This study provides data on 260 HCC patients and strongly suggests that hepatitis B virus is an important cause of HCC in The Gambia and that younger men are disproportionately affected. The study also showed that the prognosis of HCC patients in The Gambia is very poor, with most patients presenting late and with clinical, laboratory and radiological features consistent with multiple/large tumors and liver decompensation at presentation.
The demographics of our patients are consistent with previous studies (14, 15). Men are more commonly affected than women and present at a much younger age. Gender differences are unclear, but it has been speculated that: 1) Decreased adiponectin levels in men may be responsible for the increased risk of liver cancer. The decrease in adiponectin is due to JNK testosterone activation, which mediates the inhibition of adiponectin secretion, thereby increasing hepatocyte proliferation (16). 2) Other studies have shown that estrogen can act as an inhibitor of HCC cell proliferation, growth, and metastasis, and can prevent the development of liver cancer (17). Compared with a previous study, the Gambia Liver Cancer Study (GLCS) 1997-2001, the median age in our cohort was younger and there were differences by ethnicity (12). The age difference may be due to the fact that approximately 80% (32% between 35-44 years) of patients were < 54 years old, while 65% < 54 years (25% between 45-54 years). The age difference may also reflect the fact that in GLCS, a large proportion (19%) of the cause of HCC is attributed to HCV, which primarily affects older patients, although this has not been routinely tested in this cohort (15) . The fact that more patients from the original GHIS cohort now have liver disease (which is being captured) may also be a factor in the lower age group in this cohort. Ethnic differences may also be explained by including Farafenni Hospital as one of our recruitment sites, which has a large population of Wolof and Mandinka people.
The most common symptoms are weight loss, easy fatigue, abdominal pain, bloating, and early satiety, and the most common signs are hepatomegaly and abdominal tenderness. This suggests that the majority of our patients had tumor-related clinical manifestations at presentation. These findings are consistent with the clinical presentation of patients in resource-limited countries such as The Gambia, where screening programs and therapeutic interventions are limited (11). In resource-rich countries, the clinical presentation of patients with chronic hepatitis has changed significantly with the advent of ultrasound scanning and alpha-fetoprotein surveillance. Patients in the screening group had fewer symptoms and signs, fewer biochemical abnormalities, a greater chance of receiving treatment for HCC, and a higher survival rate (11).
The HBsAg carriage rate in this study was 65.4%, which was similar to previous studies (15, 18). In another study, the HBsAg carriage rate was lower by 50% (19), which may be due to the smaller sample size. Studies conducted in Senegal, Ghana, and Nigeria reported hepatitis B positivity rates of 69.5%, 75.2%, and 52% in HCC patients, respectively (20,21,22). This confirms that hepatitis B is a major risk factor for liver cancer in The Gambia and the sub-region. In this study, only 6.1% had a history of drinking alcohol. This differs from Ghana, where 39.2% of people admit to drinking alcohol. Alcohol appears to play a smaller role in the development of HCC in The Gambia than hepatitis B. However, in 2019, approximately one fifth of HCC-related deaths globally were alcohol-related (23). The study did not examine the role of hepatitis C virus and aflatoxins; therefore, further research is needed to investigate their role.
HBsAg-positive HCC patients are mainly male and younger. Compared with HBsAg-negative HCC patients, they are most likely to suffer from abdominal pain, jaundice, dark urine, and abdominal tenderness. HBsAg-negative patients diagnosed with HCC tended to be older, more likely to have hypertension, and had significantly longer median survival (41 days vs 31 days). The clinical manifestations of HBsAg-positive HCC patients are more aggressive than those of HBsAg-negative HCC patients. This further supports the need to establish screening programs for persons with chronic hepatitis B infection (10,11,24). The male-to-female ratio and the median age at presentation among HBsAg-positive HCC patients in this study were similar to previous studies (15). The male to female ratio was also more significant in HBsAg-positive HCC patients (6:1) than in HBsAg-negative HCC patients (3:1). Men are more likely to have chronic hepatitis B (10, 25). However, further research is needed to investigate the higher incidence of chronic liver disease and liver cancer in men.
< 45 岁年龄组中 HBsAg 阳性的 HCC 患者比例未能达到约 80%，而 GCLS 研究中该比例> 90%. However, the percentage of HBsAg-positive HCC patients in the 55–64-year-old age group increased significantly, from 20% in GCLS to 50% in the present study (13, 15). The reason for this can be explained by the effect of hepatitis B vaccination that began in 1986 (25,26,27,28) and the aging of the unvaccinated population.
Laboratory tests also revealed elevated transaminases and cholestatic enzymes and hypoalbuminemia, consistent with hepatic decompensation at presentation. The AST/ALT ratio is also high. It is well known that high GGT and AST/ALT were found to be independent factors predicting poor overall survival in patients with primary liver cancer (29). HBsAg-positive HCC patients were also more likely to have elevated transaminases and decreased platelet counts compared with HBsAg-positive HCC. HBsAg-negative HCC patients. Decreased platelet counts are associated with decreased survival and are a common finding in patients with advanced fibrosis and portal hypertension (30). These findings corroborate the fact that most of our patients, especially those who were HBsAg positive, had hepatic decompensation and therefore had very severe hepatic decompensation. Overall survival is poor.
Most patients also had multifocal disease, with a median FibroScan score of 75 kPa. The majority of 143 (61.9%) patients had FIB 4 scores greater than 3.25. One hundred and twenty-one (52.2%) patients also had an APRI score greater than 2. The above results indicate that most of our patients had significant fibrosis/cirrhosis at presentation. It is known that high FIB 4 score (31) or APRI score (32, 33) is associated with poorer survival. This further supports the fact that most HCC patients present late and therefore have a poor prognosis at presentation.
The overall median survival of our patients was 33 days. This result is very poor compared with other studies (11, 34,35,36,37) but similar to HCC patients who received supportive care only in Ethiopia (38). Even among African countries, the overall median survival of HCC patients in Egypt is significantly longer than that in other African countries (37). The reasons may be 1) lack of nationwide screening, treatment and surveillance programs for hepatitis B, the major cause of HCC in The Gambia; 2) lack of skilled manpower and infrastructure, surgical and other therapeutic interventions, such as transarterial chemoembolization, radiofrequency ablation therapy, liver transplantation and other surgical interventions, and 3) our patients presented late, probably because they first consulted local herbalists before going to the medical facility. However, there is an urgent need to discover new variables/biomarkers to aid early diagnosis and prognosis in countries without screening/surveillance.
WHO performance status >1, advanced or terminal BCLC stage (C and D), and Child-Pugh stage B were most common among our patients, and none of our patients met the Milan criteria. The findings are similar to studies conducted in sub-Saharan Africa (20, 37) but differ significantly from most other studies conducted in developed countries (11, 34, 35, 36). This suggests that most of our patients were diagnosed late and, therefore, the only treatment option available to them was symptomatic treatment. WHO performance status, Child-Pugh class, and BCLC had good survival stratification across all stages of disease. Further analysis of the different staging systems using Kaplan-Meier survival analysis revealed that each system had significant differences in survival rates at different stages. The median survival rate across stages in our cohort was worse than that in Hong Kong and Japan (11, 34, 36). Other African countries have worse WHO performance status, BCLC stage, and Child-Pugh stage than Egypt (37). The above findings confirm that countries with higher socioeconomic status have better survival rates and that even in countries with limited resources, there are differences in survival rates of HCC patients.
The study has some limitations: 1) The diagnostic criteria used in this study were based on a combination of clinical, ultrasound scan, AFP levels, and in a few cases histology, rather than the preferred three-phase CT scan, which was performed during the study period. 2) The study also did not include other causes, such as hepatitis C and aflatoxin, which may also contribute to some HCC cases, 3) patients with early HCC may also be missed due to limitations of ultrasonography in diagnosing early HCC and operating techniques, etc. Multiple factors affect the sensitivity of ultrasonography in diagnosing HCC, but the study is likely to be nationally representative because patients from medical institutions across the country were referred to the only liver disease specialty clinic for patients with suspected HCC during the study period. Secondly, this study provides us with a detailed understanding of the clinical characteristics and prognosis of HCC in The Gambia, which can be compared with other future studies.
In conclusion, chronic hepatitis B infection remains a major factor in the development of liver cancer in The Gambia. HBsAg-positive HCC patients are mostly younger men, who are more likely to develop symptoms and have a much shorter survival. Liver cancer survival and prognosis in The Gambia are poor due to the lack of national screening/surveillance and treatment programs for hepatitis B and liver cancer. This study therefore demonstrates the need to establish prevention, screening, treatment and surveillance programs in resource-limited countries such as The Gambia.