Disparities in Liver Transplantation for Nonalcoholic Steatohepatitis in Women.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is the fastest-growing indication for liver transplantation (LT). Sex disparities among patients with cirrhosis on the LT waitlist are well known. We wanted to understand these disparities further in women with end-stage liver disease patients listed for NASH cirrhosis in a contemporary cohort. METHODS: We used data from the Scientific Registry of Transplant Recipients to assess sex racial, and ethnic differences in NASH patients listed for LT. Adults transplanted from August 1997 to June 2021 were included. Inferential statistics were used to evaluate differences with univariate and multivariate comparisons, including competitive risk analysis. RESULTS: During the study time period, we evaluated 12 844 LT for NASH cirrhosis. Women were transplanted at a lower rate (46.5% versus 53.5%; P < 0.001) and higher model for end-stage liver disease (MELD) (23.8 versus 22.6; P < 0.001) than men. Non-White women were transplanted at a higher MELD (26.1 versus 23.1; P < 0.001) than White women and non-White male patients (26.1 versus 24.8; P < 0.001). Graft and patient survivals were significantly different (P < 0.001) between non-White women and White women and men (White and non-White). CONCLUSIONS: Evaluation of LT candidates in the United States demonstrates women with NASH cirrhosis have a higher MELD than men at LT. Additional disparities exist among non-White women with NASH as they have higher MELD and creatinine at LT compared with White women. After LT, non-White women have worse graft and patient survival compared with men or White women. These data indicate that non-White women with NASH are the most vulnerable on the LT waitlist.

Type 1 Autoimmune Pancreatitis Unmasked by COVID-19 Vaccine.

Autoimmune pancreatitis is a rare fibro-inflammatory disease with 2 distinct subtypes of which each has their own clinical presentation, risk factors, and histopathological patterns. We present a case of newly diagnosed type 1 autoimmune pancreatitis in a symptomatic 54-year-old man with stable ulcerative colitis 1 month after COVID-19 vaccination. Previous reports have indicated that vaccinations can trigger autoimmune disease in predisposed individuals. This case discusses the occurrence of autoimmune pancreatitis triggered after COVID-19 vaccination.

Gastro-caval fistula after distal esophageal resection: a case report and review of the literature.

Peptic ulceration with fistula formation into the inferior vena cava is rare, difficult to diagnose, and associated with high mortality. The nonspecific signs and symptoms make diagnosis challenging, delaying optimal treatment. Although there have been reports on duodeno-caval fistulas, gastric communication with the inferior vena cava is very rare. We report the second case of a fatal gastro-caval fistula and performed a review of the literature on entero-caval fistulas to emphasize the importance of early suspicion and to understand the most common presentation, as well as the best diagnostic and treatment modalities of this rare pathology.

Post-endoscopic retrograde cholangiopancreatography pancreatitis prevention using topical epinephrine: systematic review and meta-analysis.

Background and study aims Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is a common complication of endoscopic retrograde cholangiopancreatography (ERCP). Multiple drugs and techniques have been studied for the prevention of PEP. Topical epinephrine has shown mixed results and is still not widely accepted as an alternative for prevention of PEP. We performed a systematic review and meta-analysis to evaluate the efficacy of topical epinephrine in preventing PEP. Methods A comprehensive literature review was conducted by searching Cochrane library database, Embase and PubMed up to August 2019, to identify all studies that evaluated use of topical epinephrine alone or in conjunction with other agents for prevention of PEP. Outcomes included prevention of PEP with use of topical epinephrine and evaluation of whether addiing epinephrine provides any additional benefit in preventing PEP. All analysis was conducted using Revman 5.3. Results Eight studies, including six randomized controlled trials and two observational studies with 4123 patients, were included in the meta-analysis. Overall, there was no difference in incidence of PEP in patients who underwent ERCP and were treated with epinephrine spray versus those who were not, RR = 0.63 (CI 0.32-1.24) with heterogeneity (I2 = 72 %). However, on a subgroup analysis, topical epinephrine significantly decreases the risk of PEP when compared to placebo alone (means no intervention was done including no rectal indomethacin)., RR = 0.32 (0.18-0.57). In another subgroup analysis, there was no statistically significant difference in using topical epinephrine along with rectal indomethacin in preventing PEP compared to rectal indomethacin alone RR = 0.87 (0.46-1.64). Conclusion Topical epinephrine does not provide any additional benefit in preventing PEP when used in conjunction with rectal indomethacin. In subgroup analysis, topical epinephrine appeared to decrease risk of PEP in the absence of rectal indomethacin, and could be considered when rectal indomethacin is unavailable or if there is a contraindication to its use.

Drug and herbal/dietary supplements-induced liver injury: A tertiary care center experience.

BACKGROUND: Drug-induced liver injury (DILI) and herbal/dietary supplements (HDS) related liver injury present unique diagnostic challenges. Collaboration between the clinician and the pathologist is required for an accurate diagnosis and management. AIM: To report our experience on the clinical-pathological findings of hepatic injury caused by drugs/HDS. METHODS: A retrospective review of clinically proven cases of DILI/HDS who presented to our institution from January 1, 2013 to December 31, 2017 was performed. Slides were reviewed for histopathological patterns of injury and correlated with the causative agent. Out of 600 patients presenting with unexplained rise in liver enzymes undergoing biopsy, 107 were suspected to have DILI/HDS. Of these, 53 had a directly linked exposure to drug/herbal supplements. Fifteen patients were excluded for concurrent known liver disease. Thirty-eight patients with clinically proven DILI/HDS were finally included. RESULTS: Thirty-eight cases of DILI/HDS with a male:female of 1:1.5 and mean age of 51 ± 3 years were identified. DILI was identified in 84.2% cases while HDS injury in 15.8%. Acute hepatitis (42.1%) was the most common pattern of injury while granulomatous hepatitis (2.6%) was the least common. We found one case of acute-cholestasis due to rivaroxaban and two cases of cholestatic-hepatitis due to rizatriptan and trimethobenzamide-hydrochloride that, to the best of our knowledge, have not been previously reported. One case of steatohepatitis due to trimethoprim-sulfamethoxazole and three unusual cases of cholestatic-hepatitis with bile duct injury and steatosis due to dronedarone, C4-Extreme and hydroxycut, were also seen. Of our cohort, 81.6% of the patients fared well with discontinuation of drug and 18.4% underwent transplant; of which 42.9% were deceased. CONCLUSION: We describe the clinical findings, histopathological patterns of injury and clinical outcomes caused by drugs. In particular, we report a few previously unreported/ rarely observed clinical and histopathological patterns of hepatic injury.

Emergent versus urgent ERCP in acute cholangitis: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Acute cholangitis is characterized by abdominal pain, fever, and jaundice. Most patients respond to medical management with intravenous hydration and antibiotics. About 20% to 30% require biliary drainage, and ERCP is the procedure of choice. We conducted a systematic review and meta-analysis to evaluate the impact of emergent biliary drainage on patient outcomes. METHODS: A comprehensive literature review was conducted by searching the Embase and PubMed databases from inception to April 2019 to identify all studies that evaluated the impact of timing of ERCP on patient outcomes. Our primary outcome was in-hospital mortality (IHM), and secondary outcomes were length of stay (LOS), organ failure, and 30-day mortality. Fixed and random effects models were used to generate pooled measures of IHM, 30-day mortality, and LOS. RESULTS: Nine observational studies involving 7534 patients were included in the primary meta-analysis. IHM was significantly lower in patients who underwent emergent biliary drainage within 48 hours (odds ratio [OR], 0.52; 95% confidence interval [CI], 0.28-0.98). As a sensitivity analysis, we pooled the data from 2 population registry studies of 81,893 patients, which yielded consistent results for the main outcomes. LOS was also significantly lower in patients who underwent ERCP within 48 hours with a mean difference of 5.56 days (95% CI, 1.59-9.53). Patients who underwent emergent ERCP also had lower odds of 30-day mortality (OR, 0.39; 95% CI, 0.14-1.08) and organ failure (OR, 0.69; 95% CI, 0.33-1.46). CONCLUSIONS: Our study reveals that performing emergent ERCP within 48 hours in patients with acute cholangitis is associated with lower IHM, 30-day mortality, organ failure, and shorter LOS.

Safety and efficacy of a minimally invasive cell sampling device ('Cytosponge') in the diagnosis of esophageal pathology: a systematic review.

Esophageal adenocarcinoma is an increasingly common cause of morbidity and mortality in developed countries. Most cases are considered the consequence of chronic gastroesophageal reflux disease, with subsequent Barrett's metaplasia and dysplasia. Because progression from Barrett's metaplasia to cancer occurs over many years, endoscopic screening and surveillance programs have been established, albeit with little or no consideration for cost-effectiveness. As an alternative to the expensive and resource-demanding endoscopic surveillance, the Cytosponge has been developed to sample the esophageal mucosa efficiently. The device is a compressed mesh sponge encapsulated in an ingestible gelatin pill attached to a string. After swallowing, the capsule dissolves allowing the sponge to expand in the stomach. As it is pulled out, cells are collected from the esophagogastric junction and throughout the esophagus. The cellular samples can be analyzed by cytology, immunohistochemistry, and molecular markers. We conducted a systematic review of all recent relevant studies to help define the role of this novel technology, including studies of screening and surveillance of Barrett's esophagus, esophageal squamous dysplasia detection, detection of eosinophilic esophagitis, and evaluation of benign esophageal diseases. With the major limitation that most studies were performed by a single investigative group that developed the technology, the device yielded overall impressive results against the endoscopy/biopsy gold standard. Patient acceptability was high. If these promising early results are validated by other investigators in other populations, the Cytosponge represents an important new advance in the detection of esophageal pathology that could potentially decrease the burden of endoscopic esophageal sampling.

Non-alcoholic Fatty Liver Disease: A Review of Anti-diabetic Pharmacologic Therapies.

Non-alcoholic fatty liver disease (NAFLD), the most common cause of liver disease, affects approximately 75 to 100 million Americans. Patients with concurrent NAFLD and type 2 diabetes mellitus have a higher risk of progressing to advanced fibrosis and non-alcoholic steatohepatitis compared to non-diabetics. Lifestyle modifications, including weight loss, remain the mainstay of treatment for NAFLD, as there are no medications currently indicated for this disease state. Anti-diabetic pharmacologic therapies aimed at improving insulin sensitivity and decreasing insulin production have been studied to determine their potential role in slowing the progression of NAFLD. In this review, we focus on the evidence surrounding anti-diabetic medications and their ability to improve disease progression in patients with NAFLD.

Early biliary drainage is associated with favourable outcomes in critically-ill patients with acute cholangitis.

INTRODUCTION: Acute cholangitis (AC) is a clinical condition that requires prompt medical management with IV fluids, antibiotics, and biliary drainage (BD). The optimal timing for BD remains unclear. AIM: To investigate the effect of biliary drainage timing on clinical outcomes in AC. MATERIAL AND METHODS: We conducted a retrospective study of patients with AC admitted to the ICU using the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) database. Emergency department to BD time, hospital death, length of stay (LOS), and severity scores were extracted from the database. We investigated the effect of BD timing on mortality rates, persistent organ failure, and LOS. RESULTS: A total of 177 patients were included; 50% were males; median age was 75 years, in-hospital mortality was 9.6%, mean time-to-ERCP was 32 h (range: 0.42-229.6) with 76% meeting the Tokyo Guidelines (TG13) criteria for severe cholangitis, and median Simplified Acute Physiology Score II (SAPS II) was 42 (IQR: 33-51). Using 24 h as a cut-off, patients who underwent BD ≤ 24 h had less persistent organ failure (OR = 0.49; 95% CI: 0.26-0.96, p = 0.040), shorter ICU LOS (3.25 vs. 4.95 days, p = 0.040), shorter hospital LOS (7.71 vs. 13.57 days, p = 0.001), but no difference in either in-hospital mortality (OR = 0.47, 95% CI: 0.17-1.29, p = 0.146) or 28-day mortality (OR = 0.61, 95% CI: 0.24-1.53, p = 0.297). CONCLUSIONS: In critically-ill patients with acute cholangitis, early biliary drainage ≤ 24 h is associated with less persistent organ failure and shorter length of stay but had no effect on patient survival.

Effects of infection on post-transplant outcomes: living versus deceased donor liver transplants.

INTRODUCTION: Post-transplant infections have been studied widely but data on comparisons of deceased donor liver transplants (DDLT) and living donor liver transplants (LDLT), type and timings of infections, and their relations to outcomes are not explored. MATERIAL AND METHODS: We analysed data from 612 participants of the Adult-to-Adult Living Donor Liver Transplantation Study (A2ALL), a retrospective data set of LDLT and DDLT. We compared the type and timing of the first post-transplant infection in relation to transplant outcomes between the two groups. RESULTS: Out of 611 patients, 24.5% experienced the first post-transplant infection, the majority of which were bacterial (35.3%), followed by fungal (11%) and viral infections (4.2%). There was no significant difference in the rate, type or timing of infection between LDLT and DDLT. Patients with late (> 1 year) first infection were 1.8 times more likely to die (95% CI: 1.12-2.98, p = 0.015) and 9 times more likely to have graft failures (95% CI: 3.26-24.8, p < 0.001). DDLT recipients who experienced bacterial infection had a significantly lower survival rate compared to LDLT recipients (p < 0.001). CONCLUSIONS: Late infection is associated with lower survival in both DDLT and LDLT. Bacterial infection might be more detrimental for DDLT than LDLT. Late infection should be managed aggressively to improve outcomes.

Helicobacter pylori Infection: An Update for the Internist in the Age of Increasing Global Antibiotic Resistance.

Helicobacter pylori infects approximately half the world's population and is especially prevalent in the developing world. H. pylori is an important cause of global ill health due to its known etiological role in peptic ulcer disease, dyspepsia, gastric cancer, lymphoma, and more recently, recognized in iron deficiency anemia and idiopathic thrombocytopenic purpura. Increased antibiotic usage worldwide has led to antibiotic resistance among many bacteria, including H. pylori, resulting in falling success rates of first-line anti-H. pylori therapies. Eradication failures are principally due to resistance to clarithromycin, levofloxacin, and metronidazole. Several new treatment options or modifications of established regimens are now recommended by updated practice guidelines for primary or secondary therapy. Because these updated recommendations were published in the gastroenterological literature, internists and primary care physicians, who commonly manage H. pylori, may be unaware of these advances. In this review, we outline the changing epidemiology of H. pylori, advise on diagnostic test selection for patients not undergoing endoscopy, and highlight current management options in this era of growing antibacterial resistance.

Prognostic Significance of Elevated Cardiac Troponin in Acute Gastrointestinal Bleeding.

BACKGROUND: Acute gastrointestinal bleeding (AGIB) is responsible for over 140,000 hospitalizations annually. Cardiovascular-related deaths account for 30% of the patients surviving the initial episode of AGIB. The purpose of this study was to identify the impact of elevated troponin on short-term mortality and length of stay (LOS) of these patients. METHODS: From July 2013 to July 2016, 290 patients admitted with a diagnosis of AGIB and who had cardiac troponin I measured within 24 h of presentation were retrospectively reviewed. Clinical variables including 30-day mortality, 30-day readmission and LOS were then compared between the groups of troponin elevation and no troponin elevation. RESULTS: The overall 30-day mortality among patients with AGIB was 6.5% (19/290). Cardiac troponin was elevated in 10% of patients (29/290). Among patients with normal troponin, 5% (13/261) died within 30 days. In patients with troponin elevation, 21% died in the same period (6/29, P = 0.001). The LOS was also higher in patients with troponin elevation (6 vs. 5 days, P = 0.02). There was no difference in 30-day readmission among the two groups. Past history of coronary artery disease, congestive heart failure, hypertension, aspirin use and elevated creatinine was more common in patients with troponin elevation. On multivariate analysis, troponin elevation on presentation is associated with increased mortality (odds: 5.50, CI: 1.73 - 17.47, P = 0.004). CONCLUSION: In patients admitted to the inpatient service with AGIB, elevated troponin I on presentation is associated with high short-term mortality and longer hospital stay.

Rising Rate of Liver Transplantation in the Baby Boomer Generation with Non-alcoholic Steatohepatitis in the United States.

Background and Aims: Nonalcoholic steatohepatitis (NASH) is the most rapidly growing indication for liver transplantation (LT) in the United States and is on a trajectory to become the leading indication for LT in the next decade. We aimed to study the trends in NASH-related LT among persons born between 1945 and 1965, the baby boomer (BB) generation. Methods: We performed a retrospective cohort analysis using population-based data from the United Network for Organ Sharing/Organ Procurement and Transplantation Network registry from 2004-2015 to evaluate the birth cohort-specific trends in liver transplant waitlist registrations and liver transplant surgeries in patients with NASH. We stratified our study population into three birth cohorts: 1) birth before 1945, 2) birth between 1945 and 1965, and 3) birth after 1965. Results: The overall rates of NASH-related waitlist registrations and liver transplant surgeries steadily increased from 2004 to 2015 and were reflective of a sharp rise noted in the NASH BB sub-group. From 2004 to 2015, the proportion of BB patients with NASH added to LT waitlist demonstrated an incremental growth, 60.6% in 2004 versus 83.2% in 2015 (p < 0.01). Among the liver transplant recipients with NASH, the proportion represented by the BB cohort increased from 56.3% in 2004 to 80.0% in 2015 (p < 0.01). Conclusions: We report rising rates of waitlist registration and LT for the indication of NASH. More importantly, the BB sub-cohort was mainly responsible for these alarming trends.

The importance of a multidisciplinary approach to hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. The rising incidence, genetic heterogeneity, multiple etiologies, and concurrent chronic liver diseases make diagnosis, staging, and selection of treatment options challenging in patients with HCC. The best approach to optimize the management of HCC is one that utilizes a core multidisciplinary liver tumor board, consisting of hepatologists, pathologists, interventional radiologists, oncologists, hepatobiliary and transplant surgeons, nurses, and general practitioners. In most cases, HCC is diagnosed by abdominal imaging studies, preferably with a triphasic computed tomography scan of the abdomen or magnetic resonance imaging of the abdomen. Histopathological diagnosis using a guided liver biopsy may be needed in noncirrhotic patients or when radiological diagnostic criteria are not fulfilled in the setting of cirrhosis. The Barcelona Clinic Liver Cancer staging system facilitates a standardized therapeutic strategy based on the tumor burden, extent of metastasis, severity of hepatic decompensation, comorbid medical illnesses, functional status of patient, HCC-related symptoms, and preference of the patient. Treatment options include curative surgery (hepatic resection and liver transplantation) and palliative measures (radiofrequency ablation, transarterial chemoembolization, and chemotherapy with sorafenib). The role of the multidisciplinary team is crucial in promptly reconfirming the diagnosis, staging the HCC, and formulating an individualized treatment plan. In potential liver transplant candidates, timely liver transplant evaluation and coordinating bridging/downsizing treatment modalities, such as radiofrequency ablation and transarterial chemoembolization, can be time-consuming. In summary, a multidisciplinary team approach provides a timely, individualized treatment plan, which can vary from curative surgery in patients with early-stage HCC to palliative/hospice care in patients with metastatic HCC. In most tertiary care centers in the US, a multidisciplinary liver tumor board has become the standard of care and a key component of best practice protocol for patients with HCC.

Hepatic encephalopathy: what the multidisciplinary team can do.

Hepatic encephalopathy (HE) is a complex disease requiring a multidisciplinary approach among specialists, primary care team, family, and caregivers. HE is currently a diagnosis of exclusion, requiring an extensive workup to exclude other possible etiologies, including mental status changes, metabolic, infectious, traumatic, and iatrogenic causes. The categorization of HE encompasses a continuum, varying from the clinically silent minimal HE (MHE), which is only detectable using psychometric tests, to overt HE, which is further divided into four grades of severity. While there has been an increased effort to create fast and reliable methods for the detection of MHE, screening is still underperformed due to the lack of standardization and efficient methods of diagnosis. The management of HE requires consultation from various disciplines, including hepatology, primary care physicians, neurology, psychiatry, dietician/nutritionist, social workers, and other medical and surgical subspecialties based on clinical presentation and clear communication among these disciplines to best manage patients with HE throughout their course. The first-line therapy for HE is lactulose with or without rifaximin. Following the initial episode of overt HE, secondary prophylaxis with lactulose and/or rifaximin is indicated with the goal to prevent recurrent episodes and improve quality of life. Recent studies have demonstrated the negative impact of MHE on quality of life and clinical outcomes. In light of all this, we emphasize the importance of screening and treating MHE in patients with liver cirrhosis, particularly through a multidisciplinary team approach.

A Case of Ileus and ST Segment Elevation.

ST segment elevation is associated with non-cardiac pathologies but is not as well reported as myocardial infarction. We present a case of a 63-year-old man who was admitted for an overdose on cyclobenzaprine with signs of anti-cholinergic toxicity. He developed signs of ileus on imaging and became progressively obtunded. He was noted to have ST segment elevations on electrocardiogram (EKG) with no troponin elevation. Patient required urgent catheterization which showed normal coronary arteries. His bowel was decompressed subsequently resulting in resolution of the ST segment changes. Other cases of ST segment elevations with gastrointestinal pathologies including cholecystitis, pancreatitis and gastric dilation have been reported but the etiology is still unclear. This case illustrates the importance of understanding EKGs in the clinical context. ST segment elevation on EKG, if there is contradicting symptomology and lab reports, should be further investigated to prevent unnecessary work-up and potentially dangerous therapies. [Full article available at http://rimed.org/rimedicaljournal-2016-11.asp].

Fluid Choice Matters in Critically-ill Patients with Acute Pancreatitis: Lactated Ringer's vs. Isotonic Saline.

OBJECTIVES: To investigate the effect of different crystal- loid solutions on clinical outcomes in critically-ill patients with acute pancreatitis (AP). METHODS: We conducted a retrospective study of patients with AP admitted to the ICU using the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) database. We investigated the effect of fluid type; lactated ringer's (LR) vs. isotonic saline (IS) on hospital mortality rates, and ICU length of stay (LOS). RESULTS: Hospital mortality of the 198 included patients was 12%. For fluid type, 32.9% were resuscitated with LR vs. 67.1% with IS. Hospital mortality was lower in the LR group (5.8%) vs. 14.9% for IS group, odds ratio of 3.10 [P=0.041]. This effect was still observed after adjusting for confounders. However, ICU LOS was longer in LR compared to IS group; 6.2±6.9 vs. 4.2±4.49 days respectively [P= 0.020]. CONCLUSION: The type of fluid used for resuscitation in AP may affect the outcome. LR may have survival benefit over IS in critically-ill patients with AP. [Full article available at http://rimed.org/rimedicaljournal-2016-10.asp].