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.     

Preconditioning by extracorporeal liver support (MARS) of patients with cirrhosis and severe liver failure evaluated for living donor liver transplantation -- a pilot study.

PURPOSE: The aim of this prospective study was to evaluate the effectiveness of preconditioning molecular adsorbent recirculating system (MARS) treatment on patients with acute-on-chronic liver failure (AoCLF), who were awaiting living donor liver transplantation (LDLT). PATIENTS AND METHODS: Between January and December 2001, 10 consecutive AoCLF patients (with progressive hyperbilirubinemia (>20 mg/dl) and hepatic encephalopathy grade > or =2) were studied. MARS was used in eight of these patients who were evaluated for LDLT during 2001. Three AoCLF patients who received LDLT before clinical use of MARS were used as historical controls. RESULTS: Because of a shortage of donors, only five out of 10 patients considered for LDLT could receive transplants. Three patients were treated with MARS for 8 h the day before receiving LDLT, and all three survived. The remaining two patients who received transplants, and who were not pretreated with MARS, died from sepsis and multi-organ failure within 2 weeks. Four of the patients who did not receive transplants because of donor shortage died despite 1 or 3 MARS treatments, however bilirubin levels and grade of encephalopathy were significantly reduced in these patients. CONCLUSIONS: Results of this small pilot study suggest that MARS, by reducing the severity of jaundice and encephalopathy, might be effective as a bridging option in AoCLF patients awaiting LDLT.     

Etiology and outcome of acute liver failure: Retrospective analysis of 50 patients treated at a single center

Background and Aim:  Acute liver failure (ALF) remains a devastating disease carrying considerable mortality. Since deceased donor liver transplantation is rarely performed in Japan, the artificial liver support system (ALS) and living donor liver transplantation (LDLT) are the main modalities used for treatment of ALF. The aim of this study was to analyze the outcome of ALF patients and to evaluate therapies for ALF according to etiology.
Methods:  Fifty consecutive patients with ALF were treated between January 1990 and December 2006. Prior to 1997, patients received ALS only. After 1997, ALS and/or LDLT were applied. LDLT was performed in 10 patients.
Results:  Four of 15 (27%) pre-1997 ALF patients survived, and 16 of 35 (46%) post-1997 ALF patients survived, including eight who underwent LDLT. The causes of ALF were acute hepatitis B virus (HBV) infection in 18%, severe acute exacerbation (SAE) of chronic HBV infection in 18%, autoimmune hepatitis (AIH) in 8%, and cryptogenic hepatitis in 44%. In total, 67% of the patients with ALF caused by acute HBV infection and AIH were cured without LDLT; only 11% of patients with ALF caused by SAE of HBV and 24% of cryptogenic hepatitis were successfully treated without LDLT. Notably, 80% of patients with cryptogenic hepatitis who underwent LDLT survived.
Conclusion:  Since 1997, the survival rate of ALF patients has increased, mainly due to the introduction of LDLT. Liver transplantation should be performed especially in patients with ALF caused by SAE of HBV and cryptogenic hepatitis.     

Adult-to-adult living donor liver transplantation for acute liver failure in China

AIM:To investigate the long-term outcome of recipients and donors of adult-to-adult living-donor liver transplantation(AALDLT) for acute liver failure(ALF).METHODS:Between January 2005 and March 2010,170 living donor liver transplantations were performed at West China Hospital of Sichuan University.All living liver donor was voluntary and provided informed consent.Twenty ALF patients underwent AALDLT for rapid deterioration of liver function.ALF was defined based on the criteria of the American Association for the Study of Liver Diseases,including evidence of coagulation abnormality [international normalized ratio(INR) ≥ 1.5] and degree of mental alteration without pre-ex-isting cirrhosis and with an illness of 26 wk duration.We reviewed the clinical indications,operative procedure and prognosis of AALDTL performed on patients with ALF and corresponding living donors.The potential factors of recipient with ALF and corresponding donor outcome were respectively investigated using multivariate analysis.Survival rates after operation were analyzed using the Kaplan-Meier method.Receiver operator characteristic(ROC) curve analysis was undertaken to identify the threshold of potential risk factors.RESULTS:The causes of ALF were hepatitis B(n = 18),drug-induced(n = 1) and indeterminate(n = 1).The score of the model for end-stage liver disease was 37.1 ± 8.6,and the waiting duration of recipients was 5 ± 4 d.The graft types included right lobe(n = 17) and dual graft(n = 3).The mean graft weight was 623.3 ± 111.3 g,which corresponded to graft-torecipient weight ratio of 0.95% ± 0.14%.The segment Ⅴor Ⅷ hepatic vein was reconstructed in 11 right-lobe grafts.The 1-year and 3-year recipient's survival and graft survival rates were 65%(13 of 20).Postoperative results of total bilirubin,INR and creatinine showed obvious improvements in the survived patients.However,the creatinine level of the deaths was increased postoperatively and became more aggravated compared with the level of the survived recipients.Multivariate analysis showed that waiting duration was independently correlated with increased mortality(P = 0.014).Furthermore,ROC curve revealed the cut-off value of waiting time was 5 d(P = 0.011,area under the curve = 0.791) for determining the mortality.The short-term creatinine level with different recipient's waiting duration was described.The recipients with waiting duration ≥ 5 d showed the worse renal function and higher mortality than those with waiting duration 5 d(66.7% vs 9.1%,P = 0.017).In addition,all donors had no residual morbidity.Furthermore,univariate analysis did not show that short assessment time induced the high morbidity(P = 0.573).CONCLUSION:Timely AALDLT for patients with ALF greatly improves the recipient survival.However,further systemic review is needed to investigate the optimal treatment strategy for ALF.     

Extracorporeal Liver Support Therapy With Prometheus in Patients With Liver Failure in the Intensive Care Unit

Acute liver failure (ALF) and acute‐on‐chronic liver failure (AoCLF) are associated with a high mortality. In these patients an accumulation of both water‐soluble and water‐insoluble, protein‐bound, metabolic waste products occurs. Conventional extracorporeal blood purification techniques based on diffusion and/or convection such as hemodialysis or hemofiltration may only eliminate small molecular weight, water‐soluble compounds. In recent years, fractionated plasma separation and adsorption (FPSA) with the Prometheus system has been introduced for extracorporeal liver support therapy. To date, however, only limited data is available regarding the effect of this treatment on mortality and outcome of patients with advanced liver disease. Here we report on our experience with 23 patients with severe liver failure who were treated with Prometheus in our medical intensive care unit. Fourteen patients had AoCLF, and nine patients experienced ALF. The median bilirubin level at the start of Prometheus therapy was 30.5 mg/dL and the median Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 26. During 40 individual treatment sessions lasting 5–6 h, Prometheus therapy reduced serum bilirubin levels from 23.7 mg/dL to 15.0 mg/dL (median values) (P < 0.001), and the overall survival was 26%. ALF patients had a better survival compared to AoCLF patients (44% vs. 22%; P = 0.022). Apart from one patient who developed hemodynamic instability during a treatment session, Prometheus therapy was well tolerated without relevant side‐effects. In conclusion, extracorporeal liver support therapy with Prometheus is a novel and safe treatment option in patients with severe liver failure. In this series, patients with ALF showed a significantly better outcome with Prometheus therapy compared to AoCLF patients.     

Is It Possible to Gain Extra Waiting Time to Liver Transplantation in Acute Liver Failure Patients Using Albumin Dialysis?

Hepatic encephalopathy (HE)‐associated brain edema is a common cause of death in acute liver failure (ALF). Molecular Adsorbent Recirculating System (MARS) albumin dialysis detoxifies endogenous and exogenous toxins from blood and improves HE. In this study we assessed the effect of MARS on increasing the length of time available while waiting for liver graft. Thirty‐seven patients with ALF who received a high‐urgent liver transplant (LTx) were divided into three groups according to the amount of histological necrosis in the explanted liver: group I = 100% necrosis; group II = 80–99% necrosis; group III = less than 80% necrosis. MARS was used continuously until LTx. Median time (range) on MARS treatment prior to LTx in groups I–III was 7 days (2–26), 6 days (1–17), and 5 days (1–15), and the median time on the waiting list was 5 days (1–11), 3 days (0–13), and 1 day (0–12), respectively. The HE grade prior to and after MARS was similar in all groups. In two patients the HE grade decreased during MARS treatment, even though the explanted liver showed a complete lack of viable cells. Overall 30‐day and one‐year survival were 97% and 92%, respectively, without differences between the three groups. In ALF patients the liver cell damage progressed to total or near total necrosis of the liver when the waiting time was prolonged. Yet, with MARS treatment some patients with total hepatic necrosis showed an absence of encephalopathy. With MARS treatment some patients might be able to wait longer for a LTx with good results.     

Molecular adsorbent recirculating system treatment for patients with liver failure: the Hong Kong experience.

BACKGROUND: The molecular adsorbent recirculating system (MARS) is an extracorporeal liver dialysis system that allows selective removal of bilirubin and other albumin-bound toxins. We reported here our experience with the use of this technique for management of liver failure at Queen Mary Hospital, Hong Kong. METHODS: From December 2002 to 2004, a total of 74 MARS sessions were performed on 22 patients. The cause of liver failure included acute liver failure (n = 2), acute on chronic liver failure (n = 12), posthepatectomy liver failure (n = 4), and posttransplantation allograft failure (n = 4). RESULTS: MARS treatment showed significant reduction in total bilirubin level, serum ammonia level and blood urea, and nitrogen (P < 0.001 for all three parameters). Five patients (22.7%) were able to bridge to transplantation and one patient (4.5%) made a spontaneous recovery. The 30-day mortality rate was 72.7%. CONCLUSIONS: Our results indicated that MARS can effectively improve serum biochemistry and is suitable for temporarily supporting patients with liver failure where transplantation is not immediately available. There is, however, no clear evidence showing that MARS can increase survival, improve the chance of transplantation or assist liver regeneration. Future studies in the form of randomized-controlled trials are crucial to characterize the true potential of this treatment.     

Survival predictors in patients treated with a molecular adsorbent recirculating system

AIM： To identify prognostic factors for survival in patients with liver failure treated with a molecular adsorbent recirculating system （MARS）.
METHODS： MARS is a liver-assisting device that has been used in the treatment of liver failure to enable native liver recovery, and as a bridge to liver trans-plantation （LTX）. We analyzed the 1-year outcomes of 188 patients treated with MARS, from 2001 to 2007, in an intensive care unit specializing in liver disease. Demographic, clinical and laboratory parameters were recorded before and after each treatment. One-year survival and the number of LTXs were recorded. Logistic regression analysis was performed to determine factors predicting survival.
RESULTS： The study included 113 patients with acute liver failure （ALF）, 62 with acute-on-chronic liver failure （AOCLF）, 11 with graft failure （GF）, and six with miscellaneous liver failure. LTX was performed for 29% of patients with ALF, 18% with AOCLF and 55% with GF. The overall 1-year survival rate was 74% for ALF,27% for AOCLF, and 73% for GF. The poorest survival rate, 6%, was noted in non-transplanted patients with alcohol-related AOCLF and cirrhosis, whereas, patients with enlarged and steatotic liver had 55% survival. The etiology of liver failure was the most important predictor of survival （P 〈 0.0001）. Other prognostic factors were encephalopathy （P = 0.001） in paracetamol-related ALF, coagulation factors （P = 0.049） and encephalopathy （P = 0.064） in non-paracetamol-related toxic ALF, and alanine aminotransferase （P = 0.013） and factor V levels （P = 0.022） in ALF of unknown etiology.
CONCLUSION： The etiology of liver disease was the most important prognostic factor. MARS treatment appears to be ineffective in AOCLF with end-stage cirrhosis without an LTX option.     

Living donor liver transplantation: histological abnormalities found on liver biopsies of apparently healthy potential donors

OBJECTIVE: With the continued shortage of deceased donor grafts, living donor liver transplantation has become an option for adult liver transplant candidates. In the non-transplant setting, liver biopsy is typically carried out to evaluate clinical or biochemical hepatic dysfunction. In living donor liver transplantation, assessment of histological abnormalities that are undetectable by serological, biochemical and radiological methods might play an important role in donor and recipient outcome. METHODS: Seventy consecutive liver biopsies carried out as part of our evaluation of potential donor candidates for adult-to-adult or adult-to-child living donor liver transplants were analyzed. RESULTS: Of the 70 potential donor candidates who underwent liver biopsy for evaluation for living donor liver transplantation, 67% had an unexpected abnormality, of which steatosis was the most common abnormality (38.5%). A variety of other histopathological abnormalities were found including granulomas of unknown etiology (7%), chronic hepatitis (6%) and a microabscess. None of the histological abnormalities had been suspected despite extensive clinical, serological or radiological investigation. CONCLUSIONS: Among the 70 potential donor candidates for living donor liver transplantation, 34% had unremarkable liver biopsies. The most common abnormality was steatosis (38.5%). These findings suggest that all potential candidates for living donor liver transplants should undergo screening liver biopsies. The precise significance of these changes remains to be determined, including which of these changes are contraindications to liver transplantation. These findings may also have implications in the non-transplant setting as changes ascribed to specific etiologies for liver disease might include changes occurring in apparently healthy individuals.     

Debate on live related liver transplant: Pro

Abstract   Live donor liver transplantation (LDLT) in adults is life saving for patients with fulminant hepatic failure, acute on chronic liver failure and end-stage cirrhosis, particularly in Asia where cadaveric organ donation is scarce. Without this modality, 50% of adult patients waiting for deceased donor liver grafts and 95% of patients with fulminant hepatic failure died. With right lobe LDLT, the overall survival rate of patients with fulminant hepatic failure increases from 5–50% and the transplant rate of patients waiting for deceased donor grafts increased from 13–42%.     

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.     

MELD score to predict outcome in adult patients with non-acetaminophen-induced acute liver failure.

AIMS/BACKGROUND: A model for end stage liver disease (MELD) score >30 was proposed as an excellent predictor of mortality in patients with non-acetaminophen-induced acute liver failure (ALF). We analyzed the prognostic value of MELD score in our patients with ALF who were prospectively registered in our database since 1990. METHODS: Overall, 106 patients met the criteria of ALF. Excluding seven patients with acetaminophen etiology, 99 patients (42+/-15 years, 40M/59F) were studied. RESULTS: Causes were cryptogenic (n=38), viral (n=29), drugs (n=20) and miscellaneous (n=12). Of these, 37% (n=37) survived with medical management alone (group I), 16% (n=16) died (group II) and 46% (n=46) underwent liver transplantation (group III). The strongest predictors of poor outcome were advanced encephalopathy, cryptogenic/drug-induced/hepatitis B etiology and a high MELD score. At the time of diagnosis, King's College Hospital criteria and MELD score >30 had similar high negative predictive value (92% and 91%, respectively) and low positive predictive value (52% and 56%, respectively). The predictive values improved only slightly during follow-up. The best cut-off point for MELD score to discriminate between survivors and nonsurvivors was >35, with a sensitivity and specificity of 86% and 75%, respectively. CONCLUSIONS: MELD score, which mostly takes into consideration the degree of liver impairment, has a similar prognostic value as King's College Hospital criteria to predict outcome in adult patients with nonacetaminophen-induced ALF. Overall, all current scores miss accuracy and therefore there is a clear need for factors that can better predict the regeneration of the liver in this setting.     

Acute liver failure secondary to acute antibody mediated rejection after compatible liver transplant: A case report

BACKGROUNDThe liver has traditionally been regarded as resistant to antibody-mediated rejection (AMR). AMR in liver transplants is a field in its infancy compared to kidney and lung transplants. In our case we present a patient with alpha-1-antitrypsin disease who underwent ABO compatible liver transplant complicated by acute liver failure (ALF) with evidence of antibody mediated rejection on allograft biopsy and elevated serum donor-specific antibodies (DSA). This case highlights the need for further investigations and heightened awareness for timely diagnosis.CASE SUMMARYA 56 year-old woman with alpha-1-antitrypsin disease underwent ABO compatible liver transplant from a deceased donor. The recipient MELD at the time of transplant was 28. The flow cytometric crossmatches were noted to be positive for T and B lymphocytes. The patient had an uneventful recovery postoperatively. Starting on postoperative day 5 the patient developed fevers, elevated liver function tests, distributive shock, renal failure, and hepatic encephalopathy. She went into ALF with evidence of antibody mediated rejection with portal inflammation, bile duct injury, endothelitis, and extensive centrizonal necrosis, and C4d staining on allograft biopsy and elevated DSA. Despite various interventions including plasmapheresis and immunomodulating therapy, she continued to deteriorate. She was relisted and successfully underwent liver retransplantation.CONCLUSIONThis very rare case highlights AMR as the cause of ALF following liver transplant requiring retransplantation.     

Hepatitis C Virus Recurrence in Living Donor Liver Transplant Recipients

Recurrence of hepatitis C virus (HCV) after liver transplantation (LT) is a universal phenomenon. Recent reports have suggested an earlier and more aggressive recurrence in the living donor liver transplant (LDLT) population. The aim of this study was to compare the histological recurrence of HCV after LDLT versus deceased donor transplantation (DDT). Twenty-nine patients underwent LT for HCV-related end-stage liver disease at our institution between April 2001 and March 2003 (42 months). Twenty patients underwent DDT, and nine patients LDLT. Laboratory data were collected on a weekly to biweekly basis and HCV PCR was performed before LT and 3-4 months and yearly post-LT. Liver biopsies were performed as needed and per institutional protocol at 7 days, at 4 months, and yearly thereafter. All biopsies were evaluated by a single pathologist and scored for rejection (Banff score) and chronic hepatitis (Ishak score system). The predominant genotype in the DDT and LDLT groups was genotype 1 (DDT = 70%, LDLT = 79%). HCV RNA titers pre-LT and 3-4 months after LT did not differ. The incidence of rejection was higher in the DDT group (P < 0.05). There was a trend toward improved Ishak stage and grade in the LDLT group at 4 and 12 months post-LT, however, this trend did not reach statistical significance. No histological difference in the recurrence or severity rate was observed at 4 or 12 months post-LT in the DDT group vs. the LDLT group.     

Effect of Extracorporeal Liver Support by Molecular Adsorbents Recirculating System and Prometheus on Redox State of Albumin in Acute‐on‐Chronic Liver Failure

Oxidative stress is believed to play an important role in acute‐on‐chronic liver failure (AoCLF). Albumin, an important transport vehicle, was found to be severely oxidized in AoCLF patients. Extracorporeal liver support systems may exert beneficial effects in AoCLF via removal of albumin‐bound toxins. At present, two systems are commercially available, the molecular adsorbents recirculating system (MARS) and fractionated plasma separation, adsorption and dialysis (FPAD, also known as Prometheus). The aim of this study was to compare the effect of MARS and Prometheus treatments on the redox state of human serum albumin. Eight patients with AoCLF underwent alternating treatments with either MARS or Prometheus in a randomized cross‐over design. Sixteen treatments (eight MARS and eight Prometheus) were available for analysis. The fraction of human mercaptalbumin (HMA), human nonmercaptalbumin‐1 (HNA1), and human nonmercaptalbumin‐2 (HNA2) were measured before and after single MARS and Prometheus treatments and during follow‐up. In AoCLF patients the oxidized fractions of albumin, HNA1, and HNA2 were markedly increased. Both MARS and Prometheus treatments resulted in a shift of HNA1 to HMA, while HNA2 was not significantly affected. This shift in albumin fractions was transient and disappeared within 24 h after treatment. There were no significant differences between MARS and Prometheus treatments with respect to the redox state of albumin. Both MARS and Prometheus treatments lead to transient improvements of the redox state of albumin, which could be beneficial in the treatment of AoCLF.     

Problem of living liver donation in the absence of deceased liver transplantation program: Mansoura experience

We report our experience with potential donors for living donor liver transplantation (LDLT), which is the first report from an area where there is no legalized deceased donation program. This is a single center retrospective analysis of potential living donors (n = 1004) between May 2004 and December 2012. This report focuses on the analysis of causes, duration, cost, and various implications of donor exclusion (n = 792). Most of the transplant candidates (82.3%) had an experience with more than one excluded donor (median = 3). Some recipients travelled abroad for a deceased donor transplant (n = 12) and some died before finding a suitable donor (n = 14). The evaluation of an excluded donor is a time-consuming process (median = 3 d, range 1 d to 47 d). It is also a costly process with a median cost of approximately 70 USD (range 35 USD to 885 USD). From these results, living donor exclusion has negative implications on the patients and transplant program with ethical dilemmas and an economic impact. Many strategies are adopted by other centers to expand the donor pool; however, they are not all applicable in our locality. We conclude that an active legalized deceased donor transplantation program is necessary to overcome the shortage of available liver grafts in Egypt.     

Adefovir dipivoxil therapy in liver transplant recipients for recurrence of hepatitis B virus infection despite lamivudine plus hepatitis B immunoglobulin prophylaxis

BACKGROUND: Treatment of post-transplantation recurrence of hepatitis B virus (HBV) infection despite prophylaxis with hepatitis B immunoglobulin (HBIG) and lamivudine combination therapy is not easy. Because HBV reinfection has a severe course and could result in graft failure in liver transplant recipients, prompt medication is essential. Herein is reported the authors' experience with adefovir dipivoxil (AD) therapy in 11 liver transplant recipients who had HBV reinfection despite the administration of lamivudine and HBIG. METHOD: Two-hundred and nine patients underwent liver transplantation (100 deceased donor liver transplantations [DDLT], 109 living donor liver transplantation [LDLT]) due to chronic hepatitis B infection between April 1997 and May 2005 in Ege University Medical School, Liver Transplantation Unit. Patients had prophylaxis with lamivudine and low-dose HBIG combination after liver transplantation. Treatment of recurrence consisted of AD 10 mg once a day and lamivudine 300 mg/daily and HBIG was discontinued in those patients. RESULTS: In total there were 11 HBV recurrences: five occurred in DDLT recipients and six in LDLT recipients, at a median follow up of 18 months (range, 6-48 months). In one of 11 patients, pretransplant HBV-DNA and HBeAg were positive. Three patients had a severe course and one patient had fibrosing cholestatic hepatitis. After AD treatment, HBV-DNA level decreased in all patients and became negative in seven patients. Two patients died due to hepatocellular carcinoma recurrence after 12 and 14 months of follow up. Serum creatinine level increased mildly in one patient and no other side-effect was observed, and all patients continued therapy. CONCLUSION: Adefovir dipivoxil is a safe, effective treatment option for post-transplant HBV recurrence even among patients with fibrosing cholestatic hepatitis caused by lamivudine-resistant HBV.     

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.     

Kluyvera co‐infection in two solid organ transplant recipients: an emerging pathogen or a colonizer bystander?

Kluyvera species are opportunistic, gram-negative bacilli in the family Enterobacteriaceae. Ordinarily occurring as a commensal, Kluyvera have been reported to cause serious infections in immunosuppressed and immunocompetent hosts, causing diarrhea, urinary infections, peritonitis, and cholecystitis. We report Kluyvera infections in 2 solid organ transplant recipients. An 18-year-old female with alpha-1 antitrypsin deficiency underwent living donor liver transplantation and presented 6 months later with a liver abscess. The abscess aspirate grew mixed organisms including Kluyvera cryocrescens. A 22-year-old female with renal failure secondary to focal segmental glomerulosclerosis underwent a deceased donor kidney transplant and presented 3 months later with pyelonephritis; the urine culture grew Kluyvera ascorbata. Both patients improved only when their antibiotic coverage was broadened to include Kluyvera. The isolation of Kluyvera as a pathogen in transplant patients emphasizes that this commensal organism may be virulent in this patient population.     

Live donor liver transplantation for acute liver failure: A single center experience

Introduction

Acute liver failure (ALF) is an indication for emergency liver transplantation (LT). Although centers performing only deceased donor liver transplants (DDLT) have shown improved outcomes in this situation, they still have relatively long waiting lists. An alternative would be living donor liver transplantation (LDLT), which has shown equivalent outcomes in the elective situation but there is limited evidence of its results in ALF.

Aim

The purpose of this study was to assess the outcomes in patients with ALF undergoing emergency LDLT in our center in Delhi, India.

Methods

We prospectively collected data on 479 patients who underwent LT in our hospital between January 2009 and December 2015 to evaluate the outcomes of those with ALF. The ALF patients were listed for transplantation after they met the Kings’ College criteria and rapid evaluation was done following a protocol consisting of three phases. Patients with grade III/IV encephalopathy were put on mechanical ventilation. Data regarding their postoperative course, morbidity, and mortality were analyzed.

Results

Thirty-six (7.5%) out of the 479 patients underwent emergency LT for ALF. Their mean age was 27.5 years (range 4–59 years) and the male to female ratio of 2:3. Preoperative intubation was required in 15 of 25 patients who had encephalopathy. Wilson’s disease was the most common cause of ALF in children while in adults, it was acute viral hepatitis. The time interval between listing and transplantation was a mean of 36?±?12.4 h. The mean graft to recipient weight ratio (GRWR) was 1.06?±?0.3. The recipients were extubated postoperatively after a mean period of 2.6 days and their mean ICU stay was 6.3 days. Postoperative infection was the most common complication and required upgradation of antifungal and antibiotic treatments. Neurological complications occurred in five patients. Thirty-one of 36 (86.1%) patients survived and progressive cerebral edema and sepsis were the most common causes of mortality. Patients who died had higher model for end-stage liver disease scores, longer cold ischemia time (CIT), and higher grades of encephalopathy (though 80% patients with encephalopathy survived). There was no donor mortality. At long-term follow up of a median of 56 months, 29 (80.5%) of 36 patients were still alive.

Conclusions

In our experience, LDLT is an alternative procedure to DDLT in patients with ALF and is associated with good outcomes even in patients with high grades of encephalopathy.