Role of Markers of Heavy Metal Metabolism in Identification of Hepatic Fibrosis in Patients With Non-Alcoholic Fatty Liver Disease (NAFLD)

Role of Markers of Heavy Metal Metabolism in Identification of Hepatic Fibrosis in Patients With Non-Alcoholic Fatty Liver Disease (NAFLD)

Aggarwal Manik;Mitchell B;Singh AD;Kasumov T;McCullough A

American Journal Of Gastroenterology

2020

2020-10

INTRODUCTION: Fibrosis & nonalcoholic steatohepatitis (NASH) are important predictors of long term prognosis in patients with non-alcoholic fatty liver disease (NAFLD). Oxidative stress (OS) has been shown to play a central role in progression of NAFLD, & changes in proteins associated with metal homeostasis may exacerbate OS. We investigated relationship of proteins related to transition metal metabolism with fibrosis in NAFLD. METHODS: Adult patients (>18y) who underwent liver biopsy for clinically suspected NAFLD at our institution were included. We retrospectively collected serum levels of ceruloplasmin (Cp), ferritin, iron, & transferrin saturation (Tsat) within 3 months of liver biopsy & calculated Cp/Tsat ratio (CT ratio) & Cp/Ferritin ratio (CF ratio). Histologic features were scored by an experienced pathologist using Non-alcoholic Steatohepatitis Clinical Research Network criteria. Fibrosis was staged as (0 - 4). Independent T test were used to compare the means & receiver operating characteristics (ROC) curves were plotted for assessing area under curve (AUC), sensitivity (Sn) & specificity (Sp). RESULTS: 174 patients were included in final analysis. The mean age of subjects was 48 y. Baseline features are depicted in Table 1. Biopsy proven NASH was seen in 61.5% of liver biopsies. No fibrosis was seen in 29.3% of liver biopsies & Stage 1, 2,3& 4 fibrosis were seen in 29.9%, 10.9%, 14.3% & 15.55% of samples. Mean Tsat was significantly higher (24.41% v/s 38.27%, P < 0.0001) & Cp (mg/dl) (27.82 v/s 24.91, P = 0.03) significantly lower between patients with advanced fibrosis (AF) (3-4) v/s early fibrosis (EF) (0-2). The mean CT ratio was also higher in patients with EF v/s AF (1.54 v/s 1.02, P = 0.01). The mean Tsat of patients with fibrosis v/s without fibrosis was higher (31.4% v/s 21.57% P < 0.005) however mean Cp (mg/dl) values were not significantly different (27.88 v/s 27.58, P = 0.42). The ROC curves show CF ratio (Figure 1) at a cut off of 0.10 had AUC = 0.61 (Sn = 70%, Sp = 52% P = 0.01) to detect any fibrosis & CT ratio (Figure 2) at a cut off 0.86 had AUC = 0.65 (Sn = 69%, Sp = 50% P = 0.002) for differentiating EF v/s AF. CONCLUSION: Our data reveals changes in ceruloplasmin: transferrin system, which decreases the content of toxic ions of Fe2+ in NAFLD. Tsat, Cp, CF ratio & CT ratio are useful non-invasive biomarkers in identifying NAFLD patients with fibrosis. Markers of heavy metal metabolism can spare patients from liver biopsies & can be potential therapeutic targets in future.

Oxidative stress; hepatic fibrosis; non-alcoholic fatty liver disease; Heavy Metals; non-alcoholic steatohepatitis (NASH)

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S564-S565

S

115

0002-9270

NEOMED College of Pharmacy

Department of Pharmaceutical Sciences

February 2021 List