Long-term outcome of liver transplant patients with Budd-Chiari syndrome secondary to myeloproliferative neoplasms.

BACKGROUND: A considerable proportion of patients receiving liver transplants for Budd-Chiari syndrome (BCS) suffer from myeloproliferative neoplasms (MPN). This study evaluated the long-term prognosis of liver-transplanted patients with BCS secondary to MPN and the effect of immunosuppression on MPN progression. METHODS: A total of 78 patients with BCS were evaluated between 1982 and 2013. Of those, 40 patients suffered from polycythaemia vera (PV) and essential thrombocythaemia (ET). One patient had primary myelofibrosis (PMF). All patients received the standard immunosuppressive regimen. We retrospectively evaluated the long-term survival, clinical course and laboratory parameters of patients with MPN. RESULTS: Exactly 29/41 patients (71%) with MPN survived ≥ 3 years [mean age 36 ± 11 years; females n = 27 (93%)]. Mean follow-up after orthotopic liver transplantation (OLT) was 12.4 ± 7.3 years (range 3-28 years). Five- and 10-year survival rates were not significantly different in patients with and without MPN (P = 0.81 and P = 0.66 respectively) or in patients with PV and ET (P = 0.29 and P = 0.55 respectively). Thrombosis and bleeding developed in 7/29 (24%) long-term MPN survivors with no significant difference between ET and PV (P = 0.18). In the long-term follow-up, there was no evidence of progression to overt myelofibrosis or acute myeloid leukaemia (AML). In the uni- and multivariate Cox-regression analyses, MPN did not influence survival after OLT. CONCLUSIONS: Budd-Chiari syndrome patients with and without underlying MPN had similar long-term survival rates after OLT. There was no evidence of enhanced progression of MPN after OLT secondary to immunosuppressive therapy. However, major haemorrhage and recurrent thrombosis contributed to morbidity and mortality after OLT in those patients.

Good long-term outcome of Budd-Chiari syndrome with a step-wise management.

UNLABELLED: Budd-Chiari syndrome (BCS) is a rare, life-threatening disease caused by obstruction of hepatic venous outflow. The aim of the study was to assess long-term outcome and identify prognostic factors in BCS patients managed by a step-wise approach using anticoagulation, angioplasty/thrombolysis, transjugular intrahepatic portosystemic shunting (TIPS), and orthotopic liver transplantation (OLT). We reviewed long-term data on 157 patients previously included by the European Network for Vascular Disorders of the Liver, a multicenter prospective study of newly diagnosed BCS patients in nine European countries. Patients were followed for a median of 50 months (range, 0.1-74.0). During the study, 88 patients (56%) received at least one invasive intervention (22 patients angioplasty/thrombolysis, 62 TIPS, and 20 OLT) and 36 (22.9%) died. Most interventions and/or deaths occurred in the first 2 years after diagnosis. The Rotterdam score was excellent in predicting intervention-free survival, and no other variable could significantly improve its prognostic ability. Moreover, BCS-TIPS prognostic index (PI) score (based on international normalized ratio, bilirubin, and age) was strongly associated with survival and had a discriminative capacity, which was superior to the Rotterdam score. CONCLUSIONS: The current study confirms, in a large cohort of patients with BCS recruited over a short period, that a step-wise treatment approach provides good long-term survival. In addition, the study validates the Rotterdam score for predicting intervention-free survival and the BCS-TIPS PI score for predicting survival.

Ultrasound presentation of abdominal tuberculosis in a German tertiary care center.

OBJECTIVE: Abdominal tuberculosis (TB) is a relatively rare disease in most of Europe and the typical clinical and sonographic findings in this setting have not been studied. We aimed to define sonographic findings that should alert an examiner to the possibility of abdominal TB in a low endemic region. METHODS: Case records of 17 patients with proven (n = 11) or highly likely (n = 6) abdominal TB detected in the gastrointestinal ultrasound unit at a German tertiary care center in 2003-2013 were analyzed retrospectively. Findings were compared with reported series from high-prevalence regions. RESULTS: While 76% of patients had an immigrant background, only 35% had a condition associated with immunosuppression. Lymphadenopathy was present in all cases of abdominal TB, while it was absent in 28% of patients from a control group with proven abdominal sarcoidosis. Moreover, retroperitoneal lymphadenopathy was significantly more common in TB. Other findings in patients with abdominal TB in descending order of frequency were ascites, altered hepatic texture, splenomegaly, splenic lesions, peritoneal thickening, intestinal wall lesions, hepatic lesions and hepatomegaly. 76% of abdominal TB patients had 2 or more pathological findings. CONCLUSIONS: Multiple pathological intra-abdominal findings including lymphadenopathy should alert the examiner to the possibility of abdominal TB.

Effects of fractionated plasma separation and adsorption on survival in patients with acute-on-chronic liver failure.

BACKGROUND & AIMS: Fractionated plasma separation and adsorption (FPSA) is an extracorporeal procedure that supports liver function by removing endogenous toxins that cause complications from acute-on-chronic liver failure (AOCLF). We performed a randomized trial to investigate survival of patients with AOCLF treated with FPSA. METHODS: Patients with AOCLF were randomly assigned to groups given a combination of FPSA and standard medical therapy (SMT) (FPSA group, n = 77) or only SMT (SMT group, n = 68). The Prometheus liver support system was used to provide 8 to 11 rounds of FPSA (minimum of 4 hours each) for 3 weeks. Primary end points were survival probabilities at days 28 and 90, irrespective of liver transplantation. RESULTS: Baseline clinical parameters and number of transplant patients were similar between study arms. Serum bilirubin level decreased significantly in the FPSA group but not in the SMT group. In an intention-to-treat analysis, the probabilities of survival on day 28 were 66% in the FPSA group and 63% in the SMT group (P = .70); on day 90, they were 47% and 38%, respectively (P = .35). Baseline factors independently associated with poor prognosis were high SOFA score, bleeding, female sex, spontaneous bacterial peritonitis, intermediate increases in serum creatinine concentration, and combination of alcoholic and viral etiology of liver disease. There were no differences between the 2 groups in the incidence of side effects. CONCLUSIONS: Among all patients with AOCLF, extracorporeal liver support with FPSA does not increase the probability of survival. Further studies are needed to assess whether therapy might be beneficial in specific subsets of patients.

No evidence of substantial growth progression or complications of large focal nodular hyperplasia during pregnancy.

OBJECTIVE: Focal nodular hyperplasia (FNH) is a benign liver tumor considered to develop under the influence of estrogens. Whether women with known FNH are at higher risk of growth progression and complications during pregnancy is still controversially discussed. The authors investigated the growth pattern of FNH during pregnancy and possible related complications. MATERIALS AND METHODS: Twenty pregnant women with FNH were followed by the authors' center. Before pregnancy, diagnosis of FNH was usually established by contrast-enhanced ultrasound. During pregnancy, monitoring of FNH was performed by conventional ultrasound. Furthermore, a questionnaire was sent to all patients. RESULTS: Patient's age ranged from 24 to 36 years. Mean size of FNH before pregnancy was 58.5 ± 22.7 mm. It did not vary significantly during pregnancy (fourth month of pregnancy: 58.1 ± 23.0 mm; after pregnancy: 55.5 ± 26.8 mm; -8%; n.s.). Only in three patients, growth of FNH by 18 ± 6% was observed, while FNH size remained constant in 7 patients and even declined by -11 ± 6% in 10 patients. There were no FNH-related complications. The questionnaire was sent back by 16 patients (80%). All responding patients took oral contraceptives in the past over a mean 12.4 ± 4.4 years. Previous pregnancies were reported by 38% of patients. FNH-related fears were expressed by 63% of patients, but no FNH-related complications or symptoms during pregnancy were noted. CONCLUSIONS: This study demonstrates that women with FNH are not at risk of significant growth progression or FNH-related complications. Pregnancy should not be discouraged in these patients but careful advice and guidance are necessary.

High rate of unperceived hearing loss in patients after liver transplantation.

AIM: We recently published the high frequency of perceived hearing impairment in adults after orthotopic liver transplantation (OLT). To obtain objective data in addition to the questionnaires, audiometric data of 70 patients' post-OLT were analyzed. METHODS: Hearing tests were obtained from 70 patients who were in follow-up 6.5 ± 4.3 yr after OLT. Thirty-eight of these patients (53%) reported the development of a hearing problem post-OLT, while 14 patients already noticed hearing loss prior to OLT (21%). Eighteen patients did not report any hearing problems (26%). RESULTS: Audiometry was within the normal range only in five patients (7%). Signs of mild or moderate hearing loss were found in 12 (17%) and 28 patients (40%), respectively. In 25 patients, audiometry revealed even severe hearing loss (36%). In 86% of patients, hearing loss was bilateral affecting all frequency areas in 63%. Of the 18 patients without subjective hearing impairment, moderate or severe hearing loss was found in 50% of audiometries. Mean maximal hearing loss was -62 ± 30 dB with worse results in patients reporting hearing problems (p < 0.03). CONCLUSIONS: We confirmed the high incidence of reported hearing loss in adults post-OLT by objective audiometric data. Pathological hearing tests were even found in many patients without perception of hearing impairment.

Fractionated plasma separation and adsorption: current practice and future options.

Fractionated plasma separation and adsorption (FPSA) is a method of albumin dialysis that is integrated into an extracorporeal liver support device (Prometheus(®)). This concept allows the effective removal of both protein-bound and water-soluble substances without the need for external albumin. Several studies comparing the in vivo extraction capacities of FPSA and molecular adsorbent recirculating system (MARS) concluded that detoxification by FPSA seems to be more effective than by MARS. Overall, FPSA therapy has been shown to be safe. Over the last few years, the anticoagulation protocol for FPSA therapy was optimised by using regional anticoagulation with citrate to avoid clotting of system components. Recently, the results of a large randomised-controlled multicentre trial (HELIOS) have been presented. Survival after 1 and 3 months was evaluated in 145 patients with acute-on-chronic liver failure comparing FPSA therapy with standard medical treatment versus standard medical treatment alone. There was no statistically significant survival benefit for patients undergoing FPSA therapy. However, patients with hepatorenal syndrome type I or MELD score >30 showed a significant survival benefit under FPSA in a predefined subgroup analysis. Furthermore, there have been promising results with FPSA in the treatment of refractory cholestatic pruritus. Regarding acute liver failure, only few data are currently available.

Liver transplantation: A new risk factor for intestinal intussusceptions.

BACKGROUND: Intestinal intussusception in adults is associated with chronic inflammatory bowel disease, celiac disease, abdominal tumors or previous abdominal surgery but most often of unknown origin. AIM: The aim of our study was to evaluate circumstances and identify risk factors for intussusceptions. METHODS: All 65,928 abdominal ultrasound examinations performed at our tertiary medical center between January 2001 and June 2008 were analyzed retrospectively for the diagnosis "intussusception". After identifying individuals with sonographically proven intussusception we analyzed various patients' characteristics including age, gender and underlying disease as well as sonographic findings such as localization of the intussusception, absence or presence of ascites and lymph nodes. RESULTS: We identified 32 cases of intussusceptions [mean age 45 years (range 18 to 88); 18 patients were male]. Twelve patients (38%) had a history of abdominal surgery including 8 patients who had undergone liver transplantation (2 patients with primary sclerosing cholangitis, 1 patient with cystic fibrosis, 1 patient with sarcoidosis, 1 patient with hepatocellular carcinoma and HCV infection, 1 patient with autoimmune hepatitis, 1 patient with Crigler-Najar-syndrome and one patient with echinococcus). A hepaticojejunostomy had been performed in 4 of the patients after liver transplantation. Liver transplanted patients were significantly overrepresented in the intussusceptions group compared with the overall cohort of patients undergoing abdominal ultrasound examination (25% vs. 8%, Chi-Square-test, p = 0.0023). CONCLUSION: In our retrospective study liver transplantation, in particular with hepaticojejunostomy, was identified as a new major risk factor for intestinal intussusceptions

Membranous Budd-Chiari syndrome in Caucasians.

OBJECTIVE: Budd-Chiari syndrome (BCS) is characterized by an obstruction of hepatic venous outflow. Membranous obstruction of the inferior vena cava (IVC) is a curable cause of primary BCS but is very rare in Western Europe. To date, there is only very limited information on membranous BCS in the Western world. We here report the diagnosis and management of five Caucasian patients with membranous BCS. MATERIAL AND METHODS: Out of 23 patients with BCS diagnosed between 2004 and 2007 we identified five with a membranous web of the IVC. Diagnostic evaluation of BCS included laboratory tests, ultrasound Doppler imaging, CT and MRI. RESULTS: The clinical presentation of membranous BCS was heterogeneous. The time frame from first clinical symptoms to diagnosis ranged from 3 weeks to 60 years. Liver cirrhosis was misdiagnosed in 4/5 patients. CT did not establish the correct diagnosis of membranous BCS in any of our patients. In contrast, abdominal Doppler ultrasonography showed collaterals and a web in the IVC which was confirmed by Doppler-MRI and hepatovenography. Four patients underwent interventional treatment with balloon dilatation of short-segment venous stenoses or complete occlusions. Therapy was successful: in all cases it resulted in a normalized extrahepatic blood flow and reduction of spleen size. CONCLUSIONS: Membranous BCS may be underdiagnosed in Caucasians. Doppler ultrasound should be used as the initial diagnostic procedure for membranous BCS. Although CT is considered the "gold standard" in addition to angiography, it could not detect membranous obliteration in our cases. Patients can be effectively treated by interventional endovascular therapy.

Removal of asymmetric dimethylarginine during artificial liver support using fractionated plasma separation and adsorption.

OBJECTIVE: Asymmetric dimethylarginine (ADMA) is the most potent endogenous nitric oxide synthase inhibitor. Elevated ADMA levels have been linked to increased mortality in different patient populations. Key regulation of ADMA levels mainly takes place in the liver. Hence, ADMA is elevated in liver disease. There is no specific pharmacological treatment to lower the elevated ADMA levels. Hemodialysis is of limited efficiency in removing ADMA as it is highly protein bound. Prometheus is an extracorporeal liver support system which allows the removal of protein-bound toxins. We assessed the efficiency of the Prometheus system in reducing high ADMA levels in patients with liver failure. MATERIAL AND METHODS: We studied nine patients with acute-on-chronic liver failure and concomitant renal failure already necessitating hemodialysis. Seven patients needed intensive care treatment. Two consecutive sessions of Prometheus therapy of each 4 h were performed in all patients. ADMA and its structural isomer symmetrical dimethylarginine (SDMA) were determined using liquid chromatography-mass spectrometry. RESULTS: ADMA levels correlated to model for end stage liver disease (MELD) score (r(s) = 0.62; p < 0.0001). Before Prometheus was started, levels of ADMA and SDMA were elevated (1.36 +/- 0.5 micromol/l and 1.90 +/- 0.4 micromol/l, respectively). During Prometheus treatments, plasma levels of ADMA dropped by a mean 25% (p < 0.0001) and SDMA levels by 22% (p < 0.0001). However, there was a significant rebound of ADMA levels between the two therapy sessions (p < 0.01). CONCLUSIONS: This study shows for the first time that plasma levels of ADMA can be effectively lowered by an artificial liver support system (Prometheus). Effective elimination of ADMA might explain some of the beneficial clinical effects of these systems in patients with liver failure.

Changes in plasma amino acids during extracorporeal liver support by fractionated plasma separation and adsorption.

In patients with liver failure, amino acid dysbalance is common and associated with hepatic encephalopathy. Prometheus is a newly designed extracorporeal liver support system based upon fractionated plasma separation and adsorption (FPSA). We evaluated the influence of FPSA on plasma amino acid patterns in patients with liver failure and hepatic encephalopathy. We studied nine patients with acute-on-chronic liver failure, hepatic encephalopathy, and concomitant renal failure. A single session of FPSA therapy for 5 +/- 1 h was performed in all patients. Twenty-six different plasma amino acids were measured by high-performance liquid chromatography before and after FPSA treatment. Total amino acids as well as Fischer index were calculated. Additionally, a variety of clinical and biochemical parameters were assessed. Before FPSA was started, plasma levels of most amino acids were elevated. Plasma ammonia levels correlated with glutamine levels (P < 0.04). During FPSA, plasma levels of nearly all amino acids significantly decreased except for branched-chain amino acids. The Fischer index improved without reaching statistical significance. FPSA therapy tends to normalize plasma amino acids in patients with combined liver and renal failure. This may contribute to positive pathophysiologic effects, especially on hepatic encephalopathy. However, the clinical significance of these findings needs to be further evaluated.

Efficacy and safety of anticoagulation with heparin versus heparin plus epoprostenol in patients undergoing extracorporeal liver support with Prometheus.

Anticoagulation for extracorporeal liver support is delicate due to underlying coagulation disorders in patients with liver failure and to the associated elevated bleeding risk. To date, there has been no detailed report on anticoagulation issues in patients treated with Prometheus, a device based on the principle of fractionated plasma separation and adsorption. We studied 17 patients from two centers treated with Prometheus, comparing standard anticoagulation with heparin (15 treatments) and a combination of heparin and the synthetic prostacyclin epoprostenol (22 treatments). Standard coagulation tests, proteins C and S, and thrombin-antithrombin (TAT) complex were determined, and adverse events were recorded. All but two treatments could be completed as scheduled, although filter exchange due to filter clotting was required in 24% of the treatments. Three out of 17 patients developed severe bleeding complications within 24 h of treatment. There were no overt thrombotic events. Addition of epoprostenol neither reduced coagulation-related adverse events nor improved standard coagulation parameters. Protein C, but not protein S, showed a significant reduction (23 +/- 18%) after Prometheus treatments, but levels rebounded to baseline within 18 h. TAT levels--a measure for activation of coagulation--were only altered by Prometheus in patients where TAT was already elevated before treatment. In conclusion, anticoagulation of Prometheus with heparin is feasible but still associated with a relatively high frequency of filter clotting and a considerable risk of severe bleeding in this high-risk patient population. As addition of epoprostenol did not prove beneficial, other strategies, such as regional anticoagulation with citrate, should be further evaluated.

The treatment of acute liver failure with fractionated plasma separation and adsorption system: Experience in 85 applications.

INTRODUCTION: Artificial liver support systems represent a potential useful option for the treatment of liver failure. The outcomes of patients treated with the fractionated plasma separation and adsorption (FPSA) system are presented. PATIENTS AND METHODS: FPSA was performed 85 times for 27 patients (median 3 treatments/patient) with liver failure [85.2% acute liver failure (ALF) and 14.8% acute-on-chronic liver failure] using the Prometheus 4008H (Fresenius Medical Care) unit. Citrate was used for anticoagulation. A variety of clinical and biochemical parameters were assessed. Comparisons between pretreatment and post-treatment data were performed using paired t-test. RESULTS: The 85 sessions had a mean duration of 6 h. There were significant decreases in total bilirubin (13.18 +/- 9.46 mg/dL vs. 9.76 +/- 7.05 mg/dL; P < 0.0001), ammonia (167.6 +/- 75 mg/dL vs. 120 +/- 43.8 mg/dL; P < 0.0001), blood urea nitrogen (BUN; 12.55 +/- 13.03 mg/dL vs. 8.18 +/- 8.15 mg/dL; P < 0.0001), creatinine (0.54 +/- 0.47 mg/dL vs. 0.46 +/- 0.37 mg/dL; P = 0.0022) levels, and in pH (7.48 +/- 0.05 vs. 7.44 +/- 0.08; P = 0.0045). Four patients (14.8%) received liver transplantation after the treatments; in nine patients, transplantation was not necessary anymore (33%); the remaining 14 patients did not receive a transplantation because they were either not appropriate candidates or no organ was available. Overall survival was 48.1% (4 transplanted and 9 treated patients). No hematological complications related to FPSA were observed. CONCLUSIONS: FPSA system is a safe and effective detoxification method for patients with liver dysfunction, including ALF. The system is useful as a symptomatic treatment before liver transplantation; in up to 1/3 of the cases, it can even be used as a sole method of treatment.

Evaluation of sound speed for detection of liver fibrosis: prospective comparison with transient dynamic elastography and histology.

OBJECTIVE: The degree of liver fibrosis determines the prognosis and treatment of patients with chronic viral hepatitis. Transient elastography (TE) has been accepted as a noninvasive method for assessment of liver fibrosis. Sound velocity (SV) changes are also dependent on elastic properties of tissue. The aim of this pilot study was to evaluate whether SV estimation of liver tissue allows the determination of fibrosis stages in patients with chronic viral hepatitis. METHODS: Prospectively, 50 healthy volunteers and 149 patients received stiffness (TE, 50-Hz vibrator, 5-MHz array) and SV (conventional ultrasound, C5-2-MHz transducer) measurements. Eighty-four patients received representative liver biopsies. The estimated SV and stiffness were compared using liver biopsy as a reference (METAVIR fibrosis stage [F] scoring system [Hepatology 1996; 24:289-293]). Descriptive statistics, analysis of variance, receiver operating characteristic curve analysis, and box plot analysis as well as intra-operator and interoperator reproducibility analyses were performed. RESULTS: The SV ranged from 1540 to 1650 m/s. The mean SV ± SD was significantly different between healthy volunteers (1559 ± 11 m/s) and patients with F0-F3 (1575 ± 21 mm/s) and F4 (1594 ± 18 m/s) disease (P < .001). For detection of liver cirrhosis, the area under the receiver operating characteristic curve for SV was 0.80 (95% confidence interval, 0.69-0.89). With a cutoff value of 1589 m/s, the sensitivity, specificity, and positive and negative predictive values of SV for detection of liver cirrhosis were 82%, 76%, 70%, and 86%, respectively. Sound velocity measurements were reproducible (15%) and had acceptable operator independence (19%). CONCLUSIONS: The SV of liver tissue depends on the fibrosis stage. An SV of 1589 m/s or higher detects cirrhosis with high sensitivity. Therefore, SV measurement appears to be a promising new method for noninvasive quantification of liver fibrosis.

Food intake increases liver stiffness in patients with chronic or resolved hepatitis C virus infection.

BACKGROUND AND AIMS: Transient elastography is increasingly being used in patients with chronic liver disease. It has proven particularly useful to identify patients with advanced fibrosis or cirrhosis, while classification of no or little fibrosis appears to be difficult. In general, stiffness values <6 kPa are considered normal, whereas patients with higher levels are candidates for a disease-specific treatment or further diagnostic evaluation. Parameters influencing liver stiffness may include food intake that increases liver blood flow. METHODS: In a pilot study, transient elastography was performed in eight patients with chronic hepatitis C at fasting and serially for 180 min after intake of a standardized breakfast. Confirmatory, 56 patients and 19 controls underwent liver stiffness determination at fasting, directly after meal intake and 1 h after breakfast. RESULTS: Liver stiffness significantly increased immediately after food intake for up to 60 min (P=0.01) before normalizing after 180 min. An intraindividual analysis showed a significant increase in 22 out of 43 patients with an initial liver stiffness 6 kPa after food intake, potentially leading to unnecessary treatment or diagnostic procedures. CONCLUSION: Food intake increases liver stiffness in patients with hepatitis C virus infection and healthy controls. To standardize liver stiffness evaluation, we suggest measurement in the fasting condition.

Prevalence of alpha-fodrin antibodies in patients with chronic hepatitis C infection and Sjögren syndrome.

OBJECTIVE: Hepatitis C virus infection (HCV) is associated with various extrahepatic manifestations. Antibodies against alpha-fodrin are associated with sicca symptoms and may valuable diagnostic markers in patients with primary Sjögren syndrome (SS) lacking Ro antibodies. The frequency and role of alpha-fodrin antibodies in patients with chronic HCV infection are unknown. The aim of this study was to investigate the prevalence of alpha-fodrin antibodies in HCV-infected patients with SS. MATERIAL AND METHODS: Alpha-fodrin antibodies were detected more often in hepatitis C patients (25%; n=142) than in HBV-infected individuals (8%; n=49) and healthy controls (6%; n=174) (p<0.01). Based on these findings, we investigated the frequency of sicca symptoms in a second cohort and studied other antibodies associated with SS. RESULTS: HCV-infected individuals showed sicca symptoms in 53% of cases as determined by the Saxon and Schirmer tests, which was more frequent than in healthy controls (1%, p<0.01) but not in patients with autoimmune liver disease (51%). Antibodies specific for Ro (SS-A) were significantly more common in patients with autoimmune liver disease than in HCV-infected patients and healthy controls (16% versus 1% and 0%, p<0.003). SS was found in 18% of patients with HCV, in 15% of patients with autoimmune liver disease and in 1% of healthy controls. However, we found no correlation between sicca symptoms and the presence of antibodies against alpha-fodrin, Ro and La. CONCLUSIONS: Patients with chronic HCV infection show a high prevalence of sicca symptoms and antibodies against alpha-fodrin. However, neither the frequency nor the severity of symptoms correlated with the presence of alpha-fodrin antibodies.

Prognostic implications of lactate, bilirubin, and etiology in German patients with acute liver failure.

BACKGROUND & AIMS: Among the potentially helpful indicators of poor prognosis in acute liver failure (ALF) are etiology, encephalopathy grade, blood lactate, and King's College Criteria (KCC). The accuracy of these parameters in predicting transplantation or death shows significant variation in different countries. METHODS: We retrospectively analyzed 102 patients with ALF treated at our institution between 1996 and 2005. Baseline parameters, simplified acute physiology score III (SAPS-III), KCC, Model for End-Stage Liver Disease (MELD) score, and a novel score of bilirubin, lactate, and etiology (BiLE score) were compared between transplant-free survivors and patients who required liver transplantation or died, by using multivariate linear regression analysis and receiver operating characteristics (ROC). RESULTS: The most common causes of ALF were indeterminate liver failure (21%), acute hepatitis B (18%), acetaminophen ingestion (16%), and Budd-Chiari syndrome (9%). Transplantation-free survival was 38%, 44% of patients underwent liver transplantation, and 18% died without transplantation. Eight-week survival was 77%. The BiLE score was the best predictor of death or need of transplantation, with 79% sensitivity and 84% specificity. ROC analysis revealed a better performance of BiLE score when compared with bilirubin, lactate, MELD score, and SAPS-III (area under the curve: 0.87 +/- 0.04, 0.73 +/- 0.51, 0.73 +/- 0.52, 0.71 +/- 0.05, and 0.68 +/- 0.59, respectively). CONCLUSIONS: The simple, combined BiLE score emerged as the best predictor of poor outcome in our patient cohort and should be prospectively evaluated in other populations.

Antibody to hepatitis B surface antigen trough levels and half-lives do not differ after intravenous and intramuscular hepatitis B immunoglobulin administration after liver transplantation.

Hepatitis B immunoglobulin (HBIG) administration remains an essential component of standard reinfection prophylaxis after liver transplantation for hepatitis B virus-related liver disease. Previous studies have suggested that intramuscular (IM) HBIG administration compared to intravenous (IV) HBIG administration may be cost-effective and dose-saving. To compare antibody against hepatitis B surface antigen (anti-HBs) kinetics after IV HBIG administration versus IM HBIG administration, 24 patients received 2000 IU of HBIG every 6 weeks over a study period of 48 weeks in a crossover design. HBIG was started intravenously in 12 patients (group A) and intramuscularly in 12 patients (group B). After 4 doses, at week 24 HBIG administration was switched from IM to IV and vice versa. Anti-HBs kinetics of 22 patients were evaluated. Mean anti-HBs levels measured 2, 4, and 6 weeks after each HBIG administration did not differ significantly (480 +/- 166, 319 +/- 126, and 221 +/- 106 IU/L after IV administration versus 457 +/- 166, 310 +/- 147, and 218 +/- 112 IU/L after IM administration). Half-lives of anti-HBs decline (IV, 25.5 +/- 6.0 days, versus IM, 24.7 +/- 6.2 days) and area under the curve values from week 2 to 6 (IV, 9.4 +/- 3.6 IU*day/mL, versus IM, 9.0 +/- 3.9 IU*day/mL) also showed no significant difference. Variation of anti-HBs levels after IV HBIG administration versus IM HBIG administration was neither significantly different within patients (intraindividual variance) nor between patients (interindividual variance). However, intraindividual variance was lower than interindividual variance after IV (P < 0.05) and IM (P < 0.05) HBIG administration at every time point (2, 4, and 6 weeks). In conclusion, IV HBIG administration and IM HBIG administration are equally effective with respect to the crucial pharmacokinetic parameters. That is, IM HBIG is not dose-saving; however, it may be cost-effective if the price per unit is lower. Individualized dosing intervals should be further evaluated as a cost-effective alternative to fixed dosing schemes.

Extracorporeal albumin dialysis.

Patients with liver failure still present a high mortality. It can only be significantly improved by the rare resource of liver transplantation. Extracorporeal liver support devices have been developed to temporarily support liver detoxification. Artificial devices without hepatocytes ("liver dialysis" or "albumin dialysis") are already widely used in Europe. The two best-known systems, MARS and Prometheus, use a different technical approach to remove water-soluble as well as albumin-bound toxins from the blood. In MARS, toxins diffuse along a concentration gradient through an albumin-impermeable membrane into a secondary circuit that is pre-filled with an albumin solution. The albumin is continuously "recycled" inside the secondary circuit by different adsorber and low flux dialysis. In contrast, Prometheus includes an albumin-permeable filter allowing separation of the albumin fraction into the secondary circuit where the albumin-bound toxins are directly removed by two adsorbers. Thereafter, high flux dialysis is performed inside the primary circuit. For both extracorporeal systems, an improvement of hepatic encephalopathy and biochemical markers such as bilirubin is consistently reported. In-vivo comparisons of both systems showed significantly higher extraction capacities for protein-bound and water-soluble substances under Prometheus than under MARS treatment. Possible pathophysiological mechanisms could be a reduction of portal pressure or a removal of vasoactive cytokines. However, only few randomised controlled trials with low patient numbers and conflictive results regarding patient survival exist. Nevertheless, a Cochrane meta-analysis revealed a significant survival benefit for extracorporeal liver support devices in patients with acute-on-chronic liver failure. Other promising indications are severe refractory cholestatic pruritus, intoxication with protein-bound substances and graft dysfunction after liver transplantation. As large randomised controlled multi-center trials are currently underway, better evidence will be available soon to define the clinical role of extracorporeal liver support devices.

Ethanol sclerotherapy or polidocanol sclerotherapy for symptomatic hepatic cysts.

BACKGROUND: Over the past decades, multiple approaches to aspiration sclerotherapy of large symptomatic hepatic cysts have been investigated. However, comparative data are scarce. OBJECTIVE: The objective of this article is to compare cyst reduction, symptomatic relief, and adverse events between ethanol sclerotherapy and polidocanol sclerotherapy. METHODS: This retrospective study included adults having a symptomatic hepatic cyst treated at a European tertiary referral center with ethanol sclerotherapy (Center 1) or polidocanol-sclerotherapy (Center 2). We compared cyst diameter reduction (%) and symptom improvement (yes/no) within 12 months' post-treatment between centers using multivariate regression analyses adjusted for confounding factors. Finally, we compared adverse events using Fisher's exact test. RESULTS: We included 71 patients from Center 1 and 66 patients from Center 2 (median age 57 years; 126/137 (92%) female). Cyst reduction was comparable between Centers 1 and 2: 37.5% (IQR 15.7-61.0%) versus 44.2% (IQR 24.6-60.5%), respectively (p = 0.35). Correspondingly, symptomatic relief was comparable: 30/53 (56.6%) versus 43/66 (65.2%), respectively (p = 0.88). Center 1 reported significantly more (11 versus 3; p = 0.047) adverse events than Center 2. CONCLUSION: We found comparable cyst reduction and symptomatic relief rates between ethanol- and polidocanol sclerotherapy, while adverse events occurred more often in the ethanol group. Prospective studies focused on clinical response are needed to further explore differences between approaches.