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PubMed1977

Epidemiology of chronic liver diseases.

In the GDR mortality from liver cirrhosis decreases in contrast to most other countries though the alcohol consumption of the population is continuously increasing. In Capital Berlin and in the industrialized districts mortality from cirrhosis is higher than in the rural areas. Within a period of 6 years the number of inpatients with chronic liver diseases has risen from 11.600 to 14.200. From the epidemiologic point of view, virus hepatitis is not the main source of liver cirrhosis. The total recovery rate of acute hepatitis has increased from 80% to 94% over a period of some 8 to 10 years, liver cirrhosis was found to have developed only in 0.3%. 70% of cirrhotic patients did never suffer from virus hepatitis, as their anamnesis revealed. 73% of 1.8 million blood donors that were subjected to SGPT and HBAg-screening tests showed histologic changes of the liver. With the use of these screening methods it has been possible to register 7% persons with liver diseases among these blood donors. Early recognition and treatment of chronic liver diseases seem to result in a reduction of mortality from liver cirrhosis.

Alanine Transaminase↗

PubMed1989

Autonomic neuropathy and chronic liver disease.

Autonomic neuropathy has been reported in association with alcoholic cirrhosis but there is no information on its occurrence in non-alcoholic liver disease. We have examined autonomic function in 64 patients with biopsy-proven liver disease (22 with alcoholic liver disease and 42 with non-alcoholic liver disease) together with 29 age-matched controls. Forty-five per cent of patients with alcoholic liver disease and 43 per cent with non-alcoholic liver disease showed evidence of parasympathetic damage; 11 per cent of patients with alcoholic liver disease and 12 per cent with non-alcoholic liver disease had sympathetic damage. Forty-five per cent of patients with alcoholic liver disease and 22 per cent with non-alcoholic liver disease had peripheral neuropathy on clinical examination. Sixty-eight per cent of those with peripheral neuropathy also had autonomic neuropathy. This study confirms that autonomic neuropathy is common in alcoholic patients but the fact that it is found with comparable frequency in non-alcoholic liver disease suggests that the neurological defect may be secondary to the disturbed liver function. The implications of these observations with regard to prognosis of chronic liver disease are discussed.

Adult↗

PubMed1992

[Evaluation of plasma thrombomodulin (TM) levels in patients with liver disease].

Plasma TM levels in patients with various liver diseases were determined by using EIA. In normal subject (n = 58), it's concentration was 15.9 +/- 3.5 ng/ml (mean +/- SD). In liver diseases, the level increased: Acute hepatitis (n = 16), 23.0 +/- 6.5, chronic active hepatitis (n = 21) 22.2 +/- 6.6, compensated liver cirrhosis (n = 20) 27.8 +/- 10.1, decompensated liver cirrhosis (n = 14) 47.6 +/- 17.5, compensated liver cirrhosis with hepatocellular carcinoma (n = 7) 26.3 +/- 7.9, decompensated liver cirrhosis with hepatocellular carcinoma (n = 4) 46.0 +/- 11.8, and fulminant hepatitis (n = 9) 42.0 +/- 20.4. The percentages of abnormal values higher than 22.9 ng/ml, which is mean + 2SD in control subject was 38-100% in liver diseases, especially 100% in patients with liver cirrhosis or with fulminant hepatitis. There was little correlation between plasma TM levels and conventional liver function tests in various liver diseases. Immunohistochemical study of liver tissue showed that an increase of plasma TM level was partially caused by damage and regeneration of endothelial cell. Based on these results the measurement of plasma TM concentration could be an useful marker for detection of hepatic failure.

Biomarkers↗

PubMed1996

Parasitological and bacteriological studies in recurrent diarrhoea in patients with chronic liver diseases.

Sixty patients with chronic liver disease complaining of persistent or recurrent diarrhoea where studied. The stools were examined by direct smear, formol ether concentration method and modified Ziehl Neelsen technique for Cryptosporidium in addition to stool cultures for enteric pathogenic bacteria as Salmonella, Shigella and E. coli. Giardia lamblia was the most prevalent pathogen responsible for diarrhoea in 23.3% of cases followed by Entamoeba histolytica in 21.6%, Schistosoma mansoni in 5% and Hymenolepis nana and Ascaris lumbricoides in 1.6%. Concerning bacteria, Salmonella was detected (10%), Shigella (6.7%) and E. coli (13.3%). In conclusion, Cryptosporidium was not a cause of diarrhoea in patients with chronic liver disease.

Adolescent↗

PubMed2026

Recombinant Human Thrombopoietin Reduces the Need for Platelet Transfusion in Patients With Chronic Liver Disease and Thrombocytopenia.

Chronic liver disease (CLD)-related thrombocytopenia can limit the feasibility of invasive procedures. Recombinant human thrombopoietin (rhTPO) has demonstrated a favorable safety profile without hepatotoxicity. We evaluated the efficacy and safety of rhTPO in patients with CLD-related thrombocytopenia who were undergoing elective invasive procedures. In this multicenter, randomized (2:1), double-blind, placebo-controlled phase III trial, 120 adult Chinese patients with CLD-related thrombocytopenia (platelet count < 50 × 109/L) received rhTPO (n = 80) or placebo (n = 40) once daily for up to 5 or 7 days. The primary endpoint was the proportion of patients with sustained platelet counts ≥ 50 × 109/L from 24 h before invasive procedure to 7 days post-procedure, without requiring emergency bleeding management. The primary endpoint was achieved by 85.0% of patients in the rhTPO group versus 12.5% in the placebo group (p < 0.0001). Preoperatively, platelet counts ≥ 50 × 109/L were achieved in 92.5% and 20.0% of patients in the rhTPO and placebo groups, respectively (p < 0.0001). Platelet transfusion was avoided in 92.5% of rhTPO-treated patients versus 25.0% of placebo-treated patients (p < 0.0001). The median duration of platelet counts ≥ 50 × 109/L was significantly longer with rhTPO than with placebo (21.0 vs. 3.0 days, p = 0.0007). Treatment-related treatment-emergent adverse events (TEAEs) occurred in 12.5% of patients in both the rhTPO and placebo groups. No treatment-related serious adverse events were reported. Overall, rhTPO was effective and well tolerated in patients with CLD-related thrombocytopenia and may represent a viable therapeutic option for those undergoing elective invasive procedures. Trial Registration: www.chinadrugtrials.org.cn: number CTR20230919.

Humans↗

PubMed1998

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

BACKGROUND: 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. AIMS: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adult↗

PubMedDate not supplied

Sinusoidal caliber in alcoholic and nonalcoholic liver disease: diagnostic and pathogenic implications.

Portal hypertension in alcoholic liver disease has been attributed to an increased resistance to blood flow either of sinusoidal or of postsinusoidal origin. The former should be accompanied by sinusoidal compression while the latter is expected to result in an increased or a normal sinusoidal diameter. Patients with alcoholic liver disease showed a marked reduction (p less than 0.001) in relative sinusoidal area (995 +/- 135 micron 2; n = 19) when compared to nonalcoholic patients with normal liver histology (5,100 +/- 389 micron 2; n = 6), or to patients with nonalcoholic liver disease (6,242 +/- 467 micron 2; n = 19). Hepatocyte surface area was significantly increased in patients with alcoholic liver disease when compared to hepatocytes from normal biopsies (563 +/- 32 micron 2 vs. 301 +/- 26 micron 2; p less than 0.001). Patients with nonalcoholic liver disease had hepatocyte surface areas within the normal range (327 +/- 14 micron 2). There was a significant inverse correlation between hepatocyte size and sinusoidal area (r = -0.63; p less than 10(-6); n = 44), indicating that larger hepatocytes were associated with sinusoidal compression. In the alcoholic patients, portal pressure correlated inversely (r = -0.77; p less than 0.01) with sinusoidal area only after the sinusoidal area was markedly reduced to areas below 20% of normal. Such a threshold was not reached in patients with nonalcoholic liver disease, in whom no correlation between sinusoidal area and portal pressure was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2003

Gene expression profiling of alcoholic liver disease in the baboon (Papio hamadryas) and human liver.

The molecular pathogenesis of alcoholic liver disease (ALD) is not well understood. Gene expression profiling has the potential to identify new pathways and altered molecules in ALD. Gene expression profiles of ALD in a baboon model and humans were compared using DNA arrays. Reverse transcriptase-polymerase chain reaction and immunohistochemistry were used for downstream analysis of array results. cDNA array analysis revealed differential expression of several novel genes and pathways in addition to genes known to be involved in ALD pathogenesis. Overall gene expression profiles were similar in both species, with a majority of genes involved with fibrogenesis and xenobiotic metabolism, as well as inflammation, oxidant stress, and cell signaling. Genes associated with stellate cell activation (collagens, matrix metalloproteinases, tissue inhibitors of matrix metalloproteinase) were up-regulated in humans. Decreased expression of several metallothioneins was unexpected. Fourteen molecules related to the annexin family were up-regulated, including annexin A1 and A2. Immunofluorescence revealed a marked overexpression of annexin A2 in proliferating bile duct cells, hepatocyte cell surface, and selective co-localization with CD14-positive cells in human ALD. The gene expression profile of ALD is dominated by alcohol metabolism and inflammation and differs from other liver diseases. Annexins may play a role in the progression of fibrosis in ALD.

Adult↗

PubMed1998

Ultrasound-guided fine needle cutting biopsy for the characterization of diffuse liver diseases in bone marrow transplant patients.

Liver disease is a frequent complication in bone marrow transplant recipients and may occur early or late in the post-transplant period. Using ultrasound-guided fine needle (1.2 mm, 18 G) cutting biopsy, we studied six patients with undefined late post-BMT liver disease. No procedure-related complications occurred and all liver biopsies were informative, leading to changes in therapeutic approach. In our small series, the most frequent cause of hepatic damage was drug toxicity. US-guided fine needle cutting biopsy is a useful and easy tool for the work-up of unexplained post-BMT liver disease.

Adolescent↗

PubMed1994

Androgen receptor in human liver: characterization and quantitation in normal and diseased liver.

Liver is responsive to sex hormones. The role of androgens in normal human liver function is not well understood, although androgens have been implicated in several liver diseases. Because the human hepatic androgen receptor has not been adequately characterized, we analyzed cytosolic and nuclear fractions from normal human liver of both sexes for androgen-binding activity using multipoint saturation analysis with the androgenic radioligand methyltrienelone (R1881). Both cytosolic and nuclear fractions of both sexes displayed high affinity R1881 binding (dissociation constants = nanomolar range). The R1881 binding in both fractions is highly specific in that potent androgens compete well, and the antiandrogens hydroxyflutamide and cyproterone acetate show partial competition; other nonandrogenic steroid hormones do not compete. The cytosolic R1881 receptor displays physicochemical characteristics of androgen receptors in other tissues in that it is retained by heparin-Sepharose and by DNA cellulose after activation, and it displays a molybdate-stabilized 8S form on sucrose gradients and a 7.3-nm species on gel filtration chromatography. Receptor activity was also quantitated in specimens of hepatic adenoma, focal nodular hyperplasia and metastatic carcinoma to the liver and in samples of adjacent histologically normal specimens when available. In general, both the diseased and normal portions of the livers from the patients with hepatic adenoma and metastatic carcinoma to the liver, but not focal nodular hyperplasia, demonstrated reduced total androgen-receptor activity as compared with liver from normal individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed2002

Prospective surveillance of acute serious liver disease unrelated to infectious, obstructive, or metabolic diseases: epidemiological and clinical features, and exposure to drugs.

BACKGROUND/AIMS: Acute serious liver disease which is unrelated to infectious, obstructive, or metabolic disease is uncommon. Many drugs have been implicated. Data on its epidemiology are scarce. We performed a population-based prospective study of acute serious liver disease in Catalonia (Spain). METHODS: A collaborating hospital network was set up. All patients with acute serious liver disease and negative viral hepatitis serological markers, without an obvious cause of liver disease, were included. RESULTS: The incidence of acute serious liver disease was 7.4 per 10(6) inhabitants per year (95% CI; 6.0-8.8), which increased with age. The incidence of hepatocellular acute serious liver disease (3.84 per 10(6) per year) was greater than that of cholestatic and mixed patterns. The case-fatality ratio was 11.9% and mortality 0.8 per million person-years. The risk of death was similar among patients with hepatocellular and cholestatic patterns. Non-steroidal antiinflammatory drugs, analgesics, and antibacterials were the most frequently used drugs. CONCLUSIONS: Acute serious liver disease which is unrelated to infectious, obstructive, or metabolic disease is rare. Its incidence increases with age. The prognosis of cholestatic acute serious liver disease does not significantly differ from that of the hepatocellular pattern. Non-steroidal antiinflammatory drugs, analgesics, and antibacterials were the most common drugs likely to be responsible for acute liver disease.

Acute Disease↗

PubMed2004

Effect of body mass index on nonalcoholic fatty liver disease in patients undergoing minimally invasive bariatric surgery.

The risk factors for nonalcoholic fatty liver disease in patients undergoing bariatric surgery are under study. We wanted to determine the correlation between nonalcoholic fatty liver disease and patient factors such as obesity and liver function tests. A retrospective analysis was performed on 177 nonalcoholic morbidly obese patients who underwent laparoscopic Roux-en-Y gastric bypass with liver biopsy, to identify risk factors for nonalcoholic fatty liver disease. The histologic grade of liver disease was compared with preoperative body mass index, age, and liver function tests. Simple steatosis and steatohepatitis were present in 90% and 42% of patients, respectively. Elevated transaminase levels were an independent risk for liver disease. Body mass index and liver disease were not correlated with univariate analysis. Regression analysis performed on age, body mass index, and liver disease demonstrated that the risk for liver disease increased with body mass index in the younger (<35 years old) age group and decreased with body mass index in the older (>45 years old) age group. There was a high incidence of steatosis and steatohepatitis in these nonalcoholic bariatric patients, and elevated transaminase level was indicative of disease. Body mass index was a positive risk factor for liver disease in younger patients but a negative risk factor in the older patients.

Adult↗

PubMed1981

[Ultrasound measurement of gallbladder response to cholecystokinin in patients with chronic liver disease (author's transl)].

Size of gallbladder after overnight fasting and the kinetics of gallbladder contraction following i.v. injection of 1 I. U. of CCK was investigated in patients with chronic liver disease (liver cirrhosis: n = 26; chronic hepatitis: = 12; fatty liver: n = 5). The results were compared with those obtained in an age and sex matched control group of subjects without symptoms of diseases of the liver or gastrointestinal tract (n = 15). Ultrasound was used for continuous monitoring of gallbladder emptying. In the cirrhotics the cartographically determined initial area of the gallbladder was significantly greater than in the controls (p less than 0,01). The kinetic of gallbladder emptying following CCK-pancreozymin stimulation was similar in the groups of patients with liver diseases to that of the control subjects. However, the residual area of the gallbladder following maximal contraction was again significantly greater in the cirrhotics when compared to the control group (p less than 0.05). The area of the gallbladder in patients with chronic hepatitis exhibited similar changes of the values in the fasting state and after maximal contraction as seen in the patients with liver cirrhosis, although the differences when compared to the control group were not significant. The results show that in spite of distinct signs of a hypotonic state of the unstimulated gallbladder in patients with chronic liver disease the kinetic of contraction following an exogenous stimulus with CCK remains normal.

Adult↗

PubMedDate not supplied

Endoscopic findings in alcoholic liver disease: does gender make a difference?

Alcohol abuse and alcoholic liver disease are major health problems in many parts of the world. The prevalence of alcoholic liver disease is directly related to both rate and duration of alcohol intake. It is a widely held belief that women are more susceptible to the hepatotoxic effects of ethanol, and develop alcohol-related liver disease more readily than do men. A lower volume of distribution for alcohol, greater immune reactivity and higher activity of alcohol metabolizing enzymes in women are considered, at least in part, to be responsible for the greater susceptibility of women to alcoholic liver disease. Little data exist as to the extent of gastrointestinal involvement in advanced alcoholic liver disease, and even less, as to the relationship of these potential gastrointestinal lesions with gender, and whether or not female patients develop gastrointestinal complications at an earlier time in their liver disease natural history and whether when it occurs it is more severe than that seen in males. To answer these questions, 75 subjects (49 men and 26 women) with alcoholic liver disease underwent elective upper and lower gastrointestinal endoscopy while they were clinically stable. The prevalence of the various gastrointestinal lesions did not differ significantly between male and female alcoholics except for gastric ulcer (GU) and nonspecific inflammatory changes of the colon which were more common in females than in males (23.1% vs. 6.1% and 11.1% vs. 0%, respectively; both p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Digestive System↗

PubMed1983

Outcome of liver disease associated with alpha 1 antitrypsin deficiency (PiZ). Implications for genetic counselling and antenatal diagnosis.

We reviewed the hepatic features in 136 children with alpha 1 antitrypsin deficiency (PiZ). Eighty two were studied prospectively, 74 of whom had chronic liver disease. Sixty seven children with liver disease presented in the first four months of life, four were older infants and children with chronic liver disease, 10 (three with liver disease) were identified in studies of the family of these propositi, and one was identified when she had liver disease associated with infectious mononucleosis. By 17 years of age 20 of these 74 children with chronic liver disease had died, 20 had established cirrhosis, 19 had persisting liver disease, and only 15 had made a complete, clinical and biochemical recovery. The outcome of liver disease was similar in a further 39 previously unreported PiZ infants and children with liver disease who were not prospectively studied. Because liver disease affects only a proportion of infants with PiZ phenotype and because the severity of their liver disease is so variable, we have analysed the outcome of liver disease in 27 observed families and in 20 previously reported families with more than one child with PiZ. In 34 families the outcome of liver disease was similar in the two children. From an analysis of the families with a severely affected child, we conclude that if the first PiZ child of PiZ heterozygote parents has unresolved liver disease, there is a 78% chance that a second PiZ child will have similar liver disease. After careful counselling, fetoscopy, fetal blood sampling, and protease inhibitor phenotyping, possible termination of pregnancy should be carefully considered in these families.

Adolescent↗

PubMed2006

The hepatic transcriptome in human liver disease.

The transcriptome is the mRNA transcript pool in a cell, organ or tissue with the liver transcriptome being amongst the most complex of any organ. Functional genomics methodologies are now being widely utilized to study transcriptomes including the hepatic transcriptome. This review outlines commonly used methods of transcriptome analysis, especially gene array analysis, focusing on publications utilizing these methods to understand human liver disease. Additionally, we have outlined the relationship between transcript and protein expressions as well as summarizing what is known about the variability of the transcriptome in non-diseased liver tissue. The approaches covered include gene array analysis, serial analysis of gene expression, subtractive hybridization and differential display. The discussion focuses on primate whole organ studies and in-vitro cell culture systems utilized. It is now clear that there are a vast number research opportunities for transcriptome analysis of human liver disease as we attempt to better understand both non-diseased and disease hepatic mRNA expression. We conclude that hepatic transcriptome analysis has already made significant contributions to the understanding of human liver pathobiology.

Journal Article↗

PubMed1994

Liver disease in the immunocompromised patient.

This chapter reviews the most common diseases of the liver that are associated immunodeficiencies resulting from AIDS, chemotherapy and radiation, and bone marrow and solid organ transplantation. Conditions described include liver disease, infection, venoocclusive disease, graft versus host disease, and others.

Acquired Immunodeficiency Syndrome↗

PubMed2004

Nonalcoholic fatty liver disease (NAFLD): a comprehensive review.

Nonalcoholic fatty liver disease (NAFLD) is defined as fatty infiltration of the liver exceeding 5% to 10% by weight. It is a spectrum of disorders ranging from simple fatty liver (steatosis without liver injury), nonalcoholic steatohepatitis (steatosis with inflammation), and fibrosis/cirrhosis that resembles alcohol-induced liver disease but which develops in individuals who are not heavy drinkers. NAFLD is likely the most common cause of chronic liver disease in many countries. NAFLD may also potentiate liver damage induced by other agents, such as alcohol, industrial toxins and hepatatrophic viruses. The lack of specific and sensitive noninvasive tests for NAFLD limits reliable detection of the disease. It is often diagnosed on a presumptive basis when liver enzyme elevations are noted in overweight or obese individuals without identifiable etiology for liver disease, or when imaging studies suggest hepatic steatosis. NAFLD is now considered to be a component of the insulin resistance syndrome (metabolic syndrome X). Controversy exists relative to optimal recognition, diagnosis and management of these conditions, and treatment recommendations are evolving.

Biopsy, Needle↗