Bone loss is common in advanced cirrhosis, although the precise mechanisms underlying bone loss in cirrhosis are unknown. We studied the profile and functionality of bone‐forming cells and bone‐building proteins in bone marrow (BM) of individuals with cirrhosis (n = 61) and individuals without cirrhosis as normal controls (n = 50). We also performed dual energy X‐ray absorptiometry for clinical correlation. BM mesenchymal cells (MSCs) were analyzed for colony‐forming units‐fibroblasts and their osteogenic (fibronectin‐1 [FN1], insulin‐like growth factor binding protein 3 [IGFBP3], collagen type 1 alpha 1 chain [COL1A1], runt‐related transcription factor 2 [RUNX2], and alkaline phosphatase, liver [ALPL]) and adipogenic ( adiponectin, C1Q, and collagen domain containing [ADIPOQ], peroxisome proliferator‐activated receptor gamma [PPARγ], and fatty acid binding protein 4 [FABP4]) potentials. Colony‐forming units‐fibroblasts were lower in patients with cirrhosis (P = 0.002) than in controls. Cirrhotic BM‐MSCs showed >2‐fold decrease in osteogenic markers. Compared to controls, patients with cirrhosis showed fewer osteocytes (P = 0.05), osteoblasts, chondroblasts, osteocalcin‐positive (osteocalcin+) area, clusters of differentiation (CD)169+ macrophages (P < 0.001, each), and nestin+ MSCs (P = 0.001); this was more apparent in Child‐Turcotte‐Pugh (CTP) class C than A (P < 0.001). Multivariate logistic regression showed low nestin+ MSCs (P = 0.004) as a predictor of bone loss. Bone‐resolving osteoclasts were comparable among CTP groups, but >2‐fold decreased anti‐osteoclastic and increased pro‐osteoclastic factors were noted in patients with CTP C compared to CTP A. Bone‐building proteins (osteocalcin [P = 0.008], osteonectin [P < 0.001], and bone morphogenic protein 2 [P = 0.001]) were decreased while anti‐bone repair factors (fibroblast growth factor 23 [P = 0.015] and dipeptidyl peptidase 4 [P < 0.001]) were increased in BM and peripheral blood; this was more apparent in advanced cirrhosis. The dual energy X‐ray absorptiometry scan T score significantly correlated with the population of osteoblasts, osteocytes, MSCs, and CD169+ macrophages. Conclusion: Osteoprogenitor cells are substantially reduced in patients with cirrhosis and more so in advanced disease. Additionally, increased anti‐bone repair proteins enhance the ineffective bone repair and development of osteoporosis in cirrhosis. Hepatology Communications 2018;0:0‐0)

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Low functional protein C level correlated with markers of liver dysfunction, inflammation and sepsis and independently predicted mortality at 3 months in cirrhotics, especially if functional levels were <52%.

There is great variation in cytopenias in cirrhotic patients with same severity and hypersplenism and their causative factors are not clear. Recent studies have highlighted the role of gut microbiome in regulation of constant and emergency hematopoiesis. Broad-spectrum antibiotics can disrupt the homeostatic or adaptive microbiota in cirrhosis, leading to impaired hematopoiesis and a higher susceptibility to infections. We studied all patients with cirrhosis with cytopenia (anemia, leucopenia, and/or thrombocytopenia), admitted in the Institute of Liver & Biliary Sciences, between January 2016 and July 2017, who underwent a bone marrow examination. The effect of the different antimicrobial agents on peripheral blood counts and bone marrow cellularity was assessed. A total of 196 patients' data was analyzed for this study. Patients on antimicrobials (n = 115) had significantly lower hemoglobin (p < 0.001), total leucocyte count (p = 0.048), and platelet count (p = 0.043) compared to patients not on antimicrobials. On unadjusted analysis, significant association with thrombocytopenia existed in beta-lactams (OR = 1.56, 95% CI = 1.06–2.40), quinolones (OR = 1.66, 95% CI = 1.11–2.61), and antifungals (OR = 2.24, 95% CI = 1.96–4.34). Cephalosporins were found to be significantly associated with anemia (OR = 1.91, 95% CI = 1.07–3.41). Patients who received antimicrobials had hypocellular marrow (p < 0.001) as compared to nonrecipients of antibiotics. The adjusted analysis showed that quinolones and beta-lactam antibiotics are the drug classes having significant association with thrombocytopenia and alternative class of drug should be explored in these patients to avoid severe thrombocytopenia.

CONTEXT: Inflammatory pseudotumor (IPT) of the liver is a rare, tumor-like lesion that is considered to be biologically benign but often mimics malignancy. AIMS: The aim of the study was construe clinicopathological features, imaging findings, differential diagnosis, management, and follow-up of IPT involving the liver. SETTINGS AND DESIGN: It is a retrospective study. SUBJECTS AND METHODS: Cases included were of IPT, diagnosed on histopathology, at our center from June 2009 to December 2016. Details studied were clinical presentation, imaging studies, laboratory investigations, pathological features, treatment, and follow-up of the cases and compared with reports in the literature. RESULTS: A total of cases of IPT included were 17. The age of the patients ranged from 21 to 62 years. Common presenting features were intermittent fever, upper abdominal pain, and weight loss. Radiological diagnosis varied from neoplastic (13) to infectious etiologies (4), with hepatocellular carcinoma being the most common differential (7/17). Laboratory investigations revealed leukocytosis, hyperbilirubinemia, raised transaminases, and raised serum alkaline phosphatase. Core biopsy of a tumor conceded increased fibrosis along with mixed inflammatory cell infiltrates. Eleven cases were managed conservatively and showed regression or complete recovery. Six patients underwent surgical resection. None of these had any recurrence in median follow-up of 22 months. CONCLUSIONS: IPT of the liver can masquerade as a fatality, either primary or metastatic. It will be well managed with conservative modalities and can avoid redundant hepatectomy, reserved for complicated cases. For this intent, accurate preoperative diagnosis is the requisite, and needle biopsy with or without fine-needle aspiration cytology plays as a significant rescuer in this field.