ALCOHOLISM/LIVER FUNCTION TESTS
| ALCOHOLISM IN YOUR PRACTICE: DIAGNOSIS AND TREATMENT —Shannon Robinson, MD, Associate Clinical
Professor, Department of Psychiatry, University of California, San Diego, School of Medicine
|
| Prevalence: 90% of US population have had one drink; 60% current drinkers; >40% have had temporary problem due to
alcohol; 10% to 20% meet criteria for alcohol abuse at some point; 3% to 10% meet criteria for alcohol dependence at
some time; 95% of alcoholics appear normal; only 5% homeless
|
| Economic and social impact: $300 billion annually; 22 000 deaths and 2 million injuries annually; 15% to 25% of
health care budget; 90% of liver disease; 72% of pancreatitis; 41% of seizure disorders
|
| Definition of one drink: 10 g of alcohol; 12 oz of beer; 4-oz glass of wine; one shot (1.5 oz) of 80-proof alcohol; patient
may define one drink as large can of beer or large glass of wine or spirits; misconception about intoxication—1
drink per hour safe; true for 200-lb man, but not for smaller man and not for 200-lb woman or smaller woman
|
| Natural course of alcoholism: after problem with alcohol (eg, driving citation), person stops drinking (for days or
even years); tends to resume drinking, setting limits, eg, only on weekend or only 2 drinks; tends to start drinking more
and more, although some alcoholics spontaneously remit and stay sober for years; people involved in Alcoholics Anonymous
(AA) more likely to stay sober for longer periods
|
| Chronic disease model: viewing alcoholism as one would view diabetes or hypertension leads to more effective treatment;
each has genetic and behavioral components
|
 | Tolerance: needing to drink more for same effect; presence of withdrawal symptoms—recurrent hangovers; autonomic
instability (elevations in temperature; sweating; hypertension; tachycardia); nausea; emesis; seizures and delirium tremens
(rare)
|
| Consuming larger amounts over longer periods than intended
|
| Desire or inability to cut down or control drinking
|
| Much time spent obtaining and using alcohol or recovering from drinking
|
| Giving up or reducing important activities, eg, social, occupational, family
|
| Use of alcohol despite knowing problems exacerbated by use, eg, medical, psychiatric, social, legal problems
|
| Failure to fulfill major role obligations: eg, attending school, going to work, or going to work despite hangover and being
impaired
|
| Use in hazardous situations: driving while intoxicated or while performing positionally risky occupation (eg, painters,
construction workers)
|
| Legal problems: eg, driving penalties, public intoxication, fights
|
| Abuse vs dependence: abuse reserved for those who never fulfilled criteria for dependence
|
| Problem areas: personal relationships; school or work; accidents, eg, falling, cutting self during cooking while intoxicated;
arrests; medical and psychiatric health
|
| Medical comorbidities: heart disease main cause of death, followed by cancer, accidents, and suicide; hypertension
(common; >2 drinks per day may contribute; “heart healthy” endorsement may lead to excessive drinking); gastroesophageal
reflux disease (GERD); gastritis; ulcers; hepatitis
|
| Laboratory tests: inform patient when mild elevation of liver function test (LFT) results reported; γ-glutamyl-transferase
(GGT; often not routinely included in liver panel) more sensitive for alcohol damage than aspartate aminotransferase
(AST) and alanine aminotransferase (ALT); macrocytosis (common in alcoholics; mild elevation of mean corpuscular
volume [MCV] indicates drinking); 90% of combined elevated GGT and MCV due to alcohol
|
| Other medical comorbidities: peripheral neuropathy; myopathy; erectile dysfunction; tremor; ataxia; gout; seizures; restless
leg syndrome; not uncommon for alcoholics to have average of 3 to 8 medical conditions, 90% of which directly
related to alcohol consumption
|
| Psychiatric comorbidities: depression; anxiety; psychosis; cognitive disorders; insomnia; suicide; abstinence from
alcohol beneficial — after 4 wk in treatment program, number of patients meeting criteria for major depression or
anxiety disorder declines from 40% to 6%; merely prescribing selective serotonin reuptake inhibitors (SSRIs) may fail
to produce improvement; psychosis — occurs during intoxication and withdrawal
|
| Cognitive dysfunction and insomnia: take longer to resolve than other problems; may persist up to 6 mo after treatment;
work with patient on sleep hygiene techniques; reassure patient that time required for return to baseline
|
| Psychiatric disorders: substance use disorder present in 47% of patients with schizophrenia, 56% of those with bipolar
disorder, and ≈25% of those with major depression or anxiety disorder
|
| Identification of problem: patient may ask for help; more likely to present with medical comorbidities (eg, hypertension;
GERD; gout; elevated vital signs and LFTs); talking to patient about problem—data show two 15-min discussions
in primary care setting can lead to significant decreases in drinking or to abstinence (true in office and emergency
settings)
|
| Detoxification: symptoms appear ≈8 hr after last drink, peaking on day 2 to 3
|
| Who needs medication: determine how much patient drinking and whether withdrawal symptoms occurred after past
attempts to stop drinking; patients drinking in morning because of tremor need medication, as do those consuming 1
bottle of wine daily, >1 6-pack of beer, or >6 shots
|
| Managing medications: use long-acting benzodiazepine (eg, chlordiazepoxide [Librium], diazepam [Valium]); if short-
acting agents (eg, lorazepam [Ativan]) used to control symptoms when tapering long-acting agents, withdrawal
symptoms likely to occur between doses toward end of taper; dosing—25 mg q6h for average functioning alcoholic
(eg, 1 L wine daily); patient consuming larger quantities may require ≥50 mg q6h; tell patient—if sedation occurs,
take q8h or take 25 mg at next dose; if withdrawal symptoms occur between doses, call physician (if at night, take
more medication and call in morning)
|
| After detoxification: problems persist; refer for further treatment
|
| Rehabilitation: therapists try to—increase motivation for abstinence; discuss how alcohol related to problems, eg, legal,
social, occupational; improve coping, recreational, and communication skills; relapse prevention— avoiding high-
risk situations; broadening social circle beyond drinkers; engaging in activities not requiring alcohol; using medications;
AA—peer-support group in community; participation essential (eg, talking to another participant before or after
meeting); sponsor needed to help patient pursue 12-step program; outcomes—depend on pretreatment functional level;
abstinence at 1 yr more likely in patients who remain married, still have job, home, and friends who do not always
drink; earlier intervention improves prognosis
|
| Medications: disulfiram (Antabuse)—not recommended; many medical contraindications and adverse drug interactions;
patient can stop medication to resume drinking; naltrexone—opiate antagonist; decreases time to first drink and
time to heavy drinking; side effects include nausea, headache, and some sedation, but generally well tolerated; contraindicated
in patients requiring opiates for pain; doses >100 mg associated with liver toxicity; acamprosate—N-
methyl-D-aspartate (NMDA) receptor modulator that affects glutamate and γ-aminobutyric acid (GABA) systems;
found effective in short- and long-term studies; available in Europe since 1989; expensive; not contraindicated with
opiates or cirrhosis; well tolerated
|
| Prescribing for alcoholics: be careful prescribing central nervous system depressants in patients with history of alcohol
dependence; potential problems include overdose, accidents, addiction, and increased alcohol consumption; try nonnarcotics
first; despite manufacturers’ claims, some drugs (eg, zolpidem [Ambien], zaleplon [Sonata], tramadol [Ultram])
potentially addictive CNS depressants that have additive effects with alcohol; caveat—no evidence that
naltrexone or acamprosate work for those not in psychosocial rehabilitation programs
|
| INTERPRETING LIVER FUNCTION TESTS —Paul Martin, MD, Professor of Medicine, Mount Sinai School of Medicine,
New York, NY
|
| Approach to patient: 35-yr-old man referred for evaluation of abnormal LFTs; told LFTs abnormal 12 mo earlier, so
unlikely to resolve spontaneously; “social alcohol user”; nonsmoker; denied intravenous (IV) drug use; no other problems
noted; no regular use of medications; herbal products—patients evade admitting use; may be cause of abnormal
LFTs; test results — AST higher than ALT (suggests alcoholic liver disease); bilirubin slightly elevated; platelet count
low (probably best LFT; suggests portal hypertension)
|
| Hepatitis B: once most commonly contracted (by patients born in United States) through sexual contact or illicit drug
use; now more common in immigrants infected at early age (infection at <5 yr of age likely to become chronic; infection
at >5 yr of age usually results in recovery); consequences—cirrhosis and primary liver cancer (develop over 20 to
30 yr; mortality risk ≤40% when infection occurs at early age); vaccine—led to dramatic decline in acute disease over
last ≈15 yr in those born in United States; rise in mortality—result of immigration from areas of high disease prevalence
(much of Asia and Latin America; Sub-Saharan Africa); estimated 40000 to 60000 legal immigrants with
chronic infection arrive each year
|
| Hepatitis B serologies: if hepatitis B surface antigen (HBsAg) positive, patient has hepatitis B; determine whether disease
acute or chronic by IgM anti-HB core (anti-HBc) antibody test; if negative, patient has chronic hepatitis B; order hepatitis
B e antigen (HbeAg) test and HBV DNA to determine whether patient candidate for antiviral therapy (ie, actively
replicating virus); treatment—alters natural history of disease; study shows therapy, eg, lamivudine, results in decreased
incidence of hepatocellular carcinoma (HCC) in 2.5 yr; institute therapy or consider referring patient
|
| Hepatitis C: ≈7 million individuals infected in United States; main indication for liver transplantation; prevalence higher
in IV drug users, alcohol abusers, and immigrants; study—of 283 immigrants from former Soviet Union who underwent
screening tests in New York, 28% infected, most during medical care; diagnostic tests—antibody (enzyme immunoassay)
sensitive and specific; molecular tests assess viral load and genotype (which do not predict severity of
liver disease); disease progression—≥20 yr from infection to cirrhosis, HCC, and need for liver transplant (indolent
disease); prognosis—improved by avoiding excessive alcohol; poorer in men, obese patients, and HIV or hepatitis B
coinfection
|
| Treatment: goals—eradicate virus; arrest progression of liver disease; improve quality of life; absence of virus ≥6 mo
after conclusion of therapy indicates virus permanently cleared; regression of liver disease possible; regimen—
pegylated interferon (once weekly) combined with ribavirin; response weaker in genotype 1; most patients tolerate
therapy well
|
| Diagnostic considerations: hepatitis A infection resolves after 6 mo; Wilson’s disease—exclude in patients ≤40 yr
of age; presents with liver disease, neurologic dysfunction (eg, tremor), hemolytic anemia, and psychiatric disturbance in
children; tests include urinary copper, serum ceruloplasmin, Kayser-Fleischer rings (not invariable), and liver biopsy (definitive);
lifelong therapy helps prevent HCC
|
| Autoimmune hepatitis: more common in women; may present as acute liver failure; associated with hypergammaglobulinemia,
positive autoantibodies, including antinuclear antibody (ANA) and anti-smooth-muscle antibody (SMA);
systemic complaints frequent, eg, prodrome of disturbed menses; responds rapidly to steroids; other forms include seronegative
variants and liver-kidney microsomal autoantibody (LKM1)
|
| Cholestatic liver disease: primary biliary cirrhosis (antimitochondrial antibody [AMA]; more common in women);
primary sclerosing cholangitis (more common in men; often with inflammatory bowel disease; cholangiography may be
normal and liver biopsy required to detect disease); ursodeoxycholic acid beneficial for both diseases
|
| Alcoholic liver disease: develops with daily consumption of ≤60 g for men, ≤20 g for women; 10 g equals 1 drink; risk
increased by binge drinking, drinking between meals, and perhaps alcohol type (less with wine); CAGE criteria— ever
needed to cut down on alcohol; ever felt angry at comment on alcohol use; ever felt guilty about drinking; ever needed
an eye-opener
|
| Nonalcoholic fatty liver disease: major form of outpatient liver disease (may be present in ≈25% of US population);
signs and symptoms identical to alcoholic liver disease; associated with diabetes, obesity, and hyperlipidemia; therapy—
weight loss; statin therapy; oral antidiabetic agents under investigation (onset of insulin resistance key event in pathogenesis)
|
| Hereditary hemochromatosis: most common recessive disorder in patients of northern European ancestry; genetic
test available (HFE gene; major mutation C282Y; 30% of whites heterozygous for mutation); normal life expectancy
with early iron depletion
|
| Wrap-up on patient: initial test results—HbsAg; anti-hepatitis C virus (HCV) positive; genotype 1; further
findings—citation for drunk driving indicated drinking more than admitted; used cocaine in past (assumed to be source
of HCV infection); liver biopsy found fibrosis (explains low platelet count); therapy—stop drinking; start interferon
therapy
|
Suggested Reading
Bischof G et al: Brief intervention for medical inpatients with unhealthy alcohol use. Ann Intern Med 147:589,
2007; Bronowicki JP et al: Effect of ribavirin in genotype 1 patients with hepatitis C responding to pegylated interferon
alfa-2a plus ribavirin. Gastroenterology 131:1040, 2006; Chapman M: Drugs and alcohol workplace
trends. Occup Health Saf 76:32, 34, 2007; Charlton M et al: Natural history and management of hepatitis C infection
after liver transplantation. Semin Liver Dis 24 Suppl 2:79, 2004; Charlton MR et al: Impact of obesity on
treatment of chronic hepatitis C. Hepatology 43:1177, 2006; Chevaliez S et al: Hepatitis C virus serologic and virologic
tests and clinical diagnosis of HCV-related liver disease. Int J Med Sci 3:35, 2006; Chu CM et al: Predictive
factors for reactivation of hepatitis B following hepatitis B e antigen seroconversion in chronic hepatitis B.
Gastroenterology 133:1458, 2007; Hartsell Z et al: Managing alcohol withdrawal in hospitalized patients. JAAPA
20:20, 2007; Huebner RB et al: The search for mechanisms of behavior change in evidence-based behavioral
treatments for alcohol use disorders: overview. Alcohol Clin Exp Res 31:1s, 2007; Liaw YF et al: Impact of acute
hepatitis C virus superinfection in patients with chronic hepatitis B virus infection. Gastroenterology 126:1024, 2004;
Prati D et al: Spectrum of NAFLD and diagnostic implications of the proposed new normal range for serum ALT
in obese women. Hepatology 42:1460, 2005; Pungpapong S et al: Natural history of hepatitis B virus infection: an
update for clinicians. Mayo Clin Proc 82:967, 2007; Reuben A: Alcohol and the liver. Curr Opin Gastroenterol
23:283, 2007; Shiffman ML et al: Chronic hepatitis C in patients with persistently normal alanine transaminase
levels. Clin Gastroenterol Hepatol 4:645, 2006; Skelly MM et al: Findings on liver biopsy to investigate abnormal
liver function tests in the absence of diagnostic serology. J Hepatol 35:195, 2001; Thomas DL et al: Natural history
of hepatitis C. Clin Liver Dis 9:383, 2005; Willenbring ML: Medications to treat alcohol dependence: adding
to the continuum of care. JAMA 298:1691, 2007; Yang HI et al: Hepatitis B e antigen and the risk of hepatocellular
carcinoma. N Engl J Med 347:168, 2002; Yeh MM et al: Pathology of nonalcoholic fatty liver disease. Am J Clin
Pathol 128:837, 2007; Zeuzem S et al: Review article: management of patients with chronic hepatitis C virus infection
and "normal" alanine aminotransferase activity. Aliment Pharmacol Ther 24:1133, 2006.
Educational Objectives
| The goal of this program is to improve the diagnosis and treatment of alcoholism and the interpretation of liver function
tests (LFTs). After hearing and assimilating this program, the clinician will be better able to:
|
| 1. Explain the natural history of alcoholism.
|
| 2. List the criteria for alcohol abuse and alcohol dependence.
|
| 3. Identify the stages of treatment of alcoholism.
|
| 4. Diagnose diseases detected with abnormal LFTs, including hepatitis B, C, and A, cholestatic liver disease, and
nonalcoholic fatty liver disease.
|
| 5. Treat liver diseases associated with abnormal LFTs.
|
Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and planning committee
members to disclose relevant financial relationships within the past 12 months that might create any personal conflicts
of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in
health care and not a proprietary business or commercial interest. For this program, the following has been disclosed:
Dr. Martin — Roche, Bristol-Myers Squibb Company, Gilead (speaker; consultant). Dr. Robinson and the planning
committee reported nothing to disclose.
Acknowledgements
Dr. Robinson was recorded at Topics and Advances in Internal Medicine, sponsored by the University of California,
San Diego, School of Medicine, February 27-28, 2007, in San Diego; Dr. Martin at 3rd Annual Challenges in Internal
Medicine, sponsored by the Mount Sinai School of Medicine, June 20-22, 2007, in New York, NY. The Audio-Digest
Foundation thanks the speakers and sponsors for their cooperation in the production of this program. Information about
upcoming meetings by these sponsors is available at http://cme.ucsd.edu and http://fusion.mssm.edu/cme.
|
