Huntington disease (HD) is a neurodegenerative condition associated with pathologic involvement beyond the striatum including involvement of the autonomic nervous system. Bowel dysfunction is found in patients with HD, but the exact mechanism is poorly understood and not well reported. Patients may be affected with problems such as dysphagia, weight loss, nutritional deficiencies, esophagitis, and gastritis. Lower bowel symptoms are more prevalent with longer disease course. We present a case of a patient with late-stage HD who presents with severe esophagitis causing gastrointestinal hemorrhage, significant dysmotility including chronic dysphagia requiring gastrostomy tube, and chronic small bowel and colonic ileus.

Introduction: Vanishing bile duct syndrome (VBDS) is a rare condition characterized by progressive destruction and disappearance of the intrahepatic bile ducts with resulting cholestasis. Several causes have been associated with VBDS, including autoimmune conditions, infections, drug toxicities, and neoplasms. Outcomes vary between complete resolution and liver transplantation based on the degree of ductal injury and the underlying cause reversibility. Case Description/Methods: A 29-year-old man with Hodgkin's lymphoma (who started the first cycle of chemotherapy two weeks ago with nivolumab and adriamycin, vinblastine, and dacarbazine is admitted for neutropenic fever. The hepatology team is consulted for hyperbilirubinemia (Total bilirubin 11.8 mg/dl). The patient reported itching, pale stools, and dark urine. LFTs at the time AST 149 U/L, ALT 304 U/L, ALP 354 U/L, GGT 755 U/L, direct bilirubin 10 mg/dl, and INR 1. Hepatitis, metabolic, and autoimmune work-up was unremarkable. Abdominal ultrasound and MRCP showed hepatosplenomegaly, but otherwise unremarkable. PET scan showed no evidence of solid organ or bony involvement. However, his LFTs continued to worsen during admission, so a liver biopsy was obtained, consistent with VBDS thought to be secondary to his underlying lymphoma. Therefore, he continued his chemotherapy sessions and was started on ursodiol for symptom management. Although initial subsequent LFTs continued to worsen, he was not in liver failure or listed for transplant, given his underlying active lymphoma. Nonetheless, he was being followed in the transplant clinic as an outpatient. After completing his full course of chemotherapy, he has achieved complete metabolic and radiological responses, and his LFTs have improved significantly AST 58 U/L, ALT 77 U/L, ALP 554 U/L, GGT 515 U/L, total bilirubin 0.9 mg/dl, direct bilirubin 0.6 mg/dl, and INR 1. Discussion: Although rare, VBDS should be considered in patients with lymphoma and cholestasis, and a liver biopsy should be obtained for confirmation as there are reports of VBDS presenting as a paraneoplastic syndrome after diagnosis with lymphomas. VBDS patients typically respond to treatment of the underlying condition. However, some patients may require a transplant. Ursodiol is the treatment of choice as it works as an anti-inflammatory and cytoprotective medication (Figure 1).Figure 1.: Liver biopsy specimen (a) with a portal tract almost devoid of bile ducts (H and E, ×20) and (b) absence of CK7 staining consistent with bile duct loss (×20).

Acute gastrointestinal bleeding (acute GIB) is a major cause of mortality and morbidity in patients despite various advances in diagnosis and treatment. In the United States, around 390,000 patients are admitted with acute GIB annually, and mortality rates range from 3 to 8.8%.[1] The presentation of these patients can vary from minor, self-limited bleeding that can be managed in outpatient settings to life-threatening bleeding that requires aggressive resuscitation and emergent intervention.[1] Early and accurate diagnosis followed by prompt and appropriate treatment is imperative in the management of acute GIB. In this review, we will discuss the epidemiology, presentation, diagnosis, and management of acute GIB, with particular focus on diagnostic imaging and endovascular management.

Liver transplantation offers a life-saving option for those with liver cirrhosis, but it is associated with signi fi cant healthcare costs with some

Introduction: Sickle cell hepatopathy (SCH) is a spectrum of liver injury seen with sickle cell disease (SCD) that varies from mild to severe, requiring exchange transfusion and rarely liver transplantation. Sickle cell intrahepatic cholestasis (SCIC) is a severe complication of SCD, with high mortality and limited known cases. Sickling of erythrocytes within the hepatic sinusoids, hepatocyte ballooning, dilation of canaliculi, and bile plugs, lead to hyperbilirubinemia, transaminitis, coagulopathy, and acute liver failure in severe cases. Nodular regenerative hyperplasia (NRH) of the liver is an under recognized condition where normal liver parenchyma transforms into regenerative nodules, leading over time to noncirrhotic portal hypertension. It is associated with hematologic and rheumatologic disorders. We describe a case of suspected acute SCIC in hemoglobin SS SCD with biopsy showing NRH. Case Description/Methods: A 44-year-old man history of SCD, pulmonary hypertension presented with back pain, cough, and fevers with concerns for vaso occlusive crises (VOC) including acute chest syndrome. He developed multi-organ failure secondary to VOC: acute hypoxic respiratory syndrome, shock, and renal failure requiring renal replacement therapy. Notably, his liver enzymes during admission peaked to AST 601 u/L, ALT 278 u/L, total bilirubin 36.3 mg/dL, ALP 314 u/L. Viral serologies negative. Imaging showed hepatomegaly, and no evidence of extra and intrahepatic biliary dilation. Trans-jugular liver biopsy (2 days after bilirubin peak) was consistent with NRH without fibrosis (Figure 1) with wedged hepatic and free hepatic venous pressures 21 and 18mmHg respectively with a gradient of 3 mmHg confirming congestive hepatopathy and no portal hypertension. Course improved post exchange transfusion, with down trending of liver enzymes and bilirubin. Discussion: We report an uncommon finding of NRH in a patient with suspected SCIC. Patient likely had acute intrahepatic cholestasis, indicated by severe hyperbilirubinemia. Absence of SCIC on liver biopsy was discordant with the severity of the clinical picture, but could be explained by delay in obtaining tissue sample due to medical stabilization by 2 days. SCD patients often suffer from multi-system organ dysfunction with acute on chronic insults, such as our patient. Thus, it is important to evaluate them for not just acute hepatic crises but also determine the presence of underlying chronic liver disease to better ascertain the disease activity and prognosis.Figure 1.: Liver biopsy on H&E stain, 100x magnification. Marked sinusoidal dilatation (black arrow) can be seen with thinning of centrilobular liver cell plates, representative of nodular regenerative hyperplasia without significant inflammation, fibrosis, or steatosis.

Introduction: Acute graft-vs host disease (GVHD) is a serious complication of hematopoietic stem cell transplantation, though can rarely present after solid organ transplantation (SOT). This condition occurs when passenger lymphocytes within the transplanted donor organ(s) become activated and attack host tissues. GVHD after SOT is associated with a mortality rate of 70%-85%. Case Description/Methods: A 66-year-old woman with a history of non-alcoholic steatohepatitis cirrhosis and end-stage renal disease underwent a simultaneous liver and kidney transplant and re-presented one month after transplantation with urosepsis and diarrhea. She was initially treated with antibiotics; however, within 2 days of admission, she developed an acute-onset diffuse rash and sloughing of the skin and mucosa. Physical exam was notable for painful erythematous erosions present to the face, chest, back, anogenital regions, and oral mucosa. Skin biopsies demonstrated subepidermal blistering without full-thickness necrosis concerning for acute GVHD or Stevens Johnson Syndrome. Regarding diarrhea, the patient was experiencing 5 to 10 episodes of non-bloody diarrhea per day. Bidirectional endoscopy demonstrated grossly friable and hypervascular mucosa, and pathology showed diffuse apoptosis and crypt injury with features suggestive of GVHD or drug-related injury. During this hospitalization, the patient also experienced pancytopenia (white blood cell 0.1 k/uL, hemoglobin 7.9 g/dL, platelets 1 k/uL). Bone marrow biopsy demonstrated hypoplasia and stromal damage. Marrow fluorescence in situ hybridization chimerism studies revealed 60% involvement of donor cells, concerning for macrochimerism. Given the presentation of multi-organ involvement (skin, gastrointestinal tract, and marrow) with histopathology suggestive of GVHD, and significant donor macrochimerism, the patient met criteria for acute GVHD and was started on IV immunosuppression. The patient’s clinical status continued to worsen and given the poor prognosis, she elected for palliative measures and expired the next day. Discussion: This case illustrates a case of acute GVHD after simultaneous liver/kidney transplantation. GVHD after SOT is difficult to diagnose early given the rarity of the condition and clinical similarity to processes such as infection and drug-related injury. However, it is important to have a high index of suspicion as it may quickly progress to multi-organ dysfunction and death.

Diaphragm plication is a surgical treatment of unilateral diaphragm paralysis, in which the affected diaphragm is sutured in place. Because the right diaphragm sits on top of the liver, right-sided diaphragm plication can injure the liver and lead to hepatic compartment syndrome resulting in acute liver injury. We report a case of a 59-year-old woman with a history of multilevel disk degeneration and alcohol use disorder who underwent right-sided diaphragm plication. After surgery, she complained of abdominal pain and was found to have severely elevated liver-associated enzymes and evidence of acute liver injury, which resolved with supportive care.

The ongoing burden of COVID-19 in persons with end stage liver failure necessitates the development of sound and rational policies for organ transplantation in this population. Following our initial experience with two COVID-19 recovered recipients who died shortly after transplant, we adjusted our center policies, re-evaluated outcomes, and retrospectively analyzed the clinical course of the subsequent seven COVID-19 recovered recipients. There were two early deaths and 5 successful outcomes. Both deceased patients shared common characteristics in that they had positive SARS-CoV2 PCR tests proximal to transplant (7-17 days), had acute on chronic liver failure, and suffered thromboembolic phenomena. After a careful review of clinical and virological outcome predictors, we instituted policy changes to avoid transplantation in these circumstances. We believe that our series offers useful insights into the unique challenges that confront transplant centers in the COVID-19 era and could guide future discussions regarding this important area.

Introduction The development of portal hypertension leads to a majority of complications associated with chronic liver disease. Therefore, adequate treatment of portal hypertension is crucial in the management of such patients. Current treatment options are limited and consist mainly of medications that decrease the hyperdynamic circulation, such as non-selective beta blockers, and treatment of hypervolemia with diuretics. Despite these options, mortality rates have not improved over the last two decades. Newer, more effective treatment options are necessary to help improve survival and quality of life in these patients. Areas covered Multiple preclinical models and clinical studies have demonstrated potential efficacy of a variety of new treatment modalities. We introduce treatment options including the use of vasodilation promotors, vasoconstriction inhibitors, anticoagulants, antiangiogenics, and anti-inflammatory drugs. We examine the most recent studies for treatment options within these drug classes and offer insights as to which show the most promise in this field. Methodology Published studies that identified novel medical treatment options of portal hypertension were searched using PubMed (https://pubmed.ncbi.nlm.nih.gov/). Clinical trials listed in Clinicaltrials.gov were also searched with a focus on more recent and ongoing studies, including those with completed recruitment. Searching with key terms including “portal hypertension” as well as individually searching specific treatment medications that were listed in other publications was carried out. Finally, current societal guidelines and recent review articles relevant to the management of portal hypertension were evaluated, and listed references of interest were included. Conclusion Many ongoing early phase studies demonstrate promising results and may shape the field of portal hypertension management in future. As concrete results become available, larger RCTs will be required before making definitive conclusions regarding safety and efficacy and whether or not they can be incorporated into routine clinical practice. Statins, anticoagulants, and PDE inhibitors have been among the most studied and appear to be most promising.

Barrett’s esophagus (BE), a complication of long-term gastroesophageal reflux disease (GERD), has been reported to affect 6–8% of those with heartburn. Most patients are males, Caucasians and middle aged. However, there are no recent demographic studies that evaluated the proportion trends of BE. We aimed to assess proportion trends of BE over an 11-year period, using a very large national dataset. This was a population-based analysis of the national Explorys dataset. Explorys is an aggregate of electronic medical record database representing over 54 million patients. Proportions of BE’s variables such as age, gender, race, BMI, and treatment with PPI were recorded during an 11-year period. BE patients were classified into seven age groups (15–19, 20–29, 30–39, 40–49, 50–59, 60–69, ≥ 70 years old). Secular trends of the proportion of BE were assessed over time for each age group. The majority of patients diagnosed with BE were ≥ 70 years old across all calendar years. However, the proportion of BE patients who were ≥ 70 years old has significantly decreased between 2006 and 2016 (− 19.9%, p < 0.001). The proportion of patients with BE increased in all age groups but most prominently in the age groups, 30–39: 2.07%, 40–49: 3.64%, 50–59: 6.89%, 60–69: 6.18%, p < 0.001. BE was significantly more common in those who were Caucasian and male. PPI usage fell significantly in those who were ≥ 70 years old (− 20.8%, p < 0.001), but increased in the other remaining age groups. The proportion of BE patients who are 70 years and older has significantly dropped. Younger patients’ groups have demonstrated the highest increase in the proportion of BE patients, especially those in the age group of 30–39 years old.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder in western countries and an increasing cause of end-stage liver disease and hepatocellular carcinoma. NAFLD is known to coexist in patients with inflammatory bowel disease (IBD). This study aims to examine the prevalence of NAFLD, as well as trends in NAFLD-associated fibrosis, in a well-characterized IBD cohort utilizing a validated noninvasive test. We conducted a single-center retrospective chart review of patients at a large academic IBD center between 2007 and 2017. Patients with IBD and concurrent hepatic steatosis were identified. Charts were reviewed for baseline characteristics and laboratory data in order to calculate and trend NAFLD progression over time by a noninvasive marker, the NAFLD fibrosis score (NFS). Of 207 patients with IBD and concurrent NAFLD, NFS was able to be calculated for 138 patients at index diagnosis. A subsequent NFS was able to be calculated at 5-year follow-up for 56 patients. Over 5 years, 9 patients (16%) had worsening in NFS category, 4 patients (7%) had improvement in NFS category, and the remaining 43 patients (77%) stayed within their index NFS category. IBD patients with NAFLD tend to have stable liver disease over 4–6 years, and the risk of liver disease progression is low. This is the first study to document the progression of NAFLD by noninvasive testing over time.

INTRODUCTION: Hepatocellular carcinoma (HCC) is the most common liver malignancy and diagnosed when the Liver Imaging Reporting and Data System (LIRADs) criteria are applied to an imaging study. When detected lesions do not meet LIRADS criteria, it is essential to pursue further workup, including liver biopsy. We present a rare vascular tumor hepatic epithelioid hemangioepithelioma (HEHE) masquerading as metastatic HCC to highlight the importance of confirming the imaging diagnosis. CASE DESCRIPTION/METHODS: A 63-year-old male with a past medical history of untreated hepatitis B and hepatitis C, compensated cirrhosis who presented with ascending cholangitis and persistent transaminitis despite Endoscopic retrograde cholangiopancreatography (ERCP). He underwent an emergency ERCP with stone removal and stent placement, but his total bilirubin 2.5, AST 320, and ALT 260 continued to be elevated. An MRI liver and MRCP was significant for an enhancing lesion measuring 2.9 × 3.3 cm within segment 2 without arterial enhancement, LIRADS-M (Figures 1 and 2). Chest CT showed multiple bilateral lung nodules concerning for possible metastases. The team was concerned for metastatic HCC, but the liver lesion did not meet diagnostic criteria. In the setting of uncertainty, a liver and lung biopsy was performed, which was consistent with a HEHE and septic emboli, respectively. After medical optimization, the patient will proceed with surgical resection of the tumor. DISCUSSION: The LIRADS criteria is a reporting system that describes hepatic masses. LI-RADS 5 lesions have a specificity of 86.2% for HCC, while LIRADS M, such as our patient, suggests a malignant lesion with a specificity of 93%. LIRADS M lesions should be biopsied because of diagnostic uncertainty, as highlighted in this case. Our patient was diagnosed with HEHE, which has an incidence is 1:1000.000 and is a tumor found in multiple organs such as the liver and lung. HEHE can mimic other radiological findings, for example, targertoid and lollipop lesions, which make a biopsy necessary for diagnosis. HEHE epithelioid cells surround the sinusoids, and there are atypical nuclei with prominent nucleoli in the peripheral zone. Also, it is associated with CD 34 and CD 31 immunohistochemical stain. This case highlights a rare malignant liver neoplasm masquerading as metastatic HCC, which highlights the importance of performing a liver biopsy in patients where there is diagnostic uncertainty.Figure 1.: The lesion is not seen on the arterial enhancement phase.Figure 2.: T2 hypointense enhancement within liver segment 2 of 2.9 × 3.3 cm.

Hepatitis B virus (HBV) infection is one of the most common viral infections worldwide with an estimated 2 billion people exposed to HBV and 240 million with active chronic infection. Despite this, less than 1% of patients with chronic HBV infection receive treatment, and less than 3% of those achieve functional cure with traditional therapies. This review summarizes recent advances in the treatment of chronic HBV utilizing nucleic acid polymers (NAP) and entry inhibitors (EI). A recent phase 2 study evaluating the use of NAP following tenofovir and pegylated interferon (PEG-IFN) demonstrated increased rates of functional cure which persisted in 35% of patients after 48 weeks of follow-up. In addition, the EI Myrcludex B has demonstrated HBsAg response in up to 40% of patients when used in combination with PEG-IFN at week 72. Functional cure is considered the “holy grail” of treatment, and many new therapies are under investigation for the treatment of chronic HBV. As we work towards functional cure for chronic HBV, NAPs and EIs have shown efficacy in reducing HBV DNA and HBsAg levels and have emerged as potential therapeutic agents that may lead to a functional cure for HBV.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) rates in mono-infected human immunodeficiency virus (HIV) patients and determinants of nonalcoholic steatohepatitis (NASH)-related fibrosis in the HIV population are poorly understood. The aims of this study were to (a) estimate the prevalence of NAFLD in an urban population mono-infected with HIV and (b) to better characterize risk factors and predictors of fibrosis in this cohort. METHODS: We conducted a retrospective chart review of patients linked to our HIV clinic from 2017 to 2018 (n = 2974). Patients with hepatic steatosis were identified by characteristic findings on imaging (ultrasonography, computed tomography, or magnetic resonance imaging) or liver biopsy. If patients had radiologic or histologic evidence of hepatic steatosis, cross-sectional data including patient demographics, comorbidities, laboratory results, and medications were collected. Non-alcoholic fatty liver disease Fibrosis Score (NFS), Fibrosis-4 Index (FIB-4), and AST to Platelet Ratio Index (APRI) were calculated for each patient at the time of initial diagnosis. Exclusion criteria included acute liver injury, alcohol use disorder, or viral hepatitis B/C. RESULTS: Of the 2974 patient charts assessed, 1537 had available imaging or biopsy data, and of these, 139 had radiologic/histologic evidence of hepatic steatosis (9%). After exclusions, 57 patients were included in the analysis. 47 patients were African American (82%), 32 had a Body Mass Index (BMI) >30 (56%), and 41 had hyperlipidemia (76%). The median BMI for the study population was 30. Ten patients (18%) had a NFS >0.676, correlating with a high likelihood of NASH. Variables significantly associated with higher NFS included age >45 (P = 0.01), African American race (P = <0.01), higher BMI (P = <0.01), presence of hyperlipidemia (P = 0.01), and diabetes (P = 0.02). CONCLUSION: This analysis of HIV mono-infected individuals from an urban practice demonstrates that the prevalence of NAFLD is lower (9.0%) than in the general US population. Age, obesity, diabetes, and hyperlipidemia were all significantly associated with a higher NFS, which is consistent with prior studies. It is not clear whether African American race confers additional fibrosis risk. The identification and risk-stratification of patients with HIV and NAFLD are important in counseling and triaging of patients to disease altering therapy. Future studies will focus on correlation of serum based fibrosis markers with other modalities of assessing fibrosis.

Introduction: Worldwide an estimated 844 million people have chronic liver disease (CLD) with an annual mortality rate of 2 million.Causes for CLD such as viral hepatitis and alcohol use disorder are often stigmatized and lead to underreporting.CLD can be missed by clinicians because of a normal clinical exam and limited biochemical abnormalities.CLD symptoms often overlap with other medical comorbidities further confounding identification.Additionally, physicians' knowledge about CLD, including the interpretation of viral serologies and recognition of fatty liver, is suboptimal, leading to underdiagnosis.Studies reporting the types of symptoms, their prevalence, and how these symptoms affect patients is lacking in the literature.Purpose To assess symptom prevalence and interference amongst a cohort of patients with end stage liver disease.Methods Patients were recruited from liver clinics within 2 healthcare systems as part of a larger study (NINR: 1R01NR016017-01).Eligibility requirements were Medical End Stage Liver Disease (MELD) score ≥ 15, absence of liver cancer, absence of prior liver transplant, absence of active hepatitis C treatment at enrollment, and the presence of a caregiver or other support person.Patients underwent extensive assessment including the Condensed Memorial Symptom Assessment Scale (CMSAS) which reports on 14 symptoms and their global symptom distress on a 0-4 scale.Demographic and descriptive statistics were used to summarize results from survey data.Results A total of 154 baseline surveys were available for extraction.Most patients were Child-Turcotte-Pugh (CTP) class B (54%) and C (40%).Mean age was 54, 65% were male and 88% were Caucasian.The average Charlson Comorbidity Index score was 3.6±1.8and average MELD score for the group was 17.1±4.2.The etiologies of liver disease included alcohol (35%), NASH/cryptogenic (30%) and viral hepatitis (24%).The mean number of symptoms reported per patient was 8.5.The most prevalent symptoms were lack of energy (93%), drowsiness (77%), difficulty sleeping (75%), worrying (69%) and pain (65%).The symptoms which interfered with activity the most included lack of energy (3.7), difficulty sleeping (3.6), pain (3.4), drowsiness (3.3), and difficulty concentrating (3.0).Conclusion In patients with predominantly CTP B and C cirrhosis, symptom prevalence was almost universal and multiple.Symptom interference and symptom prevalence did not have complete correlation with difficulty sleeping and pain causing more interference with activities yet being slightly less prevalent.The early analysis of this longitudinal study data demonstrates both a high prevalence of symptoms in advanced cirrhosis as well as significant global symptom distress scores.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in western countries and an increasing cause of end stage liver disease and hepatocellular carcinoma (HCC). While patients with inflammatory bowel disease (IBD) are traditionally viewed as underweight and malnourished, increasingly effective therapies have led to similar rates of obesity in these patients when compared to the average population. The aims of this study were to 1) characterize rates of NAFLD in a large cohort of patients with IBD and 2) identify IBD-related predictors of NAFLD. METHODS: We conducted a single-center retrospective chart review of patients referred to our IBD program from 2007-2017. NAFLD was defined as imaging or biopsy findings of hepatic steatosis without coexisting liver disease or significant alcohol use. Relevant patient demographic and clinical data was collected within one year of NAFLD diagnosis. Comparisons between NAFLD rates in various groups were made using chi squared tests and one-way ANOVA tests. RESULTS: 1673 unique patients presented to our IBD program between the years 2007-2017. While patients were receiving care at our program, 237 (14%) had imaging or biopsy findings of hepatic steatosis. Of those 237 patients, 28 were excluded from analysis due to concurrent diagnosis of hepatitis C (n = 7) or B virus infection (n = 1), HIV infection (n = 2), significant alcohol use (n = 10), methotrexate-related liver injury (n = 2), sarcoidosis of the liver (n = 1), or primary sclerosing cholangitis (n = 5). As expected, increasing BMI was associated with higher NAFLD rates (P = 0.05). NAFLD rates were also significantly different between different types of IBD (P = 0.02). 63% of NAFLD patients had Crohn's disease (n = 132/209) and 19% had ulcerative colitis (n = 39/209). In patients with Crohn's, disease location in the proximal colon and rectum was positively associated with NAFLD (P = 0.02 and 0.02 respectively). NAFLD rates were not significantly different between types of Crohn's disease phenotypes including inflammatory, obstructing, and perforating (P = 0.77). CONCLUSION: NAFLD rates among patients with Crohn's disease are high. Disease location in the proximal colon and rectum was associated with NAFLD while disease behavior was not. Further research is needed to determine mechanisms driving development NAFLD in patients with Crohn's disease.