Case Presentations: Genes and Liver Disease Victor Ankoma-Sey, MD Director, Liver Transplant Program, Houston Methodist Hospital Director, Liver Associates of Texas, PA

Case # 1 28YOWF presents with jaundice x 1 week and lethargy PMH: No prior liver disease PSH:Nil Meds: Multivitamin FH: Mother has hypothyroidism SH: no etoh, no illicit drugs, nonsmoker, single

Case # 1 P/E: VSS HEENT:Sclera- icteric, Conj: pallor+ Chest: Clear COR : nl Abdo: nl Ext: no pedal edema Neuro: Lethargic, Nonfocal, Asterixis +

Case # 1 Bilirubin (total) mg/dL22.4 Bilirubin (Direct) mg/dL 6.6 ALT IU/l16 AST IU/l97 Alk Phos IU/l24 Creatinine mg/dL0.6 Protein g/dL5.6 Albuming/dL2.8 Retic Count12.6% LDH IU/l766 Direct Coomb’s(DAT)- WBC3.8 Hemoglobin7.4 Platelets109,000 INR3.1 HAV Ab- HBsAg- HCV Ab- ANA/ASMAb-/-

What is the Diagnosis? A.A. Acetaminophen (Tylenol) Hepatotoxicity B.B. Autoimmune Hepatitis C.C. Acute Hemolytic Crises with Fulminant Liver Failure in Wilson’s Disease D.D. Mushroom poisoning E.E. Heatstroke

What is the next Step in Mx ? A.Start urgent D-Penicillamine treatment B.Transfer to Transplant ICU: emergent evaluation for liver transplantation C.Start plasmapheresis as an outpatient D.Begin Trientine immediately E.Initiate IV Acetylcysteine (Mucomyst)

Acute Hemolytic Crises with Fulminant Liver Failure in Wilson’s Disease Rare presentation of Wilson’s disease Prompt liver transplantation is crucial to survival Low alkaline phosphatase and uric acid : are clues Coomb’s Negative Hemolytic anemia and liver failure: a diagnostic pointer

Case # 2 A 40 yr Male is brought to ER with hypotension, N/V and diarrhea PMH: DM, Arthritis Meds: Metformin, Motrin FH: Father: CHF and DM SH: Drinks 4-6 beers/day + 3 martinis x many years, mechanic, married. No illicit drugs or smoking h/o. Lives in Galveston, TX ROS: Ate raw oysters 2 days prior to admission

Case #2 P/E BP : 80/40 P:120/min T-102F, RR:22 Heent: Sclera- icteric, Conj -pink Chest: Clear COR: RRR Abdo: hepatomegaly+ Ext: pedal edema- Skin: bullous skin lesions-purpuric, nonblanching. Tanned skin Neuro: A & O x3, Nonfocal

Case # 2 Bilirubin (total)3.5 Bilirubin (Direct)2.5 ALT112 AST228 Alk Phos156 Glucose114 Protein6.1 Albumin3.2 WBC3.1 Hemoglobin9.9 Platelets109,000 INR1.4 HAV Ab- HBsAg- HCV Ab- ANA/ASMAb-/- % Fe saturation93% Ferritin1500

What is the most likely diagnosis ? A.Acute Alcoholic hepatitis B.Acetaminophen Hepatoxicity C.Acute Hepatitis A D.Vibrio Vulnificus Infection in a Hemochromatosis patient with active etoh use E.Malingering

Case # 3 What is his prognosis ? A.Excellent B.Guarded

Vibrio vulnificus V. vulnificus is concentrated in ocean filter feeders: oysters and clams Primary Sepsis/septicemia: Acquired from ingestion of raw shellfish Wound Infection: rapidly progressive, associated with exposure to estuarine waters Growth of the bacterium is exponential when Fe saturation is > 70%

Vibrio vulnificus Primary Sepsis Risk Factors Hereditary Hemochromatosis: 12% of patients Alcoholic cirrhosis: 31-43% of patients Underlying liver diseases including cirrhosis and chronic hepatitis : 24-31% of patients Alcohol abuse without documented liver disease: 12-27% of patients Chronic diseases: DM, RA, thalasemmia major, Chr renal failure and lymphoma: 7-8% of patients

Vibrio vulnificus Primary Sepsis 1/3 present in shock or become hypotensive within 12 hrs of admission Thrombocytopenia and DIC is common A serious illness: -Among all reported foodborne infections in the US, it is associated with highest case fatality rate (39%) -Case fatality rate > 90% when hypotensive at presentation

16 Case #3 58 y/o Caucasian female referred for > 3 year h/o elevated liver enzymes C/O fatigue, RUQ abdo pain Past Medical History – Obesity (BMI:40), DM, hyperlipidemia, HTN, back pain, arthritis, depression No alcohol history FH: Mother died from cirrhosis/NAFLD Meds: – Lipitor, Motrin, Effexor, Norvasc, Metformin

17 Case #3 Laboratory – ALT:72 – AST:55 – ALk Phos:115 – Albumin:4.0 – Platelets: 160,000 – INR:1.1 – Fasting insulin:30 – Fasting glucose:100 HBV, HCV: negative Fasting iron panel: normal ANA :80 ASMA, AMA: negative TSH: 0.8 Celiac Panel: - A1AT level: normal

18 Case #3

What are your initial Recommendations A.A. Dietary modifications B.B. Exercise C.C. Cognitive behavior therapy D.D. Control DM, Rx Hyperlipidemia E.E. All of above

Which test will help determine her prognosis in the long term? A.CT Scan Liver Protocol B.Ultrasound C.Liver Biopsy D.Serial fasting Insulin Level E.Waist circumference

STEATOHEPATITISSTEATOSIS NAFLD Alone or non-specific inflammation Hepatic cell injury + Inflammation balloning

NAFLD: At risk for advanced disease Age > 50 years Diabetes mellitus-Type II Metabolic Syndrome Obesity (BMI > 30) ? AST or ALT > 2X ULN Dorsocervical fat pad

23 NAFLD Prevalence increasing Distinction between simple fatty liver and NASH with moderate to advanced fibrosis is important Non-invasive testing may assist in triaging patients for liver biopsy Therapeutic options remain focused on improving insulin resistance – Heart healthy, low processed carbohydrate diet to produce deficit of cal/day – Exercise, as adjunct to diet, focusing on aerobic activity for 30 minutes/day

NASH - Pharmacologic options Most evidence-based data : glitazones Glitazones improve : certainly steatosis and ALT, inflammation and liver cell injury but not fibrosis The relationship between hepatic and metabolic improvement need to be better understood Hepatoprotectants need to be developed Phase II studies with biochemical end-points are needed Individualized therapy and integrative approaches with diet and lifestyle modifications need to be optimized

Question Key The key to my questions are as follows: A. Case #1: Ques 1What is Diagnosis? Ans: C Ques2: Next step.. Ans: B B. Case #2 Ques1: Most likely.. Ans:D Ques2: Prognosis..Ans:B C. Case #3 Ques 1..Recs.. Ans: E Ques 2.. Prognosis: C