The cause for liver cancer in Asia is undergoing a transition from viral to non-viral factors, with non-alcoholic fatty liver disease emerging as a leading risk factor.
Liver cancer is one of the leading causes of cancer-related deaths around the world. Up to 1,837 people die from liver cancer every day, which is roughly 76 people every hour. In Asia alone, liver cancer is identified as the fifth most common cancer and second most common cause of cancer-related death.
While significant advances have been made in early diagnosis and surgical resection of liver cancer during the last few decades, the prognosis of this disease remains unsatisfactory.
Non-alcoholic fatty liver overtaking Hep-B as primary cause
The most common risk factor for liver cancer globally, and in Asia-Pacific (except Japan), is the hepatitis B virus (HBV). Individuals infected with HBV have a 25 to 40% lifetime risk of developing liver cancer. It is estimated that between 25 to 50% of HBV carriers can expect to die prematurely, either due to chronic liver inflammation and liver failure (cirrhosis), or the development of liver cancer.
In Singapore, where the incidence of liver cancer is 5.7%, with a mortality of 10.2%, HBV infection accounted for most of the cases. About 66.6% of the liver cancer-related deaths were due to HBV infection, according to the WHO General Health Estimates 2015. In Malaysia, more than half (51.3%) of liver cancer cases in 2018 were attributed to HBV.
However, non-alcoholic fatty liver disease (NAFLD) seems to be overtaking HBV as a primary cause for liver disease in Asia. NAFLD is a condition where there is more than 5% fat accumulation in liver cells, with the absence of HBV or Hepatitis C (HCV) infection, and without excessive alcohol consumption.
The estimated prevalence of NAFLD in Singapore and Malaysia was 40.0% in 2021 and 37.4% in 2018, respectively. Several studies in Malaysia have shown that NAFLD and non-alcoholic steatohepatitis (NASH) are the leading causes of liver cancer, which correlates with the rising incidence of diabetes and obesity in Malaysia.
According to Dr Tan Chih Kiang, Consultant Clinical Oncologist at Thomson Hospital, Kota Damansara, Kuala Lumpur, Malaysia, “In Malaysia, there is a worrying trend in the rise of liver cancer due to non-alcoholic fatty liver disease (NAFLD). Historically, most cases of liver cancer have been due to the Hepatitis B virus from vertical transmission, that is from mother to child. However, with the implementation of the HBV vaccines in young children since 1989, this risk factor has been reduced significantly.”
“Conversely, NAFLD is a growing concern due to the rise in the twin epidemics of obesity and diabetes. The development of NAFLD is strongly associated with metabolic syndrome, with 90% of patients demonstrating more than one feature of metabolic syndrome, and 33% having three or more criteria. Being overweight leads to increased lipid peroxidation and oxidative stress, which then makes it easier for chronic hepatitis B to progress into liver cancer. Diabetes also contributes to a higher risk of liver cancer progression and all-cause mortality in patients with liver cancer,” explains Dr Tan.
According to the National Population Health Survey 2022, obesity rates in Singapore have increased from 10.5% in 2020 to 11.6% in 2022, while close to 1 in 10 adults suffer from diabetes. Meanwhile in Asia, it was estimated that more than 30 million adults are living with obesity, and this figure is expected to increase to over 52.4 million adults in 2030.
Novel therapies prolong survival rates
When liver cancer is detected early, that is in Stage I or II, before it has spread to the patient’s blood vessels, physicians can perform a resection, also called a partial hepatectomy, to remove the tumour. With successful curative surgery, the chance of survival beyond five years is more than 40%. Unfortunately, the majority of liver cancer patients are not the best candidates for surgery as their cancers are detected at an advanced stage.
Dr Choo Su Pin, Senior Consultant Oncologist at Curie Oncology, Mount Elizabeth Novena Medical Centre, and Council Member of the Singapore Cancer Society in Singapore, says, “In more advanced Stage II and III cancers which are still localised to the liver, loco-regional therapies like radiofrequency ablation (using heat to destroy the cancer), chemotherapy directed into the liver (TACE), or radiation directed into the liver (radiation beads released directly into the liver tumour), are commonly used. However, with late diagnosis, treatment options are limited.”
“Fortunately, the development of novel immunotherapy interventions in the early 2000s to treat advanced liver cancer, has radically changed the treatment landscape. Nowadays, more advanced immunotherapy drugs and tyrosine kinase inhibitors (TKIs) are offering renewed hope to liver cancer patients. A combination of immunotherapy drugs with TKIs is becoming the standard first-line treatment for advanced liver cancer, marking a significant breakthrough after years of limited options,” says Dr Choo.
The availability of a second-line treatment, should the first-line treatment be ineffective, has significantly increased the median survival time for advanced liver cancer patients – from six months to less than a year previously, to two years or more.
When ignorance is not bliss
Despite breakthroughs in research and innovative therapies, the lack of understanding and awareness of liver cancer remains a key barrier in lowering the mortality rates for the disease. The Malaysian Cancer Registry showed that 86% of males and 87% of females were only detected at Stage III and IV of their liver cancer, while in Singapore, about 50% of liver cancer cases were detected in the same advanced stages.
“Even though treatment options are available in the earlier stages of liver cancer, the average life expectancy of a newly diagnosed liver cancer patient in Malaysia is less than a year due to late diagnoses. Many patients only consult their physicians when they start experiencing the symptoms of liver cancer such as abdominal pain, abdominal distension, unexplained weight loss and/or loss of appetite. By this time, the cancer is usually in stage III or IV, which complicates treatment options and reduces their survival chances,” says Dr Tan.
“Liver cancer is often picked up by chance when patients are being treated and examined for other health conditions. As long as they are symptom-free, they believe they are well,” he adds.
Recent surveys reveal that despite a majority (92.8%) of Malaysians agreeing that regular screening was important for liver health, only 67% underwent recent health screening and one-fifth were unlikely to seek medical consultation upon exposure to viral hepatitis risk factors. Reasons for the low urgency included the perception of being healthy, cost-related concerns, and societal discrimination. Similarly in Singapore, 91.2% of respondents agreed that regular screening was important for liver health, but only 65.4% underwent health screening in the last 2 years.
Studies show that early diagnosis and treatment can increase the survival rate for liver cancer by up to 50%.
Stronger prevention measures and early screening critical
Singapore was one of the first countries in Asia to adopt universal HBV vaccination for babies in 1987, which led to a significant decline in the prevalence of HBV and liver cancer over subsequent decades. Malaysia followed suit with the introduction of the nationwide HBV vaccination for neonates in 1989 as part of the “Expanded Programme for Immunisation”.
While the strategy has been successful in reducing the prevalence of chronic HBV infection, and subsequently slowing liver cancer rates, the rising incidence of non-alcoholic fatty liver disease must also be curtailed.
Dr Choo elaborates, “Compulsory vaccination at birth against HBV, which we already have in Singapore, is the first and most important step. Then it is largely a matter of lifestyle choices. Exercise and eat a healthy balanced diet to maintain a healthy weight to avoid diabetes and fatty liver disease. If everyone followed these, we could dramatically reduce the rates of liver cancer and many other diseases.”
Dr Tan says that both patients and healthcare professionals play a role in liver cancer surveillance and prevention.
“There isn’t a specific type of test to detect liver cancer, unlike a mammogram for breast cancer or the prostate-specific antigen test for prostate cancer. Hence, it is crucial that patients educate themselves about the risk factors and undergo routine (annual) blood tests for HBV and HCV, and a liver ultrasound especially if they suspect potential cirrhosis or fatty liver disease. These tests can determine if the patient is at higher risk of developing liver cancer,” explains Dr Tan.
“Physicians too must be vigilant and proactive in identifying potential red flags during routine exams. By sending patients for further testing or referring them to a specialist as soon as they suspect something is amiss, can help promote earlier detection and better outcomes for patients. It is a collaborative effort, where informed patients and attentive healthcare professionals can play a part in the management of liver cancer,” he says.
Some organisations that offer support for patients with cancer, including liver cancer are:
Singapore:
1. NCIS Cancer Fund: The fund caters to patients in need.
2. The National Cancer Centre Singapore (NCCS): Offers support throughout the cancer journey, for patients, survivors, and caregivers.
3. Singapore Cancer Society (SCS): Offers a range of support services for cancer patients, including financial assistance, home hospice care, counseling, and etc.
Malaysia:
1. Social Security Organisation (PERKESO): Provides financial relief for cancer patients unable to work.
2. Malaysian Cancer Council (MAKNA): Offers financial aid, focusing on underprivileged patients and supporting cancer awareness and research.
3. National Cancer Society Malaysia (NCSM): Provides psychosocial services like counselling, nutrition advice, and peer groups for emotional support.
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