Faculty Bibliography

Introduction: Non-Wilsonian hepatolenticular degeneration (NWHD) is a heterogeneous neurological disorder occurring secondary to chronic acquired liver disease. Genetically determined familial NWHD is rare, poorly understood, and often mistaken for Wilson's disease (WD). We present a case of a 65-year-old woman with a family history of NWHD, found to have dystonia, parkinsonism, tremor, cerebellar ataxia, progression of behavioral abnormalities who presented with cognitive decline and progression of liver failure. The patient was evaluated for and later underwent Orthotopic liver transplant (OLT) Case Description/Methods: 65-year-old woman with family history of early-onset cirrhosis with dystonia and dyskinesia in her father, sister, and daughter is transferred to our institution after she was noted to have accelerated progression of her neurological decline which started the year prior. The patient was not obese (BMI 27) and did not use any alcohol. Huntington's disease workup was negative. Workup for causes of cirrhosis did not yield any findings including multiple 24-hour urine copper collections, and no finding of Kayser Fleischer rings on ophthalmology exam. Multiple CT and MRI brain showed linear abnormal signal foci noted along a medial portion of the bilateral lentiform nucleus in anterior to posterior orientation. The patient was diagnosed with NWHD and underwent OLT. Pathology on explanted native liver showed focal steatohepatitis, Mallory-Denk bodies, and focal mixed inflammatory infiltrates. The copper stain was negative. Post liver transplant our patient's dystonia, parkinsonism, tremor, cerebellar ataxia, and behavioral abnormalities all resolved.
Discussion(s): Degeneration of basal ganglia leads to movement neurological disorders. There is an association between basal ganglia-related neurological disorders and cirrhosis of the liver in the absence of acquired liver disease such as Wilson's disease. NWHD is a distinct disease entity. Specific areas of the brain, such as the basal ganglia, are more likely to be injured from liver failure. The basal ganglia is involved in control of movement. If damage to this area is not from copper, this condition is the "non-Wilsonian" type. Non-Wilsonian hepatolenticular degeneration may represent a disorder of other poorly known toxic depositions. We demonstrate that with liver transplantation this damage can be reversible

Introduction: Ketamine is used routinely in the hospital for anesthesia, but is also used recreationally for its hallucinogenic and dissociative side effects. Chronic recreational use has been linked to bile duct damage and ulcerative cystitis. We report a case of ketamine induced sclerosing cholangiopathy. Case Description/Methods: A 42-year-old Cantonese woman with past medical history of bilateral hydronephrosis with stents leading to chronic kidney disease presented with abdominal pain associated with abnormal transaminases. Alkaline phosphatase was high at 1,017 IU/L with gamma glutamyl transferase of 2,310 IU/L with normal bilirubin. Abdominal imaging showed diffuse dilatation of the common bile duct. Viral serologies and anti-mitochondrial antibody were negative. She reported chronically elevated liver tests of unknown etiology. Social history was notable for prior alcohol abuse. She denied family history of liver diseases. Her pain resolved and plan was for outpatient follow-up, but she re-presented with sepsis with a rise in bilirubin to 2.9 mg/dL (Table 1). Given prior abnormal imaging, a magnetic resonance cholangiopancreatography was obtained, which showed increased intra- and extrahepatic bile duct dilation with irregular appearance of the central intrahepatic ducts with possible stricture. Differential diagnoses were recurrent pyogenic cholangitis, sclerosing cholangitis, and IgG4 disease. Her IgG level was high at 2,779 mg/dL with IgG4 elevated at 213 mg/dL. Liver biopsy showed chronic cholestatic liver injury consistent with sclerosing cholangitis (Image 1). IgG4 stain was negative. Upon further investigation, patient admitted to at least a decade of daily ketamine use, which was likely the culprit of both her kidney and liver diseases.
Discussion(s): Due to her age, race, gender and rarity of ketamine induced cholangiopathy, she was not directly asked about ketamine use. Since the early 2000s, ketamine has emerged as the illicit drug of choice in Hong Kong and has seen increased use throughout Asia. The biliary damage from ketamine has been studied by a Chinese group that found 62% of the 257 chronic ketamine users had biliary tract anomalies. The greater the alkaline phosphatase, the higher the likelihood of finding biliary tract anomalies on imaging. Ketamine cessation has resulted in normalization of liver tests and imaging, however worsening cholangiopathy has been seen despite abstinence. In patients who present with unexplained cholangiopathy, chronic ketamine use should be considered

Introduction: Advance care planning (ACP) aims to provide care at the end of life (EOL) that is consistent with a patient's wishes, but it is infrequently performed in patients with decompensated cirrhosis. We implemented a quality improvement (QI) initiative in a hepatology fellows clinic at a major tertiary medical center with the goal of increasing advance directive (AD) completion among patients with decompensated cirrhosis. The goal of this analysis is to describe factors related to successful AD completion and preliminary effects of AD completion on EOL outcomes.
Method(s): The QI intervention, consisting of provider education, electronic health record templates, and standardized workflows, was conducted between November 2018 and March 2021. We performed a retrospective chart review of adult patients with decompensated cirrhosis seen during this period. We collected data on whether an AD was successfully completed and type of AD (first completed, if multiple). We also assessed location of death and receipt of hospice care among decedent patients. Descriptive statistics and univariate logistic regression were performed using STATA 14.2.
Result(s): A total of 120 patients with decompensated cirrhosis were seen during the QI intervention. Our cohort was mostly male (62%), Latino (55%), Medicaid-insured (70%) and non-transplant candidates (86%). AD completion improved from 8% (N=0) to 44% (N=53) by the end of the study period. Most ADs were completed in the outpatient setting (N=38, 72%) and were healthcare proxy designation forms (N=41, 77%). A diagnosis of NASH (OR: 4.25, 95% CI: 1.11-16.2) and divorced marital status (OR: 10.23, CI: 2.04-51.3) were the only factors associated with successful AD completion. Seventeen (14%) patients died during the study period, of which 12 (71%) had an AD. Decedents with an AD were more likely overall to receive hospice (67% vs. 20%) and die under hospice care (42% vs. 20%).
Conclusion(s): Following our QI intervention, 44% of patients with decompensated cirrhosis had an AD, which were largely health care proxy forms completed in the outpatient setting. No significant disparities in AD completion by age, gender, or race were observed from our intervention. AD completion was associated with higher rates of receiving hospice among decedents. These findings suggest benefits of AD completion on EOL care in this population

Background: Individuals with decompensated cirrhosis (DC) experience uncertain illness trajectories and significant healthcare burden towards the end of life (EOL) Advance care planning (ACP) has been associated with improved EOL outcomes in patients with serious illnesses We implemented a quality improvement (QI) intervention from November 2018 to March 2020 that aimed to increase advance directive (AD) completion among patients with DC seen in a once-weekly hepatology clinic staffed by transplant hepatology fellows, gastroenterology fellows, and attending hepatologists The goal of this study was to evaluate the effect of our QI intervention on EOL care, including the hospital length of stay (LOS) and concordance between documented preferences and care received Methods: We performed a retrospective chart review of adult patients with DC seen in our clinic during the QI intervention We followed patients from the time of their first appointment through June 2020, or until date of death We collected data on whether an AD was completed, along with contents of the most recent document Among decedents, we collected data on location of death, goals of care discussions (GCDs), LOS, and receipt of comfortfocused care Descriptive statistics were calculated and Wilcoxon rank sum tests were performed to compare LOS All analyses were conducted using STATA 14 2 Results: A total of 95 patients were seen during the follow-up period Our cohort consisted mostly of men (60%), of Latinx origin (60%), Medicaid-insured (69%) and with a mean age of 56 (standard deviation [SD]: 12) years The primary cause of cirrhosis was alcohol use (36%) Most patients had history of ascites (71%) or hepatic encephalopathy (57%). At first visit, the mean Model of End-Stage Liver Disease-Sodium (MELDNa) score was 13 9 (SD: 6 0), and most patients were never evaluated for transplant (77%) or declined for listing (11%) AD completion improved from 9 to 40% Nine (9%) patients died during follow-up, of which 8 were hospitalized Among decedents, 5 (56%) had a prior AD, of which all designated a healthcare proxy (HCP) and 4 designated care preferences at the EOL The care of 5 decedents (56%) involved GCDs, of which 4 (80%) included specialty palliative care (SPC) services All patients previously opting for limits to care received comfort care at the EOL and experienced shorter hospitalizations compared to patients with fully aggressive or unreported preferences (median LOS: 11 vs 14 days), though this difference was not statistically significant (p=0.30) (Table 1)
Conclusion(s): AD completion significantly improved over the follow-up period All patients who previously documented limits to care received goal-concordant care at the EOL and tended to have shorter hospitalizations Future iterations of this quality improvement project will involve more patients, longer follow up periods, and formal assessments of patient and family satisfaction at the EOL. (Table Presented)

BACKGROUND AND AIMS/OBJECTIVE:Liver injury due to COVID-19 is being increasingly recognized. Abnormal liver chemistry tests of varying severities occur in a majority of patients. However, there is a dearth of accompanying liver histologic studies in these patients. METHODS:The current report details the clinical courses of two patients having severe COVID-19 hepatitis. Liver biopsies were analyzed under light microscopy, portions of liver tissue were hybridized with a target probe to the SARS-CoV-2 S gene, and small sections from formalin-fixed paraffin embedded liver tissue were processed for electron microscopy. RESULTS:The liver histology of both cases showed a mixed inflammatory infiltrate with prominent bile duct damage, endotheliitis and many apoptotic bodies. In-situ hybridization and electron microscopy suggest the intrahepatic presence of the severe acute respiratory syndrome corona virus-2 (SARS-CoV-2), the findings of which may indicate the possibility of direct cell injury. CONCLUSIONS:Based on the abundant apoptosis and severe cholangiocyte injury, these histopathological changes suggest a direct cytopathic injury. Furthermore, some of the histopathological changes may resemble acute cellular rejection occurring after liver transplantation. These two cases demonstrate that severe COVID-19 hepatitis can occur even in the absence of significant involvement of other organs.

BACKGROUND AND AIMS:Prior studies have shown a high prevalence of gastrointestinal (GI) symptoms, diagnoses of functional GI diseases (FGIDs), and pelvic floor symptoms associated with Ehlers-Danlos syndrome (EDS). It is unclear if Marfan syndrome (MFS), another common hereditary noninflammatory connective tissue disorder, is also associated these symptoms. This study evaluates the prevalence of and compares FGIDs and pelvic floor symptoms in a national cohort of EDS and MFS patients. METHODS:A questionnaire was sent to members of local and national MFS and EDS societies. The questionnaire evaluated the presence of GI and pelvic floor symptoms and diagnoses. The presence of FGIDs was confirmed using Rome III criteria. Quality of life was evaluated and scored with the CDC quality of life. KEY RESULTS:Overall, 3934 patients completed the questionnaire, from which 1804 reported that they had some form of EDS and 600 had MFS. In total, 93% of patients with EDS complained of GI symptoms and qualified for at least one FGID compared with 69.8% of patients with MFS. When comparing EDS prevalence of upper and lower GI symptoms as well as FGIDs, subjects with EDS reported significantly higher prevalence of Rome III FGIDs as compared with those with MFS. Irritable bowel syndrome (57.8% vs. 27.0%, P<0.001), functional dyspepsia (FD) (55.4% vs. 25.0%, P<0.001), postprandial distress (49.6% vs. 21.7%, P<0.001), heartburn (33.1% vs. 16.8%, P<0.001), dysphagia (28.5% vs. 18.3%, P<0.001), aerophagia (24.7% vs. 12.3%, P<0.001), and nausea (24.7% vs. 7.2%, P<0.001) were all significantly greater in the EDS population compared with MFS population. The prevalence of FGIDs was similar across subtypes of EDS. In general, participants with EDS were more likely to have nearly all pelvic floor symptoms as compared with participants with MFS. CONCLUSIONS:The prevalence of FGIDs and pelvic floor symptoms in EDS is higher than that found in MFS. The prevalence of FGIDs were similar across EDS subtypes. This study supports the mounting evidence for FGIDs in those with connective tissue diseases, but more specifically, in EDS.