Alcoholism is known to be greatly underdiagnosed in death certificates, a fact that biases in estimates of alcohol-related mortality. An autopsy series of 1658 cases (920 with natural cause of death and 738 nonnatural) was reviewed to evaluate the extent of this bias, and also to see how well different sources of information served as indicators of alcoholism when alcohol-related disease diagnosed at autopsy was considered as a gold standard. A stepwise logistic regression model adjusted by age and sex showed police reports of individual's alcohol usage and blood alcohol concentration (BAC) of > 2.9/1000 at autopsy to be the two most significant predictors of chronic alcohol abuse (p 2.9/1000), due to its high specificity, as particularly suggestive of chronic heavy drinking. However, it is wise to use these parameters only as an aid in decision-making, not as sole indicators of alcoholism. Deaths associated with chronic heavy drinking were frequent, 50.5% of the total series (male 56.4%, female 37.1%). For all but one age-group (male 45-64 years), however, death certificates mentioned alcohol-related diseases in less than half of these cases. Especially evident underdiagnosis was found for female and males 65 years and older. These results indicate that alcoholism is frequent in such a highly selected population as a series of forensic autopsies and suggest that estimates of prevalence of alcoholism based only on review of death certificates are to be considered with great caution.(ABSTRACT TRUNCATED AT 250 WORDS)
In 110 consecutive, medicolegal autopsies of young and middle-aged women (range 20-54 years) the breasts were examined by an extensive histopathologic method and by correlative specimen radiography. Malignancy was found in 22 women (20%) of which only one was known to have had clinical invasive breast cancer (IBC). At autopsy 2 women had IBC (2%), the remaining in situ carcinoma (in situ BC) of microfocal type (18%), i.e. 15 (14%) intraductal carcinomas (DCIS), 4 (3%) lobular carcinoma in situ (LCIS) and one (1%) both DCIS and LCIS. Forty-five per cent of the women with malignancy had multicentric and 41% had bilateral lesions. Forty-five per cent of all histologically confirmed malignant lesions were identified by specimen radiography. Adenosis, benign epithelial hyperplasia, papilloma and duct ectasia were positively associated with malignancy. In addition malignancy was significantly more frequent among women aged more than 40 years, with late age at first full-term pregnancy, with alcohol abuse and with steatosis or cirrhosis of the liver. The results suggest that clinically occult in situ BC are frequent in young and middle-aged women.
Both alcohol abuse and liver cirrhosis are known risk factors for various cancers. This article was aimed to assess the long-term risk of malignancies among patients with severe alcoholic liver disease (ALD), i.e., alcoholic liver cirrhosis and alcoholic hepatitis. A cohort of 8,796 male and 3,077 female ALD patients from 1996 to 2012 was identified from the Finnish National Hospital Discharge Register. This nationwide cohort was combined with the data from the Finnish Cancer Registry for incidence of malignancies during the years 1996-2013. The cancer cases diagnosed were compared with the number of cancers in the general population. The number of malignancies in our cohort was 1,052 vs. 368 expected. There was statistically significant excess of cancers of the liver, (standardized incidence ratio [SIR] 59.20; 95% CI 53.11-65.61), pancreas (SIR 3.71; 95% CI 2.72-4.94), pharynx (SIR 9.25; 95% CI 6.05-13.56), mouth (SIR 8.31; 95% CI 4.84-13,29), oesophagus (SIR 7.92; 95% CI 5.49-11.07), tongue (SIR 7,21; 95% CI 3.60-12.89), larynx (SIR 5.20; 95% CI 2.77-8.89), lung (SIR 2.77; 95% CI 2.27-3.32), stomach (SIR 2.76; 95% CI 1.79-4.07), kidney (SIR 2.69; 95% CI 1.84-3.79) and colon (SIR 2.33; 95% CI 1.70-3.11). There was no decreased risk of any cancer among ALD patients. Severe ALD is associated with markedly increased risk of malignancies. The risk is especially high for hepatocellular carcinoma, but also significantly increased for cancers of the upper aerodigestive tract, pancreas and kidneys, and warrants cancer surveillance in selected cases.
Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Harborview Medical Center, 325 Ninth Avenue, Seattle, WA 98144, USA. jdscott@u.washington.edu
A structured literature review was performed to detail the frequency and etiology of chronic liver disease (CLD) in Aboriginal North Americans. CLD affects Aboriginal North Americans disproportionately and is now one of the most common causes of death. Alcoholic liver disease is the leading etiology of CLD, but viral hepatitis, particularly hepatitis C, is an important and growing cause of CLD. High rates of autoimmune hepatitis and primary biliary cirrhosis (PBC) are reported in regions of coastal British Columbia and southeastern Alaska. Non-alcoholic liver disease is a common, but understudied, cause of CLD. Future research should monitor the incidence and etiology of CLD and should be geographically inclusive. In addition, more research is needed on the treatment of hepatitis C virus (HCV) infection and non-alcoholic fatty liver disease (NAFLD) in this population.
Five years' follow-up of patients with elevated carcinoembryonic antigen (CEA) and alcoholic liver disease, with special reference to mortality rate and development of malignancy.
Plasma-carcinoembryonic antigen (CEA) was analyzed by a modified CEA-Roche radioimmunoassay (RIA) in 109 alcoholics with various degrees of liver disorders. The total mortality rate during the 5-year observation period was 48%, compared with an expected mortality rate of 12% (p less than 0.001). Sixty-one per cent of 46 alcoholics with CEA values greater than or equal to 5.0 micrograms/l died during the observation period of 5 years, compared with 38% of 63 cases with normal CEA values (p less than 0.05), indicating a possible prognostic value of CEA. Ten patients developed malignancies during the observation period, which is more than three times the expected cancer frequency in this groups. The frequency of malignant disease was not higher in alcoholics with initially elevated CEA than in those with normal values. Thus, CEA seems to be of no value for predicting malignancy in alcoholics.
Fulminant hepatitis is a rare complication of acute hepatitis A virus (HAV) infection. We report three cases of fulminant hepatic failure with death due to HAV infection in patients with pre-existing chronic liver disease. Data from the literature also indicate a high case fatality rate during HAV superinfection in patients with chronic hepatitis B, particularly those with cirrhosis, and in patients with alcoholic cirrhosis. In patients with chronic hepatitis C, results are conflicting with some reports indicating a high fatality rate of HAV superinfection and others not, irrespective of the presence or absence of cirrhosis. Based on our observations and this review of the literature, we suggest that patients with chronic liver disease should be vaccinated against hepatitis A.
Studies in experimental animals have indicated that enhanced lipid peroxidation may play a role in the hepatic injury produced by iron overload or by excessive alcohol consumption. The aim of this study was to compare the formation of lipid peroxidation-derived aldehydes in the liver of patients with hereditary hemochromatosis (HH) and alcohol abuse. Liver biopsy specimens from 10 nondrinking patients with HH were evaluated. These patients were classified as having HH based on hepatic iron index or human leukocyte antigen identity with a known proband. All patients were homozygous for the Cys282Tyr mutation. In addition, 8 patients with alcoholic liver disease were examined, 2 of whom also had hemochromatosis. For comparison, 17 patients with liver diseases unrelated to iron overload or alcohol abuse were studied. Liver biopsy specimens were immunostained for protein adducts with malondialdehyde and 4-hydroxynonenal. Both malondialdehyde- and 4-hydroxynonenal-protein adducts were found from liver specimens of patients with HH and alcohol abuse in more abundant amounts than from patients in a control group. In alcoholics the adducts were primarily in zone 3, whereas in hemochromatosis staining had an acinar zone 1 predominance, which followed the localization of iron. The most abundant amounts of protein adducts were noted in patients with alcohol abuse plus iron overload. The data support the concept that both chronic alcohol use and iron overload induce hepatic lipid peroxidation. Through formation of reactive aldehydic products, excessive alcohol consumption and iron overload may have additive hepatotoxic effects.
Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-7234, USA. welzlt@mail.nih.gov
Recently, the incidence of intrahepatic cholangiocarcinoma (ICC) has been increasing in a number of developed (Western) countries. However, risk factors in these low-risk populations are poorly understood. In this nationwide population based case-control study in Denmark, we examined the relationship between selected medical conditions and subsequent ICC risk to provide additional clues to etiopathogenesis. All histologically confirmed ICC cases diagnosed in Denmark between 1978 and 1991 were identified from the Danish cancer registry. Population controls were selected from the central population registry and were matched 4:1 to cases on sex and year of birth. Cases and controls were linked to the Danish hospital discharge registry to obtain information on prior hospital diagnoses. Odds ratios (OR) and 95% confidence intervals (95% CI) were derived using conditional logistic regression. A total of 764 ICC cases and 3,056 population controls were included in the study. Chronic liver diseases were significantly related to ICC: alcoholic liver disease (OR = 19.22, 95% CI = 5.55-66.54), unspecified cirrhosis (OR = 75.9, 95% CI 10.2-565.7). Bile duct diseases were also associated with risk: cholangitis (OR = 6.3, 95% CI = 2.3-17.5), choledocholithiasis (OR = 23.97, 95% CI = 2.9-198.9), cholecystolithiasis (OR = 4.0, 95% CI = 2.0-7.99), though gallbladder removal did not change risk (OR = 1.6, 95% CI = 0.65-3.7). Among other conditions, chronic inflammatory bowel disease (OR = 4.7, 95% CI = 1.65-13.9) was significantly associated with ICC. Diabetes was associated with risk in the year prior to diagnosis of ICC (OR = 3.02, 95% CI = 1.05-8.69). Obesity was unrelated to risk. These results confirm that prior bile duct diseases increase risk of ICC and suggest that alcoholic liver disease and diabetes may also increase risk.
