Comparative Analysis of Outcomes of Patients with Hepatitis C Virus-Related Cirrhosis and Those with Hepatitis C Virus-Related Hepatocellular Carcinoma

Mehriban Huseynova Rafael *

Department of I Surgical Diseases, Azerbaijan Medical University, Baku, Azerbaijan.

Nuru Bayramov Yusif

Department of I Surgical Diseases, Azerbaijan Medical University, Baku, Azerbaijan.

Brian I. Carr

Liver Transplant Institute, Inonu University, Malatya, Turkey.

*Author to whom correspondence should be addressed.


Objective: We attempted to identify risk factors for the development of HCC by comparing the parameters of patients with HCV related liver cirrhosis without HCC (HCV-LC-without HCC) and those with HCV related liver cirrhosis plus HCC (HCV-LC-HCC).

Materials and Methods: We retrospectively analysed our database of 40 patients with HCV-LC without HCC and 42 patients with HCV-LC-HCC. A diagnosis of cirrhosis was based on the results of histological examination and/or elastography. HCC was diagnosed histologically or by the detection of consistent findings using at least two imaging techniques from among US, CT, or MRI. Hepatitis C virus infection was detected by enzyme linked immunosorbent assay (ELISA). Other baseline laboratory investigations such as CBC, liver function tests, including serum total bilirubin, ALT, AST, GGT, ALKP, AFP and serum albumin levels, and serum creatinine levels were also measured.

Results: HCC patients had significantly higher serum levels of NLR, PLR, GLR, ALKP and AFP and lower albumin levels, than the non-HCC patients. For the HCC patients, 33.3% had low AFP levels, 35.7% had macroscopic PVT and only 48.1% had a tumor diameter <5cm. Patients with high AFP, PVT and large tumor size had characteristic differences from those with low AFP, absent PVT and smaller tumor size.

Conclusions: Older age, male gender, increased levels of NLR, PLR, GLR, ALKP, AFP and decreased levels of albumin in HCV-related cirrhosis are associated with an increased risk of HCC. In addition, high levels of ALKP, very high levels of AFP (>1000 IU/ml), and presence of large (≥5 cm) tumors increase suspicion of presence of portal vein thrombosis. Consideration of these indicators in routine monitoring may be useful in early diagnosis and treatment of HCC in HCV-related cirrhosis.

Keywords: Carcinoma, hepatocellular, liver cirrhosis, hepatitis C

How to Cite

Rafael , M. H., Yusif , N. B., & Carr , B. I. (2024). Comparative Analysis of Outcomes of Patients with Hepatitis C Virus-Related Cirrhosis and Those with Hepatitis C Virus-Related Hepatocellular Carcinoma. Asian Journal of Research and Reports in Gastroenterology, 7(1), 6–12. Retrieved from


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Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69-90 [PMID: 21296855 DOI: 10.3322/ caac. 201 07].

Maluccio M, Covey A. Recent progress in understanding, diagnosing, and treating hepatocellular carcinoma. CA Can- cer J Clin. 2012;62:394-399. [PMID: 23070690 DOI: 10.3322/ caac. 21161].

Hepatitis C factsheet. World Health Organization. Updated April; 2014. Available: factsheets/fs164/en/

Kanwal F. et al. Risk of hepatocellular cancer in HCV patients treated with direct- acting antiviral agents. Gastroenterology. 2017;153:996–1005.e1.

Ioannou GN. et al. Increased risk for hepatocellular carcinoma persists up to 10 years after HCV eradication in patients with baseline cirrhosis or high FIB-4 scores. Gastroenterology. 2019;157:1264–1278.e4.

Llovet JM. & Villanueva A. Effect of HCV clearance with direct- acting antiviral agents on HCC. Nat. Rev. Gastroenterol. Hepatol. 2016;13:561–562.

Kikuchi LO, Paranagua-Vezozzo DC, Chagas AL, et al. Nodule less than 20mm and vascular invasion are predictors of survival in small hepatocellular carcinoma. J Clin Gastroenterol 2009; 43:191-5.

Xu K, Meng XY, Wu JW, Shen B, Shi YC, Wei Q. Diagnostic value of serum gamma-glutamyl transferase isoenzyme for hepatocellular carcinoma: a 10-year study. Am J Gastroenterol. 1992;87:991-995. [PMID: 1353662].

Witjes CD, Polak WG, Verhoef C, Eskens FA, Dwarkasing RS, Verheij J, de Man RA, Ijzermans JN. Increased alpha-feto- protein serum level is predictive for survival and recurrence of hepatocellular carcinoma in non-cirrhotic livers. Dig Surg. 2012;29:522-528. [PMID: 23548745 DOI: 10.1159/000348669].

Shim JH, Yoon DL, Han S, Lee YJ, Lee SG, Kim KM, Lim YS, Lee HC, Chung YH, Lee YS. Is serum alpha-fetoprotein useful for predicting recurrence and mortality specific to hepatocellular carcinoma after hepatectomy? A test based on propensity scores and competing risks analysis. Ann Surg Oncol. 2012;19:3687-3696. [PMID: 22644512 DOI: 10.1245/ s10434-012-2416-1].

Zhao Y, Si G, Zhu F, Hui J, Cai S. Prognostic role of platelet to lymphocyte ratio in hepatocellular carcinoma: a systematic review and meta-analysis. Oncotarget. 2017;8:22854–22862. [PubMed: 28206965].

Li X, Chen ZH, Xing YF, Wang TT, Wu DH. Platelet-to-lymphocyte ratio acts as a prognostic factor for patients with advanced hepatocellular carcinoma. Tumour Biol. 2015; 36: 2263 – 2269. [PubMed: 25409616].

Chen K, Zhan MX, Hu BS, Li Y. Combination of the neutrophil to lymphocyte ratio and the platelet to lymphocyte ratio as a useful predictor for recurrence following radiofrequency ablation of hepatocellular carcinoma. Oncol Lett. 2018;15:315–323. [PubMed: 29285194].

Arrieta O, Cacho B, Morales-Espinosa D, et al. The progressive elevation of alpha- fetoprotein for the diagnosis of hepatocellular carcinoma in patients with liver cirrhosis. BMC Cancer 2007; 7:28

Villanueva A, Minguez B, Forner A, et al. Hepatocellular carcinoma: novel molecular approaches for diagnosis, prognosis, and therapy. Annu Rev Med. 2010;61:317-28.

Templeton AJ, McNamara MG, Seruga B, Vera-Badillo FE, Aneja P, Ocana A, Leibowitz-Amit R, Sonpavde G, Knox JJ, Tran B, Tannock IF, Amir E: Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Ins. 2014;106:dju124.

European Association for the Study of the Liver. EASL clinical practice guidelines: management of hepatocellular carcinoma. J. Hepatol. 2018;69:182–236.

Marrero JA. et al. Diagnosis, staging, and management of hepatocellular carcinoma: practice guidance by the American association for the study of liver diseases. Hepatology. 2018;68, 723–750.

Hiotis SP, Rahbari NN, Villanueva GA, et al. Hepatitis B vs. hepatitis C infection on viral hepatitis-associated hepatocellular carcinoma. BMC Gastroenterol; 2012.

Tanizaki H, Ryu M, Kinoshita T, et al. Comparison of clinical features and survival in patients with hepatitis B and C virus-related hepatocellular carcinoma. Jpn J Clin Oncol; 1997.

Bray F. et al. Global cancer statistics: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA. Cancer J. Clin. 2018; 68: 394–424.

Aoyagi Y, Suzuki Y, Igarashi K, et al. Carbohydrate structures of human alpha-fetoprotein of patients with hepatocellular carcinoma: presence of fucosylated and non-fucosylated triantennary glycans Br J Cancer. 1993;67:486-92.

Wang D, Wu M, Feng FZ, Huang HF, Yang JX, Shen K, Xiang Y: Pretreatment neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios do not predict survival in patients with cervical cancer treated with neoadjuvant chemotherapy and radical hysterectomy. Chinese Med J. 2013; 126: 1464-1468.

Zhang ZM, Lai EC, Zhang C, Yu HW, Liu Z, Wan BJ, et al. The strategies for treating primary hepatocellular carcinoma with portal vein tumor thrombus. Int J Surg (London England). 2015; 20:8–16. DOI: 10.1016/j.ijsu.2015.05.009 [PubMed] [CrossRef] [Google Scholar].

Akkiz H, Carr BI, Kuran S, Karaogullanndan U, Uskudar O, Tokmak S et al. Macroscopic portal vein thrombosis in HCC patients. Can J Gastrroenterol Hepatol. 2018;2018:32120185.