Safety net systems care for patients with a high burden of liver disease yet experience many barriers to liver transplant (LT) referral. This study aimed to assess safety net providers' perspectives on barriers to LT referrals in the United States. We conducted a nationwide anonymous online survey of self-identified safety net gastroenterologists and hepatologists from March through November 2022. This 27-item survey was disseminated via e-mail, society platforms, and social media. Survey sections included practice characteristics, transplant referral practices, perceived multilevel barriers to referral, potential solutions, and respondent characteristics. Fifty complete surveys were included in analysis. A total of 60.0% of respondents self-identified as White and 54.0% male. A total of 90.0% practiced in an urban setting, 82.0% in tertiary medical centers, and 16.0% in community settings, with all 4 US regions represented. Perceived patient-level barriers ranked as most significant, followed by practice-level, then provider-level barriers. Patient-level barriers such as lack of insurance (72.0%), finances (66.0%), social support (66.0%), and stable housing/transportation (64.0%) were ranked as significant barriers to referral, while medical mistrust and lack of interest were not. Limited access to financial services (36.0%) and addiction/mental health resources (34.0%) were considered important practice-level barriers. Few reported existing access to patient navigators (12.0%), and patient navigation was ranked as most likely to improve referral practices, followed by an expedited/expanded pathway for insurance coverage for LT. In this national survey, safety net providers reported the highest barriers to LT referral at the patient level and practice level. These data can inform the development of multilevel interventions in safety net settings to enhance equity in LT access for vulnerable patients.

Background In trials conducted in India, recombinant granulocyte colony stimulating factor (GCSF) improved survival in alcohol-associated hepatitis (AH). The aim of this trial was to determine the safety and efficacy of pegfilgrastim, a long-acting recombinant GCSF, in patients with AH in the United States. Methods This prospective, randomized, open label trial conducted between March 2017 and March 2020 randomized patients with a clinical diagnosis of AH and a Maddrey discriminant function score >= 32 to standard of care (SOC) or SOC+pegfilgrastim (0.6 mg subcutaneously) on Day 1 and Day 8 (clinicaltrials.gov NCT02776059). SOC was 28 days of either pentoxifylline or prednisolone, as determined by the patient's primary physician. The second injection of pegfilgrastim was not administered if the white blood cell count exceeded 30,000/mm(3) on Day 8. Primary outcome was survival at Day 90. Secondary outcomes included the incidence of acute kidney injury (AKI), hepatorenal syndrome (HRS), hepatic encephalopathy, or infections. Findings The study was terminated early due to COVID19 pandemic. Eighteen patients were randomized to SOC and 16 to SOC+pegfilgrastim. All patients received prednisolone as SOC. Nine patients failed to receive a second dose of pegfilgrastin due to WBC > 30,000/mm(3) on Day 8. Survival at 90 days was similar in both groups (SOC: 0.83 [95% confidence interval [CI]: 0.57-0.94] vs. pegfilgrastim: 0.73 [95% CI: 0.44-0.89]; p > 0.05; CI for difference: -0.18-0.38). The incidences of AKI, HRS, hepatic encephalopathy, and infections were similar in both treatment arms and there were no serious adverse events attributed to pegfilgrastim. Interpretation This phase II trial found no survival benefit at 90 days among subjects with AH who received pegfilgrastim+prednisolone compared with subjects receiving prednisolone alone. Copyright Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/)

This case demonstrates the significance, and ongoing relevance of mycobacterial infections, especially in patients who have recently been started on immunosuppression.

INTRODUCTION: Vanishing bile duct syndrome (VBDS) is an uncommon condition of progressive bile duct loss, which often presents with immuno-allergic signs and can be fatal or necessitate liver transplantation. Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare spectrum of immune complex-mediated mucocutaneous reactions which share common immuno-allergic features and triggers with VBDS. Multiple previous case reports have described the co-occurrence of SJS/TEN and VBDS that is more common in children. Described here is a case of a young adult male who developed TEN with VBDS and subsequent hemophagocytic lymphohistiocytosis (HLH) after taking ibuprofen for influenza B. CASE DESCRIPTION/METHODS: A 26-year-old previously healthy male presented to an outside hospital with a 5-day history of fevers, chills, dry cough, and sore throat and a subsequent 7-day history of worsening rash over his back, chest, and extremities. He reported significant ibuprofen use for 3 days before the onset of his rash. Upon presentation, the patient was found to be influenza B positive and was started on oseltamivir. Exanthematous eruptions covered approximately 20% body surface area and quickly progressed to 80%. Skin biopsy findings were consistent with TEN. He was transferred to our facility for specialized burn unit care and was treated for TEN with intravenous immunoglobulin and etanercept with gradual improvement of his rash. Liver biopsy on hospital day 30 for severe cholestatic liver injury demonstrated vanishing bile ducts. Alkaline phosphatase peaked to 2278 U/L on hospital day 44 and serum total bilirubin peaked at 49.2 mg/dL on hospital day 61. Fevers, tachypnea, tachycardia, and leukocytosis persisted, and suspected HLH was diagnosed following a bone marrow biopsy. At the time of abstract submission, the patient remains hospitalized receiving HLH treatment with etoposide and high-dose steroids. DISCUSSION: This case report highlights a concurrent case of SJS/TEN and vanishing bile duct syndrome following an episode of acute influenza B. While there have been previously reported cases of VBDS with concurrent SJS/TEN, this appears to be the first reported case of SJS/TEN, VBDS, and subsequent HLH in the same patient. While this is a single case, it raises the possibility of a shared immuno-allergic pathogenesis between these three conditions.Table 1.: Peak hepatic panel lab valuesTable 2.: Hemophagocytic Lymphohistiocytosis diagnostic criteria

Within the spectrum of autoimmune liver diseases, there are patients who manifest features of more than one disease, which was previously identified as having overlap syndrome1,2 and is now referred to as variant syndromes. The most common variant syndrome is between primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH). Typically, AIH presents with elevated serum immunoglobulin (Ig) G, whereas PBC is associated with elevated serum IgM.3,4 Previous studies have suggested that plasma cells in liver biopsies of AIH patients are predominantly IgG+, whereas in PBC, there is an abundance of IgM+ cells.5,6 We wanted to determine the immunostaining pattern for IgG and IgM of liver plasma cells among Hispanic patients in Los Angeles with features of both PBC-AIH compared with those with PBC or AIH alone.

Introduction: Progressive familial intrahepatic cholestasis (PFIC3) Type 3 is an inherited cholestatic disorder caused by mutations in the ABCB4 gene encoding the Multidrug Resistance Protein 3 (MDR3).PFIC3 typically presents during infancy or early childhood, often progressing to chronic liver disease and cirrhosis.Presentation in adult life is very rare.Here we describe a novel case of late onset PFIC3 associated with identical familial heterozygous mutation in the ABCB4 gene which has not been reported before.Case Presentation: A 34 year old female with history of cholecystectomy for gallstones presented to clinic for evaluation of abnormal liver function tests (LFT).Patient was first noted to have elevated LFTs (AST-98, ALT-250, ALP-71, GGT-31, and T.Bili-0.8) at the age of 15.She had liver biopsy and was given the diagnosis of primary biliary cholangitis (PBC).She was started on Ursodiol and subsequently her LFTs improved.She stopped taking Ursodiol 10 years later.Labwork on presentation revealed elevation of LFTs again (AST-115, ALP-172, ALP-116, T.Bili-0.4).US abdomen was normal.Work up included, but was not limited to :viral hepatitis, autoimmune markers, IgG4, ceruloplasmin, alpha-1 antitrypsin, and ferritin, all of which were normal.Repeat liver biopsy showed mild sinusoidal dilatation.She was started back on Ursodiol and her LFTs normalized (AST-20, ALP-18, ALP-64, GGT 11, T.Bili-0.4).Interestingly, her family history was significant for diagnosis of PBC in her mother, and several aunts had cholestasis of pregnancy.Given her clinical presentation and family history, diagnosis of PFIC was considered.Genetic analysis supported our clinical diagnosis.Both she and her mother were tested positive for identical ABCB4 heterozygous variant (Nucleotide change: c.2828_2829delinsAT; Amino acid change: p.I943N) Discussion: MDR 3 is responsible for phospholipid transport in to bile.Decreased or absent function of MDR3 results in low phospholipid in to bile which predisposes bile epithelium to damage from hydrophobic bile salts and increased bile lithogenicity.Mutations in the ABCB4 gene located on Chromosome 7 encoding for MDR3 is associated with development of PFIC3.Several different mutations have been described in MDR3 protein in literature.Patient with homozygous or compound heterozygote mutations presents early in life with severe diseases phenotype.Patients with either missense or nonsense heterozygous mutations may present with less severe phenotypes in adult life and usually has cholelithiasis or intrahepatic cholestasis of pregnancy.We identified a unique identical familial ABCB4 heterozygous variant mutation, which was clinically thought to be causing PFIC3.This mutation is reported in cases of intrahepatic cholestasis of pregnancy and cholesterol gallstone diseases, but not with PFIC3. Mo1449

The clinical presentation of alcoholic hepatitis (AH) can be mimicked by other alcoholic liver diseases. The aim of this study was to identify clinical features that predict AH on liver biopsy. Biopsies from patients hospitalized for presumed severe AH were used to identify a derivation cohort (101 patients) and validation cohort (71 patients). Using histologic scores for hepatocyte ballooning, Mallory‐Denk bodies, and lobular inflammation, 95 patient biopsies (55%) were classified as definite AH, 55 (32%) as possible AH, and 22 (13%) as no AH. Survival was similar among the groups, but mortality was significantly increased for patients with fatty change ≤50% on initial liver biopsy. An analysis limited to uninfected patients with definite AH or no AH in the derivation cohort identified a greater leukocyte count at admission and radiographic evidence of liver surface nodularity as independent predictors of definite AH on biopsy ( P < 0.05). In the derivation cohort, the leukocyte count thresholds for ensuring 100% specificity for diagnosing definite AH were 10 × 10 9 /L if the liver surface was nodular and 14 × 10 9 /L if the liver surface was smooth, with a sensitivity of 76% and an area under the receiver operator characteristic curve of 0.88. In the validation cohort, these thresholds had a specificity of 86%, a sensitivity of 59%, and an area under the receiver operator characteristic curve of 0.72. Conclusion: The combination of an elevated leukocyte count and a nodular liver surface in the absence of active infection retrospectively identified patients with a high likelihood of histologic AH for whom liver biopsy may not be necessary. For patients with suspected severe AH who do not fulfill these criteria, liver biopsy is important to exclude other variants of alcoholic liver disease. ( Hepatology Communications 2017;1:1070–1084)

Background: Reports of recurrent severe alcoholic hepatitis (AH) do not include confirmation by liver biopsy. We describe the clinical and histologic features of three patients with recurrent episodes of jaundice and suspected acute liver injury due to alcoholic recidivism. Methods: Evaluation of 120 patients with acute alcoholic liver injury included two with distinct hospitalizations between 2005 and 2012 for the recent onset of jaundice and a suspicion for severe alcoholic hepatitis (AH) defined by a discriminant function (DF) >32 or a MELD score of >18. A third patient later identified is included. Particular to these cases, a liver biopsy was performed during the index and a subsequent episode. Results: The clinical and histologic features for the first and subsequent episodes of acute alcoholic liver injury are presented in Table 1. Each patient had resolution of jaundice within 2-5 months after the first presentation. Recurrent jaundice in the context of alcohol recidivism occurred at an interval of 1-6 years. Patient #1 had cirrhosis and two episodes of biopsy-proven AH with histologic features of hepatocyte ballooning, Mallory-Denk bodies, and neutrophilic lobular inflammation. Treatment with corticosteroids for 7 days on both occasions resulted in partial responses with calculated Lille scores of 0.23 and 0.38, respectively. Patient #2 had two episodes of acute alcoholic fatty liver with cholestasis (AFLC), without histologic evidence of AH. Cholestasis, prominent macrovesicular fat, mild portal fibrosis, and mild lymphocytic lobular inflammation were present. Treatment was supportive. Patient #3 had an initial episode of self-limited jaundice due to AFLC followed by periods of recidivism and three recurrent episodes of jaundice over a period of >6 years. During the second recurrence, a liver biopsy showed AH. A calculated Lille score after 7 days of corticosteroids was 0.21, and 28-day treatment resulted in complete resolution of jaundice.Table 1: Clinical and histologic features of three patients with alcohol recidivism and recurrent episodes of acute jaundice due to alcoholic hepatitis (AH) or alcoholic fatty liver with cholestasis (AFLC)Conclusions: After a first episode of acute alcoholic liver injury, jaundice may recur in patients with alcohol recidivism. The histologic pattern of recurrent liver injury is not always the same. Liver biopsy remains important in evaluating recurrent episodes in order to distinguish between recurrence of the first injury, including AH, or other alcoholic liver diseases, like AFLC, that can have similar clinical presentations.

Patients with a variety of systemic diseases may present with clinical indications of biliary tract disorders. This article describes a group of systemic conditions associated with bile duct abnormalities and the role of endoscopic therapy in their diagnosis and management.

4128 Background: Tumor responses of hepatocellular carcinoma (HCC) are usually classified by RECIST criteria. Residual tumor perfusion indicated by arterial phase contrast enhancement may provide additional information regarding tumor viability. We evaluated HCC responses using both RECIST and residual arterial phase contrast tumor perfusion for contributions toward prediction of survival after treatment in nontransplant patients and for likelihood of residual disease in explants. Methods: This is a retrospective analysis. Pre- and post-treatment tumor sizes and post- treatment contrast enhancement characteristics were determined by multiphase CT or MR at 0, 30, 70, and 180 seconds after contrast injection. Post-treatment scans were performed 6 weeks after last IA. Nonperfusion (NP) was defined by absence of enhancement in residual tumor. For pts not undergoing transplant survival hazard rates were estimated for multiple baseline and treatment variables using uni- and multivariate analysis. For transplanted pts, liver explants were examined for residual viable tumor. Results: 189 pts with nonmetastatic HCC were treated with intra-arterial cisplatin and mitomycin, 35 receiving salvage adriamycin and 24 percutaneous ablation. Transplant: 53 of 189 pts underwent liver transplantation. Of 27 patients achieving NP status, 12 (44.4%) had no residual disease vs. 2 of 23 patients (8.7%) with residual enhancement had no residual disease. Nontransplant: 136 patients have been followed without transplant. Multivariate analyses demonstrated predictive significance (p<0.001) for survival for RECIST response, NP status, number of treatments, and treatment toxicity. At 3 yrs, no patient with residual perfusion was alive vs. 10/55 (18.2%) patients achieving NP status. Conclusions: Response most strongly correlates with residual disease in explants and survival in nontransplanted patients considering both RECIST and perfusion status after treatment. Survival 1-year 3-year N % N % N 3-yr CR 16 11.8 14 93.8 6 84.4 PR- NP 27 19.9 13 78.3 3 40.1 PR-P 18 13.2 10 59.2 0 0 SD-NP 12 8.8 6 73.3 1 18.3 SD-P 44 32.2 11 30.6 0 0 PD 19 13.9 5 24.5 0 0 No significant financial relationships to disclose.

e15649 Background: We report our initial experience with percutaneous cryoablation of HCC in liver. Prior published series are limited. Methods: We treated 30 lesions in 23 patients (pts): Child-Pugh class A, 13 pts; B, 8 pts.; C, 2 pts Candidate pts had residual disease after intra-arterial chemotherapy. Probe placement (2.4 mm, Endocare) occurred under general anesthesia with restricted tidal volume to facilitate computer tomographic (CT) localization. An average 2.7 probes (range 1- 5) achieved an estimated margin of 0.5 cm visualizing the ice ball after two 10 min freeze cycles. Median follow-up was 342 days (range 30–947) Results: Tumors ranged from 1.3 to 5.8 cm. Three pts died within 30 days: 2 following intra-peritoneal hemorrhage despite control of bleeding and 1 from ischemic liver injury following a TIPSS for hydrothorax in a pt with refractory ascites. Two additional pts had hemorrhage with recovery. Risk of bleeding was associated with ascites (P = 0.013). One pt had cutaneous needle tract tumor seeding caused by needle repositioning prior to freezing. Survivors remained clinically stable at the 2–3 month follow-up. At the 2 month evaluation 29 lesions had no residual enhancement by CT. One lesion required a second cryoablation procedure.There were no recurrences in any target lesion (30–947 days). Thirteen pts are alive without recurrence of whom 6 had liver transplant with no (4) or < 5% (2) residual disease. Three pts have had recurrence in non-target liver and have died. Multiple tumors at baseline predicts for hepatic recurrence. Two pts have died from complications of cirrhosis, and 2 are lost to follow-up. Conclusions: Percutaneous cryoablation effectively manages selected hepatic HCC tumors. Cirrhotic pts with ascites have significant risk for hemorrhage. We recommend peri-procedure paracentesis and an immediate post-procedure CT. [Table: see text]

Palta, Renee DO1; Thobani, Salima MD1; Donovan, John A. MD1; Kanel, Gary C. MD2; Gutierrez, Guillermina MD3; Fong, Tse-Ling MD1 Author Information