For over a decade, sorafenib remained the only systemic agent with proven clinical efficacy for patients with advanced hepatocellular carcinoma (HCC). Recent years have seen a proliferation of agents. In the first line, lenvatinib was found to be non-inferior to sorafenib in terms of overall survival (OS), with significantly better progression-free survival and objective response rate. Meanwhile, encouraging efficacy signals were observed in phase I/II studies of immune checkpoint inhibitors as monotherapy in HCC. Although subsequent phase III trials failed to demonstrate statistically significant benefit in OS, other clinically meaningful outcomes were observed, including long-term disease control with a favorable toxicity profile. In addition, a synergistic response has been postulated based on the interplay between antiangiogenic molecular targeted agents and immunotherapy. On this basis, interest has turned toward combination strategies of immunotherapy with these standard-of-care medications in the hope of improving treatment efficacy for advanced HCC, while maintaining tolerable safety profiles. Indeed, preliminary results from phase I studies of lenvatinib plus pembrolizumab and atezolizumab plus bevacizumab have proved favorable, prompting phase III investigations in the frontline setting, and for atezolizumab plus bevacizumab, these positive findings have been substantiated by recent reporting of phase III data from IMbrave150. In this review, we will present the currently available data on combination therapy atezolizumab plus bevacizumab in advanced HCC, and compare these findings to other promising combination treatments, most notably that of lenvatinib plus pembrolizumab.

Among culture-negative endocarditis in the United States, Bartonella species are the most common cause, with Bartonella henselae and Bartonella quintana comprising the majority of cases. Kidney manifestations, particularly glomerulonephritis, are common sequelae of infectious endocarditis, with nearly half of all Bartonella patients demonstrating renal involvement. Although a pauci-immune pattern is a frequent finding in infectious endocarditis–associated glomerulonephritis, it is rarely reported in Bartonella endocarditis. Anti–neutrophil cytoplasmic antibody (ANCA) positivity can be seen with many pathogens causing endocarditis and has been previously reported with Bartonella species. In addition, ANCA-associated vasculitis can also present with renal and cardiac involvement, including noninfectious valvular vegetations and pauci-immune glomerulonephritis. Given the overlap in their clinical presentation, it is difficult to differentiate between Bartonella endocarditis and ANCA-associated vasculitis but imperative to do so to guide management decisions. We present a case of ANCA-positive Bartonella endocarditis with associated pauci-immune glomerulonephritis that was successfully treated with medical management alone.

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e15646 Background: American Association for the Study of Liver Disease (AASLD) guidelines endorse radiographic diagnosis of HCC if key features are present on dynamic contrast-enhanced imaging (arterial hyperenhancement and venous washout) with biopsy for those without these features. As many HCC patients (pts) are diagnosed outside liver transplant centers, we sought to describe the methods of diagnosis of HCC and factors associated with biopsy in routine care in the US. Methods: HCC cases were identified from 2 data sources: SEER-Medicare (M) 2004-2011 and North Carolina Central Cancer Registry (NCCCR) linked to Medicare, Medicaid and private claims 2004-2013. Diagnostic confirmation was identified from registries as pathologic (path) or clinical. Key covariates included age, cancer stage, cause and severity of cirrhosis, and comorbid disease. Specialty consultation, prediagnosis imaging, AFP testing were determined from claims -3 to 0 months from diagnosis. Multivariable logistic regression was used to identify factors associated with path. Results: Path was obtained in a majority of HCC pts: 68% of 10,989 in SEER-M, 72% of 1,809 in NCCCR. In SEER-M, claims for contrasted abdominal CT were more common in those with path than those without (34 vs 30%) but not for MRI (14 vs 14%). Odds of path was higher in pts with contrasted CT (adjusted odds ratio [OR] 1.48, 95% confidence interval [CI] 1.30-1.69) or MRI (OR 1.53, CI 1.31-1.80) vs pts without imaging. In NCCCR, CT (51 vs 41%) and MRI (35 vs 34%) were performed more. Both were associated with increased odds of biopsy vs pts without imaging: contrasted CT scan (OR 1.74, CI 1.22-2.47) or MRI (OR 1.48, CI 1.02-2.13). In neither cohort did ultrasound increase odds of path over no imaging. Pts seen by an oncologist (OR SEER-M 1.66, CI 1.46-1.89) were more likely to have path than pts not seen by oncology. In SEER-M, pts seen at abdominal transplant centers were less likely to have path (OR 0.87, CI 0.77-0.98). Conclusions: Most pts diagnosed with HCC had path confirmation of cancer despite internationally accepted guidelines supporting radiographic diagnosis. The use of biopsy was greater among those with cross-sectional imaging, suggesting this high biopsy rate cannot solely be explained by nondiagnostic imaging.