Samuel H. Sigal

Hepatic progenitor populations in embryonic, neonatal, and adult liver.

Abstract Oval cells, small cells with oval-shaped nuclei, are induced to proliferate in the livers of animals treated with carcinogens and are thought to be related to liver stem cells and/or committed liver progenitor cell populations. We have developed protocols for identifying and isolating antigenically related cell populations present in normal tissues using monoclonal antibodies to oval cell antigens and fluorescence-activated cell sorting. We have isolated oval cell-antigen-positive (OCAP) cells from embryonic, neonatal, and adult rat livers and have identified culture conditions permitting their growth in culture. 5 , 6 , 7 The requirements for growth of the OCAP cells included substrata of type IV collagen mixed with laminin, basal medium with complex lipids and low calcium, specific growth factors (most potently, insulin-like growth factor II and granulocyte-macrophage colony-stimulating factor), and co-cultures of embryonic, liver-specific stroma, strongly suggesting paracrine signaling between hepatic and hemopoietic precursor cells. 5 , 6 , 7 The growing OCAP cultures proved to be uniformly expressing oval cell markers but were nevertheless a mixture of hepatic and hemopoietic precursor cells. To separate the hepatic and hemopoietic subpopulations of OCAP cells, we surveyed known antibodies and found ones that uniquely identify either hepatic or hemopoietic cells. Several of these antibodies were used in panning procedures and fluorescence-activated cell sorting to eliminate contaminant cell populations, particularly hemopoietic and endothelial cells. 8 Using specific flow cytometric parameters, three cellular subpopulations could be isolated separately that were identified by immuno-chemistry and molecular hybridization assays as probable: (i) committed progenitors to hepatocytes; (ii) committed progenitors to bile ducts; or (iii) a mixed population of hemopoietic cells that contained a small percentage of hepatic blasts that are possibly pluripotent. 8 , 9 The hepatic precursor cells have been characterized using immunochemistry, flow cytometry, and molecular hybridization assays.

Clinical Impact of Depression in Cirrhosis

Purpose of ReviewDepression is the most commonly diagnosed psychiatric illness. It is prevalent in most chronic medical conditions and is associated with increased morbidity and mortality. Depression is especially common in patients with cirrhosis.Recent FindingsIn this review, we discuss the prevalence, risk factors, diagnosis, clinical impact, and treatment of depression in cirrhosis. We describe various screening tests important for diagnosis, the interaction of depression with hepatic encephalopathy, and its significant impact on medication adherence, mortality, and caregiver burden.SummaryThese findings highlight the importance of appropriate screening, diagnosis, and treatment of depression in patients with cirrhosis.

Management Strategies and Outcomes for Hyponatremia in Cirrhosis in the Hyponatremia Registry

Aim Treatment practices and effectiveness in cirrhotic patients with hyponatremia (HN) in the HN Registry were assessed. Methods Characteristics, treatments, and outcomes were compared between patients with HN at admission and during hospitalization. For HN at admission, serum sodium concentration [Na] response was analyzed until correction to > 130 mmol/L, switch to secondary therapy, or discharge or death with sodium ≤ 130 mmol/L. Results Patients with HN at admission had a lower [Na] and shorter length of stay (LOS) than those who developed HN (P < 0.001). Most common initial treatments were isotonic saline (NS, 36%), fluid restriction (FR, 33%), and no specific therapy (NST, 20%). Baseline [Na] was higher in patients treated with NST, FR, or NS versus hypertonic saline (HS) and tolvaptan (Tol) (P < 0.05). Treatment success occurred in 39%, 39%, 52%, 78%, and 81% of patients with NST, FR, NS, HS, and Tol, respectively. Relapse occurred in 55% after correction and was associated with increased LOS (9 versus 6 days, P < 0.001). 34% admitted with HN were discharged with HN corrected. Conclusions Treatment approaches for HN were variable and frequently ineffective. Success was greatest with HS and Tol. Relapse of HN is associated with increased LOS.