Liver Cancer

A comprehensive guide to understanding liver cancer, its symptoms, diagnosis, and treatment options

Overview

Liver cancer is a type of cancer that begins in the cells of your liver, a large organ that sits in the upper right portion of your abdomen, beneath your diaphragm and above your stomach. The liver performs many vital functions, including filtering toxins from the blood, producing bile to help digest fats, storing glucose, and making proteins important for blood clotting.

Primary liver cancer originates in the liver itself, while secondary or metastatic liver cancer spreads to the liver from another part of the body. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, accounting for approximately 75% of all liver cancers. The second most common type is intrahepatic cholangiocarcinoma, which develops in the bile ducts within the liver.

Liver cancer is the sixth most common cancer worldwide and the third leading cause of cancer-related death. The incidence varies significantly by geographic region, with the highest rates in East Asia and sub-Saharan Africa, largely due to the prevalence of hepatitis B and C infections. In the United States, liver cancer rates have been rising for several decades, though they've recently begun to stabilize.

The prognosis for liver cancer depends on many factors, including the stage at diagnosis, the underlying health of the liver, and the patient's overall health. Early detection significantly improves outcomes, with 5-year survival rates for localized liver cancer around 35%. However, because liver cancer often doesn't cause symptoms in its early stages, it's frequently diagnosed at an advanced stage when treatment options are more limited.

Symptoms

Liver cancer often doesn't cause symptoms in its early stages. When signs and symptoms do appear, they may be subtle and easily attributed to other conditions. As the cancer progresses, symptoms typically become more noticeable and may significantly impact quality of life.

Groin Mass

Swelling in the groin area can occur due to enlarged lymph nodes as the cancer spreads, or from fluid accumulation (ascites) that extends into the groin region.

Sharp Abdominal Pain

Sudden, intense pain in the abdomen may occur if the tumor ruptures or bleeds, or if it stretches the liver capsule. This pain is often felt in the upper right quadrant.

Upper Abdominal Pain

Persistent discomfort or pain in the upper right portion of the abdomen is common as the tumor grows and puts pressure on surrounding structures.

Decreased Appetite

Loss of appetite is common in liver cancer and may be accompanied by feeling full after eating only small amounts of food.

Stomach Bloating

Abdominal swelling can result from fluid accumulation (ascites) or from the enlarged liver itself. This may cause clothes to feel tight around the waist.

Additional Common Symptoms

  • Jaundice: Yellowing of the skin and eyes due to bile buildup
  • Unexplained weight loss: Significant weight loss without trying
  • Fatigue and weakness: Persistent tiredness that doesn't improve with rest
  • Nausea and vomiting: May be persistent and worsen over time
  • White or chalk-colored stools: Due to lack of bile reaching the intestines
  • Dark urine: Caused by excess bilirubin in the blood
  • Fever: Low-grade fever that comes and goes
  • Enlarged liver: May be felt as a mass under the ribs on the right side
  • Enlarged spleen: May cause fullness or pain on the left side
  • Itching: Caused by bile salts accumulating in the skin

Important: Many of these symptoms can be caused by other conditions, including non-cancerous liver diseases. However, if you experience any persistent symptoms, especially if you have risk factors for liver cancer, consult your healthcare provider promptly.

Causes

Liver cancer occurs when liver cells develop mutations in their DNA. These genetic changes cause cells to grow uncontrollably and eventually form a tumor. While the exact cause of these mutations isn't always clear, several factors are known to increase the likelihood of developing liver cancer.

Primary Causes

The most significant causes of liver cancer are conditions that lead to cirrhosis, a scarring of the liver that occurs in response to chronic damage:

Chronic Viral Hepatitis

  • Hepatitis B (HBV): Chronic HBV infection is the leading cause of liver cancer worldwide. The virus can integrate into liver cell DNA, directly causing mutations
  • Hepatitis C (HCV): Chronic HCV infection causes ongoing inflammation and liver damage, increasing cancer risk over decades

Cirrhosis

Any condition that causes cirrhosis increases liver cancer risk. The constant cycle of liver damage and regeneration creates opportunities for mutations to occur. Common causes of cirrhosis include:

  • Chronic alcohol abuse
  • Nonalcoholic fatty liver disease (NAFLD)
  • Autoimmune hepatitis
  • Primary biliary cholangitis
  • Hemochromatosis (iron overload)

Aflatoxin Exposure

Aflatoxins are toxic compounds produced by molds that grow on improperly stored grains and nuts. Chronic exposure to aflatoxins, particularly when combined with hepatitis B infection, significantly increases liver cancer risk. This is a major risk factor in parts of Asia and Africa.

Metabolic Disorders

Certain inherited metabolic conditions can lead to liver damage and increase cancer risk:

  • Hereditary hemochromatosis
  • Alpha-1 antitrypsin deficiency
  • Wilson's disease
  • Glycogen storage diseases

Risk Factors

Understanding risk factors for liver cancer is crucial for prevention and early detection. Some risk factors can be modified through lifestyle changes or medical treatment, while others cannot be changed.

Major Risk Factors

  • Chronic hepatitis B or C infection: The most significant risk factor globally
  • Cirrhosis: Regardless of cause, cirrhosis dramatically increases risk
  • Heavy alcohol use: Long-term excessive drinking damages liver cells
  • Nonalcoholic fatty liver disease: Increasingly common in developed countries
  • Diabetes: Type 2 diabetes doubles liver cancer risk
  • Obesity: Contributes to fatty liver disease and diabetes
  • Aflatoxin exposure: From contaminated food in certain regions

Additional Risk Factors

  • Gender: Men are 2-3 times more likely to develop liver cancer
  • Age: Most common in people over 60 in the US
  • Race/ethnicity: Higher rates in Asian Americans and Pacific Islanders
  • Family history: Increased risk with family members who have liver cancer
  • Smoking: Increases risk, especially when combined with hepatitis
  • Anabolic steroid use: Long-term use increases risk
  • Certain chemicals: Vinyl chloride, thorium dioxide exposure

Risk Stratification

Healthcare providers use risk factors to identify individuals who may benefit from enhanced surveillance:

  • High risk: Cirrhosis from any cause, chronic hepatitis B with family history of liver cancer
  • Intermediate risk: Chronic hepatitis B or C without cirrhosis, NAFLD with advanced fibrosis
  • Lower risk: Simple fatty liver, resolved hepatitis infection

Types of Liver Cancer

Liver cancer is classified based on the type of cell where the cancer begins. Understanding the different types is important for determining the most appropriate treatment approach.

Primary Liver Cancers

Hepatocellular Carcinoma (HCC)

  • Accounts for approximately 75% of liver cancers
  • Originates in hepatocytes (main liver cells)
  • Patterns of growth:
    • Single tumor: Starts as a single tumor that grows larger
    • Multiple tumors: Several small tumors throughout the liver
    • Diffuse: Not clearly defined, spreads throughout the liver
  • Subtypes include fibrolamellar HCC (rare, better prognosis)

Intrahepatic Cholangiocarcinoma (Bile Duct Cancer)

  • Accounts for 10-15% of liver cancers
  • Originates in the bile ducts within the liver
  • Often diagnosed at advanced stages
  • May be associated with liver fluke infections in endemic areas

Hepatoblastoma

  • Very rare, primarily affects children under age 3
  • Generally has better outcomes than adult liver cancers
  • May be associated with certain genetic syndromes

Angiosarcoma and Hemangiosarcoma

  • Very rare cancers that start in blood vessels of the liver
  • Associated with exposure to vinyl chloride or thorium dioxide
  • Tend to grow and spread rapidly

Secondary (Metastatic) Liver Cancer

More common than primary liver cancer in the United States. Cancers that commonly spread to the liver include:

  • Colorectal cancer
  • Breast cancer
  • Lung cancer
  • Pancreatic cancer
  • Stomach cancer
  • Melanoma

Note: Treatment approaches differ significantly between primary and metastatic liver cancers. Accurate diagnosis of the cancer type is essential for appropriate treatment planning.

Diagnosis

Diagnosing liver cancer typically involves a combination of medical history, physical examination, blood tests, imaging studies, and sometimes biopsy. Early detection is challenging because symptoms often don't appear until the disease is advanced.

Screening for High-Risk Individuals

Regular surveillance is recommended for people at high risk:

  • Ultrasound: Every 6 months for those with cirrhosis
  • Alpha-fetoprotein (AFP): Blood test often combined with ultrasound
  • MRI or CT: May be used in patients where ultrasound is inadequate

Diagnostic Tests

Blood Tests

  • Alpha-fetoprotein (AFP): Elevated in about 50-70% of HCC cases
  • Liver function tests: Assess overall liver health
  • Hepatitis serology: Check for hepatitis B and C
  • Complete blood count: May show abnormalities
  • Prothrombin time: Evaluates blood clotting ability

Imaging Studies

  1. Ultrasound: Often the first imaging test, can detect tumors and assess blood flow
  2. CT scan (multiphasic): Provides detailed images with contrast enhancement patterns
  3. MRI with contrast: Excellent for characterizing liver lesions
  4. PET scan: May help determine if cancer has spread

Biopsy

Not always necessary if imaging and blood tests are conclusive. Types include:

  • Fine needle aspiration: Uses a thin needle to extract cells
  • Core needle biopsy: Removes a small cylinder of tissue
  • Laparoscopic biopsy: Minimally invasive surgical approach

LI-RADS Classification

The Liver Imaging Reporting and Data System (LI-RADS) standardizes imaging interpretation:

  • LR-1: Definitely benign
  • LR-2: Probably benign
  • LR-3: Intermediate probability of malignancy
  • LR-4: Probably HCC
  • LR-5: Definitely HCC
  • LR-M: Probably malignant but not HCC specific

Staging

Liver cancer staging is complex because it must consider both the extent of the cancer and the underlying liver function. Several staging systems are used worldwide.

Barcelona Clinic Liver Cancer (BCLC) Staging

The most widely used system, incorporating tumor characteristics, liver function, and performance status:

Stage 0 (Very Early)
Single tumor <2 cm, preserved liver function, no symptoms
Stage A (Early)
Single tumor >2 cm or up to 3 tumors <3 cm each, preserved liver function
Stage B (Intermediate)
Multiple tumors, preserved liver function, no vascular invasion or spread
Stage C (Advanced)
Vascular invasion or spread beyond liver, still functioning adequately
Stage D (Terminal)
Poor liver function or poor performance status, any tumor burden

TNM Staging

  • T (Tumor): Size, number, and vascular invasion
  • N (Nodes): Lymph node involvement
  • M (Metastasis): Distant spread

Child-Pugh Score

Assesses liver function and helps determine treatment eligibility:

  • Class A: Well-compensated disease (5-6 points)
  • Class B: Significant functional compromise (7-9 points)
  • Class C: Decompensated disease (10-15 points)

MELD Score

Model for End-Stage Liver Disease score predicts survival and helps prioritize liver transplant candidates. Based on bilirubin, creatinine, and INR values.

Treatment Options

Treatment for liver cancer depends on the stage of disease, liver function, and overall health. A multidisciplinary team typically develops an individualized treatment plan.

Potentially Curative Treatments

Surgical Resection

  • Removal of the tumor and surrounding liver tissue
  • Best for single tumors in patients with good liver function
  • Requires adequate remaining liver volume
  • 5-year survival rates of 60-70% for appropriate candidates

Liver Transplantation

  • Replaces diseased liver with healthy donor liver
  • Best option for early-stage HCC with poor liver function
  • Milan criteria: Single tumor ≤5 cm or up to 3 tumors ≤3 cm each
  • 5-year survival rates exceeding 70%

Ablation Therapies

  • Radiofrequency ablation (RFA): Heat to destroy tumor cells
  • Microwave ablation: Similar to RFA but faster
  • Cryoablation: Extreme cold to kill cancer cells
  • Ethanol injection: Direct injection of alcohol into tumor

Palliative Treatments

Transarterial Therapies

  • TACE (Chemoembolization): Delivers chemotherapy directly to tumor while blocking blood supply
  • TARE (Radioembolization): Delivers radiation via tiny beads
  • TAE (Bland embolization): Blocks blood supply without chemotherapy

Systemic Therapies

Targeted Therapy

First-line: Sorafenib, Lenvatinib
Second-line: Regorafenib, Cabozantinib, Ramucirumab

Immunotherapy

Atezolizumab + Bevacizumab (first-line combination)
Nivolumab, Pembrolizumab (subsequent lines)

Chemotherapy

Limited role in HCC. FOLFOX regimen sometimes used.
More effective for cholangiocarcinoma

Radiation Therapy

  • SBRT (Stereotactic body radiation): Precise high-dose radiation
  • 3D-CRT: Conformal radiation therapy
  • Proton therapy: May spare more healthy liver tissue

Supportive Care

  • Management of cirrhosis complications
  • Nutritional support
  • Pain management
  • Treatment of ascites and hepatic encephalopathy
  • Palliative care for quality of life

Prevention

Many cases of liver cancer can be prevented by addressing modifiable risk factors and maintaining liver health.

Primary Prevention Strategies

Hepatitis B Prevention

  • Vaccination: Highly effective, recommended for all infants and at-risk adults
  • Safe practices: Avoid sharing needles, practice safe sex
  • Screening: Pregnant women should be tested
  • Post-exposure prophylaxis: Available for unvaccinated individuals

Hepatitis C Prevention

  • No vaccine available, focus on preventing transmission
  • Avoid sharing needles or personal items that may have blood
  • Ensure safe medical and dental procedures
  • Get tested if at risk; curative treatments are available

Lifestyle Modifications

  • Limit alcohol: No more than 1 drink/day for women, 2 for men
  • Maintain healthy weight: Prevents fatty liver disease
  • Exercise regularly: At least 150 minutes moderate activity weekly
  • Healthy diet: Mediterranean diet may reduce risk
  • Avoid tobacco: Smoking increases liver cancer risk
  • Coffee: Regular consumption may reduce risk

Secondary Prevention

  • Treat underlying conditions: Manage hepatitis, diabetes, fatty liver
  • Regular surveillance: For those with cirrhosis or chronic hepatitis
  • Aflatoxin reduction: Proper food storage in endemic areas
  • Medication review: Minimize hepatotoxic drugs when possible

Chemoprevention

Some medications may reduce liver cancer risk in certain populations:

  • Statins: May reduce risk in patients with chronic liver disease
  • Metformin: May benefit diabetic patients with liver disease
  • Aspirin: Some evidence for risk reduction, but bleeding risk must be considered

When to See a Doctor

Early detection of liver cancer significantly improves treatment outcomes. Know when to seek medical attention.

Schedule an Appointment If You Experience:

  • Persistent abdominal pain or swelling
  • Unexplained weight loss or loss of appetite
  • Persistent nausea or vomiting
  • Yellowing of skin or eyes (jaundice)
  • Dark urine or pale stools
  • Unusual fatigue or weakness
  • Fever that doesn't resolve
  • New onset of swelling in legs or abdomen

Seek Immediate Medical Care For:

  • Sudden, severe abdominal pain
  • Vomiting blood or coffee-ground material
  • Black, tarry stools
  • Confusion or altered mental state
  • Severe shortness of breath
  • High fever with abdominal pain

Regular Screening Recommendations

If you have risk factors for liver cancer, discuss screening with your doctor:

  • Cirrhosis: Ultrasound every 6 months
  • Chronic hepatitis B: Based on age, family history, and ethnicity
  • Chronic hepatitis C with advanced fibrosis: Regular surveillance
  • Hereditary hemochromatosis: Once cirrhosis develops

Medical Disclaimer: This information is for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for diagnosis and treatment of any medical condition. If you have risk factors for liver cancer, discuss appropriate screening and prevention strategies with your doctor.