"33 yo woman with incidental right sided abdomenal discomfort"

1. "33 yo woman with incidental right sided abdomenal discomfort" James M Sosman, MD

2. Case History • ID AG is a 35 yo W woman who presents for routine evaluation • CC: right sided abdomenal discomfort • HPI: AG states that she has noted discomfort for the past few months. Pain is dull and non-radiating over the right lateral side of the chest and abdomen. She states the intensity is 4-5/10. It is aggravated in some positions but is not pleuritic and is not associated with food or exercise. The discomfort is worsened with palpation over that region.

3. Case History • ROS • She denies fevers, chills, nausea or vomiting, anorexia, weight loss, jaundice, arthralgias, myalgias, rash, pruritus, and changes in her urine or stool. She also denies recent travel or any “sick” exposures • PAST MEDICAL HISTORY: • Anemia • G0P0AB0

4. Case History • MEDICATIONS: • MVI 1 a day • Ginseng once a day • NKAD • FMHx • No Hx of GI cancers or gallstones • 60 yo Father with CAD and mild Diabetes

5. Case History • SOCIAL HISTORY: • Smokes ½ ppd • occasional alcohol use • Married • works as a manicurist • Denies IDU • She walks 2 miles/day for exercise

6. Case • PHYSICAL EXAM: • Vitals: BP 139/75, HR 91, RR 16, Temp 96.8 F Weight 240lbs BMI 38 • HEENT WNL • Cardiac and Pulmonary exam WNL • Abdomen- Normoactive BS, no HSM/Mass, mild discomfort RUQ and Rt lateral Abdomen with no rebound or guarding • No LNs • Skin WNL other than a 2 yr old butterfly tattoo on her left shoulder

7. Diagnostic Options?

8. Case • Ordered a few lab tests • Advised AG to try Ranitidine 150mg PO BID • RTC in 3-4 wks or PRN

9. Case • Laboratory Studies: • WBC 10.3, Hemoglobin 12.2, PLT 215. normal differential • Sodium 137, potassium 4.5, chloride 101, CO2 27, BUN 16, Cr 1.1, glucose 110 • T Bil. 0.9, Alk phos 136, AST 45, ALT 75 • Urine Pregnancy- neg • What Next?

10. Abdomenal Ultrasound

11. Differential Diagnosis of Chronically ElevatedALT?

12. NAFLD Metabolic syndrome Alcoholic liver disease Hepatitis C IVDU, blood transfusions Medications Exposure history Hepatitis B Endemic area, IVDU, MSM Hemochromatosis Family history Autoimmune hepatitis Family history Alpha-1 AT deficiency Family history Wilson’s disease Family history Differential Diagnosis of Chronically ElevatedALT

13. Nonalcoholic Fatty Liver Disease (NAFLD) • A spectrum of disease predominantly characterized by macrovesicular steatosis of the liver that occurs despite little or no consumption of alcohol • Range of disorders from hepatic steatosis, which is generally benign, to nonalcoholic steatohepatitis (NASH), which may progress to cirrhosis and its complications • Early studies used a strict cutoff of either no alcohol consumption or < 20 g of alcohol intake per week to classify as nonalcoholic etiology • NAFLD represents the hepatic manifestation of the metabolic syndrome

14. Metabolic Syndrome • Characteristics include: • obesity, hypertension, diabetes, hypertriglyceridemia, and a low HDL level • Approximately 47 million in the US have metabolic syndrome • > 80% have NAFLD • > 90% with NAFLD have some features of metabolic syndrome • Insulin resistance is the fundamental pathophysiologic abnormality that connects NAFLD with metabolic syndrome

15. Classification of Nonalcoholic Fatty Liver

16. NAFLD: Epidemiology • Approx 33% of the US population has hepatic steatosis • Prevalence • Hispanics 45% • Blacks 24% • In an autopsy series, hepatic steatosis in 2.7% of lean individuals and 18.5% of obese individuals • Studies published before 1990 emphasized that NASH occurred mostly in women (53% to 85% of all patients) • In more recent studies NASH occurs with equal frequency in males

17. Relationship between BMI, waist circumference, and the presence of NAFLD NAFLD is directly related to BMI: More than 80% of individuals with a BMI > 35 have steatosis Waist circumference may be an even better predictor of underlying insulin resistance and NAFLD than BMI

18. Common Symptoms Among Individuals With NAFLD

19. Laboratory Abnormalities • 7.9% of the US has persistently abnormal liver enzymes despite negative tests for viral hepatitis and other common causes of liver diseases • related to BMI and other risk factors associated with NAFLD • Elevated ALT level (1-2 fold increase) most common liver enzyme abnormality • elevation is usually modest (rarely > 300 IU/L) • AST-to-ALT ratio is typically < 1

20. Natural History of NAFLD • Most studies are cross-sectional with highly selected patient populations • Increased risk of cardiovascular mortality • Was initially believed that NAFLD rarely progressed to more advanced liver disease • Steatosis may progress to more advanced liver disease in < 5% • NASH, however, can progress to cirrhosis • In a study of 103 individuals with NASH who had multiple liver biopsies taken over a median duration of 3.2 years, 37% showed fibrosis progression and 29% showed regression • Risk of NASH progression to cirrhosis is 20%

21. Natural History of NAFLD

22. Pathophysiology of NAFLD

23. Evaluation • Most of the time NAFLD is identified incidentally • 45-80% of patients are asymptomatic • Patient may have an abnormal ALT • Persistent hepatomegaly without an obvious cause • abdominal imaging performed for unrelated reasons reveals a fatty liver

24. Evaluation: Noninvasive methods for the diagnosis of NAFLD • Hepatic Ultrasound • increased hepatic parenchymal echotexture and vascular blurring • sensitive (85% to 95%) • 62% positive predictive value • Hepatic CT Scan • Hepatic steatosis decreases CT attenuation of the liver (10 or more Hounsfield units lower than the spleen on a noncontrast-enhanced scan) • 76% positive predictive value None of these methods can diagnose steatohepatitis or accurately assess the stage of the disease

25. How to Evaluate an Individual for the Presence of NAFLD • Exclude alternative causes • Assess for features of metabolic syndrome • Non diagnostic imaging (US) • Consider assessing for presence of steatohepatitis (Liver Biopsy)

26. Conditions and Factors Associated With NAFLD • Metabolic Syndrome • Drugs (amiodarone, tamoxifen, antiretroviral meds) • Wilson’s Disease • Jejuno-ilealbypass surgery • TPN

27. Drugs Used for the Treatment of NASH

28. Case • AG was told of her presumptive diagnosis (NAFLD) • She was informed to avoid potential hepatotoxins • AG was referred to a dietician and started on an aggressive exercise program • AG will try to stop smoking • She will follow up with me in about 2 months to assess progress and obtain fasting lipids