And Hepatology: Alcoholic Liver Disease, Liver Failure, and
Chronic Liver Disease
University of Iowa Family Practice Handbook, Fourth
Edition, Chapter 5
Jatinder P. S. Ahluwalia, MD, Mark A. Graber, MD, and
William B. Silverman, MD
Division of Gastroenterlogy and Hepatology and Departments of
Internal Medicine, Family Medicine, and Emergency Medicine
University of Iowa Hospitals and Clinics and College of
Peer Review Status: Externally
Peer Reviewed by Mosby
Alcoholic Liver Disease (ALD).
It is caused by chronic alcohol ingestion-consumption
exceeding 80 g/day (equivalent to six 12 oz cans of beer, 1
liter of wine, or 5-6 liquor drinks).
It is the most prevalent form of liver disease in the
developed countries and affects women and those with hepatitis
C infection at a lower consumption level than men.
Three histologic forms of ALD are recognized: hepatic
steatosis (fatty liver), alcoholic hepatitis, and alcoholic
An increased prevalence of hepatitis C in patients with
Presenting features range from non-specific signs and
symptoms to frank liver failure. Also see chronic liver
disease below for signs and symptoms.
Parotid gland hypertrophy may be present due to
Epigastric or right-sided abdominal pain, progressive
jaundice, increasing abdominal girth or lower extremity
swelling may be the reasons compelling the patient to seek
Anorexia, nausea, and vomiting are also reported by
Fever and tachycardia may be noted in the absence of an
Tender hepatomegaly may occur due to acute inflammation
of the liver.
Progressive jaundice, palmar erythema, Dupuytren’s
contractures, cutaneous telangiectasias, feminization (gynecomastia
and testicular atrophy) and complication of portal
hypertension (see below) are some of the other findings.
Alteration in mental status may be noted due to hepatic
encephalopathy (see below) and/or alcohol withdrawal.
Diagnosis and laboratory evaluation. A thorough
history of alcohol use, complete liver panel, biochemical
profile, CBC and PT with INR should be obtained on all
patients. The CAGE questionnaire can be used to screen for
alcohol abuse or dependency.
Elevated GGT in most.
AST:ALT ratio is typically between 2:1 to
8:1 with both usually being <300 IU/L. Unless associated
with acetaminophen toxicity, transaminase values higher than
seven times the upper limit of normal should make one question
the diagnosis of ALD.
Leucocytosis (with neutrophilia) in the absence
of an infection may be present due to inflammation of the
Coagulopathy persisting despite replacement of
vitamin K is indicative of decreased hepatic synthetic
Prognosis. Patients with alcoholic hepatitis and
discriminant function (DF) >32 have a poor prognosis with a
predicted probability of mortality within 1 month of ~ 50%. DF = 4.6 (PT - normal PT) + total bilirubin (mg/dl).
A liver biopsy may be necessary if the diagnosis
is unclear or if there are atypical features. It aids in the
selection of patients being considered for steroid therapy as
up to 28% of patients with a clinical picture of alcoholic
hepatitis do not have histological features consistent with
alcoholic hepatitis on the biopsy.
Alcohol abstinence and supportive care are key
to the successful treatment of ALD. Liver enzyme abnormalities
persisting for 6 months after the cessation of alcohol intake
should prompt workup to rule out other causes of liver disease
including a liver biopsy.
Symptomatic patients should be hospitalized and
given thiamine 100 mg via IV fluids initially to prevent
Treat alcohol withdrawal
Patients with ALD are usually malnourished so
protein intake should not be restricted severely. At least 60
g of protein should be given daily.
Steroids. If an infectious process has been
ruled out, patients with severe alcoholic hepatitis (hepatic
encephalopathy or DF > 32 may benefit from corticosteroids.
Prednisolone 40 mg qd x 4 weeks followed by tapering over
several days to weeks should be used.
Patients with end-stage alcoholic liver disease should
be referred for liver transplantation especially if they have
been abstinent of alcohol for 6 months.
Liver Failure and Chronic Liver Disease
Fulminant hepatic failure (FHF).
FHF develops within 2 weeks and subfulminant
hepatic failure develops within 2-8 weeks of the onset of
jaundice. It occurs due to acute onset of massive
hepatocellular necrosis resulting in sudden and severe
impairment of liver function. Encephalopathy is usually
Causes include acetaminophen toxicitiy, viral
hepatitis, drug reaction, toxins (mushroom poisoning), ishemic hepatitis, Wilson’s disease,
autoimmune chronic active hepatitis, fatty liver of pregnancy
and Reye’s syndrome.
FHF needs intensive monitoring and emergent
evaluation for orthotopic liver transplant.
Cirrhosis of the liver is a diffuse process
characterized by the formation of islands of regenerated liver
surrounded by dense fibrosis (abnormal nodules) that occurs
after a protracted insult (such as alcohol, chronic active
Most complications of cirrhosis occur as a result of
development of portal hypertension or decreased synthetic
function of the liver.
Signs and symptoms of liver failure.
FHF. One of the earliest signs of FHF is a
change is personality. Uncooperative and violent behavior is
not uncommon. Jaundice does not correlate with
neuropsychiatric changes in the early stages and is deep in
the late stage. Fetor hepaticus, flapping tremor and
hyperreflexia may be present. Spontaneous bleeding from
mucosal surfaces may occur due to coagulopathy. In later
stages, decerebrate rigidity with spasticity can be noted. In
contrast to chronic liver disease, the liver is non-nodular
and splenomegaly and vascular telan-giectasias are not
Chronic liver disease (CLD). Weight loss,
malnutrition, fatigue, easy bruising (caused by reduced levels
of factors II, VII, IX, and X), jaundice, pruritus, edema,
ascites and encephalopathy with asterixis. The patient may
also have GI bleeding from esophageal varices (caused by
portal hypertension) or coma. GI bleeding is a common
precipitant of hepatic encephalopathy and coma in liver
failure patients because of the large gastrointestinal protein
Laboratory Evaluation and Monitoring.
FHF. Obtain routine biochemical profile and
complete liver panel. Serum albumin is usually normal
initially. Hypoglycemia is found in a large percentage of
patients with FHF. Lactic acidosis develops in approximately
half the patients with grade 3 coma. Hyponatremia and
hypokalemia are found especially in the later stages. Coagulopathy
develops due to decreased hepatic synthesis of coagulation
factors. The prothrombin (PT) time is also a good prognostic
indicator. Cerebral edema can also lead to respiratory
depression and respiratory acidosis. Hence, neurologic
status and PT/INR should be followed closely in
patients with FHF.
CLD. Laboratory evaluation may show normal liver
enzymes in end-stage disease because of the small amount of
residual hepatic tissue. These patients will usually have low
serum albumin. Anemia and thrombocytopenia may also be
present. Blood ammonia levels may be elevated. Electrolyte
abnormalities include hyponatremia, hypokalemia, and free
water overload. There may also be concomitant acidosis or
For patients in FHF, a referral to a specialist should
be obtained promptly.
Since cerebral edema is an important cause of death in
patients with fulminant hepatic failure, intracranial pressure
(ICP) monitoring is used in specialized units.
Hypoglycemia is corrected with 50% glucose. If patient
is to be moved to an another medical center, patient is
started on 20% glucose infusion during transport.
Coagulopathy is managed by parenteral vitamin K 5-10 mg
SQ QD x 2-3 days and by transfusion with blood, platelets, and
fresh frozen plasma.
Hepatic encephalopathy is treated as described below.
Hypokalemia and other electrolyte abnormalities are
corrected with appropriate replacement.
Infections are sought after early and the patient
should be pancultured.
Charcoal hemoperfusion for removal of toxic metabolites
is also being tried in some centers.
A nonselective beta-blocker, such as propanolol or
nadolol, reduces the risk of initial bleeding from esophageal
varices. Propanolol can be started at a dose of 10 mg BID and
titrated (to 60 mg QD) to effect a 25% reduction in the
base-line heart rate. Nonselective beta-blockers are also the
treatment of choice for bleeding from portal hypertensive
gastropathy. Isosorbide may have an additive effect to the
beta-blocker. New studies show that endoscopic band ligation
of esophageal varices is more effective than propanolol for
the primary prevention of variceal bleeding. Endoscopic
ligation can be repeated every 4-6 weeks until the esophageal
varices have all been obliterated.
Management of other complication of chronic liver
disease is as described below under individual sections.