A Rare Cause of Gastric Variceal Bleeding

A 68-year-old woman with stage III colon cancer status after right hemicolectomy and adjuvant FOLFOX (5-fluorouracil/leucovorin/oxaliplatin) chemotherapy was hospitalized for melena and found to have new-onset esophageal and gastric varices on esophagogastroduodenoscopy. Her workup did not reveal an underlying liver disease, but her liver biopsy showed noncirrhotic portal hypertension from obliterative portal venopathy (OPV). The development of OPV is likely from her use of oxaliplatin-based chemotherapy.

Identification of Genetic Predisposition in Noncirrhotic Portal Hypertension Patients With Multiple Renal Cysts by Integrated Analysis of Whole-Genome and Single-Cell RNA Sequencing

Background and Aims: The multiple renal cysts (MRC) occur in some patients with noncirrhotic portal hypertension (NCPH) could be a subset of ciliopathy. However, the potential genetic influencers and/or determinants in NCPH with MRC are largely unknown. The aim of this study was to explore the potential candidate variants/genes associated with those patients.Methods: 8,295 cirrhotic patients with portal hypertension were enrolled in cohort 1 and 267 patients affected with NCPH were included in cohort 2. MRC was defined as at least two cysts in both kidneys within a patient detected by ultrasonography or computed tomography. Whole-genome sequencing (WGS) was performed in nine patients (four from cohort 1 and five from cohort 2). Then we integrated WGS and publicly available single-cell RNA sequencing (scRNA-seq) to prioritize potential candidate genes. Genes co-expressed with known pathogenic genes within same cell types were likely associated NCPH with MRC.Results: The prevalence of MRC in NCPH patients (19.5%, 52/267) was significantly higher than cirrhotic patients (6.2%, 513/8,295). Further, the clinical characteristics of NCPH patients with MRC were distinguishable from cirrhotic patients, including late-onset, more prominent portal hypertension however having preserved liver functions. In the nine whole genome sequenced patients, we identified three patients with early onset harboring compound rare putative pathogenic variants in the known disease gene PKHD1. For the remaining patients, by assessing cilia genes profile in kidney and liver scRNA-seq data, we identified CRB3 was the most co-expressed gene with PKHD1 that highly expressed in ureteric bud cell, kidney stromal cell and hepatoblasts. Moreover, we found a homozygous variant, CRB3 p.P114L, that caused conformational changes in the evolutional conserved domain, which may associate with NCPH with MRC.Conclusion: ScRNA-seq enables unravelling cell heterogeneity with cell specific gene expression across multiple tissues. With the boosting public accessible scRNA-seq data, we believe our proposed analytical strategy would effectively help disease risk gene identification.

Nodular Regenerative Hyperplasia of the Liver in Rheumatic Disease: Cases and Review of the Literature

Nodular regenerative hyperplasia (NRH) is a rare disease that is characterized by benign transformation of the hepatic parenchyma into small nodules with little to no fibrosis. Nodular regenerative hyperplasia is a cause of noncirrhotic portal hypertension. Symptoms can range from asymptomatic disease to more serious complications of portal hypertension such as esophageal varices and ascites. Nodular regenerative hyperplasia has been described in association with a variety of different rheumatologic, hematologic, and oncologic diseases, as well as in immune deficiency states and with exposures to certain toxins. Diagnosis is made by histology, and the treatment involves addressing the underlying disease. The first description of this rare disease was actually described in a patient with rheumatoid arthritis, neutropenia, and splenomegaly (Felty’s Syndrome). We describe 2 cases of NRH associated with underlying rheumatic disorders, in one of which NRH was actually the presenting feature of the patient’s underlying autoimmune condition. Subsequently, we provide a brief review of the literature of NRH in autoimmune disease with respect to epidemiology, cause, clinical manifestations, diagnosis, and treatment.