Risk Factors for Post-Endoscopic Retrograde Cholangio-Pancreatography Pancreatitis in Children With Chronic Pancreatitis and Its Prediction Using 4-Hour Postprocedure Serum Amylase and Lipase Levels.

BACKGROUND: Post-endoscopic retrograde cholangio-pancreatography pancreatitis (PEP) is seen in 3% to 16% of children undergoing therapeutic endoscopic retrograde cholangio-pancreatography (ERCP). We evaluated the risk factors of PEP and utility of 4-hour post-ERCP amylase and lipase for early prediction of PEP in children with chronic pancreatitis (CP). MATERIALS AND METHODS: Thirty children with CP (boys 20, 14.3 [interquartile range, 9.3-16] years) who underwent 62 ERCP procedures were studied. Clinical and procedural details with outcome were noted. Serum amylase and lipase were measured before, 4 hours, and 24 hours after ERCP. Multivariate analysis was done to identify risk factors for PEP. Cutoff scores of 4-hour amylase and lipase were identified. RESULTS: PEP occurred in 14.5% (9/62) of ERCP procedures (mild, 8; moderate, 1) with no mortality. On univariate analysis, endoscopic sphincterotomy ( P = 0.04), difficult cannulation ( P = 0.004), and prior PEP ( P = 0.036) were risk factors, while prior ERCP ( P = 0.04) was protective. Difficult cannulation (odds ratio, 5.83; 95% confidence interval, 1.329-25.592) was the independent risk factor on multivariate analysis overall and for first ERCP session alone. Amylase >3.3 times upper limit of normal (ULN) and lipase of >5 times ULN at 4 hours had best sensitivity and specificity for diagnosis of PEP. All cases with PEP were symptomatic by 6 hours and none had amylase/lipase <3 ULN at 4 hours. Amylase/lipase of <3 ULN at 4 hours could exclude PEP with good sensitivity (100%) and specificity (76% and 81%, respectively). CONCLUSIONS: PEP occurred in 14.5% of procedures in children with CP, with difficult cannulation being the independent risk factor. Asymptomatic patients with 4-hour amylase/lipase <3 times ULN can be safely discharged.

Response Guided Slow Infusion of Albumin, Vasoconstrictors and Furosemide Improves Ascites Mobilization and Survival in Acute on Chronic Liver Failure: A Proof-of-Concept Study.

Background and Aims: Acute-on-chronic liver failure (ACLF) with increasing organ failure is associated with poor outcomes. Severely deranged systemic hemodynamics and decreased effective arterial blood volume contribute to tissue damage and organ failure. Response-guided therapy with albumin, vasoconstrictors, and furosemide may help overcome effective hypovolemia, improve diuresis and impact survival. Methods: In the observation cohort, 230 patients with ACLF (CANONIC criteria) with ascites (≥Grade II) and ACLF ≥Grade I were enrolled. A total of 136 patients (GROUP I) received response-guided (urine sodium >80mmol/day) slow albumin-furosemide infusion ±â€…terlipressin (SAFI ± T), while 94 patients (GROUP II) received standard medical therapy. Twenty-eight-day survival, ascites mobilization (nil or grade 1), and adverse events were noted. In another mechanistic cohort (n = 40), laboratory evidences for improvement in various pathophysiological alterations; gut permeability, endotoxemia, cytokine storm, neutrophil dysfunction, and hemodynamic alterations following SAFI ± T/Noradrenaline (NAdr) were evaluated. Results: Age, gender, CLIF-C-ACLF, SOFA and MELD scores, ACLF grades and urine sodium were not different between the two groups in the observation cohort. Ascites was mobilized in 102/136 in GROUP I (SAFI ± T) and 23/94 in GROUP II (p < 0.05). Twenty-eight-day survival was significantly higher in GROUP I = 103/136 (75.7%) vs GROUP II = 50/94 (53.2%), (P = <0.001). All those who were unable to reach urine sodium >80 mmol/day died. Four patients in GROUP I developed scrotal gangrene. In the mechanistic cohort, 72% of patients survived with significant improvement in gut permeability, endotoxemia, serum cytokines, neutrophil dysfunction, and hemodynamic alterations. Conclusion: Ascitic fluid mobilization by response-guided SAFI ± T/NAdr therapy improves survival by improving splanchnic and systemic hemodynamics, decreasing gut congestion, gut permeability, and endotoxemia, improving neutrophil functions, and reducing pro-inflammatory cytokines in circulation.

Utility of neutrophil CD64 in distinguishing bacterial infection from inflammation in severe alcoholic hepatitis fulfilling SIRS criteria.

To assess utility of neutrophilCD64 (nCD64) expression in differentiating bacterial infection from inflammation in patients with severe alcoholic hepatitis (SAH) fulfilling systemic inflammatory response syndrome criteria. Patients with SAH and infection (n = 58), SAH without infection (n = 70), and healthy controls (n = 20) were included. Neutrophil CD64 expression by flowcytometry, serum Procalcitonin (ELISA) and C-reactive protein (Nephelometry) and neutrophil-lymphocyte ratio (NLR) were studied. Percentage of neutrophils with CD64 expression (nCD64%) was significantly higher in patients with SAH and infection than in those without infection and controls [76.2% (56.9-86.5) vs. 16% (12.6-23.1) vs. 7.05% (1.4-9.5), p < 0.05], as was their mean fluorescence intensity [MFI; 1431 (229-1828) vs. 853 (20-968) vs. 99.5 (54.7-140.7), p < 0.05]. Using a cut-off of 27%, the sensitivity and specificity of nCD64% to diagnose bacterial infection was 94% and 81%, respectively, with area under curve (AUC) of 0.95. At a cut-off value of 0.261 ng/ml, the sensitivity and specificity of serum procalcitonin was 83% and 72%, respectively, with AUC of 0.86. Serum CRP, total leukocyte count, NLR had AUCs of 0.78, 0.63 and 0.64, respectively. Quantitative measurement of nCD64 can better distinguish systemic bacterial infection and inflammation in SAH as compared to traditional biomarkers.

Breathability and Safety Testing of Personal Protective Equipment: "Human-comfort" Factor Remains Undefined.

Healthcare systems all over the world have been enormously affected by the COVID-19 pandemic. Healthcare workers (HCWs) taking care of these patients need personal protective equipments (PPEs) standardized for full protection from droplets and aerosols carrying viral load to variable distances. There has been a surge of manufacturers supplying these protective gears in India and regulatory agencies have issued technical specifications pertaining to PPEs focusing solely on synthetic blood penetration tests (SBPTs) and keeping the upper limit of non-woven fabric to 95 g/m2 (GSM). These PPE specifications are silent on air permeability (AP) and water/moisture vapor transmission rate (WVTR/MVTR) of the fabric. As a result, most of the PPE kits, despite having appropriate SBPT certifications from regulatory agencies, have extremely poor permeability and breathability. The acceptability of PPEs by HCWs can be vastly improved when the end-users are proactively invited to participate in "comfort testing" of PPEs before getting issuance of certification for marketing. "Field testing" or "end-user trials" in which HCWs don the PPE and assess it for comfort while performing different types of clinical work, e.g., in intensive care units (ICUs), operation theaters, cath labs, etc., also takes into account a hitherto often ignored "human-comfort-factor" that not only enhances the understanding of HCWs about the need for the PPEs but can also motivate them to use it without worrying about discomfort. We hereby propose that comfort fit testing (COmfort and Material Fit is an Obviously Required Test) should be a part of the mandatory testing and certification process for PPE, so that the industry invests wisely in manufacturing PPE kits that are not only certified for fabric but are also tested for comfort factors. How to cite this article: Kapoor A, Baronia AK, Azim A, Agarwal G, Prasad N, Mishra R, et al. Breathability and Safety Testing of Personal Protective Equipment: "Human-comfort" Factor Remains Undefined. Indian J Crit Care Med 2021;25(1):12-15.

Diagnostic yield of endoscopic ultrasound-guided fine-needle aspiration of tubercular lymphadenitis using combination of cytology and Gene Xpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) genes.

Diagnostic yield of an automated molecular test, Gene Xpert Mycobacterium tuberculosis/rifampicin (MTB/RIF), was evaluated in this study to simultaneously detect the MTB gene and resistance to rifampicin (RIF) on cytology samples acquired via endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNAC) in suspected tubercular lymphadenitis. Microscopy, cytology, Gene Xpert MTB/RIF assay data on Acid-fast bacillus (AFB), and traditional culture of lymph nodes were retrospectively analyzed. Thirty-one patients (median age 33.5 years, inter-quartile range [IQR] 21-66, 18, 58% female) presented with fever (28, 90%), dysphagia (2, 7%), and recurrent subacute intestinal obstruction (1, 3%). Gene Xpert showed higher sensitivity (30, 97%) compared to the other tests: cytology (23, 77%; odds ratio [OR] 8.8, 95% confidence interval [CI] 1.0-76.9; p = 0.05), AFB smears (12, 39%; OR 50, 95% CI 5.9-420.4; p = 0.00001), and conventional culture (4, 13%; OR 188.5, 95% CI 19.7-1796.3; p = 0.0000). We conclude that Gene Xpert MTB/RIF test on EUS-guided FNAC samples is very useful to diagnose tubercular lymphadenitis.

NMR-based urinary profiling of lactulose/mannitol ratio used to assess the altered intestinal permeability in acute on chronic liver failure (ACLF) patients.

The article presents a simplified NMR-based protocol for urinary profiling of lactulose/mannitol ratio (LMR) and demonstrates here its utility to assess increased intestinal permeability (IP) in patients with acute on chronic liver failure (ACLF). ACLF is a serious clinical complication associated with chronic liver disease (cirrhosis). The major risk factor in its development is increased IP ('leaky gut'), which has been linked to disease progression and to infectious complications. However, IP has seldom been investigated in patients with ACLF, even though patients frequently report gastrointestinal disorders and associated complications. To this end, we first optimized the NMR-based targeted profiling of urinary metabolites (i.e. actulose, mannitol, and creatinine) and subsequently used this resulted protocol (a) first to evaluate the altered IP in ACLF patients and then (b) to explore its utility for monitoring the treatment response in these patients. The normal profiles were obtained for 7 age and sex matched healthy volunteers. The results revealed that the urinary LMR excretion was significantly higher in ACLF patients compared to normal controls (median ~0.7, range (0.12-2.84), vs median ~0.11, range (0.02-0.28), p < 0.001) suggesting that the ACLF patients' exhibit altered IP. However, the LMR excretion in six clinically improved follow-up ACLF patients was comparable to normal controls indicating restored IP after the treatment. The protocol-as demonstrated here with ACLF-is equally applicable for evaluating IP or mucosal barrier function in other intestinal disorders with reasonable sensitivity and specificity, highlighting its general utility. Copyright © 2016 John Wiley & Sons, Ltd.

Intrahepatic biliary duct branching patterns, cystic duct anomalies, and pancreas divisum in a tertiary referral center: A magnetic resonance cholangiopancreaticographic study.

BACKGROUND: Knowledge about anatomic variations in intrahepatic biliary ducts (IHBD) is relevant for performing biliary drainage and for avoiding bile duct injury during cholecystectomy and liver resections. Low insertion of cystic duct (LICD) is a common anatomic variant. Pancreas divisum is the commonest congenital anomaly of pancreas; it has been causally linked with recurrent acute pancreatitis (RAP). METHODS: Magnetic resonance cholangiopancreaticography (MRCP) images of 500 consecutive patients were reviewed for anatomic variants of IHBD, cystic duct, and pancreatic duct. RESULTS: Anatomy of IHBD could be evaluated in 458 MRCP's, of these 301 (65.72 %) had 'typical' anatomy. The variant in 157 persons included 'triple confluence' in 56 (12.23 %), 'right posterior segmental duct (RPSD) draining to left hepatic duct (LHD)' in 64 (14 %), 'RPSD to common hepatic duct (CHD)' in 20 (4.4 %), 'RPSD to cystic duct' in 2 (0.4 %), 'accessory duct to CHD' in 3 (0.7 %), 'accessory duct to right hepatic duct (RHD)' in 1 (0.2 %), 'segment 2 and 3 separately to CHD' in 1 (0.2 %), and complex variants in 10 (2.2 %). Cystic duct could be evaluated in 338 patients; of these, 15 (4.4 %) had LICD. Patients with RAP had pancreas divisum more often than those without any pancreatic disease, (-/-,10 % and -/-, 0.8 %; p = 0.004). CONCLUSIONS: Nearly one third of MRCPs showed atypical IHBD pattern with RPSD draining to LHD being the commonest. LICD was the most common cystic duct variant. Pancreas divisum was more frequent in patients with RAP than in persons without pancreatic disease.

Thiamine deficiency related microstructural brain changes in acute and acute-on-chronic liver failure of non-alcoholic etiology.

BACKGROUND & AIMS: Mammillary body atrophy in alcoholic liver disease usually indicates thiamine deficiency. The purpose of this study was to explore the relationship among blood thiamine, mammillary bodies, major fiber bundle fractional anisotropy, and volume changes with diffusion tensor tractography in patients with acute and acute-on-chronic liver failure of non-alcoholic etiology. METHODS: Blood thiamine, mammillary bodies, fiber bundle fractional anisotropy and volume of major fiber tracts were quantified from acute and acute-on-chronic liver failure patients and compared with healthy controls. In 7 acute liver failure patients, follow-up study was done after clinical recovery at 5 weeks. RESULTS: Blood thiamine, mammillary bodies and fornix volume, and fornix fiber bundle fractional anisotropy were significantly decreased as compared to controls. Blood thiamine showed significant positive correlation with mammillary bodies' volume only. On follow-up study, acute liver failure patients showed significant reversibility only in blood thiamine level and mammillary bodies' volume. CONCLUSIONS: Mammillary bodies' volume changes are primarily a consequence of thiamine deficiency, which may secondarily result in microstructural changes in the fornix. These observable changes are known to be specific and may be reversible with restoration of blood thiamine level. These imaging changes may be used as imaging biomarker of thiamine deficiency in these patients in future.

Pro-inflammatory cytokines are raised in extrahepatic portal venous obstruction, with minimal hepatic encephalopathy.

BACKGROUND AND AIMS: Minimal hepatic encephalopathy (MHE) and hyperammonemia are seen in patients with extrahepatic portal venous obstruction (EHPVO). Inflammation has been shown to play an important role in the pathogenesis of hepatic encephalopathy in cirrhotics. This study assessed serum pro-inflammatory cytokines and their correlation with hyperammonemia, (1)H-magnetic resonance (MR) spectroscopy-derived brain glutamine, and diffusion tensor imaging (DTI)-derived metrics in patients with EPHVO, with and without MHE. METHODS: Neuropsychological tests, DTI, (1)H-MR spectroscopy, and estimation of blood ammonia and pro-inflammatory cytokines (tumor necrosis factor-α[TNF-α] and interleukin-6 [IL-6]) were done in 20 patients with EHPVO and eight healthy controls. RESULTS: Pro-inflammatory cytokines (TNF-α and IL-6), blood ammonia, brain glutamine, and mean diffusivity were increased in both patient groups, as compared to controls. Patients with MHE (n-12) had significantly higher TNF-α, IL-6, blood ammonia, brain glutamine, and mean diffusivity, signifying brain edema, than controls. A significant, positive correlation was seen between TNF-α and IL-6 and between blood ammonia and TNF-α, IL-6, and brain glutamine. Significant, positive correlations of TNF-α, IL-6, and blood ammonia with mean diffusivity values were seen in various brain regions, including spectroscopy voxel-derived mean diffusivity. CONCLUSION: Patients with extrahepatic portal vein obstruction have inflammation and hyperammonemia made evident by higher blood TNF-α, IL-6, ammonia, and brain glutamine levels. A significant correlation between hyperammonemia, pro-inflammatory cytokines, and cerebral edema on DTI in various brain regions suggests that both these factors play a role in the pathogenesis of MHE in these patients.

Serum proinflammatory cytokines correlate with diffusion tensor imaging derived metrics and 1H-MR spectroscopy in patients with acute liver failure.

Hyperammonemia and inflammation are major contributing factors in the development of cerebral edema (CE) in acute liver failure (ALF). Aim of this study was to look for the relationship between proinflammatory cytokines with diffusion tensor imaging (DTI) derived metrics and (1)H-MR spectroscopy ((1)H-MRS) derived Glutamate/Glutamine (Glx). Fourteen patients with ALF and 14 age/sex matched controls were included in this study. All subjects had undergone clinical, biochemical, MR imaging and (1)H-MRS studies. Serum proinflammatory cytokines (IL-6 and TNF-α), blood ammonia level and Glx were computed for independent t-test and Pearson correlation. Serum proinflammatory cytokines, blood ammonia level and brain Glx were significantly increased in ALF patients as compared to controls. Blood ammonia level and Glx showed significant positive correlation with proinflammatory cytokines. Spectroscopy voxel derived spherical anisotropy (CS) showed positive correlation with Glx while mean diffusivity (MD) showed negative correlation. Proinflammatory cytokines showed positive correlation with CS and negative correlation with MD in various brain regions including spectroscopy voxel. Significant correlation of Glx, CS and MD with proinflammatory cytokines suggests that both DTI derived metrics and (1)H-MRS measure the synergistic effect of hyperammonemia and proinflammatory cytokines and may be used as non-invasive tools for understanding the pathogenesis of CE in ALF.

Clinical features and predictors of outcome in acute hepatitis A and hepatitis E virus hepatitis on cirrhosis.

BACKGROUND AND OBJECTIVES: Acute hepatitis A and E are recognized triggers of hepatic decompensation in patients with cirrhosis, particularly from the Indian subcontinent. However, the resulting acute-on-chronic liver failure (ACLF) has not been well characterized and no large studies are available. Our study aimed to evaluate the clinical profile and predictors of 3-month mortality in patients with this distinctive form of liver failure. METHODS: ACLF was diagnosed in patients with acute hepatitis A or E [abrupt rise in serum bilirubin and/or alanine aminotransferase with positive immunoglobulin M anti-hepatitis A virus (HAV)/anti-hepatitis E virus (HEV)] presenting with clinical evidence of liver failure (significant ascites and/or hepatic encephalopathy) and clinical, biochemical, endoscopic (oesophageal varices at least grade II in size), ultrasonographical (presence of nodular irregular liver with porto-systemic collaterals) or histological evidence of cirrhosis. Clinical and laboratory profile were evaluated, predictors of 3-month mortality were determined using univariate and multivariate logistic regression and a prognostic model was constructed. Receiver-operating curves were plotted to measure performance of the present prognostic model, model for end-stage liver disease (MELD) score and Child-Turcotte-Pugh (CTP) score. RESULTS: ACLF occurred in 121 (3.75%) of 3220 patients (mean age 36.3+/-18.0 years; M:F 85:36) with liver cirrhosis admitted from January 2000 to June 2006. It was due to HEV in 80 (61.1%), HAV in 33 (27.2%) and both in 8 (6.1%). The underlying liver cirrhosis was due to HBV (37), alcohol (17), Wilson's disease (8), HCV (5), autoimmune (6), Budd-Chiari syndrome (2), haemochromatosis (2) and was cryptogenic in the rest (42). Common presentations were jaundice (100%), ascites (78%) and hepatic encephalopathy (55%). Mean (SD) CTP score was 11.4+/-1.6 and mean MELD score was 28.6+/-9.06. Three-month mortality was 54 (44.6%). Complications seen were sepsis in 42 (31.8%), renal failure in 45 (34%), spontaneous bacterial peritonitis in 27 (20.5%), UGI bleeding in 15(11%) and hyponatraemia in 50 (41.3%). On univariate analysis, ascites, hepatic encephalopathy, renal failure, GI bleeding, total bilirubin, hyponatraemia and coagulopathy were significant predictors of mortality. Multivariate analysis revealed grades 3 and 4 HE [odds ratio (OR 32.1)], hyponatraemia (OR 9.2) and renal failure (OR 16.8) as significant predictors of 3-month mortality and a prognostic model using these predictors was constructed. Areas under the curve for the present predicted prognostic model, MELD, and CTP were 0.952, 0.941 and 0.636 respectively. CONCLUSIONS: ACLF due to hepatitis A or E super infection results in significant short-term mortality. The predictors of ominous outcome include grades 3 and 4 encephalopathy, hyponatraemia and renal failure. Present prognostic model and MELD scoring system were better predictors of 3-month outcome than CTP score in these patients. Early recognition of those with dismal prognosis may permit timely use of liver replacement/supportive therapies.

Anatomic variations in intrahepatic bile ducts in a north Indian population.

BACKGROUND AND AIM: In the present study, we described the anatomical variations in the branching patterns of intrahepatic bile ducts (IHD) and determined the frequency of each variation in north Indian patients. There are no data from India. METHODS: The study group consisted of 253 consecutive patients (131 women) undergoing endoscopic retrograde cholangiograms for different indications. Anatomical variations in IHD were classified according to the branching pattern of the right anterior segmental duct (RASD) and the right posterior segmental duct (RPSD), presence or absence of first-order branch of left hepatic duct (LHD) and of an accessory hepatic duct. RESULTS: Anatomy of the IHD was typical in 52.9% of cases (n = 134), showing triple confluence in 11.46% (n = 29), anomalous drainage of the RPSD into the LHD in 18.2% (n = 46), anomalous drainage of the RPSD into the common hepatic duct (CHD) in 7.1% (n = 18), drainage of the right hepatic duct (RHD) into the cystic duct 0.4% (n = 1), presence of an accessory duct leading to the CHD or RHD in 4.7% (n = 12), individual drainage of the LHD into the RHD or CHD in 2.4% (n = 6), and unclassified or complex variations in 2.7% (n = 7). None had anomalous drainage of RPSD into the cystic duct. CONCLUSION: The branching pattern of IHD was atypical in 47% patients. The two most common variations were drainage of the RPSD into the LHD (18.2%) and triple confluence of the RASD, RPSD, and LHD (11.5%).

In vivo 1H 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.

Cerebral diffusion tensor imaging and in vivo proton magnetic resonance spectroscopy in patients with fulminant hepatic failure.

BACKGROUND AND AIM: Cerebral edema is a major complication in patients with fulminant hepatic failure (FHF). The aim of this study was to evaluate the metabolite alterations and cerebral edema in patients with FHF using in vivo proton magnetic resonance spectroscopy (MRS) and diffusion tensor imaging, and to look for its reversibility in survivors. METHODS: Ten FHF patients along with 10 controls were studied. Five of the 10 patients who recovered had a repeat imaging after three weeks. N-acetylaspartate, choline (Cho), glutamine (Gln), glutamine/glutamate (Glx), and myoinositol ratios were calculated with respect to creatine (Cr). Mean diffusivity (MD) and fractional anisotropy (FA) were calculated in different brain regions. RESULTS: Patients exhibited significantly increased Gln/Cr and Glx/Cr, and reduced Cho/Cr ratios, compared to controls. In the follow-up study, all metabolite ratios were normalized except Glx/Cr. Significantly decreased Cho/Cr were observed in deceased patients compared to controls. In patients, significantly decreased MD and FA values were observed in most topographical locations of the brain compared to controls. MD and FA values showed insignificant increase in the follow-up study compared to their first study. CONCLUSIONS: We conclude that the Cho/Cr ratio appears to be an in vivo marker of prognosis in FHF. Decreased MD values suggest predominant cytotoxic edema may be present. Persistence of imaging and MRS abnormalities at three weeks' clinical recovery suggests that metabolic recovery may take longer than clinical recovery in FHF patients.

Cytotoxic edema is responsible for raised intracranial pressure in fulminant hepatic failure: in vivo demonstration using diffusion-weighted MRI in human subjects.

It is not clear whether cerebral edema in fulminant hepatic failure is predominantly vasogenic or cytotoxic, though cytotoxic edema due to astrocyte swelling is more likely. Diffusion-weighted magnetic resonance imaging can differentiate vasogenic from cytotoxic edema. We performed diffusion-weighted imaging in patients with fulminant hepatic failure to clarify the issue by measuring apparent diffusion coefficient, which quantifies movement of water molecule across cell membrane. Seven patients with fulminant hepatic failure underwent conventional and diffusion-weighted magnetic resonance imaging. Apparent diffusion coefficient was measured in four cortical areas and 12 deep white and gray matter regions in both cerebral hemispheres. Thirteen healthy subjects served as controls. The apparent diffusion coefficient values in patients and controls were compared using Wilcoxon signed rank test. Two patients who survived underwent repeat imaging using same protocol. Patients with FHF had significantly lower apparent diffusion coefficient in all cortical and deep white and gray matter regions of interest compared to controls (p < 0.001), suggesting cytotoxic cell swelling. In two survivors with repeat imaging, one showed complete resolution while the changes persisted in the other, suggesting ischemic injury. Cerebral edema in fulminant hepatic failure is predominantly due to cytotoxic edema.