Chapter 6 Alcoholic liver disease
1 Alcoholic liver disease is one of the most prevalent forms of liver disease in the United States; worldwide, numerous epidemiologic studies have documented the correlation between per capita alcohol consumption and deaths from cirrhosis.
2 The risk of hepatotoxicity increases if a threshold level of alcohol consumption is exceeded, but even consistently high consumption infrequently causes cirrhosis. Variables affecting the development of cirrhosis include genetic polymorphisms of alcohol-metabolizing enzymes, gender differences, nutritional status, concomitant viral hepatitis, exposure to drugs or toxins, and immunologic factors.
3 Alcoholic liver disease encompasses a spectrum of histologic abnormalities: steatosis (fatty liver), steatohepatitis (alcoholic hepatitis), and cirrhosis (when fibrogenesis predominates). Steatosis and steatohepatitis are not necessarily progressive, and they may also develop in livers that are already cirrhotic.
4 Treatment of alcoholic liver disease includes discontinuation of alcohol consumption, treatment of extrahepatic complications of alcoholism (electrolyte abnormalities, withdrawal syndromes, cardiac dysfunction, poor nutrition, pancreatitis, gastropathy, infection), treatment of severe alcoholic hepatitis, and management of the sequelae of cirrhosis (ascites, portal hypertensive bleeding, and encephalopathy). Liver transplantation should be considered in the abstinent patient with decompensated cirrhosis.
1. Alcohol is used by three fourths of Americans; alcohol abuse and dependence are common: approximately 10% of Americans who drink experience alcohol-related problems.
2. Alcoholic liver disease is one of the most serious medical consequences of long-term alcohol abuse and is the most common cause of cirrhosis in the Western world. In 2003, approximately 44% of deaths from cirrhosis in the United States were the result of alcoholic liver disease.
3. Alcohol abuse and dependence rates are higher for men (11%) than for women (4%) and are higher for nonblack than for black persons (nonblack men, 11%; nonblack women, 4%; black men, 8%; black women, 3%). Despite these differences, progression to cirrhosis occurs at a higher rate in the black population than in the nonblack population.
1. Alcohol dependence (three items required):
Recurrent use at times when alcohol use is physically hazardous (e.g., driving while intoxicated) or frequent intoxication or withdrawal symptoms despite major obligations at work, school, or home
Continued alcohol use despite knowledge of having persistent or recurrent social, psychological, or physical problems that are caused or exacerbated by alcohol use
Marked tolerance: need for markedly increased amounts of alcohol (at least a 50% increase) to achieve intoxication or desired effect or a markedly diminished effect with continued use of the same amount
d. Have you ever had a drink first thing in the morning (eye opener) to steady your nerves or get rid of a hangover?
1. In all societies studied, a positive correlation exists between average per capita consumption of alcohol and the frequency of cirrhosis.
2. The amount ingested and the duration of intake correlate with the incidence of alcohol-related liver disease.
3. Once a threshold level of consumption is exceeded (estimated to be 60 to 80 g/day for men and 20 g/day for women), the risk of hepatotoxicity increases dramatically.
4. Consistently high intake of alcohol uncommonly induces cirrhosis; less than 20% of men consuming more than two six-packs of beer per day for 10 years become cirrhotic.
5. Several advisory committees have recommended that alcohol consumption be limited no more than two drinks per day for healthy men and no more than one drink per day for healthy nonpregnant women.
1. Gender: Women experience more toxicity per dose than men, but this cannot be explained solely by differences in body composition or alcohol distribution. Gastric mucosal alcohol dehydrogenase activity is lower in women than in men; this may permit greater hepatic metabolism of ingested alcohol in women.
2. Genetic variability in alcohol-metabolizing enzymes: Polymorphisms of the alcohol dehydrogenase and aldehyde dehydrogenase enzymes seem to protect certain persons from ethanol toxicity. For example, Asians frequently inherit a “slow” aldehyde dehydrogenase isoenzyme, thereby increasing serum levels of acetaldehyde; this causes flushing, nausea, and dysphoria (disulfiram-like reaction) and may explain why habitual alcohol use and alcoholic liver disease are rare in Asians.
3. Nutrition: Ethanol interferes with intestinal absorption and storage of nutrients and reduces appetite for nonalcoholic sources of calories; this may result in deficiencies of protein, vitamins, and minerals.
4. Presence of infections with hepatotropic viruses and other chronic liver diseases: Acute and chronic hepatitis B or C accelerate the progression of alcoholic liver disease. Fatty liver disease related to obesity and/or insulin resistance (i.e., nonalcoholic fatty liver disease) can also coexist with alcoholic liver disease, and the two may combine to cause more serious liver damage than would occur if either disease was present alone.
5. Concurrent exposure to drugs or toxins: Long-term consumption of alcohol induces the activity of microsomal enzymes and thus potentiates the metabolism of drugs, solvents, and xenobiotics. For example, therapeutic doses of acetaminophen can cause severe hepatic damage in alcoholic individuals; similarly, tolbutamide, isoniazid, and industrial solvents accelerate alcoholic liver disease.
6. Immunologic derangements: Alcoholic liver disease is modulated by alterations in the cellular immune system; these include increased reactivity of T and B cells and increased expression of major histocompatibility complex (MHC) class I and class II DR antigens. Increased levels of the immune modulatory cytokines tumor necrosis factor (TNF), interleukin-1, and interleukin-6 are also seen. Alterations of the humoral immune system include increased levels of circulating immunoglobulins, the presence of autoantibodies (against nuclear, smooth muscle, liver cell membrane, liver-specific proteins, and alcoholic hyaline antigens), and the development of antibodies against neoantigens, proteins altered by reaction to acetaldehyde, malondialdehyde, and various radicals.
1. A history of habitual alcohol consumption is useful in suggesting alcohol as the cause of liver disease.
2. The type of alcoholic beverage consumed does not influence the likelihood of developing hepatotoxicity. The amount of ethanol (in grams) consumed in spirits, wine, or beer can be estimated by multiplying the volume of the beverage in milliliters by the percentage of that beverage that is pure ethanol (spirits = 40%, wine = 12%, beer = 5%) times the specific gravity (0.8) of ethanol.
1. The clinical features of alcoholic liver disease are variable, ranging from a complete absence of symptoms to the florid features of advanced liver failure and portal hypertension. Because portal hypertension may occur in alcoholic hepatitis in the absence of established cirrhosis, alcoholic hepatitis can be difficult to distinguish from alcoholic cirrhosis without liver biopsy.
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