Type 2 diabetes mellitus is associated with the fibrosis severity in patients with nonalcoholic fatty liver disease in a large retrospective cohort of Japanese patients

Nakahara, Takashi; Hyogo, Hideyuki; Yoneda, Masato; Sumida, Yoshio; Eguchi, Yuichiro; Fujii, Hideki; Ono, Masafumi; Kawaguchi, Takumi; Imajo, Kento; Aikata, Hiroshi; Tanaka, Saiyu; Kanemasa, Kazuyuki; Fujimoto, Kazuma; Anzai, Keizo; Saibara, Toshiji; Sata, Michio; Nakajima, Atushi; Itoh, Yoshito; Chayama, Kazuaki; Okanoue, Takeshi

doi:10.1007/s00535-013-0911-1

Cited by 142 publications

(123 citation statements)

References 39 publications

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“…In chronic hepatitis B, presence of DM could prevent fibrosis regression after antiviral therapy for chronic hepatitis B and also associated with progression of liver fibrosis and complications of liver cirrhosis. 34–36 DM appears to be a significant factor of advanced liver fibrosis in NAFLD and chronic hepatitis C. 37,38 Taking together of lines of evidence indicated that DM seems to play an universal role in liver fibrosis progression either in general population or in coexisting chronic liver diseases.…”

Section: Discussionmentioning

confidence: 99%

The Application of Liver Stiffness Measurement in Residents Without Overt Liver Diseases Through a Community-Based Screening Program

Cheng

Chiu²,

Chiu³

et al. 2016

Medicine

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The application of liver stiffness measurement (LSM) by transient elastography (TE) in general population remains to clarify. This cohort study aimed to examine the usefulness of TE and to identify factors associated with significant liver fibrosis in community-based population.We conducted a hepatitis screening program in 2 remote villages of Southern Taiwan. All residents participated voluntarily and received questionnaire evaluation, blood tests, abdominal sonography, and LSM by TE. Residents with any one of following criteria including hepatitis B virus infection, hepatitis C virus infection, more than moderate alcohol drinking, and failure to obtain valid or reliable LSM were excluded.There were 831 residents participated in program. The valid and reliable LSM were obtained in 98.3% and 96.3% of residents, respectively. Finally, a total of 559 residents including 283 residents with nonalcoholic steatotic fatty liver disease (NAFLD) were enrolled for analysis. The mean liver stiffness was 4.9 ± 1.9 kPa. The liver stiffness increased in residents with diabetes mellitus (DM), higher body mass index (BMI), hypertension, abnormal waist–hip circumference ration (WHR), higher waist circumference (WC), and presence of fatty liver. Higher body weight, higher BMI, higher WC, abnormal WHR, abnormal aspartate aminotransferase (AST), abnormal alanine aminotransferase (ALT), and DM were the factors associated with significant fibrosis (liver stiffness ≥7 kPa) in either all participants or NAFLD residents. As determined by multivariate analysis, abnormal AST values and DM were the 2 independent factors in all participants (abnormal AST: OR 3.648, 95% CI 1.134–11.740, P = .03; DM: OR 2.882, 95% CI 1.282–6.478, P = .01) and in residents with NAFLD (abnormal AST: OR 4.197, 95% CI 1.154–15.262, P = .03; DM: OR 3.254, 95% CI 1.258–8.413, P = .02).LSM by TE is a useful screening tool in community. In residents, who were absence of chronic hepatitis virus infection or consumed less than moderate alcohol drinking, exhibited DM or abnormal AST values may consider a substantial group with significant fibrosis in community.

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Section: Discussionmentioning

confidence: 99%

The Application of Liver Stiffness Measurement in Residents Without Overt Liver Diseases Through a Community-Based Screening Program

Cheng

Chiu²,

Chiu³

et al. 2016

Medicine

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“…Insulin resistance and obesity are closely related to the development and progression of NAFLD [6]. The most common complications of NAFLD are type 2 diabetes mellitus and impaired glucose tolerance [6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Effects of canagliflozin, an SGLT2 inhibitor, on hepatic function in Japanese patients with type 2 diabetes mellitus: pooled and subgroup analyses of clinical trials

Seko

Sumida

Sasaki³

et al. 2017

J Gastroenterol

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Background We aimed to investigate the efficacy of canagliflozin (based on its effect on liver function and blood glucose levels) and its safety in high alanine aminotransferase (ALT) patients (ALT [30 U/L). Methods This post hoc analysis of canagliflozin in type 2 diabetes mellitus (T2DM) patients was divided into Study 1 (pooled analysis of 12-and 24-week placebo-controlled, monotherapy studies) and Study 2 (52-week monotherapy/combination therapy study). The canagliflozin 100 mg group data were compared with placebo or baseline ALT subgroup (baseline ALT [30 or B30 U/L) data. The primary endpoint was change in ALT level from baseline. Secondary endpoints were changes in efficacy-related parameters. Adverse events (AEs) were evaluated. Results The mean ALT change at 12 weeks was -10.3 ± 11.7 and -3.2 ± 17.6 U/L in the canagliflozin vs. placebo group in the high ALT subgroup (P = 0.0206); no significant difference was shown in the low ALT subgroup (Study 1). In both ALT subgroups, glycosylated hemoglobin (HbA1c) and body weight were significantly reduced in the canagliflozin vs. placebo group (all P \ 0.0001). The mean change in ALT at 52 weeks was -16.0 ± 18.8 U/L in the high ALT subgroup (P \ 0.0001, Study 2). The incidence of AEs or serious AEs in the high ALT subgroup in the canagliflozin group was similar to that in the placebo group (Study 1) or low ALT subgroup (Studies 1 and 2). Conclusions In T2DM patients with impaired liver function, canagliflozin may improve liver function, reduce HbA1c and body weight, and be well tolerated.

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“…In this review, we discuss the genetic factors implicated in steatosis, steatohepatitis, fibrosis progression, cirrhosis, and HCC in NAFLD patients. (Table 1) About half of Japanese patients with NAFLD have hyperlipidemia [7]. Lipid metabolism in the liver and peripheral tissue plays a critical role in NAFLD onset and progression.…”

Section: Introductionmentioning

confidence: 99%

Significance of genetic polymorphisms in patients with nonalcoholic fatty liver disease

Miyaaki

Nakao

2017

Clin J Gastroenterol

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Because of recent advances in genetic research such as genome-wide association studies, the underlying genetic mechanisms of nonalcoholic fatty liver disease (NAFLD) pathophysiology have been elucidated. Here, we present a review of the current literature on the impact of genetic polymorphisms in patients with NAFLD. These genetic polymorphisms, which regulate lipid metabolism, glucose metabolism, and the renin-angiotensin system, are involved in NAFLD onset, steatosis, inflammation, fibrosis, and hepatocellular carcinoma (HCC). Among these genetic polymorphisms, many studies and meta-analyses have demonstrated that position 148 (rs738409 C/G) of the patatin-like phospholipase domain-containing protein (PNPLA3) is a genetic factor associated with NAFLD pathophysiological features, such as hepatic fat level, hepatic inflammation, fibrosis, and HCC. However, the impact of genetic polymorphisms on NAFLD pathophysiology appears to differ among ethnic groups. Therefore, further studies with larger sample sizes are needed for each ethnic group.

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Type 2 diabetes mellitus is associated with the fibrosis severity in patients with nonalcoholic fatty liver disease in a large retrospective cohort of Japanese patients

Abstract: DM appeared to be a significant risk factor for advanced fibrosis in patients with NAFLD, and would therefore need to be properly managed to prevent the progression of NAFLD.

Cited by 142 publications

References 39 publications

The Application of Liver Stiffness Measurement in Residents Without Overt Liver Diseases Through a Community-Based Screening Program

The Application of Liver Stiffness Measurement in Residents Without Overt Liver Diseases Through a Community-Based Screening Program

Effects of canagliflozin, an SGLT2 inhibitor, on hepatic function in Japanese patients with type 2 diabetes mellitus: pooled and subgroup analyses of clinical trials

Significance of genetic polymorphisms in patients with nonalcoholic fatty liver disease

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