HepPar-1: Definition

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HepPar-1, short for hepatocyte paraffin 1, is a test that pathologists use to identify hepatocytes, the main working cells of the liver. Pathologists test for HepPar-1 mainly to help diagnose hepatocellular carcinoma, the most common type of cancer that starts in the liver. HepPar-1 also helps the pathologist decide whether a tumor in the liver started there or spread to the liver from another organ.

This article explains what HepPar-1 is, how pathologists use it to diagnose liver tumors, and what a HepPar-1 result in your pathology report means.

What is HepPar-1?

HepPar-1 is the name of an antibody that sticks to an enzyme called carbamoyl phosphate synthetase 1. This enzyme sits inside the mitochondria, the parts of the cell that produce energy. It helps the liver convert protein waste into urea, which then leaves the body in urine. Some reports call the test HepPar-1 or hepatocyte-specific antigen. In normal tissue, two main types of cells are positive for HepPar-1:

Hepatocytes. Normal liver cells are strongly positive throughout the liver.
Small intestine lining cells. Some cells lining the small intestine are also positive.

How do pathologists test for HepPar-1?

Pathologists test for HepPar-1 using immunohistochemistry, which uses antibodies to detect specific proteins in a thin slice of tissue. Positive cells show fine brown granules throughout their cytoplasm under the microscope. Normal liver cells next to a tumor are positive, which acts as a built-in check that the test worked.

How does HepPar-1 help diagnose liver cancer?

HepPar-1 helps diagnose liver cancer because hepatocellular carcinoma cells come from hepatocytes, and most of these cancers stay positive. Many other cancers found in the liver are negative, which helps the pathologist sort tumors into a few main groups:

Hepatocellular carcinoma. The cancer cells are usually HepPar-1 positive, especially when they still look much like normal liver cells.
Intrahepatic cholangiocarcinoma. This cancer starts in the bile ducts inside the liver, and its cells are usually HepPar-1 negative.
Metastatic carcinoma. Cancers that spread to the liver from other organs, such as the colon or pancreas, are usually negative, although a few are positive.

HepPar-1 cannot distinguish a noncancerous liver growth from cancer because normal and abnormal hepatocytes are both positive. To make that distinction, the pathologist looks at cell arrangement and uses other markers such as glypican-3.

What are the limits of HepPar-1?

HepPar-1 has some limits, so pathologists rarely rely on it alone. The main limits include:

Poorly differentiated tumors. Hepatocellular carcinomas that look very different from normal liver cells are positive less often, in only about half of cases.
Other positive cancers. Some adenocarcinomas of the stomach and intestine, and rare tumors called hepatoid carcinomas, can be positive even though they did not start in the liver.

For these reasons, pathologists usually test for HepPar-1 as part of a panel. This panel often includes arginase-1, which is positive more often in poorly differentiated hepatocellular carcinoma, and glypican-3. Your doctor may also check your alpha-fetoprotein (AFP) level in your blood.

What does a HepPar-1 result mean in my report?

A HepPar-1 result in your report describes whether the cells being studied are positive for this marker. Your report may describe the result in one of a few ways:

Positive. The tumor cells are positive for HepPar-1, which supports a tumor made of liver cells, such as hepatocellular carcinoma, when the other findings fit.
Negative. The tumor cells are negative for HepPar-1, which points to a different tumor type, although a negative result does not rule out hepatocellular carcinoma.
Positive in background liver. The normal liver around the tumor is positive, while the tumor is negative, which shows that the test worked.

Questions to ask your doctor

Were the tumor cells in my sample positive or negative for HepPar-1?
Which other markers, such as arginase-1 or glypican-3, did the pathologist test?
Did the tumor start in my liver, or did it spread there from another organ?
If it is a liver cancer, is it hepatocellular carcinoma or cholangiocarcinoma?
Does my liver show other changes, such as scarring or cirrhosis?
Should I have a blood test for alpha-fetoprotein (AFP)?