What to Know About Hep C and Liver Cancer

by Lexi Krupp Health Writer

Hepatitis C might not be a new virus, but it’s a major public health problem—more than 400,000 people around the world die from it each year, according to the World Health Organization. The virus is so serious because it infects the liver, causing permanent damage to the organ if left untreated. Curiously though, while hep C causes some people to develop fatal diseases, others fight it off without medical intervention. As scientists continue working to understand the virus, here’s what we know right now about the way hep C leads to liver damage—and possibly cancer.

Hep C virus
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Hep C Takes Over Your Liver

Little-known fact of the day: Hep C is actually a group of seven viral strains with different genetic makeup. When one of these strains enters the body, it heads for the liver, your body’s largest organ that’s responsible for removing toxins, breaking down fat, and maintaining a balance of chemicals in the blood. There, the virus hijacks individual liver cells and replicates at an astonishing speed—making billions of new copies each day, says Michael Houghton, Ph.D., a virologist at the University of Alberta, Edmonton, and one of the scientists who first discovered the hepatitis C virus.

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How Your Body Fights Back

When hep C launches an attack on your liver, your immune system gets fired up. It sends white blood cells and toxic chemicals to fight off the hep C invasion and develops antibodies designed to thwart the virus. In about one in five cases, these robust defenses are enough to destroy the virus for good. Researchers believe this is due to a complex mix of genetic factors lead some people to have more active immune systems that respond quickly—and this is key to squashing the virus. But the vast majority of people can’t stamp out hep C on their own.

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When Hep C Becomes Chronic

If you’re one of the millions of people with ongoing hepatitis C infections, you’re in a sort of no man’s land, where your immune system keeps beating away at the virus and trying to kill infected liver cells, but it can never quite clear the infection. Over time, that constant assault on your liver causes inflammation, triggered by your body’s immune response. This, combined with the direct action of the virus, damages the organ. “You have this smoldering fire in the liver,” explains Houghton.

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Scar Tissue Accumulates in the Liver

When the liver is injured it forms a scar, “the same way your skin does when you cut it,” says Ira Jacobson, M.D., a professor of medicine and director of hepatology at New York University’s Langone Medical Center. In some cases, scar tissue can build up into an extensive network that changes the texture of the organ, giving it a “lumpy, bumpy” appearance, according to Dr. Jacobson. This advanced stage of liver damage is called cirrhosis, and it means blood can no longer properly flow through your liver.

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Spotting Signs of Cirrhosis

One of the difficulties with liver disease is that symptoms often don’t crop up until advanced stages. If you do notice something, the most common signs include fatigue, nausea, weight loss, easy bleeding or bruising, jaundice, and swollen legs. Luckily, several blood and imaging tests can be used to diagnose the disease. One is called an elastography, which measures how elastic (or stiff) your liver tissue might be by transmitting sound waves through your body. Because scar tissue stiffens the liver, this scan gives clinicians a quick snapshot of the level of damage.

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Why Cirrhosis Is Worse for Some People

Close to one in four people will develop cirrhosis of the liver after living with a hep C infection for at least 20 years, according to a large review of clinical studies. Men and older people are more susceptible to the disease. In addition to genetic factors, chronic health conditions, and behaviors like heavy drinking and smoking, the type of viral strain you have can also increase the risk of cirrhosis: “Genotype 3” is particularly harmful, accounting for about 20% of infections in the U.S.

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Other Causes of Cirrhosis

If you have certain conditions like an HIV infection or hep B, in addition to your hep C diagnosis, you are at greater risk of developing advanced scarring of the liver, says Samuel Antwi, Ph.D., an epidemiologist at Mayo Clinic in Florida. Other conditions that predispose you to severe scarring include fatty liver disease, diabetes, or metabolic syndrome. But regardless of what else is going on, an untreated hep C infection is likely to lead to cirrhosis eventually, even if it takes decades, he says.

Hepatocellular Carcinoma
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Cirrhosis and Liver Cancer

When people have cirrhosis of the liver, they’re more likely to develop a type of liver cancer called hepatocellular carcinoma. Researchers don’t fully understand the link between the two conditions, but one explanation is that the buildup of scar tissue and ongoing inflammation creates an environment where cancerous tumors are more likely to grow. Regardless of exactly why scarring of the liver is linked to cancer, “anyone with cirrhosis should be screened regularly for liver cancer,” says Dr. Jacobson.

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Other Hep C and Liver Cancer Causes

There are three additional reasons why hep C might lead to liver cancer. First, an infection creates a high turnover of liver cells, as both the virus and your immune system kill cells and your body works to replace them. Due to chronic inflammation, these new liver cells may contain damaged DNA, which increases the chance of developing cancer. Meanwhile, an inflamed liver may signal to your immune system to produce toxic chemicals—and these, too, might trigger cancerous mutations. Finally, the immune system may alter certain gene activity, encouraging tumor growth.

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Who Is Most Susceptible to Liver Cancer?

Hep C patients account for roughly 20% of liver cancer patients worldwide, according to recent studies. As with cirrhosis, men and older patients are more likely to develop liver cancer, but anyone with extensive scarring of the liver is at risk. In general, people who don’t drink excessively or smoke, maintain a healthy body weight, and have their glucose levels under control have a lower risk of developing liver cancer.

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Can Hep C Treatment Lower Liver Cancer Risk?

Treatment helps, but it’s not foolproof. Between 3% and 9% of people treated for hep C with direct acting antivirals still go on to develop hepatocellular carcinoma. That's because although these drugs work to target the virus, they don’t prevent the progression of cancer. So if the early stages of cancer have already been set in motion, the treatment won’t help. And if patients receive treatment for hep C after years of infection, they might have accrued enough liver damage to cause the disease, explains Antwi. “Early treatment is crucial,” he says.

  • Global Mortality from Hep C: World Health Organization (2019). “Hepatitis C: Key Facts” who.int/news-room/fact-sheets/detail/hepatitis-c

  • Hep C Overview: Journal of Medical Virology. (2016). “Hepatitis C-A Clinical Review.” pubmed.ncbi.nlm.nih.gov/27097298/

  • Hep C Viral Strains and Vaccine Development: Journal of Virology. (2019). “A Recombinant Hepatitis C Virus Genotype 1a E1/E2 Envelope Glycoprotein Vaccine Elicits Antibodies That Differentially Neutralize Closely Related 2a Strains Through Interactions of the N-Terminal Hypervariable Region 1 of E2 With Scavenger Receptor B1.” pubmed.ncbi.nlm.nih.gov/31462563/

  • How Hep C Multiplies in the Liver: American Journal of Pathology. (2003). “Dynamics of Hepatitis C Virus Replication in Human Liver.” ncbi.nlm.nih.gov/pmc/articles/PMC1868229/

  • Incidence of Liver Cancer: International Journal of Cancer. (2018). “Fraction and Incidence of Liver Cancer Attributable to Hepatitis B and C Viruses Worldwide.” pubmed.ncbi.nlm.nih.gov/29388206/

  • Hep C and Liver Cancer: BMC Med. (2017). “Hepatitis C-related Hepatocellular Carcinoma in the Era of New Generation Antivirals.” pubmed.ncbi.nlm.nih.gov/28288626/

  • Direct Acting Antivirals and Liver Cancer: Cancer Prevention Research. (2019). “Risk of De Novo Hepatocellular Carcinoma Following Use of Direct Acting Antiviral Medications for Treatment of Chronic Hepatitis C.” pubmed.ncbi.nlm.nih.gov/31451519/

Lexi Krupp
Meet Our Writer
Lexi Krupp

Lexi Krupp is a journalist who covers health and science stories for audio and print. Before moving to New York City, she taught ecology in Wisconsin and Maine.