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BACKGROUND:Because imaging has a high sensitivity to diagnose hepatocellular carcinoma (HCC) and tissue biopsies carry risks such as bleeding, the latter are often not performed in HCC. Blood-derived circulating tumor DNA (ctDNA) analysis can identify somatic alterations, but its utility has not been characterized in HCC. MATERIALS AND METHODS:We evaluated 14 patients with advanced HCC (digital ctDNA sequencing [68 genes]). Mutant relative to wild-type allele fraction was calculated. RESULTS:All patients (100%) had somatic alterations (median = 3 alterations/patient [range, 1-8]); median mutant allele fraction, 0.29% (range, 0.1%-37.77%). Mutations were identified in several genes: TP53 (57% of patients), CTNNB1 (29%), PTEN (7%), CDKN2A (7%), ARID1A (7%), and MET (7%); amplifications, in CDK6 (14%), EGFR (14%), MYC (14%), BRAF (7%), RAF1 (7%), FGFR1 (7%), CCNE1 (7%), PIK3CA (7%), and ERBB2/HER2 (7%). Eleven patients (79%) had ≥1 theoretically actionable alteration. No two patients had identical genomic portfolios, suggesting the need for customized treatment. A patient with a CDKN2A-inactivating and a CTNNB1-activating mutation received matched treatment: palbociclib (CDK4/6 inhibitor) and celecoxib (COX-2/Wnt inhibitor); des-gamma-carboxy prothrombin level decreased by 84% at 2 months (1,410 to 242 ng/mL [normal: ≤7.4 ng/mL]; alpha fetoprotein [AFP] low at baseline). A patient with a PTEN-inactivating and a MET-activating mutation (an effect suggested by in silico molecular dynamic simulations) received sirolimus (mechanistic target of rapamycin inhibitor) and cabozantinib (MET inhibitor); AFP declined by 63% (8,320 to 3,045 ng/mL [normal: 0-15 ng/mL]). CONCLUSION:ctDNA derived from noninvasive blood tests can provide exploitable genomic profiles in patients with HCC. IMPLICATIONS FOR PRACTICE:This study reports that blood-derived circulating tumor DNA can provide therapeutically exploitable genomic profiles in hepatocellular cancer, a malignancy that is known to be difficult to biopsy.

The incidence of splenic artery aneurysm (SAA) in patients with cirrhosis ranges from 7 per cent to 17 per cent. SAA rupture after liver transplantation (LT) is reported to result in significant morbidity and mortality. We report our experience with SAA in LT candidates. From September 1995 through August 2002, 14 LT candidates were diagnosed with SAA. Twenty SAA occurred in 14 patients with an average diameter of 20 mm. Eleven patients qualified for LT; to date, seven have been transplanted. No intervention for SAA occurred prior to LT. Of the seven patients transplanted, four had SAA identified prior to LT. Three were treated at LT and are alive; the fourth had postoperative splenic artery embolization followed by splenectomy and expired on day 109 from duodenal ulcer complications. Three of seven patients had undiagnosed SAA at LT. One required emergency splenectomy for SAA rupture and is alive at 44 months. The remaining two received no treatment; one suffered a late septic death and one is alive at 15 months. No ruptures occurred in our pre-LT population, suggesting that definitive management can await LT. We recommend that all patients undergo four-phase computed tomography or magnetic resonance angiography (MRA) as part of the LT evaluation and that identified SAA be resected at transplantation.