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BackgroundIn a 72-week, randomised controlled trial of obeticholic acid (OCA) in non-alcoholic steatohepatitis (NASH), OCA was superior to placebo in improving serum ALT levels and liver histology. OCA therapy also reduced weight.AimsBecause weight loss by itself can improve histology, to perform a post hoc analysis of the effects of weight loss and OCA treatment in improving clinical and metabolic features of NASH.MethodsThe analysis was limited to the 200 patients with baseline and end-of-treatment liver biopsies. Weight loss was defined as a relative decline from baseline of 2% or more at treatment end.ResultsWeight loss occurred in 44% (45/102) of OCA and 32% (31/98) of placebo-treated patients (P = 0.08). The NAFLD Activity score (NAS) improved more in those with than without weight loss in both the OCA- (-2.4 vs -1.2, P

Background: Flavocoxid is a prescription medical food that is used to treat osteoarthritis. It is a proprietary blend of 2 flavonoids, baicalin and catechins, which are derived from the botanicals Scutellaria baicalensis and Acacia catechu, respectively.Objective: To describe characteristics of patients with acute liver injury suspected of being caused by flavocoxid.Design: Case series.Setting: Drug-Induced Liver Injury Network Prospective Study ongoing at multiple academic medical centers since 2004.Patients: Four adults with liver injury.Measurements: Clinical characteristics, liver biochemistry values, and outcomes.Results: Among 877 patients enrolled in the prospective study, 4 had liver injury suspected to have been caused by flavocoxid. All were women; ages ranged from 57 to 68 years. All developed symptoms and signs of liver injury within 1 to 3 months after initiating flavocoxid. Liver injury was characterized by marked elevations in levels of alanine aminotransferase (mean peak, 1268 U/L; range, 741 to 1540 U/L), alkaline phosphatase (mean peak, 510 U/L; range, 286 to 770 U/L), and serum bilirubin (mean peak, 160.7 µmol/L [9.4 mg/dL]; range, 34.2 to 356 µmol/L [2.0 to 20.8 mg/dL]). Liver biochemistry values decreased to the normal range within 3 to 12 weeks after flavocoxid was stopped, and all patients recovered without experiencing acute liver failure or chronic liver injury. Causality was adjudicated as highly likely in 3 patients and as possible in 1 patient.Limitation: The frequency and mechanism of liver injury could not be assessed.Conclusion: Flavocoxid can cause clinically significant liver injury, which seems to resolve within weeks after cessation. [ABSTRACT FROM AUTHOR]

Objective: To evaluate ribavirin, an oral antiviral agent, as therapy for chronic hepatitis C.Design: Randomized, double-blind, placebo-controlled study.Setting: Clinical Center of the National Institutes of Health, a tertiary referral research hospital.Patients: 29 patients with chronic hepatitis C who received oral ribavirin (600 mg twice daily) for 12 months and 29 controls with chronic hepatitis C who received placebo for 12 months.Measurements: Effects of therapy were evaluated by measuring serum aminotransferase and hepatitis C virus (HCV) RNA levels before, during, and for 6 months after therapy and by histologic examination of liver specimens before and at the end of treatment.Results: Patients treated with ribavirin had a prompt decrease in serum aminotransferase levels (54% overall) compared with levels before treatment and levels in controls (5% decrease). Serum aminotransferase levels became normal or nearly normal in 10 patients treated with ribavirin (35% [95% CI, 18% to 54%]) but in no controls (0% [CI, 0% to 12%]). Aminotransferase levels remained normal in only 2 patients after ribavirin therapy was discontinued (7% [CI, 1% to 23%]). Serum HCV RNA levels did not change during or after therapy. Liver biopsy specimens showed a decrease in hepatic inflammation and necrosis among ribavirin-treated patients whose aminotransferase levels became normal.Conclusions: Ribavirin has beneficial effects on serum aminotransferase levels and histologic findings in the liver in patients with chronic hepatitis C, but these effects are not accompanied by changes in HCV RNA levels and are not sustained when ribavirin therapy is discontinued. Thus, ribavirin alone for periods as long as 12 months is unlikely to be of value as therapy for chronic hepatitis C. [ABSTRACT FROM AUTHOR]

Background: Hyman Zimmerman observed that hepatocellular (HC) drug-induced liver injury (DILI) with jaundice had a mortality rate of ≥10% (Hy's Law). Hy's Law does not specify the timing of liver tests nor the definition of HC DILI versus cholestatic or mixed (C/M) DILI. We aimed to assess the validity of Hy's Law in the prospective Drug-Induced Liver Injury Network (DILIN) cohort., Methods: Drugs with ≥10 confirmed DILI cases with jaundice were analyzed. Four permutations of Hy's Law were applied: R≥ 5 using initial (1) or peak (2) ALT, AST and Alk P levels, and the FDA associated criteria of ALT or AST ≥ 3x ULN with Alk P ≤ 2x ULN using initial (3) or peak values (4). Mortality was death or liver transplant adjudicated to be due to DILI., Results: Using initial R values, mortality was 11.1% for HC vs 2.0% for C/M (p<0.001); using peak R values, mortality was 10.3% vs 1.6% (p<0.001). Using FDA associated definition, mortality was 7.9% vs 3.9% (p=0.04) using initial values and 7.9% vs 3.0% (p=0.01) using peak values. Using initial R values, drugs that frequently caused HC injury generally had mortality rates ≥ 10%; while drugs that typically caused C/M injury all had rates <10%. Occasional agents that caused HC injury with jaundice were associated with low mortality., Conclusions: Initial R values were the most reliable means of identifying Hy's Law cases. There were some drugs that caused HC injury with jaundice but with mortality rates <10%. Refinement of Hy's Law is warranted., (Copyright © 2024 by The American College of Gastroenterology.)

Background: The incidence of drug-induced liver injury (DILI) is not known for most prescription medications. We aimed to estimate the incidence of DILI for commonly prescribed outpatient drugs., Methods: To establish a baseline estimate of DILI incidence, we used the estimated incidence (EI) of amoxicillin/clavulanate DILI from a previous population-based study in Iceland. This was combined with the multicenter prospective DILI Network (DILIN) cohort and the US population-based Medical Expenditure Panel Survey (MEPS). From 2005 to 2019, prescription drugs with at least five bona fide DILIN cases and data from at least 10 of the 15 years from MEPS during that timeframe were included. The EI for 'drug A' was calculated as follows: EI ( drug A ) = EI AC × # DILIN cases of drug A # annual new prescriptions of drug A × # annual new prescriptions of AC # DILIN cases of AC RESULTS: In total, 30 drugs met the inclusion criteria, of which 11 were antibiotics, 4 were antiepileptic drugs (AEDs), 4 were statins, and 11 were other drug types. The highest EI was seen with azathioprine and older AEDs, with one DILI case per 349-2329 new prescriptions. The EI of antibiotics ranged greatly, with the highest risk seen for minocycline, amoxicillin/clavulanate, and nitrofurantoin (approximately 1:1000-2400 new prescriptions), and lowest risk for clindamycin, doxycycline, azithromycin, and amoxicillin (approximately 1:40,000-170,000 new prescriptions). The EI for commonly prescribed statins was approximately 1:10,000-50,000. Important medication classes with > 5 million new prescriptions from 2005 to 2019 but fewer than five DILIN cases included β-blockers, thiazide diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, selective serotonin reuptake inhibitors, and metformin, which presumably have very low DILI incidence., Conclusions: The highest EI was found for azathioprine, older antiepileptics, and minocycline. In contrast, many widely used drugs are rare causes of DILI. These findings may help clinicians better weigh potential benefits of medications against hepatotoxicity risk., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Competing Interests: The authors have no conflicts to report.

Introduction: Nonalcoholic fatty liver disease (NAFLD) is less frequent in non-Hispanic persons (NHB), but there are knowledge gaps in our understanding of disease severity and outcomes of NAFLD in NHB. We compared liver histology and clinical outcomes of NAFLD in non-Hispanic Black persons (NHB) and non-Hispanic White persons (NHW)., Methods: We compared liver histology and outcomes of 109 NHB and 1,910 NHW adults with biopsy-proven NAFLD participating in the Nonalcoholic Steatohepatitis Clinical Research Network observational studies. The relationship between self-reported NHB race/ethnicity and advanced fibrosis was assessed through multivariable logistic regression after controlling for clinical covariates and PNPLA3 genotype., Results: NHB and NHW with NAFLD had similar NAFLD activity scores (NAS, 4.4 vs 4.3, P = 0.87) and proportions with definite metabolic dysfunction-associated steatohepatitis (59% vs 58%, P = 1.0), but NHB had significantly lower rates of advanced fibrosis (22% vs 34%, P = 0.01) or cirrhosis (4.6% vs 12.1%, P = 0.010). Compared with NHW, NHB had significantly lower frequency of advanced fibrosis (Odds Ratio: 0.48, 95% Confidence Interval: 27-0.86, P = 0.01). In a comparison between 24 NHB and 655 NHW with advanced fibrosis, the NAS (5.6 vs 4.9, P = 0.01) and lobular inflammation grade (2.2 vs 1.7, P < 0.002) were significantly higher among NHB with advanced fibrosis. One NHB and 23 NHW died during follow-up (0.30 vs 0.28 per 100 person-year follow-up). Seven and zero liver-related deaths occurred in NHW and NHB with NAFLD, respectively., Discussion: The risk of advanced fibrosis in NHB with NAFLD is significantly lower, after controlling for clinical risk factors and PNPLA3 genotype. Although their risk of advanced fibrosis was low, NHB with NAFLD and advanced fibrosis had higher NAS and lobular inflammation, indicating a difference in their relationship between necroinflammation and fibrosis., (Copyright © 2024 by The American College of Gastroenterology.)

Background: Intravenous vancomycin therapy can cause liver injury as well as "drug reaction with eosinophilia and systemic symptoms" (DRESS) syndrome. This study aimed to better define the clinical features and HLA associations of vancomycin-induced liver injury., Objective: To describe clinical, biochemical, and temporal characteristics of vancomycin-induced liver injury., Methods: Cases of liver injury with recent exposure to vancomycin who were enrolled in the US Drug-induced Liver Injury Network between 2004 and 2020 were assessed. Sequencing of HLA alleles was performed on stored blood samples., Results: Among 1697 cases of drug-induced liver injury identified between 2004 and 2021, 9 (0.5%) were attributed to intravenous vancomycin. The 9 cases included 6 men, median age 60 years (range, 23-85 days), and treatment for 26 days (range, 1-34 days). The clinical presentation was DRESS syndrome in 8 patients, of whom 6 received corticosteroids. Liver injury varied from hepatocellular to cholestatic and from mild (n = 5) to fatal (n = 1). In survivors, liver injury and DRESS syndrome ultimately resolved. HLA typing demonstrated the HLA-A∗32:01 allele in 7 vancomycin cases (78%, all with DRESS syndrome), versus 1 of 81 cases (1.2%) exposed but not attributed to vancomycin, and 113 of 1708 cases (6.6%) without vancomycin exposure. The allele frequency in vancomycin cases was 0.44 compared with less than 0.04 in US populations., Conclusions: Vancomycin-induced liver injury is commonly associated with DRESS syndrome and linked to HLA-A∗32:01. HLA-A∗32:01 testing could be considered early to risk-stratify patients using long-term intravenous vancomycin therapy., (Published by Elsevier Inc.)

Aims: Evaluate patient-reported liver symptoms during treatment for chronic hepatitis B viral (HBV) infection and associations between changes in symptoms and levels of alanine aminotransferase (ALT) and viral markers., Methods: Data from 200 participants in the Hepatitis B Research Network Immune Active Trial who completed symptom assessments were analyzed. Patients were treated with tenofovir, with or without peginterferon (TDF + PegIFN vs. TDF alone) for 192 weeks. Participants completed a Symptom Checklist at baseline and every 4-12 weeks. A total symptom score was created, ranging from 0 (none) to 40 (severe). The SF-36 was completed every 48 weeks. Associations of symptom scores with ALT and viral markers were evaluated at baseline and end of treatment., Results: Participants were 65% male, 83% Asian, with a mean age of 42. Baseline symptoms were mild (median = 2, range 0-25) and associated with baseline ALT, HBV DNA levels and HBeAg + status. Patients on TDF alone experienced a more rapid and greater improvement in symptoms, but by week 192, symptom improvement was similar in both groups (54% vs 36%). Symptom improvements correlated with ALT and HBV DNA, most markedly among those with symptoms at baseline. Most patients (4 out of 6) who achieved HBsAg loss experienced symptom improvements. Overall, SF-36 scores did not change with treatment., Conclusions: Reduction in ALT and HBV DNA levels with therapy are associated with significant improvement in liver symptoms such as fatigue and pain over the liver, especially among those with higher ALT, HBV DNA, symptoms and HBeAg + status prior to treatment., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) is a predominantly drug-induced disease, with a mortality rate of 15-20%, that engages the expertise of multiple disciplines: dermatology, allergy, immunology, clinical pharmacology, burn surgery, ophthalmology, urogynecology, and psychiatry. SJS/TEN has an incidence of 1-5/million persons per year in the United States, with even higher rates globally. One of the challenges of SJS/TEN has been developing the research infrastructure and coordination to answer questions capable of transforming clinical care and leading to improved patient outcomes. SJS/TEN 2021, the third research meeting of its kind, was held as a virtual meeting on August 28-29, 2021. The meeting brought together 428 international scientists, in addition to a community of 140 SJS/TEN survivors and family members. The goal of the meeting was to brainstorm strategies to support the continued growth of an international SJS/TEN research network, bridging science and the community. The community workshop section of the meeting focused on eight primary themes: mental health, eye care, SJS/TEN in children, non-drug induced SJS/TEN, long-term health complications, new advances in mechanisms and basic science, managing long-term scarring, considerations for skin of color, and COVID-19 vaccines. The meeting featured several important updates and identified areas of unmet research and clinical need that will be highlighted in this white paper., Competing Interests: KM was employed by Stevens-Johnson Syndrome Foundation. EJP reports grants from National Institutes of Health (R01HG010863, R01AI152183, U01AI154659) and from the National Health and Medical Research Council of Australia. She receives Royalties and consulting fees from UpToDate and has received consulting fees from Janssen, Verve, Biocryst, Regeneron, AstraZeneca and Novavax. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer OI declared a shared affiliation with the author AS to the handling editor at the time of review., (Copyright © 2023 Marks, Botta, Abe, Beachkofsky, Boothman, Carleton, Chung, Cibotti, Dodiuk-Gad, Grimstein, Hasegawa, Hoofnagle, Hung, Kaffenberger, Kroshinsky, Lehloenya, Martin-Pozo, Micheletti, Mockenhaupt, Nagao, Pakala, Palubinsky, Pasieka, Peter, Pirmohamed, Reyes, Saeed, Shupp, Sukasem, Syu, Ueta, Zhou, Chang, Becker, Bellon, Bonnet, Cavalleri, Chodosh, Dewan, Dominguez, Dong, Ezhkova, Fuchs, Goldman, Himed, Mallal, Markova, McCawley, Norton, Ostrov, Phan, Sanford, Schlundt, Schneider, Shear, Shinkai, Tkaczyk, Trubiano, Volpi, Bouchard, Divito and Phillips.)

Introduction: Sulfonamides are widely used to treat and prevent various bacterial and opportunistic infections. The aim of this study was to describe the clinical presentation and outcomes of a large cohort of patients with sulfonamide hepatotoxicity., Methods: Between 2004 and 2020, 105 patients with hepatotoxicity attributed to trimethoprim/sulfamethoxazole (TMP-SMZ) (n = 93) or other sulfonamides (n = 12) were enrolled. Available liver biopsies were reviewed by a single hepatopathologist., Results: Among the 93 TMP-SMZ cases, 52% were female, 7.5% younger than 20 years, and the median time to drug-induced liver injury (DILI) onset was 22 days (range: 3-157). Younger patients were significantly more likely to have rash, fever, eosinophilia, and a hepatocellular injury pattern at onset that persisted at the peak of liver injury compared with older patients ( P < 0.05). The 18 (19%) TMP-SMZ patients treated with corticosteroids had more severe liver injury and a higher mortality but a trend toward more rapid normalization of their laboratory abnormalities compared with untreated patients. During follow-up, 6.2% of the TMP-SMZ patients died or underwent liver transplantation. Chronic DILI developed in 20% and was associated with cholestatic injury at onset and higher peak total bilirubin levels., Discussion: Sulfonamide hepatotoxicity is characterized by a short drug latency with frequent hypersensitivity features at onset. Subject age is an important determinant of the laboratory profile at presentation, and patients with cholestasis and higher total bilirubin levels were at increased risk of developing chronic DILI. Corticosteroids may benefit a subgroup of patients with severe injury, but further studies are needed., (Copyright © 2023 by The American College of Gastroenterology.)

Background & Aims: Acute hepatitis B virus (aHBV) is thought to be self-limited with clearance of hepatitis B surface antigen (HBsAg) within 6 months. There are limited reports of the presenting features and outcomes of adults with symptomatic aHBV in the United States., Methods: Demographics, clinical features, and 12-month outcomes of patients with adjudicated aHBV were captured prospectively and compared with a contemporaneous cohort of chronic HBV (cHBV) patients enrolled in the Hepatitis B Research Network., Results: Between 2011 and 2018, 60 adjudicated patients with aHBV were compared with 1534 cHBV untreated controls. Although similar in age, other features were dissimilar: aHBV patients were more often male (72% vs 51%), single (72% vs 30%), and non-Hispanic whites or blacks (75% vs 24%). They also were frequently genotype A 2 (65% vs 9%), having different risk factors: sexual exposure (75% vs 16%) or injection drug use (10% vs 2%), compared with the cHBV controls. In addition to higher serum aminotransferase and bilirubin levels, acute patients had higher HBV DNA levels (4.8 vs 3.6 log 10 IU/mL), whereas quantitative hepatitis B e antigen (HBeAg) levels were lower (1.4 vs 3.0 log 10 IU/mL), despite higher rates of HBeAg (73% vs 25%). The median time to HBsAg clearance was 27 weeks and to anti-HBs appearance, 41 weeks., Conclusions: In the current era, caucasian men infected with genotype A 2 as a result of sexual exposure or injection drug use were the predominant group in aHBV, suggesting a potential strategy for adult vaccination in North America. Strikingly, only an estimated 36% of subjects cleared HBsAg by month 6; the definition of resolution in acute hepatitis B may need to be modified. ClinicalTirals.gov number NCT01263587., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Nitrofurantoin (NTF) is widely used for the treatment (short-term) and prevention (long-term) of urinary tract infections. We aimed to describe the clinical characteristics, outcomes, and HLA risk factors for NTF-induced liver injury (NTF-DILI) among individuals enrolled in the Drug Induced Liver Injury Network (DILIN)., Methods: Seventy-eight individuals with definite, highly likely, or probable NTF-DILI were enrolled into DILIN studies between 2004-2020. HLA alleles were compared between NTF-DILI and three control groups: population (n = 14,001), idiopathic autoimmune hepatitis (n = 231), and non-NTF DILI (n = 661)., Results: Liver injury was hepatocellular in 69% and icteric in 55%. AST > ALT was more common in the 44 long-exposure (≥1 year) NTF-DILI cases than in the 18 short (≤7 days) and 16 intermediate (>7 to <365 days) exposure cases (73% vs. 33% vs. 50%, respectively, p = 0.018), as was ANA or SMA positivity (91% vs. 44% vs. 50%, respectively, p <0.001), and corticosteroid use (61% vs. 27% vs. 44%, respectively, p = 0.06). In long-term NTF-DILI, bridging fibrosis, nodularity or cirrhosis, or clinical and imaging evidence for cirrhosis were present in 38%, with massive or sub-massive necrosis in 20%. No one in the short-term exposure group died or underwent transplantation, whereas 7 (12%) patients from the other groups died or underwent transplantation. After covariate adjustments, HLA-DRB1∗11:04 was significantly more frequent in NTF-DILI compared to population controls (odds ratio [OR] 4.29, p = 1.15 × 10 -4 ), idiopathic autoimmune hepatitis (OR 11.77, p = 7.76 × 10 -5 ), and non-NTF DILI (OR 3.34, p = 0.003)., Conclusion: NTF-DILI can result in parenchymal necrosis, bridging fibrosis, cirrhosis, and death or liver transplantation, especially with long-term exposure, and is associated with HLA-DRB1∗11:04. To mitigate against serious liver injury associated with NTF, regulators should revise the prescribing information and consider other mitigation strategies., Impact and Implications: Nitrofurantoin is a recognized cause of drug-induced liver injury (DILI). In this study consisting of a large cohort of well-phenotyped individuals with nitrofurantoin-induced liver injury, two distinct patterns of liver injury were identified: liver injury associated with short-term exposure, which is generally self-limiting, and liver injury associated with long-term exposure, which can lead to advanced fibrosis, cirrhosis and liver failure. HLA DRB1∗11:04 is a risk factor for liver injury due to long-term nitrofurantoin exposure. Our findings are important for regulators as well as physicians prescribing and pharmacists dispensing nitrofurantoin., Competing Interests: Conflict of interest Dr. Chalasani has ongoing paid consulting activities (or had in preceding 12 months) with AbbVie, Madrigal, Foresite labs, Galectin, Zydus, Boehringer-Ingelheim, Lilly and Altimmune. He has grant support from Exact Sciences and DSM. These activities are not directly or significantly related to this paper. Dr. Robert Fontana reports ongoing research support from Abbvie and Gilead but not related to current study. Dr. Herbert L Bonkovsky reports recent (in preceding 12 months) or ongoing paid consulting activities with Alnylam Pharma, Disc Medicine, Protagonist Pharma, Recordati Rare Chemicals. He serves as PI for sponsored clinical research awarded to Wake Forest Baptist Medical Center from Alnylam, Gilead Sciences, Genkyotex SA, Mitsubishi-Tanabe, NA. These activities are not directly or significantly related to this paper. Dr. Nicoletti is an employee of Sema 4. She also reports ongoing piad consulting activities with Chieso Farmaceutici S.p.A and Audentes Therapeutics, but these activities are not directly or significantly related to this paper. Drs. Barnhart, Navarro, Kleiner, Hoofnagle, Phillips, Dellinger, Gu, Tae-Hwi Schwantes-An, and Lammert have no conflicts of interests to disclose. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Turmeric is a commonly used herbal product that has been implicated in causing liver injury. The aim of this case series is to describe the clinical, histologic, and human leukocyte antigen (HLA) associations of turmeric-associated liver injury cases enrolled the in US Drug-Induced Liver Injury Network (DILIN)., Methods: All adjudicated cases enrolled in DILIN between 2004 and 2022 in which turmeric was an implicated product were reviewed. Causality was assessed using a 5-point expert opinion score. Available products were analyzed for the presence of turmeric using ultra-high-performance liquid chromatography. Genetic analyses included HLA sequencing., Results: Ten cases of turmeric-associated liver injury were found, all enrolled since 2011, and 6 since 2017. Of the 10 cases, 8 were women, 9 were White, and median age was 56 years (range 35-71). Liver injury was hepatocellular in 9 patients and mixed in 1. Liver biopsies in 4 patients showed acute hepatitis or mixed cholestatic-hepatic injury with eosinophils. Five patients were hospitalized, and 1 patient died of acute liver failure. Chemical analysis confirmed the presence of turmeric in all 7 products tested; 3 also contained piperine (black pepper). HLA typing demonstrated that 7 patients carried HLA-B*35:01, 2 of whom were homozygous, yielding an allele frequency of 0.450 compared with population controls of 0.056-0.069., Conclusion: Liver injury due to turmeric appears to be increasing in the United States, perhaps reflecting usage patterns or increased combination with black pepper. Turmeric causes potentially severe liver injury that is typically hepatocellular, with a latency of 1 to 4 months and strong linkage to HLA-B*35:01., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Bile duct involvement is a key finding of primary biliary cholangitis (PBC). The aim of this study was to evaluate baseline ductopenia and disease progression., Methods: Retrospective longitudinal histological follow-up of treatment-naive patients with PBC., Results: Eighty-three patients were included, with ductopenia correlated to fibrosis stage at baseline. The cumulative incidence of severe ductopenia remained stable after 5 years, whereas fibrosis continually increased over time. Baseline AST-to-Platelet Ratio Index and elevated alkaline phosphatase >2 times the normal with abnormal bilirubin were associated with ductopenia progression., Discussion: Bile duct injury does not seem to follow the same course as fibrosis in PBC., (Copyright © 2022 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)