Hepatocellular carcinoma (HCC) is one of the most common cancers in the world and is particularly prevalent in Egypt. There are an estimated 500 000 or more new cases diagnosed each year worldwide 1. About 80% of cases occur in eastern Asia and Africa 2. Most HCCs develop in patients with underlying chronic liver disease. Chronic viral hepatitis B and C are the major causes of liver cirrhosis and HCC 3.
Two-thirds of all cirrhotic patients with a viral background have been found to have hepatitis B viral (HBV) infections in Asian countries, whereas the remaining third has hepatitis C viral (HCV) infection as a cause 4. In the USA, western countries, or Japan, however, HCV infection plays a major role in the high prevalence of nonalcoholic fatty liver disease 4–6.
The prevalence of hepatitis C in Egypt was estimated to be around 14% in the general population. The increasing prevalence of HCV is associated with an increasing trend in HCCs 7. Although no firm data are available, deaths because of HCC in Egypt appear to have increased over the last decade 8.
Aim of the study
To identify the prevalence of viral hepatitis in Egyptian patients with HCC.
Patients and methods
Data of Egyptian patients diagnosed with primary HCC in the period from January 2007 to December 2009 were retrospectively collected and analyzed. The study included five Egyptian centers for treatment of liver disease: Nasser Institute, Hepatology Institute of Cairo, Sixth of October University, El-Menofia National Liver Institute, and Zakazik University Hospital. In all these centers, the following data were extracted from patients’ files after approval from the centers’ managers and ethical committees:
- Data for the diagnosis of liver disease and the presence or absence of cirrhosis: clinical data (especially the presence of spider nevi, palmar erythema, hepatic encephalopathy, ascites, attacks of gastrointestinal bleeding, spontaneous bacterial peritonitis), complete blood count, liver profile (mainly total and direct bilirubin, serum transaminases, albumin), prothrombin concentration and international normalized ratio, abdominal ultrasound, liver biopsy, and reports of upper gastrointestinal endoscopy.
- Data for the diagnosis of etiology of liver disease included HBsAg, HBcAb, and HCVAb total for the diagnosis of viral hepatitis. HCV RNA and HBV DNA measurements were used to exclude viral infection in all patients with negative enzyme-linked immunosorbent assay tests, and results of autoimmune markers, ceruloplasmin, serum cupper, 24 h urinary cupper, iron profile, lipid profile, and liver biopsy for nonviral causes of liver disease. Evidence of Bilharziasis was reported (history, antibelharzial antibodies, or ova in rectal snip).
- Data for the diagnosis of HCC: the diagnosis of HCC was made on the basis of the presence of arterial enhancement of focal or multifocal hepatic lesions in triphasic abdominal computed tomography in addition to elevated α feto protein level or liver biopsy from the focal lesion(s) in cases with normal α feto protein.
The data collected were analyzed and patients were divided into a group without liver cirrhosis and a group with cirrhosis. The latter was further classified according to the Child–Pugh classification to class A, B, or C.
The total number of primary HCC cases diagnosed in that period was 2000 cases. The final number of cases included in the study after excluding incomplete files was 1127 cases.
Data were analyzed using the SPSS program version 15 (SPSS Inc., Chicago, Illinois, USA). Quantitative data were presented as mean and SD, and in the case of the presence of extreme values, the median and range were used. Qualitative data were compared using frequency and percentage.
Demography and clinical characteristics
The study included analysis of 1127 Egyptian patients with HCC diagnosed in the period from January 2007 through December 2009. Table 1 summarizes the demographic and clinical findings of all patients. The study population included 885 (78.53%) men and 242 (21.47%) women. The male : female ratio was 3.6 : 1. The age of the patients enrolled ranged from 30 to 76 years, mean age 54±8.6 years.
Most of the patients (91.75%) enrolled had different degrees of liver cirrhosis (as diagnosed by their clinical, laboratory, and radiological findings). On the basis of the Child–Pugh classification for liver cirrhosis, 160 patients (15.47%) were Child class A, 309 patients (29.88%) were Child class B, and the majority, 565 patients (54.65%), were Child class C. Evidence of bilharziasis (history of infection or treatment by tarter emetics or praziquantil, positive antibilharzial Abs, or schistozoma ova in rectal snip) was present in about 40% of all HCC cases.
Prevalence of viral hepatitis and its relation to the presence of cirrhosis
The primary liver disease in the study population is presented in (Table 2). The prevalence of viral hepatitis among all cases was 81.5%. Among all the patients included, HCV infection was present in 67.7%, HBV in 8.8%, and coinfection of both viruses was present in 4.8% of cases. The remaining 18.4% had liver disease secondary to other causes. Almost all patients with HCV had evidence of cirrhosis at the time of HCC diagnosis (760 out of 764 patients). In patients with HBV or coinfection of both viruses, HCC developed in cirrhotic (68+40 cases) and noncirrhotic livers (32+15 cases) (Table 2).
Tumor size and number
The average tumor size (Table 3) was 4.6±2.48 cm. Tumors were less than 2 cm in 13% of cases. Tumor size ranged from 2 to 5 cm in 44.8% of patients whereas it was greater than 5 cm in 42%. Single lesions were present in 569 patients (50.49%), two lesions in 202 patients (17.93%), and multiple tumors were present in 356 patients (31.58%).
HCC is a major public health problem worldwide. Advancements in diagnostic modalities and the increasing incidence of chronic viral hepatitis and nonalcoholic fatty liver disease, both of which are well-known risk factors for HCC, have led to the increasing incidence of HCC in developed countries 9. It is documented that the prevalence of this cancer in some parts of the Middle East is also increasing 9. Egypt is one of the nations with the highest incidence of HCC worldwide. The incidence of HCC has increased markedly in Egypt in the last decade 10. The national cancer institute pathology registry indicated that cancer liver formed 11.75% of digestive organ malignancy and 1.68% of total malignancy; about 70% of liver tumors were HCC 11.
It was important to address the current status of HCC in Egypt. In order to achieve this, we designed a retrospective multicenter study to identify the prevalence of viral hepatitis, tumor characteristics, treatment, and survival of Egyptian patients with HCC. Many patients had incomplete records and follow-up data. In addition, baseline medical data were nonuniformly recorded in different centers. This led us to exclude 873 out of a total of 2000 cases found. The treatment outcome and survival were not assessed because of incomplete follow-up data. Finally, the study included 1127 patients with primary HCC. The mean age of the patients was 54±8.6 years. The male : female ratio was 3.6 : 1. It is well known that HCC is more frequent in men than women 12, which may be because of differences in exposure to risk factors as well as the different effects of sex hormones and other X-linked genetic factors. Yang and colleagues 3,4,13,14 found HCC to be more frequent in individuals of an average age of about 64 years. The fact that we found HCC occurring at a younger age in Egypt can be attributed to early exposure to risk factors and the endemicity of HCV infection. In addition, other contributing environmental factors may play a role in liver injury in Egypt such as bilharziasis, which was present in about 40% of cases, the presence of aflatoxin in many food stuff, and contamination with insecticides 7,8.
Interestingly, 91.75% of patients diagnosed with HCC had liver cirrhosis. The degree of cirrhosis was variable and most cirrhotic patients (54.65%) were Child C cirrhosis. HCC occurred least frequently in patients with Child A liver cirrhosis (15.4%); 29.8% of the patients were Child B. The risk of development of HCC in relation to the degree of cirrhosis according to the Child–Pugh Class has not been well described in published reports. However, many authors agreed that cirrhosis is the primary risk factor for the development of HCC as it is present in 80–90% of HCC cases, but it can still occur in noncirrhotic livers 4,15–17. The majority of our patients (81.5%) had viral hepatitis; this finding explains the high incidence of liver cirrhosis in our patients.
The major factors increasing the risk of HCC are chronic hepatitis B and C as well as cirrhosis, irrespective of its etiology 18,19. In North America, Europe, and other areas of low prevalence, most patients have underlying cirrhosis unrelated to HBV or HCV infection 4. In our study, the major risk factor for cirrhosis and the subsequent development of HCC is chronic hepatitis C (67.7%) and to a lesser extent chronic hepatitis B (8.8%) and coinfection with both viruses (4.8%). Moreover, almost all cases of HCV had liver cirrhosis when HCC was diagnosed (760 out of 764). However, many patients who had HBV infection developed HCC in noncirrhotic livers: 32 of 100 cases in patients with HBV and 15 of 55 cases in patients with coinfection of both viruses. This can be explained by the fact that HBV is an oncogenic virus 20–22.
It seems that the etiological contribution of viral hepatitis toward the risk of HCC differs in different countries according to the prevalence of viral infection and other causes of liver cirrhosis. Zhang et al.23 found that chronic HBV infection is the major factor for the development of HCC in China. In Indian patients, infection with either HBV or HCV was the major risk factor 16. In Spain, Gómez Rodríguez et al.12 found that HCV was the leading cause of liver disease.
Shire et al.24 studied a sample of Somali immigrants to Minnesota who had HCC. They found that both HBV and HCV occurred frequently in this sample of immigrants; however, HCV was the major risk factor for HCC. Recently, cirrhosis because of viral causes has been identified as the main risk factor for HCC even in highly industrialized countries such as the USA 25.
In our study, 13.13% of the tumors were less than 2 cm in size and 44.87% were 2–5 cm in size. In addition, 50.49% of the tumors were single lesions. This finding is particularly interesting because it means that in Egypt, an early diagnosis was made in more than half of the cases and it reflects the awareness and implementation of surveillance programs in different centers for the early detection and management of HCC in high-risk patients. The availability of advanced imaging techniques and the ongoing training of medical personnel for interventional treatment makes it a possible goal to improve the early detection and survival of patients with HCC. As the majority of HCC occurs in the setting of cirrhosis, the implementation of the national program for the treatment of hepatitis C and hepatitis B, which was launched in the last few years, should prevent the development of cirrhosis and translate the goal of HCC prevention into reality in the future.
Conflicts of interest
There are no conflicts of interest.
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