Immunotherapy for Liver Cancer: Types, Side Effects & More

In 2020 alone, there were over 900,000 new cases of liver cancer reported globally, highlighting the widespread impact of this disease. Liver cancer ranks as the 6th most common cancer worldwide, with significant gender disparities. It holds the 5th position among men and the 9th among women. 

Liver cancer remains a significant global health concern, necessitating continued efforts in prevention, early detection, and treatment to mitigate its impact. The prevalence and impact of liver cancer underscore gender differences, emphasizing the need for targeted awareness and intervention strategies. Immunotherapy is showing potential in reducing side effects and improving survival rates, offering hope in the battle against liver cancer.

What is Liver Cancer?

Liver cancer, or hepatocellular carcinoma, is a condition where abnormal cell growth occurs in the liver. The liver, a vital organ, plays a crucial role in filtering blood, processing nutrients, and detoxifying harmful substances. When cells in the liver start multiplying uncontrollably, it forms a tumor that can interfere with the organ’s normal functions.

Several factors contribute to the development of liver cancer, including chronic viral hepatitis, cirrhosis (scarring of the liver), and exposure to toxins like aflatoxins. 

Types of Liver Cancer

Liver cancer originates within the liver and is classified into five main types based on the initial cell type.

  1. Hepatocellular Carcinoma (HCC)

Hepatocellular carcinoma, also known as hepatoma or HCC, is the main type of primary liver cancer, originating in hepatocytes, the main liver cells. This section focuses on hepatocellular carcinoma due to its common occurrence.

Developing from hepatocytes, HCC is closely linked to cirrhosis, which results from liver scarring due to past damage, like that from hepatitis B or C viruses or prolonged alcohol use. The prominence of hepatocellular carcinoma is highlighted by its higher occurrence in men and increases with age, becoming more common as people get older.

Understanding hepatocellular carcinoma is crucial, given its status as the most common primary liver cancer. The connection between HCC and cirrhosis underscores the need to address underlying causes like viral infections or alcohol misuse. Recognizing demographic trends, especially its higher incidence in men and the age-related increase, is vital for effective awareness, prevention, and early detection in managing hepatocellular carcinoma.

  1. Fibrolamellar Carcinoma

Fibrolamellar carcinoma is a rare form of liver cancer, especially uncommon among individuals in their 20s or 30s. Unlike some liver cancers, it’s not usually connected to cirrhosis or infections like hepatitis B or C.

What makes fibrolamellar carcinoma distinct is that it often doesn’t show elevated levels of a substance called alpha-fetoprotein (AFP) in the blood, which is commonly found in other liver cancer types.

Because it’s rare and has unique characteristics, understanding fibrolamellar carcinoma is important. It typically affects younger age groups, and its development isn’t tied to common liver-related factors like cirrhosis or viral infections. The absence of increased AFP levels in the blood sets it apart from other liver cancers, making it vital for healthcare professionals to recognize these specific traits for accurate diagnosis and appropriate treatment. 

  1. Bile Duct Cancer (Cholangiocarcinoma)

Bile duct cancer, known as cholangiocarcinoma, specifically targets the bile ducts – tubes connecting the liver and gallbladder to the small bowel. These ducts play a crucial role in transporting bile, produced by the liver, to aid in digesting fats from food.

Cholangiocarcinoma is a rare form of cancer. When it originates in the ducts outside the liver, it’s termed extrahepatic cholangiocarcinoma. On the other hand, if the cancer begins in the ducts within the liver, it’s referred to as intrahepatic cholangiocarcinoma. The latter is categorized as a type of primary liver cancer.

Understanding this cancer involves recognizing its connection to the bile duct system and the vital function it serves in digestion. Despite its rarity, accurate classification of extrahepatic and intrahepatic cholangiocarcinoma is essential for appropriate diagnosis and targeted treatment strategies.

  1. Angiosarcoma

Angiosarcoma, also referred to as haemangiosarcoma, is a rare form of soft tissue sarcoma originating in the blood vessels of the liver. This cancer is predominantly diagnosed in the elderly and is characterized by its rarity. Often known as liver angiosarcoma, this malignancy poses a significant medical challenge due to its uncommon occurrence. 

The disease’s distinct feature is its development within the liver’s vascular system. Given its infrequency, angiosarcoma demands specialized attention and research efforts to better understand its nature and devise effective treatment strategies for those affected by this particular form of liver cancer.

  1. Hepatoblastoma

Hepatoblastoma is an exceptionally rare primary liver cancer, typically impacting young children and frequently diagnosed before the age of 2. This uncommon malignancy necessitates specialized attention due to its distinct occurrence in pediatric cases, emphasizing the need for targeted research and tailored treatments for affected children.

Risk Factors for Liver Cancer

Explore influences, from lifestyle choices to environmental factors, that impact susceptibility to liver cancer.

  • Increased risk factors for liver cancer include cirrhosis, chronic viral hepatitis, liver fluke infestation, and prolonged use of high-dose hormonal contraceptives and smoking.
  • Obesity heightens the likelihood of liver cancer, emphasizing the importance of maintaining a healthy weight.
  • Regular alcohol consumption elevates the risk of liver cancer, highlighting the need for moderation in alcohol intake.
  • Aflatoxin-contaminated foods contribute to an increased risk of liver cancer, underscoring the importance of food safety measures.
  • Coffee consumption has a protective effect, decreasing the risk of liver cancer, advocating for the inclusion of coffee in a balanced diet.
  • Evidence suggests that incorporating fish into the diet may potentially reduce the risk of liver cancer.
  • Physical activity shows promise in decreasing the risk of liver cancer, emphasizing the benefits of an active lifestyle.
  • Cirrhosis, chronic viral hepatitis, and liver fluke infestation are strongly linked to an elevated risk of liver cancer.
  • Long-term use of oral contraceptives with high estrogen and progesterone, along with smoking, contributes to an increased risk of liver cancer.
  • Maintaining a healthy lifestyle by avoiding obesity, limiting alcohol intake, ensuring food safety, and incorporating protective factors like coffee and fish may help mitigate the risk of liver cancer.

What is Immunotherapy?

Immunotherapy, a cancer treatment, activates the immune system to eliminate cancer cells, potentially minimizing side effects and enhancing survival compared to conventional liver cancer therapies. Ongoing research is continuously refining the application of immunotherapy for liver cancer, with current usage focusing on cases where cancer has spread within the liver or to distant parts of the body.

Effective Treatments for Liver Cancer

Liver cancer treatment encompasses various options tailored to the disease stage. Standard approaches include surveillance, surgery, liver transplant, ablation, embolization, targeted therapy, and radiation. Atezolizumab is a prominent choice for advanced hepatocellular carcinoma (HCC). 

Immunotherapy Overview

Immunotherapy leverages the body’s immune system to combat cancer. Six FDA-approved options for liver cancer include:

Checkpoint Inhibitors

Atezolizumab: Approved for first-line treatment in advanced cases.

Dostarlimab: Targeting PD-1/PD-L1, approved for advanced cases with DNA mismatch repair deficiency.

Durvalumab: Combined with tremelimumab for unresectable liver cancer subsets.

CTLA-4 Pathway Inhibitor

Ipilimumab: Approved for previously treated liver cancer.

PD-1/PD-L1 Inhibitors

  • Pembrolizumab: Approved for advanced cases, particularly those with high microsatellite instability, DNA mismatch repair deficiency, or high tumor mutational burden.
  • Tremelimumab: Combined with durvalumab for unresectable liver cancer subsets.

Immunotherapy enhances immune responses, yet caution is advised for patients with a history of hepatitis infection, where immune activity may harm normal liver cells. Treatment decisions should be personalized based on individual health profiles.

Immune Checkpoint Inhibitors in Liver Cancer Treatment

The immune system, a vital defender against threats, employs “checkpoints” – proteins on immune cells regulating responses to avoid attacking normal cells. In liver cancer, these checkpoints are sometimes manipulated by cancer cells to evade immune attacks. Cutting-edge drugs targeting these checkpoints show promising results in liver cancer treatment.

PD-1 and PD-L1 Inhibitors

PD-1, found on immune cells called T cells, acts as an “off switch” when binding with PD-L1 on other cells, signaling the T cell to avoid attacking. Drugs like Atezolizumab and Durvalumab target PD-L1, disrupting this interaction, enhancing immune responses, and inhibiting tumor growth.

  • Atezolizumab, serves as a frontline treatment for inoperable or metastatic liver cancer.
  • Durvalumab, combined with tremelimumab, becomes a primary treatment for surgically unresectable liver cancer.

These drugs are administered through intravenous infusions every 2 to 4 weeks.

PD-1 Inhibitors

Pembrolizumab targets PD-1, boosting the immune response against cancer cells, potentially shrinking tumors. They find application in advanced liver cancer cases post-prior treatments, like sorafenib.

 

  • Pembrolizumab may be used alone.
  • Ipilimumab may be offered in combination with some other drug.

Intravenous infusions are administered every 2 to 6 weeks.

CTLA-4 Inhibitors

Ipilimumab and tremelimumab operate differently, blocking CTLA-4, another T cell protein. They bolster immune responses but with distinct targets.

  • Tremelimumab, paired with durvalumab, becomes a frontline treatment for unresectable liver cancer.
  • Ipilimumab, is used in post-prior treatments like sorafenib.

Intravenous infusions are typically given every 3 to 4 weeks.

Potential Side Effects

Common side effects include fatigue, fever, cough, nausea, itching, rash, loss of appetite, and muscle or joint pain. However, more severe reactions are possible:

  • Infusion Reactions: Allergic-like reactions during drug administration, including fever, chills, rash, dizziness, and breathing difficulties.
  • Autoimmune Reactions: Removal of immune system safeguards can lead to the immune system attacking other organs, potentially causing serious or life-threatening issues.

Serious side effects are observed more frequently with ipilimumab than with PD-1 and PD-L1 inhibitors. Prompt reporting of new side effects to healthcare professionals is crucial, and in case of serious complications, treatment may be halted, with high-dose corticosteroids to suppress the immune system if needed. Understanding these nuances is vital for informed decisions and effective liver cancer management.

Immunotherapy Administration For Liver Cancer

Immunotherapy for liver cancer involves the administration of drugs through intravenous (IV) infusions, with the frequency determined by the specific drugs prescribed. The process unfolds as follows:

  • Atezolizumab: Administered every 2, 3, or 4 weeks.
  • Durvalumab and Tremelimumab: Typically given every 2, 3, or 4 weeks.
  • Pembrolizumab: Scheduled every 2, 3, 4, or 6 weeks.

During the infusion, mild discomfort may be experienced, and some individuals might encounter side effects shortly after the treatment. It is crucial to communicate any observed side effects promptly to your healthcare provider for proper monitoring and management. This guided timeline aims to offer clarity on the rhythm of immunotherapy sessions, ensuring a comprehensive understanding for individuals undergoing liver cancer treatment.

Immunotherapy Success in Liver Cancer

Researchers are actively investigating the effectiveness of immunotherapy in treating liver cancer, aiming to optimize its use. The potential benefits of immunotherapy include an increase in survival rates and a reduction in side effects associated with other cancer treatments.

In a 2018 clinical trial involving individuals with advanced liver cancer, who had previously received sorafenib (Nexavar), found that 17% of those treated with pembrolizumab (Keytruda) had a complete or partial response to the immunotherapy.

These findings underscore ongoing efforts to understand and harness the potential of immunotherapy as a valuable treatment option for liver cancer, with the aim of improving outcomes and minimizing treatment-related side effects.

Who Qualifies for Liver Cancer Immunotherapy?

 

Immunotherapy is mainly for advanced liver cancer, but if you have early-stage or other types, doctors might suggest different treatments first. It’s not great for people with a history of hepatitis or liver damage because it can harm healthy liver cells. Since about 80% of liver cancer cases come from hepatitis, not everyone can get immunotherapy. But don’t worry, there are other effective treatments available for liver cancer.

Immunotherapy for Liver Cancer: Side Effects and Vigilance

Explore potential effects, from fatigue to rare reactions, ensuring informed decisions for liver cancer immunotherapy.

  • Immunotherapy side effects for liver cancer may include fatigue, weakness, cough, nausea, itchiness, rash, loss of appetite, and muscle or joint pain.
  • Additional potential side effects consist of constipation and diarrhea.
  • Rare but severe reactions may involve infusion reactions with symptoms like fever, chills, facial flushing, rashes, itchiness, dizziness, and wheezing.
  • Autoimmune reactions, where the immune system attacks healthy cells, can lead to serious complications, especially with ipilimumab, causing issues such as hormonal or lung problems.
  • Immediate medical attention is crucial for infusion reactions, while serious autoimmune reactions may have life-threatening consequences.

Your healthcare provider will walk you through these potential side effects, and it’s essential to keep them informed about any experiences you may have.

Immunotherapy & Other Liver Cancer Treatment Options

Immunotherapy activates the body’s immune system, prompting a targeted response against cancer cells. This approach harnesses the natural defense mechanisms of the body.

Surgery offers interventions like hepatectomy and liver transplant, with the effectiveness contingent on the tumor’s size and spread. Radiofrequency ablation introduces targeted heat to eliminate cancerous cells.

Radiation therapy encompasses options such as external beam radiation, albeit used less frequently due to potential side effects. Radiosurgery, brachytherapy, and stereotactic body radiation therapy (SBRT) provide focused energy delivery, often yielding painless experiences with manageable side effects.

Interventional Radiology employs minimally invasive techniques like chemoembolization, radioembolization, and percutaneous ablation. These methods either block blood flow to tumors or apply targeted heat/cold for destruction.

Chemotherapy administers potent drugs orally, intravenously, or through injection. This disrupts cancer cell growth and reproduction, facilitating the shrinkage of previously inoperable tumors.

Understanding these diverse treatment options enables healthcare professionals to tailor approaches based on individual cases, considering factors such as tumor characteristics and the overall health of the patient. Collaborative decision-making ensures the development of personalized and effective plans for managing liver cancer.

DENVAX: Dendritic Cell Therapy For Cancer

DENVAX, a groundbreaking therapy in the realm of cancer treatment, focuses on harnessing the potential of dendritic cells – the immune system’s superheroes. Specifically designed for combating solid tumors, including challenging cases like lung cancer, DENVAX seamlessly integrates into existing treatment plans without causing significant disruptions to daily life. In the landscape of cancer immunotherapy, DENVAX operates as the fourth pillar alongside surgery, radiation, and chemotherapy.

In the battle against cancer, where the immune system may overlook cancer cells, DENVAX steps in by deploying activated dendritic cells. These specialized immune cells trigger robust immune responses that traverse the body, effectively targeting and eliminating cancer cells. As an adjunct treatment, DENVAX harmoniously complements surgery, radiation, and chemotherapy, contributing to a comprehensive, multi-disciplinary approach.

Noteworthy benefits of DENVAX include its role in enhancing the quality of life, extending lifespan, and improving clinical outcomes for patients with lung cancer and other solid tumors. Its user-friendly nature and compatibility with other modalities make it an ideal choice for personalized cancer care. In cases of advanced stage IV cancer, DENVAX serves as palliative therapy, providing comfort to patients while maintaining safety and minimal toxicity. Experience the next frontier in lung cancer treatment with DENVAX, where safety and effectiveness converge for a brighter and more hopeful future.

Final Note

In the fight against liver cancer, understanding diverse treatments is key. From surgery to immunotherapy, each approach has its role. Immunotherapy, activating the body’s defenses, shows promise, especially for advanced cases. Yet, it’s not for everyone, especially those with liver damage history. Other treatments like surgery, radiation, and chemotherapy remain vital. Recognizing side effects, seeking prompt medical attention, and embracing a tailored plan with your healthcare team ensures comprehensive liver cancer management. Stay informed, stay vigilant, and together, let’s navigate the path to better liver health.

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