Publications by authors named "Hideyuki Hyogo"

154 Publications

Serum Mac-2 binding protein level predicts the development of liver-related events and colorectal cancer in patients with NAFLD.

Hepatol Commun 2022 Apr 27. Epub 2022 Apr 27.

Department of Molecular Biochemistry & Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

We previously demonstrated that Mac-2 binding protein (M2BP) is a useful biomarker for nonalcoholic fatty liver disease (NAFLD), particularly NAFLD fibrosis prediction. In the present study, we investigated the prognostic value of M2BP in patients with NAFLD. A total of 506 patients with biopsy-confirmed NAFLD from 2002 to 2013 were enrolled in this study in Japan. Three hundred fifty-three of these patients with NAFLD were available for follow-up for more than 100 days and showed no liver-related events at the time of entry. Liver-related events were defined as hepatocellular carcinoma (HCC), decompensation, and gastroesophageal varices with variceal treatment. The mean follow-up duration of all the subjects was 2716 ± 1621 days (102-7483 days). Eighteen patients developed new liver-related events (HCC, 8; decompensation, 11; varices, 8). Nine patients developed cardiovascular disease (CVD), and 24 patients developed new cancers in other organs. The median serum M2BP level was 1.603 μg/mL, and we divided our cohort into two groups according to the serum M2BP level: M2BP low group (M2BP Low) and M2BP high group (M2BP Hi). The incidence of HCC was significantly higher in M2BP Hi (n = 8) than in M2BP Low (n = 0). The incidence of liver-related events was significantly higher in M2BP Hi (n = 16) than in M2BP Low (n = 2). The incidences of death, CVD events, and cancer in other organs were not different between the groups. Interestingly, the incidence of colorectal cancer was significantly higher in M2BP Hi (n = 5) than in M2BP Low (n = 0). Conclusion: M2BP is a useful biomarker to predict liver-related events, particularly HCC. Additionally, M2BP is a potential predictive biomarker of colorectal cancer development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep4.1934DOI Listing
April 2022

Analysis of Survival and Response to Lenvatinib in Unresectable Hepatocellular Carcinoma.

Cancers (Basel) 2022 Jan 10;14(2). Epub 2022 Jan 10.

Department of Gastroenterology, National Hospital Organization Higashihiroshima Medical Center, Hiroshima 739-0041, Japan.

The association between radiological response and overall survival (OS) was retrospectively evaluated in patients treated with lenvatinib as a first-line systemic treatment for unresectable hepatocellular carcinoma. A total of 182 patients with Child-Pugh class A liver function and an Eastern Cooperative Oncology Group performance status of zero or one were enrolled. Radiological evaluation was performed using Response Evaluation Criteria in Solid Tumors (RECIST) and modified Response Evaluation Criteria in Solid Tumors (mRECIST). Initial radiological evaluation confirmed significant stratification of OS by efficacy judgment with both RECIST and mRECIST, and that initial radiological response was an independent prognostic factor for OS on multivariate analysis. Furthermore, in patients with stable disease (SD) at initial evaluation, macrovascular invasion at the initial evaluation on RECIST and modified albumin-bilirubin grade at initial evaluation on mRECIST were independent predictors of OS on multivariate analysis. In conclusion, if objective response is obtained at the initial evaluation, continuation of treatment appears desirable because prolonged OS can be expected; but, if SD is obtained at the initial evaluation, one should determine whether to continue or switch to the next treatment, with careful consideration of factors related to the tumor and hepatic reserve at the initial evaluation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers14020320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774012PMC
January 2022

Clinical Outcomes in Biopsy-Proven Nonalcoholic Fatty Liver Disease Patients: A Multicenter Registry-based Cohort Study.

Clin Gastroenterol Hepatol 2022 Jan 17. Epub 2022 Jan 17.

Department of Clinical Pharmacology and Therapeutics, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.

Background & Aims: There are no detailed reports of clinical outcomes in Asian patients with nonalcoholic fatty liver disease (NAFLD) who undergo liver biopsy. We aimed to investigate the clinical outcomes of a large cohort of Asian patients with biopsy-proven NAFLD and evaluate the specific effects of nonalcoholic steatohepatitis and fibrosis stage.

Methods: This multicenter registry-based retrospective cohort study, called the CLIONE (Clinical Outcome Nonalcoholic Fatty Liver Disease) in Asia, included 1398 patients.

Results: The median follow-up period was 4.6 years (range, 0.3-21.6 years), representing a total of 8874 person-years of follow-up. During that time, 47 patients died, and 1 patient underwent orthotopic liver transplantation. The leading cause of death was nonhepatic cancer (n = 10). The leading causes of liver-related death were liver failure (n = 9), hepatocellular carcinoma (HCC) (n = 8), and cholangiocellular carcinoma (n = 4). During follow-up, 37 patients developed HCC, 31 developed cardiovascular disease, and 68 developed nonhepatic cancer (mainly breast, stomach, and colon/rectum). Among our cohort of patients with NAFLD, liver-specific mortality was 2.34/1000 person-years (95% confidence interval [CI], 1.52-3.58), overall mortality was 5.34/1000 person-years (95% CI, 4.02-7.08), and HCC incidence was 4.17/1000 person-years (95% CI, 3.02-5.75). Liver fibrosis was independently associated with liver-related events but not overall mortality.

Conclusions: Liver-related mortality was the leading cause of mortality in Asian patients with biopsy-confirmed NAFLD. Although fibrosis stage was independently associated with liver-related events, it was not associated with overall mortality after adjusting for confounders, such as histologic features of steatohepatitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cgh.2022.01.002DOI Listing
January 2022

Clinical profiles of Asians with NAFLD: A systematic review and meta-analysis.

Dig Dis 2021 Dec 23. Epub 2021 Dec 23.

Introduction: NAFLD is increasingly prevalent in Asia, where people suffer more metabolic comorbidities at a lower body mass index (BMI), suggesting potential differences in their clinical profile. Therefore, we attempted to characterize the clinical profile of Asians with NAFLD via a meta-analytic approach.

Methods: We searched Pubmed, EMBASE, and Cochrane databases from January 1, 2000 to January 17, 2019. Two authors independently reviewed and selected 104 articles (2,247,754 persons) that identified NAFLD in Asians and reported relevant data, especially BMI and ALT, and excluded individuals with other liver disease and excessive alcohol consumption. Individual patient-level data were obtained from seven cohorts in Asia to complement meta-analyzed data.

Results: Overall, the mean age was 52.07 (95%CI:51.28-52.85) years with those from Southeast Asia (42.66, 95%CI: 32.23-53.11) being significantly younger. The mean BMI was 26.2 kg/m2, higher in moderate-severe vs. mild hepatic steatosis (28.3 vs. 25.7) patients and NFS ≥-1.455 vs. <-1.455 (27.09 vs. 26.02), with 34% having non-obese NAFLD. The mean ALT was 31.74 U/L, higher in NFS <-1.455 vs. ≥-1.455 (33.74 vs. 27.83), though no differences were found by obesity or steatosis severity. The majority of males (85.7%) and females (60.7%) had normal to minimally elevated ALT (1-1.5x 95% ULN). Individual patient-level data analysis (N=7,668) demonstrated similar results.

Conclusion: About one-third of Asians with NAFLD were non-obese and the majority did not have markedly elevated ALT. Therefore, abnormal ALT or BMI are not recommended as a criterion for NAFLD screening in this population. Additionally, there were significant differences in the clinical profiles of NAFLD among the different regions of Asia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000521662DOI Listing
December 2021

Ipragliflozin Improves the Hepatic Outcomes of Patients With Diabetes with NAFLD.

Hepatol Commun 2022 01 17;6(1):120-132. Epub 2021 Jun 17.

Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga, Japan.

Sodium glucose cotransporter-2 inhibitors (SGLT2is) are now widely used to treat diabetes, but their effects on nonalcoholic fatty liver disease (NAFLD) remain to be determined. We aimed to evaluate the effects of SGLT2is on the pathogenesis of NAFLD. A multicenter, randomized, controlled trial was conducted in patients with type 2 diabetes with NAFLD. The changes in glycemic control, obesity, and liver pathology were compared between participants taking ipragliflozin (50 mg/day for 72 weeks; IPR group) and participants being managed without SGLT2is, pioglitazone, glucagon-like peptide-1 analogs, or insulin (CTR group). In the IPR group (n = 25), there were significant decreases in hemoglobin A1c (HbA1c) and body mass index (BMI) during the study (HbA1c, -0.41%, P < 0.01; BMI, -1.06 kg/m , P < 0.01), whereas these did not change in the CTR group (n = 26). Liver pathology was evaluated in 21/25 participants in the IPR/CTR groups, and hepatic fibrosis was found in 17 (81%) and 18 (72%) participants in the IPR and CTR groups at baseline. This was ameliorated in 70.6% (12 of 17) of participants in the IPR group and 22.2 % (4 of 18) of those in the CTR group (P < 0.01). Nonalcoholic steatohepatitis (NASH) resolved in 66.7% of IPR-treated participants and 27.3% of CTR participants. None of the participants in the IPR group developed NASH, whereas 33.3% of the CTR group developed NASH. Conclusion: Long-term ipragliflozin treatment ameliorates hepatic fibrosis in patients with NAFLD. Thus, ipragliflozin might be effective for the treatment and prevention of NASH in patients with diabetes, as well as improving glycemic control and obesity. Therefore, SGLT2is may represent a therapeutic choice for patients with diabetes with NAFLD, but further larger studies are required to confirm these effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep4.1696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8710792PMC
January 2022

Predictive value of cytokeratin-18 fragment levels for diagnosing steatohepatitis in patients with nonalcoholic fatty liver disease.

Eur J Gastroenterol Hepatol 2021 11;33(11):1451-1458

Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical University, Aichi, Japan.

Objective: Several noninvasive markers have been developed to predict nonalcoholic steatohepatitis (NASH). We investigated the predictive value of the cytokeratin-18 fragment (CK18-F) level and FIB-4 index for diagnosing NASH in patients with nonalcoholic fatty liver disease (NAFLD).

Methods: A total of 246 patients histologically diagnosed with NASH (n = 185) or nonalcoholic fatty liver (n = 61) were enrolled. We analyzed weighted receiver operating characteristic (ROC) curves for the prediction of NASH and determined the relationship between the CK18-F level and the histological features of NASH. In addition, we investigated the predictive value of the combination of the CK18-F level and FIB-4 index for diagnosing NASH.

Results: The area under the ROC curve (AUROC) value of the CK18-F level was 0.77. With a CK18-F cutoff level of 260 U/L, the sensitivity and specificity for diagnosing NASH were 82.7 and 57.4%, respectively. Multiple comparisons showed that the CK18-F level did not differ among fibrosis stages but did significantly differ among hepatocyte ballooning grades. Overall, 95.7% (66/69) of patients with a FIB-4 index of ≥2.67 had NASH. In patients with a FIB-4 index of <2.67, the AUROC value of the CK18-F level for predicting NASH was 0.77 and a CK18-F cutoff level of 260 U/L resulted in a sensitivity and specificity of 82.4 and 56.9%.

Conclusions: The CK18-F level had a good predictive ability for diagnosing NASH in patients with NAFLD. Additionally, the combination of the CK18-F level and FIB-4 index accurately and noninvasively predicted NASH, even those with a low FIB-4 index.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MEG.0000000000002176DOI Listing
November 2021

Increasing incidence of non-HBV- and non-HCV-related hepatocellular carcinoma: single-institution 20-year study.

BMC Gastroenterol 2021 Jul 31;21(1):306. Epub 2021 Jul 31.

Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.

Background: We previously reported on the trends in the etiologies of hepatocellular carcinoma (HCC) diagnosed in patients between 1995 and 2009. The aims of our updated study were to evaluate the incidence, nonhepatitis B and nonhepatitis C viral (NBNC) etiologies, and clinical characteristics of HCCs occurring in patients between 1992 and 2018.

Methods: The study enrolled 2171 consecutive patients with HCC between 1992 and 2018. Their medical records were reviewed. The patients were divided into two groups, patients with early diagnoses from 1992 to 2009 and those with late diagnoses from 2010 to 2018.

Results: NBNC-HCC occurred in 514 patients (23.6%). The percentage of patients with HCC who had NBNC-HCC increased from 26.5% in 2009 to 46.3% in 2018. Patients with NBNC-HCC were older (median ages from 67 to 73 years). Type 2 diabetes mellitus (48.5-60.3%: P = 0.008), hypertension (48.5-57.4%: P = 0.047), and hyperlipidemia (39.2-53.8%: P = 0.001) increased significantly in recent years. The median FIB-4 index decreased (4.37-3.61: P = 0.026) and the median platelet count increased (15.1-17.9 × 10/μL: P = 0.013). Among the 514 patients with NBNC-HCC, 194 underwent hepatic resection for nonalcoholic steatohepatitis (NASH) (15%), alcoholic liver disease (ALD) (29%), and cryptogenic hepatitis (56%). Cirrhosis was detected in 72%, 39%, and 16% of patients with NASH, ALD, and cryptogenic hepatitis, respectively. The prevalence of cirrhosis in patients with NASH was significantly higher than the prevalence of cirrhosis in the other groups (P < 0.001). Overall, 70% of the non-malignant liver tissue of patients with NBNC-HCC was not involved with cirrhosis. On the other hand, the median FIB-4 index in patients with cryptogenic HCC was 2.56, which was a significantly lower value than those values in the other groups of patients. The FIB-4 index considered as one of useful screening of HCC.

Conclusions: The prevalence of NBNC-HCC has increased rapidly even in a regional university hospital. Metabolic syndrome may be an important risk factor for HCC. HCC was also found in patients with non-cirrhotic livers. The FIB-4 index may be a useful screening method for HCC in patients with NBNC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12876-021-01884-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325833PMC
July 2021

Clinical Outcomes of 2nd- and 3rd-Line Regorafenib for Advanced Hepatocellular Carcinoma.

Oncology 2021 17;99(8):491-498. Epub 2021 May 17.

Department of Gastroenterology, Chugoku Rosai Hospital, Hiroshima, Japan.

Introduction: This study compared clinical outcomes of 2nd- and 3rd-line regorafenib in patients with unresectable hepatocellular carcinoma.

Methods: In this retrospective cohort study, 48 patients were treated with regorafenib for unresectable hepatocellular carcinoma. Thirty-five and 13 patients were initiated on 2nd- and 3rd-line therapy, respectively. We assessed the responses to and safety of the therapy.

Results: There were no statistically significant differences in clinical characteristics at the start of 2nd- or 3rd-line regorafenib therapy. The overall response rate of 2nd- and 3rd-line regorafenib was 20 and 8%, respectively. The disease control rate was 57 and 54%, respectively. Median overall survival (mOS) from the start of 2nd-line regorafenib was 17.5 months. mOS from the start of 3rd-line regorafenib was not obtained. Median progression-free survival of 2nd- and 3rd-line regorafenib was 4.9 and 2.3 months, respectively. mOS from 1st-line therapy with tyrosine kinase inhibitor plus sorafenib-regorafenib-lenvatinib was 29.5 months; that with lenvatinib-sorafenib-regorafenib was not obtained. Patients on 3rd-line therapy tended to have better Child-Pugh scores and tumor factors at the start of 1st-line therapy than other patients.

Conclusion: Patients on 2nd- and 3rd-line regorafenib showed favorable responses. Good Child-Pugh scores and tumor factors may be associated with a better response rate and OS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000515280DOI Listing
August 2021

Efficacy and Safety of Lenvatinib-Transcatheter Arterial Chemoembolization Sequential Therapy for Patients with Intermediate-Stage Hepatocellular Carcinoma.

Oncology 2021 4;99(8):507-517. Epub 2021 May 4.

Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

Introduction: We evaluated the efficacy and safety of lenvatinib-transcatheter arterial chemoembolization (LEN-TACE) sequential therapy for patients (n = 88) with intermediate-stage hepatocellular carcinoma (HCC).

Methods: Eighty-eight patients who obtained tumor control by LEN treatment were analyzed; 30 received LEN followed by TACE (LEN-TACE sequential therapy), and 58 received LEN monotherapy. Propensity score matching was performed, and the outcomes of 19 patients in the LEN-TACE group and 19 patients in the LEN-alone group were compared. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), incidence of adverse events (AEs), and change in albumin-bilirubin (ALBI) score were evaluated.

Results: After matching, baseline characteristics were similar between the groups. The ORR was 63.2% with LEN-TACE group and 63.2% with the LEN-alone group. Multivariate analysis showed that addition of TACE during LEN treatment (hazard ratio [HR] 0.264, 95% confidence interval [CI] 0.087-0.802, p =  0.019) and Child-Pugh score 5 (HR 0.223, 95% CI 0.070-0.704, p = 0.011) were the significant factors for PFS. Median PFS was 11.6 months with LEN-TACE and 10.1 months with LEN-alone. The survival rate of the LEN-TACE group was significantly higher than that of the LEN-alone group (median survival time; not reached vs. 16.9 months, p = 0.007). The incidence of common LEN-associated AEs was similar between groups. Although elevated aspartate aminotransferase/alanine aminotransferase and fever were more frequent with LEN-TACE group, these events were manageable.

Conclusion: For patients with intermediate-stage HCC, LEN-TACE sequential therapy may provide a deep response and favorable prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000515865DOI Listing
August 2021

Type IV Collagen 7S Is the Most Accurate Test For Identifying Advanced Fibrosis in NAFLD With Type 2 Diabetes.

Hepatol Commun 2021 04 16;5(4):559-572. Epub 2020 Nov 16.

Department of Gastroenterology and Hepatology Kyoto Prefectural University of Medicine Kyoto Japan.

This study aimed to examine whether the diagnostic accuracy of four noninvasive tests (NITs) for detecting advanced fibrosis in nonalcoholic fatty liver disease (NAFLD) is maintained or is inferior to with or without the presence of type 2 diabetes. Overall, 874 patients with biopsy-proven NAFLD were enrolled. After propensity-score matching by age, sex, and the prevalence of dyslipidemia, 311 patients were enrolled in each group of with or without diabetes. To evaluate the effect of diabetes, we compared the diagnostic accuracy of the fibrosis-4 (FIB-4) index, the NAFLD fibrosis score (NFS), the aspartate aminotransferase to platelet ratio index (APRI), and type IV collagen 7S (COL4-7S) in patients with NAFLD with and without diabetes. The areas under the receiver operating characteristic curve (AUROC) for identifying advanced fibrosis in patients without diabetes were 0.879 for the FIB-4 index, 0.851 for the NFS, 0.862 for the APRI, and 0.883 for COL4-7S. The AUROCs in patients with diabetes were 0.790 for the FIB-4 index, 0.784 for the NFS, 0.771 for the APRI, and 0.872 for COL4-7S. The AUROC of COL4-7S was significantly larger than that of the other NITs in patients with NAFLD with diabetes than in those without diabetes. The optimal high and low cutoff points of COL4-7S were 5.9 ng/mL and 4.8 ng/mL, respectively. At the low cutoff point, the accuracy of COL4-7S was better than that of the other NITs, especially in patients with diabetes. COL4-7S measurement might be the best NIT for identifying advanced fibrosis in NAFLD, especially in NAFLD with diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep4.1637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034577PMC
April 2021

Gut microbiota composition associated with hepatic fibrosis in non-obese patients with non-alcoholic fatty liver disease.

J Gastroenterol Hepatol 2021 Aug 29;36(8):2275-2284. Epub 2021 Mar 29.

Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.

Background And Aim: Gut microbiota composition is associated with the pathogenesis of non-alcoholic fatty liver disease. However, the association between gut microbiota composition and non-alcoholic fatty liver disease in non-obese patients remains unclear. We compared clinical parameters and gut microbiota profiles of healthy controls and non-obese and obese patients with non-alcoholic fatty liver disease.

Methods: We examined the clinical parameters and gut microbiota profiles by 16S rRNA sequences and short-chain fatty acid levels in fecal samples from 51 non-obese patients with non-alcoholic fatty liver disease (body mass index <25 kg/m ) and 51 obese patients with non-alcoholic fatty liver disease (body mass index ≥30 kg/m ) who underwent pathological examination and 87 controls at five hospitals in Japan.

Results: Although no significant differences between the non-obese and other groups were observed in alpha diversity, a significant difference was found in beta diversity. We observed a significant decrease in serum alanine aminotransferase levels, Eubacterium population, and butyric acid levels in non-obese patients with non-alcoholic fatty liver disease compared with those in obese patients with non-alcoholic fatty liver disease. A significant negative correlation was found between the stage of hepatic fibrosis and Eubacterium abundance in non-obese patients with non-alcoholic fatty liver disease.

Conclusions: The decrease in the abundance of Eubacterium that produces butyric acid may play an important role in the development of non-alcoholic fatty liver disease in non-obese individuals. This study was registered at the University Hospital Medical Information Network clinical trial registration system (UMIN000020917).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jgh.15487DOI Listing
August 2021

FIB-4 First in the Diagnostic Algorithm of Metabolic-Dysfunction-Associated Fatty Liver Disease in the Era of the Global Metabodemic.

Life (Basel) 2021 Feb 14;11(2). Epub 2021 Feb 14.

Japan Strategic Medical Administration Research Center (J-SMARC), Nagoya, Aichi 460-0011, Japan.

The prevalence of obesity or metabolic syndrome is increasing worldwide (globally metabodemic). Approximately 25% of the adult general population is suffering from nonalcoholic fatty liver disease (NAFLD), which has become a serious health problem. In 2020, global experts suggested that the nomenclature of NAFLD should be updated to metabolic-dysfunction-associated fatty liver disease (MAFLD). Hepatic fibrosis is the most significant determinant of all cause- and liver -related mortality in MAFLD. The non-invasive test (NIT) is urgently required to evaluate hepatic fibrosis in MAFLD. The fibrosis-4 (FIB-4) index is the first triaging tool for excluding advanced fibrosis because of its accuracy, simplicity, and cheapness, especially for general physicians or endocrinologists, although the FIB-4 index has several drawbacks. Accumulating evidence has suggested that vibration-controlled transient elastography (VCTE) and the enhanced liver fibrosis (ELF) test may become useful as the second step after triaging by the FIB-4 index. The leading cause of mortality in MAFLD is cardiovascular disease (CVD), extrahepatic malignancy, and liver-related diseases. MAFLD often complicates chronic kidney disease (CKD), resulting in increased simultaneous liver kidney transplantation. The FIB-4 index could be a predictor of not only liver-related mortality and incident hepatocellular carcinoma, but also prevalent and incident CKD, CVD, and extrahepatic malignancy. Although NITs as milestones for evaluating treatment efficacy have never been established, the FIB-4 index is expected to reflect histological hepatic fibrosis after treatment in several longitudinal studies. We here review the role of the FIB-4 index in the management of MAFLD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/life11020143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917687PMC
February 2021

The epidemiology of NAFLD and lean NAFLD in Japan: a meta-analysis with individual and forecasting analysis, 1995-2040.

Hepatol Int 2021 Apr 12;15(2):366-379. Epub 2021 Feb 12.

Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, 780 Welch Road, CJ250K, Palo Alto, CA, 94304, USA.

Background: NAFLD is increasing in Asia including Japan, despite its lower obesity rate than the West. However, NAFLD can occur in lean people, but data are limited. We aimed to investigate the epidemiology of NAFLD in Japan with a focus on lean NAFLD.

Methods: We searched PubMed, Cochrane Library, EMBASE, Web of Science, and the Japan Medical Abstracts Society (inception to 5/15/2019) and included 73 eligible full-text original research studies (n = 258,531). We used random-effects model for pooled estimates, Bayesian modeling for trend and forecasting, contacted authors for individual patient data and analyzed 14,887 (7752 NAFLD; 7135 non-NAFLD-8 studies) patients.

Results: The overall NAFLD prevalence was 25.5%, higher in males (p < 0.001), varied by regions (p < 0.001), and increased over time (p = 0.015), but not by per-person income or gross prefectural productivity, which increased by 0.64% per year (1983-2012) and is forecasted to reach 39.3% in 2030 and 44.8% in 2040. The incidence of NAFLD, HCC, and overall mortality were 23.5, 7.6 and 5.9 per 1000 person-years, respectively. Individual patient-level data showed a lean NAFLD prevalence of 20.7% among the NAFLD population, with lean NAFLD persons being older and with a higher all-cause mortality rate (8.3 vs. 5.6 per 1000 person-years for non-lean NAFLD, p = 0.02). Older age, male sex, diabetes, and FIB-4 were independent predictors of mortality, but not lean NAFLD.

Conclusion: NAFLD prevalence has increased in Japan and may affect half of the population by 2040. Lean NAFLD individuals makeup 20% of the NAFLD population, were older, and had higher mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12072-021-10143-4DOI Listing
April 2021

Eradication of hepatitis C virus with direct-acting antivirals improves glycemic control in diabetes: A multicenter study.

JGH Open 2021 Feb 19;5(2):228-234. Epub 2020 Dec 19.

Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima Japan.

Background And Aim: Hepatitis C virus (HCV) infection causes insulin resistance and diabetes as extrahepatic manifestations. We aimed to analyze the effect of HCV eradication by direct-acting antiviral (DAA) agents on glucose tolerance.

Methods: The hemoglobin A1c (HbA1c) of 272 patients with HCV infection who achieved a sustained virologic response (SVR) was analyzed at baseline before DAA treatment, at the end of DAA therapy (ETR), and 12 weeks after therapy (Post12W).

Results: There were no significant differences in HbA1c between baseline, ETR, and Post12W in the overall patients. When the data were stratified according to the presence or absence of diabetes, median HbA1c significantly decreased from baseline (7.2%) to ETR (6.8%) and Post12W (6.8%) in the 55 patients with diabetes, whereas there were no significant changes in the patients without diabetes. Basal HbA1c, fasting plasma glucose, and age were independently associated with the changes in HbA1c according to multivariate analysis, and the predictive formula for changes in HbA1c was found to be ΔHbA1c (%) = 1.449-0.4* HbA1c (%) + 0.012 × Age (year). There were no changes in body mass in diabetic or nondiabetic patients. In diabetic patients taking medication, 63.4% of patients needed less medication.

Conclusions: Eradication of HCV improves glycemic control, indicated by a 0.4% decrease in HbA1c in diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jgh3.12474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857302PMC
February 2021

Prediction of Nonalcoholic Fatty Liver Disease Using Noninvasive and Non-Imaging Procedures in Japanese Health Checkup Examinees.

Diagnostics (Basel) 2021 Jan 16;11(1). Epub 2021 Jan 16.

Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga 849-8501, Japan.

Access to imaging is limited for diagnosing nonalcoholic fatty liver disease (NAFLD) in general populations. This study evaluated the diagnostic performance of noninvasive and nonimaging indexes to predict NAFLD in the general Japanese population. Health checkup examinees without hepatitis virus infection or habitual alcohol drinking were included. Fatty liver was diagnosed by ultrasonography. The hepatic steatosis index (HSI), Zhejiang University (ZJU) index, and fatty liver index (FLI) were determined, and risk of advanced liver fibrosis was evaluated by the fibrosis-4 index. NAFLD was diagnosed in 1935 (28.0%) of the 6927 subjects. The area under the receiver operating characteristic (AUROC) curve of the HSI, ZJU index, and FLI was 0.874, 0.886, and 0.884, respectively. The AUROC of the ZJU index ( < 0.001) and FLI ( = 0.002) was significantly greater than that for the HSI. In subjects with a high risk of advanced fibrosis, the sensitivity of the HSI, ZJU index, and FLI were 88.8%, 94.4%, and 83.3% with a low cut-off value and the specificity was 98.5%, 100%, and 100% with a high cut-off value. In conclusion, all indexes were useful to diagnose NAFLD in the general Japanese population and in subjects with potentially advanced liver fibrosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/diagnostics11010132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830542PMC
January 2021

ALT Levels for Asians With Metabolic Diseases: A Meta-analysis of 86 Studies With Individual Patient Data Validation.

Hepatol Commun 2020 Nov 9;4(11):1624-1636. Epub 2020 Sep 9.

Division of Gastroenterology and Hepatology Stanford University Medical Center Palo Alto CA USA.

The current alanine aminotransferase (ALT) upper limit of normal was defined using selected healthy Caucasian blood donors. Given the global rise in obesity and different body habitus in Asians, we aimed to perform a systematic review and meta-analysis combined with bootstrap modeling and individual patient data validation to estimate the ALT upper threshold for Asians, including the overweight and diabetics. We included studies from PubMed, Embase, and Cochrane database searches that identified individuals without known liver diseases (i.e., viral hepatitis, alcohol, and ultrasound-detected nonalcoholic fatty liver disease). The mean ALT (U/L) was estimated using a random-effects mixed model and upper threshold (95th-percentile value, U/L) via a bootstrap model with 10,000 resamples. We screened 4,995 studies and identified 86 studies that reported ALT values for 526,641 individuals without excessive alcohol intake or known liver diseases, yielding a mean ALT of 19 and ALT upper threshold of 32. The ALT upper threshold was 37 in males versus 31 in females, 39 in overweight versus 28 in normal-weight individuals, and 36 for diabetics versus 33 for nondiabetics. We validated our study level data with individual patient level data in 6,058 individuals from five study centers in Japan. Consistent with our study-level data, we found that the ALT upper threshold in our individual patient data analysis was indeed higher in overweight versus normal-weight individuals (39 vs. 32) and in diabetics versus nondiabetics (42 vs. 33). We provide validated reference ranges for ALT upper threshold derived from Asians without known liver disease, including individuals with ultrasound-detected nonalcoholic fatty liver disease who are normal weight, overweight, nondiabetic, and diabetic, to inform practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep4.1593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603525PMC
November 2020

Decrease in fasting insulin secretory function correlates with significant liver fibrosis in Japanese non-alcoholic fatty liver disease patients.

JGH Open 2020 Oct 9;4(5):929-936. Epub 2020 Jun 9.

Liver Center Saga University Hospital Saga Japan.

Background And Aim: Non-alcoholic fatty liver disease (NAFLD) is typically associated with metabolic syndrome and diabetes, and insulin resistance is involved in its pathogenesis. However, the relationship between insulin secretion and NAFLD is unclear. We aimed to characterize the relationship between fasting insulin secretory function (ISF), evaluated using the homeostatic model assessment-beta cell function (HOMA-β) and the severity of fibrosis during NAFLD.

Methods: A-β was calculated in 188 patients with biopsy-confirmed NAFLD, and the correlations between Log HOMA-β and clinical parameters, including hepatic fibrosis, were calculated.

Results: Log HOMA-β was significantly lower in NAFLD patients with significant fibrosis (stages 2-4) than in those in the early stages (stages 0-1) (median [interquartile range]) (2.1 [1.9-2.4] 2.0 [1.8-2.2], = 0.04). The prevalence of significant fibrosis decreased with increasing Log HOMA-β: it was 59.2% in participants with low ISF (Log HOMA-β < 1.85), 43.6% in those with intermediate ISF (1.85 ≤ Log HOMA-β < 2.25), and 68.0% in those with high ISF (Log HOMA-β ≥ 2.25). Patients with lower Log HOMA-β had lower current body mass index (BMI), BMI at 20 years of age, and peak lifetime BMI than patients with intermediate or high Log HOMA-β.

Conclusions: Fasting ISF decreased alongside the development of liver fibrosis in NAFLD, suggesting that an impaired β cell function has a characteristic finding of significant liver fibrosis in relatively nonobese Japanese patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jgh3.12367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578285PMC
October 2020

Analysis of Post-Progression Survival in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib.

Oncology 2020 3;98(11):787-797. Epub 2020 Sep 3.

Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan,

Background: Although a strong antitumor effect of lenvatinib (LEN) has been noted for patients with unresectable hepatocellular carcinoma (HCC), there are still no reports on the prognosis for patients with disease progression after first-line LEN therapy.

Methods: Patients (n = 141) with unresectable HCC, Child-Pugh class A liver function, and an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 or 1 who were treated with LEN from March 2018 to December 2019 were enrolled.

Results: One hundred and five patients were treated with LEN as first-line therapy, 53 of whom had progressive disease (PD) at the radiological evaluation. Among the 53 patients with PD, there were 27 candidates for second-line therapy, who had Child-Pugh class A liver function and an ECOG-PS of 0 or 1 at progression. After progression on first-line LEN, 28 patients were treated with a molecular targeted agent (MTA) as second-line therapy (sorafenib: n = 26; ramucirumab: n = 2). Multivariate analysis identified modified albumin-bilirubin grade 1 or 2a at LEN initiation (odds ratio 5.18, 95% confidence interval [CI] 1.465-18.31, p = 0.011) as a significant and independent factor for candidates. The median post-progression survival after PD on first-line LEN was 8.3 months. Cox hazard multivariate analysis showed that a low alpha-fetoprotein level (<400 ng/mL; hazard ratio [HR] 0.297, 95% CI 0.099-0.886, p = 0.003), a relative tumor volume <50% at the time of progression (HR 0.204, 95% CI 0.07-0.592, p = 0.03), and switching to MTAs as second-line treatment after LEN (HR 0.299, 95% CI 0.12-0.746, p = 0.01) were significant prognostic factors.

Conclusion: Among patients with PD on first-line LEN, good liver function at introduction of LEN was an important and favorable factor related to eligibility for second-line therapy. In addition, post-progression treatment with MTAs could improve the prognosis for patients who had been treated with first-line LEN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000509387DOI Listing
November 2020

Discordant pathological diagnosis of non-alcoholic fatty liver disease: A prospective multicenter study.

JGH Open 2020 Jun 17;4(3):497-502. Epub 2019 Dec 17.

Liver Center Saga University Hospital Saga Japan.

Background: Liver biopsy has been the standard procedure for diagnosing and evaluating the severity of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH); however, interobserver discordance remains a critical issue in its pathological diagnosis.

Methods And Results: We examined the concordance rates of pathological scoring and diagnosis between pathologists at individual institutions (local diagnosis) and two central pathologists specialized in liver pathology (central diagnosis). A total of 150 patients with NAFLD underwent prospective liver biopsies. NAFLD activity score (NAS) and fibrosis stage were evaluated, and NASH was determined according to Matteoni's classification. NAS, scores for all NAS components, and fibrosis stage were diagnosed at a lower degree by central compared with local diagnosis. NASH was diagnosed in 34% of the patients according to central pathologists compared with 54% according to local pathologists ( < 0.001). The concordance rates for NAS, steatosis, inflammation, ballooning, fibrosis, and NASH diagnosis were 26.7, 62.7, 51.3, 48.7, 43.3, and 50.7%, respectively. The correlation coefficient between local and central diagnoses was the lowest for the scoring of ballooning ( = 0.218).

Conclusion: Concordance rates among pathologists for the evaluation of NAFLD are currently poor, and simple and reliable diagnostic and evaluation criteria are urgently needed to improve the clinical management of NAFLD patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jgh3.12289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273711PMC
June 2020

Metabolomic/lipidomic-based analysis of plasma to diagnose hepatocellular ballooning in patients with non-alcoholic fatty liver disease: A multicenter study.

Hepatol Res 2020 Aug 15;50(8):955-965. Epub 2020 Jul 15.

Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Aim: Liver biopsy is still required for the diagnosis of hepatocellular ballooning and inflammation, which are important histological features of non-alcoholic steatohepatitis. We undertook this multicenter, cross-sectional study to identify novel blood markers for the diagnosis of hepatocellular ballooning.

Methods: We enrolled 176 patients, of whom 132 were proven by liver biopsy as having non-alcoholic fatty liver disease (NAFLD) and classified as non-ballooning (ballooning grade 0) (n = 83) or ballooning (ballooning grade 1 and 2) (n = 49) by a central pathology review. We carried out gas chromatography-mass spectrometry, hydrophilic interaction liquid chromatography tandem mass spectrometry, and lipidomics with plasma.

Results: As correlates of hepatocellular ballooning, among the clinical parameters, serum type IV collagen 7S correlated most significantly with the ballooning grade (correlation coefficient [CC] = 0.463; P < 0.001). Among the metabolic/lipidomic markers, phosphatidylcholine (PC) (aa-44:8) correlated most significantly with the ballooning grade (CC = 0.394; P < 0.001). The area under the receiver operating characteristic curve of type IV collagen 7S, choline, and lysophosphatidylethanolamine (LPE) (e-18:2), was 0.846 (95% confidence interval, 0.772-0.919).

Conclusions: Plasma levels of PC were positively correlated, and those of lysophosphatidylcholine and LPE were negatively correlated with hepatocellular ballooning in NAFLD patients. These non-invasive metabolic/lipidomic-based plasma tests might be useful to distinguish between cases of NAFLD with and without hepatocellular ballooning.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/hepr.13528DOI Listing
August 2020

Antidiabetic Therapy in the Treatment of Nonalcoholic Steatohepatitis.

Int J Mol Sci 2020 Mar 11;21(6). Epub 2020 Mar 11.

Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.

Liver-related diseases are the third-leading causes (9.3%) of mortality in type 2 diabetes (T2D) in Japan. T2D is closely associated with nonalcoholic fatty liver disease (NAFLD), which is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma (HCC) and hepatic failure. No pharmacotherapies are established for NASH patients with T2D. Though vitamin E is established as a first-line agent for NASH without T2D, its efficacy for NASH with T2D recently failed to be proven. The effects of pioglitazone on NASH histology with T2D have extensively been established, but several concerns exist, such as body weight gain, fluid retention, cancer incidence, and bone fracture. Glucagon-like peptide 1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors are expected to ameliorate NASH and NAFLD (LEAN study, LEAD trial, and E-LIFT study). Among a variety of SGLT2 inhibitors, dapagliflozin has already entered the phase 3 trial (DEAN study). A key clinical need is to determine the kinds of antidiabetic drugs that are the most appropriate for the treatment of NASH to prevent the progression of hepatic fibrosis, resulting in HCC or liver-related mortality without increasing the risk of cardiovascular or renal events. Combination therapies, such as glucagon receptor agonist/GLP-1 or gastrointestinal peptide/GLP-1, are under development. This review focused on antidiabetic agents and future perspectives on the view of the treatment of NAFLD with T2D.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21061907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139365PMC
March 2020

Serum miR-379 expression is related to the development and progression of hypercholesterolemia in non-alcoholic fatty liver disease.

PLoS One 2020 27;15(2):e0219412. Epub 2020 Feb 27.

Second Department of Internal Medicine, Tottori University School of Medicine, Yonago, Tottori, Japan.

Introduction: Non-alcoholic fatty liver disease (NAFLD) has a wide spectrum, eventually leading to cirrhosis and hepatic carcinogenesis. We previously reported that a series of microRNAs (miRNAs) mapped in the 14q32.2 maternally imprinted gene region (Dlk1-Dio3 mat) are related to NAFLD development and progression in a mouse model. We examined the suitability of miR-379, a circulating Dlk1-Dio3 mat miRNA, as a human NAFLD biomarker.

Methods: Eighty NAFLD patients were recruited for this study. miR-379 was selected from the putative Dlk1-Dio3 mat miRNA cluster because it exhibited the greatest expression difference between NAFLD and non-alcoholic steatohepatitis in our preliminary study. Real-time PCR was used to examine the expression levels of miR-379 and miR-16 as an internal control. One patient was excluded due to low RT-PCR signal.

Results: Compared to normal controls, serum miR-379 expression was significantly up-regulated in NAFLD patients. Receiver operating characteristic curve analysis suggested that miR-379 is a suitable marker for discriminating NAFLD patients from controls, with an area under the curve value of 0.72. Serum miR-379 exhibited positive correlations with alkaline phosphatase, total cholesterol, low-density-lipoprotein cholesterol and non-high-density-lipoprotein cholesterol levels in patients with early stage NAFLD (Brunt fibrosis stage 0 to 1). The correlation between serum miR-379 and cholesterol levels was lost in early stage NAFLD patients treated with statins. Software-based predictions indicated that various energy metabolism-related genes, including insulin-like growth factor-1 (IGF-1) and IGF-1 receptor, are potential targets of miR-379.

Conclusions: Serum miR-379 exhibits high potential as a biomarker for NAFLD. miR-379 appears to increase cholesterol lipotoxicity, leading to the development and progression of NAFLD, via interference with the expression of target genes, including those related to the IGF-1 signaling pathway. Our results could facilitate future research into the pathogenesis, diagnosis, and treatment of NAFLD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0219412PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046274PMC
April 2020

Infection phase is a predictor of pruritus in patients with hepatitis B virus infection.

Biomed Rep 2019 Aug 21;11(2):63-69. Epub 2019 Jun 21.

Liver Center, Saga University, Saga-Shi, Saga 849-8501, Japan.

Pruritus is a common pathogenesis in liver diseases, including chronic hepatitis B (CHB). The phases of hepatitis B virus (HBV) infection are defined in the American Association for the Study of Liver Diseases guidelines. However, it still remains unclear whether the phase independently affects pruritus. The aim of this study was to clarify the effect of HBV infection phase on pruritus in patients with HBV. Of the 1,631 patients that attended the joint research facilities and were interviewed regarding their pruritus between January and June 2016, 196 patients with HBV infection were selected for the present analysis. One-to-one propensity score-matching using 13 variables was performed between participants in the hepatitis B e antigen (HBe-Ag)-positive/negative immune-active phase group and the inactive CHB phase group. Data from 47 patients per group were included in the final analysis. The prevalence of pruritus in the inactive CHB phase was significantly lower than in the HBe-Ag-positive/negative immune-active phase (23 vs. 47%; P=0.031). Being in the inactive CHB phase was determined to be an independent risk factor for pruritus (odds ratio, 0.35; 95% confidence interval, 0.143-0.842; P=0.019). The progression to inactive CHB phase may contribute to the amelioration of pruritus in patients with HBV infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/br.2019.1224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610217PMC
August 2019

Clinical features of hepatocellular carcinoma in nonalcoholic fatty liver disease patients without advanced fibrosis.

J Gastroenterol Hepatol 2019 Sep 6;34(9):1626-1632. Epub 2019 Mar 6.

Department of Internal Medicine and Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.

Background And Aim: The prevalence of hepatocellular carcinoma (HCC) associated with nonalcoholic fatty liver disease (NAFLD-HCC) is increasing. Unfortunately, NAFLD frequently develops into HCC without liver cirrhosis. Therefore, we investigated the clinical features of HCC in NAFLD patients without advanced fibrosis.

Methods: We compared clinical characteristics, survival rates, and recurrence rates between 104 NAFLD-HCC patients diagnosed between January 2000 and December 2016, including 35 without (F0-2) and 69 with advanced fibrosis (F3-F4). Risk factors associated with survival and recurrence were evaluated.

Results: In total, 66.3% of those diagnosed had advanced fibrosis, 58.8% in men and 80.5% in women (men vs women, P = 0.03). In NAFLD-HCC without advanced fibrosis, tumor size was significantly larger and liver histological activity was lower than those in patients with advanced fibrosis. Survival rates between the two groups did not differ. Among those achieving curative treatment, the recurrence rate was significantly lower in NAFLD-HCC without advanced fibrosis (P < 0.01). Risk factors of recurrence were male gender, lower serum albumin, and advanced fibrosis.

Conclusions: In men, HCC tended to develop from NAFLD without advanced fibrosis. Although tumor size in NAFLD-HCC without advanced fibrosis is significantly larger, the recurrence rate is significantly lower. Surgical therapy should be strongly considered in these cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jgh.14608DOI Listing
September 2019

HOMA-IR: An independent predictor of advanced liver fibrosis in nondiabetic non-alcoholic fatty liver disease.

J Gastroenterol Hepatol 2019 Aug 3;34(8):1390-1395. Epub 2019 Feb 3.

Department of Hepatology, Osaka City University, Osaka, Japan.

Background And Aim: Although non-alcoholic fatty liver disease (NAFLD) is common in the general population, identifying patients with advanced fibrosis remains a challenge. We investigated whether the homeostasis model assessment parameter of insulin resistance (HOMA-IR), an index of IR and one of the most important metabolic factors, is an independent predictive factor for advanced fibrosis in nondiabetic patients with NAFLD.

Methods: This was a retrospective, cross-sectional multicenter study. We included 361 patients with biopsy-proven NAFLD who had not been diagnosed with type 2 diabetes mellitus: 175 (48%) were women and 48 (13%) had advanced fibrosis. We used simple random sampling; the sampling ratio of the estimation and validation groups was 7:3. A logistic model was constructed for both the estimation and validation groups. The explanatory variables were age ≥ 49 years, sex (women), body mass index ≥ 26.7 kg/m , the presence of hypertension, presence of dyslipidemia, fasting plasma glucose level ≥ 98 mg/dL, fasting immune reactive insulin level ≥ 12.0 μU/mL, and HOMA-IR ≥ 2.90. The median HOMA-IR of the patients was 2.88 (interquartile range: 2.1-4.8).

Results: In the estimation group, univariate and multivariate analyses showed that age, dyslipidemia, and HOMA-IR were independent predictors of advanced fibrosis. In the validation group, only age and HOMA-IR were found to be independent predictors of advanced fibrosis.

Conclusions: Homeostasis model assessment parameter of insulin resistance was an independent predictor of advanced liver fibrosis in nondiabetic patients with NAFLD. Given that most patients with NAFLD are nondiabetic, it is important to set goals with respect to improving IR to subsequently reduce liver fibrosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jgh.14595DOI Listing
August 2019

Epidemiological survey of hemoglobin A1c and liver fibrosis in a general population with non-alcoholic fatty liver disease.

Hepatol Res 2019 Mar 28;49(3):296-303. Epub 2018 Nov 28.

Liver Center, Saga University Hospital, Saga, Japan.

Aim: The association between glycemia and liver fibrosis was analyzed using hemoglobin A1c (HbA1c) and the Fibrosis-4 (FIB-4) index in a large general population cohort that underwent a health checkup.

Methods: A total of 6927 subjects without hepatitis B or C virus infection or habitual alcohol intake were enrolled. Non-alcoholic fatty liver disease (NAFLD) was diagnosed by ultrasonography and potential liver fibrosis (FIB-4 index ≥1.3) in NAFLD was analyzed in relation to HbA1c level. Factors associated with potential liver fibrosis of NAFLD were also analyzed.

Results: The overall frequency of NAFLD was 27.9% (1935 subjects) and the frequency of NAFLD by HbA1c level (<4.9%, 5.0-5.9%, 6.0-6.9%, 7.0-7.9%, ≥8.0%) was 16%, 27%, 54%, 53%, and 54%, respectively. Among the 1935 NAFLD cases, the frequency of potential liver fibrosis was 25.2% (487 subjects) overall and 19%, 22%, 30%, 52%, and 31%, respectively, by HbA1c category. From multivariate analysis, an HbA1c level ≥6.5% was significantly associated with potential liver fibrosis (P = 0.017, hazard ratio = 1.7).

Conclusions: The prevalence of NAFLD and liver fibrosis of NAFLD increased according to glycemia, up to 8.0% HbA1c. Measuring HbA1c and calculating the FIB-4 index in health checkups could help to identify potential cases of liver fibrosis of NAFLD, which should then be further evaluated using other techniques to confirm liver fibrosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/hepr.13282DOI Listing
March 2019

Overlooked muscle cramps in patients with chronic liver disease: in relation to the prevalence of muscle cramps.

Eur J Gastroenterol Hepatol 2019 03;31(3):375-381

Department of Gastroenterology and Hepatology, JA Hiroshima General Hospital, Hatsukaichi, Japan.

Introduction: Muscle cramps are common comorbidities in chronic liver disease (CLD). Although the prevalence of these has been reported in patients with liver cirrhosis (LC), that of CLD is unknown. In this study, we aimed to clarify the prevalence and characteristics of muscle cramps in individual CLD.

Patients And Methods: A total of 432 patients with CLD who visited our hospital were enrolled. The existence of muscle cramps, frequency, time zone, duration, and the degree of pain were investigated using a medical interview questionnaire.

Results: The median age of the patients was 65 years and 48.6% of the patients were women. The prevalence of muscle cramps was 25.9%. Age, female sex, lower BMI, existence of comorbid diseases, and liver fibrosis were associated significantly with muscle cramps. In LC, muscle cramps were significantly frequent, and the severity and duration of these were significantly stronger and longer compared with chronic hepatitis. Female sex [odds ratio (OR): 2.26; P=0.014], diabetes (OR: 29.4; P<0.001), chronic kidney disease (OR: 8.33; P=0.004), and lower BMI (OR: 0.853; P<0.001) were independent factors associated with muscle cramps in CLD. Muscle mass indices were significantly lower among nonalcoholic fatty liver disease patients with muscle cramps, female patients, elderly patients, and patients with advanced fibrosis.

Conclusion: The prevalence of muscle cramps was relatively high in CLD. Female sex, comorbid diabetes, and chronic kidney disease are associated with muscle cramps in CLD. Furthermore, reduced muscle mass is related to muscle cramps in nonalcoholic fatty liver disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MEG.0000000000001294DOI Listing
March 2019

Palmitate-induced lipotoxicity is crucial for the pathogenesis of nonalcoholic fatty liver disease in cooperation with gut-derived endotoxin.

Sci Rep 2018 07 27;8(1):11365. Epub 2018 Jul 27.

Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan.

Although previous studies have indicated important roles of palmitate, a saturated fatty acid, in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), it remains unclear how palmitate contributes to inflammation and fibrosis in the liver. Administration of palmitate in high fat diet (HFD)-fed but not basal diet (BD)-fed mice resulted in an increase in serum alanine aminotransferase (ALT) levels. Surprisingly, combined administration of very low dose lipopolysaccharide in palmitate-treated mice led to a marked increase in serum ALT levels despite BD-fed conditions. Administration of palmitate alone in BD-fed mice caused inflammatory cell infiltration and liver fibrosis mediated by the toll-like receptor 4 pathway without ALT elevation. In addition, a significant correlation between serum free fatty acid levels and liver fibrosis stage was observed in patients with NAFLD. These results indicate that palmitate may play crucial roles in the pathogenesis of NAFLD in the presence of gut-derived endotoxin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-29735-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6063851PMC
July 2018

A Data Mining-based Prognostic Algorithm for NAFLD-related Hepatoma Patients: A Nationwide Study by the Japan Study Group of NAFLD.

Sci Rep 2018 Jul 11;8(1):10434. Epub 2018 Jul 11.

Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia.

The prognosis of patients with nonalcoholic fatty liver disease-related hepatocellular carcinoma (NAFLD-HCC) is intricately associated with various factors. We aimed to investigate the prognostic algorithm of NAFLD-HCC patients using a data-mining analysis. A total of 247 NAFLD-HCC patients diagnosed from 2000 to 2014 were registered from 17 medical institutions in Japan. Of these, 136 patients remained alive (Alive group) and 111 patients had died at the censor time point (Deceased group). The random forest analysis demonstrated that treatment for HCC and the serum albumin level were the first and second distinguishing factors between the Alive and Deceased groups. A decision-tree algorithm revealed that the best profile comprised treatment with hepatectomy or radiofrequency ablation and a serum albumin level ≥3.7 g/dL (Group 1). The second-best profile comprised treatment with hepatectomy or radiofrequency ablation and serum albumin levels <3.7 g/dL (Group 2). The 5-year overall survival rate was significantly higher in the Group 1 than in the Group 2. Thus, we demonstrated that curative treatment for HCC and serum albumin level >3.7 g/dL was the best prognostic profile for NAFLD-HCC patients. This novel prognostic algorithm for patients with NAFLD-HCC could be used for clinical management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-28650-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6041283PMC
July 2018

Correction to: The novel cutoff points for the FIB4 index categorized by age increase the diagnostic accuracy in NAFLD: a multi-center study.

J Gastroenterol 2018 11;53(11):1225

Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.

The coauthor Masashi Yoneda's affiliation has been incorrectly published in the original publication of the article. The correct affiliation is provided in this correction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00535-018-1478-7DOI Listing
November 2018
-->