Diagnosis of HDV: From virology to non-invasive markers of fibrosis.

Hepatitis D viral infection in humans is a disease that requires the establishment of hepatitis B, relying on hepatitis B surface Ag and host cellular machinery to replicate and propagate the infection. Since its discovery in 1977, substantial progress has been made to better understand the hepatitis D viral life cycle, pathogenesis and modes of transmission along with expanding on clinical knowledge related to prevention, diagnosis, monitoring and treatment. The availability of serologic diagnostic assays for hepatitis D infection has evolved over time with current widespread availability, improved detection and standardized reporting. With human migration, the epidemiology of hepatitis D infection has changed over time. Thus, the ability to use diagnostic assays remains essential to monitor the global impact of hepatitis D infection. Separately, while liver biopsy remains the gold standard for the staging of this rapidly progressive and severe form of chronic viral hepatitis, there is an unmet need for clinical monitoring of chronic hepatitis D infection for management of progressive disease. Thus, exploration of the utility of non-invasive fibrosis markers in hepatitis D is ongoing. In this review, we discuss the virology, the evolution of diagnostics and the development of non-invasive markers for the detection and monitoring of fibrosis in patients with hepatitis D infection.

Non-alcoholic steatohepatitis is independently associated with a history of gestational diabetes mellitus.

BACKGROUND AND AIM: A recent study has demonstrated that women with gestational diabetes mellitus (GDM) are more likely to develop non-alcoholic fatty liver disease than those without GDM. In contrary to non-alcoholic fatty liver, the association of GDM with non-alcoholic steatohepatitis (NASH) has still not been well established in the current literature. Therefore, we aim to evaluate the association of a history of GDM and the development of NASH throughout their lives independently of type 2 diabetes mellitus (T2DM). METHODS: A validated research database of more than 360 hospitals was utilized to construct this study. Adult females included were divided into two groups: those with NASH (case) and individuals without NASH (control). Regression analysis was performed to account for potential cofounders. RESULTS: There were 70 632 640 individuals above the age of 18 years screened in the database. In patients with a history of GDM, NASH was most prevalent in middle age people compared with NASH alone, which was more prevalent in people aged 65 years and above. Compared with those without, patients with NASH tend to be Caucasian (odds ratio [OR]: 2.13), obese (OR: 4.83), have a history of GDM (OR: 1.23), diagnosed with hyperlipidemia (OR: 2.59), T2DM (OR: 4.52), metabolic syndrome (OR: 3.07), polycystic ovaries disease (OR: 1.72), and hypothyroidism (OR: 1.59). CONCLUSION: We demonstrated for the first time an increased odd of developing NASH in women who have had a diagnosis of gestational diabetes mellitus throughout their lives independently of any other factors that could interfere with the results.

Epidemiology and prevalence of lean nonalcoholic fatty liver disease and associated cirrhosis, hepatocellular carcinoma, and cardiovascular outcomes in the United States: a population-based study and review of literature.

BACKGROUNDS: Nonalcoholic fatty liver disease (NAFLD) is linked to obesity and metabolic syndrome conditions. However, a subset of NAFLD patients express a normal or low body mass index (lean NAFLD [L-NAFLD]). Our aim is to compare the prevalence of L-NAFLD to the obesity-associated NAFLD in the United States by assessing prevalence, potential risk factors, liver-related complications, and coronary artery disease outcomes. METHODOLOGY: A multicenter database (Explorys Inc.) of >70 million patients across the United States was screened. A cohort of patients with "nonalcoholic fatty liver" between 1999 and 2021 was identified. Two sub-cohorts of NAFLD patients were identified: those with a body mass index (BMI) < 25 kg/m2 (L-NAFLD) and those with a BMI > 30 kg/m2 (obesity-associated NAFLD). We excluded patients with age <18 and those who have viral hepatitis, hemochromatosis, Wilson's disease, biliary cirrhosis, alcoholic liver disease, cystic fibrosis, alpha-1-antitrypsin deficiency, and autoimmune hepatitis. Multivariate analysis was performed to adjust for confounders. RESULTS: 68 892 260 individuals were screened. NAFLD prevalence was four per 100 000, and L-NAFLD prevalence was 0.6 per 100 000. Compared with those without, patients with L-NAFLD tended to be older (OR 2.16), females (OR 1.28), and smokers (OR 4.67) and of Asian race (OR 2.12). L-NAFLD patients were more likely to have acute coronary syndromes (OR 30.00) and metabolic syndrome (OR 2.31) despite the normal/low BMI. Esophageal varices and hepatocellular carcinoma risks were high in both cirrhosis patients. CONCLUSION: This is the largest study to assess L-NAFLD prevalence in the United States. L-NAFLD are at a significantly higher risk for acute coronary syndromes, esophageal varices, and hepatocellular carcinoma.

Obesity Is Associated with Decreased Risk of Clostridium difficile Infection in Hospitalized Patients with Pouchitis.

BACKGROUND: Clostridium difficile infection (CDI) is one of the leading causes of health-care-associated infections in the USA. There are limited data available regarding CDI in hospitalized patients with inflammatory bowel disease-related ileal pouch. AIMS: This study aimed to evaluate the demographics, clinical features, risk factors, and admission outcomes among hospitalized patients with CDI-related pouchitis (CDP). METHODS: Retrospective chart review was performed for patients who were admitted to our institute for pouchitis between 2013 and 2016 to identify patients with CDP. Logistic regression analysis was performed to assess the risk factors associated with CDP. RESULTS: A total of 160 subjects with pouchitis had a total of 218 admissions during the study period. Primary admission diagnosis was pouchitis or inflammatory bowel disease flare-up for 202 (93%) admissions. Clostridium difficile was tested at least once for 72 patients, and the diagnosis of CDP was established for 16 (10%) patients. All patients with CDP were symptomatic, 13 (81%) had diarrhea, 8 (50%) had abdominal pain, 7 (44%) had nausea/vomiting, and 2 (13%) had gastrointestinal bleeding. On multivariable analysis, only body mass index > 25 (OR 0.25, 95% CI 0.06-0.94, p = 0.048) was significantly associated with decreased risk of CDP. No patients in CDP cohort were admitted to ICU, died at the hospital, or readmitted in 30 days after the discharge. CONCLUSIONS: In our cohort, obesity was associated with low risk of CDP among hospitalized patients with pouchitis. This finding warrants further validation in prospective studies.

Cardiotoxic Effects of Raw Opium.

While opioid drug toxicity and side effects of long-term opioid use during medical care are well studied, there is little information regarding effects of ingestion of raw opium. Characterization of the effects to a particular alkaloid is difficult since raw opium contains a number of alkaloids. Here, we present a case of poisoning due to ingestion of raw opium leading to severe myocardial suppression.

Severe Hypokalemia Mimicking Brain Death.

We discuss a case of a 20-year-old female who presented with history of fever, vomiting, and decreased oral intake for 10 days followed by one episode of generalized tonic-clonic seizure and altered sensorium for 5-6 h. On arrival in the emergency room, she had Glasgow Coma Scale 3 (E1V1M1), both pupils fixed and dilated, low blood pressure, low oxygen saturation, and few gasping breaths. She appeared to be brain dead and was assumed to have a very poor prognosis. Investigations revealed severe hypokalemia. She had also suffered acute hypoxic-ischemic injury to the brain. However, she recovered and was discharged about 2 weeks later.

Meta-analysis: Incidence of cirrhosis and hepatocellular carcinoma in patients with Fontan palliation.

BACKGROUND AND AIMS: The Fontan palliation is the final stage of surgery for many children born with univentricular physiology. Almost all Fontan patients develop liver fibrosis which may eventually lead to cirrhosis and hepatocellular carcinoma (HCC). These are important causes of morbidity and mortality in these patients. We performed a systematic review and meta-analysis to assess the incidence of cirrhosis and HCC in Fontan patients and stratify it based on time since surgery. METHODS: A literature search of seven databases identified 1158 records. Studies reporting the number of cirrhosis and HCC cases in Fontan patients and time since Fontan surgery were included. In the cirrhosis cohort, we included only those studies where all patients underwent liver biopsy. RESULTS: A total of 23 studies were included: 12 and 13 studies in the cirrhosis and HCC cohorts, respectively, with two studies included in both cohorts. The incidence of cirrhosis was 0.97 per 100 patient-years (95% CI 0.57-1.63), with the incidence and cumulative incidence ≥20 years post Fontan surgery being 1.61 per 100 patient-years (95% CI 1.24-2.08) and 32.2% (95% CI 25.8%-39.4%), respectively. The incidence of HCC was 0.12 per 100 patient-years (95% CI 0.07-0.21), with the incidence and cumulative incidence ≥20 years post Fontan surgery being 0.20 per 100 patient-years (95% CI 0.12-0.35) and 3.9% (95% CI 2.2%-6.8%), respectively. Only about 70% of patients with HCC (20/28) had underlying cirrhosis. CONCLUSION: The incidence of cirrhosis and HCC increases over time, especially at ≥20 years post Fontan surgery. Studies are needed to further identify at-risk patients in order to streamline surveillance for these highly morbid conditions.

Intramucosal Extent as a Marker for Advanced Disease and Survival in Gallbladder Adenocarcinoma.

BACKGROUND: Gallbladder cancer (GBC) is the most common biliary tract malignancy and has a poor prognosis. The clinical significance of focal vs diffuse GBC remains unclear. METHODS: A retrospective review was conducted on all patients with non-metastatic GBC at a quaternary care center. Pathology was reviewed, and gallbladder cancer pattern was defined based on the extent of mucosal involvement; "diffuse" if the tumor was multicentric or "focal" if the tumor was only in a single location. Patients undergoing liver resection and portal lymphadenectomy were considered to have definitive surgery. The primary outcome was overall survival and assessed by Kaplan-Meier curves. RESULTS: 63 patients met study criteria with 32 (50.7%) having diffuse cancer. No difference was observed in utilization of definitive surgery between the groups (14 [43.8%] with focal and 12 [38.7%] with diffuse, P = .88). Lymphovascular invasion (P = .04) and higher nodal stage (P = .04) were more common with diffuse GBC. Median overall survival was significantly improved in those with focal cancer (5.1 vs 1.2 years, P = .02). Although not statistically significant, this difference in overall survival persisted in patients who underwent definitive surgery (4.3 vs 2.4 years, P = .70). DISCUSSION: Patients with diffuse involvement of the gallbladder mucosa likely represent a subset with aggressive biology and worse overall survival compared to focal disease. These findings may aid surgeons in subsequent surgical and medical decision-making for patients with GBC.

Prospective evaluation of patients with non-cirrhotic portal hypertension: A single centre study.

BACKGROUND: Non-cirrhotic portal hypertension (NCPH) is a spectrum of liver diseases, including porto-sinusoidal vascular disorder, with portal hypertension (PH) in the absence of cirrhosis. The natural history and diagnostic approach to NCPH are not well understood. AIM: We aimed to evaluate disease progression and outcomes in NCPH. METHODS: Patients with or at risk for NCPH were enrolled in a single centre prospective study; two groups were formed based on the presence of specific features of PH, such as varices, collaterals, portal hypertensive gastropathy or portal hypertensive bleeding. All participants underwent a baseline liver biopsy. Liver stiffness measurement (LSM), and imaging were repeated every 6-12 months. RESULTS: Fifteen patients without specific features of PH (Group I), and 35 patients with specific features (Group II) were enrolled. The median follow-up time was 50 months. Group II had higher hepatic venous pressure gradients, non-invasive measures of PH and a lower platelet count (PLT) when compared to Group I. Rates of survival and decompensation were similar in both groups. Patients with PLT ≤100 K/mcL had lower survival compared to those with PLT >100 K/mcL. Patients with LSM ≥10 kPa had lower survival and survival without decompensation when compared to patients with LSM <10 kPa. CONCLUSIONS: Patients irrespective of specific features of PH had similar survival or survival without decompensation. Patients without specific features are at risk for disease progression and should be monitored closely. Thrombocytopenia and increased LSM are associated with severe forms of liver disease, which are strongly associated with outcomes.

Cirrhotic patients on proton pump inhibitors are at a twofold risk of spontaneous bacterial peritonitis independently of gastrointestinal bleeding: a population-based retrospective study.

Background: Recent findings suggest that cirrhotic patients on proton pump inhibitors (PPIs) are at a higher risk for developing spontaneous bacterial peritonitis (SBP) than non-PPI users. We aimed to identify whether PPI use is an independent risk factor for the development of SBP among cirrhotic patients in the United States (US). Methods: We enrolled a retrospective cohort using a validated multicenter database. Patients with a SNOMED-CT diagnosis of "cirrhosis" between 1999 and 2022 were identified. All patients below 18 years of age were excluded. We calculated the prevalence of individuals using PPIs in the total US population and in cirrhotic patients from 1999 to date, and the incidence of SBP in the past year. Finally, we constructed a multivariate regression model, controlling for multiple covariates. Results: The final analysis included 377,420 patients. The 20-year-period prevalence of SBP in patients with cirrhosis was 3.54% and the prevalence of patients using PPIs in the US population was 12,000 per 100,000 people (12.00%). The 1-year incidence of SBP in cirrhotic patients using PPIs was 2500 per 100,000 people. After accounting for confounders, the risk of SBP was higher among males, patients with a diagnosis of gastrointestinal bleeding, and those using ß-blockers and PPIs. Conclusions: To date, this is the largest cohort used to examine the prevalence of SBP among cirrhotic patients in the US. PPI use and hepatic encephalopathy offered the highest risk for the development of SBP, independently of gastrointestinal bleeding. Focusing on judicious PPI use should be encouraged among cirrhotic patients.

Prevalence of autoimmune, cholestatic and nonalcoholic fatty liver disease in celiac disease.

BACKGROUND: While there is higher prevalence of autoimmune, cholestatic and fatty liver disease in celiac disease (CeD), most data is from small-scale studies. We evaluated the prevalence and risk factors of the same using large cohort data. METHODS: A population-based cross-sectional study was conducted using Explorys, a multi-institutional database. Prevalence and risk factors of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and nonalcoholic fatty liver disease (NAFLD) in CeD were assessed. RESULTS: Out of 70 352 325 subjects, 136 735 had CeD (0.19%). The prevalence of AIH (0.32%), PBC (0.15%), PSC (0.004%) and NAFLD (0.7%) were high in CeD. After adjusting for age, gender, Caucasian race and anti-tissue transglutaminase antibody (anti-TTG), CeD subjects had higher odds of AIH [adjusted odds ratio (aOR) 7.06, 95% confidence interval (CI) 6.32-7.89] and PBC (aOR 4.16, 95% CI 3.46-5.0). Even after adjusting for CeD, anti-TTG positivity concurred with higher odds of AIH (aOR 4.79, 95% CI 3.88-5.92) and PBC (aOR 9.22, 95% CI 7.03-12.1). After adjusting for age, gender, Caucasian race, diabetes mellitus (DM), obesity, hypothyroidism and metabolic syndrome, there was higher prevalence of NAFLD in CeD, with the aOR in the presence of DM type 1 being 2.1 (95% CI 1.96-2.25), and in the presence of DM type 2 being 2.92 (95% CI 2.72-3.14). CONCLUSION: Subjects with CeD are more likely to have AIH, PBC, PSC and NAFLD. AIH and PBC have higher odds in the presence of anti-TTG. The odds of NAFLD in CeD are high regardless of type of DM.

Non-cirrhotic Portal Hypertension as the Initial Presentation of Limited Cutaneous Scleroderma: A Case Report.

Systemic sclerosis (SSc) is an autoimmune disease characterized by progressive skin fibrosis. It has 2 main clinical subtypes-diffuse cutaneous scleroderma and limited cutaneous scleroderma. Non-cirrhotic portal hypertension (NCPH) is defined as presence of elevated portal vein pressures without cirrhosis. It is often a manifestation of an underlying systemic disease. On histopathology, NCPH may be found to be secondary to multiple abnormalities such as nodular regenerative hyperplasia (NRH) and obliterative portal venopathy. There have been reports of NCPH in patients with both subtypes of SSc secondary to NRH. However, simultaneous presence of obliterative portal venopathy has not been reported. We present a case of NCPH due to NRH and obliterative portal venopathy as a presenting sign of limited cutaneous scleroderma. The patient was initially found to have pancytopenia and splenomegaly and was erroneously labeled as cirrhosis. She underwent workup to rule out leukemia, which was negative. She was referred to our clinic and diagnosed with NCPH. Due to pancytopenia, she could not be started on immunosuppressive therapy for her SSc. Our case describes the presence of these unique pathological findings in the liver and highlights the importance of an aggressive search for an underlying condition in all patients diagnosed with NCPH.

Prevalence and Risk Factors Associated With Inflammatory Bowel Disease in Patients Using Proton-Pump Inhibitors: A Population-Based Study.

Background and aim Proton pump inhibitor (PPI) is a heavily prescribed medication in the United States that is used to treat several gastrointestinal disorders. Although it has been considered to be safe compared to other medications, multiple gastrointestinal side effects have been reported. These effects of PPIs might stem from the progressive alteration of the intestinal microbiome. Patients with inflammatory bowel disease (IBD) using PPI are also seen to be less likely to achieve remission. However, in the current literature, there is very little evidence of the risk of developing IBD in patients who have been using PPIs. Therefore, our aim was to perform a cross-sectional population-based study with in-depth analysis to assess the prevalence and risk factors of IBD amongst PPI users in the United States. Methodology  A validated multicenter and research platform database of more than 360 hospitals from 26 different healthcare systems across the United States was utilized to construct this study. A cohort of patients with a diagnosis of ulcerative colitis (UC) and Crohn's disease (CD) between 1999-2022 was identified using the Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT). Patients aged 18 to 65 years were included. We excluded any individual who had a diagnosis of chronic liver disease, autoimmune disease (excluding IBD), or cancer. The risk of IBD was calculated using a multivariate regression analysis to account for potential confounders including non-steroidal anti-inflammatory drugs (NSAIDs) use, smoking, patients who have had a diagnosis of alcoholism, gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), and metabolic syndrome. A two-sided P-value <0.05 was considered statistically significant, and all statistical analyses were performed using R version 4.0.2 (R Foundation for Statistical Computing, Vienna, Austria, 2008). Results  A total of 79,984,328 individuals were screened in the database and 45,586,150 patients were selected in the final analysis after accounting for inclusion and exclusion criteria. Using multivariate regression analysis, the risk of developing UC and CD was calculated. The odds of having UC amongst patients on PPI was 2.02 (95%CI 1.98-2.06), P-value <0.001. Similarly, the odds of having CD were high amongst PPI users (OR 2.79, 95%CI 2.75-2.84), P- value <0.001 Conclusion  Our study demonstrates that patients on PPIs are frequently found to have UC and CD even when adjusting for common risk factors. Hence, we urge clinicians to be aware of this association in order to limit unnecessary prescriptions of PPIs, especially for patients who are at risk for autoimmune diseases.

Prevalence of non-alcoholic fatty liver disease in patients with nephrotic syndrome: A population-based study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a global health concern with a prevalence of about 25% amongst United States adults. Its increased prevalence is attributed to increase in patients with obesity and metabolic syndrome, partly due to similar mechanisms of injury. Nephrotic syndrome (NS) is a clinical entity resulting from extensive proteinuria leading to hypoalbuminemia, hyperlipidemia, edema, and other complications. Given its association with hyperlipidemia, there is concern that patients with NS may be at increased risk of NAFLD. AIM: To perform a cross-sectional population-based study to investigate the prevalence and risk factors of NAFLD in patients with NS. METHODS: A large multicenter database (Explorys Inc., Cleveland, OH, United States) was utilized for this retrospective cohort study. A cohort of 49700 patients with a diagnosis of "Non-Alcoholic fatty liver disease" using the Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT) between 1999-2022 was identified. Inclusion criteria were age ≥ 18 years, presence of NAFLD, presence of NS. There were no specific exclusion criteria. Univariate and multivariate analysis were performed to adjust for multiple risk factors including age, gender, Caucasian race, NS, type II diabetes mellitus, hypothyroidism, dyslipidemia, obesity, metabolic syndrome and chronic kidney disease. Statistical analysis was conducted using R, and for all analyses, a 2-sided P value of < 0.05 was considered statistically significant. RESULTS: Among the 78734750 individuals screened in this database, there were a total of 49700 subjects with NAFLD. In univariate analysis, the odds of having NAFLD in patients with NS, type 2 diabetes mellitus, hypothyroidism, dyslipidemia, obesity, metabolic syndrome and chronic kidney disease were 14.84 [95% confidence interval (95%CI) 13.67-16.10], 17.05 (95%CI 16.78-17.32), 6.99 (95%CI 6.87-7.11), 13.61 (95%CI 13.38-13.84), 19.19 (95%CI 18.89-19.50), 29.09 (95%CI 28.26--29.95), and 9.05 (95%CI 8.88-9.22), respectively. In multivariate analysis, the odds of having NAFLD amongst patients with NS were increased to 1.85 (95%Cl 1.70-2.02), while the odds were also remained high in patients that have type 2 diabetes mellitus [odds ratio (OR) 3.84], hypothyroidism (OR 1.57), obesity (OR 5.10), hyperlipidemia (OR 3.09), metabolic syndrome (OR 3.42) and chronic kidney disease (OR 1.33). CONCLUSION: Patients with NS are frequently found to have NAFLD, even when adjusting for common risk factors. Hence, clinicians should maintain a high index of suspicion regarding presence of NAFLD in patients with NS.

Prevalence of hypothyroidism and effect of thyroid hormone replacement therapy in patients with non-alcoholic fatty liver disease: A population-based study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is currently considered as the most common cause of chronic liver disease worldwide. Risk factors for NAFLD have been well-described, including obesity, type 2 diabetes mellites (T2DM), dyslipidemia (DLP) and metabolic syndrome. Hypothyroidism has been identified as an independent risk factor for the development of NAFLD, although the literature is inconsistent. AIM: To evaluate the prevalence of hypothyroidism in patients with NAFLD, assess if it is an independent risk factor and explore the effect of thyroxine replacement therapy. METHODS: Our cohort's data was obtained using a validated, large, multicenter database (Explorys Inc, Cleveland, OH, United States) aggregated from pooled outpatient and inpatient records of 26 different healthcare systems, consisting of a total of 360 hospitals in the United States, and utilizing Systematized Nomenclature of Medicine-Clinical Terms for coding. We evaluated a cohort of patients with hypothyroidism and NAFLD. Multivariate analysis was performed to adjust for confounding risk factors including hypertension (HTN), T2DM, DLP, obesity and metabolic syndrome. SPSS version 25, IBM Corp was used for statistical analysis, and for all analyses, a 2-sided P value of < 0.05 was considered statistically significant. Exclusion criteria were limited to age < 18 years. RESULTS: Among the 37648180 included individuals in this database who are above the age of 18 years, there were a total of 2320 patients with NAFLD (6.16 per 100000) in the last five years (2015-2020), amongst which 520 patients (22.4%) had hypothyroidism. Baseline characteristics of patients in this database are described in Table 1. Patients with NAFLD were also more likely to have obesity, T2DM, DLP, HTN, and metabolic syndrome (Table 2). While males and females were equally affected, patients in the age group 18-65 years as well as Caucasians seem to be at a higher risk. There was an increased risk of NAFLD among patients with hypothyroidism (OR = 1.587). Furthermore, thyroid hormone replacement was not associated with a decreased risk for developing NAFLD (OR = 1.106, C = 0.952-1.285, P = 0.303). CONCLUSION: Hypothyroidism seems to be an independent risk factor for the development of NAFLD. Thyroid hormone replacement did not provide a statistically significant risk reduction. Further studies are needed to evaluate the effect of thyroid hormone replacement and assess if being euthyroid while on thyroid replacement therapy affects development and/or progression of NAFLD.

Factors that Minimize Curative Resection for Gallbladder Adenocarcinoma: an Analysis of Clinical Decision-Making and Survival.

BACKGROUND: Gallbladder adenocarcinoma has a poor prognosis as it is often diagnosed incidentally, and patients have a high risk for residual and occult metastatic disease. Expert guidelines recommend definitive surgery for ≥T1b tumors; however, surgical management is inconsistent. This study evaluates the factors that affect the completion of radical resection with portal lymphadenectomy and its impact on survival. METHODS: A retrospective review of patients who underwent surgery for gallbladder cancer from 2008 to 2017 at an academic institution was performed. Patients were analyzed based on whether they underwent definitive surgical resection. Patient factors and clinical decision-making were analyzed; overall survival was compared using Kaplan-Meier analysis. RESULTS: Seventy-five patients with ≥T1b tumors were identified, of who 32 (42.7%) underwent definitive resection. Fifty-four (72%) patients had gallbladder cancer identified as an incidental diagnosis following laparoscopic cholecystectomy. Among patients who did not undergo definitive resection, the underlying factors were varied. Only 24 (55.8%) patients in the non-definitive resection group were seen by surgical oncology. Among patients who underwent re-operation for definitive resection, 12 (38.7%) were upstaged on final pathology. Of the 43 patients who did not undergo definitive resection, 4 (9.3%) had metastatic disease identified during attempted re-resection. Patients who underwent definitive resection had a significantly longer median overall survival compared to those who did not (4.3 v. 1.9 years, p = 0.02). CONCLUSIONS: Patients undergoing definitive resection have a significantly improved survival, including as part of a re-operative strategy. Universal referral to a surgical specialist is a modifiable factor resulting in increased definitive resection rates.

Systematic Review: Sweet Syndrome Associated with Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Sweet syndrome [SS] is a dermatological condition associated with both inflammatory bowel disease [IBD] and azathioprine use. We performed a systematic review to better delineate clinical characteristics and outcomes of SS in IBD patients. METHODS: Peer-reviewed, full-text journal publications from inception to April 2020 in English language and adult subjects with IBD were included. Skin biopsy was required as SS gold-standard diagnosis. Azathioprine-associated SS required recent azathioprine introduction or recurrence of SS after azathioprine re-challenge. RESULTS: We included 89 publications with 95 patients [mean age of SS diagnosis: 44 years; 59% female; 20 with azathioprine-associated SS and 75 without]. SS was diagnosed prior to IBD in 5.3%, at time of IBD diagnosis in 29.5% and after diagnosis in 64.2%. In total, 91% of patients with SS had known colonic involvement and the majority [76%] had active IBD at diagnosis; 22% had additional extra-intestinal manifestations. Successful therapies for SS included corticosteroids [90.5%], anti-tumour necrosis factor [TNF]-α inhibitor therapy [14.8%] and azathioprine [11.6%]. Azathioprine-associated SS was distinct, with 85% male patients, mean age of SS diagnosis of 50 years and a lower likelihood to be prescribed corticosteroids for treatment [75% vs 94.7% of non-azathioprine-associated SS, p = 0.008]. All patients with azathioprine-associated SS improved with medication cessation and developed recurrence after re-challenge. CONCLUSIONS: SS may precede or occur with IBD diagnosis in almost one-third of cases. Azathioprine and IBD-associated SS present and behave distinctly, especially with regard to gender, age at diagnosis and recurrence risk. Corticosteroids and TNF-α inhibitors have demonstrated efficacy in treating SS in IBD.

The Incidence of Endoscopic Retrograde Cholangiopancreatography-Related Complications in Patients With Liver Transplant: A Meta-Analysis and Systematic Review.

BACKGROUND: Existing literature on post-endoscopic retrograde cholangiopancreatography (ERCP) complications in patients with liver transplant remains scarce and largely inconsistent. We therefore aimed to systematically review and analyze the literature on complication rates associated with ERCP in patients with liver transplant. METHODS: We performed a comprehensive literature search in PubMed, PubMed Central, Embase, and ScienceDirect databases from inception through March 2020 to identify all the studies that evaluated post-ERCP complications in patients with liver transplant. Effect estimates from the individual studies were extracted and combined using the random effect, generic inverse variance method of DerSimonian and Laird, and a pooled odds ratio (OR) and event rates were calculated. Forest plots were generated, and publication bias was assessed for using conventional techniques. RESULTS: Fourteen studies with a total of 1,787 patients were analyzed. In total, 3,192 ERCPs were performed on these patients. The pooled all-complication rate was 5.2% (95% confidence interval (CI): 0.035 - 0.075). Procedural complications analyzed included post-ERCP pancreatitis 3.4% (95% CI: 0.025 - 0.047), bleeding 1.1% (95% CI: 0.006 - 0.020), infections 0.2% (95% CI: 0.025 - 0.047), and cholangitis 0.8% (95% CI: 0.004 - 0.020). No cases of periprocedural death were reported. The pooled OR for post-ERCP pancreatitis in patients with liver transplant compared to patients without liver transplant was 1.289 (95% CI: 0.455 - 3.653, P = 0.633, I2 = 72.88%). CONCLUSION: Post-ERCP complication rates in liver transplant patients are comparable to the general population and hence, peri-procedural evaluation and management may follow the current standards of care in this patient population.

Early Use of Tocilizumab May Prevent Clinical Deterioration in Select COVID-19 Patients: A Case Series.

Coronavirus disease 2019 (COVID-19) is a respiratory viral illness caused by the novel severe acute respiratory syndrome coronavirus 2. It is known to cause severe illness in certain patients, who develop acute respiratory distress syndrome (ARDS) often requiring intubation and mechanical ventilation adding to significant morbidity and mortality. Tocilizumab is an interleukin-6 inhibitor that has shown promise in improving outcomes in patients with COVID-19. It is usually administered to patients with severe COVID-19 who develop ARDS. We present three cases of COVID-19 where the patients were admitted to the hospital for observation and were found to be worsening clinically. They were believed to be developing ARDS, and intubation and mechanical ventilation were anticipated. Tocilizumab was administered in the early phase of the disease before intubation. Patients improved clinically and ultimately did not require intubation. Our findings suggest that early use of tocilizumab might be beneficial in preventing clinical deterioration and intubation in select COVID-19 patients.

Hemochromatosis As an Unusual Cause of Pancreatitis in an African-American Female of Child-bearing Age.

Hemochromatosis is a disorder of iron overload whereby there is toxic deposition of iron in various tissues and organs of the body. It can either be hereditary or secondary to some other underlying cause. Patients with mutations in the HFE gene are often predisposed to developing this disorder. It has a wide range of clinical presentation, from non-specific symptoms such as fatigue to overt development of cirrhosis, diabetes and skin pigmentation. We present an unusual case of hemochromatosis where an African-American female of child-bearing age presented to the emergency room with complaints of epigastric pain. She was found to have mildly elevated lipase and liver enzymes. Imaging studies were suggestive of acute-on-chronic pancreatitis with iron deposition in the spleen, pancreas and bone marrow. Her ferritin and transferrin saturation levels were elevated. She was diagnosed with acute-on-chronic pancreatitis secondary to alcoholism and hemochromatosis and treated with phlebotomy with good outcome. This case is one of the few reported cases of hemochromatosis in African-Americans, and emphasizes that even females in child-bearing age group can develop this condition. Elevated ferritin and transferrin saturation levels should prompt evaluation for this disorder.