Alcohol-induced Liver Cirrhosis Research Articles

Liver Transplantation for Alcohol-Related Cirrhosis: A Single Centre Long-Term Clinical and Histological Follow-Up

Alcohol-induced liver cirrhosis is one of the leading indications for liver transplantation today. Due to the general organ shortage and continuous deaths on the waiting list there has been some debate on the issue of indication and ethical problems. It was the aim of this study to critically analyse the outcome of patients with alcoholic cirrhosis transplanted at our centre with special emphasis on alcohol-recurrence frequency and long-term histological follow-up. Three hundred five patients who received LT for alcoholic cirrhosis at our institution were followed over a period of 3-10 years after transplantation. Biopsies were taken 1, 3, 5, and 10 years after LT. Specimens were analysed and staged concerning inflammation, rejection, fatty involution, and fibrosis/cirrhosis. Clinical characteristics as well as serological parameters, immunosuppressive protocols, rejection episodes, and patient and graft survival were recorded. Recurrence of alcohol abuse occurred in 27% of all patients analysed. Regardless of alcohol consumption, 5-year graft and patient survival were excellent; after 10 years abstinent patients showed significantly better survival (82% vs. 68%; P=0.017). Histological changes were slightly more pronounced among recurrent drinkers, no significant difference regarding inflammation or fibrosis was detected. Patients undergoing LT for alcohol-induced cirrhosis show excellent long-term survival rates with stable graft function. Alcohol recurrence impairs long-term prognosis; however, compared to other patient sub-populations (HCC, HCV) results are clearly above average.

Comment on: 'Lanthanum carbonate possibly responsible for acute liver failure in a patient with Child-Pugh stage A liver cirrhosis'.

Sir, De Leeuw and colleagues reported decompensation of existing liver disease in a patient with a complex history including alcohol-induced liver cirrhosis, pancreatitis and secondary diabetes [1]. The patient required hospitalization due to decreased consciousness and somnolence. The authors, noting a temporal association with lanthanum carbonate therapy, proposed that there was a causal relationship. This patient report is highly confounded by a number of factors, including concomitant medication and hypophosphataemia, which are also credible explanations for the patient's presentation. Firstly, the patient was taking lorazepam, which can cause coma in patients with reduced hepatic metabolism. Secondly, following dialysis the patient was profoundly hypophosphataemic. This is a recognized cause of irritability, paraesthaesia, confusion, convulsions and coma [2]. Evaluation of the published data on lanthanum carbonate (FOSRENOL®, Shire Pharmaceuticals, Basingstoke, UK) shows that the bioavailability is ∼0.001% and the small fraction of lanthanum absorbed is not metabolized. Animal studies have demonstrated that the presence of lanthanum in the liver is consistent with hepatic excretion via a lysosomal transcellular transport mechanism [3,4]. A long-term follow-up of clinical trial cohorts has included liver function tests and has not demonstrated any evidence of acute or chronic liver toxicity during 2 years of therapy compared to standard therapy. In uncontrolled studies, subjects have been exposed to lanthanum carbonate for up to 6 years [5,6]. In addition to over 5000 subjects in clinical studies, there is now over 60000 patient-years of post-marketing experience with lanthanum carbonate. Although no specific studies were done in patients with liver impairment, there is insufficient evidence to assume that lanthanum carbonate may contribute to a worsening of liver function in this patient population. Conflict of interest statement. M.S., B.G. and R.D.P. are employees of Shire Pharmaceuticals. Editorial Note: Dr De Leeuw et al. had been invited to reply to this letter but we did not receive a response in time.

Silymarin in the treatment of chronic liver diseases: past and future

In the treatment of chronic liver diseases adequate therapy can be chosen only in the knowledge of pathogenetic processes. In the liver diseases caused by oxidative stress (alcoholic and non-alcoholic fatty liver and steatohepatitis, drug and compound induced liver toxicity) the antioxidant drugs, like silymarin, in chronic hepatitis caused by hepatitis B and hepatitis C virus, combined peginterferon and nucleosid treatments are the primary therapy modalities to be selected. The main effects of silymarin are the membrane stabilising and antioxidant effects, it is able to help the liver cell regeneration, it can decrease the inflammatory reaction and inhibit the fibrogenesis in the liver. These results have been established by experimental and clinical trials. According to open studies, the long administration of silymarin significantly increased the survival time of patients with alcohol-induced liver cirrhosis. Recently it was demonstrated that high-dosage silibinin infusion treatment could significantly decrease the number of hepatitis C viruses after four-week application. On the basis of the results with the methods of molecular biology, silymarin is able to decrease significantly tumor cell proliferation, angiogenesis as well as insulin resistance. These results support the administration of silymarin preparations in the therapy of chronic liver diseases, especially in alcoholic and non-alcoholic steatohepatitis in current clinical practice, and as it can be awaited, also in the future. In some neoplastic diseases they could also be administered as adjuvant therapy.

Are the opportunities to prevent alcohol related liver deaths in the UK in primary or secondary care? A retrospective clinical review and prospective interview study

BackgroundDeaths from liver cirrhosis have increased at least 8 fold since the 1970's in the UK and further increases are anticipated, whereas in the rest of Europe liver deaths are decreasing. In the UK, we urgently need strategies to detect those who misuse alcohol and are at risk of developing alcoholic liver disease before they get to that point. One potential strategy is to screen admissions to hospital with alcohol related conditions for evidence of alcohol misuse.Surprisingly, there has been no research into the important question of where the opportunities are to detect those who misuse alcohol – primary or secondary care. We attempted to answer this firstly by conducting a retrospective analysis of the medical notes of 94 patients diagnosed with alcohol induced liver cirrhosis between 1st January 1995 and 31st December 2000 at Southampton General Hospital with the purpose of identifying admissions to hospital prior to a diagnosis of alcoholic liver disease. In the second part of the study, we interviewed patients with alcoholic liver disease about their contact with health services.ResultsBefore diagnosis of alcoholic liver disease, 33% (31/94) of the patients had had an admission to hospital for an alcohol related condition. There was a mean of 7 years and 1 month (SD 6 years 3 months) between the first alcohol-related admission and presentation with alcoholic liver disease (in those who had had admissions). The commonest reason for alcohol related admission was falls/fractures/injuries, followed by non-variceal gastro-intestinal bleeds. Patients with alcoholic liver disease who were interviewed had seen their General Practitioner on average at least 2 times per year.ConclusionMost patients who develop alcohol-induced cirrhosis do not have an admission to hospital with an alcohol related condition before developing alcoholic liver disease. Therefore, if we screen patients admitted to hospital with alcohol related conditions for evidence of alcohol misuse, we could potentially detect around a third of those at risk of developing cirrhosis. Although secondary care has an important role to play in detecting those at risk, the main opportunity for detection is in primary care.

Incidence and factors predictive of acute renal failure in patients with advanced liver cirrhosis

Acute renal failure (ARF) is a life-threatening entity that frequently complicates advanced liver disease. This study documents a number of factors that may predispose to or precipitate ARF and influence outcomes in patients with advanced liver disease. Comparisons are also made between subgroups of patients with viral and alcohol-induced liver cirrhosis in those with ARF. We conducted a retrospective chart review over one year of 127 consecutive hospital admissions in 82 patients who were diagnosed with advanced liver cirrhosis (Child-Pugh Class C) in a tertiary care center. A diagnosis of ARF was made in 29 admissions and another 98 admissions not complicated by ARF served as controls. This study evaluated different etiologies of ARF and developed a database which included clinical features, biochemical parameters, the etiology of cirrhosis, possible predisposing factors, and precipitating events. Version II of the Acute Physiology and Chronic Health Physiology Scoring system (APACHE II) was applied to predict short-term hospital mortality rates. ARF occurred in 29 admissions over the one-year study period (23%). The mean age of these patients was 56.8 +/- 12.0 years, and 73% were men. The patients with ARF had significant hyponatremia and higher levels of serum bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and white cell counts on admission than the controls. Patients who developed ARF were more likely to have had infection, especially septicemia, and gastrointestinal (GI) bleeding. Mortality rate in the patients with ARF was much higher than in those patients without ARF (72% vs. 13%, p < 0.001). The patients with viral cirrhosis and ARF were found to have higher leukocyte counts, serum bilirubin levels, and more frequent incidence of infection, septicemia and GI bleeding compared to the patients with alcoholic liver cirrhosis and ARF. Those with viral hepatitis were also significantly older and had more frequent incidence of ascites, but had lower levels of gamma-glutamyl transpeptidase and less frequent incidence of encephalopathy. The risk of ARF is significantly increased in patients with advanced liver cirrhosis presenting with marked hyperbilirubinemia, hyponatremia, elevated liver enzymes, infection, and GI bleeding. The presence of ARF leads to higher mortality rates in both viral and alcohol-induced liver cirrhosis.

Alcohol Causes Liver Damage But May Be Beneficial To The Cardiovascular System: A Short Discussion On The Relative Risk And Benefits Of Alcohol Consumption

Alcohol Causes Liver Damage But May Be Beneficial To The Cardiovascular System: A Short Discussion On The Relative Risk And Benefits Of Alcohol Consumption

Alcohol dehydrogenase 3∗1 genotype is associated with hepatocellular carcinoma in alcohol-induced liver cirrhosis

Alcohol dehydrogenase 3∗1 genotype is associated with hepatocellular carcinoma in alcohol-induced liver cirrhosis

Comparison of prevalence for paraumbilical vein patency in patients with viral and alcoholic liver cirrhosis

OBJECTIVES: The patent paraumbilical vein (PUV) is a venous collateral that is often found in patients with cirrhosis and portal hypertension. It can be effectively demonstrated by conventional ultrasonography (US). We conducted this prospective study to elucidate the prevalence and etiology of PUV patency for cirrhotic patients. METHODS: From August, 1997, to July, 1998, one of the authors (S.-N.L.) observed PUV patency for all cirrhotic patients during routine upper abdominal US examination. All cirrhotic patients diagnosed with portal hypertension were further analyzed. Portal hypertension was diagnosed by sonographic evidence of splenomegaly or ascites, or endoscopic varices. Cases presenting with hepatocellular carcinoma and sonographic evidence of prehepatic portal hypertension were excluded. Once a PUV patency with a diameter of ≥3 mm was suspected based on conventional US, it was confirmed by color Doppler US. Of the 493 cirrhotic patients examined, 252 with portal hypertension and without hepatoma were enrolled in this study. RESULTS: Significant PUV patency was detected in 11.1% of the enrolled patients (28 of 252). With univariate analysis, a significantly higher prevalence was demonstrated for alcoholic patients ( p < 0.0001), whereas prevalence was relatively low for those with chronic hepatitis B or C infection ( p = 0.0159). A trend toward increased prevalence was noted with Child-Pugh classification ( p = 0.001). Furthermore, a higher prevalence was noted in younger cirrhotic patients ( p = 0.0037). Alcoholism was still a significant factor despite adjustment of Child-Pugh classification using multiple logistic regression, (OR = 3.88, 95% CI = 1.34–8.55). CONCLUSION: A significantly higher prevalence of PUV patency was demonstrated for patients with alcohol-induced liver cirrhosis in comparison to those with postviral cirrhosis.

CYP2A6: a human coumarin 7-hydroxylase

Coumarin 7-hydroxylation is catalysed by a high-affinity CYP2A6 enzyme in human liver microsomes. CYP2A6 is the only enzyme catalysing this reaction and consequently the formation of 7-hydroxycoumarin can be used as ‘an in vitro and in vivo probe’ for CYP2A6. CYP2A6 is a major contributor to the oxidative metabolism of nicotine and cotinine, and it also contributes, to a larger or smaller extent, to the metabolism of a few pharmaceuticals (e.g. fadrozole), nitrosamines, other carcinogens (e.g. aflatoxin B1) and a number of coumarin-type alkaloids. CYP2A6 may be inducible by antiepileptic drugs and it is decreased in alcohol-induced severe liver cirrhosis. Several mutated or deleted CYP2A6 alleles have been characterized. Although CYP2A6 represent up to 15% of human microsomes P450 proteins, it is still one of the less well characterised cytochrome P450 enzymes.

Acetaldehyde‐Mediated Collagen Regulation in Hepatic Stellate Cells

Alcohol-induced liver cirrhosis is one of the major causes of death worldwide. Strong evidence has established that ethanol's first metabolite, acetaldehyde, is highly fibrogenic and enhances the deposition of many extracellular matrix components by hepatic stellate cells. This article reviews our current knowledge of the molecular mechanisms whereby acetaldehyde induces these activities, with particular emphasis on those related to the upregulation of type I collagen.

The beneficial effects of ciprofloxacin on survival and hepatic regenerative activity in a rat model of fulminant hepatic failure

Recently, we reported that ciprofloxacin, an antimicrobial agent with gamma-aminobutyric acid (GABA(A)) receptor antagonist properties, significantly increases hepatic regenerative activity in animal models of alcohol-induced liver disease and cirrhosis. In the present study, we documented the effects of ciprofloxacin on survival and hepatic regeneration in a D-galactosamine (D-gal)-induced model of acute hepatic injury in rats. One hundred nineteen adult, male Sprague-Dawley rats (n = 19-20/group) were treated with intraperitoneal D-gal (total dose: 2.5 g/kg), followed by gastric gavage with either saline, ciprofloxacin (10, 50, or 100 mg/kg), norfloxacin (250 mg/kg), or intraperitoneal putrescine (300 micromol/kg), a potent hepatic growth promoter. Mortality rates were then documented over a 4-day period. An additional 45 rats (n = 15/group) received a sublethal dose of D-gal (1.0 g/kg), followed by gastric gavage with either saline or ciprofloxacin (100 mg/kg), or intraperitoneal putrescine (300 micromol/kg). In these rats, hepatic regenerative activity was documented at 12, 24, and 60 hours post-D-gal by 3H-thymidine incorporation into hepatic DNA and proliferating cell nuclear antigen (PCNA) staining. In the survival study, a dose-response effect of ciprofloxacin on survival was observed (ciprofloxacin: 10 mg/kg, 10%; 50 mg/kg, 26%; and 100 mg/kg, 35%) with the results in the 100-mg/kg-treated group being significant when compared with the 5% survival rate in saline-treated controls (P < .05). Survival figures in the norfloxacin- and putrescine-treated groups were not significantly improved (15% and 25%, respectively). In the regeneration study, compared with the D-gal + saline-treated control group, DNA synthesis rates at 60 hours were increased in the D-gal + ciprofloxacin and D-gal + putrescine groups (10.2 +/- 3.3 vs. 18.2 +/- 5.1 and 18.8 +/- 6.8 x 10(3) dpm/mg DNA respectively; P < .05). The results of PCNA staining also supported enhanced hepatic regeneration in the ciprofloxacin-treated group at 60 hours (saline, 13.4 +/- 3.7; ciprofloxacin, 47.4 +/- 7.3; and putrescine, 8.4% +/- 2.8% hepatocytes staining positive). Ciprofloxacin at a dose of 100 mg/kg significantly improves survival and hepatic regenerative activity in this animal model of acute hepatic injury.

The beneficial effects of ciprofloxacin on survival and hepatic regenerative activity in a rat model of fulminant hepatic failure.

Recently, we reported that ciprofloxacin, an antimicrobial agent with gamma-aminobutyric acid (GABA(A)) receptor antagonist properties, significantly increases hepatic regenerative activity in animal models of alcohol-induced liver disease and cirrhosis. In the present study, we documented the effects of ciprofloxacin on survival and hepatic regeneration in a D-galactosamine (D-gal)-induced model of acute hepatic injury in rats. One hundred nineteen adult, male Sprague-Dawley rats (n = 19-20/group) were treated with intraperitoneal D-gal (total dose: 2.5 g/kg), followed by gastric gavage with either saline, ciprofloxacin (10, 50, or 100 mg/kg), norfloxacin (250 mg/kg), or intraperitoneal putrescine (300 micromol/kg), a potent hepatic growth promoter. Mortality rates were then documented over a 4-day period. An additional 45 rats (n = 15/group) received a sublethal dose of D-gal (1.0 g/kg), followed by gastric gavage with either saline or ciprofloxacin (100 mg/kg), or intraperitoneal putrescine (300 micromol/kg). In these rats, hepatic regenerative activity was documented at 12, 24, and 60 hours post-D-gal by 3H-thymidine incorporation into hepatic DNA and proliferating cell nuclear antigen (PCNA) staining. In the survival study, a dose-response effect of ciprofloxacin on survival was observed (ciprofloxacin: 10 mg/kg, 10%; 50 mg/kg, 26%; and 100 mg/kg, 35%) with the results in the 100-mg/kg-treated group being significant when compared with the 5% survival rate in saline-treated controls (P < .05). Survival figures in the norfloxacin- and putrescine-treated groups were not significantly improved (15% and 25%, respectively). In the regeneration study, compared with the D-gal + saline-treated control group, DNA synthesis rates at 60 hours were increased in the D-gal + ciprofloxacin and D-gal + putrescine groups (10.2 +/- 3.3 vs. 18.2 +/- 5.1 and 18.8 +/- 6.8 x 10(3) dpm/mg DNA respectively; P < .05). The results of PCNA staining also supported enhanced hepatic regeneration in the ciprofloxacin-treated group at 60 hours (saline, 13.4 +/- 3.7; ciprofloxacin, 47.4 +/- 7.3; and putrescine, 8.4% +/- 2.8% hepatocytes staining positive). Ciprofloxacin at a dose of 100 mg/kg significantly improves survival and hepatic regenerative activity in this animal model of acute hepatic injury.

O.12 Adrenaline at supraphysiological plasma concentrations does not stimulate hepatic glucose production in patients with alcohol-induced liver cirrhosis

O.12 Adrenaline at supraphysiological plasma concentrations does not stimulate hepatic glucose production in patients with alcohol-induced liver cirrhosis

Glycerol metabolism in patients with alcohol-induced liver cirrhosis

The clearance rate of glycerol has been found to be impaired in alcoholic liver disease. However it remains unclear, if this can be ascribed to a defect of hepatic gluconeogenesis. Thus, the purpose of this work was to investigate glycerol clearance and hepatic glucose production in patients with liver cirrhosis. 13 patients with alcohol-induced Child B cirrhosis and 8 healthy volunteers were studied. Rates of appearance (R a) of glycerol, glucose and alanine were determined using stable isotope techniques. In addition indocyanine green clearance (ICGC) and plasma substrate concentrations were measured. Clearance rates were calculated as R a divided by the corresponding substrate concentration. R a of glycerol in patients was not different from controls, but glycerol clearance was significantly reduced (29 ± 3 vs. 41 ± 4 ml/kg/min). No differences in R a of glucose and alanine and corresponding plasma concentrations were observed. ICGC in patients was about 35% lower than reference values. Diminished glycerol clearance in patients with liver cirrhosis was not due to impaired hepatic gluconeogenesis. Since glycerol is almost completely extracted by the liver decreased glycerol clearance possibly simply reflected compromised liver perfusion as seen by reduced ICGC.

P.102 Glycerol metabolism in patients with alcohol-induced liver cirrhosis

P.102 Glycerol metabolism in patients with alcohol-induced liver cirrhosis

Long-term effectiveness of high-dosed ornithine-aspartate on urea synthesis rate and portal hypertension in human liver cirrhosis

The effectiveness of ammonia reducing amino acids on hyperammonemia and hepatic encephalopathy is well known in patients suffering from liver cirrhosis. Data concerning long-term therapy on hepatic function and urea synthesis rate (UNSR) are still lacking. According to Vilstrup/Poulsen it is a good standard for functioning liver mass. Therefore, 25 patients with histologically proven liver cirrhosis and distinct portal hypertension were treated daily with 9 gr. ornithinasparte over 13 years (8-20 years). Shunt operations, esophageal varicosis sclerosis, or portal pressure reducing medication were not applied. Rigorous alcohol abstinence and 60 gr protein/day were prescribed. During the investigation, 3 laparoscopies and 4 liver biopsies were performed, on the average, on each individual. Significant improvements of clinical and biochemical results (Child-Pugh-Index; Composite Clinical and Laboratory Index) were obtained during the long-term therapy with ornithine-aspartate. Esophageal varicosis II-III was either reduced to 0-I or totally eliminated. Also significant was an increased urea synthesis rate and a decreased hyperammonemia.A plausible explanation for the long-term therapy effectiveness with ornithine-aspartate is the possible recovery of the functioning mass without hepatic size increase. Also important is the rigorous alcohol abstinence. It leads to a significant reduction of portal hypertension in patients suffering from alcohol induced liver cirrhosis (Reynolds, own observations).Additional favorable factors are intensive muscle training and absence of gastrointestinal bleeds.

Growth Hormone and Carbohydrate Intolerance in Cirrhosis

Patients with cirrhosis of the liver often have insulin resistance and elevated circulating growth hormone levels. This study was undertaken (a) to evaluate glucose intolerance, insulin resistance and abnormal growth hormone secretion and (b) to determine if GH suppression improves insulin resistance. Glucose tolerance tests (GTT), intravenous insulin tolerance tests (IVITT), arginine stimulation tests (AST) and glucose clamp studies before and during GH suppression with somatostatin were performed in a group of patients with alcohol-induced liver cirrhosis. During GTT cirrhotic subjects had a 2-hour plasma glucose of 200 +/- 9.8 ng/dl (N = 14) compared to 128 +/- 8.0 ng/dl in normal controls (N = 15), P less than 0.001. Basal GH was elevated in cirrhotic patients and in response to arginine stimulation reached a peak of 17.0 +/- 5.4 ng/ml (N = 7), compared to a peak of 11.3 +/- 1.8 ng/ml in 5 normal controls (P = NS). During IVITT patients with cirrhosis had a glucose nadir of 60.0 +/- 4.0 mg/dl (N = 9), compared to 29.0 +/- 7.0 mg/dl in controls (N = 5), P less than 0.001. Peak GH levels during IVITT were not significantly different in cirrhotics and controls. Glucose utilization rates in 4 patients with cirrhosis of the liver before somatostatin mediated GH suppression was 3.1 +/- 0.5 mg/kg/min and 6.5 +/- 1.5 mg/kg/min during somatostatin infusion, P less than 0.025. We conclude that patients with alcohol induced cirrhosis have sustained GH elevations resulting in insulin resistance which improves after GH suppression.

Crosslinked fibrin derivatives and fibronectin in ascitic fluid from patients with ovarian cancer compared to ascitic fluid in liver cirrhosis

Ascitic fluid from patients with ovarian cancer and from patients with alcohol induced liver cirrhosis were compared in respect to hematological and related parameters (content of fibrinogen and fibrin(ogen) degradation products, fibrinopeptide A, F-CB3 related antigen, ratio of crosslinked fibrin to non crosslinked fibrin(ogen),fibronectin and total protein). In tumor ascites all parameters except FPA were significantly elevated compared with cirrhosis ascites. Tumor ascites contains a six-fold higher level of fibrin(ogen) degradation products. A considerable portion of it constitute crosslinked (factor XIII induced) high molecular weight fibrin derivatives. Their content is approx. 10 times higher in tumor ascites than in cirrhosis ascites. Characterization of the crosslinked fibrin derivatives revealed the presence of fragments DD, DY, and some other fragments compatible with XY, DXD,DXY, YXY and DXX. The fibronectin content is also significantly higher in tumor ascites compared with cirrhosis ascites. The value ranges showed no overlap. The findings suggest a turnover of fibrinogen in both ascitic fluids via coagulation and fibrinolysis. In tumor ascites however, fibrinogen seems to be catabolized to a higher degree via the degradation of crosslinked fibrin.

Serum beta2-microglobulin in liver disease.

The concentration of beta 2-microglobulin in serum was determined in seventy-one patients with various liver disorders. Elevated values were found in most patients with chronic active or chronic persistent hepatitis and in over 80% of patients with alcohol-induced liver cirrhosis. In contrast, patients with alcohol-induced fatty liver, the serum beta 2-microglobulin concentrations were mostly within the normal range. Significant correlation (P less than 0.001) was noted between the elimination rate of galactose from blood and the serum beta 2-microglobulin concentration in patients with alcoholic liver damage but not in patients with chronic hepatitis. The reasons for the increased S-beta 2-microglobulin concentrations in liver diseases are unknown. Several explanations including a release of beta 2-microglobulin from necrotic liver cells or an increased synthesis of beta 2-microglobulin consequent to inflammation in the liver are possible. Alternatively, raised beta 2-microglobulin levels may reflect the hepatic synthesis during reparative growth.

Alcoholic cirrhosis of the liver in the Scandinavian countries 1961-1974.

The increase in mortality from alcohol induced cirrhosis of the liver in Sweden, Norway, Finland and Denmark from 1961 to 1974 is compared. Mortality from alcoholic cirrhosis of the liver increased in Finland and Denmark tenfold and fivefold respectively from 1961 to 1974. The increase has been particularly marked since 1968. In Sweden a threefold increase and in Norway a doubling of mortality in males was ascribed to alcohol induced liver cirrhosis. Mortality from non-alcoholic cirrhosis of the liver remained practically unchanged during the period. Increases in mortality from liver cirrhosis due to alcohol abuse run parallel with increases in alcohol consumption; the countries with the highest mortality have the highest consumption. The distribution of consumption of beer, wine and spirit is compared in the four countries: consumption of spirits predominates in Sweden, in Finland spirits and beer, in Denmark beer and wine and in Norway spirits and beer. Doubling of alcohol consumption in a country is followed by a fourfold increase in the number of addicts, and fourfold increase in alcohol induced diseases.