Polymorphisms in the coding region of UGT1A1 were commonly observed in Japanese patients with GS and in healthy subjects. The genetic basis of hyperbilirubinemia appears to be different between the Japanese and Caucasian populations.

Mrp3 plays an important role in the compensation of mrp2 deficiency in liver and kidney of EHBR. Hepatic expressions of mrp3, oatp1 and oatp2 changed adaptively in this animal model. This is a compensatory mechanism for reducing injury to hepatocytes from cytotoxic materials that increase in mrp2 deficiency.

SummaryBackgroundNonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease worldwide and is characterized by insulin resistance, hepatic steatosis and often prediabetes or diabetes. Canagliflozin, a selective sodium glucose cotransporter 2 inhibitor, is a new oral anti‐diabetic drug that reduces hyperglycaemia by promoting urinary glucose excretion. Glycosuria produced by canagliflozin is associated with weight loss, mainly due to reduced fat volume and improve insulin resistance. Reduced body weight and improvement of insulin resistance by canagliflozin may be an effective treatment for NAFLD.MethodsThirty‐five patients with NAFLD (17 men and 18 women) were enrolled and administered canagliflozin (100 mg). Body weight and serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma‐glutamyl transferase (γ‐GTP), low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, triglycerides (TG), blood sugar (BS), glycated haemoglobin (HbA1C), uric acid (UA) and ferritin, and fibrosis‐4 (FIB‐4) index values were measured at baseline and at 3‐month and 6‐month follow‐up visits.ResultsBody weight and serum levels of AST, ALT, γ‐GTP, TG, UA, HbA1C, BS and ferritin decreased significantly after 3 and 6 months of canagliflozin treatment. Serum BS levels and FIB‐4 index values decreased slightly following 3 months of treatment; these results reached significance after 6 months. Reduced serum ALT levels at 6 months were significantly correlated with baseline HbA1C and ferritin levels. Moreover, a significant correlation between reduced body weight and serum ALT levels was observed at 6 months. Decreased serum ALT levels were significantly correlated with decreased serum ferritin at 6 months.ConclusionsCanagliflozin significantly reduced the serum levels of BS, HbA1C, TG, UA and ferritin, as well as FIB‐4 index values and body weight, with improved liver function. Sodium glucose cotransporter 2 inhibitors may be an important therapeutic modality for improving liver injury in NAFLD patients.

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Black liver is a common finding in Dubin-Johnson syndrome (DJS), which is caused by the lack of multidrug resistance-associated protein 2 (MRP2). Impaired excretion of epinephrine metabolites is believed to be a cause of black liver in DJS. Recently, we experienced a patient with black liver whose serum bilirubin level was normal. Coarse brown granules were observed in the hepatocytes, and this finding closely resembled that observed in DJS. However, the granules were negative for Schmorl staining. The MRP2 gene did not show any mutation. Immunostaining study demonstrated MRP2 protein expression in the liver, and it was localized in the canalicular membranes of hepatocytes. This case illustrates for the first time that DJS is not the only cause of black liver.