There is significant variation in the types of cancer that dominate in different parts of the world, with special focus on the differences between industrialised and developing countries. Of the 8.1 million new cases of cancer diagnosed worldwide in 1990, the most prevalent form of cancer was lung cancer, at 12.8%, in total.1
The liver is the largest internal organ in the human body. It consists of two lobes and occupies the upper right portion of the abdomen, within the rib cage. Primary liver cancer (PLC) is a disease with the development of cancer cells in the hepatic tissues. But cancer from other locations in the body and extending to the liver is not primary liver cancer. Most of the PLCs are of epithelial cell origin, either hepatocytic or intrahepatic bile duct cell origin. The primary epithelial liver cancers are classified into 6 histological types according to their cell of origin and histological pattern. Non-epithelial liver cancers are rare.2
Five-year survival rates for certain cancers, such as hepatocellular carcinoma, are lower than 15%, and lung cancer ranges from approximately 4% to 17%. Several key risk factors for cancer development have been established, including dietary habits, alcohol use, cigarette smoking, metabolic syndrome, and diabetes. Excess weight and obesity, as well as weight fluctuation, have more recently been suggested as potential risk factors for the development of particular cancers.3
Up to now, the impact of overweight or obesity on cancer risk has not been studied properly, and there are contradictions between the results of numerous studies. Although some research indicated that obesity elevates the risk of gastric cancer, other research revealed no association.
The incidence and prevalence of Hepatocellular Carcinoma (HCC) have shown a similar increasing trend with the globally increasing rates of overweight and obesity, as measured by body mass index (BMI). This relation suggests that overweight and obesity could account significantly for the total cases of HCC. A recent meta-analysis of 11 cohort studies showed that individuals who were overweight had a 17% higher risk of Primary Liver Cancer (PLC), and those who were obese had a 90% increased risk compared to individuals with normal weight.4
Schaffner and Thaler first described nonalcoholic fatty liver disease (NAFLD) in 1986. They acquired a series of non-alcoholic patients with liver disease and liver pathology biopsy samples resembling alcoholic liver disease.5
Obesity is associated with a range of liver damage, known as nonalcoholic fatty liver disease (NAFLD), by a rise in intrahepatic triglyceride (IHTG) content (i.e. steatosis) with or without inflammation and fibrosis (i.e. steatohepatitis). NAFLD has become a major cause of public health concern because of its high prevalence, potential to progress to advanced liver disease, and association with serious cardiometabolic disturbances, including type 2 diabetes mellitus (T2DM), the metabolic syndrome and coronary heart disease (CHD).
The liver serves as a key organ in metabolic regulation, hence, it demands a high level of blood supply of about 1.5 litres per minute, provided through the hepatic artery (30%) and portal vein (70%) to carry out its various biochemical activities. It plays a crucial role in dealing with substrates, hormones, and nutrients in maintaining overall body homeostasis. Excess intrahepatic triglyceride (IHTG) accumulation, which is typical in nonalcoholic fatty liver disease (NAFLD), is associated with deranged glucose, fatty acid, and lipoprotein metabolism and inflammation.6
Whether NAFLD causes these metabolic derangements or whether these derangements are secondary to IHTG accumulation, however, is yet to be determined. Furthermore, elevated visceral fat and ectopic fat in other viscera often accompany NAFLD, each of which is independently associated with metabolic dysfunction, making it difficult to isolate the contribution of liver fat.
However, obese persons with normal composition of IHTG appear to be immune to the development of metabolic complications of obesity. Nonetheless, it is not certain that NAFLD is an effect or a cause of metabolic derangement.7
NAFLD is a spectrum of liver injury consisting of triglyceride deposition in the hepatocytes in the form of a spectrum of conditions ranging from an uncomplicated steatosis hepatis with fat accumulation not accompanied by an inflammation of the liver to a more severe form of the disease involving active liver inflammation, otherwise known as NonAlcoholic SteatoHepatitis (NASH). Active hepatic inflammation will go on to cause cirrhosis and enable hepatocellular carcinoma (HCC) development.
NASH is a histological diagnosis characterised by hepatocytic inflammation that may progress to fibrosis. Hepatic fibrosis has been classified into four stages. Stage I is mild hepatic fibrosis, stage II is moderate hepatic fibrosis, stage III is moderate to severe fibrosis, and stage IV is severe or advanced fibrosis. Advanced fibrosis stage needs to be detected, as these patients are susceptible to developing decompensated cirrhosis and end-stage liver disease. There are a few clinical variables which allow doctors to predict whether the patient will evolve into catastrophic categories of this disease.8
NASH-related cirrhosis is the primary indication for chronic liver disease and the cause of liver transplants. Increasing numbers of patients impacted strain the pool of available organs. Multiple comorbidities and risk factors have been involved in the severity and chronic liver disease development of NASH.
With the increasing incidence of NAFLD among the population, there is a rising imperative to discover non-invasive means of diagnosing and staging NAFLD. The final test should be reproducible, low cost, and have the ability to diagnose the entire range of NAFLD and fibrosis and have the ability to display changes occurring with treatment. Initial evaluation includes clinical presentation with comorbidity history, and liver function testing in the form of blood tests. Noninvasive imaging methods such as MRE and Fibroscan can provide quantitative estimates of steatosis and liver stiffness in patients without advanced cirrhosis or fibrosis.9
Weight gain and obesity are among the most extreme risk factors for developing liver cancer, particularly hepatocellular carcinoma (HCC). Excess fat, especially when it is central (visceral) around the stomach, greatly contributes to the risk, even more so than overall measures of obesity like BMI. Research shows that individuals who put on weight during adulthood, especially those who become overweight or obese, have a much higher chance of developing liver cancer. This is particularly true in individuals with non-alcoholic fatty liver disease (NAFLD) and its more aggressive variant, non-alcoholic steatohepatitis (NASH), both of which are metabolic conditions closely linked with obesity. These conditions create a pro-inflammatory and insulin-resistant condition in the liver, which sets the stage for cancer development.10
With the progression of liver cancer, the pattern of weight is normally reversed. One of the most common symptoms in patients with liver cancer is unintentional weight loss, which typically occurs due to profound metabolic derangements produced by the neoplasm itself. Loss of weight is not only the result of reduced food intake, but it is also caused by a syndrome of multifactorial aetiology known as cachexia that is marked by profound and involuntary muscle wasting. Chronic inflammation is the key feature of cachexia, with elevated levels of inflammatory mediators such as interleukin-6 (IL-6), tumour necrosis factor (TNF), and insulin-like growth factors (IGFs) stimulating the breakdown of muscle mass and altering energy metabolism. Cachexia has a significant effect on the strength, functional capacity, and tolerance to treatments like chemotherapy or surgery, often leading to poorer outcomes.11
Furthermore, the challenge of balancing liver cancer patients is the frequent coexistence of ascites, a term applied to describe fluid in the abdominal cavity. Ascites is a common presentation of end-stage liver disease and results in palpable distension of the abdomen, which can deceptively suggest a stable or even increased weight. Patients may be losing significant amounts of muscle and fat, which can be masked by the fluid. This makes traditional weight measurements, such as BMI, inaccurate in defining the patient's true nutritional and health status. BMI can’t differentiate among fat, muscle, and fluid and therefore cannot measure the degree of body composition changes that occur throughout liver cancer.12
Together, weight plays a dual and dynamic role in liver cancer. Firstly, both adult and early-life weight gain are important risk factors that predispose to liver cancer through mechanisms that include insulin resistance, inflammation, and fatty liver disease. Secondly, following cancer development, patients are predisposed to involuntary weight loss, muscle wasting, and fluid retention, all of which exert a dramatic influence on their prognosis and quality of life.13
Weight management is a vital component of both the prevention and supportive care of liver cancer. Before diagnosis, maintenance of a normal body weight is necessary to reduce the risk of developing hepatocellular carcinoma (HCC). Poor dietary habits, such as excessive consumption of saturated fats from red meat and exposure to carcinogens like aflatoxins, significantly increase the risk of liver cancer. By comparison, consumption of a high-fibre diet, fruits, vegetables, omega-3 fatty acids, and coffee yields protective benefits. The foods modulate the metabolism, inhibit inflammation, and enhance a favourable body mass index (BMI). Fibre, in particular, regulates appetite and energy intake, resulting in weight maintenance in the long term and cancer prevention.14
After a diagnosis of liver cancer, especially in those with cirrhosis, weight management becomes more complex and crucial. Unintended weight loss and wasting of muscle occur in most patients due to the metabolic demand of the cancer and the catabolic nature of chronic liver disease. Continuous and accurate nutritional assessment is required to monitor changes in body composition. Mid-arm muscle circumference, handgrip strength, and bioelectrical impedance measurements are some of the tools that can be used to detect sarcopenia, which is linked to worse treatment outcomes and lower survival.15
To counteract these effects, certain nutritional therapy needs to be implemented. More energy and protein are required in patients to meet the demands of cancer and liver failure. Recommended allowances are 30 to 45 kilocalories per kilogram per day and 1.2 to 1.5 grams of protein per kilogram per day. Small, frequent feedings are encouraged to maximise intake, and in those patients where it is not possible to eat, enteral nutrition through a nasogastric tube can be necessary. Supplementation with branched-chain amino acids is of great benefit because it maintains muscle function, improves liver function, maximises treatment response, and allows for better overall outcomes. 16 The role of registered dietitians is vital in this case. These experts are responsible for planning and adjusting individualised nutrition plans, guiding patients through nutritional adjustments, and preventing further muscle mass loss. Furthermore, the incorporation of exercise, appropriate to the patient's ability, can be helpful in the preservation of physical strength, enhancing endurance, and improving quality of life. Resistance and aerobic exercises, even at moderate intensities, contribute significantly to the preservation of body composition and functional independence.
Weight management in liver cancer requires a preventive strategy before diagnosis through healthy lifestyle habits and a conscious, individualised regimen after diagnosis. Such a combination not only reduces risk but is also responsible for tolerance to treatment, recovery, and survival.17
Weight is a significant factor in the treatment and prognosis of liver cancer, influencing the suitability for surgery, chemotherapy dosing, and survival. Obesity has been associated with better overall survival (OS) in hepatocellular carcinoma (HCC) patients, particularly those undergoing treatments like transarterial chemoembolization (TACE), an effect known as the "obesity paradox". Overweight patients have better nutritional reserves and greater tolerance to therapies, leading to less treatment interruption and improved compliance. Conversely, critically underweight or critically weight-losing patients over 5% of baseline weight have a poorer prognosis due to blunted physiologic reserves, frailty, and malnutrition.18
Chemotherapy dosing in obesity requires careful treatment consideration, as weight adjustment to maximum allows for efficacy without adding toxic potential, whereas undertreated underweights may experience difficulties in tolerability of treatment. Surgical outcomes are also impacted by weight; obesity makes surgery, such as liver resections, challenging due to technical problems and comorbidities, but malnutrition increases the risk of postoperative complications. On balance, healthy weight status and addressing malnutrition are most crucial to maximising treatment success and survival in liver cancer patients.19
Weight plays a complex, dual role in liver cancer. It is a significant risk factor through obesity and NAFLD, facilitating cancer-promoting conditions. After diagnosis, however, weight preservation and correction of malnutrition are crucial for tolerance to treatment and improved survival, highlighting the necessity of tailored weight management techniques.
