Moderate Alcohol Consumption Increases Oxidative Stress in Patients With Chronic Hepatitis C

Rigamonti, Cristina; Mottaran, Elisa; Reale, E.; Rolla, Roberta; Cipriani, Valentina; Capelli, F; Boldorini, Renzo; Vidali, Matteo; Sartori, Massimo; Albano, Emanuele

doi:10.1053/jhep.2003.50275

Cited by 107 publications

(76 citation statements)

References 38 publications

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“…8 Although the threshold level in CLD patients could be speculated as lower than in those without CLD because of possible interaction between alcohol and hepatotropic viruses (e.g., the elevation of oxidative stress observed even in moderate alcohol drinkers with HCV), 30 our data showed that the risk of HCC began to increase at about daily 3 ''go''s by comparing HCC cases with CLD patients, as well as hospital controls. This result was unchanged when the analysis was restricted to HCVAb-positive subjects (data not shown).…”

Section: Discussionmentioning

confidence: 59%

Influence of alcohol consumption and gene polymorphisms ofADH2andALDH2on hepatocellular carcinoma in a Japanese population

et al. 2005

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Although alcohol intake as well as hepatitis viruses has been associated with hepatocellular carcinoma (HCC), gene-alcohol interactions on HCC risk remain to be elucidated. We conducted a case-control study to examine whether polymorphisms of alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2) modified the HCC risk depending on the amount of alcohol intake. ADH2 and ALDH2 genotyping was performed by a duplex polymerase chain reaction with confronting two-pair primers in 209 newly diagnosed HCC cases and 2 different controls [275 hospital controls and 381 patients with chronic liver disease (CLD)]. Multiple logistic regression analyses revealed that heavy drinkers consuming 3 ''go''s/day of sake (69 g of ethanol/day) showed an increased risk of HCC based on comparison of HCC cases with hospital controls [adjusted odds ratio (OR) 5 13.5; 95% confidence interval (CI) 3.3-54.3] or CLD patients (adjusted OR 5 7.0; 95% CI 2.5-19.2), whereas the overall risk was not elevated among light to moderate drinkers consuming <3 ''go''s/day. Interestingly, light to moderate drinking was associated with an increased risk among those with ALDH2*1/*2 (adjusted OR 5 4.5 or 2.0), but not among those with ALDH2*1/*1 (adjusted OR 5 0.8 or 1.0; p interaction 5 0.03 or 0.13). However, this gene-alcohol interaction was not observed for heavy drinking. Among light to moderate drinkers, people with the combination of ALDH2*1/ *2 and ADH2*2/*2 revealed the highest risk of HCC. These findings indicate that the ALDH2 polymorphism may modify HCC risk among light to moderate drinkers. ' 2005 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 59%

Influence of alcohol consumption and gene polymorphisms ofADH2andALDH2on hepatocellular carcinoma in a Japanese population

et al. 2005

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“…The proposed priming mechanism toward oxidative injury, via keratin mutation, may also be potentiated by the observed increase in cytochrome P450 (Table 2), and is also supported by the accumulation of lipid (malondialdehyde) and protein (albumin) oxidation products. Accumulation of oxidation products is likely related to spikes of oxidative stress, and such accumulation is noted in patients with hepatitis C who consume alcohol 42 and in brains of patients with Alzheimer's disease or Parkinson's disease. 35 The normal GSH and cysteine levels (Table 3) in R89C mice is likely related to adequate compensation via diet and other contributions (Fig.…”

Section: Discussionmentioning

confidence: 99%

Keratin mutation primes mouse liver to oxidative injury†

Zhou

Chen

et al. 2005

Hepatology

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Mutation of the cytoskeletal intermediate filament proteins keratin 8 and keratin 18 (K8/K18) is associated with cirrhosis in humans, whereas transgenic mice that overexpress K18 Arg893 Cys (R89C) have significant predisposition to liver injury. To study the mechanism of keratinassociated predisposition to liver injury, we used mouse microarrays to examine genetic changes associated with hepatocyte keratin mutation and assessed the consequences of such changes. Liver gene expression was compared in R89C versus nontransgenic or wild-type K18-overexpressing mice. Microarray-defined genetic changes were confirmed by quantitative polymerase chain reaction. Nineteen genes had a more than two-fold altered expression (nine downregulated, 10 upregulated). Upregulated genes in keratin-mutant hepatocytes included the oxidative metabolism genes cytochrome P450, S-adenosylhomocysteine (SAH) hydrolase, cysteine sulfinic acid decarboxylase, and oxidation-reduction pathway genes. Downregulated genes included fatty acid binding protein 5, cyclin D1, and some signaling molecules. Several methionine metabolism-related and glutathione synthetic pathway intermediates, including S-adenosylmethionine (SAMe) and SAH, were modulated in R89C versus control mice. R89C livers had higher lipid and protein oxidation by-products as reflected by increased malondialdehyde and oxidized albumin. In conclusion, K18 point mutation in transgenic mice modulates several hepatocyte oxidative stress-related genes and leads to lipid and protein oxidative by-products. Mutationassociated decreases in SAH and SAMe could compromise needed cysteine availability to generate glutathione during oxidative stress. Hence keratin mutations may prime hepatocytes to oxidative injury, which provides a new potential mechanism for how keratin mutations may predispose patients to cirrhosis. (HEPATOLOGY 2005;41:517-525.)

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“…Alcohol consumption has been shown to increase apoptosis of hepatocytes 35 and oxidative stress in patients with chronic hepatitis C virus infection. 36 Furthermore, HCV core protein and chronic alcohol consumption additively increased lipid peroxidation and synergistically increased hepatic TNF-␣ and TGF-␤1 expression in HCV core protein-expressing transgenic mice. 37 All these fibrogenic factors -apoptosis, oxidative stress, lipid peroxidation, TNF-␣, and TGF-␤1 -may be involved in promoting the effect of alcohol on hepatic fibrosis in HCV infected patients.…”

Section: A6 Hcv and Liver Fibrosismentioning

confidence: 99%