Dynamics of serum α‑fetoprotein in viral hepatitis C without hepatocellular carcinoma

Isac,Teodora; Isac,Sebastian; Ioanitescu,Simona; Mihaly,Enyedi; Tanasescu,Maria-Daniela; Balan,Daniela Gabriela; Tulin,Adrian; Iliescu,Laura

doi:10.3892/etm.2021.10181

Dynamics of serum α‑fetoprotein in viral hepatitis C without hepatocellular carcinoma

Authors:
- Teodora Isac
- Sebastian Isac
- Simona Ioanitescu
- Enyedi Mihaly
- Maria-Daniela Tanasescu
- Daniela Gabriela Balan
- Adrian Tulin
- Laura Iliescu
View Affiliations

Affiliations: Department of Internal Medicine II, Faculty of Medicine, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania, Department of Physiology and Neuroscience, Faculty of Medicine, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania, Department of Anatomy, Faculty of Medicine, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania, Department of Medical Semiology, Discipline of Internal Medicine I and Nephrology, Faculty of Medicine, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania, Discipline of Physiology, Faculty of Dental Medicine, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
Published online on: May 12, 2021 https://doi.org/10.3892/etm.2021.10181
Article Number: 749
Copyright: © Isac et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Viral hepatitis C represents a significant liver pathology worldwide, with a detrimental impact on national health systems. The present study aimed to correlate the levels of serum α‑fetoprotein (AFP) with prognostic tools such as Fibroscan®, the presence of mixed cryoglobulinemia, and various demographic and standard biochemical markers, in patients with chronic hepatitis C, unrelated to hepatocellular carcinoma (HCC). A clinical study was designed considering three study groups: Hepatitis C virus (HCV) group including 35 patients with chronic hepatitis C and detectible viral load; sustained viral response (SVR) group including 20 HCV patients without detectable virus load 12 weeks after therapy cessation; a control group represented by 37 healthy volunteers. It was observed that serum AFP was moderately increased in the HCV and SVR groups and was positively correlated with aspartate transaminase (AST), alkaline phosphatase (AP), and γ‑glutamyl transferase (GGT). The incidence of mixed cryoglobulinemia was increased in the HCV group, and the degree of fibrosis assessed by Fibroscan® was increased in both the HCV and SVR groups. In conclusion, the data revealed that a moderate increase in AFP levels could be present in patients with HCV even in the absence of HCC, unrelated to viral load or therapy response and that there was a linear positive correlation between serum levels of AFP and the degree of hepatic cytolysis and cholestasis. Additionally, mixed cryoglobulinemia was present in HCV patients with patent viral load, decreasing in those with SVR after therapy cessation unrelated to any renal impairment, while the degree of fibrosis was increased in HCV‑infected patients, with no reversibility 12 weeks after successful therapy.

View Figures

View References

1	Petruzziello A, Marigliano S, Loquercio G, Cozzolino A and Cacciaputi C: Global epidemiology of hepatitis C virus infection: An up-date of the distribution and circulation of hepatitis C virus genotypes. World J Gastroenterol. 22:7824–7840. 2016.PubMed/NCBI View Article : Google Scholar
2	Schamberg NJ and Lake-Bakaar GV: Hepatitis C virus-related mixed cryoglobulinemia: Pathogenesis, Clinica manifestations, and new therapies. Gastroenterol Hepatol (NY). 3:695–703. 2007.PubMed/NCBI
3	Timofte D, Dragos D, Balcangiu-Stroescu AE, Tanasescu MD, Gabriela Balan D, Avino A, Tulin A, Stiru O and Ionescu D: Infection with hepatitis C virus in hemodialysis patients: An overview of the diagnosis and prevention rules within a hemodialysis center (Review). Exp Ther Med. 20:109–116. 2020.PubMed/NCBI View Article : Google Scholar
4	Balcangiu-Stroescu AE, Tanasescu MD, Diaconescu AC, Raducu L, Constantin AM, Balan DG, Tarmure V and Ionescu D: Cardiovascular comorbidities, inflammation and serum albumin levels in a group of hemodialysis patients. Rev Chim Buchar. 69:926–929. 2018.
5	Dustin LB: Innate and adaptive immune responses in chronic HCV infection. Curr Drug Targets. 18:826–843. 2017.PubMed/NCBI View Article : Google Scholar
6	Suceveanu AI, Stoian AP, Mazilu L, Voinea F, Hainarosie R, Diaconu CC, Pituru S, Nitipir C, Badiu DC, Ceausu I and Suceveanu AP: Interferon-free therapy is not a trigger for hepatocellular carcinoma in patients with chronic infection with hepatitis C virus. Farmacia. 66:904–908. 2018.
7	Marinescu I, Schenker RA, Stovicek PO, Marinescu D, Ciobanu CF, Papacocea SI, Manea MC, Papacocea RI, Manea M, Chirita R and Ciobanu AM: Biochemical factors involved in the unfavorable evolution of prostate cancer. Rev Chim. 70:3343–3347. 2019.
8	Papacocea MT, Badarau IA, Radoi M and Papacocea IR: The predictive role of biochemical plasma factors in patients with severe traumatic brain injuries. Rev Chim Buchar. 70:1754–1757. 2019.
9	Sheridan DA, Aithal G, Alazawi W, Allison M, Anstee Q, Cobbold J, Khan S, Fowell A, McPherson S, Newsome PN, et al: Care standards for non-alcoholic fatty liver disease in the United Kingdom 2016: A cross-sectional survey. Frontline Gastroenterol. 8:252–259. 2017.PubMed/NCBI View Article : Google Scholar
10	Sagnelli E, Santantonio T, Coppola N, Fasano M, Pisaturo M and Sagnelli C: Acute hepatitis C: Clinical and laboratory diagnosis, course of the disease, treatment. Infection. 42:601–610. 2014.PubMed/NCBI View Article : Google Scholar
11	Fierbinteanu-Braticevici C, Papacocea R, Tribus L and Baicus C: Role of 13C methacetin breath test for non invasive staging of liver fibrosis in patients with chronic hepatitis C. Indian J Med Res. 140:123–129. 2014.PubMed/NCBI
12	Christiansen M, Høgdall CK, Andersen JR and Nørgaard-Pedersen B: Alpha-fetoprotein in plasma and serum of healthy adults: Preanalytical, analytical and biological sources of variation and construction of age-dependent reference intervals. Scand J Clin Lab Invest. 61:205–215. 2001.PubMed/NCBI View Article : Google Scholar
13	Spătaru RI, Enculescu A and Popoiu MC: Gruber-Frantz tumor: A very rare pathological condition in children. Rom J Morphol Embryol. 55:1497–1501. 2014.PubMed/NCBI
14	Chen CH, Lin ST, Kuo CL and Nien CK: Clinical significance of elevated alpha-fetoprotein (AFP) in chronic hepatitis C without hepatocellular carcinoma. Hepatogastroenterology. 55:1423–1427. 2008.PubMed/NCBI
15	Timofte D, Mandita A, Balcangiu-Stroescu AE, Balan D, Raducu L, Tanasescu MD, Diaconescu A, Dragos D, Cosconel CI, Stoicescu SM and Ionescu D: Hyperuricemia and cardiovascular diseases-clinical and paraclinical correlations. Rev Chim. 70:1045–1046. 2019.
16	Timofte D, Dragoș D, Balcangiu-Stroescu AE, Tănăsescu MD, Gabriela Bălan D, Răducu L, Tulin A, Stiru O and Ionescu D: Abdominal aortic calcification in predialysis patients: Contribution of traditional and uremia-related risk factors. Exp Ther Med. 20:97–102. 2020.PubMed/NCBI View Article : Google Scholar
17	Timofte D, Ionescu D, Medrihan L, Mandita A, Rasina A and Damian L: Vascular calcification and bone disease in hemodialysis patient, assessment, association and risk factors. Nephrol Dial Transplant. 22:325–326. 2007.
18	Gaman MA, Dobrica EC, Pascu EG, Cozma MA, Epingeac ME, Gaman AM, Pantea Stoian AM, Bratu OG and Diaconu CC: Cardio metabolic risk factors for atrial fibrillation in type 2 diabetes mellitus: Focus on hypertension, metabolic syndrome and obesity. J Mind Med Sci. 6:157–161. 2019.
19	Emokpae MA, Adejumol BG, Abdu A and Sadiq NM: Serum alpha-fetoprotein level is higher in hepatitis C than hepatitis B infected chronic liver disease patients. Niger Med J. 54:426–429. 2013.PubMed/NCBI View Article : Google Scholar
20	Tai WC, Hu TH, Wang JH, Hung CH, Lu SN, Changchien CS and Lee CM: Clinical implications of alpha-fetoprotein in chronic hepatitis C. J Formos Med Assoc. 108:210–218. 2009.PubMed/NCBI View Article : Google Scholar
21	Di Bisceglie AM, Sterling RK, Chung RT, Everhart JE, Dienstag JL, Bonkovsky HL, Wright EC, Everson GT, Lindsay KL, Lok AS, et al: Serum alpha-fetoprotein levels in patients with advanced hepatitis C: Results from the HALT-C trial. J Hepatol. 43:434–441. 2005.PubMed/NCBI View Article : Google Scholar
22	Abdoul H, Mallet V, Pol S and Fontanet A: Serum alpha-fetoprotein predicts treatment outcome in chronic hepatitis C patients regardless of HCV genotype. PLoS One. 3(e2391)2008.PubMed/NCBI View Article : Google Scholar
23	Ozkok A and Yildiz A: Hepatitis C virus associated glomerulopathies. World J Gastroenterol. 20:7544–7554. 2014.PubMed/NCBI View Article : Google Scholar
24	Morra E: Cryoglobulinemia. Hematology Am Soc Hematol Educ Program: 368-372, 2005.
25	Gamil M, Alboraie M, El-Sayed M, Elsharkawy A, Asemn N, Elbaz T, Mokey M, Abbas B, Mehrez M and Esmat G: Novel scores combining AFP with non-invasive markers for prediction of liver fibrosis in chronic hepatitis C patients. J Med Virol. 90:1080–1086. 2018.PubMed/NCBI View Article : Google Scholar
26	Fierbinteanu-Braticevici C, Baicus C, Tribus L and Papacocea R: Predictive factors for nonalcoholic steatohepatitis (NASH) in patients with nonalcoholic fatty liver disease (NAFLD). J Gastrointestin Liv Dis. 20:153–159. 2011.PubMed/NCBI
27	Martinot-Peignoux M, Stern C, Maylin S, Ripault MP, Boyer N, Leclere L, Castelnau C, Giuily N, El Ray A, Cardoso AC, et al: Twelve weeks posttreatment follow-up is as relevant as 24 weeks to determine the sustained virologic response in patients with hepatitis C virus receiving pegylated interferon and ribavirin. Hepatology. 51:1122–1126. 2010.PubMed/NCBI View Article : Google Scholar
28	Lucero C and Brown RS Jr: Noninvasive measures of liver fibrosis and severity of liver disease. Gastroenterol Hepatol (NY). 12:33–40. 2016.PubMed/NCBI
29	He Y, Lu H and Zhang L: Serum AFP levels in patients suffering from 47 different types of cancers and noncancer diseases. Prog Mol Biol Transl Sci. 162:199–212. 2019.PubMed/NCBI View Article : Google Scholar
30	Yoo T, Lee KW, Yi NJ, Choi YR, Kim H, Suh SW, Jeong JH, Lee JM and Suh KS: Peri-transplant change in AFP level: A useful predictor of hepatocellular carcinoma recurrence following liver transplantation. J Korean Med Sci. 31:1049–1054. 2016.PubMed/NCBI View Article : Google Scholar
31	Ahn DG, Kim HJ, Kang H, Lee HW, Bae SH, Lee JH, Paik YH and Lee JS: Feasibility of α-fetoprotein as a diagnostic tool for hepatocellular carcinoma in Korea. Korean J Intern Med. 31:46–53. 2016.PubMed/NCBI View Article : Google Scholar
32	Chen TM, Huang PT, Tsai MH, Lin LF, Liu CC, Ho KS, Siauw CP, Chao PL and Tung JN: Predictors of alpha-fetoprotein elevation in patients with chronic hepatitis C, but not hepatocellular carcinoma, and its normalization after pegylated interferon alfa 2a-ribavirin combination therapy. J Gastroenterol Hepatol. 22:669–675. 2007.PubMed/NCBI View Article : Google Scholar
33	Yang JG, He XF, Huang B, Zhang HA and He YK: Rule of changes in serum GGT levels and GGT/ALT and AST/ALT ratios in primary hepatic carcinoma patients with different AFP levels. Cancer Biomark. 21:743–746. 2018.PubMed/NCBI View Article : Google Scholar
34	Landau DA, Saadoun D, Halfon P, Martinot-Peignoux M, Marcellin P, Fois E and Cacoub P: Relapse of hepatitis C virus-associated mixed cryoglobulinemia vasculitis in patients with sustained viral response. Arthritis Rheum. 58:604–611. 2008.PubMed/NCBI View Article : Google Scholar
35	Santoriello D, Pullela NK, Uday KA, Dhupar S, Radhakrishnan J, D'Agati VD and Markowitz GS: Persistent hepatitis C Virus-associated cryoglobulinemic glomerulonephritis in patients successfully treated with direct-acting antiviral therapy. Kidney Int Rep. 3:985–990. 2018.PubMed/NCBI View Article : Google Scholar
36	Pan JJ, Bao F, Du E, Skillin C, Frenette CT, Waalen J, Alaparthi L, Goodman ZD and Pockros PJ: Morphometry confirms fibrosis regression from sustained virologic response to direct-acting antivirals for hepatitis C. Hepatol Commun. 2:1320–1330. 2018.PubMed/NCBI View Article : Google Scholar
37	Ilie M, Rusu M, Rosianu C, Neagu TP, Motofei IG, Bratu OG, Socea B, Stanescu AMA, Gherghiceanu F, Pantea Stoian A, et al: Ultrasound-guided biopsy in focal liver lesions. Arch Balk Med Union. 53:364–368. 2018.
38	Wang JH, Changchien CS, Hung CH, Tung WC, Kee KM, Chen CH, Hu TH, Lee CM and Lu SN: Liver stiffness decrease after effective antiviral therapy in patients with chronic hepatitis C: Longitudinal study using FibroScan. J Gastroenterol Hepatol. 25:964–969. 2010.PubMed/NCBI View Article : Google Scholar