Katie presented an elderly man presenting with few weeks of unintentional 40lbs weight loss and abdominal pain, found to be jaundiced on exam with notable hepatomegaly. Labs notable for mild hepatitis and mix conjugated and unconjugated hyperbilirubinemia with mild coagulopathy. He was ultimately diagnosed with cirrhosis and extremely likely HCC with “numerous” masses of varying size (largest one was 10 cm) with portal vein invasion.

Please refer to this previous post on etiology of hyperbilirubinemia.

Please refer to this other post on hepatitis serologies made ridiculously simple.

Hepatomegaly and jaundice: Think infiltrative/malignant process!

For patients with cirrhosis and abdominal distension, palpating and percussing the liver can be challenging.

A strategy we went over during the last physical exam round was the scratch test, which relies on the principle of the different of sound transmission through materials of various densities.

To perform the scratch test, place your stethoscope over the RUQ just above the costal margin or just below the xiphoid, and from the RLQ, lightly scratch the patient horizontally and then slowly move superiorly toward the costal margins until the sound intensities. The location of sound intensification marks the inferior edge of the liver.

Small study re: accuracy of using the scratch test.

Hepatocellular Carcinoma

Epidemiology

• Most of the time a complication from liver cirrhosis
• Risk Factors
  • Cirrhosis, any etiology
  • Chronic HBV even without cirrhosis (oncogenic virus)
  • HCV with cirrhosis
  • Fungal aflatoxins
• Higher prevalence in East and SE Asia + Sub-Saharan African nations
• HBV inc risk by 100x

Presentation

• Variable initial presentation
  • Asx
  • Decompensated cirrhosis
  • Jaundice, abd pain, B-sx, +/- palpable pass
  • Variceal hemorrhage
  • Tumor rupture leading to acute hemorrhagic shock
  • Obstructive jaundice due to biliary tree invasion
  • 10-15% with metastatic dz at time of dx.
    • Most common sites: Lung, lymph nodes, adrenal glands.
  • Paraneoplasic: Hypoglycemia (adv HCC), erythrocytosis, hypercalcemia, diarrhea

Diagnosis

• Imaging: Sensitivity generally dec with small lesions, but imaging alone to establish dx of HCC without a biopsy in certain patient populations.
  • Contrast enhanced CT (triphasic)
    • Arterial phase hyperenhancement: Characteristic of HCC lesions but not specific, can be small hemangiomas, focal nodular hyperplasia, atypical focal fibrosis, non-HCC malignancy
    • Venous phase Washout: Again characteristic of HCC but not specific, cirrhosis nodules can be similar.
    • Capsular appearance: Pretty specific for HCC
    • All 3 of the above = diagnostic of HCC, very specific not but as sensitive.
    • Highest PPV for pts with cirrhosis with lesions > 2cm
  • MRI
    • Contraindicated in GFR < 30, Nephrogenic systemic fibrosis
    • More sensitive than CT, ~ specificity,
  • US: Can be use as diagnosis but cannot evaluate disease burden, transplant candidacy, operator dependent. 90% sensitive and 97% specifc
  • LIRADS
    • Should only be applied to pts with cirrhosis, chronic HBV, lesions identified on surveillance US for HCC, current or prior dx of HCC.
    • Should NOT be applied to: no risk factors for HCC, < 18, cirrhosis secondary to congenital hepatic fibrosis or vascular etiology.
  • LIRADS definitions for hepatocellular carcinoma based on ACR v2017:
    • LR-1: Definitely benign
    • LR-2: Probably benign
    • LR-3: Intermediate probability for HCC
    • LR-4: Probably HCC
    • LR-5 – Definitely HCC
    • LR-5V: Definitely HCC with tumor in vein
    • LR-M: Probably malignancy, not specific for HCC
    • LR-TR Viable: Treated, probably or definitely viable HCC
    • LT-TR Nonviable: Treated, probably or definitely not viable
    • LR-TR Equivocal: Treated, equivocally viable
    • LR-TR Nonevaluable: TReated, response not evaluable

• Labs
  • Alpha-fetoprotein: Elevated in 40-65% of patients with HCC
    • Normally produced during gestation, not during adulthood.
    • Levels do not correlate well with degree of disease
    • Sensitivity: 60%, spec: 80%, not good as a screening tool.
    • Higher levels > 400 are very specific for HCC.
    • May be seen in chronic liver disease so not very sensitive.
    • Elevated levels are associated with advanced fibrosis, pregnancy
• Biopsy: Reserved for indeterminate nodules that do not meet radiologic criteria for HCC.
  • Not recommended for LR1, LR2, LR3, or LR5 lesions
  • Risk: spread of tumor along needle track, sampling error (false negative), usual surgical risk (bleeding, infection, etc)
• Staging:
  • TNM
  • Barcelona Clinic Liver Cancer staging system

Management

• Surveillance for at risk patients:
  • Cirrhosis or HBV: Q6mo liver US
• Resection
  • Preferred therapy for localized disease
  • Sufficient liver reserve, can’t be worse than Child Pugh A cirrhosis
  • 5 year survival rate as high as 90%
  • Stage IIIB, IVA, and IVB are incurable by resection (any invasion of a major portal or hepatic vein, other organs, visceral peritoneum, nodal mets)
• Antiviral
  • Recommended for those with active viral infection and HBV related HCC.
• Liver transplantation
  • Milan criteria widely accepted, to be considered a candidate for transplant, pt must meet all criteria
    • Solitary tumor < 5cm or up to 3 tumors all < 3cm
    • No evidence of regional nodal or distant mets
    • No evidence of vascular invasion
• Ablation
  • Radiofrequency or microwave or localized ethanol/acetic acid/cryo localized ablation
  • Best outcomes for tumor size < 4 cm
  • Cirrhosis: Restricted to Child Class A or B
  • Can be used to bridge to liver transplant
• TACE
  • Disruption of HCC supply, usually derived from the hepatic artery
  • Leads to tumor necrosis from ischemia.
  • Usually used for tx of large unresectable HCC not amenable to other tx i.e. resection or RFA.
  • Best candidates: No vascular invasion or extrahepatic spread, Child Puph A or B
  • Relative contraindication:
    • bili > 2
    • LDH > 425
    • AST > 100
    • Tumor > 50% of liver
    • Untreated EV
    • Significant medical comorbidities
• Radiation
  • Localized external radiation vs radioembolization, HCC is radiation sensitive.
• Systemic chemo
  • Sorafenib
    • SHARP trial, prolongs survival over supportive care in pts with adv HCC)
    • Might be more beneficial for HCC related to viral etiology
  • Other agents: Regorafenib, Lenvatinib
  • Complication during tx
    • Reactivation of viral hepatitis

Prognosis

• 10-20% of cases are curable (resectable disease)
• 5-yr survival rates of about 5% or less if beyond stage III (portal vein invasion)
• Some evidence that sorafenib improves survival by around 3 months but it is a costly medication (60 tablets can cost up to $9000 after discount!)