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Aim: This study investigates the fall in total serum bilirubin levels within 1 week after surgery, as a marker to predict early outcome in biliary atresia (BA) patients post-Kasai portoenterostomy (KP). Methods: The ratio of total serum bilirubin levels at the 7th postoperative day to the preoperative level (TB7/TB0) in patients undergoing KP was calculated (January 2011-July 2015). Patients were stratified after 3-months follow-up into outcome groups depending on the clinical clearance of jaundice and TB7/TB0 ratio was correlated to outcome and liver histopathological changes in these groups. Results: Sixty-one patients (M:F = 44:17), median age 75 days were included. At the end of 3 months, 27 (44.39%) were anicteric while 26 (42.6%) were still clinically jaundiced. Patients with a higher median value of TB7/TB0, that is, 0.856 were more likely to have jaundice at the end of 3 months as compared to patients with a lower median value of 0.615 (P < 0.0001). A cutoff TB7/TB0 ratio >0.723 predicted the KP outcome with 84.6% sensitivity and 81.5% specificity. The difference in TB7/TB0 ratio between patients with varying severity of liver histopathological changes was also significant, namely, cholestasis (P = 0.01), hepatocellular damage (P = 0.03), portal inflammation (P = 0.04), and portal fibrosis (P = 0.02). Conclusions: The rapidity of fall in the total serum bilirubin levels within 1 week post-KP was able to predict the likely outcome in BA patients. [ABSTRACT FROM AUTHOR]

Background and Aim: Acute on chronic liver failure (ACLF) because of precipitating factors (variceal bleed/infections) identifies cirrhotics at risk for high short-term mortality. Information on ACLF because of acute hepatic insults is lacking. The aim of the study was to evaluate acute hepatic insults in ACLF and their effect on the course and outcome. Methods: In a prospective study, 213 consecutive patients of ACLF because of acute hepatic insults were included. Etiology of acute hepatic insult, frequency of silent, and overt chronic liver disease (CLD), organ failure (OF), and outcomes were assessed. Prognostic models such as model for endstage liver disease (MELD), acute physiology and chronic health evaluation (APACHE II), and chronic liver failure-sequential organ failure (CLIF-SOFA) were evaluated. Results: Etiologies of acute hepatic insult were hepatitis virus(es)- 81 (38%; HBV-42, HEV-39), continuous alcohol consumption-77 (33.3%), antituberculosis drugs-11 (5.2%), autoimmune hepatitis flare-5(2.3%), cryptogenic-44 (20.7%). The common causes of CLD were alcohol ( n = 85/40%), HBV( n = 52/24%), and cryptogenic( n = 50/20%). The MELD, APACHE II, and CLIF-SOFA scores were similar among silent and overt CLD and did not influence outcome. Predominant etiologies of ACLF were hepatitis virus(es) reactivation or superinfection in silent CLD(52/112, 46.4%) and alcohol among overt CLD(43/101, 43%). Independent predictors of mortality included hepatic-encephalopathy (early, HR: 4.01; advanced, HR: 6.10), serum creatinine ≥1.5 mg/dl (HR: 4.53), CLIF-SOFA ≥8(HR: 1.69), and etiology of acute hepatic insult (alcohol, HR: 4.08; cryptogenic, HR: 3.18). HEV-ACLF had lower mortality (12.8% vs. 33-54% in other etiologies; P < 0.001). OF was major determinant of mortality. With increasing number of OF, mortality increased linearly( P = 0.001). Conclusions: Hepatitis virus(es) and continuous alcohol consumption are important causes of ACLF caused by acute hepatic insults. HEV-ACLF has lower mortality. OF is an important prognostic predictor. [ABSTRACT FROM AUTHOR]

Abstract Background and Aims: Subacute hepatic failure (SHF) is a fatal complicaton of acute viral hepatitis. Renal failure has been implicated as the main cause of death in this disease. However, renal functional and structural evaluation in such patients have not been performed. The present prospective study evaluated the renal functional and structural abnormalities in patients with subacute hepatic failure. Methods: Fourteen consecutive patients with SHF, 11 with acute liver failure (ALF) and 15 with cirrhosis of the liver (Child's B or C) were included in the present study. All 40 patients had liver disease caused by hepatitis viruses. The glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) estimations were measured in all patients by the use of technetium-99m diethylenetriaminepentaacetic acid and [131I]-labeled ortho-iodohippuric acid, respectively. Ante-mortem or post-mortem liver biopsies were performed in all patients. In three patients with SHF, post-mortem kidney biopsies were also performed. Results: Thirty six percent (5/14) of patients with SHF, 18% (2/11) of patients with ALF and 20% (3/15) of patients with cirrhosis had renal failure. Seven patients with SHF, seven with ALF and nine with cirrhosis died. All the patients with renal failure in each of the three groups were among the deceased patients. Glomerular function was markedly affected among patients with SHF, which was shown by significantly higher (P < 0.05) proteinuria levels (0.367 ± 0.38 g/24 h) compared to levels in patients with ALF (0.178 ± 0.11 g/24 h) and cirrhosis (0.212 ± 0.133 g/24 h). The GFR in SHF (56 ± 27 mL/min per 1.73 m2) and cirrhotic patients (58 ± 36 mL/min per 1.73 m2) was significantly lower compared to those in ALF patients (102 ± 51 mL/min per 1.73 m2; P < 0.05). A significantly higher proportion (P < 0.05) of patients with SHF and cirrhosis (64 and 73%, respectively) had a GFR below 80 mL/min per 1.73 m2 compared to patients with ALF (18%). The GFR value among the deceased SHF patients (46 ± 26 mL/min per 1.73 m2) was significantly lower (P < 0.05) than those SHF patients who survived (65 ± 25 mL/min per 1.73 m2). However, similar features could not be documented among patients with ALF or cirrhosis. Subtle structural changes in the glomerulus were also noted in patients with SHF. These included mesangial proliferation and thickening, basal membrane thickening and increased cellularity with interstitial edema. The ERPF was markedly reduced (P = 0.058) among patients with SHF (347 ± 131 mL/min per 1.73 m2) and cirrhosis (395 ± 137 mL/min per 1.73 m2) in comparison to ERPF documented among patients with ALF (436 ± 217 mL/min per 1.73 m2). Such a reduction in renal tubular blood flow, along with histologic documentation of hyaline presence, bile and grannular cast in the tubule, indicated a possible tubular dysfunction in patients with SHF. Conclusion: It is concluded that glomerular and tubular dysfunction with subtle structural abnormalities does occur in patients with SHF. These are similar to renal changes in cirrhosis and may have similar pathogenetic mechanisms that require further evaluation. [ABSTRACT FROM AUTHOR]

Context.--The histologic features in patients with acuteon- chronic liver failure (ACLF) are evolving, and histologic indicators of patients' poor prognosis are not yet fully established. Objective.--To evaluate the independent histologic predictors of 28-day mortality in ACLF patients on coreneedle liver biopsies. Design.--Core-needle biopsies from patients with a diagnosis of ACLF (n = 152) as per the European Association for the Study of the Liver criteria were included during 8 years. Liver biopsies from 98 patients with compensated chronic liver disease were included as disease controls for histologic comparison. Features of ongoing changes, such as hepatic necrosis, hepatic apoptosis, cholestasis, hepatocyte degeneration, bile ductular proliferation, Mallory-Denk bodies, steatosis, and extent of liver fibrosis, were analyzed for predicting short-term mortality (28 days). A P value of,.05 was considered significant. Results.--In our cohort of ACLF patients, the following etiologies for acute decompensation were identified: alcohol, 47 of 152 (30.9%); sepsis, 24 of 152 (15.7%); hepatotropic viruses, 20 of 152 (13.1%); drug-induced liver injury, 11 of 152 (7.2%); autoimmune flare, 9 of 152 (5.9%); mixed etiologies, 5 of 152 (3.2%); and cryptogenic, 36 of 152 (23.6%). On histologic examination, hepatic necrosis (P < .001), dense lobular inflammation (P = .03), cholestasis (P < .001), ductular reaction (P = .001), hepatocyte degeneration (P < .001), and absence of advanced fibrosis stages (P < .001) were identified significantly more othen in ACLF patients than in disease controls on univariate analysis. On multivariate Cox regression analysis, the absence of advanced Ishak histologic activity index fibrosis stages (P = .02) and the presence of dense lobular inflammation (P = .04) were associated with increased 28-day mortality in ACLF patients. After adjusting the clinical causes of acute decompensation, only dense lobular inflammation was found as an independent predictor of short-term mortality (P = .04) in ACLF patients. Conclusions.--Dense lobular necroinflammatory activity is a clinically independent histologic predictor of 28-day short-term mortality in patients with ACLF. [ABSTRACT FROM AUTHOR]

Acute liver failure (ALF) is not an uncommon complication of a common disease such as acute hepatitis. Viral hepatitis followed by antituberculosis drug–induced hepatotoxicity are the commonest causes of ALF in India. Clinically, such patients present with appearance of jaundice, encephalopathy, and coagulopathy. Hepatic encephalopathy (HE) and cerebral edema are central and most important clinical event in the course of ALF, followed by superadded infections, and determine the outcome in these patients. The pathogenesis of encephalopathy and cerebral edema in ALF is unique and multifactorial. Ammonia plays a crucial role in the pathogenesis, and several therapies aim to correct this abnormality. The role of newer ammonia-lowering agents is still evolving. These patients are best managed at a tertiary care hospital with facility for liver transplantation (LT). Aggressive intensive medical management has been documented to salvage a substantial proportion of patients. In those with poor prognostic factors, LT is the only effective therapy that has been shown to improve survival. However, recognizing suitable patients with poor prognosis has remained a challenge. Close monitoring, early identification and treatment of complications, and couseling for transplant form the first-line approach to manage such patients. Recent research shows that use of dynamic prognostic models is better for selecting patients undergoing liver transplantation and timely transplant can save life of patients with ALF with poor prognostic factors. [ABSTRACT FROM AUTHOR]