Successful clinical application of extracorporal albumin dialysis in a patient with benign recurrent intrahepatic cholestasis (BRIC)

This is a case report of a 36 years old man who has been suffering for 20 years from benign recurrent intrahepatic cholestasis (BRIC). BRIC is a rare autosomal recessive disease characterised by prolonged episodes of intrahepatic cholestasis and pruritus alternating with periods of nearly normal liver function, and does not progress to cirrhosis. Since all former approaches to medical treatment of the patients severe pruritus were ineffective, the patient was treated by 3 sessions of albumin dialysis (MARS, Molecular Adsorbents Recirculating System). MARS dialysis decreased serum bilirubin levels by more than 60 % and effectively lowered serum bile acid levels by 45 %. The course of serum parameters was accompanied by a dramatic clinical improvement of the patients symptoms (pruritus, jaundice, fatigue etc.). MARS therapy appeared to shorten the duration of the cholestatic attack.     

Treatment of severe refractory pruritus with fractionated plasma separation and adsorption (Prometheus)

OBJECTIVE: Severe pruritus is a serious complication of cholestatic liver disease. Prometheus is a recently introduced extracorporeal liver support system with direct toxin adsorption of the patient's albumin fraction (FPSA; fractionated plasma separation and adsorption). Here we report on the effect of Prometheus therapy in patients with intractable cholestatic pruritus. MATERIAL AND METHODS: Seven patients with different liver diseases and severe pruritus refractory to all medical treatment efforts for more than 4 weeks were treated with Prometheus (3-5 times, 18+/-3 h total). Pruritus intensity was assessed using the visual analogue scale (VAS; from 0 = no pruritus to 10 = unbearable pruritus), and VAS, serum bile acids and total bilirubin were evaluated directly before and after Prometheus treatment, as well as 4 weeks later. RESULTS: After Prometheus therapy, VAS values had dropped significantly from 9+/-1 to 3+/-3 (p<0.001). Likewise, serum bile acids decreased (from 248+/-192 to 101+/-85 micromol/l; p<0.03). All patients, with the exception of one with no initial bile acid elevation, reported a pronounced improvement in pruritus with Prometheus therapy, although in two anicteric patients the amelioration lasted only a few days. In the other four patients a distinct benefit was still observed 4 weeks after the treatment. CONCLUSIONS: Prometheus therapy significantly improved refractory pruritus in all patients with elevated bile acid levels, but in some patients the clinical benefit was of short duration. The clinical findings suggest that we have to better characterize those patients who might derive a long-lasting benefit from this invasive and expensive treatment.     

Successful use of Molecular Absorbent Regenerating System (MARS) dialysis for the treatment of fulminant hepatic failure in children accidentally poisoned by toxic mushroom ingestion

Background: Acute liver failure (ALF) as a result of mushroom poisoning is associated with a high mortality (particularly in children), despite optimal medical therapy (OMT), including charcoal haemoperfusion and haemodiafiltration. MARS is a new, cell‐free, extracorporeal liver assistance method utilizing an albumin dialysate for the removal of albumin‐bound toxins. Methods: We describe the first series in the literature (also first MARS treatments in Romania) with ALF because of mushroom poisoning in children (M/F = 2/4, age = 7–16 years). Liver function was evaluated pre‐MARS and 15‐min post‐MARS, 24 h following each treatment and 30 days post‐MARS. Findings: All patients had severe hepatic dysfunction: hepatic encephalopathy (HE; four grade II, one grade III, one grade IV), ALT = 4082 (3400–5600) IU/L, bilirubin = 6.3 2 - 10 ) mg/dL, prothrombin time (PT) = 52.5 (23–141) s. MARS was uneventful and well‐tolerated. Two 6‐h sessions per patient were performed with a similar immediate impact on liver tests: mean drop in ALT of ?33 and ?35%, respectively, and in bilirubin of ?39 and ?36%, respectively. ALT levels 24 h following MARS‐1, remained unchanged but continued to drop by a further ?28% following MARS‐2. By contrast, all patients had a significant rebound in bilirubin (+39%) 24 h following MARS‐1; however, following MARS‐2 a rebound was seen only in two cases (+220%). PT improved by 37% after MARS‐1 and normalized in four patients after MARS‐2. Outcome: Four patients survived and completely recovered the hepatic function. Negative prognostic markers: lack of complete correction of PT, continuous rebound and increase in bilirubin, and lack of improvement in HE post‐MARS‐1. Survival in six well‐matched cases, treated by OMT = 0/6 (P < 0.05). Conclusions: MARS is a safe and highly effective depurative therapy in children with ALF. Survival is predicted only by the impact/results of the initial MARS sessions and not by any of the baseline parameters.     

Early Molecular Adsorbents Recirculating System Treatment of Amanita Mushroom Poisoning

Acute poisoning due to ingestion of hepatotoxic Amanita sp. mushrooms can result in a spectrum of symptoms, from mild gastrointestinal discomfort to life‐threatening acute liver failure. With conventional treatment, Amanita phalloides mushroom poisoning carries a substantial risk of mortality and many patients require liver transplantation. The molecular adsorbent recirculating system (MARS) is an artificial liver support system that can partly compensate for the detoxifying function of the liver by removing albumin‐bound and water‐soluble toxins from blood. This treatment has been used in acute liver failure to enable native liver recovery and as a bridging treatment to liver transplantation. The aim of the study is to evaluate the outcome of 10 patients with Amanita mushroom poisoning who were treated with MARS. The study was a retrospectively analyzed case series. Ten adult patients with accidental Amanita poisoning of varying severity were treated in a liver disease specialized intensive care unit from 2001 to 2007. All patients received MARS treatment and standard medical therapy for mushroom poisoning. The demographic, laboratory, and clinical data from each patient were recorded upon admission. The one‐year survival and need for liver transplantation were documented. The median times from mushroom ingestion to first‐aid at a local hospital and to MARS treatment were 18 h (range 14–36 h) and 48 h (range 26–78 h), respectively. All 10 patients survived longer than one year. One patient underwent a successful liver transplantation. No serious adverse side‐effects were observed with the MARS treatment. In conclusion, MARS treatment seems to offer a safe and effective treatment option in Amanita mushroom poisoning.     

Extracorporal albumin dialysis (MARS) improves cholestasis and normalizes low apo A-I levels in a patient with benign recurrent intrahepatic cholestasis (BRIC)

The familial cholestatic diseases Benign Recurrent Intrahepatic Cholestasis (BRIC) and Progessive Familial Intrahepatic Cholestasis type 1 (PFIC1) are characterized by intermittent or permanently elevated plasma bile salt levels, therapy-resistant extreme pruritus and peculiar biochemical abnormalities including low apolipoprotein apo A-I. Previously, symptomatic improvement has been demonstrated in BRIC patients after extracorporal albumin dialysis (MARS). We hypothesized that MARS improves cholestasis, induces changes in the bile salt profile and normalizes apo A-I serum levels in BRIC. A 17-year-old-female patient with BRIC experienced an episode of cholestasis lasting for more than 6 months with extreme pruritus and diarrhoea not responding to standard therapy. During a period of five days the patient was treated 3 x 8 h with MARS. The procedures were well tolerated and resulted in reduction of plasma bile salts by 58%. The plasma bile salt profile changed into a more hydrophilic composition after MARS. Diarrhoea discontinued and the pruritus improved significantly from 9 to 4 on a subjective scale. These effects lasted 4 months until a relapse occurred. Low plasma apo A-I levels (0.52 g/l) normalized after MARS (0.98 g/l). The procedures were well tolerated. Fatigue was noted as the only transient side-effect. In conclusion, MARS may induce a long-term symptomatic improvement and decrease of cholestatic markers in BRIC. Further studies evaluating efficacy and mechanism of MARS in patients with BRIC are needed.     

The molecular adsorbent recirculating system as a liver support system. Summary of Mexican experience

Aim. The aim of this study was to assess the effects of the molecular absorbent recirculating system (MARS) on patients with acute liver failure (ALF) and liver failure with cirrhosis (AoCLF) as well as in cholestatic patients with intractable pruritus in a Mexican population.Material and methods. From August 2003 to December 2011, MARS was used in 38 patients with ALF, 15 patients with AoCLF, and 17 cholestatic patients with intractable pruritus. The patients were examined using a standard liver function test and for vital signs, presence of ascites and encephalopathy before and after each treatment. The therapeutic response, patient status, follow-up status, and need for liver transplantation were determined.Results. Seventy-nine MARS procedures were performed. MARS was used for ALF in 54.3% of patients, AoCLF in 24.2%, and cholestatic disease in 21.5%. There were significant improvements in serum bilirubin (p = 0.000), aspartate aminotransferase (p = 0.000), alanine aminotransferase (p = 0.030), gamma-glytamyl transpeptidase (p = 0.044), alkaline phosphatase (p = 0.006), and encephalopathy grade (p = 0.000). Thirty-eight ALF patients were listed for emergency liver transplantation and treated with MARS; 20 of these patients died on a waiting list, 18 survived. only four underwent liver transplantation and 14 (37%) recovered without transplantation after the MARS procedure.Conclusion. MARS is a safe and effective procedure, especially for ALF patients. Our results suggest that MARS therapy can contribute to native liver recovery in ALF patients.     

Albumin dialysis with MARS for the treatment of anabolic steroid-induced cholestasis

Background and aims. Steroid-related hepatotoxicity has become one of the most relevant causes of drug induced liver cholestasis. Some patients do not improve after standard medical treatment (SMT) and may therefore require other approaches, like extracorporeal liver support.Material and methods. We report four cases of patients with pruritus, abnormal liver function tests and biopsy-proven anabolic steroid-induced cholestasis who were unresponsive to SMT. They underwent treatment with albumin dialysis (Molecular Adsorbent Recirculating System -MARS®-). A minimum of two MARS sessions were performed.Results. After MARS® procedure, patients’ symptoms improved, as well as liver function tests, thus avoiding liver transplantation.Conclusion. Albumin dialysis appears as a valuable therapeutic option for the management of anabolic steroid-induced cholestasis in patients that are unresponsive to SMT.     

Albumin Dialysis in Liver Failure: Comparison of Molecular Adsorbent Recirculating System and Single Pass Albumin Dialysis—A Retrospective Analysis

Despite improvement in critical care, liver failure is still associated with high mortality. Therapeutic concepts are aimed at restoring endogenous liver function or to bridge the time to liver transplantation. In addition to standard medical treatment, extracorporeal liver support with albumin dialysis is used for this purpose. The aim of this study was to analyze the efficacy of single pass albumin dialysis (SPAD) in comparison to the molecular adsorbent recirculating system (MARS) in patients treated at our university hospital intensive care unit between July 2004 and August 2008. In this retrospective analysis we studied patients presenting with liver failure who were treated with albumin dialysis. Laboratory parameters, daily health scoring, the number of transfusions, and mortality were recorded. The (paired) t‐test, Mann–Whitney U‐test, and Wilcoxon test were used for statistical analysis. In all, 163 albumin dialysis treatments, 126 with MARS and 37 with SPAD, in 57 patients were performed. MARS resulted in a significant decrease in bilirubin (?38 ± 66.5 µmol/L from a baseline of 301 ± 154.6 µmol/L), γ‐glutamyltransferase (γ‐GT), alanine aminotransferase, creatinine, and urea. SPAD resulted in a significant decrease in bilirubin (?41 ± 111.2 µmol/L from a baseline of 354 ± 189.4 µmol/L) and γ‐GT, while lactate levels increased. No differences in the need for blood transfusion, health scoring, or mortality between the two treatment modalities were detected. This retrospective analysis suggests equal efficacy of MARS and SPAD; however, prospective assessment to further define the role of SPAD in the treatment of acute or acute‐on‐chronic liver failure is needed.     

Albumin liver dialysis as pregnancy-saving procedure in cholestatic liver disease and intractable pruritus

Progressive familial intrahepatic cholestasis type 3 （PFIC3） is a rare cholestatic liver disease. Such liver disease can get worse by female hormone disorder. Albumin dialysis or Molecular Adsorbent Recirculating System （MARS） has been reported to reverse severe cholestasis-linked pruritus. Here, we report the first use of MARS during a spontaneous pregnancy and its successful outcome in a patient with PFIC3 and intractable pruritus. Albumin dialysis could be considered as a pregnancy-saving procedure in pregnant women with severe cholestasis and refractory pruritus.     

Extracorporeal liver support-albumin dialysis with the Molecular Adsorbent Recirculating System (MARS)

Extracorporeal liver support has been a much studied topic throughout the last 50 years. Albumin dialysis as a therapeutic option for patients with acute liver failure or acute decompensation of chronic liver disease was introduced in the mid-nineties. The Molecular Adsorbent Recirculating System (MARS) is based on the concept of albumin dialysis and allows for the removal of protein-bound as well as water-soluble toxins. Besides its role as a sufficient volume expander human serum albumin is an important scavenger for molecules with pathophysiological relevance in liver failure. Albumin dialysis enables the selective regeneration of patient's albumin resulting in an increase of albumin binding capacity. Clinically, an improvement of central and local hemodynamics as well as liver-, brain-, and kidney-functions were observed. Thus, the treatment can contribute to liver regeneration and stabilization of vital organ functions and thus help to bridge patients to liver transplantation or to recovery of native liver function. Proper patient selection is critical for clinical success. Aggressive treatment of infections and sepsis seems to be a decisive pre-requisite for its safe and efficient use. Cautious anticoagulation with heparin is the common standard. Citrate use is recommended for patients prone to bleeding. Today, albumin dialysis MARS is among the best studied liver support methods. It appears as a valuable therapeutic tool for the treatment of various complications of of liver failure, especially hemodynamic instability and hepatic encephalopathy. Further studies will need to help defining the optimal patient selection and technical process parameters such as session length and frequency of treatment.     

Molecular Adsorbent Recirculating System (MARS®) removal of piperacillin/tazobactam in a patient with acetaminophen‐induced acute liver failure

The objective of this study was to illustrate the pharmacokinetic removal of piperacillin/tazobactam in an anuric patient on Molecular Adsorbent Recirculating System (MARS^®). The patient was a 32‐year‐old woman who presented to a medical intensive care unit with acute liver failure secondary to an acetaminophen overdose. While awaiting transplant, she was started on MARS therapy as a bridge to liver transplant and empirically started on piperacillin/tazobactam therapy. MARS is an extracorporeal hemofiltration device, which incorporates a continuous venovenous hemofiltration (CVVHD) machine linked to an albumin‐enriched dialysate filter to normalize excess electrolytes, metabolic waste, and protein‐bound toxins. In addition to protein‐bound waste, MARS removes water‐soluble, low molecular‐weight molecules. The patient received piperacillin/tazobactam 4.5 g infused intravenously over 3 h. A steep decline in serum levels occurred between hours 4 and 6 while MARS continued and no antibiotic was infused. The elimination rate constant (k_e) for the removal of piperacillin in this patent was 0.453 h^?1 and the half‐life (λ) was 1.53 h. The k_e was 2.9‐fold higher than with CVVHD alone and the λ was 3.7‐fold shorter. Low levels of piperacillin are achieved during MARS therapy, but in the treatment of more resistant organisms, such as Pseudomonas aeruginosa, these low levels may not be adequate to achieve bactericidal activity. Drug levels following a standard infusion of 30 min would likely be even lower. Formalized pharmacokinetic studies of piperacillin/tazobactam removal in patients on MARS therapy are necessary to make clear dosing recommendations.     

MARS therapy in critically ill patients with advanced malignancy: a clinical and technical report

Abstract Background/methods: Molecular Adsorbent Recirculating System (MARS) was used in three consecutive critically ill patients at the Singapore General Hospital with advanced malignancy and acute liver failure (ALF). Case 1 was a male patient with hepatocellular carcinoma (HCC) for which initial right hepatectomy was followed by left hepatectomy 5 months later for recurrent HCC. The postoperative course following second surgery was complicated by severe methicillin‐resistant Staphylococcus aureus (MRSA) sepsis, mild azotaemia and subacute cholestatic liver failure. MARS was used thrice in this patient. Case 2 was a female patient with advanced acute lymphoblastic leukaemia (ALL) with postbone marrow transplantation (BMT) acute haemolytic–uraemic syndrome (HUS) secondary to cyclosporin A (Cy A), cytomegalovirus (CMV) infection, severe nosocomial pneumonia, acute renal failure (ARF) treated with continuous haemofiltration and acute veno‐occlusive disease resulting in Budd–Chiari syndrome. The latter precipitated ALF. MARS was instituted twice. Case 3 was a male patient with advanced, refractory Hodgkin's disease previously treated with multiple courses of chemotherapy. ALF developed secondary to acute viral hepatitis B flare. He was given a trial of MARS once in the ICU. All the three patients eventually died. Results: Mean MARS intradialytic systemic pressures were as follows: systolic pressure range was 95 ± 17 to 128 ± 17 mmHg and diastolic pressure range was 51 ± 5 to 67 ± 7 mmHg. Pressure at albumin dialysate exit point from dialyser 1 (Ae) ranged from 253 ± 11 to 339 ± 15 mmHg and that at albumin dialysate entry point into dialyser 1 (Aa) ranged from 142 ± 11 to 210 ± 6 mmHg. Ultrafiltration (UF) was 633 ± 622 mL over mean treatment duration of 6.3 ± 0.9 h with a total heparin dose of 1583 ± 817 IU. Coagulation status pre‐ and 6‐h post‐MARS was similar: aPTT (P = 0.116) and platelet count (P = 0.753). There were no bleeding complications or circuit thromboses. MARS had a significant de‐uraemization effect (pre‐ and post‐MARS serum creatinine and urea: P = 0.046 and 0.028, respectively) but did not significantly attenuate blood lactate, ammonia or total bilirubin levels. Albumin dialysate (Ae ? Aa) urea and creatinine concentrations appeared to be sharply attenuated after 6 h of MARS. In contrast, the removal of total bilirubin by albumin dialysate from the blood compartment appeared to plateau after 4 h of continuous MARS operation. Conclusions: MARS was well‐tolerated in critically ill patients with advanced and complicated cancer. Low‐dose heparin was safe and did not compromise MARS circuit integrity. Although MARS had a significant de‐uraemization effect, this appeared to be limited by the duration of MARS operation. Our data suggested that such a limit was reached earlier for total bilirubin. More data are needed to confirm the present findings and further delineate the saturation limit of MARS for different toxins that accumulate in ALF. This would affect the optimal duration of MARS therapy.     

Increase of Octanoate Concentrations During Extracorporeal Albumin Dialysis Treatments

Extracorporeal liver support procedures based on albumin dialysis require the use of pharmaceutical‐grade human serum albumin (HSA). Those preparations contain octanoate, which is added as stabilizer during the production process. For octanoate, a direct involvement in the pathogenesis of liver failure complications as well as an indirect influence by competitive displacement effects at the albumin molecule have been described. During five Single Pass Albumin Dialysis (SPAD) and three Molecular Adsorbent Recirculating System (MARS) treatments the changes of octanoate concentrations in blood and dialysate were investigated. An octanoate increase in patient blood was observed during passage of the filter for both SPAD (585 µmol/L [338–1022 µmol/L]) (median [range]) and MARS (182 µmol/L [71–437 µmol/L]) during the first three hours of treatment. The molar ratio of octanoate/albumin at the blood outflow was significantly higher during SPAD treatments (1.73 [0.86–2.64] vs. 0.54 [0.31–1.1]; P = 0.001) during MARS. Changes of octanoate blood levels during SPAD were significantly higher than during MARS (P < 0.001). The shift of octanoate from the dialysate to the patient was persistent during SPAD (median 67.6 µmol/min), whereas during MARS a decrease over time was observed (from 25.5 to 7.5 µmol/min). During albumin dialysis procedures a transfer of octanoate into patient blood occurs. The time‐course and extent are different between both albumin dialysis procedures. Given the positive clinical effects reported mainly for MARS, the clinical impact of albumin dialysis‐associated transfer of octanoate during extracorporeal liver support needs to be evaluated further.     

Effect of Prometheus liver assist system on systemic hemodynamics in patients with cirrhosis： A randomized controlled study

AIM： To evaluate treatment safety and hemodynamic changes during a single 6-h treatment with the PrometheusTM liver assist system in a randomized, controlled study. METHODS： Twenty-four patients were randomized to either the study group or to one of two control groups： Fractionated Plasma Separation Adsorption and Dialysis, PrometheusTM system （Study group; n = 8）; Molecular Adsorbent Recirculation System （MARS）TM （Control group 1, n = 8）; or hemodialysis （Control group 2; n = 8）. All patients included in the study had decompensated cirrhosis at the time of the inclusion into the study. Circulatory changes were monitored with a Swan-Ganz catheter and bilirubin and creatinine were monitored as measures of protein-bound and water-soluble toxins. RESULTS： Systemic hemodynamics did not differ between treatment and control groups apart from an increase in arterial pressure in the MARS group （P = 0.008）. No adverse effects were observed in any of the groups. Creatinine levels significantly decreased in the MARS group （P = 0.03） and hemodialysis group （P = 0.04）. Platelet count deceased in the Prometheus group （P = 0.04）.CONCLUSION： Extra-corporal liver support with Prometheus is proven to be safe in patients with endstage liver disease but does not exert the beneficial effects on arterial pressure as seen in the MARS group,     

An Australian experience with the molecular adsorbents recirculating system (Mars)

The molecular adsorbents recirculating system (MARS) is a form of artificial extracorporeal liver support which has the potential to remove substantial quantities of albumin-bound toxins postulated to contribute to the pathogenesis of liver cell damage, hemodynamic instability and multi-organ failure in patients with acute liver failure and acute-on-chronic liver failure (AoCLF). We assessed the efficacy of MARS therapy in a cohort of patients with severe liver damage unresponsive to intensive medical therapy. MARS therapy was instituted late in the clinical course of six patients with severely impaired liver function refractory to intensive medical therapy, including four with AoCLF precipitated by sepsis and two with liver dysfunction due to sepsis in the absence of pre-existing chronic liver disease. Outcome measures included markers of hemodynamic stability, renal function, serum bilirubin and bile acid levels, arterial ammonia levels, the arterial ketone body (acetoacetate/beta-hydroxybutyrate) ratio, hepatic encephalopathy grade and the plasma disappearance rate of indocyanine green. The rates of discharge from the intensive care unit and in-hospital mortality were determined. Our findings suggest that MARS treatment might be associated with some clinical efficacy even in patients with advanced multi-organ dysfunction occurring in the setting of severe liver damage and in whom treatment is instituted late in the clinical course. However, the overall survival rate (1/6; 17%) was poor. More data obtained from larger cohorts of patients enrolled in randomized controlled studies will be required in order to identify categories of liver failure patients who might benefit most from MARS treatment and to ascertain the most appropriate timing of intervention.     

Economic evaluation of MARS – preliminary results on survival and quality of life

Abstract: Objectives: The short-term medical benefit of the liver dialysis system MARS in patients with severe acute liver disease has clearly been demonstrated. An economic analysis of MARS has not been presented previously. Objective of the study is to calculate the costs per life saved and life year gained and to measure health related quality of life in patients who survived acute liver failure. First results on survival and HRQL are presented here. Study design: Cost effectiveness and cost utility analysis of MARS are performed. All patients since 1993 with chronic liver failure (Bilirubin > 300 µmol/l) of the university hospital Rostock are included in the original sample (n = 141). Survival data are calculated. Surviving patients were contacted personally, thus quality of life data (EQ 5D and SF12) determined. Patients were compared in case control study design. In a later stage inpatient hospital costs, direct and indirect outpatients costs are included in the analysis. Preliminary results: MARS-Patients show a higher survival: Kaplan-Meier cumulative survival after 100 days: 0.59 after MARS, 0.39 without (P <0.05). There was no significant difference in health related quality of life (SF12 and EQ-D). Calculations of quality adjusted life years (QALYs) result in 0.116 QALYs gained by treatment of one patient with MARS in one year. Discussion: First preliminary results suggest that 1 year after therapy MARS seems to have a positive effect concerning survival rate, survival time and QALYs gained. Final results of cost-effectiveness and cost-utility analysis will soon be presented.     

Long-term efficacy of sertraline as a treatment for cholestatic pruritus in patients with primary biliary cirrhosis

OBJECTIVES: Generalized pruritus is a common complication of cholestatic liver diseases, although its pathogenesis remains elusive. Current treatments are often inadequate and may be poorly tolerated, so the clinician is sometimes faced with a patient in misery and no good therapeutic options. Because, in our experience, several patients with primary biliary cirrhosis (PBC) claimed that sertraline had improved their pruritus, we sought to determine whether sertraline use was associated with changes in pruritus medications or self-reported severity of pruritus in a large cohort of patients with PBC. METHODS: The self-reported severity of pruritus was followed prospectively in 40 patients with PBC for a mean of 7.5 +/- 1.3 yr. These data were then retrospectively examined to determine the effect of sertraline on pruritus in all subjects who had received sertraline at some time during the study. RESULTS: For 28 of 32 patients with pruritus, itching was stable or fluctuated slightly over the follow-up period. No patient experienced rapid progression of pruritus, and four patients experienced a sustained resolution of their pruritus. Ten subjects started sertraline and continued it long enough (>6 months) to determine its lasting effect on pruritus. Three of these individuals did not have significant pruritus before or after sertraline. Of the seven patients with pruritus, six (86%) recorded a significant reduction or resolution of pruritus in their weekly diaries and also decreased or completely stopped other medications for pruritus. CONCLUSIONS: Sertraline use is associated with an improvement in cholestatic pruritus. This novel observation implies that serotonergic fibers are important in regulating the perception of itch.     

Benign recurrent intrahepatic cholestasis with secondary renal impairment treated with extracorporeal albumin dialysis

Benign recurrent intrahepatic cholestasis (BRIC) is a rare autosomal recessive condition characterized by intermittent episodes of pruritis and jaundice that may last days to months. Treatment is often ineffective and symptoms, particularly pruritis, can be severe. Extracorporeal albumin dialysis (molecular adsorbent recycling system, MARS) is a novel treatment which removes albumin bound toxins including bilirubin and bile salts. We describe a case of a 34-year-old man with BRIC and secondary renal impairment who, having failed standard medical therapy, was treated with MARS. The treatment immediately improved his symptoms, renal and liver function tests and appeared to terminate the episode of cholestasis. We conclude that MARS is a safe and effective treatment for BRIC with associated renal impairment.     

Risk factors for hepatic decompensation in patients with primary biliary cirrhosis

AIM:To examine the clinical features and analyze prognostic factors in a prospective study of primary biliary cirrhosis(PBC) patients.METHODS:From 1995 to 2010,PBC patients without hepatic decompensation seen at the Peking Union Medical College Hospital were enrolled.Clinical signs and manifestations(pruritus,persistent fatigue,jaundice and pain in the right hypochondrium),laboratory parameters(auto-antibodies for autoimmune hepatic disease,biliary and hepatic enzymes,immunoglobulin,bilirubin,and albumin) and imaging findings were recorded at entry and at specific time points during follow-up.Cox regression and Kaplan-Meier analyses,respectively,assessed the risk factors for hepatic decompensation and survival.RESULTS:Two hundred and sixty-two PBC patients were enrolled with a median follow-up of 75.2 mo(range,21-201 mo).The 240 patients were aged 51.5 ± 10.2 years at diagnosis and 91.6% were female.Two hundred and forty-five(93.5%) were seropositive for anti-mitochondrial antibodies.At presentation,170 patients(64.9%) were symptomatic,while 96 patients(36.6%) had extra-hepatic autoimmune disease.During the follow-up period,62(23.7%) patients developed hepatic decompensation of whom four underwent liver transplantation and 17 died.The cumulative survival rate and median survival time were 83.9% and 181.7 mo,respectively.Cox regression analysis revealed that an incomplete ursodeoxycholic acid(UDCA) response or inconsistent treatment [P < 0.001;hazard risk(HR) 95%CI = 2.423-7.541],anti-centromere antibodies(ACA) positivity(P < 0.001;HR 95%CI = 2.516-7.137),alanine aminotransferase ratio(AAR) elevations(P < 0.001;HR 95%CI = 1.357-2.678),and histological advanced liver disease(P = 0.006;HR 95%CI = 1.481-10.847) were predictors of hepatic decompensation.The clinical features and survival of PBC in China are consistent with those described in Western countries.CONCLUSION:Incomplete UDCA response or inconsistent treatment,ACA positivity,AAR elevations,and advanced histological stage are predictors of decompen