The Epidemiology of Alcoholic Liver Disease

Robert E. Mann, Ph.D., Reginald G. Smart, Ph.D., and Richard Govoni, Ph.D.

This article describes the various forms of alcoholic liver disease (ALD), with particular emphasis on cirrhosis, the form of liver disease that often is most associated with alcohol abuse and about which the most information is available. Epidemiological research has evaluated the prevalence of ALD and the factors that often contribute to the disease. Although the most potent factor in ALD is the excessive consumption of alcoholic beverages, gender and ethnic differences also account for some important variations in rates of liver disease. Mortality rates from cirrhosis have declined in the United States and some other countries since the 1970s. A number of factors may have contributed to this decline, including increased participation in treatment for alcohol problems and Alcoholics Anonymous membership, decreases in alcohol consumption, and changes in the consumption of certain types of alcoholic beverages. KEY WORDS: alcoholic liver cirrhosis; epidemiological indicators; gender differences; ethnic differences; AODR (alcohol and other drug related) mortality; morbidity; AOD (alcohol and other drug) use pattern; risk factors; trend; aggregate AOD consumption; beneficial vs adverse drug effect; Alcoholics Anonymous; United States; survey of research

ne of the most enduring insights Alcohol consumption increased into the effects of alcohol has substantially in many countries after ROBERT E. MANN, PH.D., is a senior Obeen the assertion that heavy World War II, which spurred greater scientist in the Department of Social, alcohol consumption increases mortality interest in the effects of alcohol con- Prevention and Health Policy Research rates, especially those from cirrhosis of sumption on cirrhosis and other forms at the Centre for Addiction and Mental the liver and other forms of liver disease of alcoholic liver disease (ALD). One Health and an associate professor in the (see the sidebar, p. 211). The scientific of the most influential efforts to sum- Department of Public Health Sciences study of alcohol-related mortality marize research in this area was under- at the University of Toronto, both in began in the 1920s with Pearl’s studies taken in 1975 by an international Toronto, Canada. (1926) of death rates among various group of scientists sponsored by the REGINALD G. SMART, PH.D., is a principal types of drinkers. He and others found World Health Organization (WHO). and senior scientist in the Department of that heavy drinkers had higher rates of The resulting book, Alcohol Control Social, Prevention and Health Policy overall mortality and of mortality from Policies in Public Health Perspective (Bruun et al. 1975), reviewed studies of clinical Research at the Centre for Addiction and cirrhosis than did lighter drinkers or and nonclinical populations of heavy Mental Health in Toronto, Canada. abstainers. Since then, mortality studies drinkers. All studies found that a greater have continued to demonstrate that proportion of heavy drinkers died of RICHARD GOVONI, PH.D., is a research heavy drinkers and alcoholics die from cirrhosis than would be expected based fellow in the Department of Public Health cirrhosis at a much higher rate than the on rates of cirrhosis deaths in the Sciences at the University of Toronto and general population (Mann et al. 1993; general population (i.e., liver cirrhosis an assistant professor in the Department Pell and D’Alonzo 1973; Schmidt and deaths among heavy drinkers ranged of Psychology at the University of Windsor de Lint 1972; Thun et al. 1997). In from 2 to 23 times higher than the in Windsor, Canada. addition, laboratory studies conducted rate that would be expected in the gen- in the 1930s established that feeding eral population). The preparation of this work was supported large amounts of alcohol to rats and This research established a firm in part by a fellowship to R. Govoni other animals caused liver disease connection between heavy alcohol con- from the Ontario Problem Gambling (Lelbach 1974). sumption and liver disease. Investigators Research Centre.

Vol. 27, No. 3, 2003 209 Ode to the Liver

measuring and transferring or its mortar wastes away, Modest, in your hidden the eyes of the rose are gone, organized alchemical the teeth of the carnation wilted friend, chamber. and the maiden silent in the river. underground Yellow Austere portion worker, is the matrix or the whole let me give you of your red hydraulic flow, of myself, the wing of my song, diver grandfather the thrust of the most perilous of the heart, of the air, depths of man, generator the soaring there forever hidden, of energy: of my ode: everlasting, I sing to you it is born in the factory, and I fear you of your invisible noiseless. as though you were judge, machinery, And every feeling meter, it flies or impulse implacable indicator, from your tireless grew in your machinery, and if I can not confined mill, received some drop surrender myself in shackles to austerity, delicate of your tireless if the surfeit of powerful elaboration, delicacies, entrail, to love you added or the hereditary wine of my country ever alive and dark. fire or melancholy, dared While let one tiny cell to disturb my health the heart resounds and attracts be in error or the equilibrium of my poetry, the music of the mandolin, or one fiber be worn from you, there, inside, in your labor dark monarch, you filter and the pilot flies into the wrong sky, giver of syrups and of poisons, and apportion, the tenor collapses in a wheeze, regulator of salts, you separate the astronomer loses a planet. from you I hope for justice: and divide, Up above, how I love life: Do not betray me! Work on! you multiply the bewitching eyes of the rose Do not arrest my song. and lubricate, and the lips you raise of the matinal carnation and gather sparkle! the threads and the grams How the maiden Pablo Neruda, 1904–1973 of life, the final in the river laughs! Nobel Laureate in Literature, 1971 distillate, And down below, Translation by Oriana Josseau Kalant the intimate essences. the filter and the balance, “Oda al Higado,” by Pablo Neruda, Submerged the delicate chemistry viscus, translated by Oriana Josseau of the liver, Kalant, as published in Alcohol measurer the storehouse Liver Pathology (J.M. Khana, of the blood, of the subtle changes: Y. Israel, and H. Kalant, editors) you live no one © 1975. Reprinted with permis­ full of hands sees or celebrates it, sion of the Centre for Addiction and full of eyes, but, when it ages and Mental Health, Toronto.

210 Alcohol Research & Health The Epidemiology of Alcoholic Liver Disease also have observed that the price of availability and includes recommenda­ Drinking Patterns and alcohol is a significant determinant tions to control cirrhosis and other Alcoholic Liver Disease of alcohol consumption and thus of alcohol-related problems through tax­ cirrhosis mortality rates (Bruun et al. ation (Chaloupka et al. 2002; Cook Many studies show that the amount 1975; Edwards et al. 1994; Seeley and Tauchen 1982). The validity of of alcohol consumed and the dura­ 1960). These findings have laid the this availability-control approach has tion of that consumption are closely foundation for an influential public been widely supported (e.g., Edwards associated with cirrhosis.1 One of the health approach to controlling liver et al. 1994), and investigations of the best demonstrations of this associa­ disease and other alcohol problems that epidemiology of ALD have continued tion was presented by Lelbach emphasizes the control of alcohol’s to be central to it (e.g., Ramstedt 2001). (1974), who studied 319 patients in Types of Alcoholic Liver Disease

The most prevalent types of alcoholic liver disease are changes; white nails; thickening and widening of the fatty liver, alcoholic hepatitis, and cirrhosis. Often, as fingers and nails (clubbing); liver enlargement or people continue to drink heavily, they progress from inflammation; and abnormal accumulation of fat fatty liver to hepatitis to cirrhosis. The disorders can in normal liver cells (fatty infiltration). Diagnosis of also occur together, however, and liver biopsies can show cirrhosis must be made with biopsies, although labo­ signs of all three in some people (Kirsh et al. 1995). ratory tests can be helpful as well. About 10 percent to 15 percent of people with alco­ Alcoholic Fatty Liver holism develop cirrhosis, but many survive it. Many are unaware that they have it, and about 30 percent to 40 percent About 20 percent of alcoholics and heavy drinkers of cirrhosis cases are discovered at autopsy (Anand 1999). develop fatty liver, or steatosis. In many cases there The 5-year survival rate for people with cirrhosis who stop are no clinical symptoms except for an enlarged liver drinking is about 90 percent, compared with 70 percent (hepatomegaly). Fatty liver can be reversed if alcohol of those who do not stop drinking. However, for late-stage consumption is stopped or significantly reduced, but cirrhosis—that is, when jaundice, accumulation of fluid the condition can lead to death if alcohol consump­ in the abdomen (ascites), or gastrointestinal bleeding have tion is not reduced or stopped. Some biopsies from occurred—the survival rate is only 60 percent for those people with fatty liver show inflammatory changes, who stop drinking and 35 percent for those who do not. an early sign of more serious liver disease. Other Forms of Liver Disease Affected by Alcohol Alcoholic Hepatitis Alcohol can be a factor in other forms of liver disease Alcoholic hepatitis usually is diagnosed when a liver not specifically attributed to it, and alcohol may interact biopsy indicates inflammatory changes, liver degener­ with risk factors for other forms of liver disease. For ation, fibrosis, and other changes to liver cells. Com­ example, people with alcohol-related cirrhosis are at mon clinical signs of alcoholic hepatitis include much higher risk for the development of liver cancer swollen liver, nausea, vomiting, and abdominal pain. (Hall 1995). Likewise, heavy drinking in combination Patients also may experience fever, jaundice, liver fail­ with hepatitis B or C substantially increases the risk of ure, and bleeding. The rate of mortality in severe liver cirrhosis, compared with the risk associated with cases is about 50 percent. If heavy drinking continues, heavy drinking alone (Corrao et al. 1998). about 40 percent of cases of alcoholic hepatitis will — Robert E. Mann, Reginald G. Smart, develop into cirrhosis. and Richard Govoni References Alcoholic Cirrhosis ANAND, B.S. Cirrhosis of the liver. Western Journal of Medicine 171: Cirrhosis of the liver is the most serious form of ALD 110–115, 1999. and a cause of many deaths and serious illnesses. In CORRAO, G.; ZAMBON, A.; TORCHIO, P.; ET AL. Attributable risk for symp­ cirrhosis, scar tissue replaces normal liver tissue, dis­ tomatic liver cirrhosis in Italy. Journal of Hepatology 28:608–614, 1998. rupting blood flow through the liver and preventing HALL, P. Pathological spectrum of alcoholic liver disease. In: Hall, P., it from working properly. Clinical signs of cirrhosis ed. Alcoholic Liver Disease: Pathobiology and Pathogenesis. 2d ed. include redness of the palms caused by capillary dila­ London: Edward Arnold, 1995. pp. 41–68. tion (palmar erythema); shortening of muscles in the KIRSH, R.; ROBSON, S.; AND TREY, C. Diagnosis and Management of fingers (contractures) caused by toxic effects or fibrous Liver Disease. London: Chapman and Hall, 1995.

Vol. 27, No. 3, 2003 211 an alcoholism clinic in Germany. He Cirrhosis Morbidity and nificance in the middle of the 20th calculated the average amount of alco­ Mortality and Average century, when several researchers began hol consumed per hour in a 24-hour Alcohol Consumption exploring cirrhosis as a potential day. As shown in table 1, patients marker for levels of alcohol problems in with normal liver function consumed The strong link between heavy or populations (Jellinek and Keller 1952; far less alcohol than did those with cirrhosis. Those who did not have excessive alcohol use and the develop­ Ledermann 1956; Seeley 1960; Terris cirrhosis but did have other liver mal­ ment of liver disease took on added sig­ 1967). Of particular importance was functions had intermediate rates of alcohol intake. In addition, patients Table 1 Liver Function and Alcohol Intake with normal liver function had been drinking heavily for only about 8 years Mean Daily Alcohol Average on average, whereas those with cirrhosis Intake (milligrams of Duration of had been drinking heavily for more No. of alcohol/kilograms of Alcohol Abuse than 17 years on average. As this research Liver Function Cases body weight) per Hour (years) illustrates, the risk of developing Normal liver function 70 90 7.7 cirrhosis is a function of both quantity and duration of alcohol consump­ Uncomplicated fatty liver 118 109 7.8 tion. Bellentani and Tiribelli (2001) Severe steatofibrosis with 48 127 10.3 recently proposed that cirrhosis does inflammatory reactions not develop below a lifetime alcohol Chronic alcoholic hepatitis 78 125 11.9 ingestion of 100 kg of undiluted alcohol. Cirrhosis 39 147 17.1 This amount corresponds to an average NOTES: Patients with normal liver function consumed far less alcohol and had been drinking for fewer years daily intake of 30 grams of alcohol than those with cirrhosis. Those who did not have cirrhosis but did have other liver malfunctions had intermedi­ 2 (between two and three drinks ) for 10 ate rates of alcohol intake. See sidebar, p. 211, for definitions of alcoholic liver disease. years. These investigators also noted SOURCE: Adapted from Lelbach 1974. that consuming alcohol with food resulted in somewhat lower levels of risk than consuming alcohol by itself. More recent studies confirm the close 16 association between alcohol consumption Coates et al. 1986 (w) Tuyns & Péquignot 1984 (w) and cirrhosis risk. Anderson (1995) exam­ 14 Coates et al. 1986 (m) ined data from four case control studies Tuyns & Péquignot 1984 (m) in men and women. (Figure 1 shows 12 results from representative studies [Coates et al. 1986, and Tuyns and Péquignot 10 1984].) This investigation showed that the risk of cirrhosis was related to the 8 amount of alcohol consumption in every study. In addition, as alcohol con­ 6 sumption increased, the risk of cirrhosis Relative Risk increased more rapidly for females than it did for males. The link between gen­ 4 der and risk for cirrhosis is addressed in detail in the section on page 215. 2

1In examining trends in alcoholic liver disease, some authors 0 have considered only those cases directly attributable to 0 10 20 30 40 50 60 70 alcohol (e.g., Douds et al. 2003). Other authors have deter­ mined that many cirrhosis deaths coded as not involving Alcohol Consumption (grams/day) alcohol are in fact alcohol related (particularly for some age groups, including the middle-aged); thus these authors have examined total cirrhosis deaths when evaluating trends (e.g., Figure 1 Alcohol consumption and incidence of cirrhosis of the liver in men (m) Ramstedt 2001). and women (w). Studies have shown a close relationship between alco­ 2The National Institute on Alcohol Abuse and Alcoholism hol consumption and cirrhosis risk. (NIAAA) defines a standard drink as 11–14 grams (g) of alcohol, which corresponds to approximately one shot of NOTE: Data truncated at 70 g/day. 80-proof alcohol (about 14 g alcohol), one glass of wine (11 g), or one 12-oz beer (12.8 g).

212 Alcohol Research & Health The Epidemiology of Alcoholic Liver Disease

the discovery of a relationship between fourth leading cause of death. In rela­ see the article by Schiff and Ozden in cirrhosis mortality rates and per capita tion to the cirrhosis mortality rate in this issue.) levels of alcohol consumption in the other countries, the United States is population. This relationship has proved in the middle range, as are countries to be remarkably strong and has been such as Belgium and Canada (WHO Reasons for Decreases in consistently observed across time peri­ 2000). Higher rates are seen in countries Cirrhosis Death Rates ods and in various regions of the world where people traditionally consume (Bruun et al. 1975; Ramstedt 2001; more alcohol than in the United States, Smart and Mann 1991). European such as Spain, France, and Italy. In Changes in Per Capita Alcohol researchers have observed a lagged rela­ countries where alcohol consumption Consumption tionship between cirrhosis mortality and is traditionally lower—Iceland, New Changes in per capita consumption of consumption measures, with the rate Zealand, and Norway, for example— of cirrhosis mortality in a year being alcohol must be considered a leading cirrhosis death rates are lower. candidate for the cause of recent reduc­ influenced by the alcohol consumption Cirrhosis mortality rates in the rates of several previous years (Corrao tions in cirrhosis mortality rates. Research United States have changed substantially demonstrates that, over a long period, 1998; Ramstedt 2001). To account for over time. Early in the 20th century, this effect, Skog (1980) developed a changes in per capita consumption are these rates were at their highest point. broadly consistent with changes in cir­ “distributed lag model,” in which the As shown in figure 2, overall cirrhosis effects of alcohol consumption in a year rhosis mortality rates (Ramstedt 2001; mortality rates declined precipitously Singh and Hoyert 2000; Xie et al. are distributed over the next several years. with the introduction of Prohibition. Using this model, he was able to explain 2000) (see figure 2). However, cirrhosis When Prohibition ended, alcohol mortality in the United States, Canada, an apparent inverse relationship between consumption and cirrhosis mortality consumption and cirrhosis mortality and some other regions began to decline rates increased until the late 1960s in the mid-1970s, before per capita rates in Great Britain between 1931 and and early 1970s, when these rates began 1958 (Popham 1970). Incorporating consumption rates began to go down to approach levels seen in the first (also see figure 2). This is the opposite the distributed lag model into the data decade of the century. However, in the produced the expected positive rela­ of what would be expected based on mid-1970s cirrhosis mortality rates the hypothesized lagged relationship tionship between consumption and began to decline as they had with the cirrhosis mortality. between per capita consumption and introduction of Prohibition; cirrhosis cirrhosis mortality rates. Thus, researchers was the 8th leading cause of death in are considering whether other factors Trends in Cirrhosis 1977 (Galambos 1985) but the 12th also have influenced cirrhosis mortality Mortality Rates leading cause of death by 2000. Similar rates in recent years. declines in cirrhosis mortality rates have been observed in many developed Liver cirrhosis is a major cause of Beverage-Specific Effects death in the United States (Yoon et al. countries (including Canada, Sweden, 2002; Minino et al. 2002). In 2000, it France, and Italy), but in other devel­ The relationship between cirrhosis was the 12th leading cause of death, oped countries (e.g., Great Britain, mortality and alcohol consumption may accounting for 1.1 percent of all deaths, Finland, Denmark) cirrhosis death vary depending on the type of alco­ with an age-adjusted death rate3 of rates have increased (Ramstedt 2001). holic beverage—beer, wine, or spirits— 9.6 per 100,000 population. Cirrhosis The reasons for the dramatic reduc­ consumed. Any such beverage-specific mortality rates vary substantially tions remain a source of considerable effects could help explain why cirrhosis among age groups: They are very low interest, as will be discussed below. mortality began to decline in the 1970s among the young but increase consid­ Cirrhosis mortality rates may con­ despite the continued rise in total alco­ erably in middle age, reaching a peak tinue to decline if alcohol consumption hol consumption. of 31.1 per 100,000 among people rates remain low or fall further. How­ Researchers over the past four ages 75 to 84. Because of the increase ever, the increase in cases of hepatitis decades have investigated this question in cirrhosis mortality rates in middle C infection in the United States, which (e.g., Terris 1967; Gruenewald and age, the contribution of cirrhosis to are predicted to peak by 2015 (Arm­ Ponicki 1995; Schmidt and Bronetto total deaths reaches a peak in the strong et al. 2000), may affect the rate 1962). Recently, Roizen and colleagues 45–54 age group, for which it is the of cirrhosis deaths. Because people (1999) and Kerr and colleagues (2000) infected with hepatitis C are more have proposed that cirrhosis mortality 3Age adjustment is a statistical method of adjusting for is more strongly associated with con­ age differences, between populations or over time, that likely to develop cirrhosis when they might otherwise distort mortality trends. In the case of drink, death rates from cirrhosis may sumption of spirits than with other chronic diseases, including cirrhosis of the liver, unadjusted increase in the future, even if drinking alcoholic beverages, and that this rela­ mortality rates may appear to be higher for older popula­ tions than for younger populations because mortality levels decline. (For more information tionship accounts for the apparent dis­ rates are higher, on average, in older people. on hepatitis C infection and alcohol, crepancy between per capita alcohol

Vol. 27, No. 3, 2003 213 consumption measures and cirrhosis sumption and cirrhosis mortality dur­ types of alcoholic beverage may be more mortality rates. Roizen and colleagues ing the 1970s, when cirrhosis mortality toxic to the liver than others (Lelbach (1999) examined U.S. cirrhosis mortal­ rates began to decline in the United 1974; Schmidt and Bronetto 1962). In ity data from 1949 to 1994 and States, suggests that the discrepancy addition, consumption of certain alco­ observed that consumption of spirits between cirrhosis rates and per capita holic beverages may be associated with was more strongly related to cirrhosis alcohol consumption observed at that different drinking styles (Smart mortality than was total alcohol con­ time arose because research did not 1996)—that is, people who tend to sumption, a finding that is consistent focus on spirits, the beverage most drink frequently and heavily, and thus with earlier observations of U.S. data strongly related to cirrhosis mortality. are at greatest risk for developing cir­ (Terris 1967). Kerr and colleagues The stronger association between rhosis, also may tend to drink spirits (2000) extended this analysis to several cirrhosis mortality and consumption of rather than beer or wine. Thus, drink­ other countries, with similar results. spirits may be attributable to biological ing style may collude with biological The relationship between spirits con­ and sociobehavioral mechanisms. Some mechanisms to significantly raise some

25 3.2 Both sexes

Males 3.0 Females 2.8 20 Alcohol consumption

2.6

2.4 15 2.2

2.0 10 1.8 Alcohol Gallons of Rate per 100,000 Population 1.6

5 1.4

1.2

0 0.0 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000 Year

Figure 2 Age-adjusted death rates of liver cirrhosis by gender, 1910–1932 in death registration States, and 1933–1977 in entire United States. U.S. cirrhosis mortality rates were high at the beginning of the 20th century, declined precipitously with the introduction of Prohibition, and increased again when Prohibition ended. Mortality rates continued to increase until the early to mid-1970s, when these rates began to approach the levels seen in the first decade of the century. In the mid-1970s cirrhosis mortality rates began to decline again, as they had with the introduction of Prohibition, and they have continued to decline. INSET (shaded area): Per capita alcohol consumption for the years 1935 to 1999, illustrating the link between alcohol consumption and cirrhosis mortality.

SOURCES: Mortality rate data adapted from Yoon et al. 2001; consumption data from Nephew et al. 2002.

214 Alcohol Research & Health The Epidemiology of Alcoholic Liver Disease

drinkers’ risk of liver disease. This pital discharges during the period differences in cirrhosis mortality risk interesting and important issue is the could be predicted, depending on the and mortality rates. As shown in fig­ subject of ongoing investigation. degree of overlap between treatment ure 2, cirrhosis mortality rates are and AA membership that was assumed. about two times higher in men than Increased Participation in Other studies of the relationship in women. These rates reflect the fact Treatment and Alcoholics between cirrhosis mortality rates and that men typically drink more than Anonymous Programs aggregate, or population, levels of women, and that the proportion of treatment and AA membership rates heavy drinkers and alcoholics is much Another possible reason for declines support the hypothesis that increases higher among men. However, as noted in cirrhosis mortality has been increased in treatment and AA membership previously, it also appears that at any participation in treatment for alcohol helped reduce cirrhosis mortality rates, given level of alcohol consumption, abuse and in Alcoholics Anonymous both in the United States and elsewhere. women have a higher likelihood of meetings (Mann et al. 1988a, b; Holder Several studies (for a review, see Smart developing cirrhosis than men (see and Parker 1992; Romelsjö 1987; and Mann 2000) have found an asso­ figure 1) (Tuyns and Péquignot 1984). Smart and Mann 2000). Specifically, ciation between reductions in cirrhosis This phenomenon is poorly understood, cirrhosis morbidity and mortality rates morbidity and mortality and increased but several possible explanations have could be influenced if participation levels of treatment and AA member­ been offered. One is that levels of in alcoholism treatment and AA are ship in Canada (Mann et al. 1988b), alcohol dehydrogenase, an enzyme in some degree effective in reducing the United States (Mann et al. 1991), involved in breaking down alcohol, excessive drinking among heavy or and Sweden (Leifman and Romelsjö may be lower in the stomachs of abusive drinkers, if sufficient treatment 1997; Romelsjö 1987). Examining females than in males, which would occurs, and if enough alcoholics become monthly cirrhosis mortality data from result in a higher blood alcohol con­ members of AA or receive other treat­ North Carolina, Holder and Parker tent for females than for males who ment services. The 1970s and 1980s (1992) found that alcohol abuse treat­ consume equivalent amounts of alcohol saw large increases in AA participation ment had a significant short-term lagged (Frezza et al. 1990). Because damage and in the number of people who relationship with cirrhosis mortality, to the liver is a function of blood received alcoholism treatment services with an increase in treatment being alcohol levels and exposure time, fac­ (Mann et al. 1988b, 1991). Smart and followed 3 months later by a decline tors that lead to higher blood alcohol Mann (1993) examined whether these in cirrhosis mortality. Finally, Smart concentrations could at least partially increases in treatment and AA partici­ and colleagues (1996) found that explain females’ higher risk for alcohol- pation could affect cirrhosis morbid­ increased funding for alcoholism related cirrhosis. Another possible ity and mortality rates. According to treatment was associated with cirrhosis explanation is that estrogen may estimates derived from the research: mortality reductions across the United increase the susceptibility of the liver States. Thus, the data so far provide to alcohol-related damage (Ikejima • Alcoholics seeking treatment drink strong support for the proposition et al. 1998; Colantoni et al. 2003). an average of 160 g of undiluted that if a large enough portion of the Behavioral factors, including drinking alcohol per day. population participates, AA member­ patterns and diet, also may contribute ship and alcohol abuse treatment can to females’ higher cirrhosis risk. •About 14 percent of alcoholics will influence cirrhosis morbidity and Genetic factors, including those develop cirrhosis if they drink this mortality rates at the population level. that influence alcohol metabolism and quantity for a period of 8 years. risk for alcoholism, also may be involved in the increased risk for cirrhosis seen •About 50 percent of alcoholics Other Factors Associated in women (Reed et al. 1996), but receiving treatment or attending With Increased Rates of there still is considerable debate on AA meetings improve sufficiently Cirrhosis Morbidity and this issue, and further research is to postpone the development of Mortality needed on the nature and the extent cirrhosis or avoid death if they of such genetic contributions. already have cirrhosis. In a recent study, Corrao and col­ Gender Differences leagues (1998) found that 98.1 percent The authors applied these figures of cirrhosis cases in men but only to the actual number of people who As discussed above, historically the 67.0 percent of cases in women could were AA members or were receiving epidemiology of cirrhosis has been be attributed to alcohol consumption, alcohol abuse treatment in 1975 and linked closely to types and patterns hepatitis C, and hepatitis B. The risk 1986 in Ontario and the United States. of alcohol consumption. Other factors factors for cirrhosis appear to be more Based on this analysis, between 25 also may be at work in the development complex for women than they are for percent and 100 percent of the actual of liver disease. For example, there are men, and more research will be required reduction in cirrhosis deaths and hos­ important and long-standing gender to identify and understand them.

Vol. 27, No. 3, 2003 215 Ethnic Differences pretation. For example, in recent years, prevalent among Hispanics than in alcohol consumption among Blacks Black and White populations (Yen et Important differences in cirrhosis rates has been less than or comparable with al. 2003). Ethnic group differences in and cirrhosis mortality also exist among that of Whites (see table 2). cirrhosis risk and mortality may be ethnic groups. Although ethnic group Several reasons for ethnic group linked to the possibility that, over time, differences have been declining in recent differences in cirrhosis rates have been general health status has improved years, cirrhosis rates remain higher for proposed, including demographic more for some ethnic groups than Blacks than for Whites in the United factors related to gender, age, income, others. However, as summarized in States (see figure 3), and the highest education, and employment; biological table 3, two general health indicators— cirrhosis mortality rates currently are factors, such as family history of age-adjusted death rate and life observed among Hispanic groups drinking problems; and environmen­ expectancy at birth—showed compa­ (Stinson et al. 2001). Although these tal factors, such as stress (for a review, rable gains for Blacks and Whites differences in cirrhosis rates among see Jones-Webb 1998). Other suggested between 1970 and 2000. Thus, it is Blacks, Whites, and Hispanics seem to factors are differential access to alco­ not yet possible to attribute changes suggest higher alcohol consumption holism treatment services (Singh and in cirrhosis rates to changes in general levels among Hispanics and Blacks Hoyert 2000), although as yet no data health indicators of various groups. than among Whites, studies of alco­ are available to support this explana­ As this discussion indicates, cirrhosis hol consumption patterns in these tion; and differing rates of hepatitis C rates in subpopulations, such as those groups tend not to support this inter­ infection, which appears to be more based on gender or ethnicity, can show

20 Wht. Hisp. males White females Wht. Hisp. females White males Wht. non-Hisp. males Wht. non-Hisp. females Black females Blk. Hisp. males Black males Blk. Hisp. females 16 Blk. non-Hisp. males Blk. non-Hisp. females

Hispanic origin detail shown at right

12

8 Rate per 100,000 Population

4

0 1970 1972 1974 1976 1978 1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 1991 1992 1993 1994 1995 1996 1997 1998 Year Year

Figure 3 Age-adjusted rates of alcohol-related cirrhosis by gender and ethnic group (Black, White, and Hispanic), United States, 1970–1998.

SOURCE: Yoon et al. 2001. (Categories shown in this figure were those used in the source study.)

216 Alcohol Research & Health The Epidemiology of Alcoholic Liver Disease

significant deviations from the rates Table 2 Consumption Patterns for Blacks and Whites, 1984 and 1992 of cirrhosis that would be expected from alcohol consumption levels 1984 1992 alone. These differences, which are not yet well understood, have impor­ Consumption Level Blacks (%) Whites (%) Blacks (%) Whites (%) tant implications for research and prevention initiatives. From a public Males health perspective, an understanding of subpopulation dynamics is critical Abstainer 29 23 35 28 to the development of programs for preventing alcoholic liver disease. Infrequent 13 13 6 9

Less frequent 12 16 19 21 Conclusion Frequent 30 27 25 29 Alcoholic liver disease is a major Frequent heavy 16 19 15 12 source of alcohol-related morbidity Females and mortality. Heavy drinkers and alcoholics may progress from fatty Abstainer 46 31 51 36 liver to alcoholic hepatitis to cirrhosis, and it is estimated that 10 percent to Infrequent 18 23 24 22 15 percent of alcoholics will develop Less frequent 19 19 12 24 cirrhosis. The likelihood of developing ALD is, to a large extent, a function Frequent 13 23 8 15 of both the duration and amount of Frequent heavy 4 4 5 3 heavy drinking, and the per capita consumption of alcohol within popu­

NOTES: In recent years, alcohol consumption among Blacks has been comparable to or less than that of lations has been shown to be a strong Whites. determinant of cirrhosis mortality Some columns do not total 100 percent because of rounding. rates. Recent studies also suggest that SOURCE: Adapted from Jones-Webb 1998. alcohol and hepatitis C may exert a multiplicative effect on risk for cirrho­ sis and other liver disease. Table 3 General Health Indicators for U.S. Blacks and Whites, 1970 and 2000 Although ALD remains a major cause of death, important declines in Black White Black White ALD death rates have been observed Males Males Females Females in recent years. Undoubtedly these declines were caused in part by changes Age-Adjusted Death Rate in alcohol consumption rates, but per 100,000 Population* because the mortality rate decline began when consumption was still 1970 1,873.9 1,513.7 1,228.7 1,193.3 increasing, other factors appear to be 2000 1,377.8 1,018.2 947.9 739.1 involved as well. To date, the evidence indicates that increases in participation Percent change –26.5 –32.7 –22.9 –30.1 in AA and other treatment for alcohol abuse have played an important role Life Expectancy (years) in reducing cirrhosis mortality rates. 1970 60.0 68.0 68.3 75.6 Other research has suggested that cir­ rhosis mortality rates may be more 2000 68.2 74.8 74.9 80.0 closely related to consumption of certain alcoholic beverages—specifi- Percent change +13.7 +10.0 +9.7 +5.8 cally spirits—than to total alcohol consumption, and that beverage-specific *Standardized to 2000 age distribution. effects can account for the fact that NOTE: Between 1970 and 2000, Blacks and Whites showed comparable gains in age-adjusted death rate and life expectancy at birth. cirrhosis rates appeared to decrease SOURCE: Minino et al. 2002. although consumption rates were increasing in the 1970s. Important

Vol. 27, No. 3, 2003 217 differences in ALD rates in men and FREZZA, M.; DI PADOVA, C.; POZZATO, G.; ET AL. MANN, R.E.; ANGLIN, L.; WILKINS, K.; ET AL. women and among different ethnic High blood alcohol levels in women: The role of Mortality in a sample of convicted drinking groups have been found as well. decreased gastric alcohol dehydrogenase activity and drivers. Addiction 88:643–647, 1993. first-pass metabolism. New England Journal of Medicine Further research into these differences 322:95–99, 1990. MININO, A.; ARIAS, E.; KOCHANEK, K.D.; ET AL. is likely to lead to improved preven­ Deaths: Final data for 2000. National Vital Statis­ tion and treatment of alcohol-related GALAMBOS, J. Epidemiology of cirrhosis in the tics Reports 50:1–107, 2002. ■ United States of America. In: Hall, P., ed. Alcoholic liver disease. Liver Disease: Pathobiology, Epidemiology, and NEPHEW, T.M.; WILLIAMS, G.D.; YI, H.-Y.; ET Clinical Aspects. New York: John Wiley & Sons, AL. 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