Features Of Alcoholic Liver Disease Research Articles

Correlation of alcohol consumption with liver histological features in non-cirrhotic patients

The association between alcohol consumption and the risk of liver disease remains unclear. The aim of our study was to determine liver morphological features directly related to the mean lifetime daily alcohol intake (LTDAI) in non-cirrhotic patients. Medical records of all consecutive patients who reported alcohol consumption up to the time of hospital admission and who had undergone a liver biopsy in the Gastroenterology Unit of the University Hospital Centre of Tirana (Albania), were reviewed. Patients with established cirrhosis and/or with other possible causes of liver damage were excluded by the study. The histological features revealed in the biopsy samples of 51 non-cirrhotic patients were: steatosis in 46 patients (91%), six of whom (13%) showed also alcoholic foamy degeneration; alteration of hepatocytes in 40 patients (78%), diffuse mononuclear inflammation in 37 patients (73%), polymorphonuclear inflammation in 11 patients (22%) and perivenular fibrosis in 18 patients (35%). Diffuse steatosis was directly correlated with alcohol consumption (P<0.01). No association was found between alcohol consumption and the presence of degenerative alterations of hepatocytes, Mallory bodies or hepatocellular necrosis. Fibrosis was more prevalent in patients who reported a LTDAI > or = 80 g in comparison with patients who reported a LTDAI > or = 40 to <80 g (48% vs 25%; P<0.05). In non-cirrhotic patients liver steatosis and fibrosis were more common features among patients who reported a higher alcoholic consumption, but no clear-cut association between typical histological features of alcoholic liver disease and alcohol consumption was found.

Hemochromatosis and alcoholic liver disease

The close association of excessive alcohol consumption and clinical expression of hemochromatosis has been of widespread interest for many years. In most populations of northern European extraction, more than 90% of patients with overt hemochromatosis are homozygous for the C282Y mutation in the HFE gene. Nevertheless, the strong association of heavy alcohol intake with the clinical expression of hemochromatosis remains. We (individually or in association with colleagues from our laboratories) have performed three relevant studies in which this association was explored. In the first, performed in 1975 before the cloning of the HFE gene, the frequency of clinical symptoms and signs was compared in patients with classical hemochromatosis who consumed 100 g or more of alcohol per day versus in nondrinkers or moderate drinkers who consumed less than 100 g of alcohol per day. The results showed no difference between the two groups except for features of complications of alcoholism in the first group, especially jaundice, peripheral neuritis, and hepatic failure. Twenty-five percent of those with heavy alcohol consumption showed histologic features of alcoholic liver disease (including cirrhosis) together with heavy iron overload. It was concluded that these patients had the genetic disease complicated by alcoholic liver disease. In the second study (2002), 206 subjects with classical HFE-associated hemochromatosis in whom liver biopsy had been performed were evaluated to quantify the contribution of excess alcohol consumption to the development of cirrhosis in hemochromatosis. Cirrhosis was approximately nine times more likely to develop in subjects with hemochromatosis who consumed more than 60 g of alcohol per day than in those who drank less than this amount. In the third study (2002), 371 C282Y-homozygous relatives of patients with HFE-associated hemochromatosis were assessed. Eleven subjects had cirrhosis on liver biopsy and four of these drank 60 g or more of alcohol per day. The reason why heavy alcohol consumption accentuates the clinical expression of hemochromatosis is unclear. Increased dietary iron or increased iron absorption is unlikely. The most likely explanation would seem to be the added co-factor effect of iron and alcohol, both of which cause oxidative stress, hepatic stellate cell activation, and hepatic fibrogenesis. In addition, the cumulative effects of other forms of liver injury may result when iron and alcohol are present concurrently. Clearly, the addition of dietary iron in subjects homozygous for hemochromatosis would be unwise.

Folate deficiency, methionine metabolism, and alcoholic liver disease

Methionine metabolism is regulated by folate, and both folate deficiency and abnormal hepatic methionine metabolism are recognized features of alcoholic liver disease (ALD). Previously, histological features of ALD were induced in castrated male micropigs fed diets containing ethanol at 40% of kilocalories for 12 months, whereas in male micropigs fed the same diets for 12 months abnormal methionine metabolism and hepatocellular apoptosis developed. Folate deficiency may promote the development of ALD by accentuating abnormal methionine metabolism. Intact male micropigs received eucaloric diets that were folate sufficient, folate deficient, or each containing 40% of kilocalories as ethanol for 14 weeks. Folate deficiency alone reduced hepatic folates by one half, and ethanol feeding alone reduced methionine synthase, S-adenosylmethionine (SAM), and glutathione (GSH) levels and elevated plasma malondialdehyde (MDA) levels. The combined regimen elevated plasma homocysteine, hepatic S-adenosylhomocysteine (SAH), urinary 8-hydroxy-2-deoxyguanosine (oxy 8dG), an index of DNA oxidation, and serum aspartate aminotransferase (AST) levels. Terminal hepatic histopathologic characteristics included typical features of steatonecrosis and focal inflammation in pigs fed the combined diet, with no changes in the other groups. Hepatic SAM levels correlated with those of GSH, whereas urinary oxy 8dG and plasma MDA levels correlated with the SAM:SAH ratio and to hepatic GSH. The results demonstrate the linkage of abnormal methionine metabolism to products of DNA and lipid oxidation and to liver injury. The finding of steatonecrosis and focal inflammation only in the combined diet group supports the suggestion that folate deficiency promotes and folate sufficiency protects against the early onset of methionine cycle–mediated ALD.

Neutrophilic infiltration in alcoholic hepatitis

Leukocyte infiltration in the liver is one of the most important features of alcoholic liver disease. However, in alcoholic hepatitis, the role of polymorphonuclear neutrophils (PMNs) in liver injury still remains to be fully elucidated. Furthermore, the migration of PMNs and their presence in the liver during alcoholic hepatitis have not been fully investigated. Up-regulation of chemokine secretion and adhesion molecule expression on effector cells (i.e., PMNs) and target cells (i.e., hepatocytes) are important factors in neutrophilic infiltration of the liver. The CXC chemokines—that is, interleukin (IL)-8 (in human beings), cytokine-induced neutrophil chemoattractant (CINC) (in rats), and KC (in mice)—are proneutrophilic agents. They are up-regulated during chronic—that is, several years of—alcohol use in human beings and in up to 30 weeks in experimental models of ethanol intoxication in mice and rats. Up-regulation of these chemokines in the circulation and tissues is also associated with enhanced neutrophilic infiltration in the liver. In the rat, the up-regulation of CXC chemokine production is time dependent. For example, after 16 weeks of feeding, up-regulation of CXC chemokine is observed, whereas after 32 weeks, CC chemokines are enhanced. Concomitantly, selective migration of PMNs and mononuclear cells is observed. In another model, in which both CXC and CC chemokines were enhanced after chronic ethanol use for 12 weeks in mice, neutrophilic and mononuclear/lymphocytic infiltrations were also seen. This model correlates closely with alcoholic hepatitis in human beings, characterized by increased IL-8, RANTES (regulated upon activation, normal T cell expressed and secreted), and macrophage inflammatory protein-1 (MIP-1) and profound increases in neutrophils and lymphocytes in the liver.

Role of CYP2E1 in the pathogenesis of alcoholic liver disease: modifications by cAMP and ubiquitin-proteasome pathway.

The ethanol inducible isoform of cytochrome P450, CYP2E1, may play a role in ethanol-induced liver injury. Therefore, the factors which govern CYP2E1 degradation and turnover were investigated. These factors include cAMP, ubiquitin, proteasomal enzymes and CYP2E1 mRNA. Rats fed ethanol or pair-fed isocaloric dextrose were pair-fed with rats fed ethanol or dextrose treated with cAMP for 2 months. The liver pathology, regenerative activity, fatty acid composition, NFkappaB activation, ubiquitin conjugates and proteasomal enzymes were measured as were the apoprotein levels of CYP2E1, CYP3A, CYP4A and mRNA levels for CYP2E1 and ubiquitin expression. The results showed, that the cAMP treatment ameliorated the increase liver fat storage and changes in the fatty acid composition in the livers of ethanol fed rats. Other histologic features of alcoholic liver disease were not changed. Western blot quantitation showed that the amount of ubiquitin and ubiquitin conjugates were markedly reduced by ethanol treatment. Similarly, ethanol decreased the level of ubiquitin mRNA. cAMP ameliorated the inhibition of the proteasomal enzyme proteolysis caused by ethanol feeding. The ethanol-induced increase in the CYP2E1 protein was partially inhibited by cAMP treatment. cAMP treatment decreased CYP2E1 mRNA levels in both ethanol-fed and pair fed control rats. Likewise NFkappaB activation was not increased by ethanol but cAMP reduced the level of NFkappaB activation. CAMP treatment also reduced CYP4A but not CYP3A. The results support the concept that cAMP treatment partially protects the liver from ethanol-induced fatty liver by reducing CYP2E1 induction through cAMP's effects on CYP2E1 synthesis.

Serum IgA antibodies to human gut luminal aspirates and human liver in alcoholic liver disease.

Elevation of serum IgA is a characteristic feature of alcoholic liver disease. It has been proposed that this occurs partly as an antigenic response to gut-derived proteins or acetaldehyde-modified liver proteins, but the principal antigens responsible remain unknown. The goal of this study was to determine if serum IgA antibodies were present against human gut luminal antigens or liver antigens in alcoholic liver disease. Twenty-nine patients with alcoholic liver disease, 10 with primary biliary cirrhosis, 12 with "other" liver diseases, 8 alcoholics, and 20 healthy subjects were studied. Western blotting was used to examine the reactivity of sera from these groups against human small and large bowel aspirates and liver tissue from alcoholic liver disease patients. Serum IgA antibodies to a 140 kDa colonic luminal protein were found in 22 (76%) patients in the alcoholic liver disease group (p < 0.0001), and 7 (24%) patients had serum IgA antibodies to a 40 kDa colonic luminal protein (p = 0.04). These responses were confined to colonic aspirates and not observed in other disease groups, alcoholics or healthy subjects. There was no significant serum IgA response to human liver proteins in alcoholic liver disease. Serum IgA antibodies to a human 140 kDa colonic luminal protein are frequently found in alcoholic liver disease. This novel antigen may contribute to the increased levels of circulating IgA in alcoholic liver disease.

ALCOHOLIC LIVER DISEASE

Alcohol has been implicated in the genesis of liver disease for centuries. Significant progress has been made in our understanding of the pathogenesis of ALD. It is now apparent that both the consumption and the metabolism of alcohol promote the production of inflammatory mediators (cytokines) that result in hepatotoxicity and fibrogenesis. With time, this leads to progressively severe liver injury and, eventually, causes cirrhosis. Unfortunately, effective therapies for most individuals with ALD have not been found. High per capita consumption of alcohol, coupled with the dearth of effective treatments and the failure of most affected individuals to abstain from alcohol, explains why ALD is one of the most prevalent forms of disabling, chronic liver disease in the United States.

Serum intercellular adhesion molecule-1 in alcoholic liver disease and its relationship with histological disease severity

Background: Infilitration of the liver by leukocytes is a histological feature of alcoholic liver disease. Intercellular adhesion molecule-1 (ICAM-1) mediates the migration of lymphocytes from the circulation to target sites of inflammation. It has been demonstrated in the liver of alcoholic liver disease subjects and as a circulating soluble form (sICAM-1). The origin of sICAM-1 and its relationship to disease severity is unknown, although it has been postulated that it may arise from activated T lymphocytes and is an inflammatory marker. Aims: The aim of the study was to determine the relationship of sICAM-1 to clinical and histological severity of alcoholic liver disease and toserum T-cell (soluble interleukin-2 receptor (sIL-2R), β 2-microglobulin) and monocyte (neopterin) immune activation markers. Methods: Serum from 48 outpatients with biopsy proven alcoholic liver disease (steatosis=9, cirrhosis=28, hepatitis±cirrhosis=11), 31 with primary biliary cirrhosis and 27 normals was assayed for sICAM-1, sIL-2R, β 2-microglobulin, and neopterin. Results: sICAM-1 was significantly elevated, p=0.0001, in alcoholic liver disease and primary biliary cirrhosis patients compared to normals. Circulating sIL-2R ( p=0.0001) and β 2-miroglobulin ( p=0.0034) were significantly elevated in alcoholic liver disease compared to controls. There was a highly significant correlation between levels of sICAM-1 and histological grade of disease, Rs=0.80 ( p=0.0001), but no significant correlation with clinical correlates of disease severity of circulating immune activation markers. Conclusions: sICAM-1 is elevated in alcoholic liver disease, is a marker of histological severity of disease and does not appear to originate from activated T lymphocytes. Measurements of sICAM-1 may be useful in assessing histological severity of alcoholic liver disease.

Post mortem markers of chronic alcoholism

We compared the post mortem diagnostic value of γ-glutamyltransferase (GGT), carbohydrate-deficient transferrin (CDT), alcoholic liver disease (ALD), blood alcohol concentration (BAC), the presence of multiple bruises and poor hygiene of the feet as markers of chronic alcoholism (heavy continuous drinking) in 32 alcoholics with 32 age-sex matched controls drawn from a forensic autopsy population. Alcoholics and controls were selected on the basis of positive and negative medical history but controls were excluded if BAC exceeded 70 mg%. Femoral venous blood, urine and vitreous humour alcohol concentrations were determined by headspace gas chromatography (GC). BAC was positive in 19 alcoholics (mean 234 mg%, range 2–570 mg%) and six controls (mean 32 mg%, range 2–52 mg%). Serum GGT was measured by a kinetic photometric method, and CDT by both isoelectric focusing/laser densitometry and by a commercial radioimmunoassay kit (CDTect ™). Features of alcoholic liver disease were graded histologically using two weighted scoring systems. Eleven alcoholics tested positive for GGT, CDTq and ALD, nine were positive for two tests, five for one test and three were negative for all three tests. No controls were positive for all three tests but six were positive for two tests and nine for only one test; 17 were negative for all three tests. Using the normal clinical cut-off values GGT, CDTq and CDTect ™ gave poor specificity which was improved at moderate cost to sensitivity by raising cut off values for each test. Comparison of receiver operating characteristic curves, likelihood ratios and post-test odds showed CDT to be the best individual test, followed by ALD and GGT. Quantitation of CDT by IEF/laser densitometry performed slightly better than MAEC/RIA by CDTect ™. CDT shows considerable promise as a post mortem marker of chronic alcoholism.

Alcoholism in hereditary hemochromatosis revisited: Prevalence and clinical consequences among homozygous siblings

The relationship between alcoholism and hereditary hemochromatosis remains controversial. Previous studies have included patients with alcoholic siderosis rather than hereditary hemochromatosis. In this retrospective study, the clinical features, iron status, alcohol history, liver histology, and long-term survival were reviewed in 105 homozygotes for hemochromatosis using rigid diagnostic criteria including an HLA identical sibling with iron overload. Heavy alcohol consumption (>80 g ethanol/day) was found in 15 percent of hemochromatosis patients. Histological features of alcoholic liver disease (Mallory's hyaline bodies, pericentral fibrosis, polymorphonuclear infiltrate, and fatty infiltration) were uncommon in hemochromatosis. Hemochromatosis patients with heavy alcohol consumption had a higher prevalence of cirrhosis than hemochromatosis patients without heavy alcohol consumption. Hepatic iron concentration and hepatic iron index did not significantly differ between these two hemochromatosis groups. Long-term survival was significantly reduced in patients with heavy alcohol consumption (mean follow-up, 9.22 years). This suggests that chronic alcohol consumption has an additive hepatotoxic effect despite the paucity of histological features of alcoholic liver disease. (Hepatology 1996 Apr;23(4):724-7)

Alcoholism in hereditary hemochromatosis revisited: prevalence and clinical consequences among homozygous siblings.

The relationship between alcoholism and hereditary hemochromatosis remains controversial. Previous studies have included patients with alcoholic siderosis rather than hereditary hemochromatosis. In this retrospective study, the clinical features, iron status, alcohol history, liver histology, and long-term survival were reviewed in 105 homozygotes for hemochromatosis using rigid diagnostic criteria including an HLA identical sibling with iron overload. Heavy alcohol consumption (>80 g ethanol/day) was found in 15 percent of hemochromatosis patients. Histological features of alcoholic liver disease (Mallory's hyaline bodies, pericentral fibrosis, polymorphonuclear infiltrate, and fatty infiltration) were uncommon in hemochromatosis. Hemochromatosis patients with heavy alcohol consumption had a higher prevalence of cirrhosis than hemochromatosis patients without heavy alcohol consumption. Hepatic iron concentration and hepatic iron index did not significantly differ between these two hemochromatosis groups. Long-term survival was significantly reduced in patients with heavy alcohol consumption (mean follow-up, 9.22 years). This suggests that chronic alcohol consumption has an additive hepatotoxic effect despite the paucity of histological features of alcoholic liver disease.

Lack of plasma complement activation in severe acute alcoholic hepatitis.

To investigate whether complement pathway activation contributes to the clinical and histological features of acute alcoholic hepatitis, we studied the activation of the classical and alternative pathways in patients with alcoholic hepatitis (n = 20), inactive alcoholic cirrhosis (n = 8), heavy drinkers without alcoholic liver disease (n = 10), patients with liver disease of nonalcoholic etiology (n = 11), and healthy control subjects (n = 18). Complement activation was evaluated in the alcoholic hepatitis patients by its correlation with a number of clinical and laboratory features indicative of the severity of liver injury, as well as by comparison of the patient groups. There was no significant difference in circulating C3 [1.02 g/liter, confidence interval (CI) = 0.76-1.28] or C4 (0.25 g/liter, CI = 0.17-0.33) in patients with alcoholic hepatitis when compared with the four control groups. Factor B levels (0.24 g/liter, CI = 0.21-0.27) were higher in the alcoholic hepatitis patients than the control groups (p < 0.01). However, activation of complement (given by the ratios C3d/C3, C4d/C4, and Ba/factor B) was not different in alcoholic hepatitis patients when compared with the control groups. Univariate analysis of a wide range of clinical and laboratory features in the alcoholic hepatitis subjects showed a positive correlation between plasma C3 and serum alkaline phosphatase (r = 0.68, p = 0.0014), AST (r = 0.55, p = 0.015), and gamma-glutamyltranspeptidase (r = 0.47, p = 0.035), but no correlation with clinical or laboratory features associated with high morbidity or mortality. There is no relationship between clinical or laboratory indicators of disease severity and complement activation, and it is unlikely that complement activation contributes to the clinical and histological features of alcoholic liver disease.

Clinical features of alcoholic liver disease

The severity and range of histological liver lesions caused by alcohol abuse varies considerably; these lesions are not specific for alcoholic damage, and diagnosis of alcoholic liver disease depends on obtaining an adequate history of prolonged alcohol abuse and on excluding other known causes of liver disease. The clinical features of alcoholic liver disease vary greatly and they have been classified into various syndromes. However, the syndromes overlap, the histological features underlying them also overlap and they represent part of a wide clinical spectrum. Alcoholic fatty liver occurs more in younger patients and has a much better prognosis than alcoholic hepatitis or alcoholic cirrhosis, but the previous view that alcoholic fatty liver is an innocuous lesion can no longer be maintained. Alcoholic hepatitis and alcoholic cirrhosis cause more severe syndromes and more florid clinical features, and mortality is related to features of liver failure and variceal bleeding. Abstinence is the only means of ensuring the best possible survival.

Alcohol consumption and alcoholic liver disease: evidence of a threshold level of effects of ethanol.

The effects of long-term moderate or "social" alcohol consumption (10-80 g daily intake) on the incidence of features of alcoholic liver disease (ALD) were delineated in a consecutive autopsy series of 210 males. The subjects' daily intake, as well as duration of alcohol consumption, was determined by an interview with the spouse or a close acquaintance and compared with semiquantitative histological scores for stage of ALD. No significant increase in the incidence of features of ALD could be related to all-year daily intake of ethanol below 40 g (40 g equals 1.1 liter of beer, 0.44 liter of wine, and 0.11 liter of spirits). However, daily intake between 40-80 g increased relative liver weight on average 3.1 g/kg of body weight (p < 0.02), the frequency of fatty liver from 11.7 to 47.2% [relative risk (RR) = 4.4], and the frequency of mainly slight alcoholic hepatitis up to 16.7% (RR = 7.5). The incidence of both bridging fibrosis and liver cirrhosis increased significantly (RR = 8.8) only when daily intake exceeded 80 g. Amounts of ethanol exceeding 80 g did not relate to further increases in incidence of bridging fibrosis or liver cirrhosis. These findings suggest that, in males, daily ingestion of ethanol below 40 g for a period of 25 years does not increase the risk of alcohol-related liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of HCV infection and its subtypes on clinical course of alcoholic liver disease.

Since the assay of HCV antibody has been developed, it became clear that HCV is involved not only in patients with non-A non-B hepatitis but also in some alcoholic patients. The aim of this study is to examine the prevalence of HCV in chronic alcoholics and to elucidate the influence of HCV and its subtypes on pathogenesis and clinical feature of alcoholic liver disease. To that effect, sera from 100 alcoholics were tested for antibody against C100 of HCV by ELISA and for HCV RNA by reverse transcriptation and the PCR method. The incidence of HCV Ab/RNA was 0%/17% in patients with non specific reactive hepatitis, 0%/0% in fatty liver, 17%/17% in alcoholic hepatitis, 50%/73% in chronic hepatitis, 15%/18% in liver fibrosis and 19%/31% in liver cirrhosis. HCV Ab and RNA were positive in 21% and 31% of alcoholics, respectively. Subtypes of HCV were identified by dot blot hybridization method. Type K1, K2a and K2b were detected in 68%, 25% and 7% of 28 patients with positive HCV RNA, respectively. Type PT was not detected. In addition, serum transaminase activities were evaluated after 4 weeks abstinence. The incidence of normalization of the enzyme activity was lower in patients with positive HCV RNA than that with negative HCV RNA. Furthermore, when it was estimated in relation to HCV subtypes, the incidence of normalization in patients with type K1 was lower than that with type K2. In conclusion, the prevalence of HCV infection in alcoholic patients was much greater than general population.(ABSTRACT TRUNCATED AT 250 WORDS)

Characteristic features of alcoholic liver disease in Japan: a review.

The characteristics of alcoholic liver disease (ALD) in Japanese patients were reviewed and compared with those in Western countries. From the study in Japanese cases, it became clear that alcoholic fibrosis and chronic hepatitis induced by alcohol were types of ALD other than the traditional 3 types. Liver injury in Japanese cases was clearly milder than that in American cases. In American cases, the injury may be fully developed, because of greater alcohol and fat intake. This may be one reason why the two above types of ALD have not been mentioned in the literature of Western countries. In Japanese patients, hepatitis C virus (HCV) infection is not related to alcoholic fibrosis and alcoholic hepatitis. On the other hand, the prevalence of HCV markers was high in chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) patients. Alcoholic hepatitis and chronic hepatitis are the high risk groups for the development of cirrhosis and the chronic hepatitis group is at high risk for the development of HCC. Although the risk is low in alcoholic fibrosis, some patients also develop cirrhosis. About half of the cases of cirrhosis may develop from alcoholic hepatitis and alcoholic fibrosis, and the remaining half cases may develop from chronic hepatitis. Over 80% of HCC cases may develop from chronic hepatitis in Japan. Chronic alcoholism enhanced the development of HCV-related HCC. Recent increase of HCC in alcoholic cirrhosis in Japan may be related to the increase of alcohol consumption, the increase of blood transfusions, and longer survival of cirrhosis patients.

Chronic Hepatitis C in Alcoholic Patients: Studies with Various Hcv Assay Procedures

Chronic hepatitis (CH) is one of the features of alcoholic liver disease (ALD). The role of hepatitis C virus (HCV) infection was investigated in 50 alcoholic patients with CH, employing various types of HCV antibody. All patients had a drinking history of more than 80 g/day of ethanol and the diagnosis of CH was made by liver histology within 2 weeks of abstinence. We assayed serum HCV using C100-3 antibody (Ortho EIA and RIA), the second generation (HCV-2nd) (DAINABOT EIA and PHA), and we also examined HCV-RNA by PCR. The positive rate of C100-3 antibody was 56% by EIA and 66% by RIA. The HCV-2nd was much higher; 80% and 82% by EIA and PHA, respectively. The HCV-RNA was positive in 82% of patients. The positive rate for either of the HCV markers was 92% (46/50). In patients positive for C100-3, serum aminotransferase levels were still elevated even after abstinence and most of them showed chronic active hepatitis by liver histology. Follow-up liver biopsies showed histological progression even after abstinence. On the other hand, in some patients positive only for HCV-2nd and/or HCV-RNA, serum aminotransferase levels were normalized and histological improvement was observed soon after abstinence. These results suggest that histological determined CH in alcoholics is attributed mainly to the infection of HCV, HCV plays an important role in the histological deterioration after abstinence, and that the presence of C100-3 antibody reflects the activity of liver disease caused by HCV.(ABSTRACT TRUNCATED AT 250 WORDS)

Type IV Collagen and Laminin Contents of Livers from Patients with Alcoholic Liver Disease

Characteristic histological features of alcoholic liver disease (ALD) are pericellular and perivenular fibrosis. It has been emphasized from immunohistochemical studies that pericellular and perivenular fibrosis may be caused by the increase of type IV collagen (IV-C) and/or laminin (LM). However, quantitative changes of hepatic IV-C and LM contents in ALD are not well known. Recently, we have developed assay systems for IV-C and LM contents in liver biopsy specimens. In the present study, hepatic IV-C and LM contents in ALD and non-ALD patients were measured. Liver biopsy specimens were obtained from 36 patients with ALD, 24 patients with non-ALD and five patients without liver disease. IV-C and LM contents in liver biopsy specimens were measured using the one-step sandwich enzyme immunoassay system for human serum IV-C and LM levels. Total collagen (T-C) content was also measured by the method of Leon and Rojkind. Hepatic IV-C, LM and T-C contents were significantly higher in all types of liver disease than in controls, and tended to increase with the progression of fibrosis. Especially in ALD, both IV-C and LM contents increased from the early stage, and the values in each type of ALD were significantly higher than those in the corresponding type of non-ALD. The ratio of IV-C or LM to T-C was also significantly higher in ALD than in the corresponding non-ALD. The prominent increases of IV-C and LM at the early stage of fibrosis may be one of the characteristics of collagen metabolism in ALD.(ABSTRACT TRUNCATED AT 250 WORDS)

Liver histopathology in chronic common bile duct stenosis due to chronic alcoholic pancreatitis.

The liver histopathology in 40 liver biopsies from 24 patients with verified chronic common bile duct stenosis due to chronic alcoholic pancreatitis has been reviewed code-blinded. This represents an 8% prevalence of this complication in approximately 300 patients with alcoholic pancreatitis screened biochemically for alkaline phosphatase greater than two-fold for less than 1 month. The majority were anicteric with no symptoms other than from acute exacerbations of chronic pancreatitis. Biliary obstructive liver histopathology of varying severity was diagnosed in 19 patients (79%), seven of whom (29%) had secondary biliary cirrhosis. In 3 of these 7 cases, progression to biliary cirrhosis was documented with sequential biopsies. The remainder demonstrated this histologic picture when first diagnosed, supporting this insidious nature of this process. Stromal edema of the portal tracts, increased portal connective tissue, and marked proliferation of interlobular bile ducts and ductules were the most striking histologic features. Histologic cholangitis, although frequent, was generally mild or absent, reflecting the incomplete nature of the duct obstruction. Features of alcoholic liver disease were observed in only two cases. The results indicate that (1) chronic alcoholic pancreatitis with incomplete duct obstruction frequently causes secondary biliary cirrhosis, (2) significant alcoholic liver disease very infrequently coexists with persistent common bile duct stricture from alcoholic pancreatitis, and (3) surgical biliary decompression should be considered in any patient with documented persistent common bile duct stenosis from alcoholic pancreatitis.