Cryptogenic Cirrhosis Research Articles

Hypomorphic splice site IL2RG variants associated with Cryptosporidium liver disease

BackgroundX-linked severe combined immunodeficiency (X-SCID) is caused by mutations in IL2RG encoding for the common gamma chain (γc). This disease is typically fatal within the first year without immune reconstitution. We present two patients with IL2RG variants leading to a phenotype of Cryptosporidium-related sclerosing cholangitis. MethodsMedical history and laboratories were reviewed for two patients with IL2RG variants at c.270G. For one patient, we examined cDNA, γc expression, TCR repertoire, cytokine signaling, in vitro B-cell plasmablast differentiation, and in vitro T-cell differentiation of peripheral blood CD34+ cells. ResultsTwo unrelated male patients (17 and 21 years old) were identified with liver disease, recurrent childhood pneumonia and resultant bronchiectasis. P1 has persistent warts. Elevated transaminases in P1 led to liver imaging and biopsy consistent with sclerosing cholangitis. Stool PCR was positive for Cryptosporidium. P2 was diagnosed at age 6 with cryptogenic cirrhosis. He underwent orthotopic liver transplant at age 19; diarrhea and cholestatic liver disease developed 4 months post-transplant, and cryptosporidium was found in stool and liver. Cryptococcus meningitis also developed on immunosuppression. Both patients were hemizygous for an IL2RG variant resulting in p.W90C (P1:c.270G>T; P2:c.270G>C). P1 had mildly reduced CD4+ lymphocytes, CD4+ and CD8+ central/ effector memory T-lymphocytes, memory B-lymphocytes, and normal NK counts. P1 cDNA revealed a leaky splicing defect with a mix of exons 2–4 skipping along with full-length transcript encoding p.W90C. Cells from heterozygous mother expressed wild-type sequence suggesting skewed X-inactivation. Surface protein expression and distribution of TCR V-Beta repertoire was largely normal. IL-2-mediated STAT5 phosphorylation was impaired in T- and NK-cells. P1’s B-lymphocytes proliferated in response to in vitro IL-21/CD40L co-stimulation but failed to differentiate into CD27+CD38+ plasmablasts (< 1%). In vitro T-cell differentiation showed impaired survival of developing thymocytes, despite capability of maturing intoTCRaB+ CD3+ T cells. ConclusionsWe present two patients hemizygous for IL2RG variants leading to milder clinical phenotype compared to classic X-SCID. Consistent with other diseases of impaired IL-21 signaling, there was significant Cryptosporidium-related liver disease in addition to clinical manifestations of hypomorphic IL-2 signaling defect. Further work is necessary to address restoring IL-21 signaling to improve liver disease.

Updates in the Management of Hepatobiliary Cancers

Hepatobiliary cancers are aggressive tumors that affect the liver and biliary tract and are responsible for nearly 550,000 deaths per year. The most common malignancy is hepatocellular carcinoma, and risk factors include viral hepatitis infection, nonalcoholic steatohepatitis, and excessive alcohol use. Other etiologies include Wilson’s disease, α1-antitrypsin deficiency, and cryptogenic cirrhosis. Clinicians should be aware of underlying conditions and how they influence treatment decisions.

Short Telomere Syndrome presenting with pulmonary fibrosis, liver cirrhosis and hepatopulmonary syndrome: a case report

BackgroundIdiopathic pulmonary fibrosis is thought to result from aberrant post-injury activation of epithelial cells leading to fibroblast proliferation and activation. A number of genetic aetiologies have been implicated in this disease process, including, among others, the short telomere syndromes. Short telomere syndromes follow an autosomal dominant pattern of inheritance resulting in shortened telomere length, which consequently leads to accelerated cell death. Organs with rapid cell turnover are most affected.Case presentationWe describe a case of a 53-year-old man with a chief complaint of cough and dyspnea on exertion. His presentation was otherwise significant for features of accelerated aging, including a history of osteoporosis and early greying, and a family history of pulmonary fibrosis in his father. Pulmonary function testing revealed a restrictive pattern with severely reduced diffusion capacity and high resolution CT of the chest showed diffuse lung disease with mild fibrosis, in pattern suggesting an alternative diagnosis to IPF. Biopsy of the lung was in keeping with chronic fibrosing interstitial pneumonia. Imaging of the abdomen showed splenomegaly, hepatic cirrhosis and portal hypertension. Transthoracic contrast echocardiogram showed intrapulmonary shunting consistent with hepatopulmonary syndrome. Given the constellation of early aging, idiopathic pulmonary fibrosis, cryptogenic cirrhosis and a family history of pulmonary fibrosis in this patient, the Short Telomere Syndrome was suspected. Peripheral blood was sent for Flow-cytometry FISH, which demonstrated granulocyte telomere length below the 10th percentile for the patient’s age, consistent with a diagnosis of Short Telomere Syndrome in this clinical context. Targeted genetic testing of mutations known to be associated with short telomere was negative though it was acknowledged that the full spectrum of disease-causing mutations remains unknown. Given the extensive fibrosis on biopsy and his progressive hypoxemia he was treated with mycophenolate and prednisone. Ultimately, he developed progressive respiratory failure and underwent double lung and concurrent liver transplant 18 months after the initial diagnosis was made.ConclusionsShort Telomere Syndrome is a rare cause of end stage organ disease and testing lacks sensitivity making diagnosis challenging. Organ transplant is still the mainstay of treatment. Nevertheless, disease identification is important because of implications for family member screening and the possibility of future treatment options.

NAFLD: A pretransplant and post-transplant conundrum.

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A Rare Cause of Hypergonadotropic Hypogonadism: Transaldolase Deficiency in Two Siblings.

Transaldolase deficiency is a rare inborn autosomal recessive disorder caused by biallelic mutations in the TALDO1 gene. It is characterized by intrauterine growth restriction, dysmorphism, abnormal skin, cytopenia, hepatosplenomegaly, liver cirrhosis, endocrine problems, renal and cardiac abnormalities. We present two siblings of Turkish origin with early-onset form of transaldolase deficiency and hypergonadotropic hypogonadism in both sexes. The girl (index) was followed-up with cryptogenic cirrhosis, leukopenia and thrombocytopenia, skin abnormalities, congenital heart defects, hypercalciuria, nephrolithiasis, proteinuria, chronic kidney disease throughout childhood. She developed hypergonadotropic hypogonadism in adolescence period. Whole exome sequencing due to the multisystemic involvement revealed a previously described homozygous inframe deletion in TALDO1 gene. Her brother was born as a small for gestational age baby and was also followed-up with cryptogenic cirrhosis since his infancy, together with cytopenia, congenital heart defects, bilateral cryptorchidism, short stature, hypercalciuria, proteinuria and chronic kidney disease in childhood. He presented with testicular microlithiasis and hypergonadotropic hypogonadism in adolescence. Sanger sequencing of TALDO1 gene confirmed the presence of the same homozygous deletion with his sister. The mother was found to be a heterozygous carrier for this deletion. We describe two patients with multisystemic involvement since neonatal period who presented with an additional hypergonadotropic hypogonadism in adolescence. The diagnosis of transaldolase deficiency should be kept in mind for these patients, and they must be evaluated for gonadal functions especially during puberty.

Celiac disease screening in patients with cryptogenic cirrhosis.

We write a letter to the editor commenting the article "Who to screen and how to screen for celiac disease". We discuss the present literature on cirrhosis and celiac disease (CD) and recommend screening and treating CD in individuals with cryptogenic cirrhosis.

Prevalence of Celiac Disease in Patients With Liver Diseases: A Systematic Review and Meta-Analyses.

A subset of patients with celiac disease (CeD) has liver involvement in the form of hypertransaminasemia, liver cirrhosis, and autoimmune hepatitis. We conducted a systematic review with meta-analyses to determine the pooled prevalence of CeD in patients with cryptogenic cirrhosis, all-cause cirrhosis, cryptogenic hypertransaminasemia, and all-cause hypertransaminasemia. We searched PubMed and EMBASE up to January 2022. Cross-sectional, case-control, and prospective cohort studies performing serological tests and/or intestinal biopsy for CeD on patients with cryptogenic cirrhosis, all-cause cirrhosis, cryptogenic hypertransaminasemia, and all-cause hypertransaminasemia were included to calculate pooled estimates of seroprevalence and the prevalence of biopsy-confirmed CeD in these 4 groups. Of 6,871 articles screened, 20 articles were included finally in 3 meta-analyses for cryptogenic cirrhosis, all-cause cirrhosis, and cryptogenic hypertransaminasemia. For the all-cause hypertransaminasemia group, a qualitative review of 4 studies was conducted instead of a meta-analysis due to significant differences in studies. The pooled prevalence (95% confidence interval) of biopsy-confirmed CeD in cryptogenic cirrhosis was 4.6% (2.2%-7.5%) while the pooled prevalence of biopsy-confirmed CeD in all-cause cirrhosis was 0.8% (0%-3.4%). The pooled prevalence of biopsy-confirmed CeD in cryptogenic hypertransaminasemia was 5.7% (3.2%-8.8%). Nearly 1 in 20 patients each with cryptogenic cirrhosis and cryptogenic hypertransaminasemia have CeD; hence, they should both be considered high-risk groups for CeD. While the prevalence of CeD in those with all-cause cirrhosis is similar to that in general population, it may be worth screening them for CeD because liver pathology has the potential for reversal in them.

Reverse Takotsubo Stress Cardiomyopathy During Liver Transplantation

Reverse Takotsubo Stress Cardiomyopathy During Liver Transplantation

ABO-incompatible Pediatric Liver Transplantation With Antibody and B-cell Depletion-free Immunosuppressive Protocol in High Consanguinity Communities.

From November 2010 to June 2015, 176 children aged 0.2-to18 y were transplanted in the King Faisal Specialist Hospital and Research Center. Out of those, 19 children were transplanted across blood group barriers (ABO incompatible). The underlying diseases were biliary atresia (n = 6); progressive familial intrahepatic cholestasis type 2 (n = 4); Crigler-Najjar syndrome (n = 3); hepatoblastoma (n = 2); and urea cycle disorder, Caroli disease, cryptogenic cirrhosis, and neonatal sclerosing cholangitis (n = 1 each). Immunosuppression consisted of basiliximab, mycophenolate, tacrolimus, and steroids. Pretransplant prophylactic plasmapheresis, high-dose immunoglobulins, and rituximab were not administered. The grafts were from living donors (n = 17) and deceased donors (n = 2). Living donor morbidity was nil. The recipient median age was 21 mo (5-70 mo). After a median follow-up of 44 mo, 2 recipients (10%) died because of sepsis, 1 because of uncontrolled acute myeloid leukemia. The overall rejection rate was 7%, and no grafts were lost because of antibody-mediated rejection (AMR). HLA matching was 3.8 of 6 (A, B, DR), and there were 2 patients presented with acute cellular rejection, 1 patient with AMR, and 1 patient with biliary strictures. ABO incompatible liver transplantation is a feasible and life-saving option even with antibody and B-cell depletion-free protocol without increasing the risks for AMR. We speculate that this excellent result is most likely because of presence of relatively low titer ABO isoagglutinins and the high HLA match compatibility caused by habit of longstanding interfamilial marriages as typical of Saudi Arabia.

Study of Serum Lipid Profile and Aminotransferases (ALT and AST) in Non-obese, Non-diabetic Nonalcoholic Fatty Liver Disease

Background: Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of liver diseases characterized by simple steatosis to nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. It is the most common cause of cryptogenic cirrhosis. NAFLD is associated with obesity, insulin resistance, hypertension, type 2 diabetes mellitus, and dyslipidemia.&#x0D; Objective: The study aimed to assess the changes in lipid profile and aminotransferases (ALT and AST) in Non-alcoholic fatty liver disease (NAFLD).&#x0D; Methods: This observational cross-sectional study was carried out in the department of Biochemistry, Mymensingh Medical College in cooperation with the Centre for Nuclear Medicine and Ultrasound, Mymensingh from January 2012 to June 2013 after the approval of the protocol. A total of 120 subjects were included through purposive sampling, among them, 60 subjects were with fatty liver disease (group-I) and another 60 were without fatty liver (group-II) with ultrasonography. The sampling method was purposive (non-random). Relevant laboratory investigations were performed by using established methods to achieve the objectives.&#x0D; Results: The majority of the subjects with NAFLD (33.33%) were in 51-60 years (in Group-I). Mean serum total cholesterol, triacylglycerol, LDL-cholesterol, and HDL-cholesterol were 203.33±21.83, 184.41±33.31, 126.28±18.75, and 40.17±6.32 mg/dl in group-I and 167.65±9.83, 128.77±11.65, 101.74±9.29 and 40.16±3.55 mg/dl in group-II respectively. Significant differences were found in the case of total cholesterol (p&lt;0.001), triacylglycerol (p&lt;0.001), and LDL-cholesterol (&lt;0.001), but no significant difference was found in the case of HDL-cholesterol (p&gt;0.05). Serum ALT and AST were 49.43±16.98, 45.20±13.56 U/L in group-I and 32.83±4.54, 28.68±4.31 U/L in the group- II respectively. Significant differences were found in case of ALT (p &lt;0.001) and AST (p &lt;0.001).&#x0D; Conclusion: Nonalcoholic fatty liver disease is associated with dyslipidemia and with the elevation of serum ALT and AST.&#x0D; J Rang Med Col. September 2022; Vol. 7, No. 2:35-39

Platelet Spleen Index is a Noninvasive Technique to Detect Esophageal Varices in Cirrhotics

Background: noninvasive esophageal parameters may prevent the need for an esophagogastroduodenoscopy. Liver cirrhosis patients may benefit from the PC/SD ratio and the platelet count to spleen diameter (PC/SD) ratio, both of which are noninvasive yet useful indicators of liver cirrhosis progression. Objective: This study aimed to evaluate the diagnostic accuracy of the platelet spleen index for the diagnosis of gastric varices in patients with cirrhosis, using esophagogastroduodenoscopy as the reference standard. Methodology: A-Cross-sectional descriptive validation The study was conducted over the course of three months, from October, 2019 to December 2019. At the Gastroenterology A tertiary care hospital. The study comprised 90 participants. In addition to the requisite blood tests, abdominal ultrasonography was used to evaluate the size of the spleen. TYPE SIZE The sensitivity is 83%, the specificity is 66%, and the accuracy is 83% Variations were found in 24% of cirrhotic individuals. Cirrhosis was defined in accordance with the operational definition. Patients' blood samples were collected at the hospital laboratory for a complete blood count, abdominal ultrasound was performed in the Radiology department, and upper GI endoscopy was performed in the endoscopic suite for screeningpurposes. Results: With reverence to study the ages of the study's patients varied from 55.0 to 89.8. Ninety patients (44.7%) were women, while the remaining 48 (55.3%) were males. Hepatitis C was the most common diagnosis (almost 50%), followed by hepatitis B, cryptogenic cirrhosis, and Wilson's disease. Hepatitis A and B accounted for the remaining cases. (1.2% of the total). There were three distinct severity levels for esophageal varices. 12 patients (14.2%), 23 patients (27.7%), 32 patients (37.7%), and 38 esophageal varies (21.8%). Out of the total 90, 69.5% were determined to be in Child's Pugh stage A, 24.9% in stage B, and 4.7% in grade C. In a two-by-two table, we calculated the likelihood ratio (sensitivity plus specificity plus positive and negative predictive values) of the platelet spleen index for the diagnosis of gastro esophageal varices, and it came out to 78%. A ROC curve was also generated. The patients were stratified according to their age, gender, the cause of their cirrhosis, and the severity of their condition. Practical implications: This study will provide data to the health care workers to use non-invasive technique to lower procedure costs and associated complications to detect Esophageal varices in cirrhotics Conclusion: It is possible that the amount of unnecessary esophagogastroduodenoscopies may be reduced if a noninvasive method for diagnosing gastroesophageal varices were widely used. keywords: Esophageal varies, Cirrhosis, Platelet spleen index, Non invasive method, esophagogastroduodenoscopy

S3221 Adult Onset Progressive Familial Intrahepatic Cholestasis: A Rare Presentation

Introduction: Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of autosomal recessive childhood genetic disorders that disrupt intrahepatic biliary secretion. PFIC accounts for 10 to 15% of children's cholestatic diseases and liver transplantation. Although all patients will require liver transplantation at a certain point, early diagnosis and intervention can delay complications and transplantation. Case Description/Methods: A 41-year-old male presented with cryptogenic cirrhosis and a MELD score of 35 for transplantation evaluation. He had a childhood history of abnormal liver enzymes with a mixed pattern and cholecystectomy due to recurrent gallstones. Prior liver biopsy showed autoimmune features; however, there was no significant response to the conventional therapy with prednisone and azathioprine. However, a re-evaluation of his liver biopsy favored biliary disease: subsequent MRCP with normal bile ducts. Given the insidious onset of his cirrhosis without an identifiable etiology and the suggestion of biliary cause, PFIC was considered during pre-transplantation workup. Genetic testing for ABCB4 confirmed PFIC type 3; subsequently, he underwent liver transplantation with an unremarkable post-operative course. Discussion: This case highlights the impact of exploring a diagnosis of PFIC in adults referred for liver transplantation with long-standing cholestatic liver disease and negative initial workup. While currently, liver transplantation is the primary treatment option for end-stage liver disease from PFIC, advances in gene therapy have led to potentially curative treatments. As such, improved provider awareness and having a lower threshold for diagnostic testing may lead to an earlier diagnosis which is critical for optimal management, delaying the onset of end-stage liver disease, and offering to screen for family members.

S1809 Portal Cavernoma Cholangiopathy Presenting With Acute Cholangitis

Introduction: Portal cavernoma cholangiopathy (PCC) is defined as abnormalities in the biliary tree due to a portal cavernoma. Most cases occur in non-cirrhotic patients who remain asymptomatic. 5-30% of patients develop symptomatic disease and only 8% of symptomatic cases present with acute cholangitis. This case describes PCC as an uncommon cause of acute cholangitis. Case Description/Methods: A 26-year-old male with a medical history of acute lymphocytic leukemia in remission, cryptogenic cirrhosis, and portal vein thrombosis (PVT) on warfarin presented with 2-weeks of worsening abdominal pain, darkening of the urine, and weight loss. On examination, he was febrile to 101°F, normotensive, and had both scleral and palatal icterus. Initial labs revealed White blood count: 13.5 x10(3)/mcL, total bilirubin 7.5mg/dL, & ALP 398U/L. MRCP showed biliary dilation related to extensive portal vein cavernous transformation and narrowing in the common bile duct (CBD) due to compression by cavernous vessels in porta hepatis (Figure). Endoscopic ultrasound (EUS) showed PVT and collateral flow. Endoscopic retrograde cholangiopancreatography (ERCP) revealed biliary narrowing and beading. These findings were diagnostic of cavernous transformation with cholangiopathy. The patient improved after biliary stent placement with repeat stenting 6 months later. There was a discussion about TIPS and Portal vein reconstruction. However, the patient did not follow through. Discussion: PCC develops through PVT-related ischemia that underlies the development of collateral flow, biliary stricture, and dysmotility predisposing patients to cholangitis. Management is only indicated with symptomatic disease with endoscopic and surgical intervention. We report a rare presentation of PCC successfully managed with ERCP.Figure 1.: A) MRCP: Cavernous transformation of the portal vein. B) EUS: A portal vein thrombus involving area of portal vein confluence and collateral flow consistent with cavernous transformation. C) ERCP: Abnormal areas of narrowing and beading throughout the biliary system with extrinsic stenosis.

S1285 Association Between Distance to a Radiology Center and HCC Surveillance Among Patients With Cirrhosis in Florida

Introduction: Hepatocellular carcinoma (HCC) is a leading cause of morbidity and mortality in patients with cirrhosis, and HCC survival is directly correlated with stage at diagnosis. Current guidelines recommend HCC surveillance with an abdominal ultrasound every 6 months, but unfortunately many patients do not meet this threshold.1 Our aim was to determine whether distance to a radiology center, measured in travel time, was associated with HCC surveillance rates. Methods: We included data on adult patients with cirrhosis within the OneFlorida Clinical Research Consortium from October 1, 2015- December 31, 2019. The primary outcome was a continuous measure of the percentage of time up to date with HCC surveillance (PTUDS) based on abdominal ultrasound (US), triple phase CT, and/or MRI with contrast. Travel time was calculated using ArcGIS geomodelling software as the estimated minimum travel time between the geographic centroid of patient’s zip code and the nearest American College of Radiology-accredited center for US, CT, and/or MRI. Linear regression models were fit with PTUDS as the outcome; all covariates with a p< 0.05 were included in the final multivariable model. (Figure) Results: Among 25,299 patients with cirrhosis (median follow-up=4.1 years), the median PTUDS was 10.0% (interquartile range 0-29.9%). Variables found to have a statistically significant association with PTUDS are displayed in Table. Travel time, hepatic encephalopathy at baseline, and ascites at baseline were associated with increased PTUDS. Patients with alcohol-related liver disease, nonalcoholic steatohepatitis, and cryptogenic cirrhosis had lower PTUDS compared with patients with HCV. Conclusion: Travel time to the nearest radiology center is not associated with lower HCC surveillance rates while race, etiology of liver disease, and disease severity do appear to variably influence surveillance. By establishing factors associated with currently suboptimal surveillance rates, we can create targeted interventions to improve surveillance and, ultimately, patient outcomes.Figure 1.: Median PTUDS by County Table 1. - Multivariable Linear Regression Model of Factors Associated with HCC Surveillance Variable Beta Coefficient, 95% CI P-Value Travel Time 0.0016 (0.0012-0.0020) <0.001 Liver Disease Etiology Hepatitis C Virus Reference - Hepatitis B Virus 0.0246 (0.0019-0.0473) 0.034 Wilson's Disease 0.0137 (-0.571-0.0845) 0.704 Hemochromatosis 0.0067 (-0.0220-0.0354) 0.647 a1-Antitrypsin Deficiency 0.0673 (0.0200-0.1145) 0.005 Alcohol-Related Liver Disease -0.0720 (-0.0801- -0.0639) <0.001 Primary Biliary Cholangitis -0.0037 (-0.0261- 0.0186) 0.745 Autoimmune Hepatitis -0.0193 (-0.0406- 0.0019) 0.075 Primary Sclerosing Cholangitis 0.0123 (-0.0462- 0.0708) 0.680 Nonalcoholic Steatohepatitis -0.0835 (-0.0917- -0.0752) <0.001 Unknown/Cryptogenic -0.01566 (-0.1664- -0.1467) <0.001 Race White/Caucasian Reference - American Indian/Alaskan -0.0207 (-0.0871- 0.0457) 0.541 Asian 0.0531 (0.0258- 0.0805) <0.001 Black 0.0171 (0.0082- 0.0260) <0.001 Native Hawaiian/Pacific Islander -0.0075 (-0.1109- 0.0959) 0.887 Multiple Race -0.0474 (-0.0781- -0.0168) 0.002 Refuse to answer 0.0904 (0.0212- 0.1596) 0.010 No information 0.0575 (0.0283- 0.0866) <0.001 Other 0.0050 (-0.0048- 0.0148) 0.318 Unknown -0.0591 (-0.0837- -0.0346) <0.001 Disease Severity Hepatic Encephalopathy at Baseline 0.0431 (0.0328- 0.0534) <0.001 Ascites at Baseline 0.0638 (0.0551- 0.0724) <0.001

S2740 Incidentally Discovered Cryptogenic Cirrhosis in a Patient With Untreated Celiac Disease

Introduction: Celiac disease is an autoimmune enteropathy that affects around 1% of the general population and primarily manifests its effects on the small bowel. However, the systemic nature of this condition, especially regarding the liver, has been gaining some recognition in the literature. Mild liver disease is common, but few cases progress to cirrhotic liver disease. In this case report, cryptogenic cirrhosis was incidentally discovered in a patient with a long history of untreated celiac disease with no evidence of any other underlying cause for the cirrhosis. Case Description/Methods: A 78-year-old male with past medical history of longstanding celiac disease, atrial fibrillation, CHF, T2DM, CKD III, and thoracic aortic aneurysm underwent a CT scan for thoracic aortic aneurysm surveillance. Incidentally, on CT scan, a 1.2 cm enhancing focus in left hepatic lobe, cirrhotic liver morphology, and sclerosing mesenteritis were discovered. Initial lab work-up was remarkable for an elevated alkaline phosphatase of 171 and initial tissue transglutaminase (TTG) was >100. Confirmatory ultrasound showed a liver with heterogeneous echotexture, 1.2cm cyst on the left hepatic lobe, and patent main portal vein. Further laboratory workup showed negative anti-smooth muscle antibody, negative antimitochondrial antibody, negative liver kidney microsomal antibody, and alpha-fetoprotein < 2. Patient reported a history of constipation but denied any other gastrointestinal symptoms, including abdominal pain, hematochezia, diarrhea, nausea, or vomiting. Patient had a remote history of alcohol use, with only occasional recreational use at presentation. The patient had never followed a gluten-free diet. (Figure) Discussion: Celiac disease is now thought to be a systemic condition, with up to 30% of patients displaying extraintestinal manifestations. Multiple studies have shown an increased incidence of celiac disease in patients with cirrhosis, and that cessation of gluten can improve not only the small bowel, but also liver function. This suggests that there is utility in monitoring liver function in patients with celiac disease and screening patients with cirrhosis for celiac disease on initial workup. It is also important to inform patients of these connections, as compliance with a gluten-free diet may prevent the progression of the enteropathy and protect its systemic targets.Figure 1.: Sagittal View of Cirrhotic Liver Morphology on Right Upper Quadrant Ultrasound.

S1359 Post-Liver Transplant Metabolic Changes After One Year

Introduction: Elevations in HbA1c and BMI preoperatively and postoperatively are associated with post-transplant complications that impact long-term morbidity and mortality. The aim of this study is to evaluate the impact of transplant indications and demographic background on postoperative changes in HbA1c and BMI. Understanding factors associated with elevations in HbA1c and BMI can help determine at-risk patient groups. Methods: We performed an IRB-approved retrospective study. We obtained records of patients who underwent liver transplantation at Thomas Jefferson University Hospital from January 2002 to December 2020. We analyzed changes in BMI/HbA1c at transplant and one year post-transplant by age, race, gender, and indication for transplant using STATA statistical software 14.2. Results: Of the 100 liver transplant patients included in our study, 57 (63.3%) were male, and 33 (36.7%) were female. The average age was 63.26 years (61.13- 65.38, 95% CI), and the mean BMI and HbA1c at the time of transplant were 31.01 kg/m2(29.90-32.13, 95% CI) and 6.26 (5.89-6.62, 95% CI), respectively. There was no statistically significant (P >0.05) change in preoperative and one year postoperative BMI in transplant patients who had the following indications: NASH, Alcohol Cirrhosis, HCV, HBV, PSC, HCC, and cryptogenic cirrhosis. There was also no significant change in preoperative and one year postoperative BMI when stratifying patients by gender, race, and age or in preoperative and one year postoperative HbA1c when stratifying by indication for liver transplant, gender, and race. Patients < 50 years had a significantly greater one year postoperative HbA1c compared to their preoperative HbA1c (5.10 vs 6.09, p =0.048). There was no significant difference in preoperative and one year postoperative HbA1c in patients ≥50 years. (Table) Conclusion: Significant elevations in HbA1c post-transplant may predispose patients to post-transplant diabetes, which is associated with transplant dysfunction and mortality, and may cause post-transplant metabolic syndrome, which increases the risk of and complications from cardiovascular events. Our data showed that patients under the age of 50 need careful monitoring to minimize modifiable metabolic abnormalities. Determining high-risk populations for post-transplant complications is crucial to reduce long-term post-transplant morbidity and mortality. Further research is needed to elucidate additional risk factors for post-transplant complications. Table 1. - Metabolic Changes After 1 Year Liver Transplant Total Patients (%) Mean BMI (95% CI) At Transplant At 1 year after Transplant p-value Overall 90 (100) 31.01 (29.90-32.13) 30.88 (29.59-32.17) 0.16 Indication for Transplant NASH/NAFLD 27 (30.7) 33.08 (31.12-35.03) 32.30 (31.55-33.06) 0.21 Alcohol 11 (12.5) 26.19 (23.22-29.16) 25.96 (24.12-27.80) 0.45 HCV 9 (10.2) 30.81 (27.35-34.27) 31.23 (28.83-33.62) 0.36 HBV 2 (2.3) 37.2 (49.12-25.28) 34.40 (57.76-11.04) 0.13 PSC 1 (1.1) 25.8 (n/a) 26.3 (n/a) n/a HCC 3 (3.4) 29.00 (25.88-32.12) 28.53 (24.20-32.86) 0.30 Cirrhosis NOS/Cryptogenic 13 (14.8) 28.57 (25.65-31.49) 29.54 (27.89-31.19) 0.21 HCV + HCC 18 (20.5) 32.09 (29.65-34.53) 31.63 (30.47-32.79) 0.19 NASH + HCC 2 (2.3) 31.40 (19.48-43.32) 33.72 (10.36-57.08) 0.13 Alcohol + HCC 2 (2.3) 30.00 (20.45-39.55) 28.51 (9.80-47.23) 0.37 HCC=hepatocellular carcinoma, NASH= nonalcoholic steatohepatitis, HBV= Hepatitis B, HCV= Hepatitis C, PSC=primary sclerosing cholangitis.

S3025 Hepatic Sarcoidosis Presenting as Decompensated Liver Cirrhosis

Introduction: Sarcoidosis is a disorder characterized by the formation of non-caseating granulomas in multiple organ systems. While pulmonary manifestation is the most common presentation, hepatic involvement can be seen in many patients. Most patients with liver involvement are asymptomatic; however, some can present with symptoms of liver injury. The presentation of hepatic sarcoidosis can resemble many other disease processes. Since definite diagnostic criteria have not yet been formalized for hepatic sarcoidosis, it can often be challenging for providers to make a prompt diagnosis. Case Description/Methods: We present the case of a 36-year-old female who was evaluated for generalized abdominal pain and left flank pain. On presentation, labs were notable for calcium at 13 mg/dl, ionized calcium at 1.62 mmol/l, PTH at 8 pg/ml, 1,25-dihydoxyvitamin D at 96.4 pg/ml, alkaline phosphatase at 192 IU/L, AST at 51 IU/L and ALT at 47 IU/L. Eight months prior, the patient was admitted to an outside hospital in the setting of hematemesis. EGD with variceal banding was performed, and she was diagnosed with cryptogenic liver cirrhosis. CT A/P demonstrated marked heterogeneity of the liver. MRI of the abdomen showed mild hepatosplenomegaly and “diffuse small areas of altered signal intensity throughout the liver suspicious for diffuse hepatic metastatic disease” (Figure A). The patient just had her first visit with an oncologist prior to her presentation to our hospital. Her physical exam was notable for hepatomegaly, abdominal distension and RUQ tenderness. Her hypercalcemia was treated with fluids. Infectious and autoimmune workup came back negative. Different tumor markers including CA 19-9, CA 27-29 and CA 125 were normal. Liver biopsy showed hepatic parenchyma with numerous non-necrotizing granulomas and associated fibrosis. IL-2R receptor-serum came back elevated at 2916.1 pg/ml. The patient was then started on 20 mg prednisone daily for treatment of hepatic sarcoidosis. Discussion: Hepatic sarcoidosis can have a wide spectrum of clinical presentation, ranging from incidental finding to end-stage liver disease. When a patient is diagnosed with a new hepatic disease, keeping hepatic sarcoidosis on the differential is very important. In case of hepatic sarcoidosis, assessing symptoms of liver involvement and biochemical evidence of cholestasis is crucial. While observation is indicated for asymptomatic liver disease, corticosteroids and/or ursodeoxycholic acid are the first line agents for symptomatic disease.Figure 1.: Hypointense liver lesions on MRI, initially presumed suspicious for diffuse hepatic metastatic disease, later confirmed to be sarcoid lesions.

S3117 Partial Splenic Artery Embolization for Patients With Portal Hypertension Undergoing Organ Transplant Evaluation: A Case Series

Introduction: Partial splenic artery embolization (PSAE) is an infrequently utilized approach to reduce portal hypertension (PHT) by reducing splenic arterial inflow and thereby splenic vein flow into the portal vein. We describe three patients who underwent PSAE to address diverse manifestations of PHT due to contraindications to transjugular intrahepatic portosystemic shunts (TIPS). Case Description/Methods: Case 1: A 50-year-old male with CKD stage 4 and idiopathic PHT had diuretic-refractory ascites and thrombocytopenia, precluding surgery for an arteriovenous fistula (AVF) and kidney transplantation. He was not a candidate for TIPS due to extensive portal vein thrombosis but underwent PSAE leading to resolution of ascites and marked improvement in thrombocytopenia (Figure 1). The patient ultimately received an AVF and was placed on the kidney transplant waitlist. He has been followed for 30 months with sustained clinical improvement. Case 2: A 60-year-old male with prior hepatocellular carcinoma (HCC) status post right partial hepatectomy and hepatitis C cirrhosis complicated by severe thrombocytopenia and refractory ascites, had two previously aborted TIPS procedures due to unusual hepatic vein anatomy. He underwent PSAE that led to a reduction in frequency of therapeutic paracenteses and improvement of thrombocytopenia (Figure 1). Eight months later, TIPS was reattempted and resulted in complete ascites control for over six years. He is currently on the waitlist for liver transplantation. Case 3: A 60-year-old male had cryptogenic cirrhosis complicated by mild ascites, significant thrombocytopenia, and massive splenomegaly with mass effects. He underwent successful PSAE to alleviate splenic compression of the bladder. One year later, he had a repeat PSAE for diaphragmatic compression secondary to splenic hypertrophy. His thrombocytopenia also mildly improved (Figure 1). The patient was declined for liver transplant due to lack of social support. He expired from advanced HCC after two years of follow-up. Discussion: We report three cases of PSAE in patients with PHT awaiting organ transplantation. All three cases had improvement in ascites, splenomegaly, and thrombocytopenia. Although PSAE is not the primary treatment for PHT, it may have a therapeutic role in advanced cases, particularly in transplant candidates when other interventions like TIPS are not possible. Future studies should be conducted to further evaluate the role of PSAE in patients with PHT awaiting organ transplantation.Figure 1.: *2nd PSAE attempt in case 3 represented at time 0.

S2585 Does Size Matter? A Case Series on Management of Duodenal Varices

Introduction: Duodenal varices (DVs) are a rare cause of life-threatening bleeding in cirrhotic patients. No standardized guidelines for their management exist. We present two cases of DV hemorrhage who were successfully managed by endoscopic variceal band ligation (EVL) and coil embolization respectively. Case Description/Methods: Case 1: A 63-year-old male with cirrhosis was admitted for upper GI bleeding and Hemoglobin (hgb) of 7.1. Endoscopy showed small to medium-sized DVs with stigmata of recent bleeding with a platelet plug in the second portion of duodenum. EVL was done with adequate decompression and no immediate bleeding. One week later, he developed recurrent hematochezia. Full GI work up including upper endoscopy, small bowel capsule and colonoscopy showed previously noted non-bleeding ulcers in the duodenum with no new active bleeding sites. Case 2: A 68-year-old male with cryptogenic cirrhosis complicated by large hepatocellular carcinoma causing portal vein obstruction was admitted for GI bleeding and hgb of 4.3. Endoscopy showed multiple large DVs with active bleeding. Successful hemostasis was achieved using three hemostatic clips but without adequate decompression. However, given the size of the varix, the patient then underwent successful percutaneous transsplenic porto-venous variceal coil embolization by interventional radiology (IR). Discussion: Variceal bleeding occurs in 25-30% of cirrhotic patients with ectopic varices accounting for 1-5% of these bleeds. DVs are uncommon but can cause massive hemorrhage with a high mortality up to 40%, due to challenges with treatment. Management options include EVL, sclerotherapy, clipping or IR guided Trans Jugular Intrahepatic Portosystemic Shunt (TIPS), Balloon-Occluded or Coil Assisted Retrograde Transvenous obliteration. One concern with EVL is the size of the DV and risk of re-bleeding. Among case reports using EVL, re-bleeding was seen only in 3/19 cases with hemostasis achieved with repeat banding in 2 out of the three cases. However, for successful band ligation, accessibility, and size of the varices to fit into the banding cap are important factors to consider. Small – medium duodenal varices (case 1) were adequately managed by EVL, however endoscopic decompression could not be completely achieved in large varices (case 2) and eventually required IR guided coil embolization. Therefore, the size and location of the duodenal varices are important factors to be considered in choosing the appropriate management modality for DVs (Figure 1).Figure 1.: A, Percutaneous transsplenic splenic venogram demonstrating large duodenal varix(white arrows) with linear endoscopically placed clip corresponding with site of hemorrhage in the vertical segment of the duodenum (black arrow). The splenic vein (white arrowhead) drains via the large varix as the main portal vein is occluded secondary to hepatic tumor; B, Percutaneous transsplenic splenic venogram demonstrating successful coil embolization of the varix (black arrowheads); C, Endoscopic view of large varices in second portion of duodenum, post hemostatic clip placement.

S2001 Chronic Norovirus Infection in a Double Solid Organ Transplant Patient

Introduction: Infectious diarrhea is a common complication in the postoperative course of a solid organ transplant (SOT) recipient. While self-limiting in immunocompetent patients, transplant patients on long-term immunosuppression can have severe, prolonged disease with significant morbidity. We present a case of chronic diarrhea due to recurrent norovirus infection in a double SOT patient to encourage early recognition. Case Description/Methods: A 61-year-old male presented with 35-pound weight loss despite a good appetite and large-volume watery diarrhea intermittently for 2 years. He had a liver-kidney transplant 14 years prior secondary to cryptogenic cirrhosis and renal cell carcinoma. Immunosuppression consisted of prednisone, tacrolimus, and mycophenolate mofetil (MMF). Stool PCR was positive for norovirus and negative for other viruses, bacteria, and parasites. His MMF dose was reduced with no benefit. He was discharged with supportive care with initial improvement in the diarrhea but returned to the hospital 4 other times with worsening diarrhea and weight loss. Infectious workup was persistently positive for norovirus. Bi-directional endoscopy with biopsies revealed colonic mucosa with rare epithelial apoptosis, chronic duodenitis, and increased intraepithelial lymphocytosis in the duodenum and ileum consistent with chronic norovirus (Figure). The full diagnostic workup is detailed in Table 1. He was managed conservatively during each hospitalization with fluids and antimotility agents and recently discharged home with plans to start nitazoxanide outpatient. Discussion: Norovirus infection among SOT patients can lead to severe and symptomatic chronic infection. Patients can develop dehydration, transplant rejection, and malnutrition making them higher risk for hospitalizations and death. It is unclear why some immunocompromised patients recover spontaneously while others demonstrate a protracted course but supportive care is the mainstay of therapy. Limited case series have shown nitazoxanide to be effective in treating SOT patients with chronic norovirus infection. However, nitazoxanide needs to be continued until stool RNA studies become negative. This case highlights the importance of considering chronic norovirus when a SOT patient presents with chronic diarrhea and weight loss. Early initiation of supportive care and nutrition consultation are imperative in reducing morbidity in these patients. Nitazoxanide can be effective in patients that are refractory to supportive therapy.Figure 1.: Duodenal biopsy (A): Focal intraepithelial lymphocytosis and lamina propria plasma cell infiltrates. Terminal ileum biopsies (B,C): Focal intraepithelial lymphocytosis and lamina propria plasma cell infiltrates (B); popcorn-like epithelial apoptosis (C). Table 1. - Diagnostic Workup Test/Procedure Result Creatinine, serum 2.1 mg/dl (baseline 1 mg/dl) Stool PCR -Positive for norovirus-Negative for Clostridium difficile toxins, Salmonella, Shigella, Yersinia, and Campylobacter Osmolality, feces 420 mOsm/kg Fecal fat Abnormal Duodenal biopsy -Mucosa with intraepithelial lymphocytosis, dense plasma cell infiltrates in the lamina propria, and rare apoptotic bodies-Negative for CMV, EBV, HSV Stomach biopsy -Gastric antral and oxyntic gland mucosa with chronic inactive gastritis-Negative for H. pylori Right colon biopsy Rare epithelial apoptosis Left colon biopsy Rare epithelial apoptosis Terminal ileum biopsy Mucosa with intraepithelial lymphocytosis, dense plasma cell infiltrates in lamina propria, and rare apoptotic bodies