Kinan Rifai

Prometheus® – a new extracorporeal system for the treatment of liver failure☆

BACKGROUND/AIMS Extracorporeal detoxification systems for supportive therapy of liver failure have recently gained much interest. We herein report results from the first clinical application of Prometheus, a new liver support system in which albumin-bound substances are directly removed from blood by special adsorber. In a simultaneous step, high-flux hemodialysis is performed. We assessed safety, adsorber efficiency and clinical efficacy of the Prometheus system. METHODS Eleven patients with acute-on-chronic liver failure and accompanying renal failure were treated with Prometheus on 2 consecutive days for >4 h. RESULTS Prometheus treatment significantly improved serum levels of conjugated bilirubin, bile acids, ammonia, cholinesterase, creatinine, urea and blood pH. There were no significant changes in hemoglobin and platelet levels, whereas leucocytes increased without signs of systemic infection. No treatment-related complications except a blood pressure drop in two patients with systemic infection were noted. In one patient (Child-Pugh score: 15) Prometheus treatment could not be completed due to onset of uncontrolled bleeding 16 h after dialysis. CONCLUSIONS Prometheus is a safe supportive therapy for patients with liver failure. A significant improvement of the biochemical milieu was observed already after two treatments. Prospective controlled studies with the Prometheus system are necessary to evaluate hard clinical end-points.

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.

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.

Long-term outcome of liver transplantation for autoimmune hepatitis

Abstract:  Background:  Liver transplantation is the final therapeutic option for about 10% of patients with autoimmune hepatitis (AIH) who do not respond to medical therapy. The aim of this study was to evaluate the long‐term outcome in serologically defined subgroups of AIH after transplantation.

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

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. (HEPATOLOGY 2013;)

Clinical feasibility of liver elastography by acoustic radiation force impulse imaging (ARFI)

BACKGROUND Transient elastography is increasingly used for assessment of liver fibrosis. Acoustic radiation force impulse imaging (ARFI) is a new technology to perform liver elastography. AIMS We evaluated the clinical feasibility, validity and accuracy of the ARFI method and compared it to Fibroscan(®) and liver histology. METHODS Ultrasonographic elastography of the liver using ARFI was performed in 29 patients with liver cirrhosis, 70 patients with liver disease and 23 healthy controls. RESULTS ARFI was feasible in all patients providing a mean propagation velocity of 1.65±0.93 m/s. ARFI results of the right and left liver lobes were comparable (p<0.001). In cirrhotic patients, ARFI gave significantly higher values than in the other patients (p<0.001). Rate of invalid measurements was lower in ARFI than in Fibroscan(®) (p<0.04). Both elastography methods were highly correlated to each other (p<0.001). Furthermore, ARFI correlated to histological grading of liver fibrosis (p<0.001) and to inflammatory activity (p<0.05). Liver steatosis had no statistical influence on ARFI results (p=0.2) in contrast to Fibroscan(®) (p<0.05). CONCLUSIONS The new ultrasonographic method of ARFI elastography allows valid, accurate and flexible evaluation of liver stiffness. It seems more feasible in patients with liver cirrhosis than Fibroscan(®). ARFI elastography of the left liver lobe is also possible. Liver steatosis does not seem to influence ARFI elastography.

Outcome and quality of life in patients with polycystic liver disease after liver or combined liver‐kidney transplantation

In advanced stages of polycystic liver disease, often associated with polycystic kidney disease, a curative therapy is liver or combined liver‐kidney transplantation. However, little is known about long‐term outcome and quality of life. Between 1990 and 2003, 36 patients (32 female, 4 male) with polycystic liver or combined liver‐kidney disease underwent liver (n = 21) or liver‐kidney (n = 15) transplantation at our center. Main indications for liver transplantation were cachexia, muscle atrophy, loss of weight, recurrent cyst infections, portal hypertension, and ascites. Apart from clinical parameters, 2 anonymous questionnaires (standard short form 36 and self‐designed) addressing quality of life and social status were evaluated. Five patients (14 %) died due to sepsis or myocardial infarction with pneumonia, all within 61 days after transplantation. The follow‐up time of the remaining 31 patients ranged from 5 to 156 months, with a mean of 62 months. Of the 23 (74%) answered the questionnaires, 91% of patients felt “much better” or “better,” only 9% felt “worse” than before, and 52% of patients participated in sports regularly. Fatigue, physical fitness, loss of appetite, and vomiting improved significantly after transplantation. Physical attractiveness and interest in sex increased as well. Professional occupation did not change for 71% of patients. Family situation before and after transplantation changed in 1 case only. Finally, 78% of patients said they would opt for transplantation again, while 17% were undecided; 1 patient would not repeat transplantation. In conclusion, patients with advanced polycystic liver or polycystic liver‐kidney disease have an excellent survival rate and an improved quality of life after liver or combined liver‐kidney transplantation. Liver Transpl 12:1268‐1277, 2006.

Failure of hepatitis B vaccination with conventional HBsAg vaccine in patients with continuous HBIG prophylaxis after liver transplantation

Hepatitis B vaccination after liver transplantation for hepatitis B–related liver disease has been investigated as an alternative strategy to reinfection prophylaxis with hepatitis B immunoglobulin (HBIG) with conflicting results. In most studies, HBIG treatment was discontinued before vaccination. An outstanding good response was achieved with vaccination under continuous HBIG administration using hepatitis B surface antigen (HBsAg)‐based vaccine containing special adjuvants. Both, adjuvants and continuous HBIG administration have been discussed as crucial factors for good response. Twenty‐four patients were vaccinated with conventional double dose recombinant vaccine containing 40 μg HBsAg up to 12 times at weeks 0, 2, 4 (cycle 1), 12, 14, 16 (cycle 2), 24, 26, 28 (cycle 3), and 36, 38, 40 (cycle 4). All patients received 2,000 IU HBIG every 6 weeks (4 times intravenously and 4 times intramuscularly). A significant response was defined as reconfirmed increase of anti‐HBs‐antigen (anti‐HBs) unexplained by HBIG administration or lack of anti‐HBs decrease below 100 IU/L after discontinuation of HBIG treatment after week 48. Only 2 of 24 patients (8.3%) responded significantly. Anti‐HBs started to increase after the seventh vaccination (cycle 3, during intramuscular HBIG administration) in 1 patient and after 12th vaccination (cycle 4, during intravenous HBIG administration) in the other. Maximum anti‐HBs levels were >1,000 IU/L in both patients and decreased significantly slower as compared to passive prophylaxis during follow‐up. In conclusion, the conventional HBsAg vaccine failed to induce a significant humoral immune response in most patients despite continued HBIG treatment. Further studies should address the question, of whether the use of potent adjuvant systems results in higher response rates. Liver Transpl 13: 367–373, 2007.

The Prometheus® Device for Extracorporeal Support of Combined Liver and Renal Failure

Background/Aims: Prometheus® is a newly developed extracorporeal liver support system that combines removal of albumin-bound substances (adsorption on resin adsorbers) and water-soluble substances (diffusion during high-flux hemodialysis). Therefore, it is a promising treatment option for patients with hepatorenal syndrome (HRS). Methods: We studied 10 patients with HRS in a prospective clinical study. All patients underwent 2 consecutive Prometheus treatments. A variety of clinical and biochemical parameters were assessed. Results: Prometheus treatment was uncomplicated and safe. A statistically significant improvement of serum creatinine and urea concentrations as well as blood pH was observed after Prometheus treatment. Furthermore, liver detoxification was supported by a significant decrease of serum levels of conjugated bilirubin, bile acids and ammonia. Conclusions: Prometheus is a safe treatment for patients with HRS. Both, albumin-bound and water-soluble substances were effectively removed. Controlled studies will evaluate the effect of this new treatment option on survival in patients with HRS.

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 Kings 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.