Liver Cancer

What is liver cancer?

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, accounting for approximately 90% of cases. This aggressive malignancy typically develops in the setting of chronic liver disease, with cirrhosis being a major risk factor. The incidence of HCC has been rising globally, largely due to the increasing prevalence of chronic hepatitis B and C infections, alcohol-related liver disease, and non-alcoholic fatty liver disease associated with obesity and diabetes. In the United States, HCC is the fastest-growing cause of cancer-related deaths. Given the often asymptomatic nature of early-stage HCC, regular screening of high-risk individuals using ultrasound and alpha-fetoprotein (AFP) testing is crucial for early detection and improved outcomes. Timely diagnosis of HCC can significantly impact treatment options and patient survival.

Liver cancer can be caused by a primary cancer of liver cells or metastatic cancer to the liver from another part of the body. Primary liver cancer is almost always caused by an underlying chronic condition affecting the liver (virus, toxins, etc).

Many liver cancers do not start causing symptoms until a late stage of the disease. The main symptoms include pain in the upper right quadrant of the liver, a palpable mass, jaundice, early satiety, and unexplained weight loss.

Treatment focuses on surgical removal of cancer. Liver transplants may be required and are curative.

You should schedule a visit with your primary care physician (PCP). It is likely imaging will be performed as well as blood tests to inform next steps.

Liver cancer symptoms

Main symptoms

Liver cancer often remains asymptomatic until late into the disease or is masked by a coexisting condition like cirrhosis, or chronic scarring of the liver. The following symptoms are most commonly associated with liver cancer.

• Right upper quadrant pain: The right upper quadrant is the location of the abdomen that contains the liver and the gallbladder. The liver is encased in a sheet of connective tissue called Glisson's capsule. This capsule is highly sensitive to stretching, so when a mass starts expanding outwards from the liver, it can cause pain.
• Palpable mass: As liver cancer progresses, the tumor usually starts to grow. Once it gets large enough, you may be able to feel a mass protruding outward on palpation of the right upper abdomen.
• Jaundice: Jaundice is yellowing of the skin or eyes. It can be a symptom of liver cancer that has progressed enough to obstruct the gallbladder, the organ adjacent to the liver that contains bile. When the outflow of bile is obstructed, bilirubin, one of the components of bile, can seep out into the blood, causing yellowing.
• Early satiety: As liver cancer progresses, and the tumor grows larger, it can begin to obstruct surrounding structures of the GI tract. A tumor that is large enough can begin to compress the stomach or small intestine, leading to feelings of fullness.
• Weight loss: Weight loss is a non-specific symptom of many cancers. Any cancer with a growing tumor increases the body's caloric demand in order to grow the tissue. This increased metabolic activity associated with cancer can result in weight loss.

Other symptoms

Liver cancer can present with a variety of other symptoms listed below. However, these symptoms are not specific for liver cancer and should prompt further workup rather than be used as a diagnostic indicator.

• Fever: Many people with different types of cancer may experience fever as the body is in an inflammatory state. Fever in liver cancer is often the result of necrosis, or tissue death, as the tumor utilizes the liver's blood supply.
• Diarrhea: Cancer can alter the electrolyte balance within a person's body. The presence of liver cancer can also increase secretion of certain hormones (gastrin, vasoactive intestinal peptide) that can predispose a person to diarrhea.
• Hypercalcemia: Hypercalcemia is excess calcium in the bloodstream. Liver cancer can lead to excess secretion of a hormone called (PTHrP) which is associated with a number of different cancers. Excess PTHrP can lead to the breakdown of bones, thereby leading to excess calcium. Too much PTHrP and calcium in the blood can cause bone pain, kidney stones, abdominal pain, or psychological changes.
• Skin changes: An uncommon manifestation of liver cancer is skin changes. Skin changes can be associated with a variety of different cancers. Skin findings can include color changes or newly appearing lesions on the face, trunk, or extremities.

Liver cancer causes

Liver cancer is either caused by a primary tumor of the liver tissue or metastatic cancer from another site in the body. Metastatic cancer to the liver is more common than primary liver cancer. The most common sources of cancers metastasizing to the liver are colon, pancreas, lung, and breast carcinomas as well as melanoma. The liver is a very common site also for other cancers throughout the body to metastasize.

Other risk factors

Primary liver cancer, also referred to as hepatocellular carcinoma, is the fifth most commonly diagnosed cancer in men and the ninth most-diagnosed cancer in women internationally. Chronic infection with hepatitis B or hepatitis C are the two most common causes of primary liver cancer. Other risk factors include heavy alcohol use, cirrhosis, hemochromatosis (a disease of excess iron), obesity, diabetes, and fatty liver disease.

Diagnosis

In high-risk individuals presenting with symptoms, imaging is the first step in the diagnosis of liver cancer. Liver cancer can be detected with CT, MRI, or ultrasound. People with a lesion measuring less than 1 centimeter in diameter should be observed. People with a lesion measured more than 1 centimeter are usually recommended to pursue further imaging. Many liver cancers can be diagnosed from imaging alone, though indeterminate lesions may require tissue biopsy. One of the blood tests associated with liver cancer is called alpha-fetoprotein (AFP). People with liver cancer may have elevated levels of AFP. AFP has been estimated to have a sensitivity of 60 percent and specificity of 80 percent.

Treatment options and prevention for liver cancer

The management of therapy for liver cancer is surgical removal, if possible, given the aggressive nature of the lesion. The median survival after diagnosis of liver cancer is six to 20 months.

• Surgical resection: This is typically limited to people with small tumors that have not yet invaded the liver blood supply or other surrounding organs.
• Anti-virals: Anyone who has liver cancer concurrent with hepatitis should also be treated with these therapies if they underwent surgical resection for the cancer.

Other treatments

For people who do not have a lesion that is curable by surgical resection, the following may be beneficial or even curative.

• A liver transplant: This is the only other option that is likely to provide a full cure.
• Chemical or radio wave ablation or embolization: These are other treatment options for people who are not candidates for surgical resection or liver transplant. These treatment modalities are aimed at slowing tumor progression by interrupting the lesion's blood supply.

Prevention

Given that the majority of primary liver cancers arise as a result of an underlying condition affecting the liver, prevention of liver cancer is aimed at avoiding risk factors for hepatitis, cirrhosis, and obesity. The most common modifiable risk factors for avoiding hepatitis B and hepatitis C include the following.

• Intravenous drug use
• Excess alcohol intake
• Unprotected sexual intercourse
• Obesity and non-alcoholic fatty liver disease: These have also been correlated with increased rates of liver cancer. These conditions result from a number of factors.

When to seek further consultation for liver cancer

As previously discussed, liver cancer often does not present with symptoms until late in the course of the disease. As such, anyone who feels a new mass in the right upper quadrant or is experiencing right upper quadrant pain or jaundice should seek consultation. It is particularly important if you have risk factors for liver disease to seek care from your physician if symptoms develop.