"33 yo woman with incidental right sided abdomenal

discomfort"

James M Sosman, MD

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.

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

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

Case History

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

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

Diagnostic Options?

Case

Ordered a few lab tests Advised AG to try Ranitidine 150mg

PO BID RTC in 3-4 wks or PRN

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?

Abdomenal Ultrasound

Differential Diagnosis of Chronically Elevated

ALT?

Differential Diagnosis of Chronically ElevatedALT

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

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

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

Classification of Nonalcoholic Fatty Liver

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

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

Common Symptoms Among Individuals With NAFLD

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

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%

Natural History of NAFLD

Pathophysiology of NAFLD

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

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

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)

Conditions and Factors Associated With NAFLD

Metabolic Syndrome Drugs (amiodarone, tamoxifen,

antiretroviral meds) Wilson’s Disease Jejuno-ilealbypass surgery TPN

Drugs Used for the Treatment of NASH

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