Screening and diagnosis

Classification and risk stratification

Perioperative care

Quality improvement

Patient education

Nonpharmacologic interventions

Therapeutic procedures

Respiratory support

Follow-up and surveillance

Specific circumstances

Preventative measures

Medical management

Surgical interventions

Inpatient care

Diagnostic procedures

Diagnostic investigations

Insufficient evidence to make a recommendation.

Strongly favor this test or intervention.

The Milan criteria for liver transplantation help determine if a patient qualifies for liver transplant based on specific medical conditions. This evaluation considers three key factors related to liver tumors and cancer spread. Here's how it works:

The inputs involve checking if the following conditions are satisfied:

- Presence of a single liver tumor that is 5 cm or smaller, or the presence of two to three tumors, each no larger than 3 cm.
- Absence of vascular invasion, indicating the tumor has not spread into blood vessels.
- Absence of extrahepatic metastases, signifying that the cancer has not extended beyond the liver.

For each condition:

- Condition A is met if the tumor size and count criteria are satisfied.
- Condition B is met if there's no evidence of vascular invasion.
- Condition C is satisfied if there are no signs of cancer spreading beyond the liver.

The outcome is based on checking all these conditions:

- If all three conditions (A, B, and C) are true, the result is that the patient meets the criteria for liver transplantation.
- If even one condition is false, the criteria are not met, and the patient does not qualify under the Milan criteria for liver transplantation.

These criteria aim to identify patients with a favorable prognosis following liver transplantation, thus prioritizing those who are most likely to benefit from the procedure.

The Milan Criteria is a clinical scoring system used to determine eligibility for liver transplantation in patients with hepatocellular carcinoma (HCC). This criteria is specifically applicable to patients with HCC who are being considered for liver transplantation. 

The clinical utility of the Milan Criteria is to identify those patients who are likely to have the most favorable outcomes following liver transplantation. It is based on the size and number of liver tumors, with patients meeting the criteria having a single tumor less than or equal to 5 cm in diameter, or up to three tumors each less than or equal to 3 cm in diameter, and no evidence of macrovascular invasion or extrahepatic spread.

Exclusion criteria for the use of the Milan Criteria include patients with tumors larger than the specified size, more than three tumors, evidence of macrovascular invasion, or extrahepatic disease. These patients are considered to have a higher risk of recurrence post-transplantation and are typically not considered suitable candidates for liver transplantation.

Milan criteria for liver transplantation

The function is designed to evaluate the risk of liver decompensation and mortality following a hepatectomy in patients with hepatocellular carcinoma. It does this by considering three important factors: the presence of portal hypertension, the extent of the hepatectomy, and the Model for End-Stage Liver Disease (MELD) score.

To carry out the assessment, the function requires the following inputs:
- Portal hypertension: You need to specify if the patient has portal hypertension. The options are "Yes" or "No."
- Extension of hepatectomy: You must indicate the scale of the hepatectomy surgery, choosing between "Minor (removal of < 3 liver segments)" and "Major (removal of >= 3 liver segments)."
- MELD score: This is crucial for determining overall liver function. You need to select either "<= 9" or "> 9."

The calculation uses these inputs to categorize the patient's risk into different scenarios. 

- If the patient does not have portal hypertension, has undergone a minor hepatectomy, and has a MELD score of 9 or less, the risk of liver decompensation is considered low, at 4.9%. The risk of 7-day mortality in this scenario is 4.4%.

- Different combinations of factors lead to an intermediate risk level. If the patient either has no portal hypertension with a minor hepatectomy and a MELD score above 9, or has no portal hypertension with major hepatectomy, or has portal hypertension with minor hepatectomy, the risk of liver decompensation becomes intermediate, at 28.6%. In these cases, the risk of mortality within 8 days is 9%.

- The highest risk is attributed to patients who meet both conditions of having portal hypertension and undergoing a major hepatectomy. For these individuals, the likelihood of liver decompensation escalates to 60%, and the risk of 11-day mortality rises to 25%.

By structuring these calculations, the function provides a clear framework for clinicians to assess and stratify risk, helping them to make informed decisions about the patient's post-operative care based on specific input combinations.

The calculator in question is the "Liver Decompensation Risk After Hepatectomy in Hepatocellular Carcinoma" calculator. This tool is specifically designed for patients diagnosed with hepatocellular carcinoma (HCC) who are undergoing hepatectomy, a surgical procedure to remove part or all of the liver. 

The clinical utility of this calculator is to predict the risk of postoperative liver decompensation, a serious complication that can occur after hepatectomy. Liver decompensation refers to a significant decline in liver function, which can lead to life-threatening conditions such as hepatic encephalopathy, ascites, or variceal bleeding. 

This calculator helps clinicians to make informed decisions about the appropriateness of hepatectomy in individual patients, by balancing the potential benefits of surgery against the risk of postoperative liver decompensation. 

Exclusion criteria for the use of this calculator may include patients with non-hepatocellular liver cancers, those who are not candidates for surgery due to other medical conditions, or those with pre-existing severe liver dysfunction.

Liver decompensation risk after hepatectomy in hepatocellular carcinoma

This calculator estimates the risk of hepatocellular carcinoma (HCC) in individuals with chronic hepatitis B using the REACH-B model. Inputs include categorical data regarding the patient's sex, age, ALT levels, HBeAg status, and hepatitis B virus DNA level. Each category is assigned a unique numeric score based on predefined criteria.

The calculator includes the following components for scoring:

1. Sex: Female (0 points), Male (2 points)
2. Age Years:
   - 30-34 (0 points)
   - 35-39 (1 point)
   - 40-44 (2 points)
   - 45-49 (3 points)
   - 50-54 (4 points)
   - 55-59 (5 points)
   - 60-65 (6 points)
3. ALT, U/L:
   - < 15 (0 points)
   - 15-44 (1 point)
   - >= 45 (2 points)
4. HBeAg: Negative (0 points), Positive (2 points)
5. Hepatitis B Virus DNA Level, copies/mL:
   - < 300 undetectable (0 points)
   - 300-9,999 (0 points)
   - 10,000-99,999 (3 points)
   - 100,000-999,999 (5 points)
   - >= 1,000,000 (4 points)

The total score is determined by adding the points assigned to each input. Based on this score, the model provides an interpretation of the patient's risk of developing hepatocellular carcinoma over different periods (3, 5, and 10 years).

Interpretations based on score:

- Score 0: Risk is 0.0% in 10 years, 5 years, and 3 years.
- Score 1: Risk is 0.1% in 10 years, 0.0% in 5 and 3 years.
- Score 2: Risk is 0.1% in 10 years, 0.0% in 5 and 3 years.
- Score 3: Risk is 0.2% in 10 years, 0.1% in 5 years, 0.0% in 3 years.
- Score 4: Risk is 0.3% in 10 years, 0.1% in 5 years, 0.0% in 3 years.
- Score 5: Risk is 0.5% in 10 years, 0.2% in 5 years, 0.1% in 3 years.
- Score 6: Risk is 0.7% in 10 years, 0.3% in 5 years, 0.1% in 3 years.
- Score 7: Risk is 1.2% in 10 years, 0.5% in 5 years, 0.2% in 3 years.
- Score 8: Risk is 2.0% in 10 years, 0.8% in 5 years, 0.3% in 3 years.
- Score 9: Risk is 3.2% in 10 years, 1.2% in 5 years, 0.5% in 3 years.
- Score 10: Risk is 5.2% in 10 years, 2.0% in 5 years, 0.9% in 3 years.
- Score 11: Risk is 8.4% in 10 years, 3.3% in 5 years, 1.4% in 3 years.
- Score 12: Risk is 13.4% in 10 years, 5.3% in 5 years, 2.3% in 3 years.
- Score 13: Risk is 21.0% in 10 years, 8.5% in 5 years, 3.7% in 3 years.
- Score 14: Risk is 32.0% in 10 years, 13.6% in 5 years, 6.0% in 3 years.
- Score 15: Risk is 46.8% in 10 years, 21.3% in 5 years, 9.6% in 3 years.
- Score 16: Risk is 64.4% in 10 years, 32.4% in 5 years, 15.2% in 3 years.
- Score 17: Risk is 81.6% in 10 years, 47.4% in 5 years, 23.6% in 3 years.

The final score, ranging from 0 to 17, offers a specific and easy-to-understand percentage that predicts the likelihood of developing HCC within specified timeframes.

The Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B (REACH-B) is a clinical calculator used to predict the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B infection. This scoring system is particularly useful for clinicians in stratifying patients based on their risk of developing HCC, which can guide decisions regarding surveillance and treatment strategies. The REACH-B score takes into account several factors including age, gender, serum ALT level, HBeAg status, and liver cirrhosis status. It is important to note that this calculator is specifically designed for patients with chronic hepatitis B and may not be applicable or accurate for patients with other types of liver disease or those who have already been diagnosed with HCC.

Risk estimation for hepatocellular carcinoma in chronic hepatitis B (REACH-B)

The Eastern Cooperative Oncology Group (ECOG) performance status calculator is designed to evaluate a patient's functional ability and categorize it into a specific score from 0 to 5. This quantitative measure helps clinicians make informed decisions about treatment based on the patient's capacity for daily activities and self-care. Here's how it operates:

The user provides input by selecting the description that best matches the patient's current condition from a list of predefined options. These options encapsulate various levels of activity and ability:

- A patient who is "Fully active, able to carry on all pre-disease performance without restriction" is assigned a score of ECOG PS 0. This indicates that the patient is not limited in any capacity by their disease.
- If a patient is "Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, such as light housework, office work," they receive an ECOG PS 1. This means the patient can perform some self-care and work activities but faces restrictions with strenuous tasks.
- "Ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours" corresponds to an ECOG PS 2. This reflects moderate impairment, where the patient is active for the majority of the day but not capable of work activities.
- A patient who is "Capable of only limited self-care, confined to bed or chair more than 50% of waking hours" gets an ECOG PS 3. This score denotes significant limitation, as the patient is mobile for less than 50% of the time and requires assistance for most activities.
- With "Completely disabled, cannot carry on any self-care, totally confined to bed or chair," the patient is categorized as ECOG PS 4, indicating severe impairment and complete dependency.
- Finally, if the patient is "Dead," they are assigned an ECOG PS 5.

These score assignments help standardize assessments, providing an objective measure of a patient's status which can be pivotal in guiding medical decisions and evaluating treatment options.

The Eastern Cooperative Oncology Group (ECOG) performance status, also known as the ECOG score, is a widely used tool in oncology to assess a patient's level of functioning in terms of their ability to care for themselves, daily activity, and physical ability (walking, working, etc.). It is applicable to patients with cancer of any type and at any stage.

The ECOG score ranges from 0 to 5, with 0 indicating fully active and able to carry on all pre-disease activities without restriction, and 5 indicating death. The score is used to determine a patient's prognosis, assess how a disease is progressing, and to determine appropriate treatment strategies. It is also often used in clinical trials to assess eligibility and to monitor patient progress.

There are no specific exclusion criteria for the use of the ECOG score, but it is important to note that it is a subjective measure and may not fully capture a patient's functional status. It is also less useful in patients with fluctuating or rapidly changing conditions.

Eastern Cooperative Oncology Group performance status (ECOG score)

The Karnofsky Performance Scale (KPS) provides a practical method to evaluate a patient's functional ability and the extent of care required based on their health status. The scale ranges from 0% to 100%, where higher percentages signify better functional capacity and health.

This tool involves selecting a descriptive statement that best reflects a patient's current condition from a predefined list. Each statement is connected to a specific KPS percentage that indicates the patient’s ability to perform daily activities and their dependency levels. Here’s how the assessment works:

- When a patient is described as "Normal, no complaints, no evidence of disease," this is assessed as KPS 100%. At this level, the individual can engage in all regular activities, including work, without needing special care.

- If a patient can "carry on normal activity" but exhibits "minor signs or symptoms of disease," they are scored at KPS 90%, indicating the capability to maintain routine activities without requiring special care.

- A description of "Normal activity with effort, some signs or symptoms of disease" aligns with KPS 80%. This suggests the patient can still carry out normal activities but might require some extra effort.

- When the condition reflects "Cares for self, unable to carry on normal activity or to do active work," it corresponds to KPS 70%. The patient can handle most personal needs independently but may need occasional assistance.

- "Requires occasional assistance but is able to care for most personal needs" is rated as KPS 60%, implying increased dependency on assistance though the patient remains mostly self-sufficient.

- At KPS 50%, for conditions described as "Requires considerable assistance and frequent medical care," the patient can live at home but needs considerable help with personal care.

- As the need for care intensifies, with descriptions like "Disabled, requires special care and assistance," the KPS drops to 40%. This marks a significant deterioration in self-care ability.

- "Severely disabled, hospital admission is indicated, death not imminent" corresponds to KPS 30%, highlighting a need for hospitalization without immediate life-threatening conditions.

- For those "Very sick," necessitating hospital admission and "active supportive treatment," the KPS is 20%, indicating critical care requirements.

- At KPS 10%, "Moribund" denotes an inability to care for oneself, with urgent need for hospital-level care and a poor prognosis.

- Lastly, "Dead" is considered as KPS 0%.

This scale is instrumental in providing a quick overview of a patient's ability to function independently and their need for medical support, thereby facilitating better care planning and resource allocation.

The Karnofsky Performance Status Scale (KPSS) is a clinical calculator used primarily in patients with cancer. It is a simple, numerical scale that measures a patient's functional status, ability to perform daily activities, and overall quality of life. The KPSS ranges from 0 (indicating death) to 100 (indicating perfect health). 

The clinical utility of the KPSS is to assess a patient's prognosis, determine appropriate treatment strategies, and monitor changes in a patient's condition over time. It is particularly useful in oncology for determining eligibility for certain treatments, such as chemotherapy or surgery, and for predicting survival outcomes. 

There are no specific exclusion criteria for the use of the KPSS. However, it is less useful in patients with non-cancer illnesses or in those with cognitive impairment who may not be able to accurately self-report their functional status.

Karnofsky Performance Scale

The Modified Glasgow Prognostic Score (mGPS) is a key tool in predicting cancer outcomes, relying on the assessment of two biochemical markers: C-reactive protein (CRP) and albumin. This score helps to categorize the prognosis into three levels: good, intermediate, and poor.

To compute the mGPS:

- C-reactive protein is evaluated first. Two options are considered:  
  - If the CRP is less than or equal to 10 mg/L, it indicates lower systemic inflammation.
  - If the CRP is greater than 10 mg/L, it signifies higher inflammation levels.

- Albumin is the second marker, with two possibilities:  
  - An albumin level of less than 3.5 g/dL [35 g/L] suggests malnutrition or potential inflammatory conditions.
  - An albumin level equal to or greater than 3.5 g/dL [35 g/L] signifies a normal nutritional status and protein reserves.

The mGPS score is derived based on the following systematic interpretation:

- If CRP is <= 10 mg/L, regardless of the albumin level, the score is mGPS 0, corresponding to a good prognosis. This combination indicates a low level of inflammation, which is a favorable signal in cancer outcomes.
 
- If CRP is > 10 mg/L and albumin is >= 3.5 g/dL [35 g/L], the score is mGPS 1, associated with an intermediate prognosis. This combination suggests elevated inflammation yet with sufficient nutritional status, resulting in a moderate outlook.

- If CRP is > 10 mg/L and albumin is < 3.5 g/dL [35 g/L], the result is mGPS 2, indicating a poor prognosis. This reflects high inflammation levels coupled with low albumin, suggesting a more severe condition.

Here's a concise summary table for reference:

| C-reactive Protein | Albumin               | mGPS Score | Interpretation          |
|---------------------|-----------------------|-------------|-----------------------|
| <= 10 mg/L          | < 3.5 or >= 3.5 g/dL  | 0           | Good prognosis         |
| > 10 mg/L           | >= 3.5 g/dL           | 1           | Intermediate prognosis |
| > 10 mg/L           | < 3.5 g/dL            | 2           | Poor prognosis         |

This systematic approach enables healthcare providers to improve risk stratification in cancer patients, allowing for more tailored treatment planning.

The Modified Glasgow Prognostic Score (mGPS) is a clinical calculator used in the field of oncology to predict the prognosis of patients with cancer. It is applicable to a wide range of cancer types and stages, making it a versatile tool for clinicians. The mGPS is based on two simple, routinely measured inflammatory markers: C-reactive protein (CRP) and albumin levels. 

The clinical utility of the mGPS lies in its ability to stratify patients into different risk groups based on their inflammatory response to cancer. This can guide clinicians in making decisions about treatment strategies and follow-up plans. It can also provide valuable prognostic information to patients and their families.

There are no specific exclusion criteria for the use of the mGPS. However, it should be noted that the score may not be as accurate in patients with concurrent inflammatory or infectious conditions, as these can also affect CRP and albumin levels. Additionally, the mGPS may not be applicable to patients with rare types of cancer or those with very early or very advanced disease, as it has not been extensively validated in these groups.

Modified Glasgow Prognostic Score for cancer outcomes (mGPS)

Hepatocellular carcinoma

Management of resectable disease

Management of resectable disease, indications for surgical resection

Postoperative care

Postoperative care (antiemetics)

Intraoperative care

Intraoperative care (anesthesia and analgesia)

Transarterial therapies

Transarterial therapies, selective internal radiotherapy

Preoperative care

Preoperative care (nutrition)

Hepatitis B immunization

Post-treatment follow-up

Diagnostic criteria

Management of resectable disease, technical considerations for surgical resection

Public health measures

Choice of screening tests

Postoperative care (early mobilization)

Management of early disease

Management of early disease, local ablation

Postoperative care (laxatives)

External beam radiation therapy

External beam radiation therapy, indications

Management of chronic liver disease

Preoperative care (rehabilitation)

Liver transplantation

Liver transplantation, bridging therapy

Chemoprevention

Coffee consumption

Staging

Management of viral hepatitis

Postoperative care (thromboprophylaxis)

Liver biopsy

Preoperative care, antibiotic prophylaxis

Management of advanced disease

Management of advanced disease, first-line systemic therapy

Indications for screening

Indications for screening (occupational liver disease)

Preoperative care (biliary drainage)

Management of resectable disease, adjuvant therapy

Psychosocial and nutritional support

External beam radiation therapy (technical considerations)

Intraoperative care (temperature management)

Lifestyle modifications

Preoperative care (preanesthetic medication)

Liver transplantation, indications

Indications for screening (hemochromatosis)

Intraoperative care (fluid management)

Indications for screening, MASLD

Preoperative care (corticosteroids)

Postoperative care (nutrition)

Indications for screening, liver cirrhosis

Indications for screening, liver transplant candidates

Ancillary testing

Preoperative care (counseling)

Transarterial therapies, transarterial embolization/chemoembolization

Surveillance for hepatic nodules

Pregnant patients

Preoperative assessment

Management of early disease (watchful waiting)

Management of pain

Palliative care

Palliative care, radiotherapy

Management of resectable disease, neoadjuvant therapy

Management of advanced disease, second-line systemic therapy

General principles

Palliative care, general principles

Updated 2024 ASCO guidelines for systemic therapy in advanced hepatocellular carcinoma


Updated 2024 BSG guidelines for the diagnosis and management of hepatocellular carcinoma


Updated 2025 EASL guidelines for the diagnosis and management of hepatocellular carcinoma


The European Society of Medical Oncology (ESMO) has updated its guidelines for the diagnosis and management of hepatocellular carcinoma (HCC). Screening with abdominal ultrasound or multiphasic cross-sectional imaging (with or without alpha-fetoprotein) is recommended for patients with liver cirrhosis and viral hepatitis. Diagnosis should be based on histology and/or contrast-enhanced imaging findings, while liquid biopsy and ctDNA testing are not recommended. For early- and intermediate-stage disease, recommended treatments include surgical resection, tumor ablation, and transarterial therapies, with no adjuvant systemic therapy. For advanced disease, definitive systemic therapy is recommended, with first-line options including atezolizumab/bevacizumab, durvalumab/tremelimumab, camrelizumab/rivoceranib, nivolumab/ipilimumab, durvalumab, tislelizumab, lenvatinib, and sorafenib. Systemic chemotherapy is not recommended. External beam radiotherapy is suggested for painful bone metastases or hepatic pain.


Hepatocellular carcinoma

Background

Overview

Guidelines

Key sources