Medicine chapters
Hepatocellular carcinoma and liver transplant
Risk factors, surveillance, diagnosis and treatment of hepatocellular carcinoma, other liver tumours in brief, and liver transplantation: who qualifies, who cannot, rejection, immunosuppression and outcome.
- HCC arises mostly in a cirrhotic liver (HBV, HCV, alcohol, NAFLD, haemochromatosis); HBV can cause it without cirrhosis; aflatoxin adds risk. Survey cirrhotics with 6-monthly ultrasound ± AFP.
- Diagnose by multiphase CT or MRI: arterial enhancement with washout; biopsy is rarely needed. Treat small tumours by resection, ablation or transplant (Milan criteria), intermediate by TACE, advanced by systemic drugs.
- Liver transplant is for acute liver failure and end-stage cirrhosis (Child C or MELD 20+); ABO match is needed, HLA match is not; watch for acute rejection at 5–10 days and hepatic artery thrombosis.
On this page
Overview
Hepatocellular carcinoma (HCC) is the main primary cancer of the liver and one of the most common cancers worldwide. In Pakistan, where hepatitis B and C are widespread, it is a frequent cause of death in patients with cirrhosis. Most cases occur in a cirrhotic liver, so surveillance of cirrhotic patients finds tumours early enough to treat.
Liver transplantation is the only cure for end-stage liver disease and for selected small HCCs. In Pakistan most liver transplants use living related donors, under national transplant law.
Liver tumours at a glance
| Tumour | Key points |
|---|---|
| Metastases | Most common malignant liver tumour overall; from gut (portal spread), breast, lung; usually multiple; ALP almost always raised |
| HCC | Commonest primary malignant tumour; usually on cirrhosis |
| Fibrolamellar HCC | Young adults, no cirrhosis, normal AFP, central fibrous scar, better outlook |
| Cholangiocarcinoma | Bile duct cancer; linked to PSC, ulcerative colitis, liver flukes, choledochal cyst; jaundice with hilar tumours |
| Hepatoblastoma | Young children; very high AFP |
| Haemangioma | Commonest benign tumour; incidental; no treatment |
| Hepatic adenoma | Young women on the combined pill or anabolic steroids; can bleed; resect if large (over 5 cm) or persistent after stopping the pill |
| Focal nodular hyperplasia | Benign, central scar, no bleeding risk |
Hepatocellular carcinoma
Risk factors
- Chronic hepatitis B: risk is high even without cirrhosis, because HBV DNA integrates into the host genome and the HBx protein promotes cancer. Risk rises with viral load.
- Chronic hepatitis C: risk is mainly once cirrhosis has formed (about 1% per year in HCV cirrhosis).
- Cirrhosis of any cause: alcohol, NAFLD, haemochromatosis (high risk once cirrhotic), α1-antitrypsin deficiency.
- Aflatoxin B1: toxin from Aspergillus mould on stored groundnuts and maize; causes a p53 mutation.
- Male sex, older age, smoking, diabetes, obesity, anabolic steroids.
HBV can cause HCC without cirrhosis; HCV almost always needs cirrhosis first.
Pathology and spread
Single mass, several nodules, or diffuse infiltration. Cells look like hepatocytes. HCC tends to invade the portal vein (tumour thrombus) and hepatic veins, then spreads to lungs, bones and lymph nodes. It gets most of its blood from the hepatic artery, unlike normal liver, which is mostly portal-fed.
Clinical features
- Often no symptoms; found on surveillance.
- Weight loss, anorexia, fever, right upper quadrant ache, hard irregular tender liver, sometimes a bruit over the liver.
- Sudden decompensation of stable cirrhosis: new ascites (often blood-stained), jaundice, variceal bleeding from portal vein tumour thrombus, encephalopathy.
- Rupture with intraperitoneal bleeding.
- Paraneoplastic: hypoglycaemia, polycythaemia (erythropoietin), hypercalcaemia.
A previously stable cirrhotic who quickly develops ascites, jaundice and bleeding varices should be checked for HCC with portal vein invasion.
Surveillance
- Who: all patients with cirrhosis (if fit for treatment), and chronic HBV carriers at high risk even without cirrhosis (Kumar suggests men over 40 and women over 50, and those with a family history).
- How: ultrasound every 6 months, with or without AFP.
Investigations
- Alpha-fetoprotein (AFP): raised in many, and very high values (over about 200 ng/mL) strongly suggest HCC, but at least a third of tumours have a normal AFP. Also raised in hepatoblastoma, germ cell tumours and pregnancy (neural tube defects).
- Ultrasound: finds most lesions; first test.
- Multiphase contrast CT or MRI: the key test. HCC shows arterial-phase enhancement (hypervascular) and washout in the portal venous or delayed phase. In a cirrhotic liver, these features in a nodule over 1 cm are diagnostic without biopsy.
- Biopsy: only if imaging is not typical; it risks seeding along the needle track and bleeding.
- Staging: CT chest, assessment of liver function (Child-Pugh, MELD), portal hypertension and performance status. The BCLC system links stage to treatment.
In cirrhosis, arterial enhancement plus washout on CT or MRI diagnoses HCC; a biopsy is usually not needed.
Treatment
| Situation | Treatment |
|---|---|
| Small tumour, well-preserved liver, no portal hypertension | Surgical resection |
| Small tumour within Milan criteria, poor liver function | Liver transplant (treats tumour and cirrhosis) |
| Small tumour (especially up to 3 cm), not for surgery | Radiofrequency or microwave ablation |
| Intermediate stage: large or multiple, no vascular invasion, good liver function | Transarterial chemoembolisation (TACE) or radioembolisation |
| Advanced: vascular invasion or spread, good liver function | Systemic therapy: immunotherapy combinations (e.g. atezolizumab with bevacizumab) or tyrosine kinase inhibitors (sorafenib, lenvatinib) |
| End-stage liver function or poor performance status | Best supportive care |
- Milan criteria: one tumour up to 5 cm, or up to three tumours each up to 3 cm, with no vascular invasion and no spread outside the liver. Inside these limits, transplant results are good; outside them, recurrence is high.
- TACE works because HCC is fed mainly by the hepatic artery; chemotherapy and embolic particles are delivered into the tumour's artery while the surrounding liver survives on portal blood.
- Kumar notes that sorafenib extends survival only modestly (to about 10 months) in unresectable disease.
A raised AFP is not specific to HCC: it is also high in hepatoblastoma, yolk sac (germ cell) tumours, pregnancy with neural tube defects, and mildly in active hepatitis.
Prevention
- Hepatitis B vaccination (the birth dose matters most) has reduced HCC in vaccinated populations.
- Treating HBV (tenofovir, entecavir) and curing HCV with oral antivirals lowers risk, but cirrhotic patients still need surveillance after cure.
- Safe injection practice, blood screening, avoiding alcohol, controlling weight and diabetes, and proper grain storage (aflatoxin).
HCC risk "ABCD-H": Aflatoxin and Alcohol, Hepatitis B, Hepatitis C, Diabetes/fatty liver, Haemochromatosis.
Liver transplantation
Indications
- Acute liver failure meeting poor-prognosis criteria (e.g. King's College criteria; paracetamol, viral, drugs, Wilson disease).
- End-stage chronic liver disease with complications no longer controlled: Child-Pugh C, MELD 20 or more, refractory ascites, SBP, hepatorenal syndrome, recurrent variceal bleeding, encephalopathy, poor quality of life.
- HCC within Milan criteria.
- Specific diseases: primary biliary cholangitis (bilirubin persistently over 100 µmol/L or intractable itch), primary sclerosing cholangitis, autoimmune hepatitis not responding, alcohol-related disease after a period of proven abstinence, NASH cirrhosis, hepatitis B (graft protected with HBIG and antivirals), metabolic disorders (Wilson disease, haemochromatosis, α1-antitrypsin deficiency).
- Extrahepatic problems cured by transplant: hepatopulmonary syndrome, portopulmonary hypertension.
MELD score
Bilirubin 3 mg/dL, creatinine 1.5 mg/dL, INR 2.0
MELD = 3.8 × ln(3) + 9.6 × ln(1.5) + 11.2 × ln(2) + 6.4
= 3.8 × 1.099 + 9.6 × 0.405 + 11.2 × 0.693 + 6.4
= 4.17 + 3.89 + 7.76 + 6.4 = about 22 → 20 or more, refer to a transplant centre
(In practice an online calculator is used; values below 1 are set to 1.)
Contraindications
- Absolute: malignancy outside the liver, liver metastases (except some neuroendocrine), active sepsis outside the hepatobiliary tree, ongoing alcohol or drug misuse and lack of commitment to lifelong treatment, severe heart or lung disease that makes surgery unsafe.
- Relative: older age (usually not over 70), extensive portal/splanchnic vein thrombosis, HIV (now often acceptable), poor social support.
Donor and operation
- Donor and recipient must be ABO compatible; HLA matching is not needed (the liver is relatively protected from rejection).
- Sources: deceased donors (whole or split grafts) and living donors (usually the right lobe; donor mortality roughly 1 in 200 to 1 in 400).
- Grafts are stored cold; the operation takes several hours.
Immunosuppression
Lifelong, usually a calcineurin inhibitor (tacrolimus, or ciclosporin) with mycophenolate or azathioprine and early steroids; sirolimus in some. Side effects: nephrotoxicity, hypertension, diabetes, neurotoxicity (tremor), infections and cancers (skin cancer, post-transplant lymphoproliferative disorder).
Complications
| Timing | Complication | Points |
|---|---|---|
| Days | Primary graft non-function | Needs urgent retransplant |
| Early | Hepatic artery thrombosis | Bile ducts depend only on arterial blood, so it causes biliary necrosis, strictures, bile leaks and abscesses; detect with Doppler ultrasound |
| 5–10 days | Acute cellular rejection | Fever or rising enzymes; biopsy: portal infiltrate with eosinophils, bile duct damage, endothelialitis; responds to more immunosuppression (steroid pulses) |
| 6 weeks to 9 months | Chronic (ductopenic) rejection | Vanishing bile duct syndrome, arteriopathy; often needs retransplant |
| Any time | Infections | Bacterial early; CMV, fungal and other opportunistic infections in the first months |
| Long term | Recurrence of original disease, drug toxicity, cancers | HCV, HCC, PSC, AIH can recur |
After transplant, no hepatic artery flow on Doppler + bile duct strictures = hepatic artery thrombosis, because the biliary tree has no portal blood supply.
Outcome
Kumar quotes about 90% survival at 1 year and 70–85% at 5 years for elective transplant in low-risk patients. Most deaths occur in the first 3 months from sepsis and bleeding.
Expect: HBV causing HCC without cirrhosis (integration, HBx); aflatoxin and p53; AFP use and limits (normal in a third); 6-monthly ultrasound surveillance; arterial enhancement with washout; portal vein tumour thrombus causing sudden decompensation; hepatic arterial supply and TACE; Milan criteria; ablation, resection, sorafenib or lenvatinib; fibrolamellar variant (young, no cirrhosis, normal AFP); metastases as the commonest liver tumour, haemangioma as the commonest benign one, adenoma with the pill; transplant indications (Child C, MELD 20+), contraindications, ABO but not HLA matching, timing of acute and chronic rejection, hepatic artery thrombosis and biliary strictures, tacrolimus toxicity.
Quick revision
- HCC: mostly on cirrhosis; HBV can skip cirrhosis; aflatoxin causes p53 mutation.
- Survey cirrhosis with ultrasound every 6 months ± AFP.
- AFP normal in at least a third; very high levels strongly suggest HCC.
- CT/MRI: arterial enhancement + washout = HCC; biopsy rarely needed.
- Milan: one up to 5 cm, or up to three each up to 3 cm.
- Small: resect, ablate or transplant; intermediate: TACE; advanced: systemic drugs.
- Fibrolamellar: young, no cirrhosis, normal AFP, better outlook.
- Transplant: Child C or MELD 20+; ABO match, no HLA match.
- Acute rejection at 5–10 days; chronic = vanishing bile ducts; hepatic artery thrombosis → biliary strictures.
Written by The House Job from standard references (Kumar and Clark's Clinical Medicine).
FAQ
Is a normal AFP enough to exclude hepatocellular carcinoma?
No. At least a third of patients have a normal AFP, so surveillance relies on ultrasound and suspicious lesions need multiphase CT or MRI.
Why is a biopsy usually avoided in suspected HCC?
Typical imaging in a cirrhotic liver is diagnostic, and a needle biopsy can seed tumour along its track and cause bleeding.
Why does chemoembolisation work for HCC?
The tumour draws most of its blood from the hepatic artery, while normal liver relies mainly on the portal vein, so blocking the tumour's artery spares healthy tissue.
Does a liver transplant need tissue (HLA) matching?
No. Blood group (ABO) compatibility is required, but HLA matching is not needed for liver grafts.