In vivo1H magnetic resonance spectroscopy‐derived metabolite variations between acute‐on‐chronic liver failure and acute liver failure

Background and Aims: Acute‐on‐chronic liver failure (ACLF), acute liver failure (ALF) and chronic liver disease (CLD) are common forms of liver failure and present with similar clinical profiles. The aim of this study was to compare brain metabolite alterations in all the three groups of patients with controls, using in vivo proton magnetic resonance spectroscopy (MRS), and to look for any significant differences in metabolites that may help in differentiating between these three conditions. Methods: Nine patients with ACLF, 10 with ALF, 10 patients with CLD and 10 age‐matched controls were studied. The relative concentrations of N‐acetylaspartate (NAA), choline (Cho), glutamine/glutamate (Glx) and myoinositol (mI) with respect to creatine (Cr) were measured. Results: ACLF (3.07±0.72), ALF (4.39±1.25) and CLD (3.15±0.69) patients exhibited significantly increased Glx/Cr ratios compared with controls (2.14±0.42). The NAA/Cr ratio was significantly decreased in both ACLF (mean=0.84±0.28) and CLD (mean=0.97±0.21) patients as compared with that in controls (mean=1.24±0.20). No significant difference among ALF, ACLF and CLD patients was noted in the Cho/Cr ratios. ACLF patients showed significantly lower mI/Cr and Glx/Cr ratios compared with the ALF group. Conclusion: In vivo proton MRS‐derived cerebral metabolite alterations in hepatic encephalopathy owing to ALF are significantly different from the one owing to ACLF and CLD; these may be due to the differences in the pathogenesis of these two overlapping clinical conditions.     

Evaluation of indocyanine green clearance and model for end‐stage liver disease for estimation of short‐term prognosis in decompensated cirrhosis

Background: Indocyanine green (ICG) clearance has been proposed as a quantitative liver function test several decades ago. Interest in this method has been renewed following the development of finger pulse densitometry for noninvasive estimation of the ICG plasma disappearance rate (PDR). On the other hand, the model for end‐stage liver disease (MELD), which is based on routine laboratory parameters, is widely used for estimation of short‐term survival in cirrhosis, but its prognostic value in critically ill cirrhotic patients is unclear. Aims: The aim of the present study was to compare the diagnostic accuracy of ICG PDR vs. MELD for estimation of short‐term prognosis in cirrhotic patients. Methods: Ninety consecutive cirrhotic patients who were admitted for decompensated disease or were being evaluated for liver transplantation were screened. Patients who underwent liver transplantation within the following 90 days and those with hepatocellular carcinoma were excluded. In the remaining 70 patients, routine laboratory parameters and ICG clearance were analysed. Following an injection of ICG 0.25 mg/kg, PDR was measured by finger pulse densitometry. The diagnostic accuracy of ICG PDR and MELD for prediction of 90‐day survival was assessed by receiver–operating characteristic (ROC) curve analysis. Results: ROC curve analysis revealed superior diagnostic accuracy for MELD as compared with ICG PDR in predicting 90‐day survival (area under the ROC curve 0.89 vs. 0.71). A MELD cut‐off of 22 provided the best discrimination for prediction of 90‐day survival. Conclusions: MELD is superior to ICG PDR for estimation of short‐term survival in patients with decompensated cirrhosis.     

Predictive value of serum actin‐free Gc‐globulin for complications and outcome in acute liver failure

This prospective study was designed to evaluate whether early changes in actin‐free Gc‐globulin levels were associated with complications and outcomes and to identify factors associated with persistent low actin‐free Gc‐globulin levels in acute liver failure (ALF). Thirty‐two consecutive ALF patients admitted from October 2011 to December 2012 were followed up until death or complete recovery. All had serum actin‐free Gc‐globulin estimation at admission and at day three or expiry. Logistic regression analysis was performed to identify independent predictors of mortality. A receiver operating characteristic curve analysis was also performed. Nonsurvivors had significantly lower median actin‐free Gc‐globulin levels than survivors (87.32 vs 180 mg/L; P < 0.001). A receiver operating characteristic curve analysis revealed an area under curve (AUC) of 0.771 and showed that serum actin‐free Gc‐globulin level of ≤124 mg/L would predict mortality with 92% sensitivity and 71.4% specificity. Patients with lower serum actin‐free Gc‐globulin levels and decreasing trend in serum actin‐free Gc‐globulin levels were found to have more mortality and developed more complications. Logistic regression analysis showed that serum actin‐free Gc‐globulin, total leucocyte count and serum creatinine at admission were independent predictors of mortality. Incorporating these variables, a score predicting mortality risk at admission was derived. The scoring system was compared to MELD score and King's College Criteria as individual predictor of mortality. Serum actin‐free Gc‐globulin level at presentation is predictive of outcome and can be used for risk stratification. Its persistent low‐level predicts mortality and is correlated with various complications.     

Molecular adsorbent recirculating system: albumin dialysis-based extracorporeal liver assist device

Extracorporeal liver assist devices have been used for more than five decades to support patients with liver failure. Numerous modifications have been made to both biological as well as mechanical liver assist devices. Possibly, an ideal liver assist device would be one that would perform optimal detoxification and synthetic functions of the liver, be simple to set up and yet be cost-effective. An albumin dialysis-based device that uses a hybrid albumin-impregnated membrane to get rid of albumin-bound toxins that circulate in abundance in liver failure, called the molecular adsorbent recirculating system (MARS) has been in clinical use for nearly four years now. Results with the use of this device in both acute and acute-on-chronic liver failure have shown consistent improvement in biochemical profile, resolution of encephalopathy, correction in hemodynamics, reduction in intracranial pressure and some improvement in the synthetic function of the liver. In a number of studies, albeit of small sample size, survival advantage has also been observed. The timing of initiation of therapy with MARS, duration of treatment, frequency of sessions and 'maintenance therapy' are still some of the unresolved issues with the use of this device. Large multicentric trials on the use of this technique are expected to throw light on these issues and help optimize the potential of this liver assist device.     

Successful liver transplantation and delivery in a woman with fulminant hepatic failure occurring during the second trimester of pregnancy.

BACKGROUND: Severe liver dysfunction occurring during pregnancy is an unusual but dramatic event that poses special technical and ethical issues because it involves two lives. METHODS AND RESULTS: We report the case of a 35-year-old woman with cryptogenic fulminant hepatic failure who underwent successful orthotopic liver transplantation at 22 weeks of pregnancy. After a relatively uneventful post-operative course she delivered a normal offspring at the 27th week of gestation. There were no obstetrical complications and neonatal outcome was excellent. After a year of follow-up, the patient is doing well,and the newborn has exhibited normal psychomotor and weight/height development. CONCLUSION: This case illustrates the challenge of treating fulminant hepatic failure during pregnancy and demonstrates that liver transplantation is a feasible therapeutic option for treatment of patients with this condition, allowing successful completion of pregnancy.     

Efficacy of short‐term dexamethasone therapy in acute‐on‐chronic pre‐liver failure

Aim: Acute‐on‐chronic pre‐liver failure (pre‐ACLF) is defined as a severe acute episode of chronic hepatitis B characterized by serum bilirubin of 171 µmol/L or more, alanine aminotransferase of five times or more the upper limit of normal and prothrombin activity of more than 40%, having a potential for progression to acute‐on‐chronic liver failure (ACLF). This study is to evaluate the efficacy of short‐term dexamethasone in pre‐ACLF. Methods: One hundred and seventy patients were assigned to dexamethasone therapy and control group at a ratio of 1:2. For the two groups, we compared biochemical indicators, the incidence of ACLF and mortality. The influential factors on the mortality of patients with pre‐ACLF were studied by Cox proportional hazards models. Results: The significantly lower incidence of ACLF and higher survival rate were observed in patients on dexamethasone therapy (8.9%, 96.4%, respectively) than in control patients (70.2%, 52.6%, respectively; P < 0.001). Dexamethasone treatment was an independent factor influencing the survival rate (P < 0.001, odds ratio = 0.055, 95% confidence interval = 0.013–0.225). During 4 weeks of treatment, serum bilirubin levels of survival patients were significantly lower in the dexamethasone group than control group. Conclusion: Five‐day dexamethasone therapy is effective in improving the liver function and survival rate of patients with pre‐ACLF.     

The diagnosis and management of idiosyncratic drug‐induced liver injury

Drug‐induced liver injury (DILI) is an uncommon but important cause of liver disease that can arise after exposure to a multitude of drugs and herbal and dietary supplements. The severity of idiosyncratic DILI varies from mild serum aminotransferase elevations to the development of severe liver injury that can progress to acute liver failure resulting in death or liver transplantation within days of DILI onset. Chronic liver injury that persists for more than 6 months after DILI onset is also becoming increasingly recognized in up to 20% of DILI patients. Host demographic (age, gender, race), clinical and laboratory features at DILI onset have been associated with the severity and outcome of liver injury in DILI patients. In addition to cessation of the suspect drug, other medical interventions including the use of N‐acetylcysteine and corticosteroids in selected patients have shown some clinical benefit, but additional prospective studies are needed. A number of promising diagnostic, prognostic and mechanistic serum and genetic biomarkers may help improve our understanding of the pathogenesis and treatment of idiosyncratic DILI.     

Experimental research on TECA-I bioartificial liver support system to treat canines with acute liver failure

AIM To evaluate the efficacy and safety of the TECA-Ibloartificial liver support system(BALSS)in treatingcanines with acute liver failure(ALF).METHODS Ten canines with ALF induced by 80% liverresection received BALSS treatment(BALSS group).Blood was perfused through a hollow fiber tube containing1×10~(10) porcine hepatocytes.Four canines with ALF weretreated with BALSS without porcine hepatocytes(controlgroup),and five canines with ALF received drugtreatment(drug group).Each treatment lasted 6 hours.RESULTS BALSS treatment yielded beneficial effects forpartial liver resection-induced ALF canines with survivaland decreased plasma ammonia,ALT,AST and BIL.Therewas an obvious decrease in PT level and increase in PAlevel,and there were no changes in the count oflymphocytes,immunoglobulins(IgA,IgG and IgM)andcomplement(C3 and CA)levels after BALSS treatment.Incontrast,for the canines with ALF in non-hepatocyteBALSS group(control group)and drug group,there wereno significant changes in ammonia,ALT,AST,BIL,PTand PA levels.ALF canines in BALSS group,controlgroup and drug group lived respectively an average timeof 108.0h±12.0h,24.0h±6.0h and 20.4h±6.4h,andthree canines with ALF survived in BALSS group.CONCLUSION TECA-I BALSS is efficacious and safe forALF canines induced by parcial liver resection.