Hepatocellular Carcinoma

Also known as: HCC, Liver cancer

Primary malignancy of hepatocytes, arising overwhelmingly in the context of chronic liver disease, most commonly cirrhosis from chronic hepatitis B, chronic hepatitis C, alcohol related liver disease, and increasingly MASLD.

Hepatitis B carries a unique ability to cause hepatocellular carcinoma even without cirrhosis, through direct viral integration into the host genome, which is why surveillance in high risk hepatitis B carriers begins independent of fibrosis stage in some guidelines (for example, Asian men over 40 and African patients over 20, per the risk thresholds noted in the Hepatitis B entry).

Often detected through surveillance in an asymptomatic patient with known cirrhosis.
Symptomatic presentation reflects advanced disease: right upper quadrant pain, weight loss, worsening ascites, new or worsening jaundice, and decompensation of previously stable cirrhosis.
A palpable liver mass or bruit may be present. Rupture with intraperitoneal hemorrhage is a rare but recognized acute presentation, causing sudden severe abdominal pain and hypovolemic shock.

In a cirrhotic patient, hepatocellular carcinoma can be diagnosed radiologically without biopsy if a lesion above 1 cm shows the characteristic pattern of arterial phase hyperenhancement with portal venous or delayed phase washout on contrast enhanced CT or MRI (the LI-RADS classification formalizes this).

Biopsy is reserved for atypical imaging or a non-cirrhotic liver.

AFP (alpha-fetoprotein) supports diagnosis and is used for monitoring treatment response, though it lacks sufficient sensitivity to be used alone for surveillance or diagnosis.

Surveillance in at risk patients (cirrhosis of any cause, and high risk hepatitis B carriers as above) uses six monthly ultrasound with or without AFP.

Staging uses the Barcelona Clinic Liver Cancer (BCLC) system, which uniquely incorporates tumor burden, liver function (Child-Pugh class), and performance status together, since treatment options and prognosis in hepatocellular carcinoma depend as much on underlying liver reserve as on tumor stage.

Differentials include other focal liver lesions in a cirrhotic liver (regenerative or dysplastic nodules, hemangioma), intrahepatic cholangiocarcinoma, and metastatic disease to the liver.

Management follows BCLC staged treatment allocation.

Very early and early stage disease (BCLC 0 to A) in patients with preserved liver function is treated with surgical resection, liver transplantation (particularly attractive since it treats both the tumor and the underlying cirrhosis, using Milan criteria to select appropriate candidates), or percutaneous ablation (radiofrequency or microwave ablation) for small tumors unsuitable for resection.

Intermediate stage disease (BCLC B, multinodular, preserved liver function) is treated with transarterial chemoembolization (TACE), delivering chemotherapy directly to the tumor via its arterial supply while embolizing the vessel.

Advanced stage disease (BCLC C, vascular invasion or extrahepatic spread) is treated with systemic therapy, including tyrosine kinase inhibitors (sorafenib, lenvatinib) and, increasingly first-line, combination immunotherapy (atezolizumab with bevacizumab).

Terminal stage disease (BCLC D, poor liver function or performance status) receives best supportive and palliative care, since aggressive treatment offers no benefit and may cause harm in this group.

Referral: hepatobiliary surgery, hepatology, and oncology multidisciplinary team for all confirmed or suspected cases; liver transplant unit assessment where criteria may be met.

Clinical toolsCalculators

BMI GCS EDD Parkland Formula

Corrected Sodium Corrected Calcium Anion Gap Creatinine Clearance Insulin Calculations qSOFA Wells PE Wells DVT CHA₂DS₂-VASc HAS-BLED CURB-65 Centor/McIsaac

Acute Liver Failure

Also known as: Fulminant hepatic failure

Rapid onset severe liver injury with synthetic dysfunction (coagulopathy, INR greater than 1.5) and hepatic encephalopathy, occurring in a patient without pre-existing chronic liver disease, within 26 weeks of the onset of symptoms.

Subclassified by interval from jaundice to encephalopathy: hyperacute (within 7 days, often paracetamol or viral hepatitis, better prognosis per unit of severity despite dramatic presentation), acute (8 to 28 days), and subacute (29 to 26 weeks, often drug induced or seronegative, generally worse prognosis).

Major causes include paracetamol overdose (leading cause in many high income settings), viral hepatitis (A, B, and E particularly, E notably in pregnancy where it carries high mortality), drug induced liver injury (idiosyncratic reactions, including anti-tuberculous therapy and certain antibiotics), autoimmune hepatitis, Wilson disease (particularly in younger patients, see separate entry), acute fatty liver of pregnancy and HELLP syndrome, ischemic hepatitis (shock liver), Budd-Chiari syndrome, and Amanita mushroom poisoning.

Jaundice, coagulopathy manifesting as easy bruising or spontaneous bleeding, and hepatic encephalopathy ranging from subtle confusion and mood change through to coma (see Hepatic Encephalopathy entry for grading).
Additional features include nausea and vomiting, right upper quadrant discomfort, fetor hepaticus, asterixis, and, as the condition progresses, signs of cerebral edema (papilledema, hypertension, bradycardia, decerebrate posturing) which carries a significant mortality risk and requires urgent recognition.
Multi-organ involvement is common in severe cases: acute kidney injury (hepatorenal physiology or direct toxic injury), hypoglycemia (impaired gluconeogenesis, requires frequent monitoring), and hemodynamic instability resembling septic shock from systemic inflammatory response.

Coagulation profile (INR, essential for diagnosis and prognostication), LFTs (marked transaminase elevation, though the degree does not correlate well with severity), ammonia (supports encephalopathy diagnosis though levels correlate poorly with grade), glucose (frequent bedside monitoring given hypoglycemia risk), U&E and creatinine, arterial blood gas and lactate, and paracetamol level in every case regardless of reported history, since accidental or concealed overdose is common and treatable.
Viral hepatitis serology, autoimmune markers, ceruloplasmin and slit lamp examination for Kayser-Fleischer rings if Wilson disease is suspected, and toxicology screen complete the etiological workup. Imaging (ultrasound with Doppler) assesses liver size, texture, and hepatic vein patency to exclude Budd-Chiari syndrome.
Prognostic scoring, most commonly the King's College Hospital criteria, guides transplant listing decisions and differs by paracetamol versus non-paracetamol etiology.

Differentials include acute on chronic liver failure (decompensation of previously unrecognized cirrhosis, an important distinction since management and prognosis differ substantially) and other causes of encephalopathy (sepsis, intracranial pathology, drug intoxication).

Management is best delivered in a liver unit with ICU capability, ideally with early transfer to a transplant center once the diagnosis is suspected, given how rapidly deterioration can occur.

N-acetylcysteine is given for paracetamol induced liver failure regardless of time since ingestion, and increasingly used empirically in non-paracetamol acute liver failure given a plausible benefit and low risk.
Coagulopathy is generally not corrected prophylactically (INR is a prognostic marker that correction would obscure), reserving blood product support for active bleeding or before invasive procedures.
Hepatic encephalopathy and cerebral edema are managed with head elevation, avoidance of stimulation, mannitol or hypertonic saline for evidence of raised intracranial pressure, and, in some centers, invasive intracranial pressure monitoring in high grade encephalopathy. Hypoglycemia is corrected aggressively with dextrose infusion.
Renal replacement therapy is used early for evolving acute kidney injury, both for renal support and to assist ammonia clearance.
Infection is a leading cause of death and should be sought and treated aggressively, with a low threshold for empirical broad spectrum antibiotics given blunted normal inflammatory markers in liver failure.
Specific antidotes are given where relevant (N-acetylcysteine for paracetamol, penicillin or silibinin for Amanita poisoning, antivirals for HBV related failure).
Emergency liver transplantation is the definitive treatment for patients meeting poor prognostic criteria who have no contraindication, and survival without transplant is poor once King's College criteria are met.

Referral: immediate discussion with a specialist liver unit or transplant center for any patient with coagulopathy and altered mental status in the context of acute liver injury; this should not be delayed pending full investigation.

Hepatocellular Carcinoma

Overview

Clinical Features

Diagnosis

Management

Overview

Clinical Features

Diagnosis

Management