Acute on Chronic Liver Failure: Clinical Profile, Precipitating Factors, Outcome and Predictors of Mortality

INTRODUCTION : Liver failure can develop acutely in a patient with no preexisting liver disease (Acute Liver Failure) or as an acute decompensation of a chronic liver disease. Recently it has been noted that a subgroup of patients develops acute deterioration in previously compensated cirrhosis and are considered to have acute on chronic liver failure (ACLF). This deterioration is secondary to an acute event and multi organ failure leading to increased mortality at three months. In contrast to chronic liver disease these patients have a rapid downhill course with the development of multiorgan failure and high short term mortality. One important concept in this group of patients is the potential reversibility. The term reversibility does not mean that underlying chronic liver damage is reversible, but rather the acute deterioration of the liver function due to the precipitating event is reversible. The pathophysiological basis ACLF was initially described by Jalan [et al.]. There is no clear cut definition of ACLF in the western literature. Asia Pacific association of study of liver (APASL) has defined it as acute hepatic insult manifested by jaundice and coagulopathy complicated within four weeks by ascites or encephalopathy. The cause for acute deterioration can vary from infectious causes like sepsis, viral hepatitis and non hepatotrophic viruses’ infection or noninfectious causes like alcohol, drugs, gastrointestinal bleeding, toxins and surgery. There is controversy 2 regarding whether sepsis can precipitate ACLF or it is the result of ACLF. Though numerous studies have been published in western literature on cirrhotic patients admitted to ICU, most of them have not differentiated organ failure as part of progressive worsening in end stage cirrhosis from acute on chronic liver failure. There are very few studies from India in this subject. H Garg [et al.] have recently published a prospective study on ACLF patients. Etiology of chronic liver disease and the acute precipitants differ between various geographical locations. AS ACLF carries a high mortality it is essential to identify prognostic factors. In general it has been noted that score evaluating the severity of disease like APACHE and SOFA score are better than liver specific score like Child Pugh score. Management of ACLF requires good intensive care to prevent the development of organ failure or to support the failing organs. Use of various extracorporeal liver support systems have been studied in various studies. Even though there is an improvement in biochemical parameters and in hepatic encephalopathy ,there is no significant survival benefit. Liver transplantation is the only curative treatment. This prospective study aims to look at the clinical profile, precipitating factors, outcome prognostic factors in ACLF admitted in a tertiary care hospital. AIM OF THE STUDY : The aims of the study are as follows, 1. To study the clinical profile of patients with acute on chronic liver failure, 2. To study the underlying chronic aetiology and acute precipitants, 3. To study the 30 day and 90 day mortality, 4. To study the various predictors of mortality. CONCLUSION : Acute on chronic liver failure is a unique entity. It is characterized by rapidly deteriorating course in a previously diagnosed or undiagnosed chronic liver disease with a potential for reversibility. Our study shows that it has high short term mortality (44%). Most common aetiology for underlying chronic liver disease in our centre is alcoholic liver disease (64.5%) followed by hepatitis B (20%) and other causes. The most common acute precipitant is super added alcoholic hepatitis (82%) in alcoholic liver disease and reactivation of hepatitis B (66%) in chronic hepatitis B. Other causes of acute worsening include acute hepatitis E and drug induced liver injury. Most common cause of death is the multi organ failure. Increasing number of organ failures is associated with increasing risk of death. High serum bilirubin, high INR, renal failure, low sodium, and high CRP are all poor prognostic markers. SOFA and MELD are better predictors of mortality than Child score. Early referral for liver transplantation is essential in patients at high risk of death. Acute on chronic liver failure is a disease which is still being defined and large prospective studies are needed to better delineate the acute precipitants and the prognostic markers

Esophagojejunal anastomotic leak managed with self expandable metallic stent

Esophagealjejunal anastomotic leak after gastrectomy is a serious surgical emergency with high mortality. This report describes a 57-year-old male with esophagojejunal anastomotic leak following total gastrectomy for gastric cancer and was managed successfully with self-expandable metallic stent. To our knowledge this is the first such report from India. This case report highlights the need of interdisciplinary coordination in managing this difficult clinical situation. Endotherapy with self-expandable metallic stent (SEM) provided twin benefits of improving respiratory embarrassment and the joy of eating. Therapy of such difficult cases must be individualized; however, and SEM stent usage is a viable optio

High-pressure Raman and infrared study of ZrV2O7

The room-temperature Raman and infrared spectra of zirconium vanadate (ZrV2O7) were observed up to pressures of 12 GPa and 5.7 GPa, respectively. The frequencies of the optically active modes at ambient pressure were calculated using direct methods and compared with experimental values. Average mode Gruneisen parameters were calculated for the Raman and infrared active modes. Changes in the spectra under pressure indicate a phase transition at similar to 1.6 GPa, which is consistent with the previously observed a (cubic) to (pseudo-tetragonal) phase transition, and changes in the spectra at similar to 4 GPa are consistent with an irreversible transformation to an amorphous structure. (C) 2007 Elsevier Ltd. All rights reserved

Computational and Experimental Study of the Mechanism of Hydrogen Generation from Water by a Molecular Molybdenum-Oxo Electrocatalyst

We investigate the mechanism for the electrocatalytic generation of hydrogen from water by the molecular molybdenum-oxo complex, [(PY5Me₂)­MoO]²⁺ (PY5Me₂ = 2,6-bis­(1,1-bis­(2-pyridyl)­ethyl)­pyridine). Computational and experimental evidence suggests that the electrocatalysis consists of three distinct electrochemical reductions, which precede the onset of catalysis. Cyclic voltammetry studies indicate that the first two reductions are accompanied by protonations to afford the Mo-aqua complex, [(PY5Me₂)­Mo­(OH₂)]⁺. Calculations support hydrogen evolution from this complex upon the third reduction, via the oxidative addition of a proton from the bound water to the metal center and finally an α-H abstraction to release hydrogen. Calculations further suggest that introducing electron-withdrawing substituents such as fluorides in the <i>para</i> positions of the pyridine rings can reduce the potential associated with the reductive steps, without substantially affecting the kinetics. After the third reduction, there are kinetic bottlenecks to the formation of the Mo-hydride and subsequent hydrogen release. Computational evidence also suggests an alternative to direct α-H abstraction as a mechanism for H₂ release which exhibits a lower barrier. The new mechanism is one in which a water acts as an intramolecular proton relay between the protons of the hydroxide and the hydride ligands. The calculated kinetics are in reasonable agreement with experimental measurements. Additionally, we propose a mechanism for the stoichiometric reaction of [(PY5Me₂)­Mo­(CF₃SO₃)]⁺ with water to yield hydrogen and [(PY₅Me₂)­MoO]²⁺ along with the implications for the viability of an alternate catalytic cycle involving just two reductions to generate the active catalyst