|Year : 2017 | Volume
| Issue : 1 | Page : 43-47
Epidemiology and clinical features of patients with hepatocellular carcinoma at a tertiary hospital in Jeddah
YA Qari, MH Mosli
Department of Medicine, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
|Date of Acceptance||28-Feb-2016|
|Date of Web Publication||12-Dec-2016|
Dr. Y A Qari
King Abdulaziz University, P. O. Box 80215, Jeddah 21589
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: This study describes the epidemiology and clinical features of hepatocellular carcinoma (HCC), and it investigates any association between Child-Pugh's classification and HCC.
Materials and Methods: A retrospective chart review was performed for HCC cases diagnosed between 2008 and 2014 at King Abdulaziz University Hospital. We documented the age at cancer diagnosis, gender, occupation, ethnic origin, HCC etiology, Child-Pugh scores, tumor characteristics, alpha-fetoprotein (AFP), and alkaline phosphatase (ALP) levels at diagnosis, and treatment administered. The Chi-square test was used to determine differences between categorical variables.
Results: We included 128 patients. Hepatitis B and C viral infections were documented in 24.2% and 33.6% of the patients, respectively. Patients with tumors >5 cm were more likely to have Child's Class C disease, whereas those with tumors ≤2 cm were more likely to have Child's Class A (P < 0.001). Similarly, patients with bilobular or metastatic tumors were more likely to have Child's Class C disease (P = 0.001 and 0.002, respectively). No difference in Child-Pugh score was found between patients with single or multiple tumors (P = 0.480). Furthermore, patients who were both hepatitis B and C positive were more likely to have Child's Class C disease (P = 0.018). Likewise, those who had abnormal AFP and ALP levels ≥1000 ng/mL were more likely to have Child-Pugh's Class C liver disease (P = 0.021 in both cases).
Conclusion: Hepatitis C and B infections were the main risk factors associated with HCC.
Keywords: Child-Pugh criteria, cirrhosis, epidemiology, hepatitis, hepatocellular carcinoma
|How to cite this article:|
Qari Y A, Mosli M H. Epidemiology and clinical features of patients with hepatocellular carcinoma at a tertiary hospital in Jeddah. Niger J Clin Pract 2017;20:43-7
|How to cite this URL:|
Qari Y A, Mosli M H. Epidemiology and clinical features of patients with hepatocellular carcinoma at a tertiary hospital in Jeddah. Niger J Clin Pract [serial online] 2017 [cited 2020 Mar 29];20:43-7. Available from: http://www.njcponline.com/text.asp?2017/20/1/43/180062
| Introduction|| |
Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is the third highest cause of cancer deaths worldwide. It is the fifth most common type of cancer in men and the seventh in women. A recent report indicates a sharp increase in the incidence of HCC over the last decade in Gulf countries. The sudden increase in HCC is attributed to a rise in the incidence of infection from the hepatitis C virus (HCV), escalating obesity, and an increase of diabetes mellitus cases.
In Saudi Arabia (SA), liver cancer is unevenly distributed among gender and age. The uneven distribution is evidenced by the fact that men have approximately 3 times the risk of developing liver cancer compared to women. The risk of a patient developing HCC also increases with age. According to a previous hospital-based study, approximately 80% of primary liver cancer cases seen in SA are the result of underlying chronic hepatitis B and C viral infections. Recent findings have demonstrated a decrease in the overall prevalence of viral hepatitis; however, the substantial population of infected patients is at high risk of developing HCC. Furthermore, another study reported that the incidence of HCC is expected to rise dramatically in SA in the next three decades.
A small number of hospital-based studies conducted in SA have assessed the clinical and epidemiologic characteristics of patients with HCC.,, According to multiple sources, HCC has a higher incidence in men., Most patients present to the hospital with comorbid diagnoses of advanced cancer and chronic liver disease. This study describes the epidemiologic and clinical features of HCC as well as investigates any association between Child-Pugh's classification and HCC.
| Materials and Methods|| |
This was a retrospective chart review of the electronic medical records of cancer cases diagnosed between 2008 and 2014 at King Abdulaziz University Hospital (KAUH), a tertiary hospital in Jeddah, Western Province, with a bed capacity of 845 beds and serves the main population of Jeddah.
Adult patients were included by utilizing criteria for HCC from the International Classification for Disease, 10th edition. All types of secondary liver cancer were excluded from analysis. The procedures followed were in accordance with the ethical standards of the Biomedical Ethics Committee of KAUH and the Helsinki Declaration of 1975. Permission to conduct this study was granted by the Biomedical Ethics Committee of KAUH (reference number, 57–15 year, 2015).
After identifying the cases that fulfilled the inclusion criteria, we then collected demographic and clinical data such as the patient's age at the time of HCC diagnosis, gender, occupation, ethnic origin, history of alcohol consumption, etiology of liver disease, and the Child-Pugh score. Other pertinent information gathered involved data on tumor characteristics (distribution, size, stage, and the presence of cirrhosis), alpha-fetoprotein (AFP), and alkaline phosphatase (ALP) levels at diagnosis, as well as treatment administered.
The data were entered and analyzed using the Statistical Package for the Social Sciences (SPSS Inc., Chicago, IL, USA), version 16. Descriptive statistics were performed for all variables. The Chi-square test was used to determine differences between categorical variables. Differences were considered statistically significant at the 0.05 level. Results are expressed as frequency (percent).
| Results|| |
We included 128 patients. Men comprised approximately three-quarters of the sample [Table 1]. Most patients were of a low socioeconomic status; nonsaudis accounted for two-thirds of the sample. Less than 5% of the sample had a documented history of alcohol consumption. Abdominal pain was the chief complaint in 18.8% of the patients. In 68.0% of the cases, patients presented with multiple complaints.
AFP levels were normal in 25.0% of the sample, whereas 40.6% had AFP levels ≥1000 ng/mL. Cirrhosis was diagnosed in 60.2% of the patients, and approximately two-fifths had Child's Class B disease [Table 2]; a smaller proportion had Child's Class A (22.7%) or Class C cirrhosis (35.2%). Palliation was offered to 68.0% of the patients while 14.1% underwent multiple therapies. Less than 2% of the patients survived to 5 years. Disease duration ranged from ≤3 months to >5 years, with 29.7% of the patients having a duration of ≤3 months.
The most common risk factors included HBV and HCV infections, documented in 24.2% and 33.6% of the patients, respectively. More than half of the patients (60.2%) had multiple liver tumors, and approximately 50.8% of the cases had tumors >5 cm in diameter. Patients with unilobular lesions comprised about two-fifths of the sample [Table 3]. Metastatic disease was documented in 44.6% of the patients; 28.1% and 27.3% had localized and locoregional disease, respectively.
|Table 3: Etiology of liver cancer and tumor characteristics among the patients|
Click here to view
Patients with tumors >5 cm were more likely to have Child's Class C disease, whereas those with tumors ≤2 cm were more likely to have Child's Class A [P < 0.001; [Table 4]. Similarly, patients with bilobular or metastatic tumors were more likely to have Child's Class C disease (P = 0.001 and 0.002, respectively). No difference in Child-Pugh score was found between patients with single or multiple tumors (P = 0.480).
[Table 5] shows that patients who were both HBV and HCV positive were more likely to have Child's Class C disease (P = 0.018). Likewise, those who had abnormal ALP levels, and AFP levels ≥ 1000 ng/mL were more likely to have Child-Pugh's Class C liver disease (P = 0.021 in both cases).
| Discussion|| |
The present work is a 7-year analysis of HCC cases at KAUH. Our analysis revealed that HCV and HBV infection were the most common risk factors, similar to another report that investigated the presentation of HCC at our institution. In patients with HCC, it is thought that carcinogenesis results from chronic hepatitis and cirrhosis caused by HBV and HCV. Unlike HBV, HCV is a single-stranded RNA virus that does not integrate into the genome of the host. There is currently no evidence to substantiate that HCV has oncogenic properties; however, HCC has been reported in rare cases of noncirrhotic HCV infection, implying that a direct oncogenic effect cannot be totally excluded. Interestingly, about one-third of the patients in our study developed HCC in the absence of any clinical evidence of cirrhosis. While other etiologic factors may be responsible for HCC in our patients, we believe that further investigations may be necessary to explain the occurrence of HCC among noncirrhotic patients.
According to a previous study conducted at KAUH, HCV-associated cirrhosis was the most frequent cause of HCC, followed by HBV-associated cirrhosis. Similar findings have been reported in other hospital-based studies conducted in SA,, contrary to the fact that HBV-associated disease was previously reported as the predominant cause of HCC in SA. The decrease in HBV-associated HCC has been linked to the Saudi Ministry of Health's implementation of HBV vaccination programs approximately three decades ago.
As previously stated, men comprised nearly three-quarters of our sample. This finding coincides with the report of other authors , who found that HCC showed a strong affinity for male gender, being 4 times more common in men as compared to women. While this finding may, in part, be due to the cumulative result of other associated factors (the higher incidence of cirrhosis and higher frequency of smoking and alcohol intake in men), experimental models , suggested that sex hormones and/or hormone receptors may be responsible.
Less than 5% of our patients reported a history of alcohol consumption. Other studies conducted among HCC patients in SA ,, did not mention the role of alcohol as a potential risk factor for liver disease. Relevant to the fact that importation and distribution of alcohol are banned in SA, alcohol consumption is not currently deemed a public health problem. Chronic alcohol abuse often complicates HCC, and there is evidence that alcohol may have a cocarcinogenic role in the presence of other agents such as tobacco, HBV, HCV, and hepatotoxins.
Cirrhosis, the most common condition associated with HCC, was diagnosed in over half of the patients in the current study. Approximately two-fifths had Child's Class B disease, a smaller proportion had Child's Class A (22.7%) or Class C disease (35.2%). Furthermore, patients with tumors >5 cm were more likely to have Child's Class C disease, whereas those with tumors ≤2 cm were more likely to have Child's Class A. Previous reports , state that the relationship between tumor size and Child-Pugh classification varies, and staging systems incorporate tumor size and Child-Pugh classification to link stage with prognosis or a treatment algorithm. The Cancer of the Liver Italian Program Criteria, for example, incorporate the Child-Pugh criteria with tumor characteristics: The features of the tumor, whether unifocal, multifocal, or diffuse, whether there is vascular involvement or elevated AFP levels.
In the current report, HBV and HCV positive patients were more likely to have Child's Class C disease, a finding that we believe is related to the natural history and cytopathogenic effect of the hepatitis viruses on hepatocytes. We also cannot exclude the fact that patients with viral hepatitis typically present to our institution late in the disease process. Most are asymptomatic, and sometimes the infection is detected incidentally during screening or blood donation. We also determined that patients with abnormal ALP and AFP levels ≥1000 ng/mL were more likely to have Child-Pugh's Class C liver disease. Previous investigations ,, of patients with HCC demonstrated that preoperative serum ALP and AFP levels predicted their outcome. While the role of AFP as a diagnostic and prognostic factor is controversial, some researchers reported that it can be nonspecifically high in patients with cirrhosis and viral hepatitis. As a result, AFP levels can vary in patients with HCC based on the etiology of underlying hepatic disease.
This retrospective analysis has all the limitations inherent in retrospective studies. We did not control for confounding factors such as age, family history, alcohol consumption, smoking, and exposure to hepatotoxins, which have been reported as risk factors for HCC. Due to insufficient data regarding risk factors and lifestyle, it may be beneficial to conduct a cross-sectional study to explore clinical and epidemiological features of HCC at our institution.
| Conclusion|| |
Hepatitis C and B viral infections are the main risk factors associated with HCC among our patients. A large amount of information has been accumulated on the clinical and epidemiological aspects of HBV and HCV infections in our context, but more research should be conducted to explore risk and prognostic factors among patients with HCC. Our finding of a relevant association between Child-Pugh score and HCC further supports the fact that a system incorporating the Child-Pugh's criteria can be useful in staging HCC.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. GLOBOCAN 2008 v2.0. Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 10; 2010. Available from: http://www.globocan.iarc.fr
. [Last cited on 2015 Jun 25].
International Agency for Research on Cancer. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. Available from: http://www.globocan.iarc.fr/
. [Last cited on 2015 Jan 26].
Poustchi H, Sepanlou S, Esmaili S, Mehrabi N, Ansarymoghadam A. Hepatocellular carcinoma in the world and the middle East. Middle East J Dig Dis 2010;2:31-41.
Alswat KA, Sanai FM, Altuwaijri M, Albenmousa A, Almadi M, Al-Hamoudi WK, et al.
Clinical characteristics of patients with hepatocellular carcinoma in a middle eastern population. Hepat Mon 2013;13:e7612.
Memish ZA, Knawy BA, El-Saed A. Incidence trends of viral hepatitis A, B, and C seropositivity over eight years of surveillance in Saudi Arabia. Int J Infect Dis 2010;14:e115-20.
Abdo AA, Al Abdul Karim H, Al Fuhaid T, Sanai FM, Kabbani M, Al Jumah AR, et al.
Saudi gastroenterology association guidelines for the diagnosis and management of hepatocellular carcinoma: Summary of recommendations. Saudi J Gastroenterol 2007;13:45-8.
Alsohaibani F, Porter G, Al-Ashgar H, Walsh M, Berry R, Molinari M, et al.
Comparison of cancer care for hepatocellular carcinoma at two tertiary-care referral centers from high and low endemic regions for viral hepatitis. J Gastrointest Cancer 2011;42:228-35.
Alkhayyat S, Fallatah HI, Akbar HO, Al Ahwal MS, Al Ghamdi WS. Causes and stages of hepatocellular carcinoma at patient presentation at a tertiary medical center in Western Saudi Arabia. J Cancer Ther 2014;5:1303-10.
Leong TY, Leong AS. Epidemiology and carcinogenesis of hepatocellular carcinoma. HPB (Oxford) 2005;7:5-15.
Lemon SM, McGivern DR. Is hepatitis C virus carcinogenic? Gastroenterology 2012;142:1274-8.
Ayoola EA, Gadour MO. Hepatocellular carcinoma in Saudi Arabia: Role of hepatitis B and C infection. J Gastroenterol Hepatol 2004;19:665-9.
Alfaleh F, Alshehri S, Alansari S, Aljeffri M, Almazrou Y, Shaffi A, et al.
Long-term protection of hepatitis B vaccine 18 years after vaccination. J Infect 2008;57:404-9.
Xiao W, Zhang Q, Habermacher G, Yang X, Zhang AY, Cai X, et al.
U19/Eaf2 knockout causes lung adenocarcinoma, B-cell lymphoma, hepatocellular carcinoma and prostatic intraepithelial neoplasia. Oncogene 2008;27:1536-44.
Granata OM, Cocciadifero L, Campisi I, Miceli V, Montalto G, Polito LM, et al.
Androgen metabolism and biotransformation in nontumoral and malignant human liver tissues and cells. J Steroid Biochem Mol Biol 2009;113:290-5.
Abu-Hilal M, Primrose JN, Casaril A, McPhail MJ, Pearce NW, Nicoli N. Surgical resection versus radiofrequency ablation in the treatment of small unifocal hepatocellular carcinoma. J Gastrointest Surg 2008;12:1521-6.
Dhanasekaran R, Limaye A, Cabrera R. Hepatocellular carcinoma: Current trends in worldwide epidemiology, risk factors, diagnosis, and therapeutics. Hepat Med 2012;4:19-37.
Levy I, Sherman M; Liver Cancer Study Group of the University of Toronto. Staging of hepatocellular carcinoma: Assessment of the CLIP, Okuda, and Child-Pugh staging systems in a cohort of 257 patients in Toronto. Gut 2002;50:881-5.
Liang X, Liu Y, Zhang Q, Gao L, Han L, Ma C, et al.
Hepatitis B virus sensitizes hepatocytes to TRAIL-induced apoptosis through Bax. J Immunol 2007;178:503-10.
Akbar HO, Al Ghamdi A, Qattan F, Fallatah HI, Al Rumani M. Chronic hepatitis C in Saudi Arabia: Three years local experience in a university hospital. Hepat Mon 2012;12:e6178.
Chen CH, Hu FC, Huang GT, Lee PH, Tsang YM, Cheng AL, et al.
Applicability of staging systems for patients with hepatocellular carcinoma is dependent on treatment method – Analysis of 2010 Taiwanese patients. Eur J Cancer 2009;45:1630-9.
Tong MJ, Chavalitdhamrong D, Lu DS, Raman SS, Gomes A, Duffy JP, et al.
Survival in Asian Americans after treatments for hepatocellular carcinoma: A seven-year experience at UCLA. J Clin Gastroenterol 2010;44:e63-70.
Kim JM, Kwon CH, Joh JW, Park JB, Ko JS, Lee JH, et al.
The effect of alkaline phosphatase and intrahepatic metastases in large hepatocellular carcinoma. World J Surg Oncol 2013;11:40.
Farinati F, Marino D, De Giorgio M, Baldan A, Cantarini M, Cursaro C, et al.
Diagnostic and prognostic role of alpha-fetoprotein in hepatocellular carcinoma: Both or neither? Am J Gastroenterol 2006;101:524-32.
Kim HS, Park JW, Jang JS, Kim HJ, Shin WG, Kim KH, et al.
Prognostic values of alpha-fetoprotein and protein induced by Vitamin K absence or antagonist-II in hepatitis B virus-related hepatocellular carcinoma: A prospective study. J Clin Gastroenterol 2009;43:482-8.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
|This article has been cited by|
||MiR-342 regulates cell proliferation and apoptosis in hepatocellular carcinoma through Wnt/ß-catenin signaling pathway
| ||Chang Lu,Shengnan Jia,Shutao Zhao,Xue Shao |
| ||Cancer Biomarkers. 2019; : 1 |
|[Pubmed] | [DOI]|
||Hepatitis viruses take advantage of traditional practices to increase the burden of hepatocellular carcinoma in Tunisia
| ||Ines Dhifallah,Marwa Khedhiri,Anissa Chouikha,Ghassen Kharroubi,Walid Hammami,Amel Sadraoui,Mohamed Msaddek Azzouz,Nadia Maamouri,Tahar Khalfallah,Henda Triki,Pascal Pineau,Olfa Bahri |
| ||Archives of Virology. 2019; |
|[Pubmed] | [DOI]|
||Liver Cancer Mortality at National and Provincial Levels in Iran Between 1990 and 2015: A Meta Regression Analysis
| ||Negar Rezaei,Farshad Farzad Far,Sara Khademiureh,Ali Sheidaei,Kimiya Gohari,Farnaz Delavari,Mahboubeh Parsaeian,Alireza Delavari,Mahtab Maghsoudlu,Hamid Mohaghegh Shalmani,Zahra Madadi,Anita Mansouri,Moein Yoosefi,Mohsen Asadi-Lari |
| ||Hepatitis Monthly. 2018; In Press(In Press) |
|[Pubmed] | [DOI]|
||In vivo and in vitro effects of microRNA-221 on hepatocellular carcinoma development and progression through the JAK-STAT3 signaling pathway by targeting SOCS3
| ||Shan Huang,Da Zhou,Yu-Xuan Li,Zhi-Yong Ming,Ke-Zhi Li,Guo-Bin Wu,Chuang Chen,Yin-Nong Zhao |
| ||Journal of Cellular Physiology. 2018; |
|[Pubmed] | [DOI]|