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Robert G Batey

Publications and source records attributed to Robert G Batey.

7 recordsLinked to original sources
PubMed2002

Factors associated with severity of hepatic fibrosis in people with chronic hepatitis C infection.

OBJECTIVE: To determine factors associated with hepatic fibrosis development in people with chronic hepatitis C virus (HCV) infection. METHODS: As a requirement for access to interferon therapy through the S100 scheme in Australia, individual pretreatment demographic and clinical information was collected on 2986 patients from 61 hospital-based liver clinics from 1 October 1994 through 31 December 1996. Patients with both a hepatic fibrosis score and an estimated duration of HCV infection (910) were divided into 540 with no or minimal hepatic fibrosis (stage 0-1) and 370 with moderate to severe hepatic fibrosis (stage 2-3). Seven factors were examined: age at HCV infection, sex, ethnicity, source of infection, duration of infection, alcohol intake, and mean ALT level. A further analysis was performed for all 1135 patients with a hepatic fibrosis score disregarding age at and duration of HCV infection. RESULTS: In multivariate analysis, four factors were significantly associated with moderate to severe hepatic fibrosis: age at infection (OR, 2.33 for age 31-40 years, 5.27 for age > 40 years, and 0.20 for age < 15 years, compared with 15-20 years); duration of infection (OR, 1.44 for 11-20 years, 2.74 for 21-30 years, and 8.71 for > 30 years, compared with < 11 years); alcohol intake in previous six months (OR, 1.51 for any intake, compared with none); and mean ALT level (OR, 1.81 for 2-3 times, 2.27 for > 3 times, compared with 1.5-2 times the upper limit of normal). In the analysis disregarding age at HCV infection and duration of HCV infection, older age was strongly associated with moderate to severe hepatic fibrosis (OR, 2.32 for age 36-40 years, 2.46 for age 41-50 years, 7.87 for age 51-60 years, and 7.15 for age > 60 years, compared with 16-30 years). There was no association in either analysis with sex or source of HCV infection. CONCLUSION: These factors may assist in targeting patients for both liver biopsy-based investigation and therapeutic intervention.

Adolescent↗
PubMed2002

Molecular pathogenesis of T lymphocyte-induced liver injury in alcoholic hepatitis.

The development of alcohol-induced liver injury is, in part, a consequence of the immunological/inflammatory response that alcohol stimulates. The abnormalities of immune function in heavy drinkers have been documented well. Cytokines, especially TNF alpha, produced from macrophages/Kupffer cells, play a role in the induction of liver cell necrosis and apoptosis. TNF alpha can cause liver cell apoptosis through the TNF alpha receptor or Fas/CD95 which is expressed by liver cells. Furthermore, chronic ethanol consumption may damage the liver by inhibiting the hepatotrophic and hepatoprotective actions of TNF alpha and other cytokines. There exists an intrinsic lymphocyte population in the normal liver. Intrahepatic T lymphocytes consist of a heterogeneous population of cells that has many and varied functional characteristics in addition to classical T cell activity. The population of intrahepatic T lymphocytes may arise via a thymus-independent pathway. Our recent work has demonstrated the role of liver-associated T lymphocytes in the pathogenesis of alcohol related liver injury initiated by a variety of stimuli such as endotoxin (lipopolysaccharide, LPS) or concanavalin A (Con A). Our studies have, for the first time, suggested that alcohol consumption alone does not lead to the development of marked liver necrosis (at least in the rat), but rather that a second insult is required for this to occur. Liver-associated T lymphocytes in rats spontaneously secrete interleukin-1 alpha, interleukin-6 and TNF alpha in vitro culture. There is a significant decline in the amounts of interleukin-1 alpha and TNF alpha secreted in ethanol-consuming rats compared with non-ethanol consuming rats. The numbers of T cells, NK cells and Kupffer cells in liver perfusates remains stable over a prolonged period of ethanol consumption. However, following Con A injection, there was an inappropriate increase in the amounts of interleukin-6 and TNF alpha secreted in in vitro culture of liver-associated T lymphocytes and a significant increase in the percentage of CD4+ T cells and CD25+ T cells in liver perfusates compared with non-ethanol consuming rats. It suggested that liver-associated T lymphocytes are involved in the inflammatory process associated with alcohol related liver injury through increased cytokine secretion (TNF alpha).

Animals↗
PubMed2002

Lymphocyte-mediated liver injury in alcohol-related hepatitis.

The pathogenesis of alcohol-related liver disease (ALD) remains inadequately explained. Increasing alcohol intake is associated with an increased risk of ALD, but many heavy drinkers develop no liver damage. An explanation for ALD susceptibility requires theories that extend beyond a biochemical understanding of alcohol metabolism. Several hepatic cell populations are involved in the pathogenesis of liver injury. The liver-associated lymphocyte (LAL) response to alcohol intake plus immune stimulation may determine susceptibility to liver damage. We have isolated rat LALs and demonstrated the following: (1) Liver-associated lymphocytes differ from the peripheral blood lymphocyte pool; the CD8:CD4 ratio is higher in the LAL population than in peripheral blood. (2) Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 production by these cells is suppressed by regular alcohol intake. (3) Tumor necrosis factor-alpha and interleukin-6 production by LALs is increased after parenteral administration of concanavalin A (Con A) and by Con A in in vitro LAL cultures obtained from healthy (control) and ethanol-consuming rats. (4) In vivo stimuli that lead to increased cytokine production by LALs lead, within 12-24 h, to increased hepatocyte necrosis [elevated alanine aminotransferase (ALT) levels] and apoptosis. (5) Liver-associated lymphocytes isolated from ethanol-consuming rats, transferred to non-ethanol-consuming rats, confer on the latter animals an ethanol-consuming response to Con A. (6) Cytokine release by LALs is quantitatively as significant as that from Kupffer cells after exposure to lipopolysaccharide. (7) In co-culture studies inhibition of TNF-alpha activity reduces hepatocyte apoptosis induced in the presence of activated LALs. (8) Finally, nuclear factor-kappa B inhibition decreases production of nitric oxide and TNF-alpha, with an associated reduction in hepatocyte apoptosis. In summary, our study findings support the suggestion that a role for LALs exists in the pathogenesis of alcohol and Con A-mediated liver disease.

Animals↗