Elevated Liver Enzymes and

Weight Loss
9/13/2006
Nick Siebers, M.D.

My wife made me come in

50 y/o man returns to our clinic after a 13
year absence.
CC: My wife made me come in
But wants to discuss recent labs done
for a life insurance physical.

Life insurance labs

AST was elevated at 36 with the normal
range for the lab being up to 33.
ALT was 55 with normal being up to 45.
Alkaline phosphatase, bilirubin, GGT, total
protein and albumin were all normal.
Hepatitis C antibody was negative.
Cholesterol panel was normal, HIV was
negative, normal urinalysis.

HPI
Feeling well.
No abdominal pain, nausea, emesis,
jaundice or pruritits, fever, chills or night
sweats.
Does acknowledge a 20-30 pound
unintentional weight loss over last 18
months, although this has been stable
over last 4 months.

Past Medical History

Colon cancer in 1993 s/p hemicolectomy
and 5FU x 1 year at GHC
Liver imaging several lesions probable
hemangiomas on ultrasound
Serial CT scans Minimal change,
maybe slightly larger - last in 1996
Pt told No need for further follow-up of
liver. Colonoscopy negative 2 years ago.
No other history liver disease

PMHx Contd

Arthritis/low back pain

Multiple lipomas removed superficially
Leukocytopenia, resolves with exercise
H/o blood transfusion
Ankle fracture
Allergic rhinitis

Family and Social History

Father - CAD s/p CABG at age 63
Mother - Breast cancer survivor, thyroid
disease
Aunt and grandfather with colon cancer
Works as an auto mechanic
Drinks about 12 drinks per week, 2 per day
and up to 4 each weekend day
Never smoker, no other drugs, no STD
concerns

ROS

Weight loss as above

Occasional fatigue
Rare GERD symptoms in past, better recently
Hemorrhoids and occasional rectal bleeding,
including over the preceding few weeks.
Slight chronic cough, rarely productive
Some mild anxiety and insomnia, relatively new,
no depressive symptoms

Exam

Temp 97.0, Pulse 88 and regular, BMI 21

No jaundice or icterus, no oral lesions
No thyromegaly noted
Heart, lungs normal
Abdomen soft non-tender; liver edge palpable 23 cm below ribs with inspiration, smooth and
non-tender; no splenomegaly
Rectal brown stool, guaiac (+), palpable
internal hemorrhoid.

What do I do about these

abnormal liver enzymes?
Does the evidence help us at all?

Is it a real problem?

What diagnoses to consider?

Table 2821. Liver Diseases

Inherited hyperbilirubinemia:

Gilbert's syndrome

Crigler-Najjar syndrome types I and II

Dubin-Johnson syndrome

Rotor syndrome
Viral hepatitis:

Hepatitis A

Hepatitis B

Hepatitis C

Hepatitis D

Hepatitis E

Others (mononucleosis, herpes, adenovirus hepatitis)

Cryptogenic hepatitis
Immune and autoimmune liver diseases:
Primary biliary cirrhosis
Autoimmune hepatitis
Sclerosing cholangitis
Overlap syndromes
Graft-vs-host disease
Allograft rejection

Genetic liver diseases

Alpha-1-Antitrypsin deficiency
Hemochromatosis
Wilson's disease
Benign recurrent intrahepatic cholestasis (BRIC)
Familial intrahepatic cholestasis (FIC), types IIII
Others (galactosemia, tyrosinemia, cystic fibrosis, Newman-Pick
disease, Gaucher's disease)
Alcoholic liver disease
Acute fatty liver
Acute alcoholic hepatitis
Laennec's cirrhosis
Nonalcoholic fatty liver
Steatosis
Steatohepatitis
Acute fatty liver of pregnancy
Liver involvement in systemic diseases
Sarcoidosis
Amyloidosis
Glycogen storage diseases
Celiac disease
Tuberculosis
Myobacterium avium intracellulare

Cholestatic syndromes

Benign postoperative cholestasis

Jaundice of sepsis

Total parenteral nutrition (TPN)induced jaundice

Cholestasis of pregnancy

Cholangitis and cholecystitis

Extrahepatic biliary obstruction (stone, stricture, cancer)

Biliary atresia

Caroli's disease

Cryptosporidiosis

Drug-induced liver disease

Hepatocellular patterns (isoniazid, acetaminophen)

Cholestatic patterns (methyltestosterone)

Mixed patterns (sulfonamides, phenytoin)

Micro- and macrovesicular steatosis (methotrexate, fialuridine)

Vascular injury

Venoocclusive disease

Budd-Chiari syndrome

Ischemic hepatitis

Passive congestion

Portal vein thrombosis

Nodular regenerative hyperplasia

Mass lesions

Hepatocellular carcinoma

Cholangiocarcinoma

Adenoma

Focal nodular hyperplasia

Metastatic tumors

Abscess

Cysts
From Harrison's Internal Medicine Copyright 2006 The McGraw-Hill
Companies. All rights reserved.

National Health and Nutrition

Examination Survey (NHANES)
1999-2002

Population survey w/ 6,823 participants

Abnormal ALT in 8.9% of respondents
Abnormal AST in 4.3%
Either abnormal in 9.8%

NHANES 1999-2002
When history of excessive alcohol
consumption and Hep C antibody
positive excluded :
ALT abnormal 7.3%
AST abnormal 3.6%
Either 8.1%
Increased compared with NHANES 19881994 but possibly from differences in
specimen handling

NHANES 1988-1994
7.9% with elevated ALT or AST
31% of these were explained by alcohol
consumption, Hep B or C or high
transferrin saturation.
69% were not!

Unexplained Liver Test Elevations

In NHANES 1988-1994 and 1999-2002,
unexplained ALT and AST elevation correlated
with:
BMI and waist circumference
Serum Triglycerides
Fasting insulin
Low HDL
Suggests Fatty Liver Disease as contributing,
although other causes are likely included.

Does it represent disease?

In 1993, Kundrotas et al. surveyed 19,877 Air
Force recruits
99 with ALT >2.25 SD above normal (0.5%)
Cause found in only 12 (0.06% of population)
fatty liver disease not evaluated
Recommended serial ALT testing before further
work-up, frequency and repetitions not clear
Later recommendations suggest work up if
chronically elevated for 6 months.

Hultcranz et al. 1986

149 Scandanavian blood donors with
elevated ALT, who all had a biopsy:
64% with fatty liver
20% with chronic active or persistent
hepatitis
6% with cirrhosis
Real disease is possible!

Estimates of disease prevalence

Estimates of cause of elevated ALT/AST vary
widely by population studied
Two studies of 249 blood donors:
Alcoholic liver disease 11-48%
Fatty liver 22-56%
Hepatitis C 17-20%
Alpha-1-antitrypsin deficiency 0-4%
Other established dx 4-8%
No Dx 2-9%

Up To Date Recommendations
Approach to the patient with abnormal
liver function tests - Daniel S. Pratt author
4 step approach to chronically abnormal
aminotransferases
1) Check for common liver diseases
2) Check for non-hepatic causes
3) Check less common liver diseases
4) Biopsy or observe

1) Common Liver Diseases

Medications, herbal therapies, recreational
substances
Alcohol abuse
Hepatitis B and C serology
Screen for hemochromatosis
Evaluate for fatty liver - ultrasound

2) Non-Hepatic sources

Muscle disorders
Thyroid disease, hypo- or hyperthyroidism
Celiac disease
Adrenal Insufficiency

3) Less Common liver disease

Autoimmune hepatitis
Wilsons disease (if less than 40 y/o)
Alpha-1-antitrypsin deficiency
Other diagnoses

Step 4) if less than twice upper limit can

observe, otherwise biopsy

Labs 2 weeks off alcohol

AST 28 (0-50)
ALT 66 (0-65)
Alk Phos 134 (35-130)
Total bili 0.6
GGT 23
Iron 138
TIBC 313
Iron Saturation 44%
Hepatitis A and B serologies (-)
CEA < 0.7 undetectable

CT Abdomen and Pelvis

1. Three discrete low-attenuation lesions within
the posterior segment of the right hepatic lobe.
The imaging features are highly suggestive of
cavernous hemangioma. Given prior description
of similar-appearing lesions from 10 years ago,
hemangiomas are even more likely.
2. Postsurgical changes of right hemicolectomy.
3. No evidence to suggest metastatic disease.

Thyroid tests?

TSH <0.06 - undetectable

Free T4 = 3.5 (0.7-1.8)
Repeat testing was the same. Hes hyperthryroid!
Thyroid uptake and scan findings: The I-131 uptake in 24
hours was normal at 18%. Thyroid scan reveals
homogeneous distribution of radioactivity within the
thyroid gland with no evidence for salivary gland uptake.
IMPRESSION: Data consistent with Graves' disease.
However the 24-hour radioiodine uptake is 18%, and not
in the range of Graves' disease, because of the contrast
material that he received on June 6, 2006 for CT of the
abdomen.

Thyroid disease and liver disease

Long documented associations, going back to
1874 Exophthalmic goitre; heart disease;
jaundice; death. Lancet by Habershon, SO.
Liver disease can cause alteration in thyroid
function.
Thyroid disease can cause abnormal liver tests;
even severe elevations, jaundice and prolonged
PT.
Case reports exist of chronic active hepatitis that
resolved with treatment of hyperthyroidism
alone.

Hyperthyroidism and liver tests

Test

% with abnormality

AST

27%

ALT

37%

Alk Phos

64%

GGT

17%

Bilirubin

5%

ANY

76%

Hyperthyroidism and liver tests

Mechanism unclear
Abnormalities seen on biopsy of
hyperthyroidism, but not correlated with
lever test abnormalities - 1967
Couldnt find more recent literature, and
specialists in GI and Endocrine were not
able to enlighten me.

Prognosis of abnormal liver tests

Many normalize with treatment of thyroid
disease
Some transient elevation of ALT and
especially Alk Phos with PTU treatment
usually no serious sequella, can continue
therapy unless overt hepatitis develops.

Mr. N
Seen by endocrine! And his thyroid wasnt felt to
be enlarged.
Being treated for Graves Disease with PTU,
plan treatment for one year then withdraw and
monitor.
ALT has normalized, alk phos up slightly
He feels great and is VERY happy with these
results decreased tremor and anxiety, better
sleep, weight going up, no cancer.
Per Dr. Nolten hyperthyroidism is likely the
cause of his abnormal liver tests.

Conclusions
Work up common liver diseases first, with
focus as per history
If abnormal liver tests think of the
thyroid!
It is possible to get a patient in to see
endocrine, although it takes some doing.

References

Pratt, DS. Approach to the patient with abnormal liver function tests. Up To Date
2006.
Katkov, WN, et al. Elevated serum alanine aminotransferase levels in blood donors:
the contiburion of hepatitis C virus. Annals ot Internal Medicine 1991; 115:882.
Hulcrantz, R, et al. Liver investigations in 149 asymptomatic patients with moderately
elevated activities of serum aminotransferases. Scandanavian Journal of
Gastroenterology 1986; 21:109.
Ioannou, GN, et al. the Prevalence and Predictors of Elevated Serum
Aminotransferase Activity in the United States in 1999-2002. American Journal of
Gastroenterology 2006; 101:76-82.
Huang, M, et al. Sequential Liver and Bone Biochemical Changes in Hyperthyroidism:
Prospective Controlled Follow-up Study. American Journal of Gastroenterology 1994;
89:1071-1076
Fong, T, Et al. Hyperthyroidism and Hepatic Dysfunction: A case Series Analysis.
Journal of Clinical Gastroenterology 1992; 14:240-244.
Leeuwenburgh, I, et al. Recovery of Chronic Hepatitis by Treatment of Concomitant
Hyperthyroidism. European Journal of Gastroenterology and Hepatology 2001:
13:1389-1392.
Harrison's Internal Medicine Online - Copyright 2006