Liver cancer is the sixth most common cancer worldwide, with 841,080 new liver cancer cases in 2018 and the fourth leading cause of cancer-related death globally. The highest incidence and mortality of Hepatocellular Carcinoma (HCC) are observed in East Asia and Africa, although HCC incidence and mortality are increasing in different parts of Europe and in the USA.
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Indeed, HCC is the fastest increasing cause of cancer-related death in the USA since the early 2000s and HCC is projected to become the third leading cause of cancer-related death by 2030 if these trends continued. According to these available data the age adjusted incidence rate of HCC in India for men ranges from 4 to 7.5 and for women 1.2 to 2.2 per 100,000 population per year while the male:female ratio for HCC in India is 4:1 and the age of presentation varies from 40 to 70 years.
In an interview with HT Lifestyle, Dr Vikram Raut, Director- Liver Transplantation and HPB Surgery at Medicover Hospitals in Navi Mumbai, revealed the risk factors responsible for HCC:
1. Hepatitis B virus infection
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HBV infection accounts for 60% of HCC cases in Asia and Africa. HBV increases the risk of HCC even in the absence of cirrhosis, although most patients with HBV-induced HCC have cirrhosis at presentation. In Africa, patients in their early 30s or 40s present with HCC, likely because of exposure to aflatoxin B1, which acts synergistically with HBV to increase the risk of HCC. HBV vaccination programmes have led to a decrease in HCC incidence in some parts of Asia, although many jurisdictions are yet to implement universal vaccination programmes.
2. Hepatitis C virus infection
Chronic HCV infection is the most common underlying liver disease among patients with HCC in North America, Europe and Japan. With the use of direct-acting antiviral (DAA) therapy, an increasing proportion of patients with HCV infection have been successfully treated to achieve an SVR, resulting in a 50–80% reduction in the risk of HCC. However, several patients, particularly, racial minorities, ethnic minorities or people from low socioeconomic regions, are yet to be tested for HCV and remain unaware of their infection. Additionally, patients with HCV-induced cirrhosis continue to have a persistent risk of developing HCC (>2% per year) even after SVR and should therefore remain under close surveillance.
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3. Alcohol
Excessive alcohol intake causes alcoholic liver disease, cirrhosis and HCC. Currently, an increasing number of persons have cirrhosis from chronic alcohol consumption or NASH. Alcohol-related cirrhosis has an annual incidence ranging from 1% in population-based studies to 2–3% in tertiary care referral centres and accounts for ~15–30% of HCC cases depending on the geographical region. Chronic alcohol intake can also increase the risk of HCC from other aetiologies; for example, several studies reveal an increased risk of HCC in HBV carriers who consume alcohol compared with those who do not consume alcohol. Although alcohol consumption shares many pathophysiological processes with other forms of cirrhosis, in particular NASH, there is evidence supporting distinct alcohol-specific pro-tumorigenic mechanisms in patients.
4. NASH
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Another common aetiological factor for cirrhosis in people is NASH, which is the precursor step in the development of HCC in patients with diabetes mellitus or obesity. Owing to the increasing prevalence of obesity, NASH has become the most common cause of cirrhosis in most regions of the world. Since 2010, the proportion of HCC attributed to NASH has rapidly increased, currently representing 15–20% of cases in the West. Although the annual incidence of HCC is lower in NASH-related cirrhosis (1–2% per year) than in viral-mediated cirrhosis (3–5% per year), the incidence is >1.1 per 100 person-years, indicating that surveillance is cost-effective and should therefore be implemented.