- Forouzanfar M.H.
- Afshin A.
- Alexander L.T.
- Anderson H.R.
- Bhutta Z.A.
- Biryukov S.
- et al.
|Strength||Magnitude of the association||Current smokers attributable risk fraction for HCC |
|Consistency||Reproducibility in different studies||Smoking history as a predisposing factor for PBC |
|Specificity||One-to-one relationships||Liver metabolises tobacco chemicals into carcinogens |
|Temporality||Exposure must precede the outcome||Tobacco smoking impacts liver transplantation outcomes |
|Biological gradient||Dose-response curve and reversibility||Increased fibrosis severity in NAFLD and PBC |
|Plausibility||Known bio-pathological mechanism||Induced AMPK inactivation involved in fatty acid synthesis |
|Coherence||Consistent with existent knowledge||Profibrogenic effect of tobacco in different organs |
|Experiment||Animal models experimental evidence||Cigarette smoking increases hepatic lipogenesis |
|Analogy||Similarities with other associations||NAFLD and smoking are linked to metabolic syndrome features |
Smoking and fatty liver disease
- Ajmera V.
- Belt P.
- Wilson L.A.
- Gill R.M.
- Loomba R.
- Kleiner D.E.
- et al.
Among patients with nonalcoholic fatty liver disease, modest alcohol use is associated with less improvement in histologic steatosis and steatohepatitis.
Smoking in the progression of other chronic liver diseases
|Study||Patients, n (country)||Design||Smoking assessment||Smoking prevalence||Gold standard||Results|
|Kleiner DE, 2019|
|446 with NAFLD (USA)||Prospective, NASH CRN longitudinal||Interview, grouping by status||9% active, 37% ever smoker||Histology||Current smoker ↓ fibrosis regression (p = 0.03)|
|Ou H, 2019|
|225 with NAFLD (China)||Retrospective cross-sectional case-control||n.a., smoking index (nº cig/day ∗ duration of smoking)||44% smokers||Liver stiffness||Smoking index ↑ liver fibrosis (OR 1.3; 1.1–2.1)|
|Xiong M, 2019|
|2,144 males with CHB (China)||Prospective, longitudinal cohort, propensity score matched||Interview, grouping by pack-years||47% smokers||Liver stiffness||Smokers ↑ advanced fibrosis (OR 1.5; 1.1–1.9), dose-response (≥10 pack-years ↓ fibrosis regression p = 0.02)|
|Mantaka A, 2018|
|117 with PBC (Greece)||Retrospective cross-sectional case-control||Interview, grouping by status and pack-years||26% active, 30% ex-smoker||Histology||Smoking history ↑ advanced fibrosis (p = 0.04), dose-response (OR 3.2; 2.0–6.3)|
|Musterman ID, 2017|
|56 with NAFLD (Netherlands)||Retrospective cross-sectional case-control||Chart review and interview||39% history of smoking||Histology||Smoking history ↑ fibrosis score (p = 0.04), dose-response (nº of pack-years ↑ advanced fibrosis)|
|Dam MK, 2013|
|18,479 from the general population (Denmark)||Population-based cohort||Interview, groups: ex, never, ≤ and >10 cig/day||56% ♀|
|Hospital register: cirrhosis ICD code||Adjusted HR for >10 cig/day: ♀ 2.2; 1.4–3.4 ♂1.4; 0.9–2.2|
|Corpechot C, 2012 |
|164 with PBC (France)||Prospective, cohort||Interview, grouping by pack-years||11% active smokers, 26% smoking history||Histology||Smoking history ↑ advanced fibrosis (OR 3.6; 1.5–8.5), dose-response (OR 1.2; 1.0–1.3)|
|Zein CO, 2011 |
|1,091 with NAFLD (USA)||Prospective, NASH CRN cross-sectional studies||Interview, significant smoking: ≥10 pack-years||24% with significant smoking history||Histology||Significant smoking ↑ advanced fibrosis (OR 1.6; 1.2–2.2)|
|TsochatzisE, 2009 |
|271 with CHB and CHC (Greece)||Prospective, cross-sectional case-control||Interview, groups: never, smoker, ≥20 pack-years||42% CHB|
61% CHC smokers
|Histology||No association with CH fibrosis. ≥20 pack-years ↑ CHC advanced fibrosis (OR 3.9; 1.4–11.3)|
|Dev A, 2006 |
|244 with CHC (USA)||Retrospective, cross-sectional case-control||Medical records, grouping by nº of cig/day||25% smokers||Histology||Smoking ↑ risk of fibrosis (OR 1.3; 1.0–1.8)|
|Zein CO, 2006 |
|97 with PBC (USA)||Retrospective, cross-validated case-control||Interview, significant smoking: ≥10 pack-years||44% with significant smoking history||Histology||Smoking history ↑ advanced fibrosis (p <0.001), dose-response (≥10 pack-years: OR 13.3; 4.3–49.3)|
|Hézode C, 2003 |
|244 with CHC (France)||Prospective, cross-sectional case-control||Interview, grouping by nº of cig/day||44% smokers, 25% >15 cig/day||Histology||No association with fibrosis (p = 0.5), >15 cig/day ↑ activity grade|
(OR 3.6; 1.5-8.8)
|Pessione F, 2001|
|310 with CHC (France)||Retrospective, cross-sectional case-control||n.a., grouping by pack-years||57% smokers||Histology||Smoking ↑ fibrosis score (p = 0.03), dose-response (≥15 pack-years: OR 1.9; 1.1-3.6)|
|Yu MW, 1997|
|1,506 with CHB (Taiwan)||Prospective, longitudinal||Interview, groups: 0,|
<20 and ≥20 cig/day
|43% smokers||Ultrasound image of cirrhosis||≥20 cig/day|
↑ risk of cirrhosis (OR 2.1; 1.2-3.7)
|Steatosis (S1-3)||Current S1: 29%||No steatosis (S0)||Current: 14-29%|
|Current S2: 32%|
|Current S3: 28%|
|NASH||Former: 38%||Simple steatosis||Former: 33%|
|Current: 9%||Current: 11%|
|F3-4||Former: 34%||F0-2||Former: 9%|
|Current: 10%||Current: 9%|
|>10 pack-years: 43%||>10 pack-years: 28%|
The effect of drinking coffee and smoking cigarettes on the risk of cirrhosis associated with alcohol consumption. A case-control study. Provincial Group for the Study of Chronic Liver Disease.
Eur J Epidemiol. 1994; 10: 657-664
|Alcohol-related cirrhosis||Current: 60-78%||General population||Current: 12%|
|Other CLD cirrhosis||Current: 71%|
|F3-4||Current: 40-56%||F0-2||Current: 42-44%|
|>20 pack-years: 28%||>20 pack-years: 17%|
|Cirrhosis||Current: 59%||No cirrhosis||Current: 42%|
|>20 pack-years: 27%||>20 pack-years: 18%|
|F3-4||Former: 19%||F0-2||Former: 18%|
|Current: 54-63%||Current: 57-61%|
|>20 pack-years: 43%||>20 pack-years: 22%|
|A2-3||Current: 48%||A0-1||Current: 34%|
|S1-3||>20 pack-years: 32%||S0||>20 pack-years: 12%|
|F3-4||Current: 21-71%||F0-2||Current: 19-33%|
|>10 pack-years: 71%||>10 pack-years: 19%|
|A2-3||Former: 20-25%||A0-1||Former: 18%|
|Current: 10-23%||Current: 16%|
- •Release of transforming growth factor-β1 with activation and proliferation of resident fibrogenic cells. In response to injury, transforming growth factor-β1 stimulates the production of extracellular matrix proteins, mainly collagen synthesis by hepatic stellate cells (HSCs), and plays a key role in the regulation of fibrosis.
- •Increased production of proinflammatory cytokines (interleukin [IL]-1, IL-6 and tumour necrosis factor-α) and recruitment of inflammatory cells such as neutrophils and monocyte-macrophages.,
- •Toll-like receptor 4 activation, a key pathway promoting fibrosis in steatohepatitis.Cigarette smoking is associated with impaired intestinal barrier, increased permeability and bacterial translocation.Toll-like receptor 4 is activated on the surface of HSCs by intestinal bacterial lipopolysaccharides derived from the gut, triggering cell activation and fibrogenesis.This mechanism links fibrosis to the microbiome.
- •Activation of reactive oxygen species (ROS) production by NADPH oxidase. Subsequent oxidative stress can lead to lipid peroxidation and hepatocellular damage.
- •Increase of carboxyhaemoglobin and decreased oxygen-carrying capacity of red blood cells which leads to tissue hypoxia. Induced erythropoietin production and secondary polycythaemia contribute to the accumulation of iron in macrophages and hepatocytes, enhancing liver injury and fibrosis.In this line, an interaction between current smoking and haemoglobin levels and the risk of NAFLD-advanced fibrosis have been shown.
Heavy cigarette smoking induces hypoxic polycythemia (erythrocytosis) and hyperuricemia in chronic hepatitis C patients with reversal of clinical symptoms and laboratory parameters with therapeutic phlebotomy.Am J Gastroenterol. 2002; 97: 1264-1265
- El-Zayadi A.R.
- Selim O.
- Hamdy H.
- El-Tawil A.
- Moustafa H.
- •Changes in the microvasculature such as endothelial dysfunction, smooth muscle cell proliferation and vasoconstriction, leading to an impairment in nitric oxide delivery and tissue hypoxia.In response to liver hypoxia, expression of vascular endothelial growth factor and type I collagen are increased in activated HSCs, enhancing fibrogenesis.,
Smoking and hepatocellular carcinoma
- Forouzanfar M.H.
- Afshin A.
- Alexander L.T.
- Anderson H.R.
- Bhutta Z.A.
- Biryukov S.
- et al.
- Tanaka K.
- Tsuji I.
- Wakai K.
- Nagata C.
- Mizoue T.
- Inoue M.
- et al.
Cigarette smoking and liver cancer risk: an evaluation based on a systematic review of epidemiologic evidence among Japanese.
Impact of smoking on clinical outcomes in patients with liver disease
- Corrao G.
- Lepore A.R.
- Torchio P.
- Valenti M.
- Galatola G.
- D'Amicis A.
- et al.
Electronic cigarette exposure and liver disease
Conflict of interest
- Multimedia component 1
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