an area under the receiver operating characteristic curve of 0.89 and Hosmer-Lemeshow goodness of fit chi(2) (p value) of 8.9 (0.35) for predicting cirrhosis in alcoholics. A MCALD score > 5.5 corresponded to an increased likelihood of cirrhosis (LR: 6.5, 95% CI: 4.3, 11.0) and a MCALD score < 5.5 corresponded to decreased likelihood of cirrhosis in alcoholics (LR: 0.25, 95% CI: 0.19, 0.36). Sobriety platelet count (after alcohol abstinence) at a cutoff of 160*10(3) had positive LR of 7.9 (95% CI: 4.4, 14) and negative LR of 0.42 (95% CI: 0.34, 0.52) for predicting cirrhosis in alcoholics. CONCLUSIONS: A simple model of platelet count and INR has good diagnostic accuracy for identifying cirrhosis in alcoholics.

Factors that predict 1-month mortality in patients with pregnancy-specific liver disease.

BACKGROUND & AIMS: Pregnancy-specific liver diseases such as acute fatty liver of pregnancy; hemolysis, elevated liver enzymes and low platelet syndrome; and preeclampsia-associated liver disease are associated with considerable morbidity and mortality. We investigated the ability of the model for end-stage liver disease (MELD) to predict 1-month mortality among patients with pregnancy-specific liver diseases. We also developed and tested a model to predict mortality based on features of pregnancy-specific liver diseases. METHODS: We performed a retrospective study, analyzing hospital admission, clinical, hematologic, and biochemical data collected from 130 patients with pregnancy-specific liver diseases admitted to the St. John's Medical College Hospital (Bangalore, India) from January 2000 through April 2011. Patients were followed up until 3 months after delivery or death. Logistic regression models were fitted using the MELD score and other variables identified as clinically or statistically significant. The predictive accuracy and calibration of the models were assessed by receiver operating characteristic curves and the Hosmer-Lemeshow goodness-of-fit test. RESULTS: Thirty-two patients (24.6%) died. Mortalities from pregnancy-specific liver diseases within 1 month of admission among patients with MELD scores of 20 to 29, 30 to 39, or 40 or greater were 24.2%, 45.45%, and 90.9%, respectively. Univariate analysis identified encephalopathy, ascites, serum total protein, bilirubin, platelet count, alkaline phosphatase, serum creatinine, and international normalized ratio (INR) as significant variables. Multivariate analysis identified total bilirubin (P < .001) and INR (P < .003) as significant predictors of mortality. MELD score and a model based on only 2 variables (bilirubin level and INR) accurately predicted mortality (C statistics, 0.83 and 0.86, respectively) and were well calibrated (Hosmer-Lemeshow χ(2) = 9.7 [P = .28] and 1.9 [P = .98], respectively). CONCLUSIONS: A new logistic model based on only 2 variables (INR and total bilirubin) was comparable with the MELD model in predicting mortality among women with pregnancy-specific liver diseases.

Optimal alpha-1 antitrypsin level cutoffs for genotype identification in patients with chronic liver disease.

BACKGROUND: Controversy exists whether alpha-1 antitrypsin (A1AT) genotype testing should be performed as a first-line screening for A1AT heterozygous variants. METHODS: We calculated the median and interquartile range of A1AT level for each genotype in 4378 patients with chronic liver disease and "miss rate" of MZ genotype identification at various cutoff levels. FINDINGS: Significant overlap in A1AT level noted with Pi*MM, MZ, and MS variants. Miss rate of Pi*MZ at a cutoff level <100 was 29%, <110 was 18%, <120 was 8%, and <130 was 4%. We suggest simultaneous measurement of A1AT level and genotype in patients with chronic liver disease.