Mechanisms Of Liver Damage Research Articles

Oxidative stress of liver in hamsters infected with Leishmania (L.) chagasi.

Oxidative stress as a mediator of hepatic tissue damage concurrent with Leishmania (L.) chagasi infection was investigated. Chemiluminescence in liver supernatant of hamsters infected with Leishmania (L.) chagasi showed a ratio of 1.53/ mg protein and 2.10/liver weight 90 days after infection when compared with the control. The malondialdehyde (MDA) levels also increased significantly both with and without addition of Fe3+/ascorbic acid in the reaction mixture, with a ratio of 2.12 and 1.55/mg protein or 2.91 and 2.12/liver weight, respectively. The parasite burden in the spleen, as a measure of infection severity, was 9.1+/-1.33 x 10(8) parasites/organ. On the 10th day of infection, the chemiluminescence also was significantly higher in infected hamsters than in the controls (ratio = 1.36/mg protein or 1.34/liver weight); however, the MDA levels were not different from those of controls. After 90 days of infection, significant correlations were observed between chemiluminescence and MDA concentration with and without the presence of Fe3+/ascorbic acid (r = 0.54, P = 0.0001; r = 0.56, P = 0.0001; respectively). The high infection/control ratio of both chemiluminescence and MDA concentration and the significant correlation between those events strongly indicate the occurrence of oxidative stress and lipid peroxidation as a mechanism of liver damage in cases of chronic infection by L. chagasi. The significant increase in chemiluminescence at 10 days of infection demonstrates that oxidative stress occurs very early, first consuming the antioxidants and then inducing lipid peroxidative damage later in the chronic stage of this disease.

Blood lipids of patients with chronic hepatitis: differences related to viral etiology

In order to investigate whether a difference might exist in blood cholesterol and its subtractions between patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, serum cholesterol, HDL-cholesterol, triglycerides and common liver function tests were measured in 138 patients (92 male, 46 female) with biopsy-proven chronic viral hepatitis without cirrhosis. Twenty-four had hepatitis B and 114 hepatitis C. Mean serum cholesterol was lower in HCV infected in comparison to HBV infected patients (175±36 mg/dl vs. 189±28 mg/dl, p < 0.05). On multivariate analysis, etiology of hepatitis appeared to be associated with the value of serum cholesterol, independently of age, sex and liver synthetic function (improvement of chi-squalre 4.40, p < 0.05). In patients with HBV infection, circulating tumor necrosis factor-a demonstrated a correlation with serum triglycerides ( ϱ = 0.618) and an inverse correlation with serum IiDL-cholesterol ( ϱ = − 0.456); in the group of patients with HCV infection, interleukin-6 correlated with triglycerides ( ϱ = 0.370) and HDL-cholesterol ( π = − 0.355). Thus, differences in the mechanisms of liver damage and of viral clearance in hepatitis C in comparison to hepatitis B, reflected in these patients by the levels of circulating cytokines, may be mirrored by differences in their blood lipid composition.

Eosinophilic hepatitis: A new feature of the clinical spectrum of the eosinophilia-myalgia syndrome

The eosinophilia-myalgia syndrome associated with L-tryptophan-containing products is highlighted by eosinophilia, incapacitating myalgias, and diverse multisystemic manifestations. In addition to involvement of the skin, skeletal muscle, and peripheral nerves, visceral damage has been quite prominent, particularly affecting the lungs, the heart, and the liver. Hepatic involvement has been manifested by altered liver tests but is clinically silent. We report the unique case of a woman with this syndrome who developed abdominal pain, a clinical picture of hepatitis and chronically abnormal liver tests. Histologic examination of the liver disclosed eosinophilic hepatitis with piecemeal necrosis. The occurrence of clinically overt hepatic involvement has not been reported previously. Potential mechanisms of liver damage in eosinophilia-myalgia syndromes are discussed.

Immune pathogenesis of hepatitis A.

In an effort to elucidate the mechanism of liver damage resulting from Hepatitis A virus (HAV) infection, we have studied infected skin fibroblasts and autologous lymphocytes from HAV patients. We report here that HLA-restricted virus-specific T cells play an essential role in HAV-related hepatocellular injury.

α1‐antitrypsin deficiency and liver disease: Clinical presentation, diagnosis and treatment

The alpha 1-antitrypsin deficient subject (protease inhibitor (PI) phenotype ZZ) has an increased susceptibility to liver disease. The condition is most commonly identified in early infancy as a conjugated hyperbilirubinaemia with hepatitis (11%) or a bleeding state due to vitamin K malabsorption (2%). 50% of cases have cirrhosis and 25% die in the first decade of life. A further 2% present with cirrhosis in later childhood. Adult males are at risk of hepatoma development with or without cirrhosis. Diagnosis is by isoelectric focussing or allele-specific oligonucleotide hybridization. The treatment is that of cholestasis and cirrhosis including transplantation. The pathobiology of the deficiency state, the mechanism of liver damage and the vulnerability of the newborn liver are discussed in this review. A plea is made for a trial of infusions of alpha 1-antitrypsin in early infancy, as is used safely but without proven efficacy in the emphysematous PIZZ subject. Prospects of therapy by gene modification are also reviewed.

Living with Chronic Hepatitis

Chronic hepatitis (CH) may be defined as persistence of an inflammatory reaction in the liver for greater than 4 months. Different immune mechanisms of liver damage are operative in children with the three common types of CH. In autoimmune CH the cytotoxic effect is mostly confined to the non-T cell lymphocyte fraction. Autoimmune CH is steroid responsive and has a generally favorable prognosis. In hepatitis B virus (HBV) hepatitis both T and non-T lymphocytes are responsible for the cytotoxic reaction. Steroid or interferon treatment is controversial and the prognosis is less favorable. Hepatitis delta virus (HDV) hepatitis only occurs in children with HBV hepatitis as either a co-infection or superinfection. As a co-infection the HBV is usually eliminated and CH does not ensue. Superinfection with HDV, however, frequently leads to rapidly progressive liver damage and a more serious prognosis. Non-A, non-B (NANB) hepatitis is a diagnosis of exclusion. In NANB hepatitis, the cytotoxic effect is predominantly T cell. NANB hepatitis generally runs a mild course, and no treatment is usually recommended.

Halothane hepatitis.

Hepatitis following halothane anaesthesia may take two forms: a mild self-limiting disease or a more severe hepatitis with a high mortality. Whether these two forms represent two distinct entities or ends of a spectrum is unclear. Severe hepatitis is commoner after multiple exposures and has many of the characteristics of an immune-mediated hypersensitivity reaction. The incidence is very low; the best, albeit unsatisfactory, estimate of the incidence is about 1 in 3,700 patients with multiple halothane exposures. The mechanism of liver damage is uncertain: in some circumstances halothane may be directly hepatotoxic, but it remains to be conclusively proved that immune mechanisms are responsible. Studies from our unit have suggested that halothane hepatitis can positively be diagnosed by demonstration of antibodies reacting with halothane-altered liver cell determinants. The incidence of the condition can be reduced by taking a full anaesthetic history and avoiding the use of halothane in the high-risk patients, namely those who have had recent previous halothane anaesthesia and those who have had jaundice or unexplained post-operative pyrexia following earlier halothane anaesthetics. When halothane hepatitis has occurred, treatment is purely supportive with the possibility of transplantation for those in grade IV encephalopathy.

Morphological basis for hepatic failure in the early period of the crush syndrome

Disturbances of liver function are of great importance in the clinical management of the crush syndrome (CS). The results of including the allogenic and xenogenic liver in the perfusion circuit of the crushed limb under clinical and experimental conditions indicate that the state of the liver can largely determine both the victim's recovery from shock and the development of acute renal failure [5]. Depression of many functions of the liver during crushing of the soft tissues has been observed during the first few hours of decompression, and may continue for a long time after trauma [3, 7, 12, 13]. For instance, disturbanceofantitoxic function was described even 3 months after trauma [i0] and depression of the protein forming function 5 years after trauma [ii]. The mechanism of the disturbances of liver function in CS and itsmorphological basis have been inadequately studied. Nonspecific changes in the liver have been described, in the form of congestion and stasis of blood in the sinusoids, disappearance of glycogen from the hepatocytes, and microfocal necrosis [3, 4]. Insufficient attention has been paid in the pathogenesis of liver damage to the effect of the decompression factor, and no data are available on the state of the reticuloendothelial system (RES) of the liver in CS. In the investigation described below the morphological basis and possible mechanisms of liver damage in the early period of CS were studied. EXPERIMENTAL MET}IOD The liver of rats and dogs with a severe form of CS, reproduced in animals with different typological features of their nervous system was studied; this was done in order to achieve the closest possible similarity between the model and CS in man, which is characterized by diversity of its clinical manifestations. Both hind limbs of 45 rats, under open ether anesthesia, were crushed with a force of 30 kg for 6 h. The soft tissues of one thigh of 20 dogs were crushed under thiopental anesthesia by metal forceps for 9 h. Morphological changes in the liver were studied at the end of the period of decompression and 2-7 h after decompression. Paraffin sections stained with hematoxylin and eosin and after the PAS reaction were examined. Pieces of liver for electron microscopy were fixed in 1% osmic acid and sections were stained with uranyl acetate and lead and studied in the JEM-100B electron microscope.

CELL MEDIATED IMMUNE RESPONSE TO LIVER SPECIFIC ANTIGENS FOLLOWING HEPATITIS B VIRUS INFECTION IN MAN

The in-vitro correlates of cell mediated immunity (CMI) against liver specific antigens (LSA) and hepatitis B surface antigen (HBsAg) was studied in groups of subjects with acute or chronic hepatitis B virus (HBV) infection and in a population of uninfected healthy controls. The techniques of in-vitro lympho-proliferative responses (LTF) to HBsAg, LSA, phytohemagglutinin (PHA) were employed in these studies. The LSA consisted of liver tissue extracts prepared from HBV seronegative autopsy materials. No LTF response to LSA and HBsAg was observed in control population. All patients with acute HBV infection manifested significant LTF response to HBsAg as well as to LSA. Peak responses were observed at the height of clinical disease. 50% of patients with chronic HBsAg csrrier state elicited LTF response to HBsAg. Majority of these subjects also exhibited LTF response to LSA. About 15% of HBsAg carriers who failed to manifest CMI to HBsAg showed significant LTF activity to LSA. Despite the differences in LTF responses to HBsAg and LSA in different population groups, the response to PHA was generally similar although it appeared to be somewhat depressed in subjects with acute hepatitis. These observations suggest that the induction of cellular responses against native liver specific proteins may be the underlying mechanism of liver damage during acute HBV infection. It is possible that the persistence of specifically sensitized clones of T-lymphocytes may lead to establishment of chronic liver disease.

Prevention of the hepatotoxic effects of D-galactosamine by D-galactose

Galactosamine hepatitis [l] is accompanied by decreased incorporation of amino acid into protein [2,3] and of uridine into RNA in the liver [2]. Recently the inhibition of induction of rat liver tyrosine amino transferase by D-galactosamine has been reported [4]. The mechanism of liver damage is not known, and the involvement of unphysiological metabolites of galactosamine has been supposed [5-71. In this report we describe the in vitro inhibition of amino acid, uridine and orotate incorporation into mouse liver slices caused by D-galactosamine, and the enhancement of inhibition in the presence of uridine and its reversion by D-galactose. Galactosamine hepatitis is prevented by D-galactose in vivo.

The mechanism of liver damage in the graft versus host reaction

The mechanism of liver damage in the graft versus host reaction