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Table 1 Role of hepcidin as a biochemical marker in liver diseases

From: Low hepcidin in liver fibrosis and cirrhosis; a tale of progressive disorder and a case for a new biochemical marker

Condition Study characteristics Main results References
Alcoholic cirrhosis Prospective study (n = 237)
Median follow-up: 68 months
Serum hepcidin measurements with ELISA method
Cut-off value: < 8 μg/L
Low hepcidin associated with HCC occurrence [HR = 1.76 (1.01–3.06); P = 0.031]
Low hepcidin associated with overall death [HR = 2.84 (1.29–6.25), P = 0.009]
Nahon et al. 2016
ALD n = 24
Serum hepcidin measurements with ELISA method
Serum hepcidin ↓ (P = 0.001) Dostalikova-Cimburova et al. 2014
Chronic liver disease n = 332
Liver biopsy samples and serum hepcidin measurements with mass spectrometry
Serum hepcidin ↓ (P < 0.0001)a
Hepcidin/ferritin ratio ↓ (P < 0.0001)b
Hepcidin/ferritin ratio with cut-off value < 0.1 was independently associated with liver cirrhosis [OR 5.54 (95% CI 2.49–12.35, P < 0.001)]
Hepcidin/ferritin ratio ↓ distinguishes between F0 and F4 stages of fibrosis (AUC = 0.86)
Tan et al. 2012
Liver cirrhosis n = 70
Serum prohepcidin measurements with ELISA method
Serum prohepcidin in all patients ↓ (P < 0.01)
Serum prohepcidin levels ↓ in HCV and alcoholic –related cirrhosis (P < 0.01), but not in HBV-related cirrhosis
Prohepcidin/ferritin ratio correlation with Child-Pugh score in all patients: r = 0.38, P = 0.01
Prohepcidin/Child-Pugh score correlation in alcohol-related liver cirrhosis: r = 0.41, P = 0.01
Jaroszewicz et al. 2008
Chronic hepatitis and liver cirrhosis HCV patients (n = 131); HBV patients (n = 59)
Serum hepcidin measurements with ELISA method
Serum prohepcidin ↓ in HCV patients with chronic hepatitis (P = 0.01) and liver cirrhosis (P = 0.037) compared to HBV patients Nagashima et al. 2006
HCV infection Liver biopsy from n = 96 patients
Serum hepcidin measurements with ELISA method
Serum hepcidin ↓ (P < 0.001)
Serum hepcidin/histological lesions correlations: necroinflammation (r = 0.259, P = 0.011) and fibrosis (r = 0.214, P = 0.036)
Serum hepcidin is an independent predictor of liver cirrhosis [OR = 1.145 (1.007–1.301); P = 0.039]
Tsochatzis et al. 2010
HCV infection Treatment outcomes in n = 31 patients
Serum hepcidin measurements with mass spectrometry
Serum hepcidin ↑ (at 12 h) after treatment with pegylated IFN-α (P < 0.0001)
Correlations between hepcidin and markers of treatment response to pegylated IFN-α
I. Serum hepcidin/IFN-α: r = 0.44, P = 0.042
II. Serum hepcidin/IL-10: r = 0.59, P = 0.004
Ryan et al. 2012
HCV infection Treatment outcomes in n = 15 patients
Serum hepcidin measurements with mass spectrometry
Serum hepcidin ↑ (at week 1) after treatment with pegylated IFN-α (P = 0.013) van Rijnsoever et al. 2016
HCV infection Treatment outcomes in n = 73 patients
Serum hepcidin measurements with mass spectrometry
Hepcidin/ferritin ratio ↓ (P = 0.028)
Serum hepcidin ↑ in patients with SVR after 48 weeks of treatment (P < 0.01)
Hepcidin/ferritin ratio ↑ in patients with SVR after 48 weeks of treatment (P < 0.01)
Fujita et al. 2008
HCV infection Treatment outcomes
Retrospective study (n = 50)
Serum hepcidin measurements with mass spectrometry
Serum hepcidin ↓ in patients with SVR (but did not reach statistical significance) Kohjima et al. 2015
HCV infection n = 81
Serum hepcidin measurements with ELISA method
Serum hepcidin ↓ (P < 0.001)
Serum hepcidin/ferritin(quartiles) ↓ (P < 0.001)
Girelli et al. 2009
HCV infection n = 9
Serum hepcidin measurements with mass spectrometry
Hepcidin/ferritin ratio ↓ (P = 0.0068)
Hepcidin/ferritin ratio ↓ after phlebotomy (P = 0.0338)
Sugimoto et al. 2009
Chronic liver disease n = 34 (children)
Liver biopsy
Serum hepcidin measurements with ELISA method
Hepcidin/ferritin ratio ↓ in patients with Child-Pugh score B + C compared to Child-Pugh score A (P = 0.03)
Hepcidin/ferritin ratio ↓ in patients with severe fibrosis vs no fibrosis/mild fibrosis (P < 0.05)
Cakir et al. 2015
HBV-related cirrhosis n = 70
Serum hepcidin measurements with ELISA method
Serum hepcidin ↓ (P < 0.001)
Serum hepcidin/TS ratio ↓
Lin et al. 2013
Chronic HBV infection n = 46
Nanopore film-based assay
Serum hepcidin ↓ in cirrhotic HBV infection compared to non-cirrhotic HBV infection (P < 0,05)
Serum hepcidin ↓ in Child-Pugh class C compared to Child-Pugh class A (but without reaching statistical significance)
Wang et al. 2016
NAFLD n = 51
Serum hepcidin measurements with ELISA method
Hepcidin correlates with hepatic lipid content (r = 0.42, P = 0.0024)
Hepcidin ↑ in NASH vs non-NASH NAFLD (P = 0.01)
Hepcidin differentiates between early and later stages of liver fibrosis (P < 0.0001)
Hepcidin is an independent predictor of liver fibrosis [OR = 1.03 (1.00-1.05); P = 0.022]
Ryan et al. 2017
NAFLD n = 54
Serum hepcidin measurements with ELISA method
Hepcidin is an independent predictor of advanced liver fibrosis [OR = 560.72 (5.98-5255.33); P = 0.006]
Hepcidin cut-off value of 45.00 ng/mL differentiates between simple steatosis and NASH
Jamali et al. 2016
DIOS n = 18
Serum hepcidin measurements with ELISA method
Hepcidin resistance indexc ↑(P = 0.0002) Rametta et al. 2016
NAFLD, DIOS, HH-HFE, THAL n = 15 (NAFLD), n = 47 (DIOS), n = 23 (HH-HFE), n = 9 (THAL)
Serum hepcidin measurements with mass spectrometry
Serum hepcidin ↓ in HH-HFE vs controls (P < 0.01)
Serum hepcidin ↓ in HH-HFE vs DIOS (P < 0.01)
Hepcidin/ferritin ratio ↓ in DIOS vs controls (P < 0.01)
Hepcidin/ferritin ratio ↓ in HFE-HH vs controls (P < 0.01)
Hepcidin/ferritin ratio ↓ in THAL vs controls (P < 0.01)
Hepcidin/ferritin ratio ↓ in HFE-HH vs NAFLD (P < 0.01)
Hepcidin/ferritin ratio ↓ in HFE-HH vs DIOS (P < 0.01)
Ravasi et al. 2012
Liver autoimmune diseases vs NAFLD and HBV/HCV infections AICD (n = 34)
AIH (n = 16)
NAFLD (n = 32)
HBV infection (n = 23)
HCV infection (n = 21)
Serum hepcidin measurements with ELISA method
Serum hepcidin ↓ in AIH compared to NAFLD (P < 0.001), HBV infection (P < 0.001), HCV infection (P = 0.001)
Serum hepcidin/ferritin ratio ↓ in AIH compared to NAFLD (P < 0.001), HBV infection (P < 0.001), HCV infection (P < 0.001)
Serum hepcidin ↓ in AICD compared to NAFLD (P < 0.001), HBV infection (P < 0.001), HCV infection (P < 0.001)
Serum hepcidin/ferritin ratio ↓ in AICD compared to NAFLD (P < 0.001), HBV infection (P < 0.001), HCV infection (P < 0.001)
Serum hepcidin ↓ in HCV infection compared to HBV infection (P = 0.018)
Lyberopoulou et al. 2015
Biliary atresia n = 10 (early stage disease); n = 9 (late stage disease)
Liver biopsy samples
Serum hepcidin measurements with ELISA method
Hepcidin mRNA ↓ in late stage disease (cirrhosis) compared to early stage disease (P < 0.001)
Serum hepcidin ↓ in late stage disease (cirrhosis) compared to early stage disease (P = 0.02)
Huang et al. 2009
HH n = 5 (HH-HFE), n = 6 (HH-HJV)
Serum hepcidin measurements with ELISA method
Hepcidin/ferritin ratio ↓ in untreated HH-HFE
Serum hepcidin ↓ in HH-HJV (P < 0.001)
Ganz et al. 2008
Iron-overload conditions n = 13
Serum hepcidin measurements with mass spectrometry
Serum hepcidin ↓ in HH-HFE, HH-HJV, HH-TFR2 vs serum hepcidin ↑ in FPN disease (P < 0.01) Kaneko et al. 2010
HFE-HH (C282Y) n = 22
Serum hepcidin measurements with mass spectrometry
Serum hepcidin ↓ in untreated homozygotes (P < 0.01)d
Hepcidin/ferritin ratio ↓ in untreated homozygotes (P < 0.001)
van Dijk et al. 2008
HFE-HH (C282Y) n = 9
Serum hepcidin measurements with ELISA method
Serum hepcidin ↓ in untreated homozygotes (P = 0.0002)
Hepcidin response to oral iron challenge ↓ (AUC: P = 0.0127)
Sangwaiya et al. 2011
FPN disease type A n = 8
Serum prohepcidin measurements with ELISA method
Serum prohepcidin ↑ in untreated patients compared to normal control and treated patients with FPN disease Zoller et al. 2005
  1. Abbreviations: AICD autoimmune cholestatic disease, AIH autoimmune hepatitis, ALD alcoholic liver disease, AUC area under curve, DIOS dysmetabolic iron overload syndrome, ELISA enzyme-linked immunosorbent assay, FPN ferroportin, HBV hepatitis B virus, HCC hepatocellular carcinoma, HCV hepatitis C virus, HFE hemochromatosis protein, HH hemochromatosis, HJV hemojuvelin, HR hazard ratio, IFN interferon, NAFLD nonalcoholic fatty liver disease, NASH nonalcoholic steatohepatitis, OR odds ratio, SVR sustained virological response, TFR2 transferrin receptor 2, THAL thalassemia, TS transferrin saturation
  2. Up (↑) and down (↓) arrows are presented to signify changes in levels of biochemical markers or gene expression; down arrow (↓) means that a specific biochemical marker or genetic expression levels are low, while up arrow (↑) means that a specific biochemical marker or genetic expression levels are high
  3. aSignificance was observed between patients with liver conditions (ALD, AIH, HBV infection, HCV infection, NAFLD, PBC, PSC) and disease-control subjects (non-liver rheumatological, renal and hematological disease)
  4. bSignificance was observed between patients with liver conditions (ALD, AIH, HBV infection, HCV infection, NAFLD, PBC, PSC) and disease-control subjects (non-liver rheumatological, renal and hematological disease) and healthy controls
  5. cHepcidin resistance index is defined as the ability of hepcidin spike to control the rise in TS
  6. dIn HH-HFE homozygotes with high ferritin levels levels of hepcidin were lower than controls, but did not reach statistical significance