Concurrent pancreatic ductal changes in alcoholic liver disease

BACKGROUND: Alcohol is a common etiological factor in both liver disease and chronic pancreatitis, but in a single individual it does not usually produce clinically significant disease in both organs. We assessed the prevalence of pancreatic ductal changes in patients presenting with alcoholic liver disease of different stages. METHODS: Forty-six patients with alcoholic liver disease were included in the present study. Liver biopsy was performed in patients with normal coagulogram. Endoscopic retrograde pancreatogram was performed in all patients and changes in chronic pancreatitis were noted. RESULTS: Of the 46 patients with alcoholic liver disease, 31 had cirrhosis of the liver, nine had fatty liver and two patients had alcoholic hepatitis. Twenty (43.47%) patients had features of chronic pancreatitis on endoscopic retrograde pancreatogram and these consisted of minimal pancreatitis changes in 10 patients, moderate changes in nine patients and advanced changes in one patient. There was no difference in the prevalence of pancreatitis changes in cirrhotics in comparison to non-cirrhotics. There was no correlation between the amount and length of alcohol intake and changes in pancreatitis. CONCLUSION: Pancreatic ductal changes on endoscopic retrograde pancreatogram are common in patients with alcoholic liver disease.     

Oxidation Phenotyping in Alcoholics with Liver Disease of Varying Severity

The propensity to develop alcoholic cirrhosis is probably, at least in part, genetically determined. A striking similarity exists histologically between perhexiline and alcohol-related hepatitis and both are potentially precirrhotic lesions. Liver damage due to perhexiline is associated with impaired drug oxidation capacity which is genetically determined and tested by use of debrisoquine. Oxidation phenotyping might be used to predict susceptibility to perhexiline liver damage; it might also predict the potential to develop alcoholic cirrhosis. Oxidation phenotyping was therefore undertaken, using debrisoquine in 100 alcoholic patients, 30 of whom had only fatty liver despite prolonged alcohol abuse, while the remaining 70 had alcoholic hepatitis and/or cirrhosis. One hundred patients with nonalcoholic chronic liver disease served as controls. The number of patients with severely impaired drug oxidation capacity (poor metabolizer phenotype) was similar in the alcoholic group (8%) and the nonalcoholic control group (7%). In particular, the incidence of the poor metabolizer phenotype was similar in alcoholics with severe liver disease (10%) and in those with only fatty change (3%). There appears to be no association between the susceptibility to develop alcoholic cirrhosis and drug oxidizing capacity.     

Influence of liver disease on hepatic alcohol and aldehyde dehydrogenases

The hepatic activities and the isoenzyme patterns of both alcohol dehydrogenase and aldehyde dehydrogenase have been studied in 60 alcoholics with varying degrees of liver damage (from normal tissue or minimal changes to cirrhosis with alcoholic hepatitis) and in 24 nonalcoholics with chronic hepatitis or cirrhosis in order to ascertain their association with liver damage. In alcoholics both alcohol dehydrogenase and low-Km aldehyde dehydrogenase activities decreased proportionally with the severity of liver disease. In contrast, in nonalcoholics, there was a reduction of low-Km aldehyde dehydrogenase activity related to the severity of liver injury, but alcohol dehydrogenase was similar in patients with chronic hepatitis and nonalcoholic cirrhosis. There were no significant changes in total and high-Km aldehyde dehydrogenase activities among the different histologic groups studied, although the lowest activities were observed in patients with more severe liver injury. The prevalence of atypical alcohol dehydrogenase was similar in alcoholic (6.6%) and in nonalcoholic (8.3%) liver disease. All patients exhibited isoenzyme aldehyde dehydrogenase II, whereas isoenzyme I was not detected in 39.5% of the alcoholic patients and in 9.5% of those with nonalcoholic liver disease. The lack of aldehyde dehydrogenase I was observed in cases with the lowest enzymatic activities. These results suggest that the decrease of alcohol and aldehyde dehydrogenase activities in alcoholics is not a primary defect and, therefore, their decrease is secondary to liver damage. It is speculated that the diminution of alcohol dehydrogenase, found particularly in alcoholics, could be due to centrilobular cell necrosis.     

Prevalence of brain atrophy in liver cirrhosis patients with chronic persistent encephalopathy: Evaluation by computed tomography

Brain computerized axial tomography scans were performed in 18 consecutive liver cirrhosis patients with chronic persistent encephalopathy (8 alcoholic and 10 nonalcoholic) in order to evaluate the incidence of brain atrophy in this pathological condition. Fifteen patients of similar age with liver cirrhosis of Child's class B but with acute episodic hepatic encephalopathy were studied in parallel. Brain atrophy was detected in 87.5% of alcoholic and in 50% of nonalcoholic liver cirrhosis patients with chronic persistent encephalopathy, whereas the patients with acute episodic encephalopathy were normal. The high frequency of brain atrophy in alcoholic patients with chronic encephalopathy can be attributed at least in part to the toxic effect of alcohol. The presence of brain atrophy in nonalcoholic liver cirrhosis patients with chronic persistent encephalopathy seems to indicate that the chronic exposure to toxins which are involved in the pathogenesis of hepatic encephalopathy leads to neuronal alterations which develop mainly in the cortex and which can be demonstrated by in vivo imaging only in a long-lasting state of coma. Moreover, alcohol and toxins causing hepatic encephalopathy seem to potentiate each other in inducing brain atrophy.     

Prognosis and prognostic factors in chronic pancreatitis

To evaluate the prognosis and prognostic factors of chronic pancreatitis, 84 patients with alcoholic chronic pancreatitis and 51 with nonalcoholic chronic pancreatitis have been followed for 1-21 years (average of 7.1 years). The follow-up period was defined as the period from diagnosis to death in those who died and to the present in those still alive. The following conclusions were obtained. (1) Patients with alcoholic chronic pancreatitis showed a significantly higher mortality rate (26.2%) and cancer death rate (8.3%) than the age- and sex-matched population. In patients with nonalcoholic chronic pancreatitis, however, the difference did not reach the level of statistical significance, although both rates tended to be higher. (2) Patients with alcoholic chronic pancreatitis showed a significantly poorer prognosis than those with nonalcoholic chronic pancreatitis. (3) Frequent causes of death in chronic pancreatitis were cancer (11 cases) and diabetes-associated conditions (renal failure in three cases, intractable pneumonia in one, hypoglycemic shock in two, and myocardial infarction in two). Death directly from pancreatitis was observed in four. (4) Unfavorable prognostic factors in alcoholic chronic pancreatitis included heavy drinking, continuance of drinking after diagnosis, smoking, insulin-dependent diabetes, and an advanced age. In nonalcoholic chronic pancreatitis, however, patients' age was the only significant prognostic factor; smoking did not reach the level of statistical significance, although it tended to lead to a poorer prognosis.     

A prospective study of pancreatic disease in patients with alcoholic cirrhosis: comparative diagnostic value of ERCP and EUS and long-term significance of isolated parenchymal abnormalities

BACKGROUND: The prevalence of pancreatic disease in patients with alcohol-related liver cirrhosis is uncertain. We assessed the prevalence of pancreatic abnormalities in patients with alcoholic cirrhosis, and we compared endoscopic ultrasonography (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) for the detection of chronic pancreatitis and other pancreatic lesions. In addition, we assessed the long-term significance of isolated pancreatic parenchymal abnormalities detected at EUS. METHODS: EUS and ERCP were performed in each patient. Subjects with minimal parenchymal changes at initial EUS underwent clinical follow-up and subsequent EUS and/or ERCP to document the occurrence, absence, or progression of these changes. RESULTS: Seventy-two patients with alcoholic cirrhosis were recruited. Chronic pancreatitis was diagnosed in 14 patients (19%) by both methods independently. Isolated parenchymal lesions were observed in 18 patients by EUS alone. After a mean follow-up of 22 months the EUS appearance was unchanged. Ten of the 18 patients underwent follow-up ERCP and this was normal in all cases. CONCLUSIONS: This study demonstrated that (1) 19% of patients with alcoholic cirrhosis have chronic pancreatitis, (2) an additional 25% have isolated pancreatic parenchymal changes at EUS, and (3) these parenchymal abnormalities do not progress during follow-up.     

Associated liver disease in alcoholic pancreatitis

Two studies investigating the association of liver disease with acute and chronic pancreatitis in alcoholics are presented. In a retrospective study of 50 patients, no clinical liver disease was found in 9 patients with acute pancreatitis, while 23 (56%) of 41 patients with chronic pancreatitis had liver disease by clinical criteria. Of this latter group, 8 were confirmed histologically; thus 19% of patients with chronic pancreatitis had biopsy-proven cirrhosis. Fifty alcoholic patients with pancreatitis were prospectively evaluated. All who had clinical evidence of liver disease were biopsied. No cases of liver disease were encountered in the 4 patients with acute pancreatitis. Although 28 (60%) cases of clinically diagnosed liver disease were present in 46 patients with chronic pancreatitis, only 20 of these seemed significant (cirrhosis, alcoholic hepatitis, severe fatty liver), for an incidence of 43%. Thus, clinically significant alcoholic liver disease occurs quite frequently in association with alcoholic pancreatitis. This association is meaningful in more effective management of these patients in general and in preoperative assessment of the risk of surgery in particular.Presented in part, at the Annual Meeting of American Pancreatic Study Group held on November 7, 1975, in Chicage, Illinois.     

Changes in pancreatic secretion in alcoholic liver disease

By means of consecutive pancreatic stimulation, we have investigated the presence of changes of pancreatic function in alcoholic patients, with and without alcoholic liver disease, in order to detect functional alterations and possible association of hepatic and pancreatic disease. The patients were 49 chronic alcoholics (8 patients without liver disease, 11 hepatic steatosis, 9 alcoholic hepatitis and 21 alcoholic cirrhosis) and 15 non alcoholic subjects (8 normal controls and 7 cases of non alcoholic cirrhosis). In all the cases two consecutive stimulations were carried out: first with secretin and cholecystokinin (CCK) and second with CCK alone. The total volume and concentration as well as the output of bicarbonate, trypsin, amylase and total proteins were measured in the duodenal juice. Patients with alcoholic cirrhosis had larger volumes of duodenal juice and lower concentrations of bicarbonate, enzymes and proteins. There was also a tendency to larger volume and lower bicarbonate concentration as the hepatic lesion was more severe. Bicarbonate output was significatively higher in patients with alcoholic cirrhosis but for the remaining parameters the outputs were similar in all the groups. In conclusion, the alterations in pancreatic function parallel the severity of the liver disease. None of the patients had changes consistent with chronic pancreatitis.     

Exocrine Pancreatic Function in Chronic Liver Diseases

To confirm the respective influence of chronic alcoholism and liver disease on exocrine pancreatic function in cholecystokinin secretin (CS), tests were performed on patients with chronic liver cirrhosis (LC) and non-cirrhotic (nLC) disease of alcoholic (A) and nonalcoholic (nA) etiology. Results were compared in four subgroups (ALC, N = 26; AnLC, N = 45; nALC, N = 18; and nAnLC, N = 43). Volume of duodenal juice and bicarbonate output (BO) were increased and maximal bicarbonate concentration was decreased in ALC, compared with those in normal controls. Comparison of LC and nLC indicated that the volume, BO, and amylase output (AO) were greater in LC than in nLC of alcoholic etiology, but not in those of nonalcoholic etiology. The initial disappearance rate (KICG) of indocyanine green (ICG) excretion correlated with a parameter of CS test in alcoholic liver disease (vs. volume: r = -0.51, p less than 0.01 vs BO: r = -0.40, p less than 0.01), but not in nonalcoholic liver disease. Concurrent chronic pancreatitis with pain and definite exocrine insufficiency was observed in only one ALC patient and in four AnLC patients, but in none of the nonalcoholics. In alcoholic liver disease, exocrine pancreatic secretion tends to increase with severity of liver damage, but concurrence of definite chronic pancreatitis is not correlated with the severity.     

Pancreatitis associated with alcoholic liver disease

The prevalence with which alcoholic pancreatitis is associated with alcoholic liver disease is unclear. To investigate this association further, we have reviewed the autopsy findings of 1022 patients who died from alcoholic liver disease and compared these findings with those from 352 patients who died from cardiac or pulmonary disease. All patients who died from liver disease had a history of chronic alcoholism with clinical and biochemical evidence of severe liver damage. Death resulted from hepatic coma, gastrointestinal bleeding, or infection. Liver disease patients were classified into two groups: (1) those with cirrhosis (77%) and (2) those without cirrhosis but with acute and/or chronic sclerosing hyaline necrosis (23%). Anatomic and histopathologic changes characteristic of chronic pancreatitis were found in 203 patients in approximately the same frequency (20% and 18%, respectively) in both groups. Acute pancreatitis without chronic lesions was observed in 8% and 10% of both groups, respectively. In the control group of 352 autopsies (122 cardiac and 230 pulmonary patients), the overall prevalence of pancreatitis, at 2.6%, was significantly (P<0.001) lower than that observed in the alcoholic liver disease groups. A total of 22 cases (50%) dying from acute or chronic sclerosing hyaline necrosis had severe chronic calcifying pancreatitis compared to 29 patients (18%) (P<0.001) dying from cirrhosis. By contrast, dense fibrosis was significantly (P<0.001) more commonly observed in patients with cirrhosis. We conclude that pancreatitis occurs frequently in patients dying from alcoholic liver disease but is an uncommon finding in patients dying from other causes. Biliary tract pathology was more prevalent (P<0.05) in patients dying from cirrhosis without pancreatitis than those patients dying from liver disease with pancreatitis. In the control group of patients dying from pulmonary or cardiac disease, biliary pathology was far less frequently (P<0.01) observed.     

Is tobacco a risk factor for chronic pancreatitis and alcoholic cirrhosis?

In a case control study alcohol intake and tobacco use were assessed between 1975 and 1987 in 103 male patients suffering from alcoholic cirrhosis of the liver, in 145 patients with chronic pancreatitis, and in 264 control subjects. The patients with chronic pancreatitis were significantly younger than the patients with cirrhosis (mean (SD) age 41.92 (2.4) v 60.9 (11.6) years). Among the patients with chronic pancreatitis, 94% were both smokers and drinkers compared with 83% of patients with cirrhosis of the liver. The relative risks for each disease were calculated by conditional multiple logistic regression. Whereas daily intake of alcohol was a major risk factor for both cirrhosis of the liver and chronic pancreatitis, smoking was significantly related only to the risk of having chronic pancreatitis. Moreover, the mean age at onset of pancreatitis was lower among smokers.     

CD14 promoter polymorphism in Chinese alcoholic patients with cirrhosis of liver and acute pancreatitis

AIM: To investigate the relationship between genetic polymorphism of the CD14 promoter and the occurrence of alcoholic cirrhosis and alcoholic pancreatitis, and to challenge the conclusion made earlier that the patients with acute alcoholic pancreatitis and patients with alcoholic cirrhosis of liver are two different subpopulations. METHODS: Using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, we determined the polymorphism of CD14 gene and aldehyde dehydrogenase gene 2 (ALDH 2) in 335 alcoholic patients with different organ complications i.e., cirrhosis of liver (n = 100), acute pancreatitis (n = 100), esophageal cancer (n = 82) and avascular necrosis of hip joint (AVN) (n = 53) and 194 non-alcoholic controls in a Chinese group. RESULTS: The results showed that the carriage of T allele was not different among alcoholic patients with cirrhosis of liver, alcoholic patients with other complication and non-alcoholic controls. On the other hand, the carriage of the C allele was significantly more prevalent for alcoholic pancreatitis than for esophageal cancer (0.79 vs 0.60, P<0.001), alcoholic AVN (0.79 vs 0.65, P<0.025) and nonalcoholic controls (0.79 vs 0.68,P<0.025). Furthermore, when only subjects with ALDH2 1-1 genotype were examined, the C allele frequency was significantly more prevalent for alcoholic pancreatitis than for alcoholic liver cirrhosis (0.82 vs 0.69,P<0.025), esophageal cancer (0.82 vs 0.61,P><0.01), alcoholic AVN (0.82 vs 0.64, P<0.01) and non-alcoholic controls (0.82 vs 0.69, P<0.05). CONCLUSION: The C allele may be associated with some mechanism, which is important in the pathogenesis of alcoholic pancreatitis, and that alcoholic patients with acute pancreatitis and cirrhosis of liver are probably two different subpopulations.     

Neuropsychological Aspects of Portal-Systemic Encephalopathy

An extensive psychometric test program was performed in 96 patients with proven liver cirrhosis and clinical signs of portal hypertension as well as in 20 patients with alcoholic pancreatitis, in 19 patients without cirrhosis but with alcoholic cerebral atrophy and in 163 normal controls. The study population comprised six groups of subjects as follows:Group 1. 27 patients with non-alcoholic cirrhosis and normal EEG pattern " 2. 48 patients with alcoholic cirrhosis and normal EEG pattern " 3. 21 patients with cirrhosis and minimal EEG changes " 4. 20 patients with alcoholic pancreatitis " 5. 19 patients without cirrhosis but with alcoholic cerebral atrophy " 6. 163 normal controls.A one way analysis of variances comparing asymptomatic patients (group 1, 2 and 4) with controls (group 6) revealed no significant differences between patients with alcoholic and non-alcoholic cirrhosis, both cirrhotic groups scoring significantly lower than patients with alcoholic pancreatitis and normal controls, who did not differ significantly. Comparing symptomatic patients (group 3 and 5) with normal controls both patient groups scored significantly lower than controls, the cirrhotic group (group 3) scoring significantly lower than patients with alcoholic cerebral atrophy. A two way analysis of variances revealed that in clinically asymptomatic patients cerebral functional defects revealed by psychometry are only due to cirrhosis and that in patients with clinical evidence of cerebral impairment the factors alcohol and cirrhosis are additive - not synergistic. A multiple group stepwise discriminant analysis revealed that tests evaluating psychomotor functions contributed most to the discrimination. Especially line tracing proved to be most sensitive and most specific followed by dexterity, steadiness, aiming, digit symbols in sensitivity and by reaction time, steadiness and dexterity in specificity. A test program for clinical use is proposed.     

Alcoholism and alcoholic organ damage and genetic polymorphisms of alcohol metabolizing enzymes in Chinese patients

It is still not clear why some alcoholic patients acquire certain organ-specific complications of alcoholism whereas other alcoholic patients acquire different ones. As we know the liver alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and cytochrome P4502E1 (P4502E1) are polymorphic at the ADH2, ADH3, and ALDH2 loci and the 5'-flanking region of the P4502E1. The aim of this study was to investigate the differences between Chinese alcoholic patients with cirrhosis and acute pancreatitis by studying the genetic polymorphisms of ADH2, ADH3, ALDH2, and P4502E1. Genotyping of ADH2, ADH3, ALDH2, and P4502E1 was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods on peripheral white blood cell DNA from 75 alcoholic cirrhotic patients, 48 acute alcoholic pancreatitis patients, 19 heavy drinkers without liver disease or pancreatitis, and 235 controls. The results showed that the frequencies of the alleles ADH2*1 and ALDH2*1 in the alcoholic cirrhotic patients were significantly higher than those in the nonalcoholic controls. In acute alcoholic pancreatitis patients, only the frequency of allele ALDH2*1, not ADH2*1 was significantly higher than in the nonalcoholic controls. The allele frequency of ADH2*1 in acute pancreatitis patients was significantly lower (P < .01) than in alcoholic cirrhotic patients. The daily amount of alcohol consumption was significantly lower in patients with acute pancreatitis than in patients with cirrhosis (P < .0005). The genotype distributions of P4502E1, detected by RsaI and PstI, were not different among alcoholic cirrhotic patients, alcoholic pancreatitis patients, heavy drinker, and nonalcoholic controls. In conclusion, ALDH2*1 is the most important alcohol metabolizing gene affecting predisposition to alcoholism whereas the ADH2*2 gene may influence susceptibility to acute alcoholic pancreatitis. The patients with alcohol-induced cirrhosis and with alcohol-induced acute pancreatitis are of two different subpopulations.(Hepatology 1997 Jan;25(1):112-7)     

Hospital contacts with alcohol problems prior to liver cirrhosis or pancreatitis diagnosis

AIM To evaluate prior hospital contacts with alcohol problems in patients with alcoholic liver cirrhosis and pancreatitis. METHODS This was a register-based study of all patients diagnosed with alcoholic liver cirrhosis or pancreatitis during 2008-2012 in Denmark. Hospital contacts with alcohol problems(intoxication, harmful use, or dependence) in the 10-year period preceding the diagnosis of alcoholic liver cirrhosis and pancreatitis were identified.RESULTS In the 10 years prior to diagnosis, 40% of the 7719 alcoholic liver cirrhosis patients and 40% of the 1811 alcoholic pancreatitis patients had at least one prior hospital contact with alcohol problems. Every sixth patient(15%-16%) had more than five contacts. A similar pattern of prior hospital contacts was observed for alcoholic liver cirrhosis and pancreatitis. Around 30% were diagnosed with alcohol dependence and 10% with less severe alcohol diagnoses. For the majority, admission to somatic wards was the most common type of hospital care with alcohol problems. Most had their first contact with alcohol problems more than five years prior to diagnosis.CONCLUSION There may be opportunities to reach some of the patients who later develop alcoholic liver cirrhosis or pancreatitis with preventive interventions in the hospital setting.     

Comparison of portacaval shunts in patients with alcoholic and nonalcoholic liver disease

A series of 46 patients with alcoholic and nonalcoholic cirrhosis and who underwent portasystemic decompressive procedures were analyzed and compared. The two groups were similar in age and degree of dysfunction according to liver function tests and functional classification. For both emergency and elective procedures operative mortality was significantly less in the nonalcoholic group: For emergency procedures it was 20% in the nonalcoholic group, 57% in the alcoholic; for elective procedures it was 5.3% in the nonalcoholic, 20% in the alcoholic. Long-term survival and frequency of severe encephalopathy were nearly the same for both groups although 60-year-old or older nonalcoholics did better, with no operative deaths and only 1 case of severe encephalopathy. The older patients with alcoholic cirrhosis faired poorly—4 of 5 died of hepatic failure, 2 during the operative period. Three patients had active chronic hepatitis and cirrhosis. One died during the operative period; the other 2 have suffered from chronic encephalopathy requiring continuous medical therapy for control.At the VA Hospital Woodard is a Research and Education Trainee in Gastroenterology and Webster is a Medical Investigator.     

Short-term prognosis of community-acquired bacteremia in patients with liver cirrhosis or alcoholism: A population-based cohort study

BACKGROUND: Liver cirrhosis is associated with an increased risk of infection and a poor prognosis, but the role of alcoholism in these outcomes is uncertain. This study looks at the short-term prognosis for bacteremia in patients with alcoholic liver cirrhosis, nonalcoholic liver cirrhosis, and alcoholism, compared with the prognosis for other bacteremia cases. METHODS: All patients who were hospitalized with their first community-acquired bacteremia in North Jutland County, Denmark, in the period 1992 to 2002 were retrieved from a population-based bacteremia registry. Denmark's Hospital Discharge Registry then allowed us to disaggregate these patients into the following groups: 47 patients with alcoholic liver cirrhosis, 19 with nonalcoholic liver cirrhosis, 190 with alcoholism, and a comparison group of 3,535 other bacteremia cases. Using logistic regression, we estimated odds ratios (ORs) for 30-day case fatality for the main study variable, adjusted for gender, age, focus of infection, and comorbidity. RESULTS: The case fatality rate (CFR) was 43% for patients with alcoholic liver cirrhosis, 32% for patients with nonalcoholic liver cirrhosis, 24% for patients with alcoholism, and 15% for other bacteremia patients. The adjusted OR estimates for patients with alcoholic liver cirrhosis, nonalcoholic liver cirrhosis, and alcoholism compared with other bacteremia cases were 6.3 (95% CI 3.3-11.7), 2.4 (95% CI 0.9-6.7), and 2.5 (95% CI 1.7-3.7), respectively. Focus of infection and group of bacteria did not noticeably affect the increased CFR. CONCLUSION: Liver cirrhosis and alcoholism were associated with a poor short-term prognosis for community-acquired bacteremia. Liver cirrhosis and alcoholism may have independent effects on the prognosis for patients with liver cirrhosis and bacteremia.     

Plasma amino-acid patterns in liver disease.

Plasma amino-acid concentrations were measured in 167 patients with liver disease of varying aetiology and severity, all free of encephalopathy, and the results compared with those in 57 control subjects matched for age and sex. In the four groups of patients with chronic liver disease (26 patients with chronic active hepatitis, 23 with primary biliary cirrhosis, 11 with cryptogenic cirrhosis, and 48 with alcoholic hepatitis +/- cirrhosis) plasma concentrations of methionine were significantly increased, while concentrations of the three branched chain amino-acids were significantly reduced. In the first three groups of patients plasma concentrations of aspartate, serine, and one or both of the aromatic amino-acids tyrosine and phenylalanine were also significantly increased, while in the patients with alcoholic hepatitis +/- cirrhosis plasma concentrations of glycine, alanine, and phenylalanine were significantly reduced. In the three groups of patients with minimal, potentially reversible liver disease (31 patients with alcoholic fatty liver, 10 with viral hepatitis, and 18 with biliary disease) plasma concentrations of proline and the three branched chain amino-acids were significantly reduced. Patients with alcoholic fatty liver also showed significantly reduced plasma phenylalanine values. Most changes in plasma amino-acid concentrations in patients with chronic liver disease may be explained on the basis of impaired hepatic function, portal-systemic shunting of blood, and hyperinsulinaemia and hyperglucagonaemia. The changes in patients with minimal liver disease are less easily explained.     

Chinese alcoholic patients with esophageal cancer are genetically different from alcoholics with acute pancreatitis and liver cirrhosis

OBJECTIVE: It is a mystery why some alcoholic patients acquire certain organ-specific complications of alcoholism, whereas other alcoholic patients acquire different ones. The aim of this study was to investigate the differences among Chinese alcoholic patients with esophageal cancer, acute pancreatitis, and liver cirrhosis by studying the genetic polymorphisms of ADH2, ADH3, ALDH2, and P4502E1. METHODS: Liver alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and cytochrome P4502E1 (P4502E1) are polymorphic at the ADH2, ADH3, and ALDH2 loci and the 5'-flanking region of the P4502E1. Using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, we determined the polymorphism of the above-mentioned alcohol metabolizing genes in 59 alcoholics with carcinoma of the esophagus (alcoholic esophageal Ca), 87 acute alcoholic pancreatitis patients, 116 alcoholics with liver cirrhosis (alcoholic cirrhosis), 19 alcoholics with both liver cirrhosis and acute pancreatitis (alcoholic P plus C), and 241 nonalcoholic patients. RESULTS: The results showed that the allele frequency of ALDH2*2 was significantly higher in the alcoholic esophageal Ca group than in the alcoholic pancreatitis and alcoholic cirrhosis groups. The allele frequency of ADH2*1 was significantly higher in the alcoholic esophageal Ca patients than in nonalcoholic control groups. The ALDH2*2 was significantly lower in alcoholic groups (except the alcoholic esophageal Ca group) than in nonalcoholic control groups. The allele frequencies of ADH2*1 and ALDH2*2 are higher in alcoholic patients with esophageal Ca than alcoholic patients without it. The genotype distribution of P4502E1, detected by RsaI and PstI, was not different among alcoholic patients with different organ diseases. CONCLUSIONS: The allele frequency of ADH2*1 and ALDH2*1 are different among subpopulations of alcoholics, suggesting that alcoholic patients with different specific types of organ damage are genetically different. The Chinese alcoholic patients with the ADH2*1 and ALDH2*2 allele are more susceptible to esophageal Ca.