Epidemiology of Alcohol-Related Liver and Pancreatic Disease in the United States

Home , Alcoholic hepatitis, Alcoholic liver disease, Pancreatitis

ORIGINAL INVESTIGATION Epidemiology of Alcohol-Related Liver and Pancreatic Disease in the United States

Alice L. Yang, MD; Shweta Vadhavkar, MS; Gurkirpal Singh, MD; M. Bishr Omary, PhD, MD

Background: The epidemiology of acute alcoholic pan- hospital discharges per 100 000 persons for AP plus AH creatitis (AP), chronic alcoholic pancreatitis (CP), acute were 1.8; and for CP plus CH, 0.32. There were higher alcoholic hepatitis (AH), and chronic alcoholic hepati- male to female ratios for AH and CH, and less so for AP tis with cirrhosis (CH) alone or in combination is not well and CP. A markedly higher frequency of AP (63.5) and described. To better understand alcohol-related liver and CP (11.3) was seen among blacks than among whites (AP, pancreas effects on and associations with different eth- 29.6 and CP, 5.1), Hispanics (AP, 27.1 and CP, 3.7), nic groups and sexes, we analyzed the trends of AP, CP, Asians (AP, 12.8 and CP, 1.4), and American Indians (AP, AH, CH, AP plus AH, and CP plus CH in the United States. 15.5 and CP, 2.3). This higher frequency remained stable between 1994 and 2004. Overall case fatality steadily de- Methods: We examined discharge records from the Na- creased in all categories, but remains highest in CH tionwide Inpatient Sample, the largest representative (13.6%) with similar racial distributions. sample of US hospitals. Hospital discharges, case- fatality, and sex and race contributions were calculated Conclusions: In the United States, AP is the most com- from patients with discharge diagnoses of AP, CP, AH, mon discharge diagnosis among alcohol-related liver or CH, AP plus AH, or CP plus CH between 1988 and 2004. pancreas complications, while CH has the highest case fatality rate and male to female ratio. Blacks have the high- Results: The distribution of overall hospital discharges est frequency of alcohol-related pancreatic disease. per 100 000 persons between 1988 and 2004 was as fol- lows: AP, 49.2; CP, 8.1; AH, 4.5; and CH, 13.7. Overall Arch Intern Med. 2008;168(6):649-656

HE ASSOCIATION BETWEEN homogeneous population in Northern Eu- alcohol intake and pancre- rope or Asia,1,3-5,8 while 2 recent studies atic and liver diseases is specifically focused on acute pancreatitis well documented. The 4 (of all causes) in California or the United major pancreas- and liver- States.9,10 Studies in Europe and Japan re- relatedT clinical entities precipitated by al- ported that cofactors such as ethnicity, cohol intake are acute pancreatitis (AP), smoking, diet, genetic make-up, cyto- chronic pancreatitis (CP), acute alco- kines, and other inflammatory mediators holic hepatitis (AH), and chronic alco- are associated more frequently with either holic hepatitis with cirrhosis (CH).1-5 Dis- alcoholic pancreatic or liver disease.8,11,12 ability-adjusted life years, as an indirect To our knowledge, no large studies have assessment of disease burden in the United analyzed the prevalence or trends of these States, places alcohol as the fifth leading diseases in the racially diverse US popu- disease burden among men, after ische- lation, although some studies have exam- mic heart disease, road traffic accidents, ined incidence rates in Europe. For ex- bronchopulmonary cancers, and human ample, the incidence of AP in Europe is immunodeficiency virus.6 Furthermore, rising for reasons that are not well under- Author Affiliations: 1998 hospital-related US costs for these al- stood.13 Department of Medicine, cohol-related diseases were between $0.6 Limited data on CP are available for the Division of Gastroenterology billion and $1.8 billion.1 In terms of gas- United States, but in Europe the inci- and Hepatology, Veterans Affairs trointestinal and liver disease burden, al- dence rate ranges from 1.6 new cases per Palo Alto Health Care System coholic liver disease was the seventh lead- year per 100 000 population in Switzer- and Stanford University ing gastrointestinal cause of death in the land to 23 cases per year per 100 000 in (Drs Yang, Singh, and Omary), 7 5 and Institute of Clinical United States in 2001. Finland. With regard to alcohol-related Outcomes Research and Most previous epidemiologic studies of liver disease, few studies have addressed Education (Ms Vadhavkar and alcohol-related pancreatic and liver dis- acute alcoholic hepatitis in limited US sub- Dr Singh), Palo Alto, California. ease have analyzed cases in an ethnically populations focusing on trends in alco-

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Downloaded From: https://jamanetwork.com/ on 09/24/2021 holic cirrhosis incidence and mortality.1,3 It is unclear why Census Bureau contained data for the following races: white, pancreatic and/or liver disease is acquired and what de- black, Hispanic, Asian American/Pacific Islander, American In- termines the tissue predilection in a given individual. Some dian/Alaska Native. studies suggest that the coexistence of alcohol- associated pancreatic and liver disease is relatively com- HOSPITAL DISCHARGES AND mon,14,15 while others have noted infrequent involve- CASE-FATALITY DATA ment of the 2 organs simultaneously.16 In the present study, we use US national data on hos- The number of hospital discharges of each disease alone or in pital discharges to provide an up-to-date analysis of trends combination per 100 000 US residents overall and per year were in alcohol-related acute and chronic pancreatic and liver calculated for each racial and/or ethnic group and sex. The case- fatality data were obtained from the NIS and calculated as a per- diseases. We also examine the number of hospital dis- centage of all discharges. charge diagnoses of combined AP and AH and combined CP and CH. STATISTICAL ANALYSIS

METHODS Statistical analyses were performed by accounting for the survey design of the NIS database, using SAS 9.1 software (SAS DATABASE Institute, Cary, North Carolina). To define the numbers of hos- pitalized patients with specific diagnoses in different groups of The Nationwide Inpatient Sample (NIS) is the largest all- patients, we used an SAS PROC SURVEYFREQ statement that payer inpatient database in the United States and includes a strati- allowed calculation of the weighted frequency with the stan- fied random sample of hospitals that makes up approximately dard deviation (SD) using modified weights. We then calcu- 85% of all hospital discharges in the United States (www.hcup-us lated rates of hospital discharges and population-based case fa- .ahrq.gov/nisoverview.jsp). The sample includes community and talities per 100 000 population using the US Census Bureau general hospitals and academic medical centers. It is the only national population estimates. national hospital database with information on all patients, re- gardless of payer, including persons covered by Medicare, Med- RESULTS icaid, private insurance, and the uninsured. Data from NIS are available from 1988 to 2004, allowing for analysis of trends over The total number of discharges reviewed in the NIS be- time. For each hospital discharge, data include over 100 clinical and nonclinical variables for each hospital stay, such as pri- tween 1988 and 2004 was 608 584 037. The total num- mary and secondary diagnoses (up to 15) and primary and sec- ber of hospital discharges of AP (all causes) between 1988 ondary procedures (up to 15) using International Classification and 2004 was 2 999 516. Hospital discharges with diag- of Diseases, Ninth Revision (ICD-9) codes (www.cdc.gov/nchs noses of AP, CP, AH, CH, AP plus AH, or CP plus CH /icd9.htm), patient demographics (sex, age, race, median in- with 95% confidence intervals (CIs) per 100 000 US per- come, and zip codes), length of stay, and discharge status. sons per year for each year between 1988 and 2004 are shown in Figure 1A. From 1988 to 2004, the number PATIENT ELIGIBILITY of AP diagnoses per 100 000 persons has progressively increased, from 39.8 (95% CI, 37.3-42.2) to 65.0 (95% The study cohort included all hospital discharges in the NIS CI, 62.5-67.5), an increase of 63%, while the other clini- data system with 1 of the following primary ICD-9 discharge cal entities did not increase as much. The number of CH diagnoses: acute pancreatitis (577.0), chronic pancreatitis diagnoses per 100 000 persons changed from 11.9 (95% (577.1), acute alcoholic hepatitis (571.1), or alcoholic liver cir- CI, 11.0-12.8) in 1988 to 18.1 (95% CI, 16.8-19.4) in rhosis (571.2). The cohort also included patients who were di- 2004, a 52% rise. The rates per 100 000 persons of AH agnosed as having combined alcoholic AP and AH or CP and CH. All patients were discharged between 1988 and 2004. and CP diagnoses changed minimally, from 4.9 (95% CI, For the AP group, since there is no specific ICD-9 code for 4.4-5.3) to 4.2 (95% CI, 3.9-4.5) for AH and from 7.0 alcohol-related disease, those with a concurrent diagnosis of (95% CI, 7.2-7.8) to 8.1 (95% CI, 7.5-8.7) for CP acute cholecystitis (575.0), other cholecystitis (575.1), chole- (Figure 1A). The number of hospital discharge diag- cystitis unspecified (575.10), calculus of the gallbladder with noses of combined AP plus AH was much lower than that acute cholecystitis without/with obstruction (574.00-574.01), of each disease individually, but the number has nearly calculus of the gallbladder with other cholecystitis without/ doubled between 1988 and 2004, from 1.4 (95% CI, 1.2- with obstruction (574.10-574.11), calculus of the gallbladder 1.6) to 2.4 (95% CI, 2.2-2.6) cases per 100 000 persons without cholecystitis without/with obstruction (574.20- (Figure 1B). The number of hospital discharge diag- 574.21), choledocholithiasis with/without obstruction (574.3- noses per 100 000 persons of combined CP plus CH is 574.9), cholangitis (576.1), and those who underwent endoscopic retrograde cholangiopancreatography on the same also much lower than each disease individually: 0.11 (95% admission (Current Procedural Terminology codes 5110, 5111, CI, 0.07-0.14) in 1988 and 0.46 (95% CI, 0.39-0.52) in 5184, 5187, and 5213) were subtracted from the total to arrive 2004. at an estimated number of hospital discharges of acute AP. The hospital discharge diagnoses of the separate and combined alcohol-related acute and chronic pancreatic CENSUS DATA and liver complications were then analyzed in the con- text of different patient ethnic backgrounds (Table 1). The estimated national population during the 1988-2004 pe- Per 100 000 persons, a markedly higher overall fre- riod, along with sex- and race-specific population data were ob- quency of AP (63.5 cases) and CP (11.3 cases) was seen tained from the US Census Bureau (www.census.gov). The US in blacks (Table 1) than in whites (29.6 and 5.1 cases,

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20 000 Persons

3.0 B AP + AH CP + CH 2.5

2.0 No. of Hospital Discharge Diagnoses per 100

1.5

1.0

0.5

0 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 Year

Figure 1. Hospital discharge diagnoses per 100 000 persons of acute alcoholic pancreatitis (AP), chronic alcoholic pancreatitis (CP), acute alcoholic hepatitis (AH), and chronic alcoholic hepatitis with cirrhosis (CH) (A) and combination diagnoses of AP plus AH and CP plus CH (B) in the United States between 1988 and 2004. Error bars indicate 95% confidence intervals.

Table 1. Prevalence of Hospital Discharge Diagnoses of Alcohol-Related Pancreatic and Liver Disease, Alone and in Combination, by Ethnic Backgrounda

Ethnic Group AP CP AH CH AP؉AH CP؉CH All 49.2 (47.5-50.9) 8.1 (7.7-8.6) 4.5 (4.3-4.7) 13.7 (13.0-14.3) 1.8 (1.7-1.9) 0.32 (0.29-0.34) White 29.6 (28.2-30.9) 5.1 (4.7-5.5) 3.1 (2.97-3.32) 11.1 (10.5-11.8) 1.1 (0.99-1.12) 0.21 (0.19-0.23) Black 63.5 (58.5-68.4) 11.3 (10.3-12.3) 4.4 (4.0-4.8) 9.9 (9.0-10.9) 2.8 (2.6-3.1) 0.57 (0.49-0.64 Hispanic 27.1 (24.8-29.5) 3.7 (3.2-4.2) 2.9 (2.5-3.2) 16.9 (14.9-18.9) 1.0 (0.9-1.1) 0.24 (0.20-0.28) Asian 12.8 (11.2-14.5) 1.4 (1.2-1.7) 0.6 (0.48-0.73) 2.7 (2.3-3.1) 0.29 (0.22-0.37) 0.06 (0.03-0.09) American Indian 15.5 (12.8-18.2) 2.3 (1.7-3.0) 2.9 (2.2-3.6) 9.9 (7.4-12.5) 0.82 (0.6-1.1) 0.07 (0.02-0.13)

Abbreviations: AH, acute alcoholic hepatitis; AP, acute alcoholic pancreatitis; CH, chronic alcoholic hepatitis; CI, confidence interval; CP, chronic alcoholic pancreatitis. a All data are reported as averaged prevalence per 100 000 persons (95% CI) in the United States from 1988 to 2004. Ethnic background data were not available for 13 states.

respectively), Hispanics (27.1 and 3.7), Asians (12.8 and eases (AP, CP, AH, and CH) reflected that of the popu- 1.4), and American Indians (15.5 and 2.3). The high rate lation overall (Figure 2B and Table 2). The disease with per 100 000 persons of hospital discharge diagnoses of the highest overall case fatality rate was CH (13.6 per AP among blacks has been relatively constant during the 100 000), while that with the lowest case fatality was CP past 10 years (Figure 2A), but with a sharp rise occur- (0.8 per 100 000) (Table 2). ring for unknown reasons between 1991 (19.2; 95% CI, Another prominent ethnicity-related disease associa- 12.9-25.6) and 1993 (75.3; 95% CI, 65.6-85). Despite this tion per 100 000 persons was noted for CH in Hispan- high rate, the case fatality trend in blacks for all 4 dis- ics, 16.9 cases, compared with 11.1 cases among whites,

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000 Persons CH

No. of Hospital Discharge Diagnoses per 100 0

15 Case Fatality Rate, % 10

0 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 Year

Figure 2. Trends of alcohol-related pancreatic and liver disease in blacks in the United States between 1988 and 2004. Error bars indicate 95% confidence intervals.

Table 2. Case Fatality Rates of Alcohol-Related Pancreatic and Liver Disease, Alone and in Combination, by Ethnic Backgrounda

Ethnic Group AP CP AH CH AP؉AH CP؉CH All 1.9 0.8 6.6 13.6 2.2 6.5 White 2.2 0.7 7.3 13.5 2.8 6.4 Black 1.3 0.8 5.1 15.5 1.3 6.7 Hispanic 1.5 0.6 5.9 11.1 2.2 8.6 Asian 1.8 2.4 4.0 15.1 2.2 4.1 American Indian 0.7 0 5.5 11.1 2.3 0

Abbreviations: AH, acute alcoholic hepatitis; AP, acute alcoholic pancreatitis; CH, chronic alcoholic hepatitis; CP, chronic alcoholic pancreatitis. a All data are reported as percentages. Race data were not available for 13 states.

9.9 among blacks, 2.7 in Asians, and 9.9 in American In- (2.5% to 1.3% in AP, 0.9% to 0.7% in CP, 7.8% to dians (Table 1). For AH, the racial contribution was simi- 5.6% in AH, and 17.4% to 11.5% in CH) (Figure 3). lar: 3.1 cases per 100 000 persons in whites, 4.4 in blacks, Case fatality remains highest overall in CH (13.6%) 2.9 in Hispanics, and 2.9 in American Indians (Table 1). between 1988 and 2004 compared with 1.9% for AP, In general terms, Asians had the lowest hospital dis- 0.8% for CP, and 6.6% for AH, with similar racial con- charge diagnosis numbers for any of the 4 diseases stud- tributions (Table 2). The case fatality rate of combined ied (Table 1). AP plus AH also decreased (3.3% to 1.5%), as did the We also examined the overall case fatality rates asso- case fatality rate in CP plus CH (6.2% to 5.4%), which ciated with each disease. Case fatality steadily decreased was much lower than in individuals with CH alone in all 4 individual disease categories from 1988 to 2004 (Table 2).

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12 Case Fatality Rate,% B AP + AH CP + CH 10

0 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 Year

Figure 3. Overall case fatality rates of acute alcoholic pancreatitis (AP), chronic alcoholic pancreatitis (CP), acute alcoholic hepatitis (AH), and chronic alcoholic hepatitis with cirrhosis (CH) (A) and combination AP plus AH and CP plus CH (B) in the United States between 1988 and 2004.

Sex associations were also examined. There were high male to female ratios for AH (1.83) and CH (2.64) and Table 3. Prevalence of Hospital Discharge Diagnoses of Alcohol-Related Pancreatic and Liver Disease, not as high for AP (1.23) and CP (1.02) (Table 3). The Alone and in Combination, by Sexa higher incidence for men in liver but not pancreatic disease carried through when the combined acute or chronic Male to Female diseases were analyzed. For AP plus AH, the male to fe- Disease All Cases Ratio male ratio was 2.72, and in CP plus CH, the male to fe- AP 49.2 (47.5-50.9) 1.23 (1.21-1.25) male ratio was 2.41 (Table 3). The male to female ratio CP 8.1 (7.7-8.6) 1.02 (0.99-1.05) remained relatively consistent between 1988 and 2004 AH 4.5 (4.3-4.7) 1.83 (1.77-1.88) for all 6 disease groups (data not shown). CH 13.7 (13.0-14.3) 2.64 (2.58-2.69) APϩCH 1.8 (1.7-1.9) 2.72 (2.60-2.83) CPϩCH 0.32 (0.29-0.34) 2.41 (2.19-2.64) COMMENT Abbreviations: AH, acute alcoholic hepatitis; AP, acute alcoholic Alcohol-related pancreas and liver diseases include AP, pancreatitis; CH, chronic alcoholic hepatitis; CI, confidence interval; CP, 1-5 chronic alcoholic pancreatitis. CP, AH, and CH. The NIS database allowed us to study a Data are reported as hospital discharge diagnoses per 100 000 persons the epidemiology of these 4 diseases in the racially di- (95% CI) in the United States from 1988 to 2004. verse US population over the span of 17 years (1988- 2004). Similar to previous reports in Europe and the United States,8-10 we found that the number of hospital 17-year period. The case fatality rates of these 4 diseases discharge diagnoses of AP is rising steadily, followed by have decreased from 1988 to 2004, as expected, owing a slower increase in the number of alcoholic liver cir- to advances in medical and surgical care and in endo- rhosis cases. On the contrary, the hospital discharge di- scopic and radiologic diagnostic techniques. The case fa- agnoses of AH and CP changed minimally during that tality rate from alcoholic cirrhosis remains the highest.

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Downloaded From: https://jamanetwork.com/ on 09/24/2021 The reason for the increase in the number of hospital essarily influence sex, race, or trend data, but it could discharge diagnoses of AP is unclear and does not ap- cause an underestimate of the incidence of AH, CP, and pear to be related to a major shift in alcohol consump- CH. tion. Per capita consumption of all alcoholic beverages The differences among the number of hospital dis- increased between 1962 and the early 1980s, then de- charge diagnoses of alcohol-related AP and CP between creased until 1998. Since 1998, per capita alcohol con- races was striking, particularly in blacks, who had a much sumption has changed minimally (8.10 L/y in 1998 higher number of hospital diagnoses than the other eth- to 8.25 L/y in 200117). Hence, since there was a nic groups. A significantly higher rate of alcoholic AP was decrease in alcohol consumption until 1998, other fac- also noted in blacks than in other groups in an analysis tors likely contribute to the increase in AP prevalence. of the California Patient Discharge Data Set9 and for over- When 54 patients with alcohol-induced pancreatitis all AP in an analysis of the 1988-2003 National Hospital were compared with a control group of male patients Discharge Survey.10 The ethnic background differences with alcoholic cirrhosis,18 no difference was found in are unlikely to be due to differences in alcohol consump- alcohol consumption between the 2 groups, but smok- tion. In a study of 91 659 subjects, men consumed alco- ing was more common in the men with alcohol- hol more frequently than women, and whites drank al- induced pancreatitis. cohol more frequently than blacks or Asians.21 However, the pattern of drinking may be a contrib- Furthermore, the 1992 National Longitudinal Alcohol Epi- uting factor. Binge drinking (Ն5 drinks on 1 occasion demiologic Study22 did not find differences in drinking in men, Ն4 drinks in women) is common among those patterns among ethnic groups. Other likely relevant fac- 26 years or younger, and more so among men.19 Per capita tors that might account for the increased susceptibility binge drinking episodes have steadily increased be- of blacks to alcohol-related pancreatitis are genetic and tween 1993 and 2001, particularly since 1995. In this re- epigenetic parameters. Increases in aspartate aminotrans- gard, the amount of alcohol consumed during the 1 week ferase (AST) and ␥-glutamyltransferase (GGT) levels oc- prior to presentation of symptoms determines the sever- cur more frequently in blacks and Hispanics than in ity of the first episode of AP.20 In a study of Japanese men, whites, and the AST or GGT levels increased with the the high consumption of alcohol over a short period of frequency of alcohol intake.23 time was found to be an independent risk factor for the In contrast to alcohol-related pancreatic complica- severity of alcoholic CP.8 It is possible that the more al- tions, the increased frequency of alcoholic liver cirrho- cohol consumed over a shorter time increases suscepti- sis in Hispanics compared with other races may be re- bility to AP, but further studies addressing this issue are lated, at least in part, to the extent of alcohol consumption. warranted. We are unable to determine from our cohort For example, heavy drinking was found to be highest in whether smoking, potential dietary factors, changes in Hispanic men, followed by black men, and Hispanic men body mass index, or other factors contributed to the ob- were more likely than white men to persist with heavy served increase in AP. drinking habits.24 Even though Hispanics had the high- Few studies have examined the epidemiology of AP est incidence of CH (16.9 cases per 100 000 persons) due to alcohol, possibly because of the lack of a specific (Table 1), they had a relatively low incidence of AH (2.9 diagnostic code for alcohol-induced AP. The latest ICD-10 cases per 100 000 persons) (Table 1), which suggests that coding system (www.cdc.gov/nchs/about/otheract/icd9 they may harbor a greater propensity for liver disease pro- /abticd10.htm) does include a new diagnostic code for gression than those of other ethnic backgrounds. alcohol-induced AP, but that system is currently not used The male to female ratio was highest for CH, fol- in the United States. We specifically excluded AP cases lowed by AH. The sex-specific differences in alcoholic associated with a concurrent diagnosis of choledocholi- AP and CP were less prominent. A review of 18 Euro- thiasis, cholangitis, or other biliary diseases and also cases pean studies with population-based information on the with a concurrent procedure code of endoscopic retro- epidemiology of first-attack acute pancreatitis (of all grade cholangiopancreatography to primarily capture causes) showed that gallstone AP was more common in cases of alcohol-related AP. It is possible that we over- women, while alcoholic AP was more common in middle- estimated the number of alcohol-related AP cases be- aged men, and the rate of idiopathic AP was similar in cause we were unable to exclude idiopathic AP (that does both sexes.25 The male to female ratio for alcoholic AP not have a designated ICD-9 code), which according to has varied between studies and ranges from nearly 3.5 some estimates may be 80% more common than alcohol- for the year 2000 in the United States9 to 1.12 in heavy related AP.9 Alternatively, diagnostic screening criteria drinkers in Germany.26 The NIS does not provide alco- (laboratory, clinical, and radiologic criteria) for pancre- hol consumption and/or duration data; therefore, we atitis are not standardized, and some mild cases of AP were unable to determine if sex differences or similari- might not have been diagnosed in the hospital setting. ties in our report are due to alcohol consumption or This would result in underestimating the number of AP other factors. cases. Aside from alcohol-induced liver disease, chronic in- Another caveat is that the admission rate for AP might fection with hepatitis C virus (HCV) is another major de- be higher than for CP, AH, and CH, since AP is nearly terminant of liver cirrhosis. At present, about 30% of US always an indication for hospital admission, and the other liver transplantations have an indication of alcoholic cir- conditions are not. Hence, the high hospital admission rhosis, while 30% to 40% are used to treat HCV cirrho- and discharge rates for AP could be due, in part, to disease- sis.27 In our study, a subset analysis showed that the co- dependent hospital admission bias. This should not nec- existence of alcohol-related AH and HCV or CH and HCV

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1 000 Persons

CH 20 + B CH HCV

No. of Hospital Discharges per 100 15

0 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 Year

Figure 4. Coexistence of acute alcoholic hepatitis (AH) and hepatitis C virus (HCV) (A) or chronic alcoholic hepatitis with cirrhosis (CH) and HCV (B) compared with AH or CH alone between 1992 and 2004. For this analysis we considered HCV-related disease as a secondary diagnosis and used the International Classification of Diseases, Ninth Revision (ICD-9 ) code 070.54 (chronic hepatitis C without hepatic coma). For the 1994-2004 period, we also examined the coexistence of CH and chronic hepatitis B (not shown), considering chronic hepatitis B as a secondary diagnosis under ICD-9 code 070.32 (chronic viral hepatitis B without hepatic coma without hepatitis delta) or 070.33 (chronic viral hepatitis B without hepatic coma with hepatitis delta). The coexistence of CH and chronic hepatitis B infection, even when analyzed on a per-race-contribution basis, was also too small to affect our conclusions and ranged between 0.03 and 0.46 hospital discharges per 100 000 persons (not shown).

(from 1992 to 2004) was too small (compared with the pancreatogram criteria, but none of the 14 patients occurrence of AH or CH alone) to affect our conclu- had clinical symptoms of pancreatic insufficiency.29 sions (Figure 4). However, it is possible that we un- This suggests that the autopsy finding of a relatively derrepresented the impact of chronic HCV infection be- high prevalence of comorbid conditions does not cause it is unknown what sample size in the NIS database reflect clinically relevant disease. In the present study, was tested for the infection. Similarly, the coexistence of the observed number of cases of combined acute or alcohol-related CH and chronic hepatitis B infection, in- chronic pancreatic and liver disease (AP plus AH or cluding ethnic contribution, was also too small to affect CP plus CH) was significantly lower than the involve- our conclusions (data not shown). ment of either organ alone (Table 1). The reported combined frequencies of association In conclusion, we defined the US epidemiologic trends between pancreas and liver disease have varied of alcohol-related pancreatic and liver disease. The num- between studies. Higher frequencies are reported in ber of hospital discharge diagnoses of AP is increasing, autopsy than in clinical data. A review of 1022 autop- and AP is the most common of the 4 alcohol-related com- sies in which the cause of death was alcoholic liver plications. At the same time, the case fatality rates of AP, disease found histologic evidence of pancreatitis (mild CP, AH, and CH are decreasing. The incidences of the inflammation to moderate fibrosis) in 28% of cases.28 combined conditions AP plus AH or CP plus CH are mark- However, a prospective study has reported lower coex- edly lower than the incidences of any of the entities alone. istence frequencies. Fourteen of 72 patients (19%) Acute or chronic liver disease was more common in men with known alcoholic cirrhosis had chronic pancreati- than in women. A much higher number of hospital dis- tis diagnosed by endoscopic ultrasound or endoscopic charge diagnoses of acute and chronic pancreatitis was

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Downloaded From: https://jamanetwork.com/ on 09/24/2021 found in blacks than in the other ethnic groups studied, 7. Shaheen NJ, Hansen RA, Morgan DR, et al. The burden of gastrointestinal and and the highest number of hospital discharge diagnoses liver diseases, 2006. Am J Gastroenterol. 2006;101(9):2128-2138. 8. Nakamura Y, Kobayashi Y, Ishikawa A, Maruyama K, Higuchi S. Severe chronic of CH was found in Hispanics. The reasons for these eth- pancreatitis and sever liver cirrhosis have different frequencies and are indepen- nic differences, whether genetic or environmental fac- dent risk factors in male Japanese alcoholics. J Gastroenterol. 2004;39(9): tors, remain to be defined. 879-887. 9. Frey CF, Zhou H, Harvey DJ, White RH. The incidence and case-fatality rates of Accepted for Publication: October 11, 2007. acute biliary, alcoholic, and idiopathic pancreatitis in California, 1994-2001. Pancreas. 2006;33(4):336-344. Correspondence: M. Bishr Omary, PhD, MD, Depart- 10. Fagenholz PJ, Castillo CF, Harris NS, Pelletier AJ, Camargo CA. Increasing United ment of Medicine, Division of Gastroenterology and Hepa- States hospital admissions for acute pancreatitis, 1988-2003. Ann Epidemiol. tology, VA Palo Alto Health Care System and Stanford 2007;17(7):491-497. University, 3801 Miranda Ave 154J, Palo Alto, CA (mbishr 11. Noel-Jorand MC, Bras J. A comparison of nutritional profiles of patients with alcohol- @stanford.edu). related pancreatitis and cirrhosis. Alcohol Alcohol. 1994;29(1):65-74. 12. Verlaan M, Te Morsche RHM, Roelofs HMJ, et al. Genetic polymorphisms in alcohol- Author Contributions: Study concept and design: Yang, metabolizing enzymes and chronic pancreatitis. Alcohol Alcohol. 2004;39(1): Vadhavkar, Singh, and Omary. Acquisition of data: Yang, 20-24. Vadhavkar, and Singh. Analysis and interpretation of data: 13. Goldacre MJ, Roberts SE. Hospital admissions for acute pancreatitis in an En- Yang, Vadhavkar, Singh, and Omary. Drafting of the manu- glish population, 1963-98: database study of incidence and mortality. BMJ. 2004; script: Yang, Vadhavkar, Singh, and Omary. Critical re- 328(7454):1466-1469. 14. Buchner AM, Sonnenberg A. Comorbid occurrence of liver and pancreas disease vision of the manuscript for important intellectual content: in United States military veterans. Am J Gastroenterol. 2001;96(7):2231-2237. Yang, Singh, and Omary. Statistical analysis: Vadhavkar 15. Sobel WJ, Waye J. Pancreatic changes in various types of cirrhosis of the liver. and Singh. Obtained funding: Singh and Omary. Admin- Gastroenterology. 1963;45:341-344. istrative, technical, and material support: Singh and Omary. 16. Work Group III. Diseases of the pancreas. Gastroenterology. 1975;69(5):1088-1094. Study supervision: Singh and Omary. 17. Nephew TM, Williams GD, Yi H, et al. Apparent Per Capita Alcohol Consump- tion: National, State, and Regional Trends, 1977-2000. Bethesda, MD: National Financial Disclosure: None reported. Institute on Alcohol Abuse and Alcoholism; 2003. Funding/Support: This work was supported by Na- 18. Lowenfels AB, Zwemer FL, Jhangiani S, et al. Pancreatitis in a Native American tional Institutes of Health (NIH) grant DK47918 and the Indian population. Pancreas. 1987;2(6):694-697. Department of Veterans Affairs (Dr Omary) and NIH Di- 19. Naimi TS, Brewer RD, Mokdad A, et al. Binge drinking among US adults. JAMA. gestive Disease Center grant DK56339 to Stanford Uni- 2003;289(1):70-75. 20. Jaakkola M, Sillanaukee P, Lof K, Koivula T, Nordback I. Amount of alcohol is an versity. important determinant of the severity of acute alcoholic pancreatitis. Surgery. Previous Presentation: Parts of this article were pre- 1994;115(1):31-38. sented as a poster at the Digestive Disease Week annual 21. Klatsky AL, Friedman GD, Siegelaub AB, Gerard MJ. 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