283-OR: Inadequate Hepatic Mitochondrial Adaptation in Patients with NASH Is Related to the Severity of Steatohepatitis and Fibrosis Stage

Background & Aims: Mild iron overload is frequently reported in patients with nonalcoholic fatty liver disease (NAFLD). Hepcidin is the master iron-regulatory peptide and hemojuvelin (HJV) is the key regulator of iron-dependent secretion of hepcidin. The aims of this study were to evaluate serum HJV and hepcidin levels in patients with biopsy-proven NAFLD with and without hepatic iron overload, and to identify potential associations of HJV and hepcidin with the clinical characteristics of the patients enrolled. Methods: Serum levels of HJV and hepcidin were measured in 66 NAFLD patients with (n=12) and without (n=54) iron overload, and controls (n=35) by enzyme-linked immunosorbent assay. Hemojuvelin and hepcidin levels were assessed in relation to clinical characteristics and liver histologic evaluation of the participants. Results: Significantly lower serum HJV (281.1 [239.2-353.6] vs. 584.8 [440.3-661] ng/ml, p<0.001) and similar serum hepcidin levels (60.5±31.1 vs. 55.8±11.9 ng/ml, p=0.285) were found in NAFLD patients when compared to controls. İron-overloaded NAFLD patients had significantly lower HJV (249.9 [187.6-296.3] vs. 292.9 [243-435] ng/ml, p=0.032) and significantly higher hepcidin (78.4±35.5 vs. 56.5±28.9ng/ml, p=0.027) levels than NAFLD patients without iron overload. Fibrosis stage was significantly higher in iron overloaded NAFLD group (p<0.001). Ferritin levels correlated significantly both with HOMA-IR (r=0.368, p=0.002) and fibrosis stage (r=0.571, p<0.001). Conclusions: Our findings suggest that HJV levels are low in NAFLD and even lower in iron overloaded NAFLD, while hepcidin levels are higher in NAFLD with iron overload. The gradually decreased HJV and increased hepcidin concentrations in our patients most likely reflect the physiological response to iron accumulation in the liver.

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Importance of fibrosis stage in starting treatment for hepatitis B virus (HBV): Are the updated CASL/AMMI HBV clinical algorithms lost in translation?

Canadian Liver Journal ◽

10.3138/canlivj.2019-0019 ◽

2019 ◽

Vol 2 (4) ◽

pp. 131-134 ◽

Cited By ~ 1

Author(s):

Kelly Warren Burak ◽

Matthew Douglas Sadler ◽

Meredith Alison Borman ◽

Stephen Everett Congly

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Fibrosis Stage ◽

B Virus ◽

Lost In Translation ◽

Clinical Algorithms

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Liver fibrosis staging by deep learning: a visual-based explanation of diagnostic decisions of the model

European Radiology ◽

10.1007/s00330-021-08046-x ◽

2021 ◽

Author(s):

Yunchao Yin ◽

Derya Yakar ◽

Rudi A. J. O. Dierckx ◽

Kim B. Mouridsen ◽

Thomas C. Kwee ◽

...

Keyword(s):

Deep Learning ◽

Liver Fibrosis ◽

Liver Parenchyma ◽

Ct Images ◽

Fibrosis Stage ◽

Contrast Enhanced Ct ◽

Contrast Enhanced ◽

Enhanced Ct ◽

Liver Surface ◽

Fibrosis Staging

Abstract Objectives Deep learning has been proven to be able to stage liver fibrosis based on contrast-enhanced CT images. However, until now, the algorithm is used as a black box and lacks transparency. This study aimed to provide a visual-based explanation of the diagnostic decisions made by deep learning. Methods The liver fibrosis staging network (LFS network) was developed at contrast-enhanced CT images in the portal venous phase in 252 patients with histologically proven liver fibrosis stage. To give a visual explanation of the diagnostic decisions made by the LFS network, Gradient-weighted Class Activation Mapping (Grad-cam) was used to produce location maps indicating where the LFS network focuses on when predicting liver fibrosis stage. Results The LFS network had areas under the receiver operating characteristic curve of 0.92, 0.89, and 0.88 for staging significant fibrosis (F2–F4), advanced fibrosis (F3–F4), and cirrhosis (F4), respectively, on the test set. The location maps indicated that the LFS network had more focus on the liver surface in patients without liver fibrosis (F0), while it focused more on the parenchyma of the liver and spleen in case of cirrhosis (F4). Conclusions Deep learning methods are able to exploit CT-based information from the liver surface, liver parenchyma, and extrahepatic information to predict liver fibrosis stage. Therefore, we suggest using the entire upper abdomen on CT images when developing deep learning–based liver fibrosis staging algorithms. Key Points • Deep learning algorithms can stage liver fibrosis using contrast-enhanced CT images, but the algorithm is still used as a black box and lacks transparency. • Location maps produced by Gradient-weighted Class Activation Mapping can indicate the focus of the liver fibrosis staging network. • Deep learning methods use CT-based information from the liver surface, liver parenchyma, and extrahepatic information to predict liver fibrosis stage.

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Albumin platelet product as a novel score for liver fibrosis stage and prognosis

Scientific Reports ◽

10.1038/s41598-021-84719-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Koji Fujita ◽

Kazumi Yamasaki ◽

Asahiro Morishita ◽

Tingting Shi ◽

Joji Tani ◽

...

Keyword(s):

Liver Fibrosis ◽

Validation Cohort ◽

Activity Grade ◽

Fibrosis Stage ◽

Strongly Correlated ◽

The Novel ◽

Training Cohort ◽

Blood Examination ◽

Retrospective Multicenter Study ◽

Overall Mortality

AbstractFibrosis-4 index, a conventional biomarker for liver fibrosis stage, is confounded by age and hepatitis activity grade. The current retrospective multicenter study aimed to formulate the novel indices of liver fibrosis by mathematically combining items of peripheral blood examination and to evaluate ability of prognosis prediction. After a novel index was established in a training cohort, the index was tested in a validation cohort. Briefly, a total of 426 patients were enrolled in a training cohort. Albumin and platelet most strongly correlated to fibrosis stage among blood examination. Albumin platelet product (APP) = Albumin × platelet/1000 could differentiate the four stages of liver fibrosis (p < 0.05). APP indicated fibrosis stage independent from hepatitis activity grade. A cut-off value = 4.349 diagnosed cirrhosis with area under ROC more than 0.8. Multivariate analysis revealed that smaller APP independently contributed to HCC prevalence and overall mortality. The results were validated in another 707 patients with HCV infection. In conclusion, APP was not confounded by age or hepatitis activity grade contrary to Fibrosis-4 index. APP is as simple as physicians can calculate it by pen calculation. The product serves physicians in managing patients with chronic liver disease.

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Serum hepcidin levels are related to serum markers for iron metabolism and fibrosis stage in patients with chronic hepatitis B: A cross-sectional study

Arab Journal of Gastroenterology ◽

10.1016/j.ajg.2020.04.013 ◽

2020 ◽

Vol 21 (2) ◽

pp. 85-90 ◽

Cited By ~ 1

Author(s):

Hakan Çam ◽

Nimet Yılmaz

Keyword(s):

Chronic Hepatitis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Iron Metabolism ◽

Cross Sectional Study ◽

Serum Markers ◽

Fibrosis Stage ◽

Sectional Study ◽

Cross Sectional ◽

Serum Hepcidin

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Serum Aspartate Aminotransferase Level and Previous Histopathological Findings Enable Reduction of Protocol Liver Biopsies after Liver Transplantation for Hepatitis C

Canadian Journal of Gastroenterology ◽

10.1155/2013/904636 ◽

2013 ◽

Vol 27 (3) ◽

pp. 131-136 ◽

Cited By ~ 1

Author(s):

Tomohiro Tanaka ◽

George Therapondos ◽

Nazia Selzner ◽

Eberhard L Renner ◽

Leslie B Lilly

Keyword(s):

Liver Transplantation ◽

Hepatitis C ◽

Antiviral Therapy ◽

Aspartate Aminotransferase ◽

Aminotransferase Level ◽

Fibrosis Stage ◽

Protocol Biopsy ◽

Serum Aspartate Aminotransferase ◽

Histological Activity ◽

Liver Biopsies

BACKGROUND: Hepatitis C virus (HCV) infection remains the leading indication for liver transplantation (LT) worldwide. Recurrent hepatitis C following LT is universal, and significant fibrosis (SF, Metavir fibrosis stage ≥2) apparent on protocol biopsy typically prompts antiviral therapy.OBJECTIVE: To determine the optimal timing of protocol liver biopsies in this setting.METHODS: A total of 151 patients who underwent LT related to HCV infection between July 2004 and December 2009 were analyzed retrospectively. Data regarding protocol liver biopsies at six, 12 and 24 months post-LT, conventional laboratory parameters and demographic information were obtained.RESULTS: The 151 patients included in the present study had significantly lower serum aspartate aminotransferase (AST) levels than the four patients who progressed to receive antiviral treatment for SF before six months post-LT (P<0.001). AST level, but not alanine aminotransferase level, histological activity or fibrosis stage at the six-month biopsy was independently associated with the progression to SF at 12 months (P<0.05). However, AST level, histological activity and fibrosis stage at the 12-month biopsy emerged as independent parameters associated with progression to SF at 24 months (P<0.05).CONCLUSION: The protocol liver biopsy at six months could be eliminated, especially in patients who consistently exhibit low AST levels. Histological activity, the presence or absence of fibrosis, and AST values at the 12-month biopsy may lead to the decision to defer the protocol biopsy at 24 months or result in earlier introduction of antiviral therapy.

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