07. PTC: Cancer Risks for Liver Recipients

"With the notable increase in life expectancy after liver transplantation, together with the lengthy exposure to immunosuppression, transplant recpients are at risk of developing neoplastic disease, which accounts for almost 30% of deaths 10 years after liver transplantation.  The risk of malignancy is two to four times higher in transplant recipients than in an age- and sex-matched population and cancer is expected to surpass cardiovascular complications as the primary cause of death in transplanted patients within the next 2 decades . . . "
- Neoplastic disease after liver transplantation: Focus on de novo neoplasms

Why am I at greater risk of developing cancer after liver transplant?

All organ transplant recipients are at heightened risk of developing cancer after transplant. This is because although life-sustaining, long-term use of immunosuppressant drugs lowers the body’s ability to fend off certain cancers. When you are taking immunosuppressant drugs, your immune response is lowered, and this is what helps to prevent your body from rejecting your new liver. It also means that your body is less able to recognize and destroy cancer cells or infections that can cause cancer.

Additionally, because immunosuppressant drugs reduce your body’s natural monitoring and disease response, you are at increased risk of developing certain viral infections that are linked to increased cancer risk. Examples of these viruses include the Epstein-Barr virus which is associated with lymphoma, Hepatitis which is linked to liver cancer, the Herpes virus which is associated with Kaposi sarcoma, and the Human Papilloma Virus that is associated with skin cancers. There is also a very small chance that cancer was already present in the transplanted organ.

Cancer occurring after transplantation, either recurrent or de novo malignancy, is a serious complication of liver transplantation and of great concern to transplant physicians and patients. Liver Transplant (LT) recipients are at risk of developing cancer after transplantation from a variety of mechanisms.  Prior to transplantation, long-term exposure to known carcinogens such as alcohol and tobacco or infection with oncogenic viruses such as HBV and HCV place many patients with advanced liver disease at increased risk.  After transplantation, immunosuppressive medications result in decreased immune surveillance against malignant cells and increases the risk of malignancies mediated by viruses such as human papilloma virus, Epstein–Barr virus and human herpes virus-6.  With the rising incidence of hepatocellular carcinoma (HCC), an increasing number of liver transplantations are being performed for the treatment of hepatic malignancies, which may recur after LT (OPTN Data 2004).

Note: For full versions of any of the INTRO video clips below, go to the full library of ONLINE resources at https://www.triowebptc.org/link/resource-library.html

Which cancers am I at greater risk for, and how high is my risk?

For all people, cancer risk increases as a natural part of the aging process. According to the researchers writing in the Journal of Hepatology, if you used alcohol or tobacco before liver transplant, the risk of developing cancer after receiving a new liver is higher compared to those who had not used alcohol or tobacco. The risk of cancer increases with each year of immunosuppressant drug use. This means that the longer liver transplant recipients survive post-transplant, the greater the incidence of cancer. There are also certain lifestyle choices that can raise your risk of cancer, such as not getting regular exercise, tobacco use, alcohol use, or having a poor diet. According to the National Cancer Registry, approximately one out of six liver transplant recipients are at risk of developing a form of cancer in the 20 years post-transplant. The first year right after transplant is the year with the highest risk, but the survival rate has increased by over 80% in the last 30 years. When cancer does develop, on average, it occurs in people in their mid-50s.

Common cancers that present the greatest risk include: lung cancer, kidney cancer, liver cancer, lymphoma, skin cancer and non-melanoma skin cancers. Among other cancer risks, the risk levels differ based on risk characteristics like lifestyle choices and age, and intensity of immunosuppressive medications the transplant recipient is taking. Explore the look pages to learn more about each of these types of cancer and how to manage your risk.

• Skin Cancer: Research by the National Cancer Registry found that skin cancer was the most common type of cancer developed by people who received a liver transplant. Non-melanoma skin cancer including squamous cell carcinoma and basal cell carcinoma was more common among older liver recipients.
• Hepatocellular Carcinoma (HCC): HCC is one of the very common reasons why people need a new liver in the first place. For people who had HCC before receiving a new liver, they are 10-18% more likely to have HCC come back. This usually happens within two years after transplant.
• Post-transplant Lymphoproliferative Disorders (PTLD): PTLD is common for all organ recipients, and as mentioned above, is associated with Epstein-Barr virus. PTLD happens in about 2-4% of liver transplant recipients. Hepatitis C virus may also increase the risk of PTLD, but there are mixed findings on this in the research. Developing Non-Hodgkin lymphoma is more common in males, younger transplant recipients, and soon after receiving the new liver.
• Solid Tumor Cancers: These are more likely to occur soon after receiving the new liver. There is a higher risk of cervical, vulvar, and anal squamous cell carcinomas. The risk for these cancers is higher for people over 40 years old.
• Colon Cancer: (Colorectal Carcinoma, CRC): Liver recipients who have Inflammatory Bowel Disease might be more likely to develop CRC, however research findings on this are mixed.
• Oral, Laryngeal and Esophagus Cancers: People who smoke or use tobacco, and who used alcohol or had alcoholic liver disease before transplant are at higher risk of developing these cancers.

. . . We offer the option of a more more technical reading in the following section:  07a Deeper technical reading (<< click here)

With excellent long-term survival rates, the causes of morbidity and mortality of liver transplant (LT) recipients are primarily cardiovascular diseases, renal insufficiency, and de novo neoplasm, the latter of which account for almost 30% of deaths at 10 years post-transplantation.  Apart from hepatic causes, neoplasm has been reported as the most common cause of death in patients surviving at least 1 year after LT, and is responsible for approximately 40% of deaths. Overall, it is estimated that in LT recipients the incidence of neoplasms is between 3.1% and 14.4%, and the cancer-related mortality rate is between 0.6% and 8.0%.

While infection and surgical complications are prominent causes of mortality in the peri-operative and early post-transplantation period, malignancy has emerged as an important late cause of death in LT recipients. In a series of 4000 consecutive patients who underwent LT between February 1981 and April 1998 at the University of Pittsburgh, 219 died from recurrent or de novo malignancy (including PTLD). Ninety-one cancer-related deaths (42%) occurred more than 3 years after LT.  Cancer was the second most common cause of death after infection and surpassed cardiovascular disease as a cause of death among LT recipients.

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