The Progression of Liver Disease to Liver Cancer

Paul Hong, MD and Jonah Rubin, MD
Loyola University Medical Center

This presentation is an excerpt from the ALF 2021 Poster Competition. This competition showcases posters and a brief video created by early career investigators from across the country on six areas of educational focus: fatty liver disease, liver cancer, liver transplantation, pediatric liver disease, rare liver disease and viral hepatitis. Participants are tasked with translating complicated medical information into a poster which can be easily understood by patients or the public. Posters are reviewed by a formal panel of judges comprised of Medical Advisory Council members, Board Members and friends of ALF to select a winner in each category.

Liver cancers are 4th most common cause of cancer-related deaths worldwide and it is the 2nd most lethal cancer. While therapies and survival rate for other types of cancer has dramatically improved over the past decades, prognosis of liver cancer remains unfavorable and deadly. In fact, the death rate in the US has increased by more than 40% within the last two decades.

There are actually different types of liver cancers, but today I will mainly focus on hepatocellular carcinoma (or HCC), which is a primary cancer arising from the cells of the liver and it accounts for 90% of liver cancer. Majority of the HCC occurs in patients with underlying liver disease. There are many factors that can contribute, including genetic predisposition, family history, environmental exposure, and age and many others, but the underlying theme is that an HCC typically arises from an already damaged liver. They include viral hepatitis, such as hep B, hep C; alcohol disease, fatty liver disease, and now increasing prevalence of obesity and diabetes which amplify the risk of liver diseases and therefore increases the risk of development of a cancer.

The pathogenesis of a liver disease becoming an HCC is a complex multi-step process. When a liver gets damaged, the liver tries to regenerate and replace the damaged cells. This repair process involves production of collagen which are fibers that stiffen the cells.
Chronic liver disease leads to persistent activation of this repair process. It will make the liver more and more stiffer, and all the collagen will replace the healthy cells. This is what we typically call a scarring of the liver, or fibrosis. If left untreated, this scarring will continue to a severely scarred state of the liver, and we call that a cirrhosis.

Cirrhotic livers are more prone to accumulate DNA mutations. These mutations interfere with the normal cell cycle (such as the growth and division of cells) and the cells instead of regenerating properly, will accumulate together to form nodules. These are called dysplastic nodules and they are pre-cancerous.

Additional damage and prolonged inflammation will provide these abnormal cells with proliferative, invasive, and survival advantages. including evading the body’s immune system, having an exclusive vascular supply to grow unchecked, and essentially becoming immortal cancer cells. Progressively, the dysplastic nodules transform into ultimately a hepatocellular carcinoma.