Standard-Volume Plasma Exchange Improves Outcomes in Patients With Acute Liver Failure: A Randomized Controlled Trial.

BACKGROUND: High volume plasma-exchange (HVPE) improves survival in patients with acute liver failure (ALF), but apprehension regarding volume overload and worsening of cerebral edema remain. METHODS: In an open-label randomized controlled trial, 40 consecutive patients of ALF were randomized 1:1 to either standard medical treatment (SMT) or SMT with standard-volume plasma-exchange (SVPE). SVPE was performed using centrifugal apheresis [target volume of 1.5 to 2.0 plasma volumes per session] until desired response was achieved. Cerebral edema was assessed by brain imaging. Results were analyzed in an intention-to-treat analysis. Primary outcome was 21-day transplant-free survival. The levels of cytokines, damage-associated molecular patterns (DAMPs) and endotoxins were analyzed at baseline and day 5. RESULTS: ALF patients [aged 31.5 ± 12.2 years, 60% male, 78% viral, 83% hyperacute, 70% with SIRS were included. At day 5, SVPE [mean sessions 2.15 ± 1.42, median plasma volume replaced 5.049 L] compared to SMT alone, resulted in higher lactate clearance (p = .02), amelioration of SIRS (84% vs. 26%; P = .02), reduction in ammonia levels [(221.5 ± 96.9) vs.(439 ± 385.6) µg/dl, P = .02) and SOFA scores [9.9(±3.3) vs. 14.6(±4.8); P = .001]. There were no treatment related deaths. SVPE was associated with a higher 21-day transplant free-survival [75% vs. 45%; P = .04, HR 0.30, 95%CI 0.01-0.88]. A significant decrease in levels of pro-inflammatory cytokines and an increase in anti-inflammatory cytokines along with a decrease in endotoxin and DAMPs was seen with SVPE. CONCLUSION: In ALF patients with cerebral edema, SVPE is safe and effective and improves survival possibly by a reduction in cytokine storm and ammonia. CLINICALTRIAL: gov (identifier: NCT02718079).

Use of stem cells for liver diseases-current scenario.

End-stage liver disease and liver failure are major health problems worldwide leading to high mortality and morbidity and high healthcare costs. Currently, orthotropic liver transplantation is the only effective treatment available to the patients of end-stage liver disease. However, a serious shortage of liver donors, high cost, and risk of organ rejection are the major obstacles to liver transplantation. Because of the ability of stem cells for differentiation into any tissue type, they have huge potential in therapy of various end-stage or degenerative diseases and traumatic injuries. Stem cell therapy has the potential to provide a valuable adjunct and alternative to liver transplantation and has immense potential in the management of end stage liver disease and liver failure. Stem cell therapy can be mediated by either a direct contribution to the functional hepatocyte population with embryonic, induced pluripotent, or adult stem cells or by promotion of endogenous regenerative processes with bone marrow-derived stem cells. Initial translational studies have been encouraging and have suggested improved liver function in advanced chronic liver disease and enhanced liver regeneration after portal vein embolization and partial hepatic resection. Stem cells infusion in cirrhotic patients has improved liver parameters and could form a viable bridge to transplantation. The present review summarizes basic of stem cell biology relevant to clinicians and an update on recent advances on the management of liver diseases using stem cells.

Association of IL-18 promoter polymorphism with liver disease severity in HCV-infected patients.

INTRODUCTION: Interleukin (IL)-18 plays an important dual role in Th1 polarization and viral clearance, as well as in the development of liver fibrosis. Single-nucleotide promoter polymorphisms influence the transcription of IL-18 mRNA. Promoter polymorphisms are linked to delayed virus clearance and disease susceptibility in many diseases. However, there is no information about their role in hepatitis C virus (HCV) infection. AIM: To investigate the association between -607 or -137 polymorphism with susceptibility and severity of HCV infection. PATIENTS AND METHODS: Two hundred and four serologically proven patients with chronic HCV infection and 350 matched healthy controls were included in this study. Patients were segregated in 2 groups: group A with mild liver disease and group B with severe liver disease on the basis of histological activity index (HAI 5) and hepatic fibrosis score (2). IL-18 promoter genotyping was performed with sequence-specific primers. RESULTS: There was no significant difference in the frequencies of -607 and -137 allelic distribution in patients and controls. The -607 A/A allele was more common in group A patients with mild liver disease than in patients with severe liver disease on the basis of HAI (38.6% vs. 21%, P = 0.05; odds ratio [OR] = 0.424, confidence interval [CI] = 0.233-0.773; R (2) = 0.631) and stage of fibrosis (38.7% vs. 16.7%, P = 0.008; OR = 0282, CI = 0.134-0.596; R (2) = 0.434). CONCLUSIONS: IL-18 promoter polymorphism at -607 position with A/A allele is a potential protective marker, as it is associated with milder liver disease in patients with chronic HCV infection.