william bernal - Academia.edu (original) (raw)

Papers by william bernal

Research paper thumbnail of Critical care and cirrhosis

Current Opinion in Critical Care, 2011

The incidence of cirrhosis is growing steadily and this cohort of patients will present in ever-g... more The incidence of cirrhosis is growing steadily and this cohort of patients will present in ever-greater numbers to critical care with acute decompensation, usually secondary to an inter-current event or following elective surgery. This review examines the evidence for treatment options and outcomes. Outcome of cirrhotics presenting with end-organ dysfunction is steadily improving and their outcomes are not as poor as sometimes suggested. Treatment options for variceal bleeding and renal dysfunction are evolving and outcomes improving. Critical care support should be offered to patients with cirrhosis and in high-risk variceal bleed patients transhepatic portosystemic shunt should be considered.

Research paper thumbnail of Multiple organ failure and severe bone marrow dysfunction in two 18 year-old Caucasian patients: Epstein-Barr virus and the haemophagocytic syndrome

Anaesthesia, 2008

Haemophagocytic lymphohistiocytosis secondary to viral infection is an unusual but well recognise... more Haemophagocytic lymphohistiocytosis secondary to viral infection is an unusual but well recognised cause of bone marrow dysfunction and multiple organ failure in young patients. Two 18 year-old patients were admitted to a tertiary liver unit with features of acute liver failure, cardio-respiratory collapse and pancytopenia. Serological tests and bone marrow examination with in-situ hybridisation revealed severe acquired haemophagocytic lymphohistiocytosis secondary to acute Epstein–Barr virus infection. Both patients died despite full supportive therapy; the first due to pulmonary haemorrhage, the second due to acute respiratory distress syndrome refractory to high frequency oscillatory ventilation. The clinical spectrum, diagnostic features and current evidence based recommendations for treatment of this condition are explored. The diagnosis of haemophagocytic lymphohistiocytosis should be considered in young patients with marked bone marrow dysfunction and multiple organ failure. Further research into appropriate therapy for patients with acute severe forms of the disease who require intensive organ support is required.

Research paper thumbnail of Portopulmonary hypertension: Improved detection using CT and echocardiography in combination

European Radiology, 2014

To establish the relationship between CT signs of pulmonary hypertension and mean pulmonary arter... more To establish the relationship between CT signs of pulmonary hypertension and mean pulmonary artery pressure (mPAP) in patients with liver disease, and to determine the additive value of CT in the detection of portopulmonary hypertension in combination with transthoracic echocardiography. Forty-nine patients referred for liver transplantation were retrospectively reviewed. Measured CT signs included the main pulmonary artery/ascending aorta diameter ratio (PA/AAmeas) and the mean left and right main PA diameter (RLPAmeas). Enlargement of the pulmonary artery compared to the ascending aorta was also assessed visually (PA/AAvis). CT measurements were correlated with right-sided heart catheter-derived mPAP. The ability of PA/AAvis combined with echocardiogram-derived right ventricular systolic pressure (RVSP) to detect portopulmonary hypertension was tested with ROC analysis. There were moderate correlations between mPAP and both PA/AAmeas and RLPAmeas (rs = 0.41 and rs = 0.42, respectively; p < 0.005). Compared to transthoracic echocardiography alone (AUC = 0.59, p = 0.23), a diagnostic algorithm incorporating PA/AAvis and transthoracic echocardiography-derived RVSP improved the detection of portopulmonary hypertension (AUC = 0.8, p < 0.0001). CT contributes to the non-invasive detection of portopulmonary hypertension when used in a diagnostic algorithm with transthoracic echocardiography. CT may have a role in the pre-liver transplantation triage of patients with portopulmonary hypertension for right-sided heart catheterisation. • CT signs correlate with right-sided heart catheter data in portopulmonary hypertension • CT adds to the transthoracic echocardiography detection of portopulmonary hypertension • CT may have a complementary role in pre-liver transplantation triage.

Research paper thumbnail of Increased Survival for Patients With Cirrhosis and Organ Failure in Liver Intensive Care and Validation of the Chronic Liver Failure–Sequential Organ Failure Scoring System

Clinical Gastroenterology and Hepatology, 2014

During the past decade, survival has increased among patients admitted to general intensive care ... more During the past decade, survival has increased among patients admitted to general intensive care units, but it is not clear if it has increased for patients admitted with cirrhosis and organ failure. The chronic liver failure-sequential organ failure assessment (CLIF-SOFA) recently was developed as an adaptation to the SOFA to predict outcomes of patients, but requires validation. We investigated changes in outcomes of patients with cirrhosis and organ failure since 2000, compared the abilities of SOFA and CLIF-SOFA to predict patient survival, and validated the CLIF-SOFA system. In a retrospective study, we collected data from 971 patients (median age, 52 y; age range, 16-90 y; 62% male) with cirrhosis (54% alcohol associated, 12% viral, and 34% other causes). The patients were admitted under emergency conditions from January 1, 2000, to December 31, 2010, to a liver intensive therapy unit in the United Kingdom. Patient survival while in the hospital was compared with measures of illness severity, Acute Physiology and Chronic Health Evaluation (APACHE) II scores, model for end-stage liver disease (MELD) scores, SOFA scores, and CLIF-SOFA scores. Patients had a median APACHE II score of 21 (range, 5-50) and a median MELD score of 23 (range, 6-40). The median APACHE II score at admission decreased from 23 to 22 over the study period (P < .001), whereas the median MELD score at admission decreased from 23 to 18 (P < .001). Overall survival until hospital discharge was 51%; this value increased from 40% in 2000 to 63% in 2010 (P < .001). The unadjusted odds ratio for change in mortality/year was 0.87 (95% confidence interval, 0.83-0.91; P < .001). The APACHE II score adjusted odds ratio for mortality was 0.89 (95% confidence interval, 0.84-0.93; P < .001). The etiology of cirrhosis was not associated with a significant difference in survival. CLIF-SOFA and SOFA scores at the time of admission predicted patient survival with area under the receiver operating curve (AUROC) values of 0.813 and 0.799, respectively; the scores at 48 hours after admission predicted survival with AUROC values of 0.853 and 0.840, and scores after 1 week predicted survival with AUROC values of 0.842 and 0.844, respectively. These AUROC values were higher than those obtained from APACHE II or MELD scores. The proportion of patients with cirrhosis who survived after admission to intensive care increased from 2000 to 2010. SOFA and CLIF-SOFA scores during the first week of critical care appear to have similar abilities to predict patient survival.

Research paper thumbnail of Fulminant Hepatic Failure

Clavien/Medical Care of the Liver Transplant Patient, 2012

Research paper thumbnail of Reduced monocyte HLA-DR expression: A novel biomarker of disease severity and outcome in acetaminophen-induced acute liver failure

Hepatology, 2006

Acute liver failure (ALF) shares striking similarities with septic shock where a decrease in HLA-... more Acute liver failure (ALF) shares striking similarities with septic shock where a decrease in HLA-DR expression on monocytes is associated with disease severity and predicts outcome. We investigated monocyte HLA-DR expression in ALF in relation to inflammatory mediator levels and clinical outcome. Monocyte HLA-DR expression was determined in 50 patients with acetaminophen-induced ALF (AALF) and 20 non–acetaminophen-induced ALF (NAALF). AALF patients were divided into dead/transplanted (AALF-NS, n = 26) and spontaneous survivors (AALF-S, n = 24). Fifty patients with chronic liver disease (CLD) and 50 healthy volunteers served as controls. Monocyte HLA-DR expression was determined by double-color flow-cytometry with monoclonal antibodies detecting HLA-DR and monocyte specific CD14. Serum levels of interleukin (IL) -4, -6, -10, tumor necrosis factor (TNF)-α and interferon (IFN)-γ were concomitantly measured by ELISA. Compared to healthy volunteers (75%) and CLD (67%) monocyte HLA-DR percentage expression was lower in AALF (15%, P < .001) and NAALF (22 %, P < .001). Compared to AALF-S, AALF-NS had lower monocyte HLA-DR % (11% vs. 36%, P < .001) and higher levels of IL-4, IL-6, IL-10 and TNF-α (P < .001). HLA-DR percentage negatively correlated with INR, blood lactate, pH and levels of encephalopathy (r = −0.8 to −0.5, P < .01), IL-10 (r = −0.8, P < .0001), TNF-α (r = −0.4, P = .02). HLA-DR percentage level ≤15% has a 96% sensitivity and 100% specificity and 98% accuracy in predicting poor prognosis. In conclusion, the strong relationship of monocyte HLA-DR expression with indices of disease severity, mediators of inflammation and outcome indicates a key role for this molecule as a biomarker of disease severity and prognosis. (HEPATOLOGY 2006;44:34–43.)

Research paper thumbnail of Iron and acetaminophen a fatal combination?

Transplant International, 2011

Research paper thumbnail of Genetic variants of hepatic transporters and susceptibility to drug induced liver injury

Research paper thumbnail of Acute Liver Failure

New England Journal of Medicine, 2013

Research paper thumbnail of Reply

Liver Transplantation, 2014

Research paper thumbnail of Increased MELD score at the time of liver transplant results in prolonged hospitalization and overall intensive care unit costs

Liver Transplantation, 2010

Organ allocation based on Model for End-Stage Liver Disease (MELD) resulted in decreased waiting ... more Organ allocation based on Model for End-Stage Liver Disease (MELD) resulted in decreased waiting list mortality in the United States. However, reports suggest an increase in resource utilization as a consequence of this. The aim of this study is to assess the correlation of MELD at transplant with post-liver transplant (LT) intensive care unit (ICU) costs. We assessed clinical and demographic variables of 402 adult patients who underwent LT at King's College Hospital, London, UK, between January 2000 and December 2003. ICU cost calculations were based on the therapeutic intervention scoring system (TISS). Graft quality was assessed using the donor risk index (DRI). Patients with a MELD score > 24 had significantly longer post-LT ICU stay (P < 0.0001) and total post-LT hospital stay (P ¼ 0.008). In addition, they had significantly increased TISS scores, ICU cost, and need for renal replacement therapy (RRT) (P < 0.001). MELD score (by point) and MELD > 24 was associated with prolonged ICU stay (P ¼ 0.004 and P ¼ 0.005, respectively). On univariate analysis, etiology of alcohol-related liver disease (ALD), repeat LT, Budd-Chiari syndrome, and refractory ascites were associated with prolonged ICU stay. Using multivariate analysis, MELD > 24, refractory ascites, ALD and Budd-Chiari syndrome were associated with prolonged ICU stay. There was no association between using grafts with higher DRI and longer ICU stay, need for RRT, increased cost, or hospital survival on univariate analyses (P ¼ not significant). Use of MELD as a method of organ allocation results in significant increase in ICU cost after LT. Using TISS as surrogate marker for ICU costs reveals that the cost implications are related to the need for RRT and prolonged ICU stay. Liver Transpl 16:668-677,

Research paper thumbnail of Aerobic capacity during cardiopulmonary exercise testing and survival with and without liver transplantation for patients with chronic liver disease

Liver Transplantation, 2014

Chronic liver disease (CLD) is associated with muscle wasting, reduced exercise tolerance and aer... more Chronic liver disease (CLD) is associated with muscle wasting, reduced exercise tolerance and aerobic capacity (AC). Measures of AC determined with cardiopulmonary exercise testing (CPET) may predict survival after liver transplantation (LT), but the relationship with nontransplant outcomes is uncertain. In patients assessed for LT, we examined the relationship of CPET AC parameters with the severity of liver disease, nutritional state, and survival with and without LT. Patients assessed for elective first LT who underwent CPET and an anthropometric assessment at a single center were studied. CPET-derived measures of AC that were evaluated included the peak oxygen consumption (VO 2 peak) and the anaerobic threshold (AT). Three hundred ninety-nine patients underwent CPET, and 223 underwent LT; 45% of the patients had a VO 2 peak < 50% of the predicted value, and 31% had an AT < 9 mL/kg/minute. The VO 2 peak and AT values correlated with the Model for End-Stage Liver Disease score, but they more closely correlated with serum sodium and albumin levels. The handgrip strength correlated strongly with the VO 2 peak. Patients with impaired AC had prolonged hospitalization after LT, and nonsurvivors had lower AT values than survivors 1 year after transplantation (P < 0.05); this was significant in a multivariate analysis. One hundred seventy-six patients did not undergo LT; the 1-year mortality rate was 34.6%. The AT (P < 0.05) and VO 2 peak values (P < 0.001) were lower for nonsurvivors. In a multivariate analysis, AT was independently associated with nonsurvival. In conclusion, AC was markedly impaired in many patients with CLD. In patients who did not undergo transplantation, impaired AT was predictive of mortality, and in patients undergoing LT, it was related to postoperative hospitalization and survival. AC should be evaluated as a modifiable factor for improving patient survival whether or not LT is anticipated.

Research paper thumbnail of Haemodynamic response to abdominal decompression in acute Budd-Chiari syndrome

Liver International, 2011

Background: Intra-abdominal hypertension (IAH) and abdominal compartment syndrome commonly occur ... more Background: Intra-abdominal hypertension (IAH) and abdominal compartment syndrome commonly occur in patients with liver disease. Aims: We compared haemodynamic variables pre-and post-abdominal decompression in patients with acute Budd-Chiari syndrome (BCS) and patients with chronic liver disease (CLD), ascites and IAH. Methods: Patients with IAH admitted to the Liver ICU, King's College Hospital were studied. Transpulmonary thermodilution cardiac output (CO) monitoring was performed with the PiCCO s system. Results: Ten patients with decompensated BCS (median age 39 years, 20-52) and eight patients with CLD (59 years, 33-65) and tense ascites requiring paracentesis were studied. Intra-abdominal pressure (IAP) was raised in both groups pre-intervention (BSC 23 mmHg, CLD 26,. Intrathoracic blood volume (ITBVI) was persistently low in the BCS group (632 ml/m 2 , 453-924) despite volume resuscitation. Post-intervention, reduction in IAP was noted in both groups (BCS P o 0.001, CLD P o 0.0001). The ITBVI increased (P = 0.001) in the BCS group only. An increase in cardiac index (CI) and stroke volume index (SVI) was noted in both groups (BCS: CI P = 0.003, SVI: P = 0.007; CLD: CI P = 0.005, SVI P = 0.02). The central venous pressure did not change in either group and did not correlate with markers of flow (CI, SVI) or IAP. Both groups demonstrated an inverse relationship between IAP, CI and SVI. Conclusion: Patients with BCS and IAH have evidence of central hypovolaemia. In addition to raised IAP, hepatic venous obstruction and caudate lobe hypertrophy limit venous return in patients with BCS. Reduction in IAP and re-establishment of caval flow restores preload with improvement in CO.

Research paper thumbnail of Evidence of rebalanced coagulation in acute liver injury and acute liver failure as measured by thrombin generation

Liver International, 2014

Patients with liver disease often show profound abnormalities in their haemostatic system. Studie... more Patients with liver disease often show profound abnormalities in their haemostatic system. Studies using thrombin generation demonstrate rebalanced coagulation in patients with chronic liver disease. Our aim was to evaluate the haemostatic profile in patients with acute liver injury/failure (ALI/ALF) compared with healthy controls. Thrombin generation was measured in the presence and absence of thrombomodulin (TM) to activate protein C (PC) with endogenous thrombin potential (ETP; the area under the thrombin generation curve) a key parameter. Routine coagulation assays were also performed. Thirty two patients with ALI/ALF and 40 controls were recruited. Patients had grossly abnormal coagulation profiles with decreased pro- and anticoagulant factors compared with controls (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001 for all comparisons), except for median Factor VIII which was increased 247 U/dl [interquartile range: 214-347] in patients compared with 120 U/dl [97-139; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001] in controls. Mean ETP was significantly lower in patients 886 nM.min (± 436) compared with controls 1596 nM.min (± 259; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). However, when the assay was repeated with TM to activate PC, there was no significant difference in mean ETP + TM between patients and controls (632 ± 418 vs 709 ± 301 nM.min respectively; P = 0.666). Furthermore, the ETP ratio (ETP + TM/ETP) was significantly higher in patients 0.89 (0.60-0.97) compared with controls 0.48 (0.3-0.6; P = 0.002) and negatively correlated with PC (R = -0.487, P = 0.003) and Factor V (R = -0.431, P = 0.01). ALI/ALF patients have normal ETP in the presence of TM. This supports rebalanced coagulation mediated by acquired PC resistance because of the reduction in PC, Factor V and concomitant increase in Factor VIII.

Research paper thumbnail of Ammonia clearance with haemofiltration in adults with liver disease

Liver International, 2014

Background & Aims: Ammonia is recognized as a toxin central to complications of liver failure. Hy... more Background & Aims: Ammonia is recognized as a toxin central to complications of liver failure. Hyperammonaemia has important clinical consequences, but optimal means to reduce circulating levels are uncertain. In patients with liver disease, continuous renal replacement therapy (CRRT) with haemofiltration (HF) is often required to treat concurrent kidney injury, but its effects upon ammonia levels are poorly characterized. To evaluate the effect of HF at different treatment intensities on ammonia clearance (AC) and arterial ammonia concentration. Methods: Prospective study of adult patients with liver failure and arterial ammonia >100 lmol/L requiring CRRT using veno-venous HF. Arterial ammonia concentration and AC measured at 1 and 24 h after initiation of low (35 ml/kg/h) or high (90 ml/kg/h) filtration volume. Results: Twenty-four patients (10 acute liver failure, 10 chronic liver disease and 4 following liver resection) were studied. Clearance of urea and ammonia solutes correlated closely (r = 0.819, P = 0.007). Ammonia clearance correlated closely with ultrafiltration rate (r = 0.86, P < 0.001). At 1 h, AC was 39 (34-54) ml/min (low volume) vs 85 (62-105) ml/min (high volume) CRRT, (P < 0.001) and at 24 h 44 (34-63) vs 105 (82-109) ml/min, (P = 0.01). Overall, a 22% reduction in median arterial ammonia concentration was observed over 24 h of HF from 156 (137-176) to 122 (85-133) lmol/L, (P ≤ 0.0001). Conclusion: Clinically significant ammonia clearance can be achieved in adult patients with hyperammonaemia utilizing continuous VVHF. Ammonia clearance is closely correlated with ultrafiltration rate. HF was associated with a fall in arterial ammonia concentration.

Research paper thumbnail of Cerebral oedema is rare in acute-on-chronic liver failure patients presenting with high-grade hepatic encephalopathy

Liver International, 2014

Acute-on-chronic liver failure (ACLF) has a rapidly progressive disease course associated with si... more Acute-on-chronic liver failure (ACLF) has a rapidly progressive disease course associated with significant mortality. The prevalence of clinically significant cerebral oedema in ACLF is unknown. We aimed to describe the prevalence of cerebral oedema in a cohort of ACLF adult (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;18 years). We identified patients admitted to a single, specialist intensive care unit between January 2005 and January 2011 with high-grade hepatic encephalopathy (≥3) and a clinical picture of either ACLF or chronic liver disease (CLD). Patients who had undergone cranial CT imaging were identified and their imaging reviewed. The ACLF and CLD groups were compared. One thousand and eight patients with CLD were admitted. One hundred and seventy-three patients (110 male) underwent neuroimaging. Eighty-one (48 male) fulfilled criteria for ACLF. Variceal bleeding (30%) and sepsis (31%) were the most frequent precipitants of ACLF. Of those with neuroimaging from the total cohort, 30% of CT scans were normal, 30% demonstrated increased cerebral atrophy for age, 17% small vessel disease and 16% intracranial haemorrhage (ICH). Cerebral oedema was seen in three patients with ACLF only. An increased prevalence of ICH was observed in the ACLF group (23% vs. 9%, P = 0.008). The prevalence of clinically relevant cerebral oedema was low (4%) but fatal. Death was attributable to tonsillar herniation. An increased prevalence of ICH was seen in ACLF patients and remains an important differential.

Research paper thumbnail of Bacteremia, Acute Physiology and Chronic Health Evaluation II and Modified End Stage Liver Disease are independent predictors of mortality in critically ill nontransplanted patients with acute on chronic liver failure

Critical Care Medicine - CRIT CARE MED, 2010

Research paper thumbnail of Blood lactate and outcome of paracetamol-induced acute liver failure

The Lancet, 2002

Blood lactate and outcome of paracetamol-induced acute liver failure. By - Stephen M Riordan, Rog... more Blood lactate and outcome of paracetamol-induced acute liver failure. By - Stephen M Riordan, Roger Williams.

Research paper thumbnail of Hydroxyethylstarch as a risk factor for acute renal failure in severe sepsis

Research paper thumbnail of Acute liver failure

The Lancet, 2010

Acute liver failure (ALF) is an uncommon condition involving the rapid deterioration of liver fun... more Acute liver failure (ALF) is an uncommon condition involving the rapid deterioration of liver functions and coagulation in previously well patients. The loss of liver function produces a cascade of systemic effects that rapidly overwhelm patients unless acted on. The key to managing patients with ALF revolves around having the resources and expertise to manage patients with rapidly evolving multiple system failure.

Research paper thumbnail of Critical care and cirrhosis

Current Opinion in Critical Care, 2011

The incidence of cirrhosis is growing steadily and this cohort of patients will present in ever-g... more The incidence of cirrhosis is growing steadily and this cohort of patients will present in ever-greater numbers to critical care with acute decompensation, usually secondary to an inter-current event or following elective surgery. This review examines the evidence for treatment options and outcomes. Outcome of cirrhotics presenting with end-organ dysfunction is steadily improving and their outcomes are not as poor as sometimes suggested. Treatment options for variceal bleeding and renal dysfunction are evolving and outcomes improving. Critical care support should be offered to patients with cirrhosis and in high-risk variceal bleed patients transhepatic portosystemic shunt should be considered.

Research paper thumbnail of Multiple organ failure and severe bone marrow dysfunction in two 18 year-old Caucasian patients: Epstein-Barr virus and the haemophagocytic syndrome

Anaesthesia, 2008

Haemophagocytic lymphohistiocytosis secondary to viral infection is an unusual but well recognise... more Haemophagocytic lymphohistiocytosis secondary to viral infection is an unusual but well recognised cause of bone marrow dysfunction and multiple organ failure in young patients. Two 18 year-old patients were admitted to a tertiary liver unit with features of acute liver failure, cardio-respiratory collapse and pancytopenia. Serological tests and bone marrow examination with in-situ hybridisation revealed severe acquired haemophagocytic lymphohistiocytosis secondary to acute Epstein–Barr virus infection. Both patients died despite full supportive therapy; the first due to pulmonary haemorrhage, the second due to acute respiratory distress syndrome refractory to high frequency oscillatory ventilation. The clinical spectrum, diagnostic features and current evidence based recommendations for treatment of this condition are explored. The diagnosis of haemophagocytic lymphohistiocytosis should be considered in young patients with marked bone marrow dysfunction and multiple organ failure. Further research into appropriate therapy for patients with acute severe forms of the disease who require intensive organ support is required.

Research paper thumbnail of Portopulmonary hypertension: Improved detection using CT and echocardiography in combination

European Radiology, 2014

To establish the relationship between CT signs of pulmonary hypertension and mean pulmonary arter... more To establish the relationship between CT signs of pulmonary hypertension and mean pulmonary artery pressure (mPAP) in patients with liver disease, and to determine the additive value of CT in the detection of portopulmonary hypertension in combination with transthoracic echocardiography. Forty-nine patients referred for liver transplantation were retrospectively reviewed. Measured CT signs included the main pulmonary artery/ascending aorta diameter ratio (PA/AAmeas) and the mean left and right main PA diameter (RLPAmeas). Enlargement of the pulmonary artery compared to the ascending aorta was also assessed visually (PA/AAvis). CT measurements were correlated with right-sided heart catheter-derived mPAP. The ability of PA/AAvis combined with echocardiogram-derived right ventricular systolic pressure (RVSP) to detect portopulmonary hypertension was tested with ROC analysis. There were moderate correlations between mPAP and both PA/AAmeas and RLPAmeas (rs = 0.41 and rs = 0.42, respectively; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.005). Compared to transthoracic echocardiography alone (AUC = 0.59, p = 0.23), a diagnostic algorithm incorporating PA/AAvis and transthoracic echocardiography-derived RVSP improved the detection of portopulmonary hypertension (AUC = 0.8, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). CT contributes to the non-invasive detection of portopulmonary hypertension when used in a diagnostic algorithm with transthoracic echocardiography. CT may have a role in the pre-liver transplantation triage of patients with portopulmonary hypertension for right-sided heart catheterisation. • CT signs correlate with right-sided heart catheter data in portopulmonary hypertension • CT adds to the transthoracic echocardiography detection of portopulmonary hypertension • CT may have a complementary role in pre-liver transplantation triage.

Research paper thumbnail of Increased Survival for Patients With Cirrhosis and Organ Failure in Liver Intensive Care and Validation of the Chronic Liver Failure–Sequential Organ Failure Scoring System

Clinical Gastroenterology and Hepatology, 2014

During the past decade, survival has increased among patients admitted to general intensive care ... more During the past decade, survival has increased among patients admitted to general intensive care units, but it is not clear if it has increased for patients admitted with cirrhosis and organ failure. The chronic liver failure-sequential organ failure assessment (CLIF-SOFA) recently was developed as an adaptation to the SOFA to predict outcomes of patients, but requires validation. We investigated changes in outcomes of patients with cirrhosis and organ failure since 2000, compared the abilities of SOFA and CLIF-SOFA to predict patient survival, and validated the CLIF-SOFA system. In a retrospective study, we collected data from 971 patients (median age, 52 y; age range, 16-90 y; 62% male) with cirrhosis (54% alcohol associated, 12% viral, and 34% other causes). The patients were admitted under emergency conditions from January 1, 2000, to December 31, 2010, to a liver intensive therapy unit in the United Kingdom. Patient survival while in the hospital was compared with measures of illness severity, Acute Physiology and Chronic Health Evaluation (APACHE) II scores, model for end-stage liver disease (MELD) scores, SOFA scores, and CLIF-SOFA scores. Patients had a median APACHE II score of 21 (range, 5-50) and a median MELD score of 23 (range, 6-40). The median APACHE II score at admission decreased from 23 to 22 over the study period (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001), whereas the median MELD score at admission decreased from 23 to 18 (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). Overall survival until hospital discharge was 51%; this value increased from 40% in 2000 to 63% in 2010 (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). The unadjusted odds ratio for change in mortality/year was 0.87 (95% confidence interval, 0.83-0.91; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). The APACHE II score adjusted odds ratio for mortality was 0.89 (95% confidence interval, 0.84-0.93; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). The etiology of cirrhosis was not associated with a significant difference in survival. CLIF-SOFA and SOFA scores at the time of admission predicted patient survival with area under the receiver operating curve (AUROC) values of 0.813 and 0.799, respectively; the scores at 48 hours after admission predicted survival with AUROC values of 0.853 and 0.840, and scores after 1 week predicted survival with AUROC values of 0.842 and 0.844, respectively. These AUROC values were higher than those obtained from APACHE II or MELD scores. The proportion of patients with cirrhosis who survived after admission to intensive care increased from 2000 to 2010. SOFA and CLIF-SOFA scores during the first week of critical care appear to have similar abilities to predict patient survival.

Research paper thumbnail of Fulminant Hepatic Failure

Clavien/Medical Care of the Liver Transplant Patient, 2012

Research paper thumbnail of Reduced monocyte HLA-DR expression: A novel biomarker of disease severity and outcome in acetaminophen-induced acute liver failure

Hepatology, 2006

Acute liver failure (ALF) shares striking similarities with septic shock where a decrease in HLA-... more Acute liver failure (ALF) shares striking similarities with septic shock where a decrease in HLA-DR expression on monocytes is associated with disease severity and predicts outcome. We investigated monocyte HLA-DR expression in ALF in relation to inflammatory mediator levels and clinical outcome. Monocyte HLA-DR expression was determined in 50 patients with acetaminophen-induced ALF (AALF) and 20 non–acetaminophen-induced ALF (NAALF). AALF patients were divided into dead/transplanted (AALF-NS, n = 26) and spontaneous survivors (AALF-S, n = 24). Fifty patients with chronic liver disease (CLD) and 50 healthy volunteers served as controls. Monocyte HLA-DR expression was determined by double-color flow-cytometry with monoclonal antibodies detecting HLA-DR and monocyte specific CD14. Serum levels of interleukin (IL) -4, -6, -10, tumor necrosis factor (TNF)-α and interferon (IFN)-γ were concomitantly measured by ELISA. Compared to healthy volunteers (75%) and CLD (67%) monocyte HLA-DR percentage expression was lower in AALF (15%, P < .001) and NAALF (22 %, P < .001). Compared to AALF-S, AALF-NS had lower monocyte HLA-DR % (11% vs. 36%, P < .001) and higher levels of IL-4, IL-6, IL-10 and TNF-α (P < .001). HLA-DR percentage negatively correlated with INR, blood lactate, pH and levels of encephalopathy (r = −0.8 to −0.5, P < .01), IL-10 (r = −0.8, P < .0001), TNF-α (r = −0.4, P = .02). HLA-DR percentage level ≤15% has a 96% sensitivity and 100% specificity and 98% accuracy in predicting poor prognosis. In conclusion, the strong relationship of monocyte HLA-DR expression with indices of disease severity, mediators of inflammation and outcome indicates a key role for this molecule as a biomarker of disease severity and prognosis. (HEPATOLOGY 2006;44:34–43.)

Research paper thumbnail of Iron and acetaminophen a fatal combination?

Transplant International, 2011

Research paper thumbnail of Genetic variants of hepatic transporters and susceptibility to drug induced liver injury

Research paper thumbnail of Acute Liver Failure

New England Journal of Medicine, 2013

Research paper thumbnail of Reply

Liver Transplantation, 2014

Research paper thumbnail of Increased MELD score at the time of liver transplant results in prolonged hospitalization and overall intensive care unit costs

Liver Transplantation, 2010

Organ allocation based on Model for End-Stage Liver Disease (MELD) resulted in decreased waiting ... more Organ allocation based on Model for End-Stage Liver Disease (MELD) resulted in decreased waiting list mortality in the United States. However, reports suggest an increase in resource utilization as a consequence of this. The aim of this study is to assess the correlation of MELD at transplant with post-liver transplant (LT) intensive care unit (ICU) costs. We assessed clinical and demographic variables of 402 adult patients who underwent LT at King's College Hospital, London, UK, between January 2000 and December 2003. ICU cost calculations were based on the therapeutic intervention scoring system (TISS). Graft quality was assessed using the donor risk index (DRI). Patients with a MELD score > 24 had significantly longer post-LT ICU stay (P < 0.0001) and total post-LT hospital stay (P ¼ 0.008). In addition, they had significantly increased TISS scores, ICU cost, and need for renal replacement therapy (RRT) (P < 0.001). MELD score (by point) and MELD > 24 was associated with prolonged ICU stay (P ¼ 0.004 and P ¼ 0.005, respectively). On univariate analysis, etiology of alcohol-related liver disease (ALD), repeat LT, Budd-Chiari syndrome, and refractory ascites were associated with prolonged ICU stay. Using multivariate analysis, MELD > 24, refractory ascites, ALD and Budd-Chiari syndrome were associated with prolonged ICU stay. There was no association between using grafts with higher DRI and longer ICU stay, need for RRT, increased cost, or hospital survival on univariate analyses (P ¼ not significant). Use of MELD as a method of organ allocation results in significant increase in ICU cost after LT. Using TISS as surrogate marker for ICU costs reveals that the cost implications are related to the need for RRT and prolonged ICU stay. Liver Transpl 16:668-677,

Research paper thumbnail of Aerobic capacity during cardiopulmonary exercise testing and survival with and without liver transplantation for patients with chronic liver disease

Liver Transplantation, 2014

Chronic liver disease (CLD) is associated with muscle wasting, reduced exercise tolerance and aer... more Chronic liver disease (CLD) is associated with muscle wasting, reduced exercise tolerance and aerobic capacity (AC). Measures of AC determined with cardiopulmonary exercise testing (CPET) may predict survival after liver transplantation (LT), but the relationship with nontransplant outcomes is uncertain. In patients assessed for LT, we examined the relationship of CPET AC parameters with the severity of liver disease, nutritional state, and survival with and without LT. Patients assessed for elective first LT who underwent CPET and an anthropometric assessment at a single center were studied. CPET-derived measures of AC that were evaluated included the peak oxygen consumption (VO 2 peak) and the anaerobic threshold (AT). Three hundred ninety-nine patients underwent CPET, and 223 underwent LT; 45% of the patients had a VO 2 peak < 50% of the predicted value, and 31% had an AT < 9 mL/kg/minute. The VO 2 peak and AT values correlated with the Model for End-Stage Liver Disease score, but they more closely correlated with serum sodium and albumin levels. The handgrip strength correlated strongly with the VO 2 peak. Patients with impaired AC had prolonged hospitalization after LT, and nonsurvivors had lower AT values than survivors 1 year after transplantation (P < 0.05); this was significant in a multivariate analysis. One hundred seventy-six patients did not undergo LT; the 1-year mortality rate was 34.6%. The AT (P < 0.05) and VO 2 peak values (P < 0.001) were lower for nonsurvivors. In a multivariate analysis, AT was independently associated with nonsurvival. In conclusion, AC was markedly impaired in many patients with CLD. In patients who did not undergo transplantation, impaired AT was predictive of mortality, and in patients undergoing LT, it was related to postoperative hospitalization and survival. AC should be evaluated as a modifiable factor for improving patient survival whether or not LT is anticipated.

Research paper thumbnail of Haemodynamic response to abdominal decompression in acute Budd-Chiari syndrome

Liver International, 2011

Background: Intra-abdominal hypertension (IAH) and abdominal compartment syndrome commonly occur ... more Background: Intra-abdominal hypertension (IAH) and abdominal compartment syndrome commonly occur in patients with liver disease. Aims: We compared haemodynamic variables pre-and post-abdominal decompression in patients with acute Budd-Chiari syndrome (BCS) and patients with chronic liver disease (CLD), ascites and IAH. Methods: Patients with IAH admitted to the Liver ICU, King's College Hospital were studied. Transpulmonary thermodilution cardiac output (CO) monitoring was performed with the PiCCO s system. Results: Ten patients with decompensated BCS (median age 39 years, 20-52) and eight patients with CLD (59 years, 33-65) and tense ascites requiring paracentesis were studied. Intra-abdominal pressure (IAP) was raised in both groups pre-intervention (BSC 23 mmHg, CLD 26,. Intrathoracic blood volume (ITBVI) was persistently low in the BCS group (632 ml/m 2 , 453-924) despite volume resuscitation. Post-intervention, reduction in IAP was noted in both groups (BCS P o 0.001, CLD P o 0.0001). The ITBVI increased (P = 0.001) in the BCS group only. An increase in cardiac index (CI) and stroke volume index (SVI) was noted in both groups (BCS: CI P = 0.003, SVI: P = 0.007; CLD: CI P = 0.005, SVI P = 0.02). The central venous pressure did not change in either group and did not correlate with markers of flow (CI, SVI) or IAP. Both groups demonstrated an inverse relationship between IAP, CI and SVI. Conclusion: Patients with BCS and IAH have evidence of central hypovolaemia. In addition to raised IAP, hepatic venous obstruction and caudate lobe hypertrophy limit venous return in patients with BCS. Reduction in IAP and re-establishment of caval flow restores preload with improvement in CO.

Research paper thumbnail of Evidence of rebalanced coagulation in acute liver injury and acute liver failure as measured by thrombin generation

Liver International, 2014

Patients with liver disease often show profound abnormalities in their haemostatic system. Studie... more Patients with liver disease often show profound abnormalities in their haemostatic system. Studies using thrombin generation demonstrate rebalanced coagulation in patients with chronic liver disease. Our aim was to evaluate the haemostatic profile in patients with acute liver injury/failure (ALI/ALF) compared with healthy controls. Thrombin generation was measured in the presence and absence of thrombomodulin (TM) to activate protein C (PC) with endogenous thrombin potential (ETP; the area under the thrombin generation curve) a key parameter. Routine coagulation assays were also performed. Thirty two patients with ALI/ALF and 40 controls were recruited. Patients had grossly abnormal coagulation profiles with decreased pro- and anticoagulant factors compared with controls (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001 for all comparisons), except for median Factor VIII which was increased 247 U/dl [interquartile range: 214-347] in patients compared with 120 U/dl [97-139; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001] in controls. Mean ETP was significantly lower in patients 886 nM.min (± 436) compared with controls 1596 nM.min (± 259; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). However, when the assay was repeated with TM to activate PC, there was no significant difference in mean ETP + TM between patients and controls (632 ± 418 vs 709 ± 301 nM.min respectively; P = 0.666). Furthermore, the ETP ratio (ETP + TM/ETP) was significantly higher in patients 0.89 (0.60-0.97) compared with controls 0.48 (0.3-0.6; P = 0.002) and negatively correlated with PC (R = -0.487, P = 0.003) and Factor V (R = -0.431, P = 0.01). ALI/ALF patients have normal ETP in the presence of TM. This supports rebalanced coagulation mediated by acquired PC resistance because of the reduction in PC, Factor V and concomitant increase in Factor VIII.

Research paper thumbnail of Ammonia clearance with haemofiltration in adults with liver disease

Liver International, 2014

Background & Aims: Ammonia is recognized as a toxin central to complications of liver failure. Hy... more Background & Aims: Ammonia is recognized as a toxin central to complications of liver failure. Hyperammonaemia has important clinical consequences, but optimal means to reduce circulating levels are uncertain. In patients with liver disease, continuous renal replacement therapy (CRRT) with haemofiltration (HF) is often required to treat concurrent kidney injury, but its effects upon ammonia levels are poorly characterized. To evaluate the effect of HF at different treatment intensities on ammonia clearance (AC) and arterial ammonia concentration. Methods: Prospective study of adult patients with liver failure and arterial ammonia >100 lmol/L requiring CRRT using veno-venous HF. Arterial ammonia concentration and AC measured at 1 and 24 h after initiation of low (35 ml/kg/h) or high (90 ml/kg/h) filtration volume. Results: Twenty-four patients (10 acute liver failure, 10 chronic liver disease and 4 following liver resection) were studied. Clearance of urea and ammonia solutes correlated closely (r = 0.819, P = 0.007). Ammonia clearance correlated closely with ultrafiltration rate (r = 0.86, P < 0.001). At 1 h, AC was 39 (34-54) ml/min (low volume) vs 85 (62-105) ml/min (high volume) CRRT, (P < 0.001) and at 24 h 44 (34-63) vs 105 (82-109) ml/min, (P = 0.01). Overall, a 22% reduction in median arterial ammonia concentration was observed over 24 h of HF from 156 (137-176) to 122 (85-133) lmol/L, (P ≤ 0.0001). Conclusion: Clinically significant ammonia clearance can be achieved in adult patients with hyperammonaemia utilizing continuous VVHF. Ammonia clearance is closely correlated with ultrafiltration rate. HF was associated with a fall in arterial ammonia concentration.

Research paper thumbnail of Cerebral oedema is rare in acute-on-chronic liver failure patients presenting with high-grade hepatic encephalopathy

Liver International, 2014

Acute-on-chronic liver failure (ACLF) has a rapidly progressive disease course associated with si... more Acute-on-chronic liver failure (ACLF) has a rapidly progressive disease course associated with significant mortality. The prevalence of clinically significant cerebral oedema in ACLF is unknown. We aimed to describe the prevalence of cerebral oedema in a cohort of ACLF adult (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;18 years). We identified patients admitted to a single, specialist intensive care unit between January 2005 and January 2011 with high-grade hepatic encephalopathy (≥3) and a clinical picture of either ACLF or chronic liver disease (CLD). Patients who had undergone cranial CT imaging were identified and their imaging reviewed. The ACLF and CLD groups were compared. One thousand and eight patients with CLD were admitted. One hundred and seventy-three patients (110 male) underwent neuroimaging. Eighty-one (48 male) fulfilled criteria for ACLF. Variceal bleeding (30%) and sepsis (31%) were the most frequent precipitants of ACLF. Of those with neuroimaging from the total cohort, 30% of CT scans were normal, 30% demonstrated increased cerebral atrophy for age, 17% small vessel disease and 16% intracranial haemorrhage (ICH). Cerebral oedema was seen in three patients with ACLF only. An increased prevalence of ICH was observed in the ACLF group (23% vs. 9%, P = 0.008). The prevalence of clinically relevant cerebral oedema was low (4%) but fatal. Death was attributable to tonsillar herniation. An increased prevalence of ICH was seen in ACLF patients and remains an important differential.

Research paper thumbnail of Bacteremia, Acute Physiology and Chronic Health Evaluation II and Modified End Stage Liver Disease are independent predictors of mortality in critically ill nontransplanted patients with acute on chronic liver failure

Critical Care Medicine - CRIT CARE MED, 2010

Research paper thumbnail of Blood lactate and outcome of paracetamol-induced acute liver failure

The Lancet, 2002

Blood lactate and outcome of paracetamol-induced acute liver failure. By - Stephen M Riordan, Rog... more Blood lactate and outcome of paracetamol-induced acute liver failure. By - Stephen M Riordan, Roger Williams.

Research paper thumbnail of Hydroxyethylstarch as a risk factor for acute renal failure in severe sepsis

Research paper thumbnail of Acute liver failure

The Lancet, 2010

Acute liver failure (ALF) is an uncommon condition involving the rapid deterioration of liver fun... more Acute liver failure (ALF) is an uncommon condition involving the rapid deterioration of liver functions and coagulation in previously well patients. The loss of liver function produces a cascade of systemic effects that rapidly overwhelm patients unless acted on. The key to managing patients with ALF revolves around having the resources and expertise to manage patients with rapidly evolving multiple system failure.