NASH Cirrhosis Research Articles

SAT-153 PTHrP Mediated Hypercalcemia

PTHrp mediated hypercalcemiaIntroduction:PTHrp is a normal gene product, which helps tooth eruption and mammary gland development. However, PTHrp production in an adult is mostly related to solid tumor malignancy. The homology of PTHrp to PTH from the 1st to 13th amino acids decided the similar mechanism of acting at PTH-1 receptor on increasing bone resorption and calcium reabsorption at the distal renal tubule. Lung cancer is known to secrete PTHrp and PTHrp secreting hepatic cellular carcinoma (HCC) is exceedingly rare. It’s only been documented in case reports. Two cases of PTHrp secreting atypical HCC are included in this case report.Case presentation:67 year old with history of alcohol abuse with 17.8 x 8.8 cm mass in the left hepatic lobe presented with acute encephalopathy and calcium of 14.4 mg/dl. Patient was treated with zolendronic acid 4mg, IV fluid and calcitonin. Patient has a PTH level of 7 pg/ml and PTHrp level of 335 pg/ml. Bone turnover marker Beta crosslaps of 1595 pg/ml. 25-hydroxy vitD of 25 ng/ml and 1,25 dihydroxy vitD of 42 pg/ml. Liver biopsy demonstrated moderately differentiated hepatocellular carcinoma. The undifferentiated portion was positive with CD56, CAM 5.2 suggestive of neuroendocrine differentiation and epithelial lineage. Patient had negative metastatic bone scan and no pathologic fractures. Second case is a 63 year old male with NASH cirrhosis was admitted for hypercalcemia of 13.2 mg/dl. Patient was found to have metastatic atypical hepatocellular carcinoma and L4 vertebral lesion. PTHrp was 30 pg/ml and PTH 14 pg/ml. Bone turnover marker Beta crosslaps of 405 pg/ml. 25-hydroxy vitD of 48 ng/ml and 1,25 dihydroxy vitD of 9 pg/ml. Patient expired prior to biopsy.Discussion:4 cases of similar HCC were found in the literature. The treatment approach was resection of tumor, chemo or ablation. Hypercalcemia is controlled with reduction of the tumor burden and rarely by zolendronic acid alone. Both of presented cases were too advanced for surgery or chemo treatment. When tumor was not amendable for treatment, the hypercalcemia was not controllable long term. A small size study in japan administering 10mg alendronate via hepatic artery rather than IV route for patients with HCC showed enhancement of the apoptosis of HCC in addition to controlling hypercalcemia. An animal study on anti-PTHrp monoclonal murine antibody showed improved mortality of PTHrp producing pancreatic carcinoma (FA-6) in transplanted nude mice.Conclusion:Most of the patients with PTHrp mediated hypercalcemia have advance cancer that is not amendable for surgery or chemotherapy. A non-invasive treatment approach other than alendronate should be investigated to control PTHrp mediated hypercalcemia.

SUN-685 Approach to a Potential Liver Transplant Candidate with Insulin Antibody-Mediated Severe Insulin Resistance

Introduction: Insulin antibody (IA)-mediated insulin resistance is a rare autoimmune condition resulting in uncontrolled hyperglycemia. High titers of IA are associated with increased mortality secondary to severe insulin resistance and labile blood sugars. There is a paucity of standardized treatment for these patients. Although there have been reported cases of success with immunosuppressants, none of these cases involved patients with liver cirrhosis. We present a case of IA-mediated severe insulin resistance which resulted in uncontrolled hyperglycemia and ultimately delayed liver transplantation. Clinical Case: A 61-year-old male with IA-positive type 2 diabetes, decompensated hepatitis B and NASH cirrhosis presented with several episodes of diabetic ketoacidosis (DKA) and worsening insulin resistance. His liver transplant listing had been placed on hold until glycemic control is achieved. The patient was diagnosed with type 2 diabetes mellitus in 1998. He has no prior autoimmune history. His disease was controlled on Levemir 100 units daily until March 2019 when he presented with his first episode of DKA. He subsequently required 200 units of insulin degludec daily and U-500 insulin 200 units with meals. The patient was readmitted to our hospital in August 2019 for a variceal bleed. His hospital course was complicated by a second occurrence of DKA requiring 100-150 units/hour on an insulin drip for resolution. Labs were significant for HbA1c 8.7% and IA >625 uU/mL (negative if <5.0 uU/mL). He required increasing amounts of basal and prandial insulin after discharge. The patient was again admitted within two months for abdominal pain concerning for spontaneous bacterial peritonitis, which was complicated by his third episode of DKA. Glucoses remained uncontrolled in the range of 170 to 300 mg/dL despite high insulin doses upon discharge. Metformin was contraindicated due to episode of lactic acidosis in the setting of his cirrhosis and concern for repeated episodes of DKA prevented use of SGLT-2 inhibitors. Extensive multidisciplinary discussions led to the decision for an upcoming trial of mycophenolate mofetil followed by plasmapheresis. The goal is to improve glycemic control while also minimizing infection risk to ultimately list him for a liver transplant. Conclusion: This patient highlights a major therapeutic challenge related to uncontrolled hyperglycemia and insulin resistance from anti-insulin antibodies in a cirrhotic patient. This can place patients at high risk for infection, poor wound healing and most importantly prohibit liver transplantation. Immunosuppressant therapy and plasmapheresis may drastically lower insulin antibodies and improve glycemic control, however, it will increase the risk of infection.

Progression to Cirrhosis Leads to Improvement in Atherogenic Milieu.

The prevalence of coronary artery disease (CAD) is high among patients with cirrhosis; however, the impact of it on cardiovascular disease (CVD) is not known. The aim of the current study was to evaluate CVD events in patients with cirrhosis and impact of cirrhosis on biomarkers of atherogenesis. The study included 682 patients with decompensated cirrhosis referred for liver transplantation (LT) evaluation between 2010 and 2017. All patients were followed until they experienced a CVD event, non-cardiac death, liver transplantation or last follow-up. To evaluate mechanistic link, patients with NASH cirrhosis were propensity matched 1:2 to non-cirrhosis NASH patients and biomarkers of atherogenic risk were compared. The composite CVD outcome occurred in 23(3.4%) patients after a median follow-up period of 585days (IQR 139, 747). A strong association between presence of any CAD and CVD event was noted (HR = 6.8, 95% CI 2.9, 15.9) that was independent of age, gender, BMI, and MELD score. In competing risk model, the combined rate of LT and non-cardiac was significantly higher when compared to the rate of CVD events. Marker of insulin resistance and inflammation-related markers were similar in patients with and without cirrhosis. Patients with cirrhosis were more likely to have reduced VLDL, sdLDL-C, LDL-C, and triglycerides. Interestingly, patients with cirrhosis had an increase in serum HDL-2, the anti-atherogenic lipoprotein, and adiponectin, a protective serum adipokine. The risk of CVD events in patients with cirrhosis is low and may potentially be due to improvement in markers of atherogenic risk.

A91 SARCOMATOID CARCINOMA OF THE COLON PRESENTING AS IRON DEFICIENCY ANEMIA

Abstract Background Gastrointestinal malignancy is a common cause of iron deficiency and occult gastrointestinal bleeding among adults in developed countries. Given the high prevalence of colorectal cancer and adenomatous polyps in our population, it is imperative that these patients undergo early colonoscopy. Sarcomatoid carcinoma (SCA) of the colon is a very rare condition, with less than 30 cases reported in the literature. Given the highly aggressive nature of this neoplasm, it is important to familiarize oneself with its presentation, histopathology and treatment options. Aims Describe a case of SCA of the colon in a cirrhotic patient, presenting initially as iron deficiency anemia of unknown etiology. Methods Case report and literature review. Results A 69-year-old female presented to the emergency department with complaints of progressive weakness and failure to thrive. Past medical history was significant for chronic kidney disease, NASH cirrhosis Child-Pugh C and recurrent hepatocellular carcinoma despite previous radiofrequency ablation. Investigations demonstrated de novo iron deficiency anemia with the following blood results: hemoglobin of 96, iron of 8.6, iron saturation of 20% and ferritin of 56. Subsequently, gastroenterology was consulted in order to assess for an occult source of bleeding. A gastroscopy was first performed in which no abnormalities were found. She then underwent a colonoscopy, which demonstrated a very large indurated nodular ulcer in the ascending colon, suggestive of invasive neoplasm (Figure A). Indeed, the biopsies demonstrated a malignant spindle cell neoplasm consistent with SCA. On immunohistochemistry, the tumor cells stained positive for keratin AE1/AE3, weakly positive for SMA and S-100, but negative for SMM, HMB45, DOG1, C-KIT and CD31. Given her severe comorbidities, no therapeutic options were available for this patient, thus further staging investigations were not pursued. Unfortunately, the patient rapidly deteriorated and died less than 8 weeks following her diagnosis. Conclusions Sarcomatoid carcinoma of the colon is an extremely rare neoplasm with very poor prognosis. Histologically, this tumor is characterized by a typical biphasic pattern, composed of both mesenchymal and epithelial cells. However, as demonstrated in this case, some SCA display a rather predominantly mesenchymal pattern, rendering the diagnosis difficult using morphology only. Immunostaining is therefore used to identify carcinoma features and to rule out similar tumors such as sarcoma, GIST, mesothelioma and melanoma. SCA of the colon is exceedingly aggressive, with remarkably rapid tumor growth and early distant metastasis. Indeed, median survival is reported to be less than 6 months. Given its rarity, no well-defined treatment guidelines exist, however most patients are managed with early radical surgery, adjuvant chemotherapy and close follow-up. Funding Agencies None

Spontaneous Bacterial Peritonitis at University Hospitals of North Midlands NHS Trust: A Retrospective Study

Background Spontaneous bacterial peritonitis is an acute infection of ascitic fluid that is not related to an underlying intra-abdominal pathology. Methods This is a retrospective study of data on ascitic fluid samples taken during the period of January to December 2017 to assess the management of SBP patients and associated mortality. Kaplan-Meir method was used to estimate survival probability at 30 and 90 days. Cox proportional models were used to evaluate aetiology and causative organism in predicting mortality. Analyses were done using R: A language and environment for statistical computing. Results Total of 53 patients were identified as having SBP based on ascitic fluid cultures. Sixteen of these also fulfilled the national criteria of ascitic neutrophil count of more than 250 or total cell count of more than 500. Thirty-three (62.8%) samples grew pathogenic organisms. The most common pathogenic organisms were E coli (30.3%) followed by Enterococcus (21.2%) – in which four were ESBL tagged – Klebsiella (6%) and Staph Aureus (6%). In majority of the patients, the underlying aetiology of ascites was secondary to ALD (68.9%), Malignancy (11.8%) and NASH cirrhosis (11.8%). In this cohort, the overall 30-day survival was 64.2% and 90-day survival was 43.4%. About half mortality occurred during the same admission to hospital. Conclusion E coli was the most commonly isolated organism. Alcoholic Liver Disease was the most common underlying aetiology in SBP patients. SBP is associated with a high 30-day and 90-day mortality. Isolation of pathogenic organisms was associated with a four-fold higher mortality than non-pathogenic organisms.

P1768 The value of global longitudinal strain in non-alcoholic steatohepatitis-associated cirrhosis

Abstract Introduction Non-alcoholic steatohepatitis (NASH) in patients with metabolic syndrome is a common cause of cirrhosis and has been associated with increased cardiovascular mortality. In patients with liver cirrhosis systolic or diastolic dysfunction can be observed and is independent of the cirrhosis etiology. Only few studies using newer echocardiography indices such as Global Longitudinal Strain (GLS) have been published in cirrhotic patients. Purpose To evaluate GLS in patients with NASH cirrhosis when compared to other etiologies. Methods A total of consecutive 36 cirrhotic patients aged 18-70 were included in our study. Standard speckle-tracking software was used for offline analysis of standard apical views and GLS was calculated. Stroke Volume Index (SVI) was calculated with the Simpson method and a standard 2D, Doppler and Tissue Doppler examination was performed in all patients. Results Median age of the study population was 58 (IQR 50-64) years, 78% were male and 17% had ascites. Cirrhosis was considered decompensated in 21 (58%) of patients. The 28%, 42% and 19% had NASH-associated, alcoholic and viral etiology of cirrhosis, respectively. Median ejection fraction (EF) was 60% (IQR: 57%; 65%) and GLS was -21.1% (-19.7%; -23.1%) in the total population. Absolute value of GLS was lower in patients with NASH cirrhosis compared to other etiologies (p = 0.009) (figure 1). EF, SVI, left atrial volume index (LAVI), E/e’ ratio and mitral annular velocity (e’) did not differ significantly between those with NASH associated cirrhosis and the rest. GLS values were significantly correlated with EF (r=-0.588, p = 0.002), SVI (r=-0.469, p = 0.016) and BNP levels (r=-0.571, p = 0.007), but not with age, left ventricular end diastolic volume, left atrial volume index, E/e’, mitral annular velocity and blood pressure. According to a multivariable linear regression model, NASH etiology [B = 2.1 (0.6; 3.7), p = 0.008)] and EF (per 10% increase) [B=-1.7 (-3.3; -0.2), p = 0.03)] were the only independent factors associated with GLS values in cirrhotic patients. Conclusions GLS values are within normal limits in cirrhotic patients but seem to be affected in patients with NASH associated cirrhosis. Further studies are needed to assess the prognostic implications of this finding. Abstract P1768 Figure 1

Association of non-alcoholic fatty liver disease (NAFLD) and insulin resistance in type 2diabetes

Background Non-alcoholic fatty liver disease NAFLD is one of the leading causes of nonalcoholic steatohepatitis NASH cirrhosis and hepatocellular carcinoma and is a major risk factor in hepatic insulin resistance IR. IR appears to be a common pathophysiological link between NAFLD and type 2 diabetes mellitus T2DM and limited information is available on the association of NAFLD with IR in T2DM individuals. We decided to determine whether there is association of NAFLD with IR in T2DM subjects.Material amp Methods Study involving 151 53 males 98 females T2DM subjects were screened for NAFLD using abdominal ultrasound scanning clinical assessment and biochemical parameters. IR was calculated using HOMA-IR. Association between NAFLD and IR was tested by Chi-square analysis. Significant difference between NAFLD and non-NAFLD subgroups was analyzed by t-test and z-test.Results The prevalence of NAFLD IR and hypertension in T2DM subjects were found to be 73 81 and 80 respectively. There was no significant difference in the prevalence of these between male amp female. However the prevalence of obesity and central obesity was significantly high in females. The comparison between NAFLD and non-NAFLD subgroups showed significantly high prevalence of IR hypertension obesity central obesity elevated SGPT and TG in NAFLD group. However there was no significant difference in mean values of serum biochemical parameters except TG VLDL and SGPT. NAFLD showed strong association with IR OR 13.ConclusionThe study indicated high prevalence of NAFLD and IR and strong association between them in diabetic population.

NAFLD in women: Unique pathways, biomarkers and therapeutic opportunities.

In this review article we evaluate sex differences in the natural history of NAFLD and highlight distinct risk profiles of women with NAFLD, as well as unique treatment considerations and research gaps. Reproductive factors, such as menopausal status should be considered when evaluating NAFLD risk in women, as well as additional reproductive risk factors such as age at menarche, presence of polycystic ovary syndrome, and gestational diabetes. Women do appear to have lower risk for hepatocellular carcinoma from NASH, as well as lower mortality from NASH cirrhosis than men, although among women, NASH is now the leading indication for liver transplant. Data on sex differences in biomarker development and clinical trials are lacking, and researchers should be encouraged to evaluate biomarker performance by sex, and specifically report clinical trial endpoints in women.

1003 Outcomes of Patients With Nonalcoholic Steatohepatitis With Cirrhosis and Low Model for End Stage Liver Disease Score

INTRODUCTION: Subsets of patients with cirrhosis from non-alcoholic steatohepatitis and low MELD scores have slow progression of their MELD score over time. These patients may succumb to progressive liver disease prior to receiving a transplant. Early identification of this subset of patients is crucial to improve outcomes. METHODS: We retrospectively studied patients with NASH cirrhosis seen at our large tertiary care center. We collected data on demographics, clinical and laboratory variables including MELD score at diagnosis, at decompensation and at death. We recorded mortality, cause of mortality, and liver transplantation if received. Patients with MELD score&lt; 15 at the time of diagnosis were analyzed. We performed Kaplan-Meier survival analysis. Univariate logistic regression analysis was performed to identify factors predicting transplant-free survival in NASH patients with low MELD. RESULTS: Two hundred and six patients with NASH cirrhosis and MELD &lt; 15 were identified. Mean age 57.8 (12), 62 (30%) were males. Median MELD was 8 (IQR 6-10). Eight five (41%) patients developed hepatic decompensation, 82 (40%) developed ascites. Median MELD at decompensation was 10 (IQR 8-12). At a mean follow up of 5.4 (4.0) years, 8 (4%) patients had progression of their MELD score and received liver transplantation. Eight (4%) patients died of whom 6 (75%) died of progressive liver disease. Median MELD at the time of death was 18 (IQR 15-21). Kaplan Meier survival of all NASH cirrhosis patients with MELD &lt; 15 was 96% at 3 years, and 92% at 5 years. On univariate analysis, absence of ascites was the single most important predictor of transplant free survival in patients with MELD &lt; 15. Age, sex, creatinine, total bilirubin, and MELD score, were not significant predictors of survival. Kaplan Meier survival of patients with NASH cirrhosis and MELD &lt; 15 with and without ascites was 94% vs 98.9% at 3 years, and 88% vs 98.9% at 5 years respectively (P = 0.02). CONCLUSION: A significant proportion of patients (∼40%) with NASH cirrhosis have a low MELD score despite decompensation with ascites and have a poor outcome as compared to NASH patients with low MELD and without ascites. A subset of low MELD NASH cirrhosis patients with ascites die of progressive liver disease at a low MELD score before diseased donor liver transplant (DDLT) can become available. Patients with NASH cirrhosis with ascites and low MELD score should be considered for a living donor or high risk diseased donor liver transplant to improve outcomes.

2275 Anoxic Brain Injury From Hepatic Encephalopathy in Acute on Chronic Liver Failure: A Case Report

INTRODUCTION: Hepatic encephalopathy (HE) is a complication seen in both acute liver failure and acute on chronic liver failure (ACLF). There is a paucity of data regarding IV HE resulting in global anoxic brain injury in those with ACLF. We present a case of anoxic brain injury from severe HE in a patient with ACLF. CASE DESCRIPTION/METHODS: 74-year-old male with a past medical history of hypertension and CAD had recently been diagnosed with NASH cirrhosis when he presented to an outside hospital with ascites. Two months later he presented to our hospital with acute change in mental status. On presentation, the patient had normal vital signs. Physical examination revealed obtundation with response to noxious stimuli. There was no scleral icterus and labs were significant for WBC 5.1, platelet count 82, BUN/Cr 32/1.81, lactate 3.2, NH3 248, LFTs unremarkable, MELD Na 23. CT head and chest X-ray were negative for acute processes. On physical exam, patient was non-jaundiced with a mildly distended abdomen. He was started on lactulose every 6 hours. His mentation continuously deteriorated and he was intubated for airway protection and transferred to ICU 8 hours after admission, where he was started on rifaximin. Nephrology was consulted and CRRT was initiated after NH3 was noted to be &gt;500 in the ICU. Repeat CT head now showed increased intracranial pressure, and subsequent MRI one day later showed global hypoxic ischemic injury. EEG with global slowing pattern signifying anoxic brain injury. Ammonia levels normalized on CRRT (although patient required dialysis for anuria after completion of 6 days of CRRT) and SSEP was done which did show evoked potentials, however no improvement was noted on neurological exam. Family eventually made the decision to transition care to comfort measures and the patient expired soon after. DISCUSSION: Overt cerebral edema leading to coma in HE and ACLF is rare given the chronicity of high ammonia and brain adaptation. The pathophysiologic mechanism for HE in ACLF is thought to be a combination of elevated serum ammonia and systemic inflammatory changes. Our attempts with hemodialysis did not change the clinical course suggesting irreversible tissue damage. Advanced therapies including embolization of portosystemic shunts was not pursued as none were identified on contrast enhanced imaging. Preventing decompensation and early recognition may be the modifiable factor in this high mortality disease.

2326 Primary Squamous Cell Carcinoma of the Liver: A Rarity

INTRODUCTION: Primary liver squamous cell carcinoma (PLSCC) is a very rare entity with less than 40 reported cases since 1970. PLSCC has been known for late diagnosis, high malignancy rate, and poor prognosis of less than 1 year. The exact pathogenesis of PLSCC is unclear, though various theories exist. CASE DESCRIPTION/METHODS: A 72-year-old male with a history of NASH cirrhosis and hepatocellular carcinoma (HCC) status post right hepatic lobectomy 11 years prior and microwave ablation of a presumed recurrent HCC mass just 5 months prior, presented with a 2-month history of progressive fatigue, shortness of breath, lower extremity edema, and abdominal pain. He was hypotensive with an initial blood pressure of 90/54mmHg and had a distended abdomen without evidence of jaundice, encephalopathy, or acholic stools. Labs were notable for WBC 16.9 × 10^3/uL, lactic acid of 4.5mmol/L, and alpha-fetoprotein marker of 1.9ng/mL. CT Abdominal/Pelvis revealed a large burden of diffuse intrahepatic lesions spanning all lobes—findings compatible with HCC—and multiple bilateral kidney simple cysts. Patient underwent an ultrasound guided biopsy of the largest hepatic lesion measuring 2.3 × 2.0 × 2.8 cm. Unfortunately, his condition rapidly worsened with significant elevation in liver enzymes and lactic acid and he passed away. Pathology results resulted shortly after his passing and showed a partially necrotic high grade carcinoma favoring squamous cell carcinoma. It was strongly positive for immunomarkers: CK5, CK7, p40, HSP70 (non-specific), but negative for GATA3, CK20, glypican 3, Hep Par1, S100 protein. DISCUSSION: In this case, the patient was thought to have HCC, but its aggressive clinical course was highly unexpected. Data on the diagnosis of PLSCC is limited and the mechanism is uncertain, though it has a strong association with hepatic cysts, stones, and cirrhosis. Hepatic cysts were not clearly visualized on imaging, though studies do show a positive correlation between the incidence of kidney and hepatic cysts. As this patient had multiple benign bilateral kidney cysts, we suspect that hepatic cysts could have also been present which makes PLSCC very likely given the lack of evidence of a different primary source. A liver carcinoma with such an aggressive clinical course should increase clinical suspicion for PLSCC, however further understanding of the pathogenesis of this disease needs to be investigated.

2422 Post-Transplant Lymphoproliferative Disorder

INTRODUCTION: Post-transplant lymphoproliferative disorder (PTLD) is a rare but severe complication in both solid organ and hematopoietic stem cell transplantation. PTLD is caused by the dysfunction of T-cells as a result of the immunosuppressive therapy commonly used in transplant patients. This dysfunction then causes abnormal lymphoid proliferation leading to malignancy. We discuss a case of PTLD presenting in the form of a small bowel obstruction in a patient with dual liver, kidney transplantation. CASE DESCRIPTION/METHODS: A 68-year-old man with previous NASH cirrhosis status post a deceased donor liver and kidney transplant presented to the hospital with nausea, vomiting, and abdominal distension. Prior to presentation he had been maintained at home on Cellcept and Tacrolimus for many years. He was doing well until 3 months prior to presentation when he noted the onset of night sweats. He had no other symptoms until two days prior to presentation when he had the abrupt onset of abdominal pain, distention, nausea and vomiting causing his presentation to the ED. On arrival his initial work up was significant for a mild leukocytosis, anemia, and AKI. He had a CT abdomen and pelvis done which was significant for a small bowel obstruction secondary to a small bowel mass along with mesenteric and retroperitoneal lymphadenopathy, raising the concern of PTLD on initial presentation. Interventional radiology was then consulted and performed a para-aortic lymph node biopsy. EBV and CMV PCR returned negative but the surgical pathology returned as Diffuse Large B Cell Lymphoma with double expression, suggesting a diagnosis of Post Transplant Lymphoproliferative Disorder. He was started on the R-CHOP chemotherapy regimen inpatient and was discharged for further outpatient treatment. DISCUSSION: This case is a rather classic presentation of a rare complication of immunosuppressive therapy, demonstrating the possible lethal side effects of these often life saving drugs. Swift diagnosis was made possible due to early clinical suspicion and rapid involvement of a multitude of different medical specialties. This case demonstrated the need for multi-disciplinary team at all transplant centers and how close communication between consultants is key to these patients success.

2224 A Rare Complication of Post-TIPS Related Acute Cholecystitis

INTRODUCTION: Amongst the well documented TIPS-related biliary complications, there has been no reported case of acute cholecystitis. Multiple multicenter RCT comparing TIPS to large volume paracentesis reported better control of ascites, lower diuretic doses or cessation of diuretics in approximately 75% of the patients. Biliary related complications include biliary venous fistulas, biloma or biliary occlusion secondary to biliary compression. This may be the first reported case of Post TIPS acute cholecystitis. CASE DESCRIPTION/METHODS: 67-year-old white male with end-stage NASH cirrhosis was hospitalized 6 months ago for diuretic-resistant ascites. Prior to admission, he has required weekly large volume paracentesis. While hospitalized, he underwent large-volume paracentesis and was treated for acute urinary tract infection. TIPS was placed two weeks post discharged and ascites improved. Three days later while undergoing further evaluation, a liver ultrasound showed gall bladder wall thickening and gall stones, suggestive of acute cholecystitis with cholelithiasis. He subsequently developed severe pancytopenia and worsening liver function test. A percutaneous cholecystostomy tube was placed for gall bladder decompression along with a 14-day course of IV antibiotics. He later developed Choledocholithiasis and required ERCP and cholangioscopy. Multiple stones were extracted from the bile duct and complete fibrosis of the cystic duct was noted. The patient required multiple hospitalizations since then, frequent paracentesis and treatment for SBP. He recently underwent OLT with cholecystectomy which was technically challenging. DISCUSSION: TIPS insertion has been established as an effective second-line treatment for refractory ascites. There are 3 documented category of TIPS complications; technical, portosystemic and unique shunt related but no known reported case of acute cholecystitis. Hepatic encephalopathy occurs in approximately 30% of patients, early thrombosis or delayed shunt stenosis occurred in 22- 50% of patients prior to the development of polytetrafluoroethylene-covered stents. The technical intricacy of this intervention poses a potential risk, and morbidity rates as high as 20%. A broad understanding of the uncommon and unique complications can potentially decrease post-op-related complications especially in a patient undergoing OLT It is necessary for clinicians who perform this procedure to be aware of the clinical spectrum of TIPS-related complications and their management.

2276 Malignant Hepatic Epitheliod Hemangioendothelioma in a Patient With a Prior Liver Transplant

INTRODUCTION: While liver transplantation itself is an invasive and specialized procedure, often with an arduous medical course preceding the surgery; post-transplant life is rarely without complication. Permanent immune suppression introduces its own cohort of increased risks including unique infections, malignancies, and side effects of immunosuppressive or prophylactic therapies. Special consideration should be given to these patients when potential complications arise. CASE DESCRIPTION/METHODS: A 51-year-old male with a an orthotopic liver transplant 6 years prior due to NASH cirrhosis presents with rapid significant weight loss and worsening abdominal pain. MRI revealed development of T2 hyper-intense peripherally enhancing lesions throughout the liver, as well as massive splenomegaly with possible areas of splenic infarct. Transjugular liver biopsy was expedited and ultimately revealed epitheliod hemangioendothelioma (EHE). Initial infectious work up was unrevealing outside of EBV viral load returning weakly positive; however, given possible association with EHE with EBV, treatment was initiated with valgancyclovir. Immunosuppression was also adjusted from tacrolimus to everolimus given anti-neoplastic properties of mTOR inhibitors over calcineurin inhibitors. He was started on pazopanib as an outpatient given anecdotal evidence of VEGF inhibitors in treating EHE, however, treatment was complicated shortly thereafter by syncope and refractory TTP, and palliative care was ultimately pursued. DISCUSSION: Epithelioid hemangioendothelioma is a rare vascular tumor originating from mesenchymal cells. While risk of malignancy is increased post transplant due to immunomodulators, post transplant Hepatic EHE remains an exceedingly rare diagnosis. EHE is considered to have intermediate behavior between hemangioma’s and hemangiosarcoma’s however HEHE is metastatic at diagnosis in 50% of diagnoses. Common presenting symptoms include vague abdominal pain, weight loss, and weakness/fatigue. Histopathological examination via biopsy is the gold standard of diagnosis and positivity of factor VIII-dependent antigen, CD-34, and CD-31 are important. Course is variable however prognosis is poor and there is no standardized management plan. VEGF inhibitors including Bevacizumab and Pazopanib have been a target of therapy given histologic positivity for target receptors, however results have been mixed to date.

2432 Incidental Diagnosis of Merkel Cell Carcinoma in a Liver Transplant Patient Admitted for Diverticulitis

INTRODUCTION: Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine skin cancer. Most patients (80%) who develop MCC have been infected with a Merkel cell polyomavirus. Sun exposure, fair skin, and age are risk factors; however, it occurs most commonly in immunosuppressed patients, specifically organ transplant and HIV-infected patients. Though the exact mechanism is still unknown, it is thought thatimmunosuppression contributes to viral integration, mutagenesis, and carcinogenesis of the virus. CASE DESCRIPTION/METHODS: 75-year-old white male with a history of liver transplantation for NASH cirrhosis, maintained on mycophenolate and tacrolimus, was admitted to the hospital for diverticulitis. Lab results showed pancytopenia. CT abdomen showed acute diverticulitis, and a nonspecific soft tissue density near the porta hepatis encasing the common and proper hepatic arteries (Figure 1). A focused physical exam showed a large axillary mass (Figures 2 and 3). His diverticulitis improved with a course of broad-spectrum antibiotics. The mass was biopsied and positive for MCC, suggesting the lesion near the porta hepatis represented metastasis. The axillary mass was excised and he received local radiation therapy. He was unable to undergo chemotherapy due to poor performance status. Within 10 months of the diagnosis, the patient died. DISCUSSION: While MCC is most commonly associated with the long-term immunosuppression following solid-organ transplantation, its occurrence is also rising in older adults whose immune function naturally declines with time. The median onset of MCC is greater than 65 years of age, and occurs most often in white patients. The most common site of origin is the head and neck region, but it can arise anywhere in the body. The diagnosis of MCC can be challenging due to the innocuous appearance of the primary tumor. This case demonstrates the importance of understanding the potential sequela of immunosuppressive medications in organ transplant patients and performing regular and thorough physical exams in order to quickly detect and treat diseases like MCC.

2265 Umbilical Hernia Rupture Complicated by Enterocutaneous Fistula in 63-Year-Old Female With Decompensated NASH Cirrhosis

INTRODUCTION: Spontaneous umbilical hernia rupture, known commonly as Flood syndrome, is a rare complication of severe ascites in end stage liver disease. Leakage of ascitic fluid leads to skin ulceration and necrosis which poses a threat of infection in addition to risk of evisceration or incarceration of bowels. Surgical repair is often deferred due to high mortality risk in decompensated cirrhosis which further complicates management. CASE DESCRIPTION/METHODS: A 63-year-old female with decompensated NASH cirrhosis, type 2 diabetes, atrial fibrillation, chronic heart failure, and morbid obesity was admitted after she developed sudden rupture of umbilical hernia with large amount of fluid discharge after defecation. She was afebrile and normotensive and was found to have ulcerated, ruptured umbilical hernia with active leakage of yellow fluid. Labs were significant for thrombocytopenia (115 × 10^3/µL), mild creatinine elevation (1.11 mg/dl), hyperbilirubinemia (2.8 mg/dl) and hypoalbuminemia (2.2 mg/dl). CT of the abdomen and pelvis revealed large abdominal wall hernia containing large and small bowels with questionable low-grade partial small bowel obstruction. General Surgery was involved but as she didn’t want to undergo any invasive treatment and due to high surgical risk, conservative treatment was recommended. Two days later she became febrile and hypotensive, accompanied by acute kidney injury (1.40 mg/dl) and worsening bilirubin (3.5 mg/dl). Due to high likelihood of SBP, diuretics were held, and ceftriaxone and albumin were initiated. Her INR increased to 6.3 and thrombocytopenia progressed (56 × 10^3/µL). Blood cultures showed no growth, but ascitic fluid cultures revealed polymicrobial flora including Bacteroides fragilis raising concerns of enterocutaneous fistula. Fortunately, she improved with conservative management and was safely discharged. DISCUSSION: Flood syndrome is caused by increased intraabdominal pressure during coughing, vomiting or defecating, like in our patient. Treatment is challenging as surgical repair is associated with high mortality despite known benefits of hernia repair in cirrhotic patients, however, these studies did not include decompensated cirrhosis. Patients are at increased risk of intraperitoneal infection, which was likely the case in our patient, however formation of enterocutaneous fistula is extremely rare.

2313 Graft-versus-Host-Disease Following Liver Transplant

INTRODUCTION: Graft versus host disease (GVHD) is a rare, life-threatening complication of liver transplantation that may affect the skin, GI tract and bone marrow. Donor T-lymphocytes remaining in the transplanted graft primarily target the recipient causing organ injury. Presentation may be non-specific and mimic other post-transplant complications, leading to delay in diagnosis and a mortality rate of greater than 80%. There is no consensus regarding optimal management of GVHD in the setting of liver transplantation. CASE DESCRIPTION/METHODS: A 65-year-old male with a history of NASH cirrhosis underwent deceased-donor liver transplant. Induction therapy was given with basiliximab and solumedrol then immunosuppression was maintained with tacrolimus, mycophenolate mofetil (MMF) and prednisone. Three weeks post-transplant, diarrhea developed and MMF was dose-reduced. Given persistence of diarrhea, fever, neutropenia and bilateral lower extremity petechial rash, additional work-up was performed. Imaging revealed colonic inflammation and subsequent flexible sigmoidoscopy demonstrated diffuse inflammation in the sigmoid. Biopsies of the colonic mucosa and lower extremity skin rash were consistent with GVHD. Peripheral blood confirmed the presence of donor chimerism. The patient was started on empiric antibiotics for febrile neutropenia, received granulocyte stimulating factor for leukopenia, intravenous steroids, and oral budesonide. MMF was initially discontinued but later resumed at increased dose; tacrolimus was continued. The patient's condition continued to deteriorate with diffuse mucosal GI bleeding. He received antithymocyte globulin and etanercept but his illness progressed secondary to Enterococcus bacteremia leading to septic shock. The patient died 8-weeks post-transplant in the setting of multiorgan failure. DISCUSSION: While rare, GVHD after liver transplantation should be considered in patients with new onset, unexplained symptoms. By virtue of its rarity after liver transplantation, data are sparse and management decisions are challenging. This case illustrates the need for increased awareness and standardized treatment guidelines. Management decisions are currently based on small case series often with discordant strategies including increasing or decreasing immunosuppression exposure. Global registries and multicenter collaboration will be essential to increase knowledge and improve outcomes.

2154 In Situ Plastic Biliary Stents Causing Intestinal Perforation: A Case Series

INTRODUCTION: Intestinal perforation is a rare complication of plastic biliary stents which exclusively occurs in the setting of preceding stent migration. We present the first case series to our knowledge of four patients with intestinal perforation from non-migrated in-situ plastic biliary stents. CASE DESCRIPTION/METHODS: 1: A 65-year-old-woman with biliary stent placement for cholangiocarcinoma-related obstruction presented with acute right upper quadrant (RUQ) pain. She had tachycardia, RUQ tenderness, and elevated liver function tests (LFT). CT scan showed duodenal perforation, and on ERCP a stent was seen perforating through the opposite duodenal wall. Prior straight 10Frx12 cm plastic stent was exchanged for a similar stent with a full external pigtail and a ½ internal pigtail. Over the scope clip was used to close the defect. 2: A 69-year-old-man with biliary stent placement for malignancy-related biliary stricture presented with acute RUQ pain. He had tachycardia, RUQ tenderness, and leukocytosis. CT scan showed duodenal perforation from distal tip of biliary stent with proximal aspect still in the common bile duct (CBD) though ERCP showed no obvious defect. Prior straight 10Frx10 cm plastic stent was exchanged for a similar stent with a full external pigtail and a ¾ internal pigtail. 3: A 60-year-old man with metastatic colorectal carcinoma of the liver with hepatic arterial infusion pump associated biliary sclerosis and stent placement presented with acute RUQ pain. He had leukocytosis, RUQ tenderness, and an acute LFT elevation. ERCP showed biliary stent causing duodenal wall ulceration. Prior 10 F × 12 cm plastic stent was replaced with a similar stent with a full external pigtail and ¾ internal pigtail. 4: A 24-year-old man with NASH cirrhosis status post orthotopic liver transplant and stent placement for anastomotic biliary stricture presented with acute LFT elevation. On ERCP, three plastic biliary stents were seen penetrating duodenal wall with proximal tips in place. Prior straight 10Frx12 cm plastic stents were replaced with similar stents with full external pigtail and a ¾ internal pigtail. An over the scope clip was used to close duodenal defect. DISCUSSION: Complication by in-situ plastic biliary stents may be decreased with full external pigtail stents. Stent exchange was successful in all cases, except case 4. This may have been due to the benign etiology of obstruction compared to malignant etiologies for others. An over the scope clip may be used successfully to close duodenal defect.

Non-alcoholic fatty liver disease after liver transplantation in patients with non-alcoholic steatohepatitis and cryptogenic cirrhosis: the impact of pre-transplant graft steatosis

BackgroundNonalcoholic fatty liver disease (NAFLD) may occur in liver transplant recipients. This study aimed to investigate the prevalence and risk factors of NAFLD after liver transplantation in patients with NASH and cryptogenic cirrhosis, focusing on the impact of graft steatosis. MethodsPatients with NASH and cryptogenic cirrhosis who had undergone liver transplantation in Shiraz transplant center between March 2010 and March 2017 were included. NAFLD was diagnosed after liver transplantation using ultrasonography and transient elastography. Results73 patients with NASH and 389 with cryptogenic cirrhosis were included. NAFLD was diagnosed in 33 patients (56.9%) in NASH group and 96 patients (26.7%) in cryptogenic group (OR: 3.61; CI: 2.04–6.39; P-Value < 0.001), using ultrasound. Obesity and post-transplant hyperlipidemia were independent predictors of NAFLD after liver transplantation (P < 0.05). NAFLD was diagnosed in 32.9% of patients with graft macrosteatosis compared to 29.9% in patients without graft macrosteatosis (OR: 1.51; 95%CI: 0.755–1.753). 28% of the patients with macrosteatosis ≥30% had NAFLD after liver transplantation compared to 31.4% with macrosteatosis <30% (OR: 1.175; 95% CI: 0.346–2.091). ConclusionLiver graft steatosis before transplantation was not associated with the occurrence of NAFLD after liver transplantation.

Comparing Two Strategies for Pediatric Nonalcoholic Fatty Liver Disease (NAFLD) Screening

Nonalcoholic fatty liver disease (NAFLD) is a growing disease globally. It is strongly related to obesity and insulin resistance. NAFLD poses a public health issue because it may progress to NASH and subsequently to cirrhosis [1]. Currently, NASH cirrhosis is going to be the second most common cause for chronic liver disease in adult patients awaiting transplantation [2]. There is evidence that its prevalence is also increasing in children which creates an urgent need to identify patients with NAFLD and intervene early.