Hepatocellular Carcinoma
Disease Details
Family Health Simplified
- Description
- Hepatocellular carcinoma is a primary malignant tumor of the liver, usually arising in the setting of chronic liver disease and cirrhosis.
- Type
- Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. It is not typically considered a hereditary cancer, as it usually arises from chronic liver disease and cirrhosis, often due to hepatitis B or C infection, alcohol use, or non-alcoholic fatty liver disease. While there is no clear pattern of genetic transmission, certain genetic mutations and familial syndromes (e.g., hereditary hemochromatosis, alpha-1 antitrypsin deficiency) can increase the risk.
- Signs And Symptoms
- Most cases of HCC occur in people who already have signs and symptoms of chronic liver disease. They may present with worsening symptoms or without symptoms at the time of cancer detection. HCC may present with non-specific symptoms such as abdominal pain, nausea, vomiting, or feeling tired. Some symptoms that are more closely associated with liver disease include yellow skin (also called jaundice), abdominal swelling due to fluid in the abdominal cavity, easy bruising from blood clotting abnormalities, loss of appetite, unintentional weight loss, abdominal pain, nausea, vomiting, or feeling tired.
- Prognosis
- The usual outcome is poor because only 10–20% of hepatocellular carcinomas can be removed completely using surgery. If the cancer cannot be completely removed, the disease is usually deadly within 3 to 6 months. This is partially due to late presentation with tumors, but also the lack of medical expertise and facilities in the regions with high HCC prevalence. However, survival can vary, and occasionally people survive much longer than 6 months. The prognosis for metastatic or unresectable HCC has improved due to the approval of Sorafenib (Nexavar®) for advanced HCC.
- Onset
- Hepatocellular carcinoma (HCC) typically develops gradually over time, often in the context of chronic liver diseases such as hepatitis B, hepatitis C, or cirrhosis. The onset can be insidious, with symptoms appearing late in the disease course. Risk factors include chronic alcohol consumption, nonalcoholic fatty liver disease, and exposure to aflatoxins. Early detection is crucial for better outcomes, but initial stages are often asymptomatic.adv
- Prevalence
- Hepatocellular carcinoma (HCC) is a significant global health concern, especially prevalent in regions with high rates of chronic hepatitis B and C infections, such as East Asia and sub-Saharan Africa. In the United States and Europe, its incidence is rising due to increasing rates of hepatitis C and non-alcoholic fatty liver disease. Prevalence and incidence rates can vary widely based on geographical location, underlying risk factors, and population demographics.
- Epidemiology
- HCC is one of the most common tumors worldwide. The epidemiology of HCC exhibits two main patterns, one in North America and Western Europe and another in non-Western countries, such as those in sub-Saharan Africa, Central and Southeast Asia, and the Amazon basin. Males are affected more than females usually, and it is most common between the ages of 30 and 50,: 821–881 Hepatocellular carcinoma causes 662,000 deaths worldwide per year about half of them in China.
- Intractability
- Hepatocellular carcinoma (HCC) is considered challenging to treat, particularly in advanced stages. Early-stage HCC can sometimes be managed with treatments such as surgical resection, liver transplantation, or localized therapies like radiofrequency ablation. However, once the disease progresses, it often becomes more difficult to manage effectively. Advanced HCC may require systemic therapies, including targeted treatments and immunotherapy, but these often have limited efficacy and can be associated with significant side effects. Early detection and timely intervention significantly improve the prognosis, but the disease overall remains a significant clinical challenge.
- Disease Severity
- Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. It is often a severe and aggressive form of cancer with a high mortality rate. The prognosis depends on various factors including the stage at diagnosis, underlying liver function, and available treatment options. Early-stage HCC may be treated with surgical resection, liver transplantation, or local ablative therapies, but advanced stages often have fewer treatment options and poorer outcomes.
- Healthcare Professionals
- Disease Ontology ID - DOID:684
- Pathophysiology
-
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer.
Pathophysiology:
HCC typically arises in the context of chronic liver disease, particularly cirrhosis, often due to chronic hepatitis B and C infections, alcohol abuse, and non-alcoholic fatty liver disease. The pathophysiological progression from chronic liver injury to HCC involves a complex interplay of:
1. **Genetic Mutations:** Accumulation of genetic alterations in hepatocytes causes dysregulation of oncogenes and tumor suppressor genes.
2. **Chronic Inflammation:** Persistent inflammation initiates regenerative hyperplasia, promoting cellular proliferation and genomic instability.
3. **Fibrosis and Cirrhosis:** Repeated liver damage leads to fibrosis, with further progression to cirrhosis, creating a microenvironment conducive to malignant transformation.
4. **Aberrant Signaling Pathways:** Disruption in signaling pathways like Wnt/β-catenin, PI3K/AKT/mTOR, and TGF-β leads to enhanced cell proliferation and survival.
5. **Angiogenesis:** Increased vascular endothelial growth factor (VEGF) promotes neovascularization, supplying the tumor with nutrients and oxygen.
Overall, the development of HCC is a multi-step process involving a combination of genetic, epigenetic, and environmental factors. - Carrier Status
- Hepatocellular carcinoma (HCC) is primarily a cancer of the liver. Carrier status is not typically relevant for HCC itself, but chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) is a significant risk factor. Individuals who are carriers of HBV or have chronic HCV infection are at an increased risk of developing HCC.
- Mechanism
-
Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. It typically arises due to chronic liver inflammation and cirrhosis. Here are the details:
### Mechanism:
1. **Chronic Liver Disease**: HCC usually develops in the context of chronic liver disease, which can be caused by hepatitis B and C infections, alcohol abuse, and non-alcoholic fatty liver disease (NAFLD).
2. **Cirrhosis**: Persistent inflammation leads to liver cell damage, death, and regeneration, resulting in cirrhosis, which provides a milieu for malignant transformation.
3. **Genotoxic Stress**: Chronic liver disease increases genotoxic stress, leading to DNA mutations and genomic instability.
### Molecular Mechanisms:
1. **Genetic Mutations**:
- Mutations in oncogenes (e.g., CTNNB1) and tumor suppressor genes (e.g., TP53) are common in HCC.
- Mutations can also occur in the TERT promoter, telomerase reverse transcriptase, leading to uncontrolled cell division.
2. **Signaling Pathways**:
- **Wnt/β-catenin Pathway**: Activation (often through CTNNB1 mutations) promotes cell proliferation and survival.
- **PI3K/AKT/mTOR Pathway**: This pathway supports cell proliferation and growth and is often upregulated in HCC.
- **MAPK/ERK Pathway**: Overactivation leads to increased cell division and survival.
3. **Epigenetic Modifications**:
- **DNA Methylation**: Aberrant methylation patterns can silence tumor suppressor genes.
- **Histone Modifications**: Changes in histone acetylation and methylation influence gene expression.
4. **Inflammatory Cytokines**: Chronic inflammation induces cytokines like IL-6 and TNF-α, leading to a tumor-promoting environment.
5. **Angiogenesis**: Increased expression of VEGF (vascular endothelial growth factor) promotes blood vessel formation, supporting tumor growth.
Understanding these mechanisms is key in developing targeted therapies and intervention strategies for HCC. - Treatment
-
Treatment of hepatocellular carcinoma varies by the stage of disease, a person's likelihood to tolerate surgery, and availability of liver transplant:
Curative intention: for limited disease, when the cancer is limited to one or more areas of within the liver, surgically removing the malignant cells may be curative. This may be accomplished by resection the affected portion of the liver (partial hepatectomy) or in some cases by orthotopic liver transplantation of the entire organ.
"Bridging" intention: for limited disease which qualifies for potential liver transplantation, the person may undergo targeted treatment of some or all of the known tumor while waiting for a donor organ to become available.
"Downstaging" intention: for moderately advanced disease which has not spread beyond the liver, but is too advanced to qualify for curative treatment. The person may be treated by targeted therapies in order to reduce the size or number of active tumors, with the goal of once again qualifying for liver transplant after this treatment.
Palliative intention: for more advanced disease, including spread of cancer beyond the liver or in persons who may not tolerate surgery, treatment intended to decrease symptoms of disease and maximize duration of survival.Loco-regional therapy (also referred to as liver-directed therapy) refers to any one of several minimally-invasive treatment techniques to focally target HCC within the liver. These procedures are alternatives to surgery, and may be considered in combination with other strategies, such as a later liver transplantation. Generally, these treatment procedures are performed by interventional radiologists or surgeons, in coordination with a medical oncologist. Loco-regional therapy may refer to either percutaneous therapies (e.g. cryoablation), or arterial catheter-based therapies (chemoembolization or radioembolization). - Compassionate Use Treatment
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Hepatocellular carcinoma (HCC) is a primary liver cancer with various treatment options, particularly in advanced stages. Compassionate use treatment, off-label, and experimental treatments for HCC may include the following:
1. **Compassionate Use Treatments**:
- **Nivolumab (Opdivo)**: An immunotherapy drug, originally approved for other cancers, may be used under compassionate use protocols for HCC.
- **Pembrolizumab (Keytruda)**: Another immunotherapy agent, similar to Nivolumab, sometimes granted for compassionate use.
2. **Off-label Treatments**:
- **Sorafenib (Nexavar)**: Though approved for HCC, it is sometimes used off-label at different stages or in combination with other treatments.
- **Lenvatinib (Lenvima)**: Approved for HCC, may be used off-label in combination regimens or in different sequences as part of a treatment plan.
- **Cabozantinib (Cabometyx)** and **Regorafenib (Stivarga)**: While approved for second-line treatment, their use can be off-label in other sequences or combinations.
3. **Experimental Treatments**:
- **CAR-T Cell Therapy**: Clinical trials are exploring the use of genetically modified T cells targeting specific antigens on liver cancer cells.
- **Oncolytic Virus Therapy**: Viruses like Talimogene laherparepvec (T-VEC) are being investigated for their ability to selectively infect and kill cancer cells.
- **Combination Immunotherapies**: Studies are examining combinations of checkpoint inhibitors (like Nivolumab and Ipilimumab) for enhanced efficacy.
- **Targeted Therapies**: New molecules and combinations targeting specific pathways involved in cancer growth, such as FGFR inhibitors, are under research.
These treatments are continually evolving as new clinical trials provide more data on efficacy and safety for HCC. - Lifestyle Recommendations
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For hepatocellular carcinoma (HCC), lifestyle recommendations include:
1. **Avoid alcohol:** Reducing or eliminating alcohol consumption can help prevent further liver damage.
2. **Maintain a healthy weight:** Obesity can lead to fatty liver disease, which increases the risk of HCC.
3. **Healthy diet:** Eat a balanced diet rich in fruits, vegetables, whole grains, and lean proteins.
4. **Exercise regularly:** Regular physical activity helps maintain a healthy weight and supports overall liver health.
5. **Avoid tobacco:** Quit smoking to reduce the risk of liver cancer and other types of cancer.
6. **Vaccinations:** Ensure you are vaccinated against hepatitis B, as chronic hepatitis B can lead to liver cancer.
7. **Treat underlying liver conditions:** Manage chronic hepatitis B or C with appropriate antiviral treatments to lower the risk of HCC.
8. **Limit toxins:** Reduce exposure to environmental toxins and chemicals that can harm the liver.
These recommendations can help support liver health and potentially reduce the risk or progression of hepatocellular carcinoma. - Medication
- Hepatocellular carcinoma (HCC) is primarily treated depending on the stage of the disease. Medication options may include systemic therapies like sorafenib, lenvatinib, and regorafenib for advanced HCC. Immunotherapies such as nivolumab and pembrolizumab are also used. Localized therapies may involve radiofrequency ablation or transarterial chemoembolization (TACE). It's essential to consult a healthcare professional for a precise treatment plan tailored to the individual patient's condition.
- Repurposable Drugs
-
Several drugs originally developed for other conditions have shown potential for repurposing in the treatment of hepatocellular carcinoma (HCC). These include:
1. **Metformin**: Commonly used for type 2 diabetes, has shown anti-proliferative effects on liver cancer cells in various studies.
2. **Statins**: Used for lowering cholesterol, some studies suggest they may reduce the risk or slow the progression of HCC.
3. **Aspirin**: Commonly used as an anti-inflammatory and anticoagulant, has demonstrated potential in reducing the incidence and recurrence of HCC.
4. **Chloroquine and Hydroxychloroquine**: Initially used for malaria, they have shown effectiveness in inhibiting autophagy in cancer cells, including HCC.
Further clinical trials are necessary to confirm their efficacy and safety in the context of HCC treatment. - Metabolites
-
Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. Metabolites significantly involved in HCC include:
1. **Alpha-fetoprotein (AFP)**: Often elevated in patients with HCC and used as a tumor marker.
2. **Glypican-3 (GPC3)**: Overexpressed in HCC and can be found in blood serum.
3. **Des-γ-carboxy prothrombin (DCP)**: Also known as prothrombin induced by Vitamin K absence/antagonist-II (PIVKA-II), is another diagnostic marker.
4. **Bile acids**: Altered levels are often observed in HCC due to liver dysfunction.
5. **Lipids**: Changes in lipid metabolites, such as cholesterol and fatty acids, are commonly noted due to their role in cellular metabolism.
6. **Amino acids (e.g., glycine, glutamine)**: Differences in amino acid metabolism have been associated with HCC.
These biomarkers can help in diagnosing and monitoring the disease. - Nutraceuticals
-
There is currently limited evidence on the effectiveness of nutraceuticals in the treatment of hepatocellular carcinoma (HCC). Some studies suggest that certain natural compounds may have potential benefits, but these are not established as standard treatments. Promising compounds include:
1. **Curcumin**: Exhibits anti-inflammatory and antiproliferative effects.
2. **Resveratrol**: Found in grapes, may induce cancer cell apoptosis.
3. **Silymarin (Milk Thistle)**: May protect liver cells and impede cancer growth.
However, clinical trials and more comprehensive research are required to substantiate their efficacy and safety for HCC patients. If considering nutraceuticals, it is crucial to consult healthcare providers to prevent interactions with conventional treatments. - Peptides
- Navitoclax (ABT-263) is a small-molecule inhibitor targeting BCL-2 proteins that has been studied in hepatocellular carcinoma (HCC). For peptides, Glypican-3 (GPC3) peptide vaccines have been investigated for HCC treatment, targeting the GPC3 protein that is frequently overexpressed in HCC cells.