Hepatocellular carcinoma (HCC) is the 5^th most common cancer among males and the 7^th most common cancer among females, with 748,300 new HCC cases diagnosed globally each year [1] . HCC is also the second most common cause of cancer-related deaths among males and the seventh among females, with 695,900 liver cancer deaths every year, particularly in areas with chronic viral hepatitis B and C [1] - [3] . Chronic hepatitis B (CHB) infection in Saudi Arabia has been highly prevalent in the past, as reflected in the previously high rates of hepatitis B virus (HBV)-associated HCC [4] - [6] . However, the implementation of effective neonatal and early childhood HBV vaccination programs for HBV has resulted in a significant decline in the prevalence of HBV among Saudi populations [4] [7] [8] . This implementation is expected to result in a significant drop in HBV-related HCC cases in Saud Arabia. Similarly, chronic hepatitis C (CHC)-related liver cirrhosis and HCC are also frequently reported in Saudi Arabia [9] - [11] . The presentation of HCC can be variable, ranging from small focal liver lesions that could be detected during routine radiological screenings of cirrhotic patients to advanced disease with severe local invasion or even distant metastasis [3] [12] [13] . Several scoring systems have been proposed for the staging of HCC [14] - [16] . Among the major international liver associations, the most widely accepted systems are the Barcelona clinic liver cancer (BCLC) criteria and the Milan criteria [14] [15] . Early HCC detection, and hence early treatment interventions, will reduce HCC-related mortality and morbidity [14] - [16] . Several studies have evaluated the possible predictive factors that are associated with advanced HCC versus less advanced HCC, for which treatment intervention can be offered [14] [15] [17] and [18] . In the present study, we retrospectively analyzed the clinical data and outcomes of HCC patients at King Abdul Aziz University Hospital Jeddah from 2008 to 2012.

A total of 57 patients were diagnosed with HCC during the study period; 3 patients were excluded based on the exclusion criteria. Of the remaining 54 patients, 44 (81.5%) were males. The mean age was 64.54 years (SD, 11.2 years; range, 31 - 86 years). Most of the patients were Saudis, followed by Egyptians and Yemenis; the remaining 19 patients comprised 11 other nationalities. Table 1 shows the demographic data for the patients included in the study. The female patients were older compared to the male patients (66% and 64.2%, respectively; P = 0.12), but the difference was not statistically significant.

Underlying causes of liver cirrhosis:

Chronic hepatitis C virus was the most common cause of liver cirrhosis, followed by hepatitis B virus (Table 2).

Our study showed that most of our HCC patients are males with advanced disease at presentation. This finding is similar to the published data on HCC from other regions in Saudi Arabia and the data from the Saudi Cancer Registry [5] [6] [9] [19] . In contrast, the data differ from more recently published international data [3] [12] [13] [17] .

During the last 3 years of the study, the patients were diagnosed at earlier stages because the cirrhotic patients were followed regularly and because HCC was detected earlier [3] [17] . The reason for presentation with advanced disease might be that many patients with chronic viral hepatitis are not diagnosed earlier because they are asymptomatic, and their fist presentation is with advanced HCC [9] .

In our cohort, HCV-associated cirrhosis was the most frequent cause for HCC, followed by HBV-related cirrhosis. This result is similar to the recent findings of Al Sohaibani et al. in 2011 and Al Sawat et al. in 2013 [9] [20] . However, this differs from previously reported HCC data in Saudi Arabia from 1990 to 2004, which showed that HBV-associated liver disease was the predominant cause of HCC in KSA [19] [21] [22] . This recent drop in CHB as a cause for HCC and liver disease is related to the implementation of the HBV vaccination neonatal program in the country approximately 25 years ago [7] [8] . This finding aligns with several previously reported international data [3] [12] [23] .

CT or MRI was needed to confirm the diagnosis in approximately 80% of the patients, which indicates that abdominal ultrasound was inefficient in the radiological confirmation of HCC; previous data have shown similar findings [3] [24] . A poor ultrasound detection rate partially reflects the limitation of US as a highly operator- dependent exam [3] . Despite the limitations of US in the radiological diagnosis of HCC, international guidelines, even the most recent ones, still recommend US to screen cirrhotic patients [3] [17] [18] [23] because the use of CT and MRI as HCC screening methods has not been validated [3] [24] . However, contrast-related complications are another factor limiting CT and MRI as screening tests [3] . Although CT and MRI demonstrate great accuracy in diagnosing HCC, liver biopsy is still needed to diagnose some patients with HCC measuring < 2 cm [25] . In our cohort, liver biopsy was used only in 2 patients to confirm the diagnosis.

Many of the patients who presented with advanced disease were previously undiagnosed cirrhotic patients [9] . Furthermore, no local studies have confirmed the efficiency of HCC screening in cirrhotic patients or indicated the need for such data in this field [25] [26] .

In our cohort, a lower plat was the only associated factor in advance versus non-advanced HCC. Many previous reports have confirmed the association between thrombocytopenia and HCC [27] . For example, it has been suggested that thrombocytopenia in a cirrhotic patient is more commonly associated with the development of HCC compared to non-thrombocytopenic, cirrhotic patients [18] - [20] [27] . Furthermore, patients with thrombocytopenia are more likely to have advanced hepatocellular carcinoma [28] . Other studies have included prolonged PT and elevated bilirubin. The use of non-invasive biomarkers in the diagnosis of HCC has also been evaluated [9] [21] [22] [29] .

Molecular targeted therapy was effective in prolonging the survival of HCC patients, and [3] [17] [30] sorafenib was the most extensively studied medication [30] . Sorafenib alone was effective in 2 of our advanced HCC patients which had helped to delay the disease progression to disability and death for more than 18 months. New antiangiogenic medications are currently being evaluated as monotherapy or in combination with RFA [3] [17] [30] .

RFA was successful in the 20 patients who underwent procedure, and it was effective in controlling the disease progression for 6 - 18 months. The international data on the use of RFA in treating HCC are promising. With early detection, many patients are achieving a cure and excellent long-term survival rates, up to 10 years in some studies [3] [31] . We were unable to locate published data on the use of RFA in Saudi Arabia. Early detection and liver transplantation are the best long-term treatment options for HCC patients [3] [11] [17] [32] . In our cohort, the liver transplantation patient had an excellent long-term outcome.

Approximately 65% of our HCC patients had diabetes. This high rate might be related to several variables. For instance, most of the patients had CHC- and CHB-related liver cirrhosis, and the association between chronic viral hepatitis and diabetes has been frequently reported in previous studies [33] . Another explanation is the high prevalence of diabetes with increasing age in Saudi Arabia. The prevalence of diabetes has been reported to be as high as 30% in some studies, and it has been shown that diabetic HCC patients were older compared to non-diabetics [34] . A third possible reason for this phenomenon is a true association between HCC and diabetes, as shown in similar data [35] . Interestingly, the evidence had shown that this risk is lower in patients with diabetes controlled with thiazolidinedione compared to metformin [1] .

A mean 6-month survival rate in our re-study indicates that approximately two-thirds of our patients had advanced disease at the time of diagnosis. Similar survival rates have been reported for advanced HCC locally and internationally [9] [36] [37] . However, some patients in our cohort had a longer survival of up to 2 - 3 years; these patients underwent screening, and their diseases were diagnosed and treated early. Similar long-term survival data in cases of early detection have been shown in several studies [38] [39] , which emphasizes the importance of diagnosing CLD patients in Saudi Arabia and screening high risk groups to detect early stage HCC.

Our study is limited by being retrospective and by its small sample size.

In conclusion, our study showed that most of our HCC patients had advanced disease at presentation, which precluded or limited the treatment options. We recommend effective surveillance programs for cirrhotic and CHB patients in Saudi Arabia to improve the outcome for HCC patients.