Advancing diagnosis and management of liver disease in adults through exome sequencing.

BACKGROUND: Whole-exome sequencing (WES) is an effective tool for diagnosis in patients who remain undiagnosed despite a comprehensive clinical work-up. While WES is being used increasingly in pediatrics and oncology, it remains underutilized in non-oncological adult medicine, including in patients with liver disease, in part based on the faulty premise that adults are unlikely to harbor rare genetic variants with large effect size. Here, we aim to assess the burden of rare genetic variants underlying liver disease in adults at two major tertiary referral academic medical centers. METHODS: WES analysis paired with comprehensive clinical evaluation was performed in fifty-two adult patients with liver disease of unknown etiology evaluated at two US tertiary academic health care centers. FINDINGS: Exome analysis uncovered a definitive or presumed diagnosis in 33% of patients (17/52) providing insight into their disease pathogenesis, with most of these patients (12/17) not having a known family history of liver disease. Our data shows that over two-thirds of undiagnosed liver disease patients attaining a genetic diagnosis were being evaluated for cholestasis or hepatic steatosis of unknown etiology. INTERPRETATION: This study reveals an underappreciated incidence and spectrum of genetic diseases presenting in adulthood and underscores the clinical value of incorporating exome sequencing in the evaluation and management of adults with liver disease of unknown etiology. FUNDING: S.V. is supported by the NIH/NIDDK (K08 DK113109 and R01 DK131033-01A1) and the Doris Duke Charitable Foundation Grant #2019081. This work was supported in part by NIH-funded Yale Liver Center, P30 DK34989.

Outcomes of immunomodulator and advanced therapies for primary sclerosing cholangitis-associated inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) coexists in up to 80% of patients with primary sclerosing cholangitis (PSC). The aim of this study is to investigate the outcomes of immunomodulator (IMM)/advanced therapies for the treatment of PSC-IBD. METHODS: This was a single-center, retrospective study of patients with PSC from 1 January 2012 to 1 April 2021. Adult patients (age ≥ 18 years) with PSC-IBD were included. Primary outcomes were rates and predictors of IMM/advanced therapies to treat PSC-IBD. Secondary outcomes included rates of cholangitis, PSC-IBD clinical remission, and endoscopic healing. RESULTS: A total of 106 patients with PSC were reviewed and 72 (68%) with confirmed PSC-IBD were included in the study. The median age was 48 years (IQR, 33-59.5) and 69.4% were male. Overall, 28 patients (38.9%) required IMM/advanced therapies to treat PSC-IBD (22 biologic/small molecule therapy and six thiopurine monotherapy). Patients in the IMM/advanced therapies group were more likely to have small bowel involvement (32.1% vs. 4.6%; P = 0.002). In the IMM/advanced therapies group, clinical remission was achieved in 78.6% but endoscopic healing in only 50%. The rate of acute ascending cholangitis was 42.9% in the IMM/advanced therapies group compared with 31.8% in the non-IMM/advanced therapies group (P = 0.34). CONCLUSION: In our cohort, up to a third of patients with PSC-IBD required IMM/advanced therapies with only 50% of these patients achieving endoscopic healing. The use of IMM/advanced therapies was not associated with a higher risk of cholangitis, but larger studies are needed to investigate the risk with different classes of advanced therapies.

Mindfulness-based stress reduction may decrease stress, disease activity, and inflammatory cytokine levels in patients with autoimmune hepatitis.

Background & Aims: Psychological and life stressors may impact autoimmune hepatitis (AIH) disease activity and increase relapse risk. Mindfulness-based stress reduction (MBSR) is a validated course that reduces stress reactivity, and improves stress and emotion regulation. This single-arm exploratory pilot study of adult patients with AIH aimed to define the impact of an 8-week MBSR program on quality of life, disease activity, and cytokine mediators. Methods: The perceived stress survey-10 (PSS) and the brief self-control scale (BSCS) measured subjective distress and self-control. Serum alanine aminotransferase (ALT) and cytokine levels were measured, and immunosuppressant doses recorded. Results: Seventeen patients completed the MBSR program. Post-MBSR, 71% (n = 12) showed PSS score improvement at 8 weeks vs. baseline (median 15 vs. 21, p = 0.02). At 12 months, PSS improvement persisted vs. baseline (median 15 vs. 21, p = 0.02). Post-MBSR, 71% (n = 12) showed BSCS score improvement at 8 weeks vs. baseline (median 4.1 vs. 3.8, p = 0.03). At 12 months, the median BSCS score remained significant (3.9 vs. 3.8, p = 0.03). After the 8-week MBSR, the 35% of patients with ALT >34 U/L had a median ALT reduction (44.5 vs. 71.5 U/L, p = 0.06), whereas the 71% of patients on prednisone had significant dose reductions (5.75 vs. 10 mg, p = 0.02) which persisted at 12 months vs. baseline (3.75 vs. 10 mg, p = 0.02) without a compensatory increase in steroid-sparing dosing. Significant improvement was noted in peripheral blood cytokine levels (IL-6, IL-8, IL-10, IL-17, IL-23, and sCD74/MIF ratio) from baseline to 8 weeks. Conclusions: MBSR significantly improved perceived stress and self-control scores while decreasing ALT levels, steroid requirements, and inflammatory cytokine levels in this pilot study in adult AIH. Stress modification may impact quality of life and disease activity, and should be further evaluated as an intervention in AIH. Clinical Trials registration: This study is registered at ClinicalTrials.gov (NCT02950077). Lay summary: Autoimmune hepatitis can reduce quality of life and mental health, while stress may impact autoimmune hepatitis itself. We piloted mindfulness-based stress reduction as a strategy to reduce stress in adult patients with autoimmune hepatitis and found that the intervention reduced perceived stress and may have also impacted the disease by improving inflammation and medication needs. Stress reduction should be further studied to improve quality of life and possibly to impact disease activity in autoimmune hepatitis.

Primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic liver disease characterized by inflammatory destruction of the intrahepatic and/or extrahepatic bile ducts, leading to bile stasis, fibrosis, and ultimately to cirrhosis, and often requires liver transplantation (LT). PSC occurs more commonly in men, and is typically diagnosed between the ages of 30 and 40. Most cases occur in association with inflammatory bowel disease (IBD), which often precedes the development of PSC. PSC is usually diagnosed after detection of cholestasis during health evaluation or screening of patients with IBD. When symptomatic, the most common presenting symptoms are abdominal pain, pruritus, jaundice or fatigue. The etiology of PSC is poorly understood, but an increasing body of evidence supports the concept of cholangiocyte injury as a result of environmental exposure and an abnormal immune response in genetically susceptible individuals. PSC is a progressive disease, yet no effective medical therapy for halting disease progression has been identified. Management of PSC is mainly focused on treatment of symptoms and addressing complications. PSC can be complicated by bacterial cholangitis, dominant strictures (DSs), gallbladder polyps and adenocarcinoma, cholangiocarcinoma (CCA) and, in patients with IBD, colorectal malignancy. CCA is the most common malignancy in PSC with a cumulative lifetime risk of 10-20%, and accounts for a large proportion of mortality in PSC. LT is currently the only life-extending therapeutic approach for eligible patients with end-stage PSC, ultimately required in approximately 40% of patients. LT secondary to PSC has an excellent outcome compared to other LT indications, although the disease can recur and result in morbidity post-transplant.

Surveillance for hepatobiliary cancers in patients with primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a risk factor for cholangiocarcinoma (CCA) and gallbladder carcinoma (GBCa). Surveillance for GBCa is recommended, but the clinical utility of surveillance for other hepatobiliary cancers (HBCa) in PSC, namely CCA and hepatocellular carcinoma (HCC), remains unclear. We aimed to determine whether surveillance is associated with better survival after diagnosis of HBCa in patients with PSC. Medical records of PSC patients seen at the Mayo Clinic Rochester from 1995 to 2015 were reviewed. Patients were included if they had ≥1 year of follow-up and developed HBCa. Patients were categorized according to their surveillance status (abdominal imaging, carbohydrate antigen 19-9, and alpha-fetoprotein). The primary endpoints were HBCa recurrence, HBCa-related death, and all-cause mortality. Overall survival was assessed by the Kaplan-Meier survival method; HBCa-related survival was assessed using competing risk regression. Tests of significance were two-tailed, and a P value <0.05 was considered statistically significant. From 1995 to 2015, a total of 79 of 830 PSC patients were diagnosed with HBCa. Cumulative follow-up was 712 and 283 person-years pre- and post-HBCa diagnosis, respectively. Seventy-eight percent of patients (54/79) developed CCA, 21% (17/79) HCC, 6% (5/79) GBCa, 3% (2/79) both CCA and HCC, and 1% (1/79) both HCC and GBCa. Fifty-one percent (40/79) were under HBCa surveillance, and 49% (39/79) were not. Patients in the surveillance group had significantly higher 5-year overall survival (68% versus 20%, respectively; P < 0.001) and significantly lower 5-year probability of experiencing an HBCa-related adverse event (32% versus 75%, respectively; P < 0.001) compared with the no-surveillance group. CONCLUSION: This study demonstrates that HBCa surveillance significantly improves outcomes, including survival, in patients with PSC. (Hepatology 2018;67:2338-2351).

Investigational drugs in phase II clinical trials for primary biliary cholangitis.

INTRODUCTION: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease that may lead to biliary fibrosis, and eventually cirrhosis. The primary treatment for PBC is ursodeoxycholic acid (UDCA), which has favorably altered its natural history. However, up to 40% of patients have an inadequate response to UDCA, and are therefore at high risk of liver-related complications. Obeticholic acid has recently been approved for use in patients with PBC with inadequate response or who are intolerant to UDCA, but improvement in long-term outcomes has not yet been demonstrated. Alternative therapeutic options for PBC are needed. Areas covered: Recent advances in research including epidemiological, genetic and pre-clinical studies in animal models of PBC have yielded numerous agents currently at different stages of development for treatment of patients with PBC; in this review, we cover novel therapies that were recently or are recently being investigated in phase II clinical trials. Expert opinion: Despite the evolving landscape in PBC, the main challenges facing development of novel therapies remain the rarity of the disease and the limitations to design and conduct of controlled clinical trials in PBC, which are needed to determine the long-term effects of novel therapies on the clinical outcomes of PBC.

A Randomized, Placebo-Controlled Clinical Trial of Efficacy and Safety: Modafinil in the Treatment of Fatigue in Patients With Primary Biliary Cirrhosis.

BACKGROUND AND AIMS: Fatigue is a common symptom of primary biliary cirrhosis (PBC), and is associated with an impaired quality of life. STUDY QUESTION: No studies have assessed the use of modafinil in fatigue related to PBC in a controlled manner. STUDY DESIGN, MEASURES, AND OUTCOMES: A randomized, double-blind, placebo-controlled study was conducted to determine the safety and efficacy of modafinil for the treatment of fatigue in PBC. Forty patients were randomized to modafinil (n = 20) or placebo (n = 20) for 12 weeks. A verbal report of fatigue for at least 6 months was required for enrollment. Modafinil was administered at 100 mg by mouth once daily; a change by 50 mg every 2 weeks (maximum: 200 mg once daily) was allowed, depending on the subject's response to treatment. The primary outcome was defined as a ≥50% improvement in fatigue severity [quantified by the Fisk Fatigue Impact Scale (FFIS)] after 12 weeks of treatment, compared with baseline values. RESULTS: Thirty-three PBC patients completed the study. After 12 weeks of therapy, only 5 patients had a ≥50% reduction in FFIS scores: 3 patients (17.6%) in the modafinil arm and 2 (12.5%) in the placebo arm (P = 1.00). Change in median FFIS score was not statistically different between patients in the 2 treatment groups (P = 0.36). Modafinil was associated with minimal adverse events (headaches, diarrhea, and rash). CONCLUSIONS: In patients with PBC who have fatigue, treatment with modafinil for 12 weeks was safe and fairly well tolerated; however, it did not result in beneficial effects on fatigue compared with patients treated with placebo (CONSORT Table 1). ClinicalTrials.gov identifier NCT00943176.

Treatment Selection Choices Should Not Be Based on Benefits or Costs Alone: A Head-to-Head Randomized Controlled Trial of Antiviral Drugs for Hepatitis C.

BACKGROUND: Clinicians often face dilemmas with decisions related to formulary choices when two similar drugs are simultaneously available in the market. We studied the comparative safety, effectiveness, and treatment costs of the two first generation direct-acting antiviral agents (DAA), boceprevir and telaprevir as uncertainty existed regarding the drug of choice between these two seemingly equally Hepatitis-C treatment options. METHODS: We randomly assigned 50 patients in an open-label, pragmatic randomized controlled trial (RCT) at a VA Medical Center to either boceprevir or telaprevir in combination with peginterferon and ribavirin, stratified by the presence of cirrhosis and prior treatment experience. Tolerability was assessed at each visit and reasons for discontinuation of treatment and severity of adverse events due to PI treatment were adjudicated using a blinded adjudication committee. The primary outcome was difference in tolerability between boceprevir vs. telaprevir. Secondary outcomes included viral response rates and cost-per cure achieved. RESULTS: Higher rates of treatment discontinuations and/or severe DAA associated adverse events were seen in 10/25 (40%) patients randomized to telaprevir compared to 2/25 (8%) patients randomized to boceprevir (RR: 5; 95% CI: 1.2, 20; p<0.01). Cure rates did not appear to be significantly different between groups (telaprevir vs. boceprevir: RR 1.23; 95% CI: 0.76, 1.99; p = 0.39). On an intention-to-treat basis, total cost per cure was $44,329 for boceprevir vs. $57,115 for telaprevir. The significant side effect profile of telaprevir combined with the availability of highly efficacious second generation DAAs led to the early discontinuation of the trial. CONCLUSION: Telaprevir is associated with a significantly higher rate of severe adverse events leading to treatment discontinuations, hospitalizations or severe anemia and a substantially higher cost per SVR when compared to boceprevir. Real-time, point of care, pragmatic randomized controlled trials are necessary for guidance beyond just acquisition costs and to make evidence-based formulary selections when multiple effective treatments are available. (Clinicaltrials.gov registration: NCT02113631).

Obeticholic acid and budesonide for the treatment of primary biliary cirrhosis.

INTRODUCTION: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of adults. Treatments are needed when patients have incomplete response to ursodeoxycholic acid (UDCA). AREAS COVERED: Discoveries of the key role played by bile acids (BAs) and nuclear receptors (NRs) in regulating liver and metabolic homeostasis have led to promising therapeutic approaches in liver diseases. A PubMed search for the recent literature on NRs in liver disease was conducted. In particular, obeticholic acid (OCA) is a farnesoid X receptor (FXR) agonist that has an important role in the enterohepatic circulation of BAs. Preliminary studies of OCA in patients with PBC have demonstrated marked biochemical improvement when administered in combination with UDCA and alone. Pruritus is the most common side effect, limiting treatment at higher doses. Budesonide is a glucocorticoid receptor/pregnane X receptor (PXR) agonist also involved in BA synthesis, metabolism and transport. Studies with budesonide have shown positive effects of short-term combination therapy in selected patients with early stage disease and overlapping features of autoimmune hepatitis. EXPERT OPINION: Though larger studies are needed, preliminary results of agents targeting FXR and PXR have been encouraging, particularly in subsets of patients with PBC and may mark a new therapeutic era.

IgG4-associated cholangitis.

IgG4-associated cholangitis is the hepatobiliary manifestation of a recently characterized inflammatory systemic disease, associated with increased IgG4 serum levels and IgG4-positive lymphoplasmacytic infiltration. Often, patients present with obstructive jaundice, and imaging reveals stenoses of the extrahepatic or intrahepatic bile ducts, often in association with parenchymal pancreatic findings and irregularities of the pancreatic duct. The histologic findings include lymphoplasmacytic infiltrates, on occasion resulting in tumefactive lesions (which can mimic malignancy), obliterative phlebitis, and fibrotic changes. Steroid treatment is the mainstay of management, but relapse is common after discontinuation of therapy or during tapering of steroids and may require further treatment.

Long-term outcomes of patients with primary biliary cirrhosis and hepatocellular carcinoma.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is an aggressive tumor that frequently develops in patients with primary biliary cirrhosis (PBC). We determined the mortality of patients with PBC who develop HCC, and which interventions (surgery, radiofrequency ablation, chemoembolization, alcohol injection, or transplantation) increase survival times. We investigated whether the Milan criteria predict outcomes of these patients and are effective in selection for liver transplantation. METHODS: We evaluated data from 38 patients who had a confirmed diagnosis of PBC and HCC between March 1993 and February 2011. Patients were grouped based on whether or not they met the Milan criteria. Survival was assessed using the Kaplan-Meier analysis. RESULTS: Eighteen of the 38 patients (47.3%) died during the follow-up period; 49.4% survived for 5 years and 31.7% survived for 10 years. Thirty-five patients (92.0%) underwent one or a combination of interventions. Liver transplantation improved survival (risk ratio, 0.06; P < .0001), whereas surgery approached significance in causing deterioration (risk ratio, 2.87; P = .07). Mortality did not appear to be affected by meeting the Milan criteria (P = .84). CONCLUSIONS: Five- and 10-year survival times for patients with PBC who developed HCC were 49.4% and 31.7%, respectively. Patients who meet the Milan criteria receive liver transplantation as often as those who do not; we did not observe a difference in survival time between groups. Patients with PBC who develop HCC appear to benefit from aggressive therapies.

Optimizing biochemical markers as endpoints for clinical trials in primary biliary cirrhosis.

BACKGROUND: Biochemical tests have been recommended as endpoints for clinical trials in primary biliary cirrhosis (PBC) because the use of liver transplantation and death as endpoints in ursodeoxycholic acid (UDCA) therapeutic trials is unfeasible. The best inclusion criteria cut-off values and cut-off for demonstrating treatment success have not been defined. AIM: Our aim was to determine the optimal biochemical values for patient inclusion and to define values for treatment success in therapeutic trials. METHODS: We performed a retrospective review of 73 patients with PBC treated with UDCA followed over 36 months. Following one year of UDCA therapy, the likelihood of developing clinical endpoints of varices, ascites, encephalopathy, death or transplantation over the ensuing two years, based on degrees of elevation of biochemical markers, was analyzed using chi-square or Fisher's exact test. RESULTS: Patients with ALP≥2 X upper limit of normal (ULN) had a 2-fold greater likelihood of developing endpoints compared to patients with lower values (23% versus 11%), (p < 0.05). Patients with bilirubin > 1 mg/dL were 4 times more likely to develop endpoints compared to those with lower values (33% versus 8%), (p = 0.02). These values help identify the patient population for adjunctive therapy trials. Patients with ALP ≤1.67 X ULN and bilirubin ≤1mg/dL demonstrated the least likelihood of reaching adverse clinical endpoints and can be used to define treatment success. CONCLUSION: Optimal ALP and Bilirubin levels can be used as appropriate biochemical criteria for patient selection and defining treatment success in future clinical trials in patients with PBC.

High-dose ursodeoxycholic acid is associated with the development of colorectal neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis.

OBJECTIVES: Some studies have suggested that ursodeoxycholic acid (UDCA) may have a chemopreventive effect on the development of colorectal neoplasia in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). We examined the effects of high-dose (28-30 mg/kg/day) UDCA on the development of colorectal neoplasia in patients with UC and PSC. METHODS: Patients with UC and PSC enrolled in a prior, multicenter randomized placebo-controlled trial of high-dose UDCA were evaluated for the development of colorectal neoplasia. Patients with UC and PSC who received UDCA were compared with those who received placebo. We reviewed the pathology and colonoscopy reports for the development of low-grade or high-grade dysplasia or colorectal cancer. RESULTS: Fifty-six subjects were followed for a total of 235 patient years. Baseline characteristics (including duration of PSC and UC, medications, patient age, family history of colorectal cancer, and smoking status) were similar for both the groups. Patients who received high-dose UDCA had a significantly higher risk of developing colorectal neoplasia (dysplasia and cancer) during the study compared with those who received placebo (hazard ratio: 4.44, 95% confidence interval: 1.30-20.10, P=0.02). CONCLUSIONS: Long-term use of high-dose UDCA is associated with an increased risk of colorectal neoplasia in patients with UC and PSC.

Varices in early histological stage primary biliary cirrhosis.

BACKGROUND/GOALS: Esophageal varices (EV) in early histological stages of primary biliary cirrhosis (PBC) have been recognized but not well defined. We sought to determine the prevalence, clinical characteristics, and predictors of EV in early-stage PBC, as well as to evaluate the effectiveness of recent guidelines regarding EV screening in PBC patients. STUDY: We retrospectively reviewed the charts of 325 PBC patients who had undergone complete evaluation before enrollment into 2 large clinical trials at the Mayo Clinic. RESULTS: Nineteen percent (62/325) of our patient population had EV on esophagogastroduodenoscopy; 6% (8/127) of early-stage PBC patients had EV. Ninety five percent of our PBC patients with varices met at least one of the following conditions: male sex, low albumin (<3.5 g/dL), elevated bilirubin level (≥1.2 mg/dL), and/or prolonged prothrombin time (≥12.9 s). The sensitivity and specificity of these variables in combination to predict the presence of varices were 95% and 55%, respectively. Serum bilirubin ≥1.2 mg/dL and albumin <3.5 were independent predictors of varices with hazard values of 5.4 and 3.5 respectively. CONCLUSIONS: EV can occur in a minority of early-stage PBC patients. Various models may be used to identify PBC patients who are candidates for screening esophagogastroduodenoscopy for EV. Based on adequate performance and its simplicity, we propose that male sex, low albumin, elevated bilirubin, and/or prolonged prothrombin time be used as a model to noninvasively predict EV. Further validation is required.

Hepatic fibrosis and the renin-angiotensin system.

The renin-angiotensin system (RAS) is involved in hepatic fibrosis. To date there is no known effective treatment for hepatic fibrosis. Modulation of the RAS with angiotensin converting enzyme inhibitors and angiotensin receptor blockers may be a promising therapeutic option for the treatment of hepatic fibrosis. This review provides an update about the role of RAS in hepatic fibrosis, and treatment of hepatic fibrosis in the light of different studies in animals and humans is also updated. RAS induces key steps involved in hepatic fibrosis, such as activation of hepatic stellate cells and expression of transforming growth factor ß1. Treatment with angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers attenuate fibrosis progression in both animal and human studies. Further, controlled studies are required to evaluate the role of RAS inhibitors and angiotensin-converting enzyme 2 in patients with chronic liver diseases in whom the causative agent cannot be removed.

Parenteral bisphosphonates for osteoporosis in patients with primary biliary cirrhosis.

We aimed to describe the effects of parenteral bisphosphonates on bone mineral density (BMD) changes in primary biliary cirrhosis (PBC) patients with osteoporosis. Seventeen PBC patients with osteoporosis diagnosed between 1996 and 2005 were enrolled retrospectively. All patients received one of the following parenteral bisphosphonates: zoledronic acid, pamidronate disodium, or ibandronate sodium. The median (interquartile range) age of patients at osteoporosis diagnosis was 62.2 (56.4-67.9) and 94% were women. After treatment, percent change of lumbar spine bone mineral density (LS-BMD) and proximal femur BMD (PF-BMD) of patients with PBC was 2.9% and 0.4%, respectively. Eight patients (47%) showed a greater LS-BMD and/or PF-BMD with percent change of LS-BMD and PF-BMD of 8.7% and 0.8%, respectively. No serious adverse events were found. In PBC patients with osteoporosis, parenteral bisphosphonates can stabilize BMD for 47% of patients. More prospective studies are needed to evaluate the efficacy of specific parenteral bisphosphonates in patients with PBC and osteoporosis.

Comparing the simplified and international autoimmune hepatitis group criteria in primary sclerosing cholangitis.

BACKGROUND AND AIMS: Although highly sensitive and specific, the revised International Autoimmune Hepatitis Group (IAIHG) diagnostic criteria for autoimmune hepatitis (AIH) are cumbersome to use in clinical practice and rely upon a number of autoantibodies that are costly and are not widely available. The simplified scoring system for AIH attempts to rectify the complexity of the IAIHG criteria. To date, there have been few studies assessing the specificity of the simplified score for AIH when applied to patients with cholestatic liver diseases. The purpose of this study was to examine the specificity of the simplified scoring system for AIH as compared to the revised IAIHG criteria in a large cohort of patients with primary sclerosing cholangitis (PSC). METHODS: The patient population consisted of 147 patients enrolled in two prospective trials at the Mayo Clinic examining the use of ursodeoxycholic acid in PSC. All of the patients underwent baseline blood work (including standard serologic testing to exclude other liver diseases), liver biopsy, and cholangiogram to confirm PSC. Demographic, laboratory, and histologic data were extracted for each subject. Simplified and revised IAIHG scores were calculated for each subject and compared. RESULTS: The simplified scoring system identified 2 patients with probable AIH and no patients with definite AIH. Comparatively, the revised IAIHG scoring system identified no patients with probable or definite AIH. CONCLUSION: As with the revised IAIHG criteria, the simplified scoring system for AIH has excellent specificity when applied to a PSC population.