3.10 Inherited, Autoimmune & Drug-Induced Liver Disease

ABIM Internal Medicine Exam

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1 Chapter 0: The ABIM Exam, Blueprint & Study Strategy

0.1 Exam Format, Question Types & the 2026 Blueprint 0.2 Eligibility, Registration, Fees & Exam-Day Logistics 0.3 Scoring, the Passing Standard & Score Reports 0.4 Building a Blueprint-Weighted Study Plan

2 Chapter 1: Cardiovascular Disease (14% of Exam)

1.1 Ischemic Heart Disease & Acute Coronary Syndromes 1.2 Antithrombotic Therapy, Secondary Prevention & Mechanical Complications of MI 1.3 Atrial Fibrillation, Atrial Flutter & Stroke Prevention 1.4 Supraventricular Tachycardias, Ventricular Arrhythmias & Bradycardias 1.5 Heart Failure: Classification, Staging & Guideline-Directed Medical Therapy 1.6 Device Therapy, HFpEF & the Cardiomyopathies 1.7 Valvular Heart Disease & Endocarditis Prophylaxis 1.8 Pericardial Disease & Acute Aortic Syndromes 1.9 Hypertension: Classification, Diagnosis & Secondary Causes 1.10 Hypertensive Crises & Dyslipidemia 1.11 Adult Congenital Heart Disease & Coarctation of the Aorta 1.12 Syncope: Reflex, Orthostatic & Cardiac Causes 1.13 Cardiac Physical Examination, Murmurs & Antithrombotic Selection

3 Chapter 2: Endocrinology, Diabetes & Metabolism (9% of Exam)

2.1 Diabetes Mellitus: Diagnosis, Glycemic Targets & Pharmacotherapy 2.2 Insulin Therapy, Hyperglycemic Emergencies & Chronic Complications 2.3 Thyroid Function Testing & Hypothyroidism 2.4 Thyrotoxicosis, Thyroid Storm & Thyroid Nodules 2.5 Adrenal & Pituitary Disorders 2.6 Hypercalcemia, Hypocalcemia & Disorders of Mineral Metabolism 2.7 Osteoporosis & Paget Disease of Bone 2.8 Ovarian, Testicular & Reproductive Endocrine Disorders 2.9 Hypoglycemia, Endocrine Tumors, Polyglandular Syndromes & Severe Hypertriglyceridemia

4 Chapter 3: Gastroenterology & Hepatology (9% of Exam)

3.1 Esophageal Disease 3.2 Stomach & Duodenal Disease and Gastrointestinal Hemorrhage 3.3 Inflammatory Bowel Disease 3.4 Celiac Disease & Irritable Bowel Syndrome 3.5 Diverticular Disease & Colorectal Cancer Screening 3.6 Viral Hepatitis, Steatotic & Alcohol-Associated Liver Disease 3.7 Cirrhosis & the Complications of Portal Hypertension 3.8 Acute Pancreatitis 3.9 Chronic Pancreatitis & Biliary Tract Disease 3.10 Inherited, Autoimmune & Drug-Induced Liver Disease 3.11 Small Intestinal Disease, Ischemia & Gastrointestinal Complications of HIV

5 Chapter 4: Infectious Disease (9% of Exam)

4.1 Lower Respiratory Tract Infections & Sepsis Syndromes 4.2 Viral Respiratory Pathogens & Tuberculosis 4.3 Central Nervous System Infections 4.4 Skin, Soft Tissue, Bone & Joint Infections 4.5 Infective Endocarditis & Cardiovascular Infection 4.6 Clostridioides difficile & Catheter-Related Bloodstream Infection 4.7 HIV Diagnosis, Antiretroviral Therapy & Prevention 4.8 Opportunistic Infections & Sexually Transmitted Infections 4.9 Fever of Unknown Origin, Neutropenic Fever & Toxic Shock 4.10 Travel-Related Illness, Vector-Borne Disease & Outbreaks 4.11 Infection Prevention, Nosocomial Infection & Postexposure Prophylaxis 4.12 Rheumatic Fever, Poststreptococcal Disease, Enteric & Hepatic Infections

6 Chapter 5: Pulmonary Disease (9% of Exam)

5.1 COPD: Diagnosis, GOLD Classification & Initial Pharmacotherapy 5.2 Interventions That Reduce COPD Mortality & Exacerbation Management 5.3 Asthma: Diagnosis, Stepwise Therapy & Status Asthmaticus 5.4 Interstitial Lung Disease & Idiopathic Pulmonary Fibrosis 5.5 Sarcoidosis, Hypersensitivity Pneumonitis & Occupational Lung Disease 5.6 Pulmonary Embolism: Diagnosis, Risk Stratification & Anticoagulation 5.7 Pulmonary Hypertension & Sleep-Disordered Breathing 5.8 Acute Respiratory Distress Syndrome & Mechanical Ventilation 5.9 Pleural Disease, Empyema & Pneumothorax 5.10 Bronchiectasis, Cystic Fibrosis & Restrictive Lung Disease 5.11 Evaluation of Cough, Dyspnea, Hemoptysis & the Solitary Pulmonary Nodule

7 Chapter 6: Rheumatology & Orthopedics (9% of Exam)

6.1 Rheumatoid Arthritis: Diagnosis & Systemic Manifestations 6.2 Antirheumatic Pharmacotherapy & the Spondyloarthropathies 6.3 Gout: Pathophysiology & Acute Management 6.4 Urate-Lowering Therapy & Calcium Pyrophosphate Deposition Disease 6.5 Osteoarthritis 6.6 Systemic Lupus Erythematosus 6.7 Systemic Sclerosis, Sjogren Syndrome & Inflammatory Myopathies 6.8 The Vasculitides 6.9 Regional Musculoskeletal Syndromes, Back Pain & Sports Injuries 6.10 Other Primary Rheumatic Disorders & Mixed Connective Tissue Disease 6.11 Osteonecrosis & Metabolic Bone Disease

8 Chapter 7: Hematology (6% of Exam)

7.1 Approach to Anemia & the Microcytic Anemias 7.2 Macrocytic, Normocytic & Hemolytic Anemias 7.3 Hemoglobinopathies, Thalassemias & Paroxysmal Nocturnal Hemoglobinuria 7.4 Platelet Disorders, Thrombocytopenia & the Bleeding Patient 7.5 Coagulation Factor Disorders, Thrombophilia & Anticoagulant Reversal 7.6 Acute Leukemias, Chronic Leukemias & Myeloproliferative Neoplasms 7.7 Lymphomas & Plasma Cell Disorders 7.8 Myelodysplastic Syndrome, Myeloproliferative Neoplasms & Porphyria 7.9 Transfusion Medicine & Late Complications of Transplantation

9 Chapter 8: Medical Oncology (6% of Exam)

8.1 Breast, Lung, Colorectal & Prostate Cancer 8.2 Oncologic Emergencies 8.3 Genitourinary & Gynecologic Malignancies 8.4 Head and Neck, Bone & Soft Tissue Cancer and Cancer of Unknown Primary 8.5 Complications of Cancer & Its Treatment 8.6 Cancer Prevention, Survivorship & Psychosocial Care

10 Chapter 9: Nephrology & Urology (6% of Exam)

9.1 Acute Kidney Injury: Staging, Etiology & Urine Microscopy 9.2 Glomerular Disorders & Nephrotic Syndrome 9.3 Nephritic Syndromes, RPGN & Indications for Renal Replacement Therapy 9.4 Chronic Kidney Disease: Staging & Progression Retardation 9.5 Complications of Chronic Kidney Disease: Anemia, CKD-MBD & Acidosis 9.6 Hyponatremia, Hypernatremia & Water Balance 9.7 Potassium Disorders & Systematic Acid-Base Analysis 9.8 Renal Tubular Acidosis & Nephrolithiasis 9.9 Prostate Disorders, Urinary Incontinence & Other Urologic Conditions 9.10 Cystic Kidney Disease, Obstructive Uropathy, Tubulointerstitial Disease & Hematuria

11 Chapter 10: Neurology (4% of Exam)

10.1 Acute Ischemic Stroke: Syndromes & Reperfusion 10.2 Transient Ischemic Attack, Secondary Prevention & Hemorrhagic Stroke 10.3 Headache & Facial Pain 10.4 Seizures, Epilepsy & Movement Disorders 10.5 Multiple Sclerosis & Neuromuscular Junction Disorders 10.6 Motor Neuron Disease & Acute Peripheral Neuropathy 10.7 Cranial Neuropathies & Neuro-Ophthalmology 10.8 Peripheral Neuropathies, CNS Tumors & Other Neurologic Disorders

12 Chapter 11: Psychiatry & Behavioral Health (4% of Exam)

11.1 Major Depressive Disorder & Medical Mimics 11.2 Antidepressant Pharmacotherapy & Treatment-Resistant Depression 11.3 Bipolar Disorder, Mood Stabilizers & Lithium Toxicity 11.4 Anxiety, Stress-Related & Obsessive-Compulsive Disorders 11.5 Alcohol Use Disorder & Withdrawal 11.6 Pharmacotherapy for Alcohol & Opioid Use Disorder 11.7 Toxidromes, Psychiatric Emergencies & Suicide Risk Assessment 11.8 Psychotic, Somatic Symptom, Factitious & Personality Disorders 11.9 Eating Disorders, Sleep Disorders & Sexual Health

13 Chapter 12: Dermatology (3% of Exam)

12.1 Dermatitis, Papulosquamous & Inflammatory Dermatoses 12.2 Acne, Rosacea & Cutaneous Infections 12.3 Herpes Zoster & Autoimmune Blistering Diseases 12.4 Nodules, Tumors & Cutaneous Oncology 12.5 Dermatologic Emergencies & Severe Cutaneous Adverse Reactions 12.6 Pigment Disorders, Alopecia, Nail Disease & Photosensitivity 12.7 Vascular Dermatoses, Environmental Injury & Cutaneous Signs of Systemic Disease

14 Chapter 13: Obstetrics & Gynecology / Women's Health (3% of Exam)

13.1 Contraception, Preconception Care & Teratogenicity 13.2 Hypertensive Disorders of Pregnancy & Gestational Diabetes 13.3 Thyroid Disease & Venous Thromboembolism in Pregnancy 13.4 Menopause & Menopausal Hormone Therapy 13.5 Abnormal Uterine Bleeding, Endometrial Disease & Gynecologic Cancer Screening 13.6 Breast Disorders & Diseases of the Vulva and Vagina 13.7 Menstrual Disorders, Fibroids, Endometriosis & Early Pregnancy Complications

15 Chapter 14: Geriatric Syndromes (3% of Exam)

14.1 Comprehensive Geriatric Assessment & Frailty 14.2 Falls, Gait Assessment & Polypharmacy 14.3 Urinary Incontinence & Pressure Injuries in Older Adults 14.4 Mild Cognitive Impairment, Dementia & Its Subtypes 14.5 Delirium & the Pharmacotherapy of Cognitive Disorders 14.6 Palliative Care, Hospice & Advance Care Planning 14.7 Chronic Wounds, Nutrition, Swallowing, Constipation & Hip Fracture 14.8 Sensory Impairment, Dizziness, Elder Mistreatment & Care Settings

16 Chapter 15: Allergy & Immunology (2% of Exam)

15.1 Anaphylaxis: Recognition & Emergency Management 15.2 Urticaria & Angioedema 15.3 Drug Allergy, Desensitization & Adult Immunodeficiency 15.4 Food Allergy, Insect Venom Hypersensitivity, Serum Sickness & Contrast Reactions 15.5 Rhinitis, Conjunctivitis, Eosinophilic & Mast Cell Disorders

17 Chapter 16: Preventive Medicine, Immunization & Clinical Epidemiology

16.1 The USPSTF Framework & Evidence-Based Cancer Screening 16.2 Cardiovascular & Metabolic Screening and Primary Prevention 16.3 Adult Immunization & Vaccines in Special Populations 16.4 Clinical Epidemiology, Biostatistics & Study Design

18 Chapter 17: Miscellaneous - Ethics, Patient Safety & Quality Improvement (2% of Exam)

17.1 Principles of Bioethics & Decisional Capacity 17.2 Informed Consent, Treatment Refusal & Special Scenarios 17.3 Surrogate Decision-Making, Advance Directives & Confidentiality 17.4 Patient Safety Science, Medical Error & Diagnostic Reasoning 17.5 Quality Improvement Methods, Health Disparities & Health Equity

19 Chapter 18: Perioperative Medicine & Medical Consultation

18.1 Preoperative Cardiovascular Risk Assessment 18.2 Preoperative Pulmonary Risk & Perioperative Medication Management 18.3 Perioperative Anticoagulation, Bridging & Postoperative Complications

20 Chapter 19: Ophthalmology (1% of Exam)

19.1 The Acute Red Eye & Ophthalmic Emergencies 19.2 Painless Vision Loss & Chronic Ophthalmic Disease 19.3 Uveitis, Scleritis & Orbital Disease

21 Chapter 20: Otolaryngology & Dental Medicine (1% of Exam)

20.1 Dizziness, Vertigo & Epistaxis 20.2 Ear Disorders, Hearing Loss & Upper Respiratory Infections 20.3 Oral Cavity, Salivary Gland, Laryngeal & Taste and Smell Disorders

3.10 Inherited, Autoimmune & Drug-Induced Liver Disease

Key Takeaways Explain This Topic AI

Wilson disease, hemochromatosis, autoimmune hepatitis, Gilbert syndrome, Budd-Chiari syndrome, fulminant liver failure and liver transplantation are individually enumerated blueprint topics.

Gilbert syndrome causes isolated unconjugated hyperbilirubinemia with normal aminotransferases that rises with fasting, illness or stress and requires no treatment.

Wilson disease should be considered in any patient under 40 with unexplained liver disease, particularly with a low alkaline phosphatase to bilirubin ratio or a Coombs-negative hemolytic anemia.

Hereditary hemochromatosis is screened for with transferrin saturation and ferritin, and therapeutic phlebotomy is the treatment of choice.

N-acetylcysteine is given in acetaminophen-induced injury and also improves transplant-free survival in non-acetaminophen acute liver failure.

Last updated: August 2026

1. Gilbert Syndrome: The Benign Distractor

Gilbert syndrome is a common, benign, inherited reduction in UDP-glucuronosyltransferase activity. It matters on the exam because it is the correct answer whenever a well patient has an isolated bilirubin elevation and the tempting wrong answer is an expensive hepatology workup.

The signature is precise:

• Unconjugated (indirect) hyperbilirubinemia , usually below 3–4 mg/dL
• Normal aminotransferases, alkaline phosphatase and albumin
• No hemolysis — normal haptoglobin, reticulocyte count and lactate dehydrogenase

Bilirubin rises with fasting, dehydration, intercurrent illness, stress or exertion , which is why it is so often discovered during an unrelated admission

No treatment, no imaging and no biopsy are needed. One practical consequence: Gilbert syndrome impairs glucuronidation of some drugs, notably irinotecan , increasing toxicity.

The differential for unconjugated hyperbilirubinemia is short — Gilbert syndrome, hemolysis , and resorption of a large hematoma. A conjugated (direct) elevation is never Gilbert syndrome and always signals hepatocellular or cholestatic disease.

2. Hereditary Hemochromatosis

Autosomal recessive iron overload, most often from HFE C282Y homozygosity, with highest prevalence in people of northern European ancestry.

Screening sequence:

• Transferrin saturation — the most sensitive early marker; a value at or above roughly 45% is abnormal
• Ferritin — reflects total body stores but is also an acute-phase reactant
• HFE genotyping when both are elevated
• MRI quantification of hepatic iron; biopsy is now rarely required

Organ involvement produces the classic multisystem picture: cirrhosis and hepatocellular carcinoma, diabetes (bronze diabetes), skin hyperpigmentation, restrictive or dilated cardiomyopathy, hypogonadotropic hypogonadism , and a distinctive arthropathy of the second and third metacarpophalangeal joints — the blueprint lists arthropathy of hemochromatosis separately under Rheumatology.

Treatment is therapeutic phlebotomy , continued until ferritin reaches the low-normal range and then maintained. Iron chelation is reserved for those who cannot tolerate phlebotomy, typically because of anemia. Patients should avoid iron and vitamin C supplements and uncooked shellfish ( Vibrio vulnificus thrives in iron-replete hosts). Phlebotomy prevents cirrhosis if started early but does not reverse established cirrhosis , and those patients still require hepatocellular carcinoma surveillance.

3. Wilson Disease

Autosomal recessive impairment of biliary copper excretion from ATP7B mutation. Presentation is typically between the ages of 5 and 40, and the rule worth memorizing is: consider Wilson disease in any patient under 40 with unexplained liver disease.

• Domain Findings
• Hepatic Steatosis, chronic hepatitis, cirrhosis, fulminant liver failure
• Neurologic Tremor, dysarthria, dystonia, parkinsonism, ataxia
• Psychiatric Personality change, depression, psychosis
• Ocular Kayser-Fleischer rings (require slit-lamp examination)
• Hematologic Coombs-negative hemolytic anemia
• Renal Fanconi syndrome, nephrolithiasis

Screening: low serum ceruloplasmin with elevated 24-hour urinary copper . Ceruloplasmin is an acute-phase reactant and may be falsely normal during inflammation, so a normal value does not exclude the diagnosis.

The fulminant presentation has a distinctive laboratory fingerprint , frequently tested: a disproportionately low alkaline phosphatase relative to total bilirubin , with Coombs-negative hemolysis and only modest aminotransferase elevation. Fulminant Wilson disease is not salvageable medically and requires urgent transplant evaluation .

Chronic treatment uses chelation with penicillamine or trientine , or zinc to block intestinal copper absorption, plus dietary copper restriction.

4. Alpha-1 Antitrypsin Deficiency

Misfolded protein accumulates in hepatocytes (causing liver disease) while circulating levels are insufficient to protect the lung (causing panacinar, basilar-predominant emphysema ). The paired presentation — early emphysema in a minimal or non-smoker plus unexplained liver disease — should trigger measurement of the alpha-1 antitrypsin level and phenotyping. Liver biopsy shows periodic acid-Schiff-positive, diastase-resistant globules. Augmentation therapy addresses the lung disease only; it does not help the liver, because the hepatic injury results from intracellular accumulation rather than deficiency.

5. Autoimmune Hepatitis

A chronic immune-mediated hepatitis that most often affects women and frequently coexists with other autoimmune disease. It may present indolently, as an acute hepatitis, or as established cirrhosis.

Typical laboratory profile:

• Hepatocellular pattern with aminotransferases often several hundred to over a thousand
• Elevated IgG / polyclonal gammopathy — a highly characteristic feature
• Type 1: antinuclear antibody and/or anti-smooth muscle antibody
• Type 2: anti-liver-kidney microsomal type 1 antibody, typically younger patients

Liver biopsy shows interface hepatitis with a plasma-cell-rich infiltrate. Treatment is prednisone, with azathioprine added as a steroid-sparing agent ; thiopurine methyltransferase activity should be assessed before starting azathioprine. Untreated disease progresses to cirrhosis, so a positive antibody with active hepatitis should not simply be observed.

Overlap syndromes with primary biliary cholangitis or primary sclerosing cholangitis occur and are suggested by a mixed hepatocellular and cholestatic enzyme pattern.

6. Drug-Induced Liver Injury

The blueprint lists drug-induced liver disease other than acetaminophen separately, precisely because acetaminophen behaves differently from idiosyncratic injury.

• Acetaminophen (intrinsic) Idiosyncratic
• Dose relationship Dose-dependent, predictable Not dose-dependent
• Latency Hours to 1–2 days Days to months
• Aminotransferases Often >3,000 U/L Variable
• Antidote N-acetylcysteine None; withdraw the drug

Acetaminophen injury is the most common cause of acute liver failure in the United States. It occurs not only after intentional overdose but with therapeutic misadventure — repeated supratherapeutic dosing in a patient who is fasting, malnourished or consuming alcohol, all of which deplete glutathione and induce CYP2E1. N-acetylcysteine should be given when injury is suspected; it is most effective early but retains benefit late.

High-yield idiosyncratic offenders: isoniazid, amoxicillin-clavulanate (the most common cause of drug-induced cholestatic injury, often with delayed onset after the course is finished), nitrofurantoin, minocycline, methotrexate, azole antifungals, anabolic steroids and herbal or dietary supplements — green tea extract, anabolic-containing bodybuilding products and kava among them. Always ask about supplements ; patients rarely volunteer them as medications.

Hy's law identifies a high risk of fatal outcome: hepatocellular injury with aminotransferases above three times the upper limit of normal and bilirubin above twice the upper limit of normal , without biliary obstruction.

7. Budd-Chiari Syndrome

Hepatic venous outflow obstruction. The classic triad is abdominal pain, ascites and hepatomegaly , with a paradoxically high serum-ascites albumin gradient but a high ascitic protein , distinguishing it from cirrhotic ascites.

Diagnosis is by Doppler ultrasonography of the hepatic veins. Because roughly 80% of cases have an identifiable prothrombotic cause, the finding obliges a hypercoagulability evaluation — myeloproliferative neoplasms including the JAK2 V617F mutation (the single most common association), paroxysmal nocturnal hemoglobinuria, antiphospholipid syndrome, oral contraceptive use and pregnancy. Management is anticoagulation, treatment of the underlying disorder, and escalation to angioplasty, transjugular intrahepatic portosystemic shunt or transplantation.

8. Acute Liver Failure and Transplantation

Acute liver failure is coagulopathy (INR ≥ 1.5) with any degree of encephalopathy in a patient without pre-existing cirrhosis. The encephalopathy is what separates acute liver failure from severe acute hepatitis, and it mandates immediate transfer to a transplant center.

Causes in approximate order: acetaminophen, idiosyncratic drug injury, viral hepatitis, autoimmune hepatitis, Wilson disease, Budd-Chiari syndrome, and ischemic or shock liver.

N-acetylcysteine improves transplant-free survival in non-acetaminophen acute liver failure as well as in acetaminophen toxicity — a point that is frequently missed. Cerebral edema is the leading cause of death, so intracranial pressure management and avoidance of hypotonic fluids matter. Prophylactic correction of coagulopathy with plasma is generally avoided because it obscures the INR trend used to assess prognosis and transplant need.