Abstract
OBJECTIVE To evaluate the effect and safety of a Molecular Adsorbent Recycling System (MARS) in treating posthepatoectomy hepatic failure (AHF) patients surgically treated for primary hepatocellular carcinoma (HCC).
METHODS 12 AHF patients induced by resection of HCC were treated with MARS before orthotopic liver transplantation (OLT). Their vital signs, urine volume, APACHEIII and Glasgow scores were monitored. Routine laboratory blood tests, measurements of coagulatory function, liver and kidney function, serum ammonia, lactic acid and blood gas were conducted before and after treatment with MARS. All of the patients were followed up for a period of 6 months after OLT for prognosis and complication assessment.
RESULTS Each patient was treated with MARS for 2~5 times (average of 3.6) with a length of 8~24 h each time. Their mean arterial blood pressure and urine volume were Improved, APACHE III and Glasgow scores were better. Liver function was Improved with the following alterations before and after treatment with MARS: serum ammonia (127.1 ±21.4 umol/L vs. 77.4±19.7 umol/L, P<0.05), lactic acid (6.53±0.45 mmol/L vs. 3.75± 0.40 mmol/L, P<0.05) and total bilirubin (452.3±153.7 umol/L vs. 230.9± 115.2 umol/L, P <0.05). However, there was no significant change In platelet count (44.25±3.60x109/L vs. 43.19±8.26x109/L, P>0.05) on international normalized ratio (INR) (2.74±0.50 vs. 2.82±0.60, P>0.05), which showed the safety of MARS. For all patients no serious adverse effects occurred during the treatment with MARS.
CONCLUSION MARS is effective and safe for treatment of AHF patients with HCC, especially as a bridge to OLT when a donor organ is not available.
keywords
Orthotopic liver transplantation (OLT) has been performed successfully for irreversible acute and chronic hepatic failure. To improve the prognosis an artificial liver support system is important for candidates to maintain the function of major organs before OLT,lul a Molecular Adsorbent Recycling System (MARS) involves a dialysis treatment composed of a MARS membrane that mimics the hépatocyte membrane. This treatment allows albumin dialysis which is similar to the detoxification role of the liver. It successfully enables the selective removal of both water-soluble and albumin-bound toxins metabolized by the liver, and works as a bridge to OLT.3 To evaluate the effect and safety of MARS, our center used this procedure in clinical treatment of acute hepatic failure (AHF) patients induced by resection of primary hepatocellular carcinoma (HCC).
PATIENTS AND METHODS
Patients
AHF patients with HCC were treated in our center from January, 2004 to January, 2005. A Child-Pugh grade of hepatic function and APACHE HI scores were used to evaluate the patients' status.
Inclusive criteria for MARS treatment
Serum total bilirubin more than 20 mg/dl, a Child-Pugh score between 11 and 15, hepatic encephalopathy (HE) more than phase II, hepatorenal syndrome (HRS). The patients displayed at least one of the above symptoms without active hemorrhage or low blood pressure (arterial mean blood pressure, AMBP>50 mmHg without vasoactive drugs) to begin the treatment.
Exclusive criteria for MARS treatment
Active hemorrhage or low blood pressure (arterial mean blood pressure, AMBP<50 mmHg with vasoactive drugs).
Criteria for ending of MARS treatment
AMBP lower than 50 mmHg for 10 min or more, coagulation of the blood in the extracorporeal recycling system, transmembrane pressure (TMP) greater than 600, detection of a blood leak, disseminated intravascular coagulation (DIC) or active hemorrhage.
Patients included
Twelve patients with AHF induced by resection of HCC, including 10 male and 2 female of ages 36 to 60 years (mean 48.4). All of the 12 patients were Child-Pugh grade C, 2 of them with HRS and 6 of them with HE more than phase II. The patients' status is shown in Table 1
Patients' status with MARS treatment
MARS treatment procedure
The blood purification system was MARS ® Monitor made in Germany by the TERAKLIN Co. using MARS ® Treatment Kit 1112/0. Veno-venous access using a double-lumen central venous dialysis catheter (1 IF) was used for the blood supply. A total of 600 ml of 20% albumin was used to prime and fill the albumin dialysate circuit. Heparin was used to prevent blood-circuit clotting and to maintain ACT between 160 to 180 s. Data for patients observed before, during and after the treatment: blood pressure, consciousness, urine volume, blood routine, ACT (using Sonoclot), liver and kidney function, serum ammonia, lactic acid, blood gas analysis and the APACHE III score. End point of treatment: serious allergy, hemorrhage or blood circuit clotting.
Statistical method
descriptive statistics were expressed as the mean±SD, the Wilcoxon test was used to compare the data before and after MARS, with P<0.05 considered significant. All the patients were followed-up for a period of 6 months after OLT to record survival and complications.
RESULTS
Each patient was treated with MARS for 2~5 times (average of 3.6) with a length of 8~24 h each time. There was one case of rhinorrhagia and another with blood circuit clotting during the treatment. All of the 12 patients underwent OLT after MARS treatment. The length of time from initial MARS treatment to OLT was 6.67 ±1.87 days. The 1 and 6-month patient survival rates were both 100%. Occurrence rates of pneumonia and biliary complication were 25% (3/12) and 13.33% (1/12) respectively. Effect of MARS is shown in Table 2Table 3Table 4.
General status of the patients before and after MARS
Laboratory tests for the patients before and after MARS
Occurrence of complications after OLT
DISCUSSION
Orthotopic liver transplantation (OLT) has been performed successfully for irreversible acute and chronic hepatic failure. With rapid hepatic function deterioration, metabolic disturbance and dysfunction of other important organs will lead to a high mortality of 70-80% in spite of all kinds of internal medical therapy. OLT ultimately improves the prognosis of these patients.[1,2] With the shortage of donor organs, many kinds of artificial liver support systems (ALSS) have been used to maintain hepatic function and decrease mortality, including plasmapheresis (PE), bilirubin specific adsorption (BSA), continuous veno-venous hemofiltration (CWH) and MARS.[4,5,6] PE is effective in removal of serum bilirubin, endotoxin, tumor necrosis factor (TNF) and some other inflammatory factors, so it is the most widely used ALSS. But the need of large volume of fresh frozen plasma and the risk of transmitted infection limit the use of PE. Use of BSA for hemoperfusion selectively adsorbs bilirubin and a portion of bile acid, with no effect on other metabolic toxins.m CWH is effective in removal of excessive body fluid and only water-soluble toxins to maintain the equilibrium of body fluids, electrolytes and pH. MARS is composed of a hyper-penetrable sufonated dialyzer that can be combined with albumin and other circulatory factions. The MARS FLUX dialyzer, that mimics the hepatocyte membrane and albumin dialysis, which mimics the detoxification procedure of the liver, enables the system to selectively remove both albumin-bound and water-soluble toxins. This procedure mimics the metabolic function of liver to ameliorate AHF. MARS is more effective than any other kind of ALSS, so it is used as a bridge to OLT for AHF patients.[3]
Tumor resection is still the major surgical choice for HCC at present. The rate of AHF after hepatic resection for HCC may be high as 36.8% leading to poor prognosis.[8] So sufficient evaluation should be made before resection to avoid the occurrence of AHF. [9] Several researches from different centers have showed that treatment with MARS can improve the prognosis of AHF patients with HCC.[10-12]
In patients with AHF caused by hepatectomy treatment for hepatocelluar carcinoma, MARS can alleviate the severity of their general condition. Chiu et al.[13] reported on the treatment of 22 patients using MARS. The cause of liver failure in this study included 2 patients with acute liver failure, 12 patients with acute or chronic liver failure, 4 patients with posthepatectomy liver failure, and 4 patients with post-transplantation allograft failure. MARS treatment showed significant reduction in the following: total bilirubin level of over 15 mg/L and hepatic encephalopathy higher than phase II, serum ammonia level and blood urea, and nitrogen. 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%. MARS can increase survival, improve the chance of transplantation or assist liver regeneration.
Our study showed that, MARS with characteristics of both dialyzer and continuous filtration, can be used continuously and repeatedly. Its function includes effective removal of toxins, regulation of the balance of body fluids and acid-based metabolism; however, its effect on hemodynamics and blood coagulation is minimal. The therapeutic effects were shown by the efficiency and the safety of MARS treatment without disturbance of coagulation. No serious adverse effects occurred during the treatment with MARS for all the 12 patients. With these results, we feel it is effective and safe to use MARS for AHF patients induced by resection of HCC, especially as a bridge to OLT when donor organs and blood are in short supply or lacking.
- Received July 11, 2006.
- Accepted August 4, 2006.
- Copyright © 2006 by Tianjin Medical University Cancer Institute & Hospital and Springer
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