Common Types of Liver Cancer Treatment Risk

Liver cancer treatments such as surgery, chemotherapy, or liver transplant place metabolic stress on the body. Aside from treating cancer, treatments can disrupt metabolic processes and result in complications. These may include

• Insulin resistance
• Sarcopenia, also known as muscle wasting
• Gut dysbiosis, when the gut microbiome population becomes imbalanced
• Lipid metabolism, i.e., how the liver processes fats (lipid metabolism)

This article goes in-depth into these risks and complications that patients should be aware of before making treatment decisions.

The liver regulates blood sugar levels by converting glucose to glycogen and releasing it when energy is needed. However, liver cancer treatment can disrupt this balance.

Partial hepatectomy, a common surgical option for liver disease, reduces the liver's glycogen capacity. This raises the risk of high blood sugar, known as hyperglycemia. Similarly, chemotherapy and targeted therapies can disrupt glucose intake and affect insulin sensitivity. This can result in the development of new-onset diabetes mellitus.

Liver transplant recipients face additional risks. Studies have shown long-term use of immunosuppressants, especially corticosteroids, can affect glucose regulation. This has resulted in post-transplant diabetes mellitus (PTDM) in up to 30% of patients. Dietary changes, monitoring blood sugar levels and in some cases, medication can help support post-treatment metabolic health.

Protein synthesis

The liver produces proteins such as albumin, which is responsible for transporting nutrients to tissues. In liver cancer patients, increased energy demands and chronic inflammation as a result of treatment can overwhelm the liver, causing protein breakdown to exceed protein synthesis. In addition, impaired albumin production reduces nutrient delivery to tissues. This hinders the repair process and further contributes to muscle wasting.

Chronic inflammation

Radiation, chemotherapy and the cancer itself can cause systemic inflammation. This releases inflammatory cytokines (signaling molecules) that activate pathways that promote muscle protein breakdown. Inflammation also inhibits muscle protein synthesis, making it more difficult for the body to rebuild lost muscle.

Hyperammonemia

A failing liver cannot effectively process and remove ammonia, a toxic by-product of protein metabolism. Normally, the liver converts ammonia into urea via the urea cycle. When the cycle falters, muscles attempt to neutralize excess ammonia by binding it to glutamine. This process depletes muscle amino acids and accelerates muscle wasting.

Nutritional deficiencies

After surgery, the liver’s ability to metabolize and store essential nutrients is impaired, and bile production is reduced. Key deficiencies include:

• Vitamin D: Necessary for muscle protein synthesis and immune function. A deficiency in vitamin D correlates with the progression of sarcopenia.
• Zinc and magnesium: Essential for enzyme function, such as hepatic detoxification and insulin sensitivity. Reduced levels can increase metabolic stress.
• Fat-soluble vitamins (A, E, K): A damaged liver struggles to absorb and store vitamins. Vitamin E’s oxidative properties protect muscle membranes from oxidative damage, while vitamin K supports bone health.

When these vitamins are lacking, muscle loss accelerates. As muscle mass decreases, the body becomes less efficient at storing and using energy. This places even more strain on the liver. This creates a cycle where nutrient deficiencies and muscle loss reinforce each other, making it increasingly difficult for the liver to meet the body’s metabolic demands.

Liver cancer survivors frequently experience gut dysbiosis, the imbalance in gut bacteria as a result of treatment side effects and impaired liver function.

The condition involves two key shifts:

• A decrease in beneficial bacteria, such as Bifidobacterium, which reduces inflammation, and Lactobacillus, which supports immune function
• The increased growth of pro-inflammatory Proteobacteria such as E. coli and Klebsiella

These harmful bacteria release toxins such as lipopolysaccharides (LPS) that can damage the intestinal lining, enter the bloodstream, and trigger systemic inflammation. This imbalance arises from multiple treatment-related factors:

• Liver dysfunction disrupts the synthesis and secretion of bile acids essential for maintaining microbial balance and preventing the overgrowth of harmful bacteria.
• Surgical stress (e.g., hepatectomy) and chemotherapy directly damage the intestinal barrier, leading to bacterial translocation and inflammation.
• Immunosuppressants after transplantation and antibiotics for prophylaxis can indiscriminately reduce beneficial bacteria, allowing opportunistic bacteria such as Enterobacteriaceae to thrive.
• Chronic inflammation from cancer or treatment upregulates pro-inflammatory cytokines, which further disrupts communication between the liver, the intestine, and the intestine's microbiome and promotes dysbiosis.

These changes in the microbiome can lead to systemic inflammation, hinder the absorption of nutrients and disrupt bile acid metabolism, causing further complications such as sarcopenia and insulin resistance.

Insulin resistance, sarcopenia, gut dysbiosis and nutritional deficiencies are interconnected conditions that amplify each other, creating a challenging cycle for survivors. Nutritional rehabilitation and careful metabolic monitoring will be essential for restoring metabolic balance and supporting long-term recovery after treatment.