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TOPIC HIGHLIGHT
Maziyar Amini, Bruce A Runyon, Department of Gastroenter- nificant risk with equivocal benefit, and that pentoxifyl-
ology and Hepatology, Loma Linda University Medical Center, line is a better, safer and cheaper alternative. While the
Loma Linda, CA 92354, United States full details of nutritional support lie beyond the scope
Author contributions: Amini M and Runyon BA contributed of this article, nutrition is a cornerstone of therapy and
equally to this paper.
must be addressed in every patient diagnosed with AH.
Correspondence to: Bruce A Runyon, MD, Director of Hepa-
Finally, while traditional psychosocial techniques play
tology, Department of Gastroenterology and Hepatology, Loma
Linda University Medical Center, 11234 Anderson Street, #1556, a major role in post-hospitalization care of alcoholics,
Loma Linda, CA 92354, United States. brunyon@llu.edu we hope to make the medical clinician realize his or her
Telephone: +1-909-5584905 Fax: +1-909-5580274 role in reducing recidivism rates with early and frequent
Received: May 19, 2010 Revised: August 11, 2010 outpatient visits and with the use of baclofen to reduce
Accepted: August 18, 2010 alcohol craving.
Published online: October 21, 2010
© 2010 Baishideng. All rights reserved.
VOLUME OF ALCOHOL REQUIRED Table 1 Questions to ask patients with suspected alcoholic
hepatitis
Observational studies have shown an increased risk of cir-
rhosis with ingestion of greater than 10-20 g of alcohol When did you first start to drink alcohol?
per day in women and more than 20-40 g/d in men[3]. In How many days per week do you usually drink?
addition to total duration of alcohol intake, a variety of ge- How many years have you been drinking on a regular or daily basis?
How many times have you been arrested for driving under the
netic, environmental and gender-related factors appear to influence of alcohol?
independently influence the development of alcoholic liver How many times have you been arrested for public intoxication?
disease. Age, female gender, and excess body weight [body What type of alcohol do you usually drink? Beer? Wine? Hard liquor?
mass index (BMI) > 27 kg/m2 in men, BMI > 25 kg/m2 How many drinks of each type of alcohol do you drink on an average
in women] have been identified as independent risk fac- day?
Do you usually drink at home? Bars?
tors for development of liver disease including AH[3-6]. In Have you been through an alcohol rehabilitation program? What type-
addition to a smaller volume of distribution, women are inpatient or outpatient? How many times?
at higher risk due to a relative deficiency of gastric alco- Have there been prolonged times when you drank no alcohol?
hol dehydrogenase compared to men[7]. An oral dose of When was your last drink?
Laboratory data liver may be nearly invisible on a liver spleen scan and the
Laboratory findings in AH are often nonspecific, but can bone marrow may be so visible that one can count ribs
on occasion provide clues to the diagnosis. These include easily.
mild to moderately elevated transaminases, usually with an
aspartate aminotransferase (AST) to alanine aminotransfer- Liver biopsy
ase (ALT) ratio above 1.5 with AST greater than 45 U/L Liver biopsy is rarely needed outside of research protocols
but usually < 300 U/L[10,14]. However, an unusual variant or perhaps when the patient and family fabricate a story
of AH, known as alcoholic foamy degeneration, can lead of total alcohol abstinence when AH is clinically obvious.
to an AST as high as 730 U/L[15]. A serum bilirubin > This conspiracy is common when the patient is pursuing
2 mg/dL is often required to make a diagnosis, but clini- liver transplantation. A histologic diagnosis of AH rules
cal jaundice is usually present and the bilirubin is regularly out the possibility of liver transplantation, at least in the
greater than 10 mg/dL. Other nonspecific but established Unites States. Because of the high risk of recidivism,
markers of alcohol intake include gamma-glutamyltrans- organs can not be allocated to patients with a diagnosis
ferase activity (GGT) and erythrocyte mean corpuscular of AH. Only patients who survive AH and continue to
volume[14]. As the severity of alcohol-related liver injury have liver failure after 6 mo of observed and documented
increases, the bilirubin can increase with a concomitant abstinence can be listed for transplant. Patients usually im-
decrease in GGT[16]. Also, it has been our experience that prove so dramatically with several months of abstinence
total blood cholesterol levels < 100 mg/dL can predict that a transplant is not needed.
poor outcome; the lower the cholesterol, the worse the The rare biopsy is usually performed transjugularly
prognosis. Finally, a mild to very elevated leukocytosis (up because of ascites and/or coagulopathy. The most com-
to 40 000/mm3) is very characteristic of AH. While less mon characteristic finding on pathology is macrovesicular
common, reports of severe leukemoid reactions are readily steatosis which can also be seen in nonalcoholic fatty liver
found with documented peripheral white blood cell counts disease[22]. Intrahepatic cholestasis can also be seen and
> 130 000/mm3[17-20]. In general, a severe leukemoid reac- requires the clinician to rule out mechanical obstruction
tion in AH portents a very poor prognosis[17,19]. of the bile ducts, and evaluate the patient for other causes
Clinicians can be led astray by the presence of both of cholestasis such as drug toxicity or viral hepatitis. Mal-
fever and prominent leukocytosis, leading to concern for lory bodies can be seen in up to 65% of patients with AH
sepsis and overshadowing the possibility of AH, particu- but can also be found in other causes of hepatocyte injury
larly if the patient’s history is unclear or unattainable due to and has been described as indicative but not pathogno-
altered mental status. As these patients may be profoundly monic of AH[2]. Giant mitochondria, and in particular
nutrient deficient and commonly have comorbidities such Type Ⅰ megamitochondria, can also provide a diagnostic
as cirrhosis, they are generally at increased risk of infection clue for AH and correlate with the presence and amount
and therefore an evaluation for bacterial infection should of daily alcohol consumption[23,24]. Ultimately however, bi-
be performed[11]. This evaluation should, at a minimum, opsy must be correlated with the patient’s history and will
include a chest X-ray, blood cultures, abdominal para- rarely provide all the diagnostic information needed in the
centesis (ascites is frequently present), and urinalysis with absence of other details.
urine culture. More specific testing should be pursued for Some inexperienced clinicians may assume that such
localizing clinical signs of infection such as excessive spu- a biopsy could represent nonalcoholic steatohepatitis
tum production or diarrhea. However, the clinician must (NASH). However, patients with NASH do not present
also remember that profound leukocytosis can be seen with deep jaundice, ascites, coagulopathy, etc. NASH is a
without a concomitant infection, and extensive evaluation much less inflammatory condition. In fact, patients with
and prolonged use of broad spectrum antibiotics can lead NASH do not develop jaundice until their advanced cir-
to loss of time and resources, but more importantly, can
rhosis is near terminal.
carry specific risks (superinfection with resistant bacteria
or fungi) and delay appropriate therapy[17-19].
CLINICAL ASSESSMENT AND
Liver scanning
In rare instances in which diagnosis is still unclear despite
TREATMENT
a thorough history, physical examination and laboratory Once a diagnosis is made, treatment should be initiated
evaluation, a technetium sulfur colloid liver spleen scan that addresses all aspects of the disease, including alcohol
can confirm the diagnosis of AH noninvasively[21]. This is cessation, correction of nutritional deficiencies and initia-
perhaps the last remaining indication for this very old im- tion of pharmacologic therapy when needed. In fact, a
aging modality. However the single photon updated ver- 3-pronged approach can help clinicians formulate a plan
sion, otherwise known as the perfused hepatic mass, may to guide therapy from the time of presentation through
have utility in assessing prognosis in parenchymal liver hospitalization and following into the outpatient setting to
disease. help reduce recidivism and prevent recurrence.
The dramatic “colloid shift” to the bone marrow and
spleen seen in the older version of this scan is character- Nutrition
istic of severe AH and is unusual in other diagnoses. The The first consideration for the hospitalized patient, after
evaluation and treatment for any signs of alcohol with- occurs. Patients with severe AH are very intolerant of
drawal, should be nutrition and electrolyte repletion, hypotension and seldom survive shock superimposed on
because AH induces a profound catabolic state. In part AH.
because of malnutrition, AH carries a considerably high
mortality rate, therefore nutrition remains a key aspect of Pharmacologic therapy
therapy. Nutrition should be provided orally if the patient Deciding upon appropriate pharmacologic management
is able to eat or via nasojejunal feeding if nausea, vomit- of patients with AH relies heavily upon assessment of the
ing or poor appetite prevent adequate intake of calories. severity of disease. Mild forms of AH may improve with
Calorie counting is essential to assure adequate intake as abstinence and conservative management, while more
patients require a higher than average caloric intake (ap- severe disease is associated with significant mortality and
proximately 1.2-1.4 times the normal resting intake)[25]. should be treated more aggressively[27]. The Maddrey dis-
Furthermore, nighttime supplementation of nutrition criminant function (DF) [4.6 × (prothrombin time (PT)
(approximately 700 kcal/d) may prevent muscle wasting in seconds - control PT) + serum bilirubin (mg/dL)] was
and improve lean muscle mass and should be considered first introduced in 1978 in order to aid in the assessment
in hospital and beyond if the patient has any evidence of of disease and guide therapy, which at that time relied
cirrhosis[26]. Furthermore, patients with longstanding al- mostly upon corticosteroid use[28]. A cutoff value of 32
cohol abuse usually require liberal multivitamin, folic acid was used to identify patients with a mortality rate above
and thiamine supplementation. Many of these patients 50% without pharmacologic therapy. The shortcomings
are profoundly depleted of potassium due to high aldo- of the DF were outlined by Dunn et al[10], the most no-
sterone levels and lack of intake of solid food for weeks table of which are the lack of standardized PT measure-
to months. Many have been living on a total liquid alcohol ment techniques and values across different laboratories,
diet. Serum potassium levels do not accurately reflect intra- and more importantly a relatively high risk of mortality
cellular levels. It may take many days of potassium reple- (up to 17%) with DF values under 32. The model for
tion to finally achieve normokalemia. As these nutritional end-stage liver disease (MELD) has been evaluated and
considerations are being addressed, the next step for the compared with DF in predicting mortality and has helped
clinician is deciding upon whether pharmacologic therapy guide initiation of pharmacologic therapy[10,29,30]. A MELD
and anticipating potential complications of AH. score of 11 has equal sensitivity but higher specificity
then DF in predicting 30-d mortality[29]. A MELD score
Ascites of 20 or higher at the time of admission has the highest
Patients with pure severe AH in the absence of cirrhosis sensitivity and specificity for predicting in-hospital mortal-
have relatively little problem with ascites. They eat so little ity and outperformed both DF and Child-Pugh-Turcotte
that they do not take in enough sodium to retain much (CPT)[30]. We propose using a MELD score ≥ 20 or a DF
fluid. Maintenance intravenous fluids should be avoided to of 32 or higher to prompt initiation of pharmacologic
minimize fluid retention. When cirrhosis is also present, therapy (Figure 1).
they may have more problematic fluid retention. In this There may be a component of malabsorption of vi-
case, if blood urea nitrogen and creatinine are normal, spi- tamin K due to jaundice in addition to poor synthesis of
ronolactone can be given. This drug will increase urinary coagulation components by the diseased liver. The Inter-
excretion of sodium and water, increase serum potassium, national Normalized Ratio regularly decreases after 3 daily
and decrease the need for potassium supplementation. doses of 10 mg of vitamin K intravenously or subcutane-
Once serum potassium is normal without supplementa- ously. Oral dosing of vitamin K is not appropriate be-
tion, oral furosemide can be added, if needed. If azotemia cause of poor absorption in the setting of deep jaundice.
occurs, diuretics should be stopped and the patient should After diagnosing and assessing the severity of AH, the
be evaluated for hepatorenal syndrome. The first step is decision of which pharmacologic therapy to initiate has
to give 1 g of 25% albumin/kg body weight (100 g maxi- become a major point of debate among experts, but re-
mum) intravenously daily for 2 d and to monitor creati- cent publications may help narrow the choices down con-
nine. If creatinine improves with albumin, the azotemia is siderably. A few small trials had suggested that glucocorti-
probably diuretic-induced. If creatinine continues to rise, coids can improve short-term survival in patients with the
hepatorenal syndrome is probably present, as this com- severe AH (DF ≥ 32)[31]. Since then, however, significant
monly occurs in severe AH (see below). work has challenged the efficacy of steroids and raised
concerns regarding side effects. The first of these was a
Variceal hemorrhage meta-analysis by Christensen et al[32] in 1995 which did not
Similar to the situation with ascites, the authors have ob- support the routine use of glucocorticosteroids in these
served that patients with pure severe AH in the absence patients. In addition, a 2008 Cochrane review of 15 ran-
of cirrhosis have relatively little problem with upper gut domized controlled trials with a total of 721 patients con-
hemorrhage. The relatively short duration of AH usu- cluded that glucocorticosteroids did not statistically reduce
ally does not lead to formation of varices that are large mortality compared with placebo or no intervention. Only
enough to bleed. However, patients with underlying when a subset of patients with DF ≥ 32 or with encepha-
cirrhosis can bleed from esophageal varices. Urgent en- lopathy were evaluated was a mortality benefit seen[33]. In
doscopy with banding of varices is warranted when this addition to the limited efficacy found by these analyses,
stands to have a predictably poorer outcome than his Table 3 International ascites club criteria for hepatorenal
counterpart without cirrhosis. More important than the syndrome
[37]
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