GASTROENTEROLOGY & HEPATOLOGY
282
Ischemic Colitis
Most common in the elderly and in patients with atherosclerotic or cardiovas-
cular disease. Ranges from self-limited to life-threatening disease. Watershed
areas (the splenic flexure and rectosigmoid junction of the colon) are the
most common sites affected. Exsanguination and infarction are uncommon.
SYMPTOMS/EXAM
■
Crampy left lower abdominal pain, hematochezia, nausea.
■
Abdominal exam is benign or reveals mild LLQ tenderness.
DIFFERENTIAL
IBD, infectious colitis, diverticulitis.
DIAGNOSIS
■
Labs: Leukocytosis, anemia.
■
AXR: “Thumbprinting” is seen on the colon wall.
■
CT: Shows bowel wall thickening, luminal dilation, and pericolonic fat
stranding. Vascular occlusion (e.g., mesenteric venous thrombosis) is un-
common.
■
Flexible sigmoidoscopy: Contraindicated if peritoneal signs are present.
Performed with minimal insufflation. Look for segmental changes sparing
the rectum (due to preserved collateral circulation from hemorrhoidal
plexus) and hemorrhagic nodules. Pale, dusky, ulcerative mucosa.
TREATMENT
■

affects the colonic
“watershed” areas of the
splenic flexure and
rectosigmoid junction but
spares the rectum.
Ascaris lumbricoides causes
up to 20% of cases of acute
pancreatitis in Asia.
Gallstones and alcohol are the
main causes of pancreatitis in
the United States.
GASTROENTEROLOGY & HEPATOLOGY
SYMPTOMS
■
Presents with sudden-onset, persistent, deep epigastric pain, often with ra-
diation to the back, that worsens when patients are supine and improves
when they sit or lean forward.
■
Severe nausea, vomiting, and fever are also seen.
EXAM
■
Exam reveals upper abdominal tenderness with guarding and rebound.
■
Other findings include the following:
■
Severe cases: Distention, ileus, hypotension, tachycardia.
■
Rare: Umbilical (Cullen’s sign) or flank (Grey Turner’s sign) ecchy-
mosis.
■

cholithiasis (common duct stones) are often missed or have passed.
TABLE 7.13. Assessment of Pancreatitis Severity by Ranson’s Criteria
a
24 HOURS: “GA LAW” 48 HOURS: “C HOBBS”
Glucose > 200 mg/dL Ca < 8 mg/dL
Age > 55 Hematocrit drop < 10%
LDH > 350 U/L O
2
, arterial PO
2
< 60 mmHg
AST > 250 U/L Base deficit > 4 mEq/L
WBC > 16,000 /μL BUN rise > 5 mg/dL
Sequestered fluid > 6 L
a
Mortality risk: 1% with 0–2 criteria; 16% with 3–4 criteria; 40% with 5–6 criteria; 100% with
7–8 criteria.
283
CT is prognostic in severe
pancreatitis and is used to
evaluate for necrotizing
pancreatitis. Necrotizing
pancreatitis warrants empiric
antibiotics (imipenem).
GASTROENTEROLOGY & HEPATOLOGY
284
■
CT: Performed initially to exclude abdominal catastrophes. At 48–72
hours, exclude necrotizing pancreatitis. There is an ↑ risk of renal failure
from contrast dye.

ulation tissue. Occurs in approximately 30% of cases but resolves sponta-
neously in about 50%. Drainage is not required unless the pseudocyst is
present > 6–8 weeks and is enlarging and symptomatic.
■
Other: Pseudoaneurysm, renal failure, ARDS, splenic vein thrombosis
(which can lead to isolated gastric varices).
Chronic Pancreatitis
Persistent inflammation of the pancreas with irreversible histologic changes,
recurrent abdominal pain, and loss of exocrine/endocrine function. Marked
by atrophic gland, dilated ducts, and calcifications, although all are late find-
ings. Characterized by the size of pancreatic ducts injured; “big duct” injury
is from EtOH. Risk factors include EtOH (amount and duration) and smok-
ing. Associated with an ↑ risk of pancreatic cancer; 10- and 20-year survival
rates are 70% and 45%, with death usually resulting from nonpancreatic
causes. Etiologies are as follows:
■
EtOH (80%) and, to a lesser extent, hereditary pancreatitis (CF, trypsino-
gen mutation).
■
Autoimmune: Rare and associated with diffuse enlargement of the pan-
creas, ↑ IgG4, and autoantibodies; associated with other autoimmune dis-
orders (e.g., Sjögren’s, SLE, 1° sclerosing cholangitis).
■
Obstructive: Pancreas divisum, sphincter of Oddi dysfunction, mass.
■
Metabolic: Malnutrition, hyperlipidemia, hyperparathyroid-associated hy-
percalcemia.
For persistent pancreatitis, no
improvement on antibiotics (>
1 week), or suspicion of

Functional tests:
■
Often normal in “small duct” chronic pancreatitis; not ᮍ until 30–50%
of the gland is destroyed.
■
Seventy-two-hour fecal fat test on 100-g/day fat diet: ᮍ in the pres-
ence of > 7 g of fat in stool.
■
Stool chymotrypsin and elastase: Absent or low levels.
■
Secretin test: Most sensitive, but impractical. Give IV secretin and
then measure pancreatic secretion via a nasobiliary tube.
■
Structural tests: Except for endoscopic ultrasound (EUS), imaging studies
are insensitive, as architectural changes do not occur until late in the dis-
ease course; diagnosis is improved with EUS +/− FNA. Pancreatic calcifi-
cations are visualized on plain AXRs (30%); “big duct” injury is seen on
CT.
TABLE 7.14. Diagnosis of Chronic Pancreatitis
“BIG DUCT”“SMALL DUCT”
Seen on ultrasound or CT Yes No
Seen on ERCP Yes Maybe
Etiology EtOH Non-EtOH >> EtOH
Loss of function (exocrine/endocrine) Common Less common
Responsive to decompression Often Rarely
(stenting, surgery)
285
Chronic pancreatitis of the
“small duct” type may exhibit
very subtle structural changes

Other: Brittle DM, pancreatic pseudocyst, pseudoaneurysm, hemosuccus
pancreaticus (bleeding from the pancreatic duct into the GI tract), splenic
vein thrombosis, pancreatic cancer.
BILIARY DISEASE
Tables 7.15 and 7.16 classify diseases with jaundice and biliary tract disease.
Cholelithiasis (Gallstones) and Acute Cholecystitis
More common in women; incidence ↑ with age. In the United States, 10% of
men and 20% of women > 65 years of age are affected; > 70% are cholesterol
stones (see Table 7.17). Among patients with incidental asymptomatic gall-
stones, only 15% have biliary colic at 10 years, and 2–3% have cholecystitis/
cholangitis.
■
Cholecystitis: The most common complication of cholelithiasis. More
than 90% of cases are due to cholelithiasis with stone impacted in the cys-
tic duct. Spontaneous resolution occurs in > 50% of cases within 7–10
days.
■
Acalculous cholecystitis (without gallstones): Usually seen in critically ill
patients with no oral intake or following major surgical procedures; occurs
after ischemia-related chronic gallbladder distention.
SYMPTOMS
■
Cholelithiasis: Often asymptomatic or may present as follows:
■
Common: Biliary colic (crampy, wavelike RUQ pain), abdominal
bloating, dyspepsia.
■
Uncommon: Nausea/vomiting (except in small bowel obstruction from
gallstone ileus).
■

■
Cholecystitis:
■
Labs: Leukocytosis with neutrophil predominance; elevated total
bilirubin (1–4 mg/dL) and transaminases (2–4 times normal) even
without choledocholithiasis. Elevated alkaline phosphatase and amy-
lase.
■
RUQ ultrasound: Less sensitive than HIDA scan but more readily
available. Shows gallbladder wall thickening, pericholecystic fluid,
and localization of stones. A radiographic Murphy’s sign (focal gall-
TABLE 7.15. Classification of Jaundice
TYPE OF HYPERBILIRUBINEMIA LOCATION AND CAUSE
↑ bilirubin production (e.g., hemolytic anemias, hemolytic
reactions, hematoma, pulmonary infarction).
Impaired bilirubin uptake and storage (e.g., posthepatitis
hyperbilirubinemia, Gilbert’s syndrome, Crigler-Najjar syndrome,
drug reactions).
Hereditary cholestatic syndromes: Faulty excretion of bilirubin
conjugates (e.g., Dubin-Johnson syndrome, Rotor’s syndrome).
Hepatocellular dysfunction:
■
Biliary epithelial damage (e.g., hepatitis, hepatic cirrhosis).
■
Intrahepatic cholestasis (e.g., certain drugs, biliary cirrhosis, sepsis,
postoperative jaundice).
■
Hepatocellular damage or intrahepatic cholestasis resulting from
miscellaneous causes (e.g., spirochetal infections, infectious
mononucleosis, cholangitis, sarcoidosis, lymphomas, industrial

Adenomyomatosis May cause biliary colic. Normal. Oral cholecystography. Laparoscopic
cholecystectomy if
symptomatic.
Porcelain gallbladder Usually asymptomatic; Normal. X-ray or CT. Laparoscopic
high risk of gallbladder cholecystecomy.
cancer.
Acute cholecystitis Epigastric or RUQ Leukocytosis. Ultrasound, HIDA Antibiotics,
pain, nausea, scan. laparoscopic
vomiting, fever, cholecystectomy.
Murphy’s sign.
Chronic cholecystitis Biliary colic, constant Normal. Oral cholecystography, Laparoscopic
epigastric or RUQ ultrasound (stones), cholecystectomy.
pain, nausea. cholecystectomy
(nonfunctioning
gallbladder).
Choledocholithiasis Asymptomatic or Cholestatic LFTs; Ultrasound (dilated Endoscopic
biliary colic, jaundice, leukocytosis and ducts), ERCP. sphincterotomy and
fever; gallstone blood cultures in stone extraction;
pancreatitis. cholangitis; elevated antibiotics for
amylase and lipase cholangitis.
in pancreatitis.
Adapted, with permission, from Tierney LM et al. Current Medical Diagnosis & Treatment, 44th ed. New York: McGraw-Hill, 2005:
663.
GASTROENTEROLOGY & HEPATOLOGY
289
T
REATMENT
■
Asymptomatic cholelithiasis: No specific treatment is indicated (even in
DM).

forming organisms. More common in diabetics and the elderly; associated
with high mortality. Gangrene and perforation may follow.
■
Cholecystenteric fistula: Uncommon. Stone erodes through the gallblad-
der into the duodenum. Large stones (> 2.5 cm) can cause small bowel
obstruction (gallstone ileus).
■
Mirizzi’s syndrome: Common bile duct obstruction by an inflamed im-
pacted cystic duct. Uncommon.
■
Gallbladder hydrops.
■
Porcelain gallbladder: Intramural calcification. Associated with an ↑ risk
of gallbladder cancer; cholecystectomy is indicated.
TABLE 7.17. Types of Gallstones
CHOLESTEROL BLACK PIGMENTED BROWN PIGMENTED
Regional/ethnic Western countries, Pima Africa, Asia. Africa, Asia.
predictors Indians, Caucasians >>
blacks.
Risk factors Age, female gender, Chronic hemolysis (sickle cell), Biliary infections, foreign
pregnancy, estrogens, DM, cirrhosis, high-protein diet. bodies (stents, sutures),
obesity, rapid weight loss, low-protein diet.
elevated triglycerides,
prolonged fasting, ileal
disease (Crohn’s), ileal
resection, CF.
GASTROENTEROLOGY & HEPATOLOGY
290
Choledocholithiasis and Cholangitis
Choledocholithiasis is defined as stones in the common bile duct. Cholangi-

noma, cholangiocarcinoma, bulky lymphadenopathy), parasitic infection
(e.g., ascariasis), AIDS cholangiopathy, 1° sclerosing cholangitis, recurrent
pyogenic cholangitis.
■
Cholangitis: Perforated peptic ulcer, hepatitis, acute pancreatitis, appen-
dicitis, hepatic abscess, diverticulitis, right-sided pneumonia.
DIAGNOSIS
■
Choledocholithiasis:
■
Labs: No leukocytosis; elevated total bilirubin (> 2 mg/dL), transami-
nases (2–4 times normal), and alkaline phosphatase.
■
RUQ ultrasound: Has low sensitivity (< 50%).
■
CT: Has higher sensitivity than RUQ ultrasound.
■
Cholangitis:
■
Labs: Leukocytosis with neutrophil predominance; elevated total
bilirubin (> 2 mg/dL), transaminases (> 2–4 times normal), alkaline
phosphatase, and amylase; bacteremia.
■
RUQ ultrasound: Shows dilation of the common bile duct and
cholelithiasis. Less likely to visualize choledocholithiasis.
■
ERCP: Perform < 48 hours after presentation, ideally after IV antibi-
otics and fluids. Requires sedation. Both diagnostic and therapeutic.
■
MRCP: Noninvasive and sensitive for diagnosis.

otics, biliary decompression can be elective; otherwise, it is indicated
emergently.
■
ERCP: Biliary decompression and drainage (sphincterotomy, stone re-
moval, biliary stenting).
■
PTHC: A temporary alternative to ERCP that allows for biliary decom-
pression (stenting and drainage).
■
Cholecystectomy after recovery for cholangitis due to gallstones.
■
Recurrent pyogenic cholangitis: Affects Southeast Asians between 20
and 40 years of age; characterized by pigmented intrahepatic bile duct
stones, biliary strictures, and repeated cholangitis. Treatment includes
stenting and drainage. Often isolated to the left lobe of the liver; resec-
tion may be considered.
COMPLICATIONS
Gallstone pancreatitis, gram-ᮎ sepsis, intrahepatic abscesses.
AIDS Cholangiopathy
An opportunistic biliary infection caused by CMV, Cryptosporidium, or Mi-
crosporidium. CD4 is usually < 200/mL.
SYMPTOMS/EXAM
Presents with RUQ pain/tenderness, fever, hepatomegaly, and diarrhea. Jaun-
dice is uncommon.
DIFFERENTIAL
Biliary stones, cholecystitis, 1° sclerosing cholangitis.
DIAGNOSIS
■
Labs: Markedly elevated alkaline phosphatase.
■

DIAGNOSIS
■
Maintain a high clinical suspicion in patients with IBD, as the diagnosis
of IBD typically precedes that of 1° sclerosing cholangitis. Diagnosis
can be confirmed only by ERCP. Magnetic resonance cholangiography
(MRC) is less sensitive and less specific.
■
Labs: Look for a cholestatic pattern consisting of alkaline phosphatase > 1.5
times normal for six months plus a modest ↑ in bilirubin and transaminases.
■
Autoantibodies: The sensitivity of p-ANCA is 70%; that of ANA is 25%.
■
Liver biopsy: Look for pericholangitis and the classic “onion skin”
periductal fibrosis, focal proliferation and obliteration of bile ducts,
cholestasis, and copper deposition.
■
ERCP: Shows irregularity of the intra- and extrahepatic biliary tree, classi-
cally with a “beads on a string” appearance. 2° causes of sclerosing
cholangitis usually have only extrahepatic bile duct involvement except
with recurrent pyogenic cholangitis (intrahepatic biliary dilation and
stones).
TREATMENT
■
Focus on symptom control and on the prevention and management of
complications. Medical therapy to prevent or delay disease progression is
largely ineffective.
■
Symptom control: Treat pruritus (cholestyramine, ursodiol, phenobarbi-
tal, rifampin).
■

intra- and extrahepatic bile
ducts.
GASTROENTEROLOGY & HEPATOLOGY
293
1° Biliary Cirrhosis
A chronic cholestatic disease that primarily affects middle-aged women of all
races. Prevalence is 19–240 cases in one million; 90–95% are women. Age at
onset is 30–70; often associated with autoimmune disorders such as Sjögren’s,
RA, thyroid disease, celiac sprue, and CREST syndrome.
SYMPTOMS
May be asymptomatic (50–60% at the time of diagnosis) or present with fa-
tigue, severe and intractable pruritus prior to jaundice, and malabsorptive
diarrhea. Commonly associated with Sjögren’s syndrome, arthritis, and Ray-
naud’s phenomenon.
EXAM
■
Exam reveals hepatomegaly, splenomegaly, skin pigmentation, excoria-
tions (from pruritus), xanthelasma, and xanthomas. Kayser-Fleischer rings
are rare (result from copper retention, as in Wilson’s disease).
■
Late findings include jaundice and the stigmata of cirrhosis.
DIFFERENTIAL
Biliary obstruction (stones, benign or malignant mass), autoimmune hepatitis,
1° and 2° sclerosing cholangitis, drug-induced cholestasis (phenothiazines,
steroids, TMP-SMX, tolbutamide), infiltrative diseases (sarcoidosis, lym-
phoma, TB).
DIAGNOSIS
■
Suspect in the setting of unexplained cholestasis or elevated serum alka-
line phosphatase.

Ursodeoxycholic acid: The only FDA-approved disease-modifying agent;
promotes endogenous bile acid secretion and may also have immunologic
Antimitochondrial antibody
(present in 95% of patients)
and elevated serum IgM are
the best laboratory diagnostic
tools for 1° biliary cirrhosis.
GASTROENTEROLOGY & HEPATOLOGY
294
effects. Give 13–15 mg/kg/day. Colchicine and methotrexate are less com-
monly used.
■
Liver transplantation: The most effective treatment for decompensated 1°
biliary cirrhosis. Five-year survival is 85%; rates of recurrent 1° biliary cir-
rhosis at 3 and 10 years are 15% and 30%, respectively. The need for liver
transplantation can be predicted by the Mayo Clinic model (based on pa-
tient age, total bilirubin, PT, and serum albumin).
COMPLICATIONS
■
Malabsorption: Treat with fat-soluble vitamins (A, D, E, and K) and pan-
creatic enzymes.
■
Metabolic bone disease: Osteopenia (affects 33%) and osteoporosis (af-
fects 10%). Manage with calcium, vitamin D, and bisphosphonates.
■
Cirrhosis: Late ascites, encephalopathy, portal hypertension.
HEPATITIS
Hepatitis A (HAV) and Hepatitis E (HEV)
Spread by fecal-oral transmission; cause acute (not chronic) hepatitis. More
common in developing countries. The annual incidence of HAV in the

HAV: Anti-HAV IgM (acute infection); anti-HAV IgG (prior exposure,
vaccination); anti-HAV total measures IgM and IgG (acute infection,
prior exposure, vaccination).
■
HEV: Anti-HEV IgM (acute infection); anti-HEV (prior exposure).
HAV and HEV cause variably
severe acute hepatitis but do
not cause chronic hepatitis.
GASTROENTEROLOGY & HEPATOLOGY
295
T
REATMENT
■
No specific drug treatment is available for HAV or HEV.
■
Supportive care.
■
Consider early delivery for pregnant women with HEV (no proven bene-
fit).
PREVENTION
■
Vaccination: The HAV vaccine is safe and effective, but no vaccine for
HEV is currently available.
■
Indications for HAV vaccine: Travelers to endemic regions, men who
have sex with men, IV drug users, Native Americans, those with chronic
liver disease (all HCV
ᮍ), food handlers, day care center workers.
■
HAV immunoglobulin: Effective for postexposure prophylaxis. For those

Hepatocellular carcinoma can
occur before cirrhosis from
HBV, but this is not true of
HCV.
GASTROENTEROLOGY & HEPATOLOGY
296
E
XAM
■
Acute: Icteric sclera, arthritis, RUQ tenderness.
■
Chronic: Stigmata of cirrhosis (spider angiomata, palmar erythema, gyne-
comastia).
DIFFERENTIAL
■
Other acute viral diseases: HAV, HCV, mononucleosis, CMV, HSV.
■
Spirochetal (leptospirosis, syphilis) and rickettsial disease (Q fever).
■
Other chronic liver diseases: Autoimmune disease, hemochromatosis, α
1
-
antitrypsin deficiency, Wilson’s disease, alcoholic/nonalcoholic steatohep-
atitis.
DIAGNOSIS
■
HBsAg: Surface antigen indicates active infection (see Table 7.18).
■
Anti-HBs: Antibody to HBsAg indicates past viral infection or immuniza-
tion.

0
ALT
12345
HBsAg
HBeAg Anti-HBe
HBV DNA
6 12 24 36 48 60 120
Months after exposure
Anti-HBc
IgM anti-HBc
GASTROENTEROLOGY & HEPATOLOGY
297
T
REATMENT
■
Acute exposure/needlestick prophylaxis: The CDC recommends that
hepatitis B immune globulin (HBIG) be given within 24 hours along
with vaccine if the patient was not previously immunized.
■
Pegylated interferon-α
2a
: Given SQ; associated with many side effects
(e.g., constitutional, psychiatric, bone marrow toxicity, flare of autoim-
mune disease, hepatic decompensation). Contraindicated in cirrhosis. The
best responses to treatment are obtained with active hepatic inflammation
(high ALT) and low HBV DNA levels.
■
Lamivudine: Given PO. Well tolerated, but resistance may develop.
■
Adefovir: Given PO. Well tolerated and may be used to treat lamivudine-

−−IgG −−False
ᮍ; less commonly,
infection in remote past.
a
Low levels of IgM anti-HBc may also be detected.
Reproduced, with permission, from Tierney LM et al. Current Medical Diagnosis & Treatment,
44th ed. New York: McGraw-Hill, 2005: 634.
Needlestick transmission rates
follow the rule of 3’s: HBV
30%, HCV 3%, HIV 0.3%.
GASTROENTEROLOGY & HEPATOLOGY
298
highest rates of resolution in children and young women. Chronic infection
occurs in the remainder of patients. Cirrhosis occurs in 20% within 20–30
years. The risk of carcinoma is 1–4% per year after cirrhosis.
SYMPTOMS
■
Acute HCV: Presents with flulike illness, malaise, weakness, low-grade
fever, myalgias, and RUQ pain followed by jaundice. Only 30% of patients
are symptomatic in acute disease.
■
Chronic HCV: Often asymptomatic, or may present with cryoglobuline-
mia associated with a vasculitic skin rash (leukocytoclastic vasculitis),
arthralgias, sicca syndrome, and glomerulonephritis. In the setting of cir-
rhosis, presents with fatigue, muscle wasting, dependent edema, and easy
bruising.
EXAM
■
Acute: Icterus; RUQ tenderness.
■

Predictive: Quantitative PCR (a low viral load indicates a better treat-
ment response). Genotypes 2 and 3 are associated with a better treat-
ment response than genotype 1.
■
Indications for treatment: Age 18–60, HCV viremia, elevated amino-
transferase levels.
■
Contraindications: Psychosis, severe depression, symptomatic coro-
nary or cerebrovascular disease, decompensated cirrhosis, uncon-
trolled seizures, severe bone marrow insufficiency, pregnancy or inabil-
ity to use birth control, retinopathy, autoimmune disease.
■
Acute infection/needlestick prophylaxis: Currently not recommended.
■
Chronic HCV: Treatment is curative in up to 80% of genotype 2/3 cases
but is < 50% for genotype 1.
Both HCV and HBV can cause
cryoglobulinemia and
glomerulonephritis.
GASTROENTEROLOGY & HEPATOLOGY
299
■
Cryoglobulinemia: Treatment of acute flares includes plasmapheresis +/−
steroids. Long-term effectiveness is seen with interferon plus ribavirin, and
data on rituximab appear promising.
Autoimmune Hepatitis
Characterized by hypergammaglobulinemia, periportal hepatitis, and autoim-
mune markers. Typically chronic, but 25% of cases are characterized by acute
onset and rare fulminant hepatic failure. Prevalence depends on gender and
ethnicity; women are affected three times more often than men. Incidence

Extrahepatic associations: Present in 10–50% of cases.
■
Frequent: Autoimmune thyroid disease, ulcerative colitis, synovitis.
■
Uncommon: RA, DM, CREST syndrome, vitiligo, alopecia.
TREATMENT
■
Treatment indications: Active symptoms, biochemical markers (elevated
ALT, AST, or gamma globulin), histologic markers (periportal hepatitis,
bridging necrosis). The best treatment responses are obtained in the set-
ting of active hepatic inflammation (high ALT).
■
Relative contraindications: Asymptomatic patients with mild biochemical
inflammation (AST < 3 times normal); cirrhosis without histologic necro-
inflammation.
■
Prednisone monotherapy: Give 60 mg QD; tapering schedule varies and
is controversial.
Advanced liver disease is a
poor prognostic sign for
treatment response but not a
contraindication to the
treatment of autoimmune
hepatitis.
The decision to treat
autoimmune hepatitis is
dependent on the severity of
hepatic inflammation, not
hepatic dysfunction.
Autoimmune hepatitis is

factors include advanced age, female gender, use of an increasing number of
prescription drugs, underlying liver disease, renal insufficiency, and poor nu-
trition.
SYMPTOMS/EXAM
May present with constitutional symptoms, jaundice, RUQ pain, and pruritus.
Often asymptomatic.
TABLE 7.19. Differential Diagnosis of Immunologic Disease of the Liver
a
DISEASE GENDER LFTS OTHER LABS DIAGNOSIS ASSOCIATION TREATMENT
1° sclerosing M > F AP > 1.5 times p-ANCA. ERCP reveals Ulcerative colitis Liver transplant.
cholangitis ULN. “beads on a in 70%.
string.”
1° biliary F >> M AP > 3-4 times AMA (95%), IgM. Biopsy reveals Autoimmune Ursodeoxycholic
cirrhosis ULN; total paucity of bile (thyroiditis, acid → liver
bilirubin elevated. ducts and CREST, sicca in transplant.
granulomatous 50%).
cholangitis.
Autoimmune F > M Elevated AST/ ANA, ASMA, Biopsy reveals Prednisone,
hepatitis ALT. anti-LKM interface hepatitis azathioprine.
antibody, elevated and plasma cell
IgG. infiltrate.
a
ULN = upper limit of normal; AP = alkaline phosphatase; ASMA = anti–smooth muscle antibody; anti-LKM antibody =
anti–liver/kidney microsome antibody.
Elevated serum LDH suggests
drug-induced hepatitis over
viral hepatitis.
GASTROENTEROLOGY & HEPATOLOGY
DIFFERENTIAL
Viral hepatitis, ischemic hepatitis, Wilson’s disease, α

■
The most common cause of drug-induced hepatitis and drug-induced ful-
minant hepatic failure. The toxic dose is > 4 g in nonalcoholics and > 2 g
in alcoholics, but much higher doses are frequently associated with fulmi-
nant hepatic failure.
When ALT > 1000, consider
drug/toxic, ischemic,
congestive, and viral hepatitis.
TABLE 7.20. Characterization of Drug-Induced Hepatitis
INTRINSIC IDIOSYNCRATIC
Relation to dosage Dose dependent. Dose independent.
Frequency More common. Less common.
Onset Hours to days after starting Weeks to months after
drug. starting drug.
Toxicity Direct toxic effect. Immune-mediated toxicity.
Prognosis Good. Poor.
Implicated drugs Acetaminophen, carbon NSAIDs, INH,
tetrachloride, alcohol, sulfonamides, valproic
Amanita phalloides, acid, phenytoin,
aflatoxins. ketoconazole.
301
GASTROENTEROLOGY & HEPATOLOGY
302
■
Dx:
■
Maintain a high clinical suspicion with marked elevation of transami-
nases.
■
Acetaminophen level: Predict toxicity with the Rumack-Matthew

EXAM
■
Exam may reveal hepatomegaly, splenomegaly, cachexia, jaundice, spider
telangiectasias, Dupuytren’s contractures, parotid gland enlargement,
gynecomastia, and testicular atrophy.
■
There are no symptoms specific to alcoholic liver disease.
DIFFERENTIAL
Nonalcoholic steatohepatitis, nonalcoholic fatty liver disease, autoimmune
hepatitis, hemochromatosis, α
1
-antitrypsin deficiency, Wilson’s disease, viral
hepatitis, toxic or drug-induced hepatitis.
DIAGNOSIS
■
History of habitual alcohol consumption: The CAGE questionnaire is
sensitive for alcohol abuse.
■
Alcoholic steatosis: Modest elevation of AST > ALT in a 2:1 ratio; liver
biopsy shows small (microvesicular) and large (macrovesicular) fat droplets
in the cytoplasm of hepatocytes.
■
Alcoholic hepatitis: Marked leukocytosis, modest elevation of AST > ALT
in a 2:1 ratio, and markedly elevated serum bilirubin. Liver biopsy shows
steatosis, hepatocellular necrosis, Mallory bodies (eosinophilic hyaline de-
posits), ballooned hepatocytes, and lobular PMN inflammatory infiltrate.
Acetaminophen in modest
doses (e.g., < 2 g/day) is
much safer than NSAIDs for
patients with cirrhosis.

Alcoholic cirrhosis: Hepatic function can significantly improve with absti-
nence and improved nutrition.
■
Liver transplantation: Often precluded by active or recent alcohol abuse
or use. Recidivism rates are high. Most transplant centers require at least
six months of documented abstinence prior to listing for liver transplant.
Nonalcoholic Fatty Liver Disease
The spectrum of disease ranges from benign steatosis (fatty liver) to steatohep-
atitis (hepatic inflammation). Prevalence in the United States is 15–25%.
Steatohepatitis is found in 8–20% of morbidly obese individuals independent
of age. Disease is generally benign and indolent but can progress to cirrhosis
in 15–20% of cases. Risk factors for severe disease include female gender, age
> 45 years, body mass index (BMI) > 30, AST/ALT > 1, and type 2 DM.
SYMPTOMS
Presents with fatigue, malaise, and, to a lesser extent, RUQ fullness or pain.
Asymptomatic in > 50% of patients.
EXAM
■
Hepatomegaly is common, but examination may be limited in the obese.
■
Stigmata of chronic liver disease.
DIFFERENTIAL
■
Alcoholic liver disease.
■
Nutrition: TPN, kwashiorkor, rapid weight loss.
■
Drugs: Estrogens, corticosteroids, chloroquine.
■
Metabolic: Wilson’s disease, abetalipoproteinemia.

Typically ALT > AST (× 2–4) (vs. alcoholic liver disease, in which
AST > ALT); poor correlation with the presence and extent of inflam-
mation. A normal AST and ALT cannot exclude nonalcoholic fatty
liver disease.
■
The AST/ALT ratio ↑ with severity of liver disease, which is typical of
cirrhosis of all etiologies.
■
BMI is an independent predictor of the degree of hepatocellular fatty infil-
tration.
■
Ultrasound or CT scan.
■
Liver biopsy is the gold standard. The grade of inflammation and stage of
fibrosis predict disease course and response to therapeutic intervention.
TREATMENT
■
Gradual weight loss. Rapid weight loss may ↑ inflammation and fibrosis.
■
Treat hyperlipidemia and diabetes.
■
No FDA-approved therapy is available.
■
Therapeutic agents under study include metformin, rosiglitazone, urso-
deoxycholic acid,, and vitamin E.
METABOLIC LIVER DISEASE
Hereditary Hemochromatosis
An autosomal-recessive disease. Homozygote prevalence is 1 in 300 persons.
The most common genetic disease in Northern Europeans; the Caucasian
carrier rate is 1 in 10. Associated with a major mutation in chromosome 6, the

with fasting serum transferrin
saturation (TS) and ferritin; TS
> 45% with an elevated
ferritin suggests but does not
confirm the diagnosis.
Suspect hemochromatosis
with type 2 DM, degenerative
arthritis, or unexplained
hypogonadism, heart failure,
or liver disease.
GASTROENTEROLOGY & HEPATOLOGY
305
■
Fasting serum transferrin saturation (TS) and ferritin: If TS > 45% and
ferritin is elevated, hereditary hemochromatosis is suggested; check HFE
genotype. A TS < 45% and normal ferritin exclude hereditary hemochro-
matosis.
■
HFE genotyping: Homozygote is diagnostic only if (1) age < 40 years, (2)
ferritin < 1000, and (3) transaminases are normal. Otherwise, confirma-
tion with liver biopsy is necessary.
■
Liver biopsy: The best means of making a definitive diagnosis; a hepatic
Prussian blue stain with iron index > 1.9 is diagnostic. Also used for dis-
ease staging (influences prognosis; hepatocellular carcinoma screening is
needed if the patient is cirrhotic).
TREATMENT
■
Alcohol abstinence.
■

HCV markers suggests synergistic liver injury.
SYMPTOMS/EXAM
■
Neonatal cholestasis, occult cirrhosis, shortness of breath/dyspnea on exer-
tion, panniculitis.
■
Exam reveals signs of cirrhosis (spider angiomata, palmar erythema, gyne-
comastia) and emphysema (clubbing, barrel chest).
DIFFERENTIAL
■
Other metabolic liver diseases with childhood presentation: Hereditary
tyrosinemia, Gaucher’s disease, glycogen storage disease, CF.
■
Chronic liver diseases: HBV, HCV, hemochromatosis, Wilson’s disease,
autoimmune hepatitis, nonalcoholic fatty liver disease, alcohol.
Consider α
1
-antitrypsin
deficiency in any adult who
presents with chronic hepatitis
or cirrhosis of unclear
etiology.
α
1
-antitrypsin deficiency is
associated with bilateral
basilar pulmonary
emphysema.