Publications by authors named "Irun Bhan"

Background: HCC is a highly vascular tumor, and many effective drug regimens target the tumor blood vessels. Prior bulk HCC subtyping data used bulk transcriptomes, which contained a mixture of parenchymal and stromal contributions.

Methods: We utilized computational deconvolution and cell-cell interaction analyses to cell type-specific (tumor-enriched and vessel-enriched) spatial transcriptomic data collected from 41 resected HCC tissue specimens.

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Importance: Women on the liver transplant waiting list are less likely to undergo a transplant than men. Recent approaches to resolving this disparity have involved adjustments to Model for End-Stage Liver Disease (MELD) scoring, but this will not affect candidates who rely on exception scores rather than calculated MELD score, the majority of whom have hepatocellular carcinoma (HCC).

Objective: To evaluate the association between female sex, candidate size, and access to liver transplant among wait-listed patients with HCC.

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Background & Aims: Noninvasive variceal risk stratification systems have not been validated in patients with hepatocellular carcinoma (HCC), which presents logistical barriers for patients in the setting of systemic HCC therapy. We aimed to develop and validate a noninvasive algorithm for the prediction of varices in patients with unresectable HCC.

Methods: We performed a retrospective cohort study in 21 centers in the United States including adult patients with unresectable HCC and Child-Pugh A5-B7 cirrhosis diagnosed between 2007 and 2019.

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Article Synopsis
  • * The LINE-1 ORF1p protein is overexpressed in various cancers and has negligible expression in normal tissues, indicating its potential as a highly specific blood-based cancer biomarker.
  • * Advanced digital immunoassays can detect low levels of ORF1p in plasma, showing promise for early detection of ovarian cancer and monitoring treatment responses in gastroesophageal cancers, suggesting it could be a valuable tool for cancer diagnosis and prognosis.
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Background: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are the leading causes of hepatocellular carcinoma (HCC) worldwide. Limited data exist on surgical outcomes for NAFLD/NASH-related HCC compared with other HCC etiologies. We evaluated differences in clinicopathological characteristics and outcomes of patients undergoing surgical resection for NAFLD/NASH-associated HCC compared with other HCC etiologies.

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Article Synopsis
  • * The Long INterspersed Element-1 (LINE-1) open reading frame 1 protein (ORF1p) is found to be overexpressed in various cancers but not in normal tissues, highlighting its potential as a specific cancer biomarker.
  • * Researchers have developed highly sensitive digital immunoassays to detect ORF1p in blood samples, showing promise for early detection of ovarian cancer and improved monitoring of gastric and esophageal cancers, positioning it as a valuable multi-cancer biomarker.
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Cirrhosis confers a variable risk of developing hepatocellular carcinoma (HCC), but the risk varies significantly depending upon ill-defined factors. In this issue of Med, Fujiwara et al. use hepatic gene signatures and computational analysis to develop a streamlined, robust blood-based predictor of HCC risk in this population.

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Aims: The efficacy of somatostatin in altering splanchnic hemodynamics in cirrhotic portal hypertension is still controversial. We aimed to establish the dynamic effect of somatostatin on portal pressure in cirrhotic patients and compared its effect with Partial Splenic Embolization (PSE).

Methods: Eighteen patients with cirrhotic portal hypertension were prospectively recruited.

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Background: Coronavirus disease 2019 (COVID-19) is associated with elevated liver biochemistries in approximately half of hospitalized patients, with many possible etiologies.

Aim: To assess agreement on the etiology of abnormal liver biochemistries and diagnostic recommendations in COVID-19.

Methods: Twenty hepatology consultations were reviewed by three senior hepatologists who provided a differential diagnosis and diagnostic recommendations.

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Pancreatic ductal adenocarcinoma (PDAC) lethality is due to metastatic dissemination. Characterization of rare, heterogeneous circulating tumor cells (CTCs) can provide insight into metastasis and guide development of novel therapies. Using the CTC-iChip to purify CTCs from PDAC patients for RNA-seq characterization, we identify three major correlated gene sets, with stemness genes LIN28B/KLF4, WNT5A, and LGALS3 enriched in each correlated gene set; only LIN28B CTC expression was prognostic.

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The practice of transplanting hepatitis C (HCV)-infected livers into HCV-uninfected recipients has not previously been recommended in transplant guidelines, in part because of concerns over uncontrolled HCV infection of the allograft. Direct-acting antivirals (DAAs) provide an opportunity to treat donor-derived HCV-infection and should be administered early in the posttransplant period. However, evidence on the safety and efficacy of an immediate DAA treatment approach, including how to manage logistical barriers surrounding timely DAA procurement, are required prior to broader use of HCV-positive donor organs.

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Background: Low donor heart availability underscores the need to identify all potentially transplantable organs. We sought to determine whether pre-emptive administration of pangenotypic direct-acting antiviral therapy can safely prevent the development of chronic hepatitis C virus (HCV) infection in uninfected recipients of HCV-infected donor hearts.

Methods: Patients were recruited for this an open-label, single-centre, proof-of-concept study from Nov 1, 2017, to Nov 30, 2018.

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Specialty palliative care (PC) is underused for patients with end-stage liver disease (ESLD). We sought to examine attitudes of hepatologists and gastroenterologists about PC for patients with ESLD. We conducted a cross-sectional survey of these specialists who provide care to patients with ESLD.

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Background & Aims: Despite evidence for the benefits of palliative care (PC) referrals and early advance care planning (ACP) discussions for patients with chronic diseases, patients with end-stage liver disease (ESLD) often do not receive such care. We sought to examine physicians' perceptions of the barriers to PC and timely ACP discussions for patients with ESLD.

Methods: We conducted a cross-sectional survey of hepatologists and gastroenterologists who provide care to adult patients with ESLD, recruited from the American Association for the Study of Liver Diseases 2018 membership registry.

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Epithelial cells in the circulation (circulating epithelial cells, or CECs) are analyzed as a non-invasive method to detect cancers; we investigated whether analysis of hepatocytes in the circulation can identify patients with chronic liver disease or hepatocellular carcinoma (HCC). We previously developed a cell-sorting device to isolate CECs from patient blood samples and combined it with an mRNA analysis system to identify CECs with liver-specific markers. We tested the ability of this device to detect CECs of hepatocyte origin in blood samples from healthy individuals (n=10), patients with chronic liver disease without HCC (n=39), and patients with HCC (n=54), using immunofluorescence.

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Circulating tumor cells (CTCs) are shed into the bloodstream by invasive cancers, but the difficulty inherent in identifying these rare cells by microscopy has precluded their routine use in monitoring or screening for cancer. We recently described a high-throughput microfluidic CTC-iChip, which efficiently depletes hematopoietic cells from blood specimens and enriches for CTCs with well-preserved RNA. Application of RNA-based digital PCR to detect CTC-derived signatures may thus enable highly accurate tissue lineage-based cancer detection in blood specimens.

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