Prevention of Hepatocellular Carcinoma in Nonviral-Related Liver Diseases

Abstract and Introduction

Abstract

Although chronic infection with hepatitis B virus and/or hepatitis C virus are the most important risk factors for hepatocellular carcinoma (HCC) worldwide, other causes of cirrhosis can also lead to HCC. Given the high prevalence of alcoholism and the worldwide obesity epidemic, the relevant importance of nonviral liver disease-related HCC is expected to increase in the future. Some evidence supports mechanistic interactions between host or environmental factors and chronic viral hepatitis in the development of HCC. For example, food- and water-borne carcinogens have contributed to unusually high rates of HCC in parts of China and sub-Saharan Africa. With some of these conditions, appropriate public health measures to reduce the population's exposure to known etiologic agents, or early therapeutic intervention for 'at-risk' individuals before development of cirrhosis (e.g. hereditary hemochromatosis) can prevent HCC. Community-based programs to discourage and deal with excessive alcohol intake, to promote tobacco smoking awareness, to avoid exposure to aflatoxin and other food toxins, and measures to reduce the pandemic of obesity and diabetes are vital for effective interruption of the rising tide of HCC from nonviral liver disease.

Introduction

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most common cause of cancer mortality.^[1–4] Despite major efforts to improve the diagnosis and treatment, therapeutic options for HCC have not impacted on the mortality.^[3–5] The global health burden of HCC can reasonably be reduced by early detection or prevention.^[3–7] Prevention of HCC is possible because, in more than 90% of cases, this cancer occurs in the context of known risk factors, most of which are theoretically preventable.^[8] The key, as reviewed in other articles of this series, the risk factors associated with HCC include chronic hepatitis B (CHB) and/or hepatitis C (CHC), particularly with subsequent cirrhosis.^[8–10] However, cirrhosis arising from nonviral liver diseases (Table 1) is also risk for HCC, such as alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), hereditary hemochromatosis (HH) and, less commonly, drug- and toxin-induced, immune-mediated or metabolic liver diseases, that is, primary biliary cirrhosis (PBC) and α-1 antitrypsin deficiency.^[2,8,11] With some of these conditions, appropriate public health measures to reduce the population's exposure to the known etiologic agents, or early therapeutic intervention for 'at-risk' individuals before development of cirrhosis could prevent HCC. Additional factors account for some regional or individual variability in HCC risk. Other host and environmental factors can therefore influence the development of HCC, even though they may not be necessary or sufficient for hepatocarcinogenesis when present alone. Some host factors include advanced age and male gender, excessive alcohol consumption, iron overload, cigarette smoking, obesity, and type 2 diabetes.^{[1–4,8,11,12]} Food- and water-borne carcinogens, such as aflatoxin B1 and fumonisin from contaminated crops, have contributed to unusually high rates of HCC in parts of China and sub-Saharan Africa.^[1,2,4,6] Clean water and uncontaminated food supplies offer an additional basic condition to prevent HCC.

Although CHB is the most common etiologic agent of HCC in the Asia–Pacific region, with the exception of Japan, where cases of HCC are mainly related to CHC, and Australia and New Zealand where CHB and CHC are both important, nonviral liver diseases are implicated in 10–20% of cases.^{[1–3,12–16]} There is also possible interaction between host and environmental factors with chronic hepatitis B virus/hepatitis C virus (HBV/HCV) infection in the development of HCC.^[1–3,8,14]

In this review we will focus on risk factors for HCC in patients without chronic viral hepatitis, with an emphasis on opportunities for preventing chronic liver disease and development of HCC as one of its complications.

Cite this: Prevention of Hepatocellular Carcinoma in Nonviral-related Liver Diseases - Medscape - May 01, 2009.

Table 1. Causes and risk factors for HCC and general approaches to prevention
Etiology or risk factors	Major approaches to prevention
Major causes
Chronic HBV infection	Vaccination; antiviral therapy
Chronic HCV infection	Screening of blood; antiviral therapy
Alcohol liver disease	Abstinence of alcohol intake; correction of nutritional deficiencies
Minor causes
Non-alcoholic fatty liver disease	^† Treating metabolic risk factors
Hereditary hemochromatosis	Family screening; iron depletion
Primary biliary cirrhosis	^† Using ursodeoxycholic acid
Risk factors
Dietary pollution	Avoiding exposure to aflatoxins
Alcoholism	^† Screen for and treatment of alcohol dependence and abuse
Overweight/obesity	^† Diet and aerobic exercise
Type 2 diabetes	^† Optimal control of blood glucose
Tobacco smoking	^† Controlling tobacco use

^† These approaches have not yet been shown to be effective.
HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus.

Table 2. Efforts approach to reversal obesity epidemic
Increase education on diet and physical activity
Train health professionals
Restrict advertisements of high-calorie and low-nutrient foods
Limit access to unhealthy foods in schools and workplaces
Levy taxes on sugary drinks and other foods high in calories, fat, or sugar
Lower the prices of healthy foods
Promote physical activity in schools and workplaces

Table 3. Behavior modification for patients with obesity
Consume a diet low in calories and fat
Regular engage in moderate physical activity
Check body weight and abdominal circumference regularly

Table 4. Avoiding dietary aflatoxin contamination
Agricultural strategies adopted to reduce the quantity of aflatoxin in food
Genetic modification of crops to enhance fungal resistance
Biocontrol of aspergillus by flooding fields with nontoxigenic fungi
Methods to reduce humidity to limit fungal growth
Drying the crop in the sun on a mat
Discarding visibly moldy kernels or nuts before storage
Use of natural fiber sacks for storage
Placing these on wooden pallets to keep the crop dry
Shifting the staple diet from corn to rice limits exposure to aflatoxin in highly prone areas

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Prevention of Hepatocellular Carcinoma in Nonviral-related Liver Diseases

Abstract and Introduction

Abstract

Introduction

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