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Background & Aims: We examined the efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-delta agonist, in adults with primary biliary cholangitis (PBC) at risk of disease progression (alkaline phosphatase [ALP] ≥1.67xupper limit of normal [ULN]) who were receiving or intolerant to ursodeoxycholic acid., Methods: In this 52-week, phase II, dose-ranging, open-label study, patients were randomized (1:1) to seladelpar 5 mg/day (n = 53) or 10 mg/day (n = 55) or assigned to 2 mg/day (n = 11; United Kingdom sites after interim analysis) for 12 weeks. Doses could then be uptitrated to 10 mg/day. The primary efficacy endpoint was ALP change from baseline to Week 8., Results: Mean baseline ALP was 300, 345, and 295 U/L in the 2 mg, 5 mg, and 10 mg cohorts, respectively. Twenty-one percent of patients had cirrhosis, 71% had pruritus. At Week 8, mean ± standard error ALP reductions from baseline were 26 ± 2.8%, 33 ± 2.6%, and 41 ± 1.8% in the 2 mg (n = 11), 5 mg (n = 49), and 10 mg (n = 52) cohorts (all p ≤0.005), respectively. Responses were maintained or improved at Week 52, after dose escalation in 91% and 80% of the 2 mg and 5 mg cohorts, respectively. At Week 52, composite response (ALP <1.67xULN, ≥15% ALP decrease, and normal total bilirubin) rates were 64%, 53%, and 67%, and ALP normalization rates were 9%, 13%, and 33% in the 2 mg, 5 mg, and 10 mg cohorts, respectively. Pruritus visual analog scale score was decreased in the 5 mg and 10 mg cohorts. There were no treatment-related serious adverse events, and 4 patients discontinued due to adverse events., Conclusions: Seladelpar demonstrated robust, dose-dependent, clinically significant, and durable improvements in biochemical markers of cholestasis and inflammation in patients with PBC at risk of disease progression. Seladelpar appeared safe and well tolerated and was not associated with any increase in pruritus., Gov Number: NCT02955602 CLINICALTRIALSREGISTER., Eu Number: 2016-002996-91 LAY SUMMARY: Current treatment options for patients living with primary biliary cholangitis (PBC) are not optimal due to inadequate effectiveness or undesirable side effects. Patients with PBC who took seladelpar, a new treatment being developed for PBC, at increasing doses (2, 5, or 10 mg/day) for 1 year had clinically significant, dose-dependent improvements in key liver tests. Treatment appeared safe and was not associated with any worsening in patient self-reported itch scores., Competing Interests: Conflict of interest Christopher Bowlus has received grants from Arena Pharmaceuticals, Cara Therapeutics, Genfit, Genkyotex, and Novartis and grants and personal fees from CymaBay Therapeutics, Eli Lilly, Gilead, GlaxoSmithKline, and Intercept. Michael Galambos has received consulting and investigator fees from CymaBay Therapeutics. Richard Aspinall owns stock in CymaBay Therapeutics. Gideon M. Hirschfield has received personal fees from CymaBay Therapeutics, Genfit, GlaxoSmithKline, HighTide, Intercept Pharma, Mirum, and Pliant. David E. Jones has received personal fees from Abbott and Falk and personal fees and a grant from Intercept. Stuart C. Gordon has received personal fees and advisory board compensation from CymaBay Therapeutics and research support was paid to his institution by AbbVie, Brigham and Women’s Hospital, CymaBay Therapeutics, DURECT, Eiger, Genfit, Gilead, GlaxoSmithKline, Intercept, Merck, Pliant, Shire, and Viking. Stephen A. Harrison has received personal fees from AgonAB, Altimmune, Boston Pharmaceuticals, B Riley FBR, Canfite Biopharma, Echosens North America, Fibronostics, Foresite Labs, Fortress Biotech, GNS Healthcare, Histoindex Pte, Inipharm, Ionis, Kowa Research Institute, Medpace, Microba Pty, Nutrasource, Piper Sandler & Co, Prometic Pharma Smt, Ridgeline Therapeutics, Sonic Incytes Medical Corporation, and Terns; grants from Cirius Therapeutics, Galmed Research & Development, Hepion Pharmaceuticals, and Pathai; personal fees and grants from Akero Therapeutics, Axcella Health, Civi Biopharma, CymaBay Therapeutics, Enyo Pharma S.A., Galectin Therapeutics, Genfit, Gilead Sciences, High Tide, Intercept, Madrigal Pharmaceuticals, Metracrine, NGM Biopharmaceuticals, Northsea Therapeutics B.V., Novartis, Novo Nordisk, Poxel, Sagimet Biosciences, and Viking Therapeutics; advisory board compensation from 89Bio, Akero Therapeutics, Altimmune, Arrowhead Pharmaceuticals, Axcella Health, Civi Biopharma, CymaBay Therapeutics, Echosens North America, Foresite Labs, Galectin Therapeutics, Galmed Research & Development, Genfit, Gilead, Hepion Pharmaceuticals, High Tide, Histoindex Pte, Indalo Therapeutics, Intercept, Madrigal Pharmaceuticals, Medpace, Metacrine, NGM Biopharmaceuticals, Northsea Therapeutics, Novartis, Novo Nordisk, Poxel, Prometic Pharma Smt, Ridgeline Therapeutics, Sagimet Biosciences, Terns, and Theratechnologies; and owns stock in Akero Therapeutics, Cirius Therapeutics, Galectin Therapeutics, Genfit, Hepion Pharmaceuticals, Histoindex Pte, Metacrine, NGM Biopharmaceuticals, Northsea Therapeutics B.V., and Pathai. Andreas E. Kremer has received personal fees from AbbVie, Bayer, CymaBay Therapeutics, Eisai, Eli Lilly, Escient, Falk, FMC, Gilead, GlaxoSmithKline, Mirum, MSD, Myr, Newbridge, Novartis, and Zambon and personal fees and a grant from Intercept. Marlyn J. Mayo has received consulting and investigator fees from CymaBay Therapeutics. Paul J. Thuluvath has received a grant from CymaBay Therapeutics. Cynthia Levy has received grants from Genkyotex, Gilead, High Tide, Intercept, Novartis, and Zydus and grants and personal fees from Cara Therapeutics, CymaBay Therapeutics, Genfit, and GlaxoSmithKline. Mark Swain has received grants from CymaBay Therapeutics and Genfit and a grant and personal fees from Intercept. Yvonne Dörffel, Guy Neff, David Sheridan, Carmen Stanca, Christoph Berg, and Aparna Goel have nothing to disclose. Mitchell L. Shiffman has received grants from CymaBay Therapeutics, High Tide, and Genfit and grants and personal fees from Intercept. John M. Vierling has received grants from Gilead, GlaxoSmithKline, and Intercept; personal fees from Intercept and Novartis; and personal fees and grants from CymaBay Therapeutics. Pol Boudes is a former employee of CymaBay Therapeutics who owns stock in CymaBay Therapeutics and holds a patent broadly relevant to this work. Alexandra Steinberg is a former employee of CymaBay Therapeutics who owns stock in CymaBay Therapeutics. Yun-Jung Choi is an employee of and owns stock in CymaBay Therapeutics. Charles McWherter is an employee of and owns stock in CymaBay Therapeutics and holds patents broadly relevant to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 virus, is a predominantly respiratory tract infection with the capacity to affect multiple organ systems. Abnormal liver tests, mainly transaminase elevations, have been reported in hospitalized patients. We describe a syndrome of cholangiopathy in patients recovering from severe COVID-19 characterized by marked elevation in serum alkaline phosphatase (ALP) accompanied by evidence of bile duct injury on imaging., Methods: We conducted a retrospective study of COVID-19 patients admitted to our institution from March 1, 2020, to August 15, 2020, on whom the hepatology service was consulted for abnormal liver tests. Bile duct injury was identified by abnormal liver tests with serum ALP > 3x upper limit of normal and abnormal findings on magnetic resonance cholangiopacreatography. Clinical, laboratory, radiological, and histological findings were recorded in a Research Electronic Data Capture database., Results: Twelve patients were identified, 11 men and 1 woman, with a mean age of 58 years. Mean time from COVID-19 diagnosis to diagnosis of cholangiopathy was 118 days. Peak median serum alanine aminotransferase was 661 U/L and peak median serum ALP was 1855 U/L. Marked elevations of erythrocyte sedimentation rate, C-reactive protein, and D-dimers were common. Magnetic resonance cholangiopacreatography findings included beading of intrahepatic ducts (11/12, 92%), bile duct wall thickening with enhancement (7/12, 58%), and peribiliary diffusion high signal (10/12, 83%). Liver biopsy in 4 patients showed acute and/or chronic large duct obstruction without clear bile duct loss. Progressive biliary tract damage has been demonstrated radiographically. Five patients were referred for consideration of liver transplantation after experiencing persistent jaundice, hepatic insufficiency, and/or recurrent bacterial cholangitis. One patient underwent successful living donor liver transplantation., Discussion: Cholangiopathy is a late complication of severe COVID-19 with the potential for progressive biliary injury and liver failure. Further studies are required to understand pathogenesis, natural history, and therapeutic interventions., (Copyright © 2021 by The American College of Gastroenterology.)

Little is known about autoantibody pattern in liver transplantation (LT). The aim of the study was to examine autoantibodies (AAB) and immunoglobulins in patients with end-stage liver disease before and after LT. Patients with LT who underwent post-LT biopsies between 10/2008 and 8/2011 were enrolled. AAB were assessed at the time of LT and liver biopsy. Demographics, serum immunoglobulins, AAB, and liver histology (explant, post-LT biopsies) were analyzed. Two hundred and twenty patients (M/F 143/77; age at LT 54 (19-73)) were included; AAB and immunoglobulins were evaluated in 76 patients. Length of follow-up from LT was 285 (30-1462) days. Sixty-one percent of patients had hepatitis C (HCV); 83% developed recurrent HCV. A significant decrease in IgG, IgA, IgM (p < 0.001 each), anticardiolipin antibodies IgG and IgM (p = 0.02), and beta-2 microglobulin (p = 0.004) was observed post-LT. HCV patients had higher IgG (p = 0.005), rheumatoid factor (p = 0.044) before LT; elevated IgM was associated with increased inflammation in the explant (p = 0.007). Lower IgG levels and antismooth muscle antibodies were present before LT in a higher percentage in patients who would develop recurrent HCV (p = 0.004, p = 0.077, respectively). In conclusion, AAB change significantly after LT and have a different pattern in HCV. Some immunological markers are associated with HCV recurrence and advanced inflammation on explant., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Aims: Information about the natural history of small duct primary sclerosing cholangitis (SDPSC) remains scant despite literature suggesting that it constitutes 6-16% of all cases of primary sclerosing cholangitis (PSC). We combined clinical data on SDPSC cases from two tertiary care institutions with liver transplantation programs with the aim of studying the natural history of SDPSC., Methods: Medical records of 25 individuals with SDPSC were reviewed. Diagnosis of SDPSC was based on liver biopsy findings consistent with PSC, a normal cholangiogram, and elimination of known causes of secondary sclerosing cholangitis. Demographic information, symptoms, past medical history, laboratory values, and histologic data were evaluated. Our primary outcome measure was liver transplantation or death. Secondary outcome measures included evidence of end-stage liver disease, development of cholangiocarcinoma, and/or the development of classic PSC on a repeat cholangiogram., Results: Data on 25 individuals (13 males, 12 females; mean age 40 ± 15 years) diagnosed with SDPSC were analyzed. Upon presentation, 11 patients had symptoms including abdominal pain, fatigue, and pruritus. Inflammatory bowel disease was present in 14 patients (56%) at diagnosis. On initial liver biopsy, 60% had early-stage disease (I or II) and none had cirrhosis. On follow-up (1-168 months, median 17 months), malignancy or progression to classic large duct PSC was not noted. Two (8%) patients had evidence of varices and one of the two also developed ascites; one of these patients underwent liver transplantation and the other one died due to sepsis., Conclusions: SDPSC, a mild disease at presentation typically runs a benign course and likely is not an early stage of classic PSC. Further studies with a control group of classic PSC and longer follow-up are needed to study the natural history of SDPSC.

Background: Thrombocytopenia typically resolves with resolution of portal hypertension after liver transplantation (LT) but persists in some patients. Identifying risk factors associated with persistent post- LT thrombocytopenia may provide important information about its pathogenesis., Methods: Cirrhotic adults with platelet levels of <150,000 mu/L at the time of LT and followed at least 1 year were studied. A retrospective analysis of lab values, radiologic spleen index (SI), and donor data using nonparametric methods was performed to characterize patients having persistent thrombocytopenia, defined as persistently low platelet levels at 3 and 12 months after LT., Results: One hundred patients were studied: mean age 55 y (range 23-75 y); platelet count at LT 62,000/microL (range 14,000- 148,000/microL; mean total bilirubin 2.6 mg/dL; mean Mayo end-stage liver disease score 29; SI 1,476 (range 347-4,843 mL; normal 120-480 mL). Platelet count at 3 and 12 months after LT correlated with SI (r = -0.41 and -0.54; P < .001). Fifty-seven patients had persistent thrombocytopenia. Compared with patients whose platelet levels normalized by month 3 or 12, they had higher SI and lower platelet count before LT (P < .001). The SI and platelet levels at the time of LT were independent predictive factors for platelet levels at 3 and 12 months after LT (P < .001)., Conclusions: High SI and low platelet count at the time of LT are associated with persistent thrombocytopenia after LT. They are also independent predictive factors of platelet levels at 3 and 12 months after LT. This suggests that patients may have persistent thrombocytopenia after LT owing to persistence of some degree of hypersplenism and incomplete resolution of splenomegaly.

Purpose: Cirrhotic patients waiting for liver transplantation who need dental extractions are given fresh frozen plasma and/or platelets to correct coagulopathy. This is costly and may be associated with transfusion reactions and fluid overload. We evaluated the efficacy of intranasal desmopressin as an alternative to transfusion to correct the coagulopathy of cirrhotic patients undergoing dental extraction., Patients and Methods: Cirrhotic patients with platelet counts of 30,000 to 50,000/microL and/or international normalized ratio (INR) 2.0 to 3.0 were enrolled in a prospective, controlled, randomized clinical trial. Blood transfusion (fresh frozen plasma 10 mL/kg and/or 1 unit of single donor platelets, respectively) or intranasal desmopressin (300 microg) were given before dental extraction. A standard oral and maxillofacial surgical treatment protocol was performed by the same surgeon. Patients were followed for postextraction bleeding and side-effects over the next 24 to 48 hours., Results: No significant differences were noted between the 2 groups in gender, age, INR, platelet count, creatinine, total bilirubin, ALT, albumin, MELD score, or number of teeth removed (median 3 vs 4). The number of teeth removed ranged between 1 and 31 in the desmopressin group and 1 and 22 in the transfusion group. No patients in desmopressin group required rescue blood transfusion after extraction. One patient in the transfusion group had bleeding after the procedure and required an additional transfusion. Another patient experienced an allergic reaction at the end of transfusion, which was effectively treated with diphenhydramine. Treatment associated average costs were lower for desmopressin ($700/patient) compared with transfusion ($1,173/patient)., Conclusions: Intranasal desmopressin was as effective as blood transfusion in achieving hemostasis in cirrhotic patients with moderate coagulopathy undergoing dental extraction. Intranasal desmopressin was much more convenient, less expensive, and well tolerated.

Aim: This long-term study aimed to evaluate recurrence and evolution of primary biliary cirrhosis (PBC) after orthotopic liver transplantation (OLT)., Methods: We reviewed "blindly" allograft biopsy specimens of women who underwent transplantation for PBC (n = 84), and women who received a transplant for chronic hepatitis C virus infection (CHCV ) (n = 108). All needle liver biopsy specimens obtained more than 6 months post-OLT were examined, including 83 specimens from 44 PBC patients and 152 specimens from 58 CHCV patients., Results: Granulomatous destructive cholangitis was found in five biopsies from four PBC patients (P = 0.0048). Non-necrotizing epithelioid cell granulomas were present in four biopsies from four PBC patients, and in two biopsies from one CHCV patient. Piecemeal necrosis (P = 0.0002), lobular necroinflammatory activity (P < 0.0001), steatosis (P < 0.0001) and fibrosis (P < 0.0001) were more prevalent in CHCV patients than PBC patients. Four PBC patients developed histologic evidence of autoimmune hepatitis (AIH), at a mean time of 3.66 years post-OLT. One of these patients had histologic features of AIH/PBC overlap syndrome. All four patients developed bridging fibrosis (n = 2) or cirrhosis (n = 2). No other PBC patient had evidence of cirrhosis after OLT., Conclusions: Histologic findings indicative of recurrent PBC were present in 15.9% of the PBC patients undergoing biopsy in this series. However, this group of patients did not suffer significant bile duct loss or fibrosis, as compared to the control group, suggesting that recurrent PBC is a mild or slowly progressive disease. Histologic evidence of AIH was observed in allograft biopsies of some PBC patients.

Statin treatment reduces hypercholesterolemia and may be anti-inflammatory. Case reports noted decreased alkaline phosphatase and histological improvement following statin treatment in primary biliary cirrhosis. The objective of this study was to assess the long-term effects of statin treatment in primary biliary cirrhosis. A retrospective analysis compared clinical and biochemical data from 15 hypercholesterolemic individuals with primary biliary cirrhosis who were treated long-term with atorvastatin with an age and gender matched, primary biliary cirrhosis control group. A significant decrease in total cholesterol and low-density lipoprotein (LDL)-cholesterol (p < or = 0.002) was observed throughout atorvastatin treatment (median time 2.5 years). LDL-cholesterol levels in the control group were not significantly changed after 2 years (p > 0.050). No significant changes were noted in alanine aminotransferase (ALT), alkaline phosphatase, total bilirubin and Mayo Risk Score in either group (p > 0.05). Long-term atorvastatin treatment reduced LDL-cholesterol in primary biliary cirrhosis, but there was no evidence of any anti-inflammatory effect.

Primary biliary cirrhosis is characterized by chronic hepatic inflammation and immune mediated apoptosis of bile duct epithelial cells. Delayed macrophage phagocytosis of opsonized apoptotic cells, noted in other autoimmune diseases, may promote inflammation. Recent studies suggest serum anti-CD16 autoantibodies contribute to impaired macrophage phagocytosis by blocking complement receptor 3 (CR3) signaling via CD16. Therefore, serum anti-CD16 levels and the ability of monocyte derived macrophages from individuals with PBC to phagocytosis apoptotic cells were compared to controls. The mean level of anti-CD16 IgM autoantibodies (0.86+/-0.62 v. 0.35+/-0.22, respectively, p=0.031) was increased in PBC compared to control sera, and mean PBC phagocytosis of opsonized apoptotic cells was significantly decreased compared to controls (23.9+/-12.2% v. 43.9+/-14.4%, respectively, p=0.020). However, PBC phagocytosis of opsonized apoptotic cells was not significantly affected by the presence or absence of autologous serum (20.8+/-13.5% v. 23.9+/-12.2%, respectively, p=0.560). PBC phagocytosis of opsonized apoptotic cells inversely correlated with CD16 (and CR3) expression levels on Day 5 after culture in the presence or absence of autologous serum (r=-0.546, p=0.033 and r=-0.519, p=0.042, respectively). Phagocytosis of non-opsonized apoptotic cells did not correlate with CD16 or CR3 expression (p>0.050). In conclusion, PBC macrophage phagocytosis of opsonized apoptotic cells is impaired, irrespective of serum factors and may increase hepatic inflammation.

Immune-mediated liver diseases contribute significantly to morbidity and mortality due to liver failure and the need for liver transplantation. The pathogenesis of the immune-mediated chronic liver diseases, primary sclerosing cholangitis, autoimmune hepatitis, and primary biliary cirrhosis, is poorly understood. Genetic susceptibility factors may play a role, but increasing attention is being given to the association between environmental factors and these diseases. The existence of such a relationship is supported by epidemiologic surveys, animal models, and geographic clustering analyses. Unearthing the cause of this association may provide insight into the pathogenesis of immune-mediated chronic liver diseases and autoimmunity.

Background: Interferon use for post liver transplantation (LT) recurrent hepatitis C (HCV) has not consistently been associated with acute cellular rejection (ACR). We examined the incidence of chronic ductopenic rejection (CR) in patients receiving pegylated interferon alfa-2a and ribavirin (PEG) to treat recurrent HCV., Methods: A chart review of 12 patients developing CR while receiving an escalating dose regimen of PEG with protocol liver biopsies every 6 months was conducted. Values are shown as median (range)., Results: Twelve of the 70 patients treated with PEG developed CR. Median age at LT was 53 (37-63) years; immunosuppression consisted of tacrolimus or cyclosporine with prednisone. PEG was started at 3.6 (0.2-13.5) years after LT. Two patients had one episode of ACR before PEG. Four patients had first ACR while receiving PEG. CR was diagnosed after 12 (4-17) months of PEG; by then 8 patients had undetectable HCV-RNA. Tacrolimus and cyclosporine levels (ng/mL) were 7.9 (3.2-18.9) and 76 (71-93) before PEG, and 6.9 (3.7-9.7) and 130 (81-153) at CR. Six patients were treated more than 1 year with PEG; three had undetectable HCV-RNA when CR was diagnosed. Five patients are being treated for CR; one has been listed for LT; two patients were retransplanted. Five patients died as a result of sepsis partially related to CR., Conclusions: Treatment with pegylated-interferon alpha-2a and ribavirin may trigger rapidly progressive CR in patients with therapeutic immunosuppressive trough levels, with or without first inducing ACR.

Liver pathology occurring in patients with sickle cell disease is commonly related to viral hepatitis or hepatic iron deposition due to repeated transfusions; cholestasis and cirrhosis may also occur. Consequently, the differential diagnosis of abnormal liver tests in patients with sickle cell anemia is often complicated. We report the case of a patient presenting with jaundice and abnormal liver biochemistries, without typical evidence of the liver diseases associated with sickle cell anemia. Biochemical markers for viral hepatitis were negative. CT scan only showed hepatomegaly. The liver biopsy revealed marked sinusoidal congestion with red blood cells without significant steatosis or increased iron deposition. The patient's medical history corroborated with biochemical tests and histological examination of the liver suggested that worsening hemolysis related to increased sickling of erythrocytes intrahepatically led to sinusoidal dilatation and probably caused the abnormal liver tests.

Objectives: An increased ammonia level of gut bacterial origin is an important mediator in the pathogenesis of hepatic encephalopathy (HE), and constipation is a frequent precipitant of hepatic coma. Because diabetes mellitus (DM) may be associated with delayed gastrointestinal transit, we speculated that its presence in patients with HCV-related cirrhosis would predispose to and exacerbate HE., Methods: Sixty-five patients (50 men, 15 women) with HCV-related cirrhosis attending a liver transplantation clinic were assessed for severity of liver disease and presence of DM in a cross-sectional study. A modified Child-Pugh score that excluded HE was calculated. Frequency and severity of HE (absent, mild, and severe) in diabetic and nondiabetic patients were assessed. Clinical severity of cirrhosis and results of neuropsychometric testing in diabetic and nondiabetic patients with mild and severe HE were compared., Results: Fifty-four patients (83%) had HE (33 mild, 21 severe). Twenty patients (31%) had DM. HE was present in 19 (95%) patients with diabetes and 35 (78%) patients without diabetes (p = 0.087). Severity of HE was greater in diabetic (35% mild, 60% severe) than in nondiabetic patients (58% mild, 20% severe) (p = 0.007). In both the mild and severe HE categories, severity of liver disease in diabetic patients was otherwise milder than in the nondiabetic patients., Conclusions: Diabetic patients with HCV cirrhosis have more severe HE. Diabetic patients have severe HE at earlier stages of biochemical decompensation and portal hypertension compared with nondiabetic patients.

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are uncommon liver diseases of unknown etiology. Reported clustering of PBC cases may be due to environmental factors. Individuals with PBC have a high prevalence of thyroid disease and thyroid disease is reportedly more prevalent near Superfund toxic waste sites (SFS). The objective of this study was to examine the prevalence and potential clustering of individuals with PBC and PSC near SFS. De-identified clinical and demographic data were used to determine the observed prevalence for each New York City zip code (n = 174) and borough (n = 5) of patients with PBC (PBC-OLT) or PSC (PSC-OLT) who were listed for liver transplantation. The expected prevalence was calculated using Organ Procurement and Transfer Network (OPTN) and U.S. Census data. Both PBC-OLT patients and patients not listed for liver transplantation (PBC-MSSM) were included in the cluster analysis. Prevalence ratios of PBC-OLT and PSC-OLT cases were compared for each zip code and for each borough with regard to the proximity or density of SFS, respectively. SaTScan software was used to identify clusters of PBC-OLT cases and PBC-MSSM cases. Prevalence ratio of PBC-OLT, not PSC-OLT, was significantly higher in zip codes containing or adjacent to SFS (1.225 vs. 0.670, respectively, P = .025). The borough of Staten Island had the highest prevalence ratio of PBC-OLT cases and density of SFS. Significant clusters of both PBC-OLT and PBC-MSSM were identified surrounding SFS. In conclusion, toxin exposure may be a risk factor influencing the clustering of PBC cases.

Objectives: Fatigue, which may have a significant impact on quality of life, is the most common reported symptom in primary biliary cirrhosis (PBC). Multiple instruments to quantify fatigue and quality of life in liver disease have been validated, but have not been broadly applied to U.S. PBC patients. This study examines the extent of fatigue and its effect on quality of life in U.S. PBC patients., Methods: Seventy patients with PBC were administered two validated questionnaires about quality of life (the Mayo version of the NIDDK-QA) and fatigue (the Fisk Fatigue Impact Score) and a proposed physical measure of fatigue in PBC (the grip strength test) on the day of routine physician visit. Nonparametric methods were employed., Results: The fatigue and quality of life domain scores (physical functioning, liver symptoms, health satisfaction, Karnofsky index) discriminated between patients with and without self-reported fatigue (p < 0.05), as opposed to the grip strength results. Fatigue and quality of life domains correlated strongly with each other (r between 0.33 and 0.74, p