January 2016, Volume 66, Issue 1

Original Article

Frequency of deaths in hepatitis C virus infected hepatocellular carcinoma patients and its relationship with raised serum alpha-fetoprotein levels

Fida Hussain Shaikh  ( Department of Medicine/Gastroenterology, Isra University Hospital, Hala Road, Hyderabad Sindh, Pakistan. )
Shaista Zeb  ( Department of Medicine, Isra University Hospital, Hala Road, Hyderabad Sindh, Pakistan. )
Sultan Ahmed Chandio  ( Department of Medicine, Medical Unit-I, Shahid Benazir Bhutto University Teaching Hospital, Larkana, Sindh, Pakistan. )
Alvina Munaf  ( Department of Medicine, Isra University Hospital, Hala Road, Hyderabad Sindh, Pakistan. )
Muhamad Aamir Ghori  ( Department of Medicine, Isra University Hospital, Hala Road, Hyderabad Sindh, Pakistan. )
Mohammad Sadik Memon  ( Department of Medicine and Gastroenterology, Isra University Hospital, Hala Road, Hyderabad Sindh, Pakistan. )
Asif Ali Burney  ( Department of Medicine, Isra University Hospital, Hala Road, Hyderabad Sindh, Pakistan. )

Abstract

Objectives: To determine the frequency of deaths in hepatitis C virus infected hepatocellular carcinoma patients, and its relationship with raised serum alpha-fetoprotein levels.
Methods: The cross-sectional study was conducted at Isra University Hospital, Hyderabad, Pakistan, between March 2013 and April 2014, and comprised all patients diagnosed with hepatitis C virus and hepatocellular carcinoma over 30 years ofage. Blood sample was drawn for the measurement of serum Alfa fetoprotein levels. Data was analysed using SPSS 16.
Results: The mean age of the 165 patients was55.49±11.67 years. The mean tumour size was 5.63 ± 2.14cm. Of the total, 31(18.8%) patients had tumour size <3cm, 65(39.4%) 3-5cm and 69(41.8%) >5cm. The mean serum Alfa fetoprotein level was 7641.0±3665.32 IU/ml. Overall mortality rate was 70(41.9%). Tumour size >5cm was significantly associated with mortality (p=0.016).
Conclusion: Serum Alfa fetoprotein levels were a useful tool for the detection of hepatocellular carcinoma in hepatitis C virus patients.
Keywords: Hepatitis C virus, Hepatocellular carcinoma, Alpha fetoprotein levels. (JPMA 66: 34; 2016).


Introduction

A potential earliest predictable oncofoetal marker is serum Alphafetoprotein (AFP) level. During early phase of life, large amount of AFP is produced by the foetal liver, but its production stops soon after birth. Synthesis of AFP is seen in hepatocellular carcinomas (HCCs) and hepatoblastomas, and that is why it is extensively used in clinical field as a prognostic marker in hepatitis C Virus (HCV)-related HCC.1 Burden of HCV and its related complications continue to rise in the world. World Health Organisation (WHO) estimated a prevalence of about 3% in 1999 with 170 million people worldwide affected by HCV.2 Malignant Hepatoma or HCC cause primary malignancy of the liver and represent the third leading cause of cancer-related deaths worldwide among them; around 80% of the HCV-related HCC are reported in the developing countries of Asia.3 It is already well known that the progression and development of HCC is closely related to HCV, predominantly in cirrhosis, and that is why proper regular examination and assessment with serum AFP levels should be performed to evaluate the prognosis in patients with HCV-related HCC.4
The current study was planned to investigate the frequency of deaths caused by elevated serum AFP levels in HCV-related HCC patients.


Patients and Methods

The prospective cross-sectional study was conducted at the Department of Gastroenterology and Hepatology, Isra University Hospital, Hyderabad, Pakistan, from March 2013 to April 2014, and comprised all patients of HCV-HCC of age >30 years of either gender who volunteered to take part in the study. Patients with fulminant hepatic failure, HCC caused by infection other than HCV, end-stage renal disease (ESRD), those were lost to follow-up, and the ones not willing to participate were excluded.
Structured questionnaires were used to collect the relevant information, including demography, measurement of serum AFP levels, and after six weeks, patients were followed up over the phone to see the outcome.
A blood sample was drawn for the measurement of serum AFP levels in all patients who were either admitted to hospital or were visiting the outpatient department (OPD) at the time of the study.
Data was analysed usingSPSS16. Frequencies and percentages were computed for qualitative variables like gender, mortality rate, economic and educational status. Numerical variables such as age, levels of serum AFP, and tumour size were presented as mean ±standard deviation. P?0.5 was considered statistically significant.


Results

Out of 165 patients, 145(86.8%) were men and 20(12.2%) were women. The overall mean age was 55.49±11.67 years. The mean duration of HCV was 28.17±14.23years and that of HCC was 10.54±8.33 years. The mean tumour size was 5.63 ± 2.14cm. Of the total, 31(18.8%) patients had tumour size <3cm, 65(39.4%) 3-5cm and 69(41.8%) >5cm. The mean serum AFP level was 7641.0±3665.32 IU/ml (Table).

Overall mortality rate was 70(41.9%) (Figure-1) at six weeks of follow-up.


Tumour size >5cm was significantly associated with mortality (p=0.016) (Figure-2).




Discussion

HCC is one of the most prevalent liver carcinomas associated with high mortality rates both in developed and developing countries even after all the advancement in treatment strategies. The aetiology of HCC varies worldwide; in Pakistan HBV is the most common cause of HCC. Clinical studies have revealed potential relationship between AFP levels and the progression of HCC. Patients infected with HCV infection require close monitoring of their disease progression by having the levels of AFP assessed on a regular basis. Most studies have documented the association of an elevated serum AFP level in patients with HCV as a potential biomarker to determine the development of HCC.5,6
In our study, majority of the HCV-HCC patients had AFP levels over 400 IU/ml. Similar findings were observed in a local study.7 as well as an international study.8
In a north Indian study, AFP levels were raised in 65% HCC cases; the highest level recorded being 580ng/ml.9 In a south Indian study, elevated AFP levels were observed in 47.4% cases.10 These results correlate well with our study.
In the current study, mean tumour size was 5.63±2.14cm, while the mean serum AFP level was 7641.0±3665.32 IU/ml which is in line with earlier studies.1,10 Overall mortality in our study was seen in 41.9% while one study reported a much lower 18.7%; this difference is probably because of different lifestyle, hospital facilities, education and socio-economic status as well as awareness regarding the disease.
In our study, tumour size >5cm was found to be the significant cause of mortality in HCC patients (p=0.016). This finding was similar to a local study.1


Conclusion

Serum AFP levels were a useful tool for the detection of HCC. HCV-HCC patients with elevated AFP levels revealed higher mortality rates and had significant association with large tumour size.


References

1. Abbasi A, Bhutto AR, Butt N, Munir SM. Corelation of serum alpha fetoprotein and tumor size in hepatocellular carcinoma. J Pak Med Assoc 2012; 62: 33-6.
2. Obienu O, Nwokediuko S, Malu A, Lesi OA. Risk factors for hepatitis C virus transmission obscure in nigerian patients. Gastroenterol Res Pract 2011; 2011: 939673.
3. Waly RS, Yangde Z, Yuxiang C. Hepatocellular carcinoma: focus on different aspects of management. ISRN Oncol 2012; 2012: 421673.
4. Tyson GL, Duan Z, Kramer JR, Davila JA, Richardson PA, El-Serag HB. Level of alpha-fetoprotein predicts mortality among patients with hepatitis C-related hepatocellular carcinoma. Clin Gastroenterol Hepatol 2011; 9: 989-94.
5. Munaf A, Memon MS, Kumar P, Ahmed S, Kumar MB. Comparison of viral hepatitis-associated hepatocellular carcinoma due to HBV and. Asian Pac J Cancer Prev 2014; 15: 7563-7.
6. Ayub A, Ashfaq UA, Haque A. HBV induced HCC: major risk factors from genetic to molecular level. Biomed Res Int 2013; 2013: 810461.
7. Petry W, Heintges T, Hensel F, Erhardt A, Wenning M, Niederau C, et al. [Hepatocellular carcinoma in Germany. Epidemiology, etiology, clinical aspects and prognosis in 100 consecutive patients of a university clinic]. Z Gastroenterol 1997; 35: 1059-67.
8. Kapoor D, Aggarwal SR, Singh NP, Thakur V, Sarin SK. Granulocyte-macrophage colony-stimulating factor enhances the efficacy of hepatitis B virus vaccine in previously unvaccinated haemodialysis patients. J Viral Hepat 1999; 6: 405-9.
9. Francioni S, Pastore M. Alpha-fetoprotein and acute viral hepatitis type B. J Nucl Med Allied Sci 1989; 33(3 Suppl): 103-6.
10. Li P, Wang SS, Liu H, Li N, McNutt MA, Li G, et al. Elevated serum alpha fetoprotein levels promote pathological progression of hepatocellular carcinoma. World J Gastroenterol 2011; 17: 4563-71.

Journal of the Pakistan Medical Association has agreed to receive and publish manuscripts in accordance with the principles of the following committees: