Hilscher, Moira

Liver macrophages are central in maintaining hepatic homeostasis and mediating immune responses during liver injury, including fibrosis. Macrophages may have proinflammatory or antiinflammatory properties, but which properties influence fibrosis remains unclear. To explore the role of macrophages in liver fibrosis, we performed single-cell RNA-seq in a mouse model of liver injury and found that macrophage diversity was increased. Marco was among the most significantly upregulated genes, and a population of Marco hi macrophages increased with injury and spatially segregated to nonfibrotic areas. The macrophage receptor with collagenous structure (MARCO) protein is a scavenger receptor expressed by specific subsets of macrophages, and its role in liver fibrosis is unclear. In vitro induction of Marco in bone marrow–derived macrophages decreased proinflammatory gene expression, increased antiinflammatory and antifibrotic gene expression, and enhanced phagocytosis, indicating a restorative phenotype. Adoptive transfer of MARCO + macrophages in a mouse model of liver fibrosis reduced the expression of extracellular matrix–associated (ECM-associated) genes in hepatic stellate cells (HSCs) and reduced collagen deposition, which did not occur with the transfer of MARCO – macrophages. Therefore, MARCO + macrophages have a tissue restorative role in the liver and attenuate fibrogenesis through interaction with HSCs, thereby providing a potential therapeutic pathway for liver fibrosis.

ABSTRACT Hepatoid adenocarcinoma (HAC) is a rare extrahepatic tumor of non‐germ cell origin that morphologically resembles hepatocellular carcinoma (HCC). HAC has a propensity to metastasize to the liver and therefore may be mistaken for HCC. There is a lack of standardized treatment protocols, and further studies are needed to evaluate the benefit of targeted therapy and immunotherapy. Recent studies have reported that tumor protein 53 ( TP53 ) gene mutations are associated with increased expression of programmed cell death ligand‐1 (PD‐L1), which may be a predictor of response to PD‐L1 targeted checkpoint inhibitors. This review provides a clinical guidance for the management of patients with HAC by summarizing the salient clinical features, risk factors, diagnostic criteria, differential diagnosis, new therapeutic approaches, and prognosis of this rare tumor. Furthermore, we reviewed the Mayo Clinic experience to describe the clinical characteristics of 15 patients diagnosed with HAC. HAC is usually diagnosed at an advanced stage with distant metastases. In patients diagnosed with liver lesions that have similar radiologic and histologic features to HCC, particularly in the absence of underlying chronic liver disease, further evaluation should be performed to rule out HAC. Communication between medical subspecialties is important to avoid misdiagnosis and prevent further disease progression. In our patient cohort TP53 was the most frequently mutated gene (5 out of 8, 62.5%) and PD‐L1 expression showed a positive score in 3 out of 6 patients (50%). However, only a few patients received immunotherapy (6 out of 14, 42.9%) suggesting that the numbers are too small to draw a conclusion about its efficacy in treating HAC.

Fontan-associated liver disease (FALD) occurs in all patients who have undergone Fontan palliation for functional single ventricle congenital heart defects. While liver fibrosis is universal in patients who have undergone Fontan palliation, FALD may lead to more serious consequences including portal hypertension, cirrhosis, and hepatocellular carcinoma. Scientific studies of the pathophysiology and clinical management of FALD have been limited to date by the heterogeneous nature of the disease, relatively small population of patients with Fontan physiology, and inaccuracy of noninvasive staging tests. As survival after the Fontan procedure improves, the population of adults with Fontan physiology is growing, leading to more severe extracardiac complications related to the Fontan circulation and growing demand for heart and liver transplantation. The accurate evaluation, staging, and management of FALD comprises a clinical challenge which requires expert multidisciplinary input.

ABSTRACT Pancreatic diseases, including pancreatitis, may be associated with skin manifestations, and prompt recognition is crucial for diagnosis and prognosis. Pancreatic panniculitis is an uncommon dermatologic condition occurring in only 0.3%–3% of pancreatic diseases. Very rarely, the triad of pancreatitis, panniculitis, and polyarthritis syndrome can be observed. Of the scant cases in the literature, most patients received treatment with nonsteroidal anti-inflammatory drugs and/or steroids. To our knowledge, this is the first case to outline an endoscopic approach for pancreatitis, panniculitis, and polyarthritis syndrome in the setting of a pseudocyst.

Abstract The Fontan procedure is the definitive treatment for patients with single-ventricle physiology. Surgical advances have led to a growing number of patients surviving into adulthood. Fontan-associated liver disease (FALD) encompasses a spectrum of pathologic liver changes that occur secondary to altered physiology including congestion, fibrosis, and the development of liver masses. Assessment of FALD is difficult and relies on using imaging alongside of clinical, laboratory, and pathology information. Ultrasound, computed tomography, and magnetic resonance imaging are capable of demonstrating physiologic and hepatic parenchymal abnormalities commonly seen in FALD. Several novel imaging techniques including magnetic resonance elastography are under study for use as biomarkers for FALD progression. Imaging has a central role in detection and characterization of liver masses as benign or malignant. Benign FNH-like masses are commonly encountered; however, these can display atypical features and be mistaken for hepatocellular carcinoma (HCC). Fontan patients are at elevated risk for HCC, which is a feared complication and has a poor prognosis in this population. While imaging screening for HCC is widely advocated, no consensus has been reached regarding an optimal surveillance regimen.

Assessment of bone density is an important part of liver transplantation (LT) evaluation for early identification and treatment of osteoporosis. Dual‐energy X‐ray absorptiometry (DXA) is currently the standard clinical test for osteoporosis; however, it may contribute to the appointment burden on LT candidates during the cumbersome evaluation process, and there are limitations affecting its accuracy. In this study, we evaluate the utility of biomechanical analysis of vertebral images obtained during dual‐energy abdominal triple‐phase computed tomography (TPCT) in diagnosing osteoporosis among LT candidates. We retrospectively reviewed cases evaluated for LT between January 2017 and March 2018. All patients who underwent TPCT within 3 months of DXA were included. The biomechanical computed tomography (BCT) analysis was performed at a centralized laboratory (O.N. Diagnostics, Berkeley, CA) by 2 trained analysts blinded to the DXA data. DXA‐based osteoporosis was defined as a T score ≤−2.5 at the hip or spine. BCT‐based osteoporosis was defined as vertebral strength ≤4500 N for women or ≤6500 N for men or trabecular volumetric bone mineral density ≤80 mg/cm3. Comparative data were available for 91 patients who had complete data for both DXA and BCT: 31 women and 60 men, age 54 ± 11 years (mean ± standard deviation), mean body mass index 28 ± 6 kg/m2. Using DXA as the clinical reference, sensitivity of BCT to detect DXA‐defined osteoporosis was 83.3% (20/24 patients) and negative predictive value was 91.7%; specificity and positive predictive value were 65.7% and 46.5%, respectively. BCT analysis of vertebral images on triple‐phase computed tomography, routinely obtained during transplant evaluation, can reliably rule out osteoporosis in LT candidates. Patients with suspicion of osteoporosis on TPCT may need further evaluation by DXA.