Hepatorenal syndrome (HRS) occurs in patients with cirrhosis or fulminant hepatic failure and is a kind of pre-renal failure due to intense reduction of kidney perfusion induced by severe hepatic injury. While other causes of pre-renal acute kidney injury (AKI) respond to fluid infusion, HRS does not. HRS incidence is 5% in children with chronic liver conditions before liver transplantation. Type 1 HRS is an acute and rapidly progressive form that often develops after a precipitating factor, including gastrointestinal bleeding or spontaneous bacterial peritonitis, while type 2 is considered a slowly progressive form of kidney failure that often occurs spontaneously in chronic ascites settings. HRS pathogenesis is multifactorial. Cirrhosis causes portal hypertension; therefore, stasis and release of vasodilator substances occur in the hepatic vascular bed, leading to vasodilatation of splanchnic arteries and systemic hypotension. Many mechanisms seem to work together to cause this imbalance: splanchnic vasodilatation; vasoactive mediators; hyperdynamic circulation states and subsequent cardiac dysfunction; neuro-hormonal mechanisms; changes in sympathetic nervous system, renin-angiotensin system, and vasopressin. In patients with AKI and cirrhosis, fluid expansion therapy needs to be initiated as soon as possible and nephrotoxic drugs discontinued. Once HRS is diagnosed, pharmacological treatment with vasoconstrictors, mainly terlipressin plus albumin, should be initiated. If there is no response, other options can include surgical venous shunts and kidney replacement therapy. In this regard, extracorporeal liver support can be a bridge for liver transplantation, which remains as the ideal treatment. Further studies are necessary to investigate early biomarkers and alternative treatments for HRS.

Early identification of children with decompensated chronic liver disease (DCLD) at risk of short-term mortality helps improve outcome. We aimed to evaluate the predictors of outcome and role of Child-Pugh, pediatric end-stage liver disease (PELD) and pediatric chronic liver failure sequential organ failure assessment (pCLIF-SOFA) score for prognosticating 28-day mortality in children with DCLD.

DCLD children were prospectively evaluated with a clinico-laboratory proforma and followed for 28 days to determine outcome. Child-Pugh, PELD and pCLIF-SOFA were calculated at admission. Univariate and multivariate analysis was performed to identify the best predictors of outcome.

A total of 110 children (74 boys, 96 [4-204] months) were enrolled and 37 (33.6%) died at 28 days. Significant risk factors for mortality were a higher international normalized ratio (hazard ratio [HR] 1.17; 95% CI 1.04-1.31; p <0.001) and bilirubin (HR 1.04; 95% CI 1.01-1.08; p <0.001), lower albumin (HR 0.46; 95% CI 0.27-0.77; p = 0.03) and sodium (HR 0.93; 95% CI 0.89-0.98; p = 0.01), absence of treatable etiology (HR 2.00; 95% CI 1.40-2.87; p = 0.001) and presence of organ failure (HR 3.22; 95% CI 1.98-10.58; p <0.001). Organ failure and serum sodium were independent predictors of poor outcome on multivariate analysis. pCLIF-SOFA (16 [9-22] vs. 9 [5-15]), Child-Pugh (11 [9-15] vs. 10 [8-14]) and PELD (22.2 [7.5-45.3] vs. 15.3 [4.5-23.9]) scores were significantly higher in non-survivors. The area under the curve was 0.977 for pCLIF-SOFA, 0.815 for Child-Pugh score, and 0.741 for PELD score. A pCLIF-SOFA score of ≥11 identified 28-day mortality with a sensitivity and specificity of 94.9% and 91.5%, respectively.

Thirty-four percent of children with DCLD have a poor short-term outcome. Organ failure and low serum sodium are independent predictors of outcome. pCLIF-SOFA performs better than Child-Pugh and PELD in prognostication of 28-day mortality. Our study supports the use of scores based on organ failure in prognosticating children with DCLD.

The ability to predict the course of a disease is an important part of the assessment, enabling timely interventions that improve outcomes. We evaluated the outcome (death vs. survival) and compared three different scoring systems for their ability to predict mortality within 28 days in children with decompensated chronic liver disease (DCLD). One-third of children with DCLD died within 28 days and the pediatric chronic liver failure sequential organ failure assessment score, which considers the main organ systems of the body (lungs, liver, brain, kidney, blood and cardiac) fared better for identification of children with a poor outcome than the Child-Pugh and pediatric end-stage liver disease score which comprise of only liver-related parameters. Our study supports the use of scores based on organ failure in prognosticating children with DCLD.

Pediatric literature on spontaneous bacterial peritonitis (SBP) is limited. We evaluated the prevalence, subtypes, clinical profile, and effect on outcome of ascitic fluid infection (AFI) in children with liver disease.

Children with liver disease-related ascites and subjected to paracentesis were classified as no-AFI and AFI (SBP, culture-negative neutrocytic ascites [CNNA], and monomicrobial non-neutrocytic bacterascites). Clinical and laboratory parameters, in-hospital mortality, and outcome in follow-up were noted.

Two hundred sixty-two children (163 boys; age 84 [1-240] months, chronic liver disease [CLD, n = 173], non-CLD [n = 89]) were enrolled. A total of 28.6% (n = 75) had SBP/CNNA, more common in CLD than non-CLD (55/173 [31.7%] vs 20/89 [22.4%]; P = 0.1). A total of 50.6% SBP/CNNA cases were symptomatic for AFI. Gram-negative bacilli were isolated from 70% SBP cases. Twenty-five percent (18/72) CLD children with AFI had a poor hospital outcome, with INR, Child-Pugh score and gastrointestinal bleeding predicting outcome on multivariate analysis. Patients with CLD with SBP had higher in-hospital mortality (10/20 vs 5/35; P = 0.01) than those with CNNA, but similar Child-Pugh score (12[7-15] vs 11[7-14]; P = 0.1), recurrence of AFI (3/9 vs 6/24; P = 0.6) and mortality in follow-up (22.2% vs 25%; P = 0.1). Patients with CLD with SBP/CNNA had higher mortality over 1 year follow-up than no-AFI (24.2% [8/33] vs 12.2% [7/57]; P = 0.1) but the difference was not significant.

A total of 28.6% children with liver disease-related ascites have SBP/CNNA; 50% are symptomatic. Patients with CLD with SBP/CNNA have a mortality of 24% over 1year follow-up. CLD with SBP is similar to CNNA except for higher in-hospital mortality.

Acute kidney injury (AKI) is a major complication in children with hepatic failure which leads to increased morbidity and mortality. The aim of this study was to provide paediatric data on the prevalence of dialysis-dependent AKI (dAKI), the feasibility and efficacy of dialysis methods and outcome.

We conducted a retrospective analysis of 367 children listed for orthotopic liver transplantation (OLT) in our centre during the past decade.

Data on 30 children (15 boys, 15 girls) were compiled for retrospective analysis, and data on dialysis feasibility and efficacy were available for 26 of these. Median age was 3.5 (range 0.4-17.7) years. Median MELD (Model For End-Stage Liver Disease) score was 33. dAKI was caused by hepato-renal syndrome in 16 of the 30 children. Twenty-one patients were treated with continuous veno-venous haemofiltration (CVVH), and nine patients received peritoneal dialysis (PD). Overall mortality was 77%. Mortality within the PD-group was 100 % versus 67% in the CVVH-group (p = 0.039). Urea reduction rate within the first 24 h of treatment was 12.9% in the PD group and 23.5% in the CVVH group (p = 0.019).

Children with end-stage liver disease have a high risk for dAKI associated with high mortality. CVVH is associated with better efficacy and less mortality than PD.

The management of children with end-stage chronic liver disease and acute liver failure mandates a multidisciplinary approach and intense monitoring. In recent years, considerable progress has been made in developing specific and supportive medical measures, but studies and publications have mainly concerned adult patients. Therapeutic approaches to complications of end-stage chronic liver disease and acute liver failure (e.g. refractory ascites, hepatorenal syndrome, encephalopathy, and cerebral edema) that may be applied to children are reviewed in this article.Mild-to-moderate ascites should be managed by modest salt restriction and oral diuretic therapy in the first instance. Large volume paracentesis associated with colloid volume expansion and diuretic therapy may be effective for acute relief. Treatment of hepatorenal syndrome type 1 with vasopressin analogs (terlipressin) is recommended prior to liver transplantation in order to improve renal function. Prevention and treatment of chronic hepatic encephalopathy are directed primarily at controlling the events that may precipitate hepatic encephalopathy and at reducing ammonia generation and increasing its detoxification or removal. In addition to reduction of gut ammonia production using non-absorbable disaccharides such as lactulose and/or antibacterials such as neomycin, sodium benzoate may be used on a long-term basis to prevent, stabilize, or improve hepatic encephalopathy. The management of hepatic encephalopathy in acute liver failure is considerably more unsatisfactory; treatment is aimed at preventing brain edema and intracranial hypertension. Extracorporeal liver support devices are now used commonly in critically ill children with acute renal failure, advanced hepatic encephalopathy, cerebral edema, intracranial hypertension, and severe coagulopathy. Continuous renal replacement therapy could potentially help support patients until liver transplantation is performed or liver regeneration occurs. The Molecular Adsorbent Recirculating System (MARS or albumin dialysis) is the liver support system most frequently used worldwide in adults and appears to offer distinct advantages over hepatocyte-based systems. There are no specific medical therapies or devices that can correct all of the functions of the liver. Apart from a few metabolic diseases presenting with severe liver dysfunction for which specific medical therapies may preclude the need for liver transplantation, liver transplantation still remains the only definitive therapy in most instances of end-stage chronic liver disease and acute liver failure. Future research should focus on gaining a better understanding of the mechanisms responsible for liver cell death and liver regeneration, as well as developments in hepatocyte transplantation and liver-directed gene therapy.

Renal function greatly influences mortality rates in the early phase following hematological stem cell transplantation (HSCT) in childhood, as well as the quality of life in long-term survivors. Nevertheless, the number of studies in pediatric populations is limited and some important aspects of kidney function after HSCT have only been elucidated in adults. The incidence of acute renal failure (ARF) immediately after HSCT in pediatric patients is between 25% and 50%, with 5%-10% of children requiring renal replacement therapy. Doubling of serum creatinine is associated with a twofold increase in mortality. However, the need for dialysis leads to a further increase in mortality rates to 80%-90%. Specific renal syndromes appear at different times following HSCT, revealing a similar pattern in children and adult patients. In both children and adults, impaired renal function associated with liver impairment (hepatorenal syndrome) is the most important cause for ARF. Therapeutic approaches have not been able to reduce the frequency or to improve outcome so far. In adults surviving long term, bone marrow transplant (BMT) nephropathy is the most frequent renal complication, although a considerable variation in incidence (up to 70%) has been published, partly due to various definitions and manifestations. Little is known about the long-term outcome of renal function in patients treated with HSCT in childhood. However, chronic renal failure has been reported in 0%-28%, but no end-stage renal failure has been published so far. Tubular function following HSCT is rarely investigated, although its impact on long-term survivors of BMT in childhood might be of some importance, especially for growth and bone metabolism.

This paper provides a review of the practice of liver transplantation with the main emphasis on UK practice and indications for transplantation.

This section reviews the process of referral and assessment of patients with liver disease with reference to UK practice.

The practice of brainstem death and cadaveric organ donation is peculiar to individual countries and rates of donation and potential areas of improvement are addressed.

The technical innovations that have led to liver transplantation becoming a semi-elective procedure are reviewed. Specific emphasis is made to the role of liver reduction and splitting and living related liver transplantation and how this impacts on UK practice are reviewed. The complications of liver transplan-tation are also reviewed with reference to our own unit. Immunosuppression:The evolution of immunosuppression and its impact on liver transplantation are reviewed with some reference to future protocols.

The role of retransplantation is reviewed.

The results of liver transplantation are reviewed with specific emphasis on our own experience.

The future of liver transplantation is addressed.

This paper provides a review of the practice of liver transplantation with the main emphasis on UK practice and indications for transplantation.

This section reviews the process of referral and assessment of patients with liver disease with reference to UK practice.

The practice of brainstem death and cadaveric organ donation is peculiar to individual countries and rates of donation and potential areas of improvement are addressed.

The technical innovations that have led to liver transplantation becoming a semi-elective procedure are reviewed. Specific emphasis is made to the role of liver reduction and splitting and living related liver transplantation and how this impacts on UK practice are reviewed. The complications of liver transplan-tation are also reviewed with reference to our own unit. Immunosuppression:The evolution of immunosuppression and its impact on liver transplantation are reviewed with some reference to future protocols.

The role of retransplantation is reviewed.

The results of liver transplantation are reviewed with specific emphasis on our own experience.

The future of liver transplantation is addressed.

As many as 38% of combined liver-kidney transplant (LKTx) procedures performed nationally may be done for the renal diagnosis of hepatorenal syndrome (HRS). This study was designed to compare the national results with those at our medical center and to determine if combined LKTx provides any benefit over isolated liver transplant (LTx) to HRS patients.

Data on 29 combined LKTx and 79 HRS patients at our center were collected and compared with the national data on 414 LKTx and 2442 patients with serum creatinine >2.0 mg/dl receiving isolated LTx from 1988 to 1995.

United Network of Organ Sharing data revealed 5-year patient survival of 62.2% for LKTx recipients and 50.4% for patients with serum creatinine >2.0 mg/dl receiving isolated LTx (P=0.0001). Our center results demonstrated 5-year patient survival of 48.1% for LKTx patients, 67.1% for HRS patients receiving isolated LTx, and 70.1% for patients with serum creatinine >2.0 mg/dl receiving isolated LTx (P not significant comparing all groups). Intensive care unit status and preoperative dialysis rates were similar in those HRS patients who did and those who did not need future KTx.

National data would suggest a survival benefit of combined LKTx over isolated LTx for those patients with poor renal function, specifically those with HRS, whereas our center's results suggest otherwise. Unfortunately, we could not identify any preoperative risk factors in the HRS patients, or in the broader group of patients with renal insufficiency at our center, that would indicate the need for future renal transplantation. We believe that HRS patients can be successfully managed with isolated LTx.