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Prediction Value of Model for End-Stage Liver Disease Scoring System on Prognosis in the Acute on Chronic Liver Failure Patients With Plasma Exchange Treatment

Mao, Weilin*; Ye, Bo*; Lin, Sha*; Fu, Yajie*; Chen, Yuemei; Chen, Yu*

doi: 10.1097/MAT.0b013e3181e6bf13
Liver/Pancreas Support

Hepatitis B virus-related acute-on-chronic liver failure (AoCLF) is associated with a high mortality rate. Plasma exchange (PE) is useful to bridge patients with AoCLF to liver transplantation or recovery. The aim of this study was to analyze the impact of the model for end-stage liver disease (MELD) score on 30-day survival in patients with AoCLF treated with PE or conventional medications and to evaluate the therapeutic effectiveness of PE. In this study, 62 enrolled patients with AoCLF who received PE treatment were compared with 131 patients treated with conventional medications. The MELD scores were calculated according to the original formula, and the 30-day survival in patients was recorded. The 30-day survival rate of the patients who received PE versus controls was 41.9% versus 25.2% (p < 0.05). The 30-day survival rate of patients in the PE group (50.0%) with a MELD score from 20 to 30 was higher than that of the control group (31.7%, p < 0.05); for MELD scores more than 30, there was no significant difference in two groups (8.3% vs. 0%, p > 0.05). PE seems to be efficacious and safe for the treatment of patients with AoCLF and significantly increased the survival rates of patients with a MELD score of 20–30.

From the Departments of *Clinical Laboratory and †Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.

Submitted for consideration August 2009; accepted for publication in revised form March 2010.

Reprint Requests: Weilin Mao, MD, Department of Clinical Laboratory, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang, People's Republic of China, 310003. Email: maoweilin100@gmail.com.

Despite the best available intensive medical support, liver failure still carries a substantial mortality.1 In China, hepatitis B virus (HBV)-related acute-on-chronic liver failure (AoCLF) is the most familiar type of liver failure; it occurs because of sudden and severe impairment or loss of hepatocyte functions in patients with chronic liver diseases. Orthotopic liver transplantation (OLT) is the ultimate procedure to save patients suffering from AoCLF.2 However, numerous patients on liver transplantation waiting lists die because of the persistent scarcity of donor livers. In such a situation, extracorporeal liver support may improve survival by bridging patients to OLT or to regeneration of their own diseased livers.3 Plasma exchange (PE) separates and discards the plasma to remove the toxic substances (especially those binding with proteins) and compensates with an identical volume of normal fresh frozen plasma to supplement essential substances such as coagulation factors, albumin, and immunoglobin, so as to ameliorate the microenvironment of the liver and accelerate liver regeneration and functional recovery.4 However, some patients remain at a high risk of death even with PE therapy. Such patients are identified based on the obvious clinical deterioration and are the ideal candidates for emergency OLT because their livers have virtually no chance of self-regeneration. Accurate prediction for prognosis of patients with AoCLF is important to select appropriate procedures, such as internal combined therapy and liver transplantation, so as to relieve the economic and social burden. The model for end-stage liver disease (MELD) score is based on the results of three readily available, objective, and reproducible laboratory tests: the total serum bilirubin concentration, the international normalized ratio (INR) for the prothrombin time, and the serum creatinine concentration.5 In the United States, the MELD score has been used in determining priorities for organ allocation in liver transplantation since 2002.6 Yu et al. 7 reported that the model for MELD score was related to the prognosis of the patients with AoCLF. PE is useful to bridge patients with AoCLF to liver transplantation or to regenerate their own livers.8 In this study, we use the MELD scoring system to predict the 30-day prognosis of patients with AoCLF and to evaluate the therapeutic effectiveness of PE.

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Patients and Methods

A total of 193consecutive hospitalized patients with acute-on-chronic HBV liver failure (HBV-DNA ≥1 × 104 copies/ml) were selected from the Department of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, China, between January 2006 and December 2008. Of these, 62 patients with AoCLF who received PE therapy for 1–8 sessions were compared with 131 patients treated with standard medical therapy (control group). Randomization was not performed in this study. In China, PE therapy is not included in health insurance, so it cannot be offered to some patients for economic reasons. Also, some AoCLF patients in the same unit did not receive it because the plasma or machine was unavailable. The diagnosis of these patients was performed according to the criteria of diagnostic and treatment guidelines for liver failure formulated by the Chinese Medical Association.9 AoCLF is described as acute decompensation of liver function in patients with chronic preexisting liver diseases. AoCLF is defined as a syndrome with severe jaundice (total bilirubin >171 mmol/L), coagulopathy (prolonged prothrombin time, prothrombin activity <40%), or hepatic encephalopathy (above grade II). Drug hepatitis, Wilson disease, alcoholic liver disease, and autoimmune hepatitis are excluded. Patients were excluded if they had hepatitis C or D or HIV infection. The clinical characteristics of patients on admission are presented in Table 1. There was no significant difference between the PE and control groups. The study protocol was approved by the local ethics committee, and written informed consent was obtained from all patients or their next of kin.

Table 1

Table 1

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Study Protocol

The 131 patients in the medical group were given standard medical treatment. This included absolute bed rest; energy supplements and vitamins; intravenous drop infusion albumin and plasma; maintenance of water, electrolyte, and acid-base equilibrium; and prevention and treatment of complications.

Patients in the PE group underwent treatment in addition to intensive monitoring and standard medications. PE was performed using the membrane separation method marketed as Plasmacure PS-06 (Kuraray Co., Tokyo, Japan). The total volume of exchanged plasma was approximately 3500 ml, at 25–30 ml/min PE rate. A total of 3000–4500 ml of fresh frozen plasma (40–60 ml/kg) and 20–40 g of human albumin were supplied. The flow rate of blood was adjusted to 60–130 ml/min, and blood pressure and pulse were recorded continuously during treatment (Figure 1). PE therapy was carried out two or three times in the first or second week depending on vascular access, and the level of clotting factors was observed before PEs and then one time each week, depending on the clinical results, and then stopped.10 The levels of serum creatinine, the INR for prothombin time, and the level of serum total bilirubin of each AoCLF patient were recorded.

Figure 1.

Figure 1.

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Statistical Analysis

All data were analyzed using SPSS version 13.0 for Windows software. Results were expressed as mean ± SD or as number of subjects (percentage). Analysis of survival rates of the different groups was done using the chi-square test; and for all analyses, a p < 0.05 was considered statistically significant.

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Results

In all, 197 single treatments were performed on 62 patients with an average of 3.2 sessions/patient (range, 1–8 sessions/patient) at an interval of 3–5 days, PE therapies were relatively safe and tolerable under comparable conditions without any severe adverse events.

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30-Day Survival Rate in Patients With AoCLF

In the study subjects, 26 survivors and 36 nonsurvivors were in the PE group, whereas 33 survivors and 98 nonsurvivors were in the control group after 30 days treatment. Their survival rates were 41.9% and 25.2% for PE and medical therapy, respectively (p < 0.05).

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Relationship Between MELD Scores and 30-Day Survival Rate

The MELD score was calculated according to the following formula11: MELD = (0.957 × Loge [creatinine in milligram per deciliter] + 0.378 × Loge [bilirubin in milligram per deciliter] + 1.12 × Loge [INR] + 0.643) × 10). The MELD scores of all the patients at admission (day 0) were more than 20. Patients were divided into two groups according to MELD scores: 20–30 and more than 30. The 30-day survival rate of patients with a MELD score from 20 to 30 was 50.0% (25/50) in the PE group and 31.7% (33/104) in the control group, showing significant difference between the two groups (p < 0.05). The 30-day survival rate of patients with a MELD scores higher than 30 were 8.3% (1/12) in the PE and 0 (0/27) in the control group, and there was no significant difference in two groups (p > 0.05; (Figure 2).

Figure 2.

Figure 2.

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Discussion

HBV-associated AoCLF is the leading cause of liver failure worldwide and is the most common reason for liver transplantation in China. It has been reported that PE improves metabolic state in patients with hepatic failure until a donor organ is available or the diseased liver regenerates.12 Although PE cannot replace the entire spectrum of hepatic function, such techniques can substitute a few elementary liver functions and were reported to reduce mortality in cases of AoCLF when compared with standard medical therapy.13

The MELD scoring system was previously formulated to predict 3-month mortality in cirrhotic patients undergoing transjugular intrahepatic portosystemic stent shunt.14 Recent studies have demonstrated that the MELD score accurately predicted the mortality risk for a variety of different causative factors of liver disease.15 The short-term survival rates of patients with end-stage liver disease decrease gradually as the MELD score increases. This MELD scoring system was not only objective but also consistent with the characteristics of AoCLF (e.g., hyperbilirubinemia, coagulopathy, and renal function failure), so it may be used to predict the prognosis of AoCLF patients.

We studied the 30-day prognosis of patients with AoCLF after PE treatment using the MELD scoring system. The 30-day survival rate of the patients with a MELD score of 20–30 given standard medical treatment was 31.7%, whereas for those given PE was 50.0%, suggesting that PE significantly increased the short-term survival rate of these patients, so artificial liver support system treatment should be started as early as possible as a regular form of therapy. The 30-day survival rate of patients with a MELD score more than 30 given standard medical treatment was 0%, whereas for those given PE was 8.3%, suggesting that PE did not significantly increase the short-term survival rate in these patients. Liver transplantation may be the only effective therapeutic modality to save these patients' lives.

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Conclusion

In this study, we confirmed that the MELD scoring system is a reliable method for predicting the short-term survival in patients with AoCLF. PE treatment significantly increases the survival rates of patients with a MELD score from 20 to 30 compared with controls but have no effect on patients with a MELD score higher than 30. AoCLF patients with a MELD score from 20 to 30 were selected to receive PE therapy to gain the best therapeutic effects. We are aware that a randomized control study is needed to obtain a firm conclusion in this study. However, it is extremely difficult to perform a randomized study on the critically ill patients with acute liver failure who actually have very little chance to receive a liver transplantation in our country. Because of our small sample size, another causal factor may exist, and a larger study will be needed to validate the efficacy of the MELD score.

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Acknowledgment

The authors thank all the members of Department of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, for their assistance in data collection.

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References

1. Mas A, Rodes J: Fulminant hepatic failure. Lancet 349: 1081–1085, 1997.
2. Ostapowicz G, Lee WM: Acute hepatic failure: A Western perspective. J Gastroenterol Hepatol 15: 480–488, 2000.
3. Chen S, Zhang L, Shi Y, et al: Molecular adsorbent recirculating system: Clinical experience in patients with liver failure based on hepatitis B in China. Liver 22: 48–51, 2002.
4. Yoshiba M, Inoue K, Sekiyama K, Koh I: Favorable effect of new artificial liver support on survival of patients with fulminant hepatic failure. Artif Organs 20: 1169–1172, 1996.
5. Malinchoc M, Kamath PS, Gordon FD, et al: A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology 31: 864–871, 2000.
6. Freeman RB Jr, Wiesner RH, Harper A, et al: The new liver allocation system: Moving toward evidence-based transplantation policy. Liver Transpl 8: 851–858, 2002.
7. Yu JW, Wang GQ, Li SC: Prediction of the prognosis in patients with acute on chronic hepatitis using MELD scoring system. J Gastroenterol Hepatol 21: 1519–1524, 2006.
8. Matsubara S: Combination of plasma exchange and continuous hemofiltration as temporary metabolic support for patients with acute liver failure. Artif Organs 18: 363–366, 1994.
9. Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, Chinese Medical Association and Severe Liver Diseases and Artificial Liver Group: [Diagnostic and treatment guidelines for liver failure.] Zhonghua Gan Zang Bing Za Zhi 14: 643–650, 2006; in Chinese.
10. The group of the artificial liver of Society of Infectious Diseases and Parasitic Diseases, CMA. [Operating guide for artificial liver support system.] Zhonghua Gan Zang Bing Za Zhi 10: 329–333, 2002; in Chinese.
11. Bambha K, Kim WR, Kremers WK, et al. Predicting survival among patients listed for liver transplantation: an assessment of serial MELD measurements. Am J Transplant 4: 1798–1804, 2004.
12. Uchino J, Matsushita M: Strategies for the rescue of patients with liver failure. ASAIO J 40: 74–77, 1994.
13. Du WB, Li LJ, Huang JR, et al: Effects of artificial liver support system on patients with acute or chronic liver failure. Transpl Proc 37: 4359–4364, 2005.
14. Malinchoc M, Kamath PS, Gordon FD, et al: A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology 31: 864–871, 2000.
15. Kremers WK, van IJperen M, Kim WR, et al: MELD score as a predictor of pretransplant and posttransplant survival in OPTN/UNOS status I patients. Hepatology 39: 764–769, 2004.
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