Metformin-Induced Cholestatic Hepatitis

Nammour, Fadel; Fayad, Nabil; Peikin, Steven R.

doi:10.4158/ep.9.4.307

Cited by 49 publications

(30 citation statements)

References 3 publications

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“…Data are the means ± SEM of four independent experiments. ***P \ 0.001; **P \ 0.01; *P \ 0.05, when compared with control condition which is in accordance with previous case reports [44,45] describing the existence of metformin-induced hepatotoxicity. Since liver mitochondria of diabetic patients under metformin treatment are potentially exposed to high levels of this antidiabetic agent, the potential side effects of metformin should be carefully considered.…”

Section: Discussionsupporting

confidence: 80%

Metformin promotes isolated rat liver mitochondria impairment

et al. 2007

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Metformin, a drug widely used in the treatment of type 2 diabetes, has recently received attention due to the new and contrasting findings regarding its effects on mitochondrial function. In the present study, we evaluated the effect of metformin in isolated rat liver mitochondria status. We observed that metformin concentrations ‡8 mM induce an impairment of the respiratory chain characterized by a decrease in RCR and state 3 respiration. However, only metformin concentrations ‡10 mM affect the oxidative phosphorylation system by decreasing the mitochondrial transmembrane potential and increasing the repolarization lag phase. Moreover, our results show that metformin does not prevent H 2 O 2 production, neither protects against lipid peroxidation induced by the prooxidant pair ADP/Fe 2+ . In addition, we observed that metformin exacerbates Ca 2+ -induced permeability transition pore opening by decreasing the capacity of mitochondria to accumulate Ca 2+ and increasing the oxidation of thiol groups. Taken together, our results show that metformin can promote liver mitochondria injury predisposing to cell death.

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Section: Discussionsupporting

confidence: 80%

Metformin promotes isolated rat liver mitochondria impairment

et al. 2007

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“…Hemodialysis corrects acidosis and also removes metformin from plasma reducing lactate production rate [2].We applied these methods in our patient and received positive results; lactic acidosis improved. Although metformin-associated gastrointestinal discomfort and lactic acidosis is a widely recognized side effect of this drug, metformin-induced liver injury has been rarely reported [1,6,7]. Although pathophysiology of hepatotoxicity is unclear, Zheng suggested that metformin-induced liver injury was associated with concomitant intake of other hepatotoxic drugs, in most of the reported cases as in our case.…”

Section: Discussionmentioning

confidence: 61%

“…Although pathophysiology of hepatotoxicity is unclear, Zheng suggested that metformin-induced liver injury was associated with concomitant intake of other hepatotoxic drugs, in most of the reported cases as in our case. Although rare, metformin can be responsible for inducing liver damage [7]. Nammour reported a case with metformin-induced cholestatic hepatitis, treated with discontinuation of the drug, and liver enzymes normalized except for a persistently increased level of alkaline phosphatase, most likely related to a prolonged cholestatic effect of metformin [7].…”

Section: Discussionmentioning

confidence: 99%

“…Although rare, metformin can be responsible for inducing liver damage [7]. Nammour reported a case with metformin-induced cholestatic hepatitis, treated with discontinuation of the drug, and liver enzymes normalized except for a persistently increased level of alkaline phosphatase, most likely related to a prolonged cholestatic effect of metformin [7]. Hashmi suggested that in published cases with metformin-induced hepatotoxicity the number of reported cases on this subject was underestimated, probably due to the lack of a consistent terminology [8].…”

Section: Discussionmentioning

confidence: 99%

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A Rare Outcome Induced by Metformin Intoxication: Severe Lactic Acidosis and Hepatotoxicity

et al. 2016

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Metformin is a widely used oral anti-diabetic agent that decreases insulin resistance. Lactic acidosis rarely develops with this medication. Metformin-induced hepatotoxicity has been rarely reported in the literature. We describe a patient, who presented with lactic acidosis and hepatotoxicity after ingestion of 40 pills of metformin in order to commit suicide. The most important treatment step in patients with metformin-associated lactic acidosis (MALA) is high-volume hemodialysis and hemofiltration.

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“…Hepatotoxicity due to metformin, though rare, is reported in a small number of cases. 21,22 The incidence of acute liver failure is reported to be 0.12% in metformin treated patients. 23 Acute cholestatic jaundice after metformin treatment has also been reported in the literature.…”

Section: Discussionmentioning

confidence: 99%

Alterations of coagulation in metformin intoxication

Akıncı¹,

Yener²,

Bengi³

et al. 2008

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It is widely known that metformin reduces the levels of circulating pro-coagulant factors and improve fibrinolytic activity in type 2 diabetes when used in therapeutic doses. Potential alterations of coagulation have not been reported in patients with metformin intoxication. We evaluated certain components of the coagulation system in a patient with metformin intoxication upon admission and after recovery. Our results indicate that both the levels of coagulation proteins synthesized by the liver and the anti-coagulant activity decrease temporarily in metformin intoxication. Nevertheless, no change in the coagulation factors secreted by the endothelium were observed.

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Metformin-Induced Cholestatic Hepatitis

Cited by 49 publications

References 3 publications

Metformin promotes isolated rat liver mitochondria impairment

Metformin promotes isolated rat liver mitochondria impairment

A Rare Outcome Induced by Metformin Intoxication: Severe Lactic Acidosis and Hepatotoxicity

Alterations of coagulation in metformin intoxication

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