Smoking is associated with steatosis and severe fibrosis in chronic hepatitis C but not B

Second Department of Internal Medicine, Athens University Medical School, Hippokration General Hospital, Athens, Greece.
Scandinavian Journal of Gastroenterology (Impact Factor: 2.36). 04/2009; 44(6):752-9. DOI: 10.1080/00365520902803515
Source: PubMed


The results of retrospective studies suggest an association between smoking, insulin resistance, steatosis and fibrosis in patients with chronic hepatitis C (CHC); no data are available for chronic hepatitis B (CHB). The purpose of this study was to evaluate the relationship, if any, of such factors on liver fibrosis in a cohort of patients with CHB and CHC.
The study prospectively included 271 consecutive patients with CHB (n=95) or CHC (n=176) who had undergone liver biopsies. Each patient completed a questionnaire on smoking habits; anthropometric measurements and laboratory examinations were carried out and histological lesions were recorded.
In CHC patients, severe fibrosis was independently associated with a higher body mass index (BMI) (OR: 1.180, 95% CI: 1.028-1.354; p=0.019), heavy smoking (OR: 3.923, 95% CI: 1.356-11.348; p=0.012), higher alanine aminotransferase (ALAT) levels (OR: 1.010, 95% CI: 1.003-1.017; p=0.005) and alkaline phosphatase (ALP) levels (OR: 1.016, 95% CI: 1.001-1.030; p=0.03) and presence of necroinflammation (OR: 11.165, 95% CI: 1.286-96.970; p=0.029). Moreover, steatosis was independently associated with high gamma-glutamyl transpeptidase (GGT) values, heavy smoking and presence of necroinflammation. In CHB patients, no association between smoking habits and fibrosis or steatosis was noted.
Heavy smoking is associated with severe fibrosis in CHC but not CHB. Heavy smoking is also significantly associated with steatosis in CHC and this could be the link between smoking and fibrosis progression.

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Available from: Emmanuel A Tsochatzis, Oct 06, 2015
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    • "Smoking has been indicated as a risk factor for the progression of cholestatic liver diseases in several epidemiological studies. Emerging evidence indicates that exposure to cigarette smoke may stimulate the progression of chronic liver disease towards fibrosis (such as PSC, PBC, chronic hepatitis C, and non-alcoholic fatty liver disease) [8] [9] [10] [11]. A recent study has shown that long-standing nicotine abuse in patients with PSC is a risk factor for the development of hepatobiliary cancers [11]. "
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    ABSTRACT: BACKGROUND: Epidemiological studies have indicated smoking to be a risk factor for the progression of liver diseases. Nicotine is the chief addictive substance in cigarette smoke and has powerful biological properties throughout the body. Nicotine has been implicated in a number of disease processes, including increased cell proliferation and fibrosis in several organ systems. AIMS: The aim of this study was to evaluate the effects of chronic administration of nicotine on biliary proliferation and fibrosis in normal rats. METHODS: In vivo, rats were treated with nicotine by osmotic minipumps for two weeks. Proliferation, α7-nicotinic receptor and profibrotic expression were evaluated in liver tissue, cholangiocytes and a polarized cholangiocyte cell line (normal rat intrahepatic cholangiocyte). Nicotine-dependent activation of the Ca(2+)/IP3/ERK 1/2 intracellular signalling pathway was also evaluated in normal rat intrahepatic cholangiocyte. RESULTS: Cholangiocytes express α7-nicotinic receptor. Chronic administration of nicotine to normal rats stimulated biliary proliferation and profibrotic gene and protein expression such as alpha-smooth muscle actin and fibronectin 1. Activation of α7-nicotinic receptor stimulated Ca(2+)/ERK1/2-dependent cholangiocyte proliferation. CONCLUSION: Chronic exposure to nicotine contributes to biliary fibrosis by activation of cholangiocyte proliferation and expression of profibrotic genes. Modulation of α7-nicotinic receptor signalling axis may be useful for the management of biliary proliferation and fibrosis during cholangiopathies.
    Digestive and Liver Disease 04/2013; 45(9). DOI:10.1016/j.dld.2013.02.023 · 2.96 Impact Factor
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    • "A growing body of evidence suggests that cigarette smoking may also accelerate the progression of renal, pulmonary, and cardiac fibrosis [1] [2] [3]. Moreover, in smokers, with chronic liver diseases such as primary biliary cirrhosis and chronic hepatitis C there is a documented increased severity of hepatic fibrosis [4] [5] [6]. More recently , CS has been shown to exacerbate the histological severity of NAFLD in obese Zucker rats [7] and to be associated with advanced liver fibrosis in a large multi-center cohort of NAFLD patients [8]. "
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    ABSTRACT: Cigarette smoke (CS) may cause liver fibrosis but possible involved mechanisms are unclear. Among the many chemicals in CS is nicotine - which affects cells through nicotinic acetylcholine receptors (nAChR). We studied the effects of nicotine, and involved pathways, on human primary hepatic stellate cells (hHSCs), the principal fibrogenic cells in the liver. We then determined possible disease relevance by assaying nAChR in liver samples from human non-alcoholic steatohepatitis (NASH). hHSC were isolated from healthy human livers and nAChR expression analyzed - RT-PCR and Western blotting. Nicotine induction of hHSC proliferation, upregulation of collagen1-α2 and the pro-fibrogenic cytokine transforming growth factor beta 1 (TGF-β1) was determined along with involved intracellular signaling pathways. nAChR mRNA expression was finally analyzed in whole liver biopsies obtained from patients diagnosed with non-alcoholic steatohepatitis (NASH). hHSCs express muscle type (α1, β1, delta and epsilon) and neuronal type (α3, α6, α7, β2 and β4) nAChR subunits at the mRNA level. Among these subunits, α3, α7, β1 and ε were predominantly expressed as confirmed by Western blotting. Nicotine induced hHSC proliferation was attenuated by mecamylamine (p<0.05). Additionally, collagen1-α2 and TGF-β1 mRNA expression were significantly upregulated by nicotine and inhibited by mecamylamine. α1 and α3-nAChR mRNA expression was significantly upregulated in NASH fibrosis compared to normal livers. Nicotine at levels in smokers' blood is pro-fibrogenic, through actions on hHSCs expressed nAChRs. Therefore, CS, via its nicotine content, may worsen liver fibrosis. Moreover, nicotinic receptor antagonists may have utility as novel anti-fibrotic agents.
    Biochemical and Biophysical Research Communications 11/2011; 417(1):17-22. DOI:10.1016/j.bbrc.2011.10.151 · 2.30 Impact Factor
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    • "In a study of 271 patients with chronic hepatitis C or B infection, Tsochatzis et al. find that heavy smoking is associated with severe fibrosis in C but not B patients [15]. In C patients, heavy smoking is associated with steatosis, suggesting that this is the causal pathway. "
    Scandinavian Journal of Gastroenterology 01/2009; 44(6):644-645. DOI:10.1080/00365520902910302 · 2.36 Impact Factor
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