• Unintentional weight loss
• Loss of appetite
• Early satiety after small meals
• Nausea and vomiting
• Swelling in the legs and feet due to fluid retention
• Abdominal lump or mass on the upper-right side
• Persistent pain in the upper-right abdomen or right shoulder blade
• Abdominal bloating or swelling
• Yellowing of the skin or eyes (jaundice)
• Swollen belly (ascites) caused by fluid buildup in the abdomen
• Itching
• Fever
• Easy bruising or bleeding
• Severe fatigue or weakness
• Pale, clay-colored stools
• Dark urine

• Increased blood calcium levels possibly resulting in constipation, nausea, and confusion
• Decreased blood sugar levels that may lead to fatigue or feelings of faintness
• Enlarged breasts or testicular shrinkage in males
• Increased red blood cell count that might cause facial redness

• Cirrhosis: Cirrhosis is scarring of the liver. It occurs when scar tissue obstructs blood flow in the liver, impairing its function. Cirrhosis is mainly caused by chronic alcoholism and hepatitis infections. However, those with hepatitis C-related cirrhosis face a greater risk of developing liver cancer compared to those with cirrhosis from hepatitis B or alcohol consumption. Most people diagnosed with the main type of liver cancer in the United States also have cirrhosis.
• Chronic hepatitis B virus infection (HBV): Hepatitis B virus can spread through body fluids. Chronic HBV infection is the primary cause of liver cancer in Asia and Africa. Transmission can occur from mother to child during childbirth, through sexual contact, or by sharing needles.
• Chronic hepatitis C virus infection (HCV): Transmission of HCV is very similar to that of HBV. HCV can result in cirrhosis and is the primary cause of liver cancer in North America, Europe, and Japan.
• Nonalcoholic steatohepatitis (NASH): NASH is a severe type of nonalcoholic fatty liver disease (NAFLD, although now, it is often called metabolic dysfunction-associated steatotic liver disease, or MASLD) that can lead to cirrhosis, characterized by an abnormal accumulation of fat in the liver, possibly resulting in inflammation and liver cell damage.

1. Primary

• Hepatocellular carcinoma (HCC): Hepatocellular carcinoma, also known as hepatoma, originates from hepatocytes, the liver’s primary cells. HCC makes up approximately 80 percent to 90 percent of primary liver cancer cases and ranks as the third most common cause of cancer-related death globally. It’s frequently associated with cirrhosis. All other primary liver cancers are rare.
• Cholangiocarcinoma (bile duct cancer): Although cholangiocarcinoma is considered another major type of liver cancer, it is relatively rare, making up about 15 percent of liver cancer cases. The major bile ducts connect the liver and gallbladder to the small intestine while carrying bile produced by the liver to help with fat digestion. Cancer originating in the ducts outside the liver is called extrahepatic cholangiocarcinoma, while that within the liver is intrahepatic cholangiocarcinoma. Cholangiocarcinoma is a slow-growing type of cancer.
• Angiosarcoma: Angiosarcoma, also known as hemangiosarcoma, is a rare type of soft tissue sarcoma that starts in the liver’s blood vessels. It accounts for 2 percent of all primary liver cancers. It is primarily diagnosed in older people, and its cause is usually unidentified.
• Hepatoblastoma: While rare overall, hepatoblastoma is typically diagnosed in children under 2 years old. Sometimes, it can develop in older children and lead to the production of hormones that can cause precocious puberty. The cause of this cancer remains unknown.
• Fibrolamellar carcinoma: Fibrolamellar carcinoma typically affects adults in their 20s and 30s, and it is not linked to cirrhosis, hepatitis B or C, or other known risk factors. Compared to other types of liver cancer, people with fibrolamellar carcinoma may have a better prognosis if detected early, with many living for several years after the tumor is removed.

2. Secondary

• Stage 0: Very early; there is one small tumor less than 2 centimeters in size that is asymptomatic and hasn’t invaded the major blood vessels in the liver.
• Stage A: Early; there can be as many as three tumors, each smaller than 3 centimeters. There are still no symptoms or invasion into the major liver blood vessels.
• Stage B: Intermediate; there are multiple tumors in the liver, either more than three or one to three tumors, with at least one being larger than 3 centimeters. There are still no symptoms or invasion into the major liver blood vessels.
• Stage C: Advanced; the cancer has either invaded the major blood vessels in the liver or metastasized to other parts of the body, with noticeable symptoms.
• Stage D: End-stage; the cancer has either invaded the major blood vessels in the liver or metastasized to other parts of the body, and there is severe liver damage.

• T: Number of primary tumors, their size, and whether or not they have spread to nearby organs
• N: Spread of cancer to nearby lymph nodes
• M: Metastasis to other organs

• Sex: Men are twice as likely to develop liver cancer than women for unknown reasons. This may be because men drink more alcohol than women.
• Age: In the United States, primary liver cancer typically affects individuals aged 60 and older.
• Race: Liver cancer rates are highest among Asian Americans and Pacific Islanders in the United States, followed by Hispanic and Latino, American Indian, Alaska Native, African American, and white populations, in that order.
• Hepatitis infections: HBV and HCV infections are the biggest risk factor for liver cancer. However, clearing the acute hepatitis B or C virus results in complete recovery from the infection, and the increased risk of liver cancer is only present in individuals who do not clear the virus and experience persistent infection.
• Metabolic disorders: Obesity leads to fat accumulation in the liver, causing nonalcoholic fatty liver disease (NAFLD). NAFLD and its association with Type 2 diabetes pose significant risk factors for hepatocellular carcinoma in the United States.
• Smoking: The risk of developing liver cancer rises in correlation with the quantity of cigarettes smoked and the number of years the person has smoked. Fortunately, the risk of liver cancer decreases over time following smoking cessation.
• Environmental carcinogens: Exposure to specific chemicals such as vinyl chloride and plutonium or consumption of aflatoxin-contaminated food can increase liver cancer risk. Aflatoxin is produced by mold on stored nuts and grains. This risk is lower in the United States but more prevalent in regions such as sub-Saharan Africa, Southeast Asia, and China.
• Excessive alcohol consumption: This is a risk factor for liver cancer, particularly when an individual has cirrhosis or HBV/HCV infection. Specifically, heavy drinkers with cirrhosis have a 10-fold higher risk of developing liver cancer than those without.
• Betel chewing: A 2009 Taiwanese study found that chewers of betel nut (used as a mild stimulant) without HBV/HCV infection had higher risks of cirrhosis and HCC, and these risks were combined with those associated with viral hepatitis infections synergistically. There is also some evidence that betel quid, a combination of betel leaf, areca nut, and slaked lime, causes liver cancer with or without tobacco, but more research is needed to confirm this.
• Family history: People with relatives with liver cancer could be more at risk.
• Long-term steroid use: Anabolic steroids, male hormones used by athletes for muscle strength and size, slightly raise the risk of HCC with long-term use. However, cortisone-like steroids such as hydrocortisone, prednisone, and dexamethasone do not pose the same risk.
• HIV infection or AIDS: People with HIV or AIDS face a higher risk of liver cancer, likely due to their compromised immune system’s reduced ability to combat infections.
• Liver fluke infection: Liver flukes are parasitic worms. Infections typically occur due to consuming contaminated food or water.
• Birth control pills: The use of oral contraceptives for five or more years, especially older formulas, is associated with a slightly increased risk of liver cancers in women, but research has been controversial.
• Certain genetic conditions: Inherent medical conditions that may increase the risk of liver cancer include hereditary hemochromatosis, alpha-1 antitrypsin deficiency, glycogen storage disease, and Wilson’s disease. Genomic instability, which can involve changes in chromosomes or single DNA building blocks, also plays a significant role in liver cancer development. Specific genes such as TERT promoter, TP53, CTNNB1, ARID1A, and FGF, along with signaling pathways such as JAK/STAT, WntB-catenin, and PI3K-AKT-mTOR, are key drivers in causing HCC.
• Primary sclerosing cholangitis: This condition can result in inflammation and scarring of the bile ducts, leading to intrahepatic cholangiocarcinoma.

• Alpha-fetoprotein testing: Alpha-fetoprotein (AFP), a protein produced by liver tumors, is the most commonly used tumor marker for liver cancer detection. Tumor markers, or biomarkers, are substances tumors produce that can be detected in blood, fluids, or tissues. However, in addition to liver cancer, increased AFP levels can also occur in pregnancy, hepatitis, and other cancers, so AFP testing is controversial. High-risk cirrhotic patients, such as those with hepatitis C, hepatitis B, or hemochromatosis, may undergo AFP level checks every three to four months.
• Computed tomography (CT) scan: This may reveal a tumor.
• Ultrasound scan: Ultrasonography every six or 12 months is a standard screening option. However, in obese individuals, ultrasound is much less sensitive, so alternating ultrasound with MRI or CT scans should be considered.

• Physical examination: HCC patients usually have an enlarged liver. In infants, doctors typically suspect hepatoblastoma when they detect a sizable mass in the upper right area of the abdomen, especially if the infant’s health is declining.
• Blood tests: Liver function tests (LFTs), tests for viral hepatitis, blood chemistry tests (which measure the levels of various substances in the blood), complete blood count, and kidney function tests may help diagnose liver cancer. In addition, the CA 19-9 test checks for this particular marker associated with bile duct cancers in the blood and assists in predicting liver cancer prognosis.
• Imaging tests: The imaging tests listed above, as well as magnetic resonance imaging (MRI) and angiography, which visualize the arteries that provide blood to a liver tumor, may also be used. Another test, positron emission tomography (PET), is a nuclear medicine imaging method in which a small amount of radioactive sugar is injected into the body, highlighting abnormalities such as tumors. This scan can help detect bile duct cancer and is often done concurrently with a CT scan for a more comprehensive evaluation.
• Endoscopic procedures: Diagnosing cholangiocarcinoma in the bile ducts outside the liver typically involves specialized X-ray methods. Typically, upper endoscopy passes an endoscope fitted with a camera through the patient’s mouth into the esophagus so that images can be seen on a monitor during the procedure. In the case of endoscopic retrograde cholangiopancreatography (ERCP), an upper endoscopy is performed to inject dye directly into the bile ducts while taking external X-rays to illuminate the course of the dye. Cholangioscopy involves using a specialized endoscope called a cholangioscope to see and biopsy tumors inside the bile duct; it’s often performed during an ERCP procedure. Percutaneous transhepatic cholangiography involves inserting a needle through the skin into a liver bile duct and injecting contrast material to visualize the biliary tree with X-rays.
• Liver biopsy: If AFP levels are notably high and a tumor is visible on imaging scans, a diagnosis of liver cancer can be made. However, if the tests listed above are inconclusive, a liver biopsy may be recommended since it provides a definitive diagnosis. During a biopsy, liver tissue is extracted for analysis in a pathology lab to confirm cancerous tissue.

• Hepatic encephalopathy is a reversible condition marked by a range of neuropsychiatric issues caused by neurotoxic substances building up in the bloodstream and brain. Common symptoms include confusion, personality changes, disorientation, and reduced consciousness levels.
• Portal vein thrombosis refers to the constriction or obstruction of the portal vein due to a blood clot.
• Variceal bleeding occurs in the large esophageal veins.
• Obstructive jaundice occurs when the bile duct or pancreatic duct becomes narrowed or blocked, hindering the usual flow of bile from the liver to the intestines.
• Pyogenic liver abscess refers to a collection of pus enclosed within the liver.
• Intraperitoneal bleeding is internal bleeding in the abdominal cavity, the area between organs and the inner lining of the abdominal wall.
• Metastasis to other organs and tissues.
• Portal hypertension refers to increased pressure within the portal venous system, which includes the portal vein leading to the liver.
• Infection of the biliary tree (i.e., cholangitis) is a complication of cholangiocarcinoma and subsequent duct obstruction.
• Anemia.

1. Surgery

• Liver resection: Liver resection, also known as partial hepatectomy, removes the tumor along with a surgical margin of healthy tissue. This procedure is considered if the patient has no portal hypertension, normal bilirubin levels, and enough remaining healthy liver tissue post-surgery. Liver resection offers several surgical options, including resecting an entire lobe, multiple lobes (i.e., extended lobectomy), or part of a lobe (i.e., segmental resection). After the removal of cancerous tissue, a healthy liver can regrow to its normal size in about six months, but cirrhosis limits its regeneration capacity.
• Liver transplant: If the patient cannot receive a liver resection, a liver transplant may be considered. A liver transplant can be whole or partial (e.g., a split-liver transplant).

2. Ablation Therapy

• Radiofrequency ablation (RFA) uses electrical currents to generate heat to eliminate cancerous cells. At temperatures above 194 degrees Fahrenheit, the tumor starts to disintegrate.
• Percutaneous ethanol injection (PEI) involves injecting concentrated ethanol alcohol directly into a liver tumor using a needle. This method is often used for tumors located near major blood vessels in the liver.
• Microwave ablation (MWA) uses electromagnetic waves to generate heat to eradicate cancer cells.

3. Radiation Therapy

• Conformal radiation therapy uses computer technology to create a three-dimensional image of the tumor, thus customizing radiation beams to match its shape precisely. This targeted approach delivers a high radiation dose to the tumor while minimizing harm to surrounding healthy tissues.
• Proton beam radiation therapy uses high-energy protons to target and eliminate tumor cells. It is known for its precision in sparing surrounding healthy tissue from radiation exposure, and it’s especially useful if the tumor is located near critical structures or in sensitive areas.
• Stereotactic body radiation therapy (SBRT) administers highly concentrated beams of radiation directly to liver tumors. It is also considered the most effective radiation therapy for liver cancer.

4. Embolization

• Transarterial chemoembolization (TACE): Chemoembolization combines blocking the tumor’s blood supply with delivering chemotherapy drugs to the cancer. TACE is a form of chemoembolization that targets branches of the hepatic artery to treat liver cancer. It is the usual treatment for those with healthy liver function, overall good health, and no major issues such as portal hypertension or portal vein thrombosis. It is also the most frequently performed procedure to address inoperable liver tumors or for liver cancer patients awaiting a transplant.
• Transarterial radioembolization (TARE) is a form of embolization therapy that administers radioactive microspheres into specific tumor arteries, where they become caught and continue to irradiate the tumor.

5. Immunotherapy

6. Other

• Cryotherapy: Also known as cryosurgery, cryotherapy involves freezing and destroying cancer cells using a specialized instrument.
• Chemotherapy: Although chemotherapy is not very effective in treating HCC, it can be used to treat cholangiocarcinoma, and it’s also available for other types of liver cancer.
• Endoscopic retrograde cholangiopancreatography (ERCP): ERCP can be used to manage bile duct obstruction in cholangiocarcinoma. It involves using an endoscope equipped with a camera and surgical tools to unblock bile ducts and place a stent. This stent helps open up the duct, allowing bile to drain into the intestine, improving the patient’s quality of life and alleviating symptoms such as jaundice.
• Palliative care: Palliative care is specialized medical care aimed at relieving suffering and enhancing the quality of life for individuals with life-limiting illnesses that cannot be cured. It focuses on managing pain and symptoms, providing support to patients and their families, and ensuring dignity and comfort throughout the illness.

• Providing psychological resilience: The psychological burden is high in liver cancer patients, and many experience depression and anxiety. Psychological interventions and improved emotional resilience can help patients cope better with the stress and challenges of liver cancer diagnosis and treatment.
• Improved adherence to treatment: A proactive and resilient mindset can lead to better adherence to treatment plans, including medication schedules, follow-up appointments, and lifestyle changes.
• Higher quality of life: Improved mood can contribute to a higher quality of life during cancer treatment by elevating overall health and energy levels and even reducing pain. This is because mindsets can impact endogenous opioid and neuroimmune pathways, thus directly influencing physiology and affecting measurable health indicators.
• Offering coping mechanisms: A positive mindset often leads to the adoption of effective coping strategies, such as seeking social support and maintaining a healthy lifestyle.
• Supporting the immune system: Research suggests that positive attitudes and optimism may benefit the immune system, thus potentially supporting the body’s natural defenses against cancer.

1. Medicinal Herbs and Herbal Medicines

• Milk thistle (Silybum marianum): Milk thistle, also known as silymarin, has been used as a remedy for liver, kidney, and gallbladder issues for two millennia. Research indicates that compounds in milk thistle may help protect the liver. Among them, a flavonoid called dihydroquercetin can decrease fat accumulation in the liver, especially in individuals who consume alcohol, thus helping prevent fatty liver. Silymarin can protect the liver from toxins. In a pooled analysis of studies involving cirrhosis patients, milk thistle treatment was linked to a notable decrease in liver-related mortality. However, study results have been mixed regarding whether milk thistle improves liver function tests. In addition, individuals allergic to ragweed may also have an allergy to milk thistle.
• Wolfberry (Lycii fructus): Wolfberry, also known as goji berry, is a fruit from the Lycium barbarum plant and is often used in traditional Chinese medicine (TCM). The most important component of wolfberry is Lycium polysaccharide (LPP), which has various health benefits such as regulating the immune system, acting as an antioxidant, protecting nerve cells, controlling blood sugar levels, and anti-cancer effects. One 2008 study discovered that drinking juice containing polysaccharides from wolfberries can increase antioxidant biomarkers in humans. LPP was also found in a 2006 study involving both rat and human HCC cell lines to hinder the growth of liver tumor cells and prompt their death, suggesting its potential use as an anti-cancer agent.
• Zingiberaceae (ginger): In one 2010 study, a daily dose of 50 milligrams per kilogram of ginger extract effectively treated experimental cancer in rats by decreasing growth factors and the levels of alpha-fetoprotein, a liver tumor marker, indicating that ginger extract might protect against early stages of liver cancer in such rat models. Lesser galangal (Alpinia officinarum) is a member of the ginger family with antioxidant, anti‐inflammatory, antimicrobial, and cytotoxic properties. In one 2012 study, its extract and components demonstrated anti-cancer properties against lab-cultured HCC cancer cells. Some researchers have suggested that Alpinia officinarum rhizome extract might be used as a chemopreventive agent against HCC in rats.
• Huaier granules: Huaier granules are commonly used in TCM for liver cancer treatment. They contain Trametes robiniophila Murr, a medicinal fungus rich in organic compounds and minerals with polysaccharide protein as its active component. Research shows that Huaier granules target various factors and pathways in liver cancer. They inhibit growth and induce death in certain cancer cells. In addition, they interfere with signaling pathways related to tumor angiogenesis (new blood vessel formation).
• Fufang Banmao capsules (FFBMs): Fufang Banmao capsules are a highly recognized cancer drug composed of 11 traditional Chinese medicines. Their main ingredient, Banmao, contains cantharidin, which has anti-cancer properties. In one 2011 study, FFBMs were given to HCC patients either before they received TACE treatment or one week or one month after the treatment. This combined treatment significantly enhanced the immune functions of the patients with HCC.

2. Diet

• Broccoli sprouts: Broccoli sprouts are a rich source of health-promoting plant-based bioactive compounds, including polyphenols, minerals, and vitamins A, C, K, and B6, essential for overall health. Sulforaphane, a nutrient found in cruciferous vegetables such as broccoli, has been shown to have anti-cancer properties by inducing cell cycle arrest and cell death in human cancer cell cultures. One study found that broccoli sprouts significantly assisted in the suppression of liver HeP-G2, an HCC cell culture.
• Black currants: Black currants are packed with plant-based nutrients, antioxidants, vitamins, healthy fats, and minerals, including a type of rare and healthy omega-6 fat. In a 2011 rat model, black currant skin extract reduced the occurrence, number, size, and spread of early liver cancer tumors in rats in a dose-dependent way.
• Asparagus: Asparagus polysaccharide is used in clinical settings to treat different types of cancers such as breast cancer, leukemia, and lung cancer. One 2014 laboratory study found that asparagus polysaccharide can slow the growth of specific liver cancer cells, such as HeP-G2 and HeP-3B, without harming healthy liver cells, such as 7702 cells.
• Green tea (Camellia sinensis): Green tea has been used to prevent liver diseases in Asia for a long time. The main polyphenol in green tea, epigallocatechin-3-gallate (EGCG), was tested on mice with liver damage and showed promising effects in reducing injury, inflammation, and oxidative stress in the liver. Tea polyphenols may help prevent and fight liver cancer by halting cancer cell growth, promoting cancer cell death, and reducing inflammation and oxidative stress in the liver. At present, moderate doses seem helpful, while excessive doses with supplement extracts showed evidence of toxicity to healthy cells.
• Coffee: Coffee consumption has been linked to protective factors against HCC. According to a 2019 systematic review of four studies, coffee has a weak to strong inverse association with liver cancer. The researchers concluded that the Japanese population was likely to experience a decrease in the risk of primary liver cancer due to coffee consumption.

3. Supplements

• Berberine: Berberine, an alkaloid from Coptidis rhizoma, has been shown to have significant antibacterial, anti-inflammatory, antioxidant, anti-apoptotic, and anti-autophagic properties. Reports indicate its potential in treating cancer and inflammation. In one 2010 study, berberine exhibited anti-cancer effects on human HCC cell cultures by promoting cancer cell death and suppressing tumor cell proliferation.
• Resveratrol: Resveratrol is a natural compound in red grapes known for its potent antioxidant and anti-inflammatory abilities, making it highly valued in herbal medicine. Cancer cells change how they obtain energy, favoring a process called aerobic glycolysis, which helps them grow and survive. One 2015 study of four different HCC cell lines discovered that resveratrol encouraged liver cancer cell death and reduced the activity of a protein called hexokinase 2 (HK2), linked to aerobic glycolysis. Resveratrol also worked well with conventional treatments such as sorafenib to slow cancer cell culture growth. The study’s researchers concluded that blocking HK2 with resveratrol could be a promising way to treat liver cancer and stop its metastasis.

4. Alternative Medicine and Mind-Body Practices

• Acupuncture and moxibustion: Pain relief is crucial for liver cancer treatment. Acupuncture therapy is a popular pain management method used in liver cancer patients, especially in China. It can also help relieve drug-induced vomiting and other gastrointestinal reactions during liver cancer treatment, along with moxibustion.
• Meditation and yoga: Meditation and yoga can be used as relaxation methods to reduce stress in liver patients, and meditation can also relieve pain for some patients.

• Limit alcohol consumption.
• Avoid or quit smoking.
• Consider getting vaccinated against hepatitis B.
• Practice safe sex and avoid having multiple sexual partners to reduce the risk of hepatitis B and C infection.
• Avoid sharing needles or using illicit drugs.
• Treat hepatitis B and C infection, cirrhosis, and other medical conditions that may lead to liver cancer.
• Maintain a healthy weight and exercise regularly.
• Eat a balanced diet with plenty of fruits, vegetables, and whole foods.
• Avoid exposure to aflatoxins.
• Follow safety guidelines when handling chemicals or toxins that may affect the liver.
• Get regular checkups and screenings for liver health, especially if you belong to at-risk groups.