Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “LIVER DISEASE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 703 records · Page 39Linked to original sources

Eotaxin expression and eosinophil infiltrate in the liver of patients with drug-induced liver disease.

BACKGROUND: Drug-induced liver disease is due to intrinsic or idiosyncratic hepatotoxins. Liver parenchyma is then infiltrated by immunocompetent cells. Eosinophils are primarily tissue leukocytes which are attracted into tissues by various chemoattractants, including chemokines. The aim of this study was to study eosinophils in the livers of patients with drug-induced liver disease. METHODS: Immunohistochemical studies with antibodies against eosinophil cationic proteins (major basic protein, eosinophil-derived neurotoxin and eosinophil cationic protein), cytokines (interleukin 5 (IL-5), interleukin 3 (IL-3) and granulocyte-macrophage colony stimulating factor (GM-CSF)) and chemokines (eotaxin and RANTES (Regulated upon Activation Normal T cell Expressed and Secreted)) were performed to assess the in situ activation of the liver-infiltrating eosinophils of 14 patients with drug-induced liver disease and 19 controls. RESULTS: Eosinophils were only observed in patients with drug-induced liver disease. Eosinophils were morphologically normal when hepatitis was due to paracetamol whereas eosinophils had granular changes when hepatitis was due to an idiosyncratic hepatotoxin. Eotaxin was detected in all patients with drug-induced liver disease, whereas RANTES was detected in three of them. IL-5, IL-3 or GM-CSF were not detected. CONCLUSIONS: In patients with drug-induced liver disease, the recruitment of eosinophils in the liver may depend on eotaxin expression. Eosinophil changes may vary according to the type of drug.

Acetaminophen↗

General medicine and surgery for dental practitioners. Part 5: liver disease.

The liver has a number of important functions. It metabolises drugs and endogenous substances and contributes to their excretion by the body. Plasma proteins are synthesised in the liver which also acts as a storage organ for glycogen and vitamin B12. The liver is also important in the production of clotting factors for normal haemostatic function.

Anesthesia, Dental↗

Fatty acid synthesis in vitro by liver tissue from control subjects and patients with alcoholic liver disease.

Percutaneous liver biopsy specimens were obtained from 11 control subjects, 24 alcoholic patients and six diabetic patients with mild to severe fatty liver and incubated in Krebs-Henseleit buffer containing 3H2O. The incorporation of 3H into fatty acid was measured and the absolute rate of fatty acid synthesis calculated. Fatty acid synthesis rates were significantly lower in alcoholic fatty liver than in controls. Fatty acid synthesis rates were similar in controls and patients with diabetic fatty livers. Addition of 50 mmol/l ethanol did not alter the fatty acid synthesis rates in vitro. It is concluded that enhanced lipogenesis is not the major cause of fatty liver in patients with alcoholic fatty liver.

Adult↗

Gene therapy for human liver diseases.

The liver can be considered an ideal target to design gene therapy strategies because of the unique properties of hepatic cells. The great amount of work carried out in this field clearly delineates the quality of the new approaches that have been developed in the last few years and demonstrates the feasibility of this strategy in a wide range of multi-factorial and inherited disorders. However, improvement of current vectors to specifically and efficiently deliver the therapeutic gene into the target cell remains a daunting problem. In this review, we will summarize the most important approaches that are currently under investigation, the pathological conditions that can be treated by this strategy and the most important drawbacks that remain to be overcome in order to achieve long-term and high-level gene expression.

Gene Transfer Techniques↗

Mechanisms of drug-induced liver disease.

The liver is the main metabolizing organ in the body for drugs and toxins. The liver is therefore exposed to relatively high levels of electrophilic metabolites and free radicals that may induce toxicity. Furthermore, the liver performs many vital functions that may be disrupted by toxic metabolites. Despite the high exposure to reactive metabolites, drug-induced toxicity is relatively uncommon because of the redundancy of the detoxification systems present in the liver.

Animals↗

Development of a pediatric end-stage liver disease score to predict poor outcome in children awaiting liver transplantation.

BACKGROUND: A pediatric end-stage liver disease (PELD) score for children with chronic liver disease using easily obtainable, objective, verifiable parameters, would be useful to prioritize children awaiting liver transplantation. METHODS: Data from the Studies of Pediatric Liver Transplantation (SPLIT), a consortium of 29 U.S. and Canadian centers, were used to develop the PELD score. Two pretransplantation endpoints were evaluated: (1) death, n=884; and (2) death or moving to the intensive care unit (ICU), n=779. The analyses were restricted to children with chronic liver disease who were listed for a first transplant. Preliminary analyses of 17 possible factors yielded 6 parameters of interest: age <1 year, total bilirubin, international normalized ratio (INR), albumin, growth failure (height or weight Z score <-2), and calculated glomerular filtration rate. In a univariate Cox regression analysis, age, bilirubin, INR, and albumin were significant (P<0.01) predictors of both endpoints; glomerular filtration rate was not significant for either endpoint; and growth failure was significant for death/ICU but not death alone. In the multivariate analyses, age, bilirubin, and INR were significant for the death endpoint; and bilirubin, INR, growth failure, and albumin were significant for the death/ICU endpoint. From these results, three PELD models were evaluated to predict both outcomes at 3 and 6 months: PELD 1 (age, bilirubin, INR); PELD 2 (bilirubin, INR, albumin, growth failure); and PELD 3 (bilirubin, INR, albumin, growth failure, and age). The area under the receiver operating characteristic curve (AUC ROC) was used to compare models. For PELD 3, the most inclusive model, the AUC ROC at 3 months was 0.92 for death and 0.82 for "death-moved to ICU." A comparison of the AUC ROCs for the other models and for the model of end-stage liver disease ([MELD], the adult end-stage liver disease severity score model), none of which performed better than PELD 3, are presented. CONCLUSION: A model using five objective parameters can accurately predict death or death-moved to ICU in children awaiting liver transplantation.

Child, Preschool↗

[The blood coagulation system in liver diseases with special reference to liver transplantation].

The central function of the liver as place of the formation of the most plasmatic coagulation factors in expressed by coagulation disturbances in severe liver diseases. Apart for intoxications, vitamin-K-deficiency and relatively rare congenital dysproteinoses the synthesis of the coagulation factors is apparently a relatively stable and rapidly recoverable function of the hepatocyte. On the other hand, however, the pathogenetic dominance of the accelerated balance in the sense of a disseminated intravasal coagulation and a secondarily increased fibrinolysis is emphasized for the severe disturbances of haemostasis in hepatopathies. In all kinds of shock, in tumours, inflammations, sepsis and intoxications as well as in portal hypertension of any reason the activation of the coagulation system up to the consumption coagulopathy develops. In the liver transplantation in addition to the operation shock deterioratingly comes the intensive blood contact with the often heavily damaged graft cells, the effectors of the immune system (rejection), the temporary disturbance of the clearance function of the liver RES and the basic disease of the recipient which in most cases disposes to the disseminated intravasal coagulation. The reduction of thrombocytes and coagulation factors extensively transgresses the changes which are to be expected by a weakness of the synthesis during and immediately after the anhepatic phase. For the therapy the demand of rapid removal of the coagulation-activating moments (minimum times of ischaemia, careful anastomoses) and of an adequate substitution with simultaneous prevention of the disseminated intravasal coagulation by heparinisation.

Blood Coagulation Factors↗

Outcome and pattern of recurrence after curative resection for hepatocellular carcinoma in patients with a normal liver compared to patients with a diseased liver.

BACKGROUND/AIMS: The purpose of this study was to investigate whether differences existed in demography and outcome after resection for hepatocellular carcinoma (HCC) in patients with a normal liver compared to patients with a diseased liver. METHODOLOGY: Twenty-seven Caucasian patients with HCC in a histologically proven normal liver (NL group) in the Netherlands and 141 Asian patients with HCC in a diseased liver (DL group) in Japan underwent a curative liver resection. Patient and tumor characteristics, post-resectional disease-free, overall survival rates and pattern of recurrence were investigated. RESULTS: HCC's in the NL group were found to be larger, in a more advanced stage and needed more extended resections compared to HCC's in the DL group. Microvascular invasion was similar in both groups, while capsule formation was observed less in the NL group. Overall survival and disease-free survival after curative resection were not statistically different between both groups. Also even after stratification for T-stage, there was no difference in survival. Although the rate of recurrence was similar in both groups, a significantly higher number of extrahepatic metastases was observed in the NL group. CONCLUSIONS: Distinct demographic differences existed between patients with HCC in the NL group compared to patients in the DL group. Extrahepatic recurrences were more frequent after curative resection for HCC in a normal liver. No difference in survival was demonstrated between both groups.

Adult↗

Immunology of alcoholic liver disease.

Alcohol-induced liver injury is a reflection of the immunologic response of the liver to this stimulus. Reported studies of immunologic abnormalities in alcoholic liver disease (ALD) patients suggest that immunologic response plays a key role in the pathogenesis of chronic liver disease in alcoholics, and have contributed to the understanding of how some patients with ALD progress into alcoholic liver cirrhosis. The immunologic response of the liver is reflected in alcoholic fatty liver disease, hyaline necrosis, and cirrhosis, promoted by the role of neutrophils in damaging liver cells through cytotoxicity, and lymphocytes through cytotoxicity, inducing fibrogenesis of the liver and formation of immune complexes responsible for immune complex-mediated cytotoxicity, in addition to the role of different chemokines in attracting leucocytes, inducing fibrogenesis and liver cell apoptosis, with the established mechanism by which Mallory bodies evoke both cellular and humoral immunity contributing to the process of alcoholic liver cirrhosis, which plays a key role in transformation of alcoholic hepatitis to cirrhosis. At present, research is underway to find modalities to correct the induced immunologic changes, so at this time, it is necessary to avoid alcoholism, with the use of social and educational programs to stop alcoholism.

Chemokines↗

Kinetics of drug action in disease states XII: Effect of experimental liver diseases on the pharmacodynamics of phenobarbital and ethanol in rats.

This investigation was designed to determine if liver diseases can modify the pharmacodynamics of the central nervous system depressants phenobarbital and ethanol. Two experimental models of liver diseases in rats were used: extrahepatic cholestasis produced by bile duct ligation and hepatic necrosis induced by carbon tetrachloride administration. Phenobarbital (both models) or ethanol (cholestasis model only) was infused slowly intravenously until the rats lost their righting reflex. Drug concentrations in serum, brain, and cerebrospinal fluid at that time were determined in the diseased animals as well as in sham-operated or solvent-treated controls. Phenobarbital concentrations at the onset of action were not significantly different between controls and either 5-d or 12-d cholestatic rats, except for total serum concentrations which were lower in the cholestatic groups due to reduced protein binding. Ethanol concentrations were slightly but statistically significantly lower in 12-d cholestatic rats as compared with controls. Neither 5-d nor 12-d carbon tetrachloride-induced hepatic dysfunction had any significant effect on phenobarbital concentrations at the onset of loss of righting reflex, except for a marginal decrease in the cerebrospinal fluid concentration of rats that had been treated for 5 d with the hepatotoxin. It was concluded that, under the experimental conditions, the hepatic diseases investigated did not have appreciable effects on the central nervous system response to the hypnotic action of phenobarbital and ethanol.

Animals↗

Alcohol unrelated hepato-biliary disorders in the alcoholic: the role of liver biopsy in determining the aetiology of liver disease.

Alcoholics with abnormal liver function tests are generally assumed to have one of the recognised patterns of alcoholic liver injury. This report described a group of nine patients who were initially thought to have alcoholic liver disease but were found on liver biopsy to have a variety of liver disorders unrelated to alcohol. Liver biopsy showed granulomatous hepatitis in three, primary biliary cirrhosis in two, and cholestasis of unknown cause, large duct biliary obstruction, haemochromatosis with secondary carcinoma and Budd-Chiari syndrome in one each. The histological changes observed in liver biopsy samples are believed to represent a chance occurrence of liver disease due to some agent other than alcohol and illustrates that forms of hepatic disease that affect the population at large can and do occur in heavy alcohol consumers.

Aged↗

[Biological diagnosis of the type of liver disease in alcoholic patients with abnormal liver function tests].

OBJECTIVES: The histological diagnosis of the different stages of alcoholic liver disease is not systematic. The aim of this study was to assess whether common biological features were useful in identifying the different stages. METHODS: One thousand twenty six alcoholic patients with liver histology and without any associated diseases or infections likely to alter serum liver tests were studied. Diagnostic analyses were performed using stepwise discriminant analysis in the entire population and in asymptomatic patients. RESULTS: a) Serum ASAT activity levels were only normal in 39% of the patients with normal histological liver and in 14% of the patients with steatosis; b) liver failure was already present in patients with fibrosis without cirrhosis; c) betagamma block was the only biochemical parameter which confirmed the diagnosis of cirrhosis without biopsy; d) the diagnostic accuracy of common tests was weak for the diagnosis of alcoholic liver disease without cirrhosis but prothrombin time could be useful in excluding the diagnosis of cirrhosis with and without acute alcoholic hepatitis when liver biopsy is not available. CONCLUSION: Only a prothrombin time of 80% with a negative predictive value of 94% and the presence of beta-gamma [corrected] block with a positive predictive value of 98% were useful for assessing the diagnosis of cirrhosis in all patients with alcoholic liver disease.

Adult↗

Liver transplantation for alcoholic liver disease.

The role of liver transplantation as a treatment for end-stage liver disease occurring in alcoholic patients is controversial. Earlier predictions that survival of alcoholic patients after liver transplantation was worse than that of non-alcoholic liver graft recipients, or that few alcoholic patients with serious liver disease could meet stringent selection criteria, have proved false. As a result, in many liver transplant programmes, alcoholic liver disease constitutes one of the most common diagnoses among patients proceeding to transplantation. Survival of alcoholic patients after transplantation is similar to that in non-alcoholic patients, i.e. up to 80% or more alive at 1 year. A multidisciplinary selection process has been introduced which includes careful psychiatric assessment to try to identify those patients most likely to maintain long-term abstinence after transplantation. Using this method, approximately 45% of alcoholic patients referred for transplantation have been selected for surgery. Furthermore, the survival rate of alcoholic patients not selected for transplantation because they were considered a poor prognostic risk for sobriety was significantly less than that of alcoholic patients undergoing liver transplantation. The ethical foundations for this multidisciplinary approach are explained in this chapter. Good data on recidivism after transplantation are few. In many programmes, including ours, instances of recidivism, defined as a relapse to a pathologic pattern of alcohol use, are uncommon and occur in 10% or less of alcoholic patients selected for liver transplantation, at least in the first 3 postoperative years. This figure underestimates the incidence of consumption of small amounts of alcohol. The data are limited also by the relatively short period of follow-up in most studies published to date. Whether recidivism will become more common as more patients are followed beyond 3 years remains to be seen.

Humans↗

[Prediction of hepatic fibrosis using serum hyaluronic acid in patients with chronic liver disease].

BACKGROUND/AIMS: The extent of hepatic fibrosis is important in chronic liver disease. Liver biopsy is essential for diagnosis of fibrosis. However, biopsy is invasive and may not represent the whole liver state. Serum hyaluronic acid (HA), a major component of connective tissues, was introduced as a useful non-invasive index of hepatic fibrosis. The aim of this study was to evaluate the relationship among HA, the degree of fibrosis, several hematologic and biochemical parameters in patients with chronic liver diseases or post state liver transplantation (PSLT). METHODS: Total 102 cases were divided into 4 groups: 57 chronic hepatitis (CH), 12 cirrhosis, 21 hepatocellular carcinoma (HCC), 12 PSLT. HA was measured by enzyme-linked binding protein assay and evaluated in relation the degree of fibrosis, several hematologic and biochemical parameters. RESULTS: Among four groups, HCC showed the highest HA and HA of HCC significantly higher than that of CH. The degree of fibrosis were correlated with HA. HA was correlated with age, platelet count and albumin but, not with ALT and PT. There is no significant relation between HA and the presence of acute rejection in liver transplantation. CONCLUSIONS: In chronic liver diseases, HA is a useful non-invasive index of hepatic fibrosis and disease severity.

Adolescent↗

Clinical significance of complements in ascitic diseases: elevated complement levels disapproving the liver disease origin.

In a two-year period, ascitic fluid concentrations of complement 3c and complement 4 were measured in 110 patients with sterile cirrhotic ascites, 31 patients with spontaneous bacterial peritonitis, 65 patients with hepatocellular carcinoma, 36 patients with peritoneal carcinomatosis and 12 patients with miscellaneous diseases (nephrotic syndrome 4, systemic lupus erythematosus 3, secondary peritonitis 2, cardiac ascites 1, eosinophilic peritonitis 1 and tuberculosis peritonitis 1) to assess the clinical utility of ascitic fluid complements. The ascitic fluid level of complements 3c or C4 was significantly higher in patients with peritoneal carcinomatosis (32.8 +/- 10.2, 13.4 +/- 7.4 mg/dL) than in patients with sterile cirrhotic ascites (9.2 +/- 5.2, 4.5 +/- 3.9 mg/dL, p < 0.001), spontaneous bacterial peritonitis (8.2 +/- 4.1, 3.8 +/- 2.4 mg/dL, p < 0.001) or hepatocellular carcinoma (12.8 +/- 8.3, 5.6 +/- 4.4 mg/dL, p < 0.001). However, it was not significantly different from the miscellaneous disease group. To verify that ascites formation is not related to liver disease origin, diagnostic sensitivity, specificity and accuracy were 83.3%, 92.7% and 90.9%, respectively, by the ascitic fluid level of complement 3c higher than the cut-off value (20 mg/dl); or 60.4%, 89.8% and 84.3%, respectively, by the ascitic fluid level of complement 4 higher than the cut-off value (10 mg/dL). A direct correlation was found between the ascitic fluid protein level and the ascitic fluid complement 3c (r = 0.70) or complement 4 (r = 0.57) level. Based on results in this study, we can conclude that measuring ascitic fluid complements is clinically useful in disapproving the liver disease origin of ascites formation. However, it is of little value in diagnosing spontaneous bacterial peritonitis or hepatocellular carcinoma.

Ascites↗

Treatment strategies in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized health problem. Increased fat accumulation in the liver is observed in 20-30% of the population in the Western world, and in approximately 10% of this cohort it is associated with nonalcoholic steatohepatitis, which is characterized by inflammation and fibrosis. Disease presentation of NAFLD ranges from asymptomatic disease to cirrhosis with the complication of liver failure and hepatocellular carcinoma. NAFLD is suspected on the basis of various clinical aspects (an elevated alanine aminotransferase concentration, presence of obesity and diabetes) that alone are not sufficient to establish diagnosis or prognosis. The major diagnostic procedure is liver biopsy, which allows assessment of liver injury. In most cases, NAFLD is associated with insulin resistance, which is therefore the target of most current NAFLD treatment modalities. Various treatment strategies such as weight loss and/or exercise, thiazolidinediones, metformin, lipid-lowering agents and antioxidants have been studied. So far, no single intervention has convincingly improved liver histology. It is recommended that patients at high risk of developing advanced liver disease, and who are not part of controlled studies, should receive nutritional counseling and take physical exercise to achieve moderate weight loss and improve insulin sensitivity.

Angiotensin II Type 1 Receptor Blockers↗

Cerebral blood flow and metabolism in patients with chronic liver disease undergoing orthotopic liver transplantation.

Changes in cerebral hemodynamics and metabolism associated with anesthesia and liver transplantation may present particular hazards for patients with cirrhosis. Fifteen patients undergoing liver transplantation were studied, 7 of whom had encephalopathy. Cerebral blood flow (CBF) was measured at the start of surgery, during veno-venous bypass and post reperfusion, using a method based on the Kety-Schmidt method. Cerebral metabolism was assessed by measuring the cerebral metabolic rate for oxygen (CMRO2) and the lactate oxygen index (LOI). The cerebral vascular reactivity to carbon dioxide (CO2) was studied during the preanhepatic and post reperfusion phases. During the preanhepatic period, the median CBF was 44 mL/100 g/min at an arterial carbon dioxide tension (PaCO2) of 3.8 kPa. After reperfusion the CBF increased (P < .02) to 102 mL/100 g/min, the arterial hydrogen ion concentration increased from 39 nmol/L to 53 nmol/L (P < .02) and the jugular venous oxygen saturation from 74% to 89% (P < .02). CBF was similar in patients with and without encephalopathy. The cerebral vascular reactivity to CO2 remained intact, although after reperfusion, the CBF for a given PaCO2 was greater, and the slope of the CBF/CO2 response curve diminished. The CMRO2 was normal in patients without encephalopathy. In the encephalopathic patients, the CMRO2 was low during all stages of transplantation (0.54, 0.86, 1.24 mL/100 g/min, respectively). Patients with encephalopathy may be at increased risk of hypoxemic brain injury during transplantation. To minimize this possibility, more detailed neurological monitoring may be useful.

Adult↗