Clinical features and survival of patients with hepatocellular carcinoma at a cancer treatment facility

Use your smartphone to scan this QR code and download this article ABSTRACT Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths. This study aimed to determine the survival of patients with HCC at our treatment facility. Methods: We retrospectively studied 278 patients with HCC who were seen between 2007 and 2013. Of these patients, 84.4% had evidence of prior infection with hepatitis C, while 7.8% hadmarkers of hepatitis B infection. Results: Median survival was 24.6 months for transarterial chemoembolization (TACE), 61months for ablative therapies, and 31.5 months for those undergoing surgical resection. Increasing tumor size, multifocality, advanced Barcelona clinic liver cancer (BCLC) stage, and poor liver function (Child-Pugh class B-C) were significantly associated with worse prognosis; pvalues were 0.002, 0.009, <0.001, and <0.001, respectively. Conclusion: Most patients in our series presented with advanced liver disease, with multifocal tumors and were candidates for palliative treatment only. Public education tominimize hepatitis B andC transmission, screening programs to detect disease at an earlier stage, and the development of specialist liver units and liver transplant programs can bring a change in HCC survival in developing countries.


INTRODUCTION
Hepatocellular carcinoma (HCC) is common, and although it affects different regions of the world disproportionately, worldwide it remains the seventh most frequent cancer and the third most common cause of cancer-related deaths, causing approximately 600,000 deaths annually [1][2][3] . Its incidence has almost doubled in Western countries in the past 20 years, primarily due to an increase in alcohol and hepatitis C-related liver cirrhosis 4,5 . However, more than 80% of cases occur in the developing world and in areas with a high prevalence of hepatitis B and C, such as China, southeast Asia, and Sub-Saharan Africa, where its incidence is as high as >20/100,000 1,3,6 . With universal screening of high risk populations, early detection and treatment, the five-year survival rate of those with HCC can be as high as 70%, after ablation, resection or liver transplant. Patients in whom HCC is detected by surveillance have a three-year survival rate of 50.8%, compared to 28.2% in those not on a surveillance program. This difference in survival is largely due to detection at an earlier stage, with better resultant treatment options 7 .
In intermediate stage HCC, the two-year survival rate is 49%, while median survival is 16 months; in advanced stage HCC, the one-year survival is 11% with a median survival of 3-4 months 8,9 . All patients were discussed, and treatment decisions were made in multidisciplinary team meetings, which were attended by gastroenterologists/hepatologists, pathologists, surgeons with interest in liver surgery, radiologists and medical oncologists. During the period of the study, no liver transplant program existed in Pakistan, and so those who could afford to travel overseas for this procedure did so. Recently, a liver transplant facility has been established in the private sector. All other patients, including those for whom liver transplant was recommended but was not possible for financial reasons, were treated at our institution.

Statistical analysis
Cumulative survival analysis was calculated using the Kaplan-Meier method.  (Figure 2). Overall, there was a significant difference in survival by tumor size (Chi-sq.=12.61, df=2, p=0.002). Sub-group analysis showed a significant  Overall survival 23.9  (Figure 3). Table 2 shows the Chi-square values and p-values for the dif-ferences mentioned above. Several other parameters were also subjected to univariate analysis but were not found to be significant. These included AFP values, for which we used values ≤ 299 and ≥300 as cut-off values (p=0.081). Similarly, the difference in survival by risk factor was also not significant (p=0.14). However, there was a significant association between categories of AFP level (<200 and >/=200) and tumor size (up to 3 cm, >3 cm, 3-5 cm, and >5 cm.); Chi-sq.=9.45, df=2, p=0.009.

DISCUSSION
About 4.8% of the Pakistani population is estimated to be infected with hepatitis C, mainly genotype 3a, and another 2.5% are estimated to have chronic hepatitis B infection 10,11 . The incidence of HCC in Pakistan in males is about 7.5 per 100,000, while for females this estimate is 2.8 per 100,000 persons per year 12,13 . About 60-70% of these patients with HCC are infected with hepatitis C, another 20% are infected with hepatitis B, while other causes account for only 10-15% of cases 14,15 . There is high mortality in patients who develop HCC in the context of co-existent hepatitis B and HIV. The incidence and mortality of HCC have been increasing slowly in areas of low incidence and decreasing in ar-eas of high incidence. However, the WHO data shows a progressive increase in the number of patients diagnosed with primary liver cancer from 437,408 in 1990 to 716,600 in 2002 22 . In a study of 645 patients with HCC in Pakistan, 82.9% of patients were diagnosed to have HCC only when they became symptomatic, while only 8.2% were diagnosed on screening. This explains why the majority of our patients present with advanced, often multifocal disease. The absence of a national screening program means that this situation is unlikely to change soon. Even for those fortunate enough to be diagnosed early, the absence of a national liver transplant program significantly limits treatment options 15 . Most patients in our series presented with advanced liver disease with multifocal tumors and were candidates for palliative treatment only.

CONCLUSIONS
There is an urgent need for public education to minimize hepatitis B and C transmission, a nationwide screening program to detect disease at an earlier stage, and the development of specialist liver units and liver transplant programs. These are especially needed in high endemic areas of the world with hepatitis B and C, which are mostly developing countries with low educational status and significant recourse constraints.