Indian National Association for the Study of the Liver Consensus Statement on Acute Liver Failure (Part 1): Epidemiology, Pathogenesis, Presentation and Prognosis.

Acute liver failure (ALF) is an infrequent, unpredictable, potentially fatal complication of acute liver injury (ALI) consequent to varied etiologies. Etiologies of ALF as reported in the literature have regional differences, which affects the clinical presentation and natural course. In this part of the consensus article designed to reflect the clinical practices in India, disease burden, epidemiology, clinical presentation, monitoring, and prognostication have been discussed. In India, viral hepatitis is the most frequent cause of ALF, with drug-induced hepatitis due to antituberculosis drugs being the second most frequent cause. The clinical presentation of ALF is characterized by jaundice, coagulopathy, and encephalopathy. It is important to differentiate ALF from other causes of liver failure, including acute on chronic liver failure, subacute liver failure, as well as certain tropical infections which can mimic this presentation. The disease often has a fulminant clinical course with high short-term mortality. Death is usually attributable to cerebral complications, infections, and resultant multiorgan failure. Timely liver transplantation (LT) can change the outcome, and hence, it is vital to provide intensive care to patients until LT can be arranged. It is equally important to assess prognosis to select patients who are suitable for LT. Several prognostic scores have been proposed, and their comparisons show that indigenously developed dynamic scores have an edge over scores described from the Western world. Management of ALF will be described in part 2 of this document.

Development of predisposition, injury, response, organ failure model for predicting acute kidney injury in acute on chronic liver failure.

BACKGROUND AND AIM: There is limited data on predictors of acute kidney injury in acute on chronic liver failure. We developed a PIRO model (Predisposition, Injury, Response, Organ failure) for predicting acute kidney injury in a multicentric cohort of acute on chronic liver failure patients. PATIENTS AND METHODS: Data of 2360 patients from APASL-ACLF Research Consortium (AARC) was analysed. Multivariate logistic regression model (PIRO score) was developed from a derivation cohort (n=1363) which was validated in another prospective multicentric cohort of acute on chronic liver failure patients (n=997). RESULTS: Factors significant for P component were serum creatinine[(≥2 mg/dL)OR 4.52, 95% CI (3.67-5.30)], bilirubin [(<12 mg/dL,OR 1) vs (12-30 mg/dL,OR 1.45, 95% 1.1-2.63) vs (≥30 mg/dL,OR 2.6, 95% CI 1.3-5.2)], serum potassium [(<3 mmol/LOR-1) vs (3-4.9 mmol/L,OR 2.7, 95% CI 1.05-1.97) vs (≥5 mmol/L,OR 4.34, 95% CI 1.67-11.3)] and blood urea (OR 3.73, 95% CI 2.5-5.5); for I component nephrotoxic medications (OR-9.86, 95% CI 3.2-30.8); for R component,Systemic Inflammatory Response Syndrome,(OR-2.14, 95% CI 1.4-3.3); for O component, Circulatory failure (OR-3.5, 95% CI 2.2-5.5). The PIRO score predicted acute kidney injury with C-index of 0.95 and 0.96 in the derivation and validation cohort. The increasing PIRO score was also associated with mortality (P<.001) in both the derivation and validation cohorts. CONCLUSIONS: The PIRO model identifies and stratifies acute on chronic liver failure patients at risk of developing acute kidney injury. It reliably predicts mortality in these patients, underscoring the prognostic significance of acute kidney injury in patients with acute on chronic liver failure.

Patients with non-alcoholic fatty liver disease (NAFLD) have an increased risk of atherosclerosis and cardiovascular disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is now considered a hepatic component of metabolic syndrome (MS). This condition puts patients with NAFLD at an increased risk of atherosclerosis and cardiovascular disease. This study aimed to assess the prevalence of atherosclerosis and risk of cardiovascular disease in patients with NAFLDand to study its relationship with MS. METHODS: Twenty patients with NAFLD (8 men, mean age 39.90 +/- 8.73 years) and 20 age- and gender-matched controls with chronic viral hepatitis (8 men, mean age 39.30 +/- 8.21 years) were included prospectively in the study. Prevalence of atherosclerosis was studied by measuring the carotid intima-media thickness (CIMT) on carotid ultrasound and by measuring the flow-mediated dilatation% (FMD%) on brachial artery doppler ultrasound. The risk of cardiac events at 10 years (RDCE 10) was estimated by the Prospective Cardiovascular Munster study (PROCAM) score. RESULTS: The mean CIMT of both the right and left side was significantly higher (0.70 +/- 0.11 mm vs. 0.61+/- 0.08 mm) (p=0.007) and FMD% was significantly lower in patients with NAFLD (9.79 +/- 3.81%) in comparison to controls (17.02 +/- 3.39%) (p<0.0001). The mean PROCAM score was higher in patients with NAFLD (27.50 +/- 13.32 vs.20.10 +/- 7.75) (p=0.067) with the 10-year risk of acute coronary event being 3.9 +/- 6.72% in patients with NAFLD in comparison to 1.44 +/- 0.85% in controls (p=0.042). On post hoc analysis, a higher CIMT, PROCAM score and 10-year risk of acute coronary events in patients with NAFLD was dependent on MS. CONCLUSIOIN: Patients with NAFLD have an increased risk of atherosclerosis and cardiovascular disease.

Functional reconstitution of defective myeloid dendritic cells in chronic hepatitis C infection on successful antiviral treatment.

OBJECTIVE: Poor cellular trafficking and suboptimal T-cell responses in liver, the hall marks of chronic hepatitis C virus (CHC) infection, might be attributed to defective antigen presentation. Controversy exists regarding role of myeloid dendritic cells (DCs) in CHC and response to antiviral treatment. This study examines functional status of DCs before and after completion of treatment with the aim to find any modulatory effect. DESIGN: Frequency and functions of monocyte-derived DCs (mo-DCs) were evaluated in CHC (n = 25), before the start of therapy (CHC(0) ). These patients were then put on treatment with peg-interferon-α plus ribavirin for 24 or 48 weeks, and the mo-DC functions were evaluated after 6 months of completion of treatment (CHC(6) ) again, using multicolour flow cytometry, endocytosis assay, cytokine assay and mixed lymphocyte reaction. RESULTS: Pre-treatment frequency of mo-DCs in CHC(0) was lower than that in healthy controls, which became close to normal in patients who achieved virological response (SVR+, n = 20) but not in non-responders (SVR-, n = 5). Pre-treatment levels of CD83, CD80 and CD86 on mo-DC in SVR(0) +, but not SVR(0) -, got upregulated after lipopolysaccharide stimulation supporting the hypothesis that DCs play deciding role in response to therapy. Post-treatment allostimulatory and phagocytosing capacity of mo-DCs in SVR+ patients indicated regain in functional capacity in these patients but not in SVR- patients. CONCLUSIONS: Our results indicate that DCs in CHC patients exhibiting mature and functional phenotype prior to therapy achieve sustained virological response suggesting that functional modulation of defective DCs is directly associated with successful response to therapy.

Treatment of Budd-Chiari syndrome with inferior vena caval occlusion by mesoatrial shunt.

OBJECTIVE: To report the effectiveness of a mesoatrial shunt in the treatment of Budd-Chiari syndrome caused by combined hepatic vein and inferior vena caval block. DESIGN: Retrospective study. SETTING: Tertiary care hospital, India. PATIENTS: 10 patients (4 men and 6 women; mean age 28, range 18-45) who had operations for Budd-Chiari syndrome between 1994 and 2000. INTERVENTION: Mesoatrial shunt. MAIN OUTCOME MEASURES: Graft patency, survival, liver function and symptoms. RESULTS: One patient died. All grafts were patent over a mean follow up period of 40 months (range 6-71). All survivors have normal liver function and were symptom free at the time of writing. CONCLUSION: Mesoatrial shunt is effective in the treatment of Budd-Chiari syndrome caused by combined hepatic vein and vena caval occlusion.