Hepatocellular Carcinoma – liver cancer symptoms, causes and treatment

Medically reviewed: 10, March 2024

Hepatocellular Carcinoma (HCC): An In-depth Understanding and pathology outlines

Hepatocellular carcinoma (HCC) is a type of liver cancer, a complex and diverse neoplasm arising from hepatocytes, with several distinct histological patterns that define its underlying pathophysiology. Being aware of these manifestations helps medical professionals make informed decisions regarding appropriate diagnostics and potential management strategies. This outline highlights four major aspects of HCC pathology:

Architectural Growth Patterns

HCC exhibits varying growth patterns, often categorized as either expansile or infiltrative. Expansile lesions demonstrate pushing borders compressing adjacent tissue without invading sinusoids or portal tracts, whereas infiltrative variants exhibit invasion into neighboring structures causing irregular shape and ill-defined margins. Recognition of growth patterns is valuable in predicting microvascular involvement, staging accuracy, and guiding resection methods.

Morphologic Subtypes

Histologically, HCC displays different architectures based on cell organization within the tumor mass. Four main types encompass trabecular, pseudoglandular, compact, and scirrhous configurations. Trabecular morphologies consist of thickened plates of cells separated by vascular channels, while pseudoglandular forms mimic glands due to bile accumulation inside malignant cells. Compact appearances contain sheets of closely packed neoplastic cells lacking discernible architecture. Lastly, scirrhous varieties reveal extensive fibrosis amidst tumor cells indicating aggressive behavior.

Special Variants

Several special variants warrant particular attention owing to their unique clinico-pathological characteristics and implications for patient management. These include fibrolamellar HCC, characterized by dense collagen bands dividing large polygonal cells rich in eosinophilic cytoplasm. Another notable variant is clear cell HCC marked by optically empty vacuolated cells resulting from fatty change or glycogen storage. Other rare phenotypes comprise sarcomatoid, pleomorphic, and lymphoepithelioma-like carcinomas, each carrying distinctive molecular profiles influencing therapeutic choices.

Pathologists utilize specific biomarkers and grading systems to gauge biological aggressiveness, facilitating accurate risk stratification and determining suitable therapy. Key proliferation indices incorporate Ki-67 labeling index, cell cycle regulators p21 and p27 expression, and angiogenesis surrogates such as CD34 or CD31. Furthermore, the Edmondson-Steiner system quantifies nuclear grade severity ranging from well-differentiated Grade 1 to poorly differentiated Grade 4 lesions.

Alternatively, some authorities prefer alternative schemes like the World Health Organization (WHO) classification or International Consensus Group on Hepatocellular Neoplasia (ICGHN) criteria. Regardless of method adopted, consistent utilization enhances comparability among multi-institutional cohorts undergoing clinical trials or population-based studies evaluating novel adjuvant therapies.

Risk Factors Associated with HCC Development

Numerous risk factors increase susceptibility towards developing HCC, chiefly encompassing:

• Chronic Viral Hepatitis: Both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections predispose patients significantly towards HCC due to persistent inflammation and subsequent scarring (cirrhosis). Alarmingly, nearly half of global HCC cases stem directly from HBV exposure, predominantly in endemic regions lacking vaccination efforts.
• Cirrhosis: Regardless of etiologies, cirrhotic changes instigated by long-term insults—be it viral, alcoholic, non-alcoholic steatohepatitis (NASH)-related, autoimmune, or genetic disorders—progressively deteriorate healthy liver architecture increasing HCC risks.
• Genetic Predisposition: Certain inherited conditions, such as hemochromatosis, alpha-1 antitrypsin deficiency, porphyria, Wilson’s disease, and tuberous sclerosis complex, elevate HCC incidence rates owing to underlying gene mutations promoting liver damage.
• Environmental and Lifestyle Elements: Additional external determinants comprise aflatoxin B1 ingestion, aristolochic acid exposure, tobacco smoking, excessive alcohol consumption, obesity, diabetes, and poor dietary habits collectively contributing to HCC development.

Hepatocellular carcinoma (HCC) key takeaways

Hepatocellular carcinoma (HCC) is the most common form of liver cancer, primarily affecting individuals with chronic liver diseases such as cirrhosis. When dealing with HCC, here are three crucial takeaways to keep in mind:

1. Early Detection Saves Lives: Regular screening is vital for people at high risk of developing HCC, especially those diagnosed with cirrhosis caused by conditions like hepatitis B or C infection. Ultrasound examinations every six months can significantly improve survival rates when HCC is detected early. Moreover, tumor markers, such as alpha-fetoprotein (AFP) levels, may provide additional information to aid diagnosis. However, no single test has proven entirely reliable for diagnosing HCC at its earliest stages. Therefore, multidisciplinary approaches combining imaging techniques and biomarker assessments typically yield better diagnostic outcomes.
2. Comprehensive Treatment Strategies Are Crucial: Curative treatments, such as surgical resection, liver transplantation, and local ablation therapies, should be considered whenever possible for patients diagnosed with early-stage HCC. For intermediate-stage disease, transarterial chemoembolization (TACE) remains the primary treatment option. In advanced stages, systemic therapies offer palliative benefits to maintain quality of life. Sorafenib was the first approved targeted therapy for unresectable HCC; however, newer options have shown improved overall survival rates. Immunotherapy combinations also demonstrate promise in treating certain subsets of HCC patients. Collaborate with oncologists specializing in liver malignancies to develop optimal therapeutic plans tailored to individual patient needs.
3. Prevention Is Better Than Cure: Primary prevention strategies focus predominantly on preventing viral hepatitis transmission and reducing alcohol consumption. Universal vaccination programs against hepatitis B virus (HBV) infection contribute significantly to preventing new cases. Antiviral treatments targeting both HBV and hepatitis C virus (HCV) infections decrease progression towards cirrhosis and subsequent HCC development. Public health initiatives promoting healthy lifestyles, including reduced alcohol intake and dietary modifications, complement viral eradication efforts to minimize liver damage susceptibility. Tertiary preventive measures involve rigorous post-treatment surveillance to detect recurrences promptly.

Hepatocellular carcinoma (HCC): symptoms

Hepatocellular carcinoma (HCC) is a serious liver condition associated with various signs and symptoms depending on the stage and extent of the disease. While presenting symptoms might differ between individuals, being cognizant of potential indicators bolsters timely intervention and enhanced patient care. Outlined below are seven prominent symptoms frequently observed in HCC:

1. Unexplained Weight Loss: Unintentional weight loss, particularly in conjunction with decreased appetite and altered bowel habits, could signal an underlying issue like HCC necessitating evaluation.
2. Abdominal Discomfort: Persistent pain or discomfort felt in the upper abdominal region may suggest liver enlargement or distension secondary to a growing tumor, accompanied occasionally by ascites formation—excess fluid accumulating within the abdominal cavity leading to noticeable bloating.
3. Jaundice: Characteristic yellowish pigmentation of the skin and sclerae emanates from bilirubin buildup consequent to obstructed bile ducts impacted by nearby tumors.
4. Dark Urine and Pale Stools: Changes in urine color (darker hues) result from increased bilirubin excretion, while lighter stool appearance ensues from diminished bile release into the small intestines.
5. Fatigue and Weakness: Generalized exhaustion and debility experienced by many HCC patients possibly stemming from alterations in metabolism, impaired liver function, or anemia triggered by internal bleeding or nutrient deficiencies.
6. Nausea and Vomiting: Both symptoms may surface sporadically due to pressure on the stomach exerted by expanding masses or direct irritation attributable to liver dysfunction affecting digestion adversely.
7. Coagulopathies: Aberrant clotting mechanisms instigated by defective synthesis of blood proteins within the damaged liver predispose afflicted persons to spontaneous bruising, prolonged wound healing, and propensity for unprovoked hemorrhages.

Hepatocellular carcinoma diagnostic screening

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver, accounting for approximately 75-85% of all primary liver cancers. Early diagnosis and appropriate treatment significantly improve patient survival rates.

Diagnosis criteria

Early and accurate diagnosis of HCC significantly impacts treatment options and overall prognosis. Various diagnostic criteria exist to aid healthcare professionals in identifying HCC at different stages. Some widely accepted guidelines and modalities include:

1. Imaging techniques:
   • Ultrasound (US): Used as the initial screening modality, especially for high-risk patients with chronic liver disease.
   • Triphasic computed tomography (CT) scan or magnetic resonance imaging (MRI): These methods offer better sensitivity and specificity than US alone, particularly when diagnosing small lesions or distinguishing between benign and malignant nodules. Typical characteristics of HCC on these imaging tests include arterial enhancement followed by washout in the portal venous or delayed phases.
   • Contrast-enhanced ultrasound (CEUS): CEUS can improve the detection rate of early HCC compared to conventional US. However, operator expertise plays a crucial role in obtaining optimal results.
2. Biomarker analysis:
   • Alpha-fetoprotein (AFP): Serum levels greater than 400 ng/mL could indicate HCC. But due to low specificity, elevated AFP isn’t always conclusive. Levels between 20-400 ng/mL might still require additional investigation, depending on clinical context and imaging findings. Other biomarkers like des-gamma-carboxyprothrombin (DCP) may also be used alongside AFP for improved accuracy.
3. Liver biopsy: In cases where non-invasive tests cannot provide sufficient evidence, percutaneous or transjugular liver biopsies can confirm the presence of HCC. Although invasive, tissue sampling allows histological examination and helps rule out alternative diagnoses.
4. Staging systems: Once diagnosed, staging systems like the Barcelona Clinic Liver Cancer (BCLC) system or TNM classification guide therapeutic strategies based on tumor burden, liver function, and patient performance status. This information informs clinicians whether curative treatments (e.g., surgical resection, ablation, or transplantation) or palliative approaches (e.g., chemoembolization, targeted therapy, immunotherapy, or radiation therapy) would benefit the patient.

Ultrasound

Ultrasound surveillance every six months is recommended as the primary modality for HCC detection in at-risk individuals, such as those with cirrhosis or chronic viral hepatitis B or C infection. Ultrasound has high sensitivity for detecting early-stage tumors (up to 94%) when performed by experienced radiologists. However, specificity may be compromised due to low contrast resolution between lesions and surrounding liver parenchyma, potentially leading to false positives and unnecessary invasive procedures.

Computed tomography

Computed tomography (CT) scans and magnetic resonance imaging (MRI) serve as second-line modalities in cases where ultrasound results are inconclusive. Both techniques provide improved visualization compared to ultrasound but expose patients to higher radiation levels (for CT) and increased costs (for both). Consequently, their routine use for surveillance purposes remains controversial despite better overall accuracy than ultrasound alone.

Contrast-enhanced ultrasound

Contrast-enhanced ultrasound (CEUS) offers enhanced conspicuity over conventional grayscale sonography, enabling earlier detection of hypervascular HCC lesions. Microbubble contrast agents used in CEUS temporally enhance vascular structures within focal liver lesions. Nevertheless, limitations persist concerning operator dependence, availability, and regulatory constraints across different geographical regions. Thus, CEUS serves primarily as an adjunct tool rather than a first-line screening methodology.

Hepatocellular carcinoma tumor marker

In the context of diagnosing hepatocellular carcinoma (HCC), identifying suitable tumor markers plays a crucial role in facilitating accurate prognostication and therapeutic decision-making.

Tumor markers represent substances produced directly or indirectly by cancerous cells that enable objective evaluation of disease progression. For HCC, several well-established serologic biomarkers exist, each presenting distinct advantages and limitations.

Among them, alpha-fetoprotein (AFP) remains the most widely recognized tumor marker for HCC globally. Despite some controversies regarding sensitivity and specificity, particularly in early stages, AFP continues to play a vital role in HCC diagnosis and post-therapy monitoring regimes.

Other emerging biomolecules, including lectins, glypicans, Golgi protein-73, and osteopontin, show promising potential for future applications as complementary or alternative tumor markers in HCC. Combination panels incorporating multiple markers aim to boost specificity and sensitivity beyond reliance on any single analyte. Ongoing advancements in liquid biopsy technologies, such as cell-free DNA analysis and extracellular vesicle characterization, open exciting avenues towards developing innovative diagnostic solutions tailored specifically to HCC management.

Hepatocellular carcinoma treatment

Treatment for hepatocellular carcinoma (HCC) largely depends on the stage of the disease, the patient’s underlying liver function, and overall health condition. Integrating multidisciplinary teams consisting of surgeons, medical oncologists, radiologists, and hepatologists ensures personalized plans tailored to individual needs.

Curative therapies aim to eliminate detectable cancer while preserving liver functionality.

Palliative measures alleviate symptoms, enhance quality of life, and extend survival. Common interventions encompass surgery, local ablative therapies, locoregional treatments, and systemic medications.

Surgical Resection

Indicated primarily for solitary or few discrete tumors confined within a well-preserved liver. Potential candidates undergo rigorous evaluation for adequate future remnant liver volume following surgery. Post-resection morbidity includes recurrence, hence requiring close monitoring.

Liver Transplantation

For those presenting cirrhotic livers overwhelmed by HCC, orthotopic liver transplantation offers the prospect of simultaneously addressing both conditions. Milan Criteria often guides candidate eligibility—single tumor ≤5 cm or two-three nodules each ≤3 cm without macrovascular invasion nor extrahepatic spread. Adherence maximizes post-transplant survivals near 70%. Emerging expanded criteria continue exploration to broaden accessibility.

Local Ablative Therapy

Suitable alternatives for unresectable yet localized HCC involve eradicating neoplastic cells directly. Methodologies comprise:

• Radiofrequency Ablation (RFA),
• Microwave Ablation (MWA),
• ethanol injection,
• and acetic acid injection.

Each approach possesses distinct advantages contingent on tumor location, availability, cost, technical skills, and safety profiles.

Thermal ablative technologies prevail owing to superior efficacy, decreased procedural times, and tolerability versus chemical counterparts. Nevertheless, limitations persist regarding applicability amidst large masses or extensive satellite nodules.

Locoregional Treatment Modalities

Intermediate-stage HCC warrants consideration of locoregional strategies prioritizing minimally invasive procedures, lower risks, and preserved organ integrity. Examples incorporate Arterially Directed Chemotherapy & Embolization Techniques (TACE, DEB-TACE, Lipiodol-TACE, Bland Embolization, Yttrium-90 radioembolization) aimed at obliterating intravascular supply lines feeding tumoral growth via selectively targeting hepatic vasculature architecture—namely, hypervascularized areas sustained predominantly through hepatic artery perfusion juxtaposed against healthy parenchymal territories inherently reliant on dual blood supplies via portal vein inflow.

Systemic Medications

Advanced-stage HCC devoid of feasible locoregional avenues necessitate systematic drug administration intended to forestall progression, manage symptoms, prolong survival duration, and augment general wellbeing.

Available regimens consist mainly of:

• immune checkpoint inhibitors (ICIs),
• multi-kinase inhibitors (MKIs),
• vascular endothelial growth factor (VEGF)-targeted agents,
• combined ICIs + MKIs / VEGF-targeted combinations,
• antiangiogenics,
• programmed cell death protein 1 (PD-1) blockade antibodies,
• cytotoxic chemotherapies,
• monoclonal antibody sorafenib, lenvatinib, nivolumab, ipilimumab, ramucirumab, cabozantinib, atezolizumab plus bevacizumab.

Prospective targets continuously evolve fueled by translational discoveries converting novel insights gleaned from benchside explorations towards effective bedside applications.

 

Hepatocellular carcinoma (HCC) is the most common form of liver cancer, accounting for around 75-85% of primary liver cancers worldwide. Prognosis varies significantly depending on several factors such as tumor stage at diagnosis, patient characteristics, treatment options, and overall health status. In general, early detection of HCC leads to better outcomes due to increased feasibility of curative treatments. This section will discuss some key elements influencing hepatocellular carcinoma prognosis.

Hepatocellular carcinoma prognosis

1. Tumor Stage: At the time of diagnosis, determining the extent of cancer spread plays a crucial role in establishing a reliable prognosis. Common staging systems used for HCC are Barcelona Clinic Liver Cancer (BCLC), American Joint Committee on Cancer (AJCC)/TNM system, and Okuda staging. Patients diagnosed earlier tend to have improved survival rates compared to those detected late. Curative therapies, such as surgical resection, transplantation, and local ablation, offer better chances for long-term remission when applied appropriately.
2. Patient Characteristics: Various demographic factors influence the outcome of patients with HCC. Age, gender, and underlying liver disease etiology may affect life expectancy. Older individuals generally experience poorer prognoses than younger ones. Gender disparities also exist, with males having worse outcomes than females. Moreover, specific causes of chronic liver diseases associated with cirrhotic conditions can lead to variations in mortality risk. For instance, viral hepatitis B (HBV)-related HCC has shown relatively favorable results compared to non-alcoholic steatohepatitis (NASH)-induced cases.
3. Treatment Options: Therapeutic strategies play a significant part in modifying HCC prognosis. Depending on individual circumstances, physicians choose between potentially curative interventions (surgery, transplantation, or ablative techniques), locoregional treatments (transarterial chemoembolization or radioembolization), systemic agents (targeted therapy or immunotherapy), and palliative care approaches. Selecting optimal therapies based on tumor burden, liver function preservation, and comorbidity management improves life quality and extends overall survival.
4. Overall Health Status: Performance status, presence of comorbid conditions, and functional capacity considerably impact HCC prognosis. Assessments like Eastern Cooperative Oncology Group (ECOG) score or Karnofsky index provide insights into patient fitness levels. Better baseline health implies longer survival times post-diagnosis. Regular monitoring and appropriate multidisciplinary team involvement ensure proper addressing of concurrent medical concerns alongside tailored antitumoral measures.

Hepatocellular carcinoma prognosis without treatment: how long can you live?

When discussing hepatocellular carcinoma (HCC) prognosis without any treatment, there are several factors that come into play regarding how long a person could live. These factors include the stage of the cancer at diagnosis, overall health condition, age, and underlying liver damage causing the cancer. However, in general terms, the outlook tends to be unfavorable due to the aggressive nature of this particular type of liver malignancy.

Typically, advanced stages of hepatocellular carcinoma progress rapidly, leading to reduced survival rates even without active intervention. Median survival ranges approximately between three to six months following diagnosis when no conventional treatments are pursued. Nevertheless, precise longevity expectations should be established individually considering relevant clinical criteria and expert judgment.

It is imperative to mention that individual responses to cancer evolution vary drastically. Some people might succumb to the illness within weeks, whereas others may survive for over a year under similar circumstances. With recent advances in experimental drugs, novel treatment protocols, and integrative medicine, alternative modalities continue evolving beyond traditional chemotherapy, radiation, or surgery. Exploring available clinical trials and compassionate-use programs remains a valuable consideration, offering potential benefits and extending lifespan beyond initial grim forecasts.

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