Early Perivenular Sclerosis in Alcoholic Fatty Liver: An Index of Progressive Liver Injury

Waes, Leen Van; Lieber, Charles S.

doi:10.1016/s0016-5085(19)31758-5

Cited by 158 publications

(20 citation statements)

References 10 publications

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“…The cellular basis of hepatic fibrosis involves the interplay of many factors and cells including hepatic stellate cells (HSC), hepatocytes, Kupffer cells, endothelial cells, platelets and lymphocytes [1]. In liver injury, Th2 lymphocytes, characterized by elevated IL-4, appear to promote fibrogenesis relative to Th1 lymphocytes that express high levels of interferon (IFN) gamma [2][3][4][5][6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Anti-fibrotic activity of NK cells in experimental liver injury through killing of activated HSC

Melhem

Muhanna

Bishara

et al. 2006

Journal of Hepatology

244

242

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Section: Introductionmentioning

confidence: 99%

Anti-fibrotic activity of NK cells in experimental liver injury through killing of activated HSC

Melhem

Muhanna

Bishara

et al. 2006

Journal of Hepatology

244

242

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“…Hepatic fibrosis is a highly integrated cellular response to tissue injury [2], characterized essentially by activation of hepatic stellate cells (HSC), secretion and accumulation of extracellular matrix proteins [3]. The cellular basis of hepatic fibrosis involves the interplay of many factors and cells, including HSC, hepatocytes, Küpffer cells, endothelial cells, platelets and lymphocytes [4]. In liver injury, T helper type 2 (Th2) lymphocytes, characterized by elevated interleukin (IL)-4, appear to promote fibrogenesis relative to Th1 lymphocytes that express high levels of interferon (IFN)-g [5][6][7][8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Amelioration of hepatic fibrosis via Padma Hepaten is associated with altered natural killer T lymphocytes

Ginsburg¹,

Koren

Horani

et al. 2009

Clinical and Experimental Immunology

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SummaryHepatic fibrosis is the end-stage consequence of chronic liver disease, affecting many people worldwide. Unlike the anti-fibrotic effect of natural killer (NK) cells, CD8 and NK T subsets are considered as profibrogenic subsets. Padma Hepaten is a multi-compound herbal preparation derived from Tibetan medicine and has proven efficacy in some clinical trials and tests at the cellular level. In this study, we evaluate the immune efficacy of Padma Hepaten administered intraperitoneally (i.p.) and/or orally in a mice model of hepatic fibrosis. Hepatic fibrosis was induced by 6 weeks of biweekly i.p. carbon tetrachloride (CCl4) injections in male C57Bl6 mice. There were four groups, including naive mice, non-treated fibrotic mice and fibrotic mice treated by Padma Hepaten at weeks 5-6 of fibrosis induction either orally or by i.p. injections. Padma Hepaten was prepared at 10 mg/ml in saline and 250 ml (2·5 mg) were administered four times per week. After week 6, animals were killed. To isolate a Padma Hepaten-associated effect on lymphocytes, splenocytes were harvested from either naive or Padma Hepaten-treated non-fibrotic donors. Isolated splenocytes were therefore reconstituted into two groups of irradiated recipients. Recipients were then administered the same CCl4 regimen. Hepatic fibrosis was determined by sirius red staining of liver sections and by assessment of alpha smooth muscle actin expression compared with b-actin (both by mRNA as well as the protein liver extract western blotting). Hepatic fibrosis and alanine aminotransferase serum levels were decreased significantly in both Padma Hepaten-treated groups compared with the non-treated fibrotic group. Padma Hepaten treatment was associated with attenuation of lymphocyte subsets in both treated groups. Using a chemiluminescence technique to assess total anti-oxidant capacities (TAC), it was found that both the plasmas and livers of mice treated by CCl4 had significantly higher TAC compared with controls. However, the levels of TAC in animals treated either by CCl4 alone or CCl4 with Padma Hepaten were similar. Adoptive transfer of Padma Hepaten-treated lymphocytes was associated with fibrosis amelioration compared with recipients with naive lymphocytes. CCl4 generates higher levels of anti-oxidant capacities, probably as a response to oxidative stress. Padma Hepaten administration attenuated hepatic fibrogenesis significantly, accompanied by attenuation of lymphocyte but not anti-oxidant capacities.

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“…In experimental animals ethanol is a weak inducer of hepatic monooxygenase activity [4, 51, administration of ethanol in tap water does not induce the cytochrome P-450 enzyme system [I21 and animals do not develop the severe liver disease seen in man [13]. However, baboons have been shown to develop severe liver damage on continuous ethanol exposure [39].…”

Section: Discussionmentioning

confidence: 99%

Inducing efficacy of ethanol on hepatic drug metabolizing enzymes in patients

Hoensch¹,

Schreier²,

Ohnhaus³

1986

Eur J Clin Investigation

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In liver biopsy material of eighty-nine patients with suspected liver disease the drug-metabolizing function was investigated. The capacity of the liver to oxidatively metabolize drugs was assessed by determination of cytochrome P-450 dependent monooxygenase activity in vitro. The biotransformational function of these microsomal enzymes was tested with compounds representing the activity of oxidative drug metabolism (7-ethoxycoumarin, p-nitroanisol and cytochrome c). From the eight-nine patients sixty-one had various liver diseases not related to ethanol and twenty-eight abused ethanol. When both groups were matched for age, sex, smoking, treatment with sedatives, drugs and degree of liver damage the alcoholic group had significantly higher activities of 7-ethoxycoumarin O-deethylase (EOD: 76.9 +/- 31.1 pmol min-1 mg-1 protein, mean +/- SD) than the non-alcoholic liver disease group (42.7 +/- 14.1). The inducing effect of ethanol was most striking on the EOD activity, less for the O-demethylation of p-nitroanisol (PNA) and not present for the NADPH-cytochrome c reductase. The induced patients were analysed in detail to find out which factors were responsible for the observed scatter of enzyme activities within the alcoholic group. Alcoholics with fatty liver (n = 7) had the highest EOD activities (108.9 +/- 25.0), patients with alcoholic hepatitis (n = 10) had significantly less activity (66.0 +/- 1.9) than the former group. However, alcoholics without liver damage (n = 6) had activities not significantly different (46.0 +/- 15.8) from controls (39.4 +/- 9.1). These subgroups among the alcoholics were comparable in terms of sex, age, smoking and drinking habits.(ABSTRACT TRUNCATED AT 250 WORDS)

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Early Perivenular Sclerosis in Alcoholic Fatty Liver: An Index of Progressive Liver Injury

Cited by 158 publications

References 10 publications

Anti-fibrotic activity of NK cells in experimental liver injury through killing of activated HSC

Anti-fibrotic activity of NK cells in experimental liver injury through killing of activated HSC

Amelioration of hepatic fibrosis via Padma Hepaten is associated with altered natural killer T lymphocytes

Inducing efficacy of ethanol on hepatic drug metabolizing enzymes in patients

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