Renal Outcomes After Liver Transplantation in Fulminant Hepatitis A With Acute Kidney Injury: Comparison With Hepatorenal Syndrome J.Y. Parka, G.Y. Gwakb, J.M. Kimc, H.J. Ohd, N.J. Yie, K.S. Suhe, D.K. Kima, C.S. Limf, Y.S. Kima, and J.P. Leef,* a Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea; bDepartment of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; cDepartment of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; dDepartment of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea; eDepartment of Surgery, Seoul National University College of Medicine, Seoul, Korea; and fDepartment of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea
ABSTRACT Background. Liver transplantation (LT) is the treatment of choice for hepatorenal syndrome (HRS). Recently, acute kidney injury (AKI) due to acute hepatitis A (HA) is increasing, but the outcome of LT is not well established. We investigated the outcomes of LT in patients with AKI due to acute HA compared with those of patients with HRS due to other causes. Methods. We investigated the outcomes of LT in 20 patients with AKI associated with acute HA (HAV group) compared with 76 patients with hepatorenal syndrome (HRS) due to other causes (HRS group) at 3 Korea centers. Results. Preoperative mean prothrombin time and serum creatinine level were higher in the HAV group than in the HRS group. But mean total bilirubin level was lower in the HAV group. There was no difference in Model for End-Stage Liver Disease scores. Posttransplantation patient and graft survival rates were similar between the 2 groups. More patients in the HAV group needed post-transplantation hemodialysis than in the HRS group (65.0% vs 38.2%; P ¼ .043). However, post-transplantation estimated glomerular filtration rate was significantly higher in the HAV group after post-transplantation month 2 (P < .05). Conclusions. Peri-transplantation kidney function of the HAV group was poorer than that of HRS group. However, post-transplantation long-term renal outcome could be better in the HAV group.
A
CUTE hepatitis A (HA) is one of the most common infectious diseases worldwide, with a clinical spectrum ranging from asymptomatic to fulminant hepatitis, which occurs in 50 mmol, in a patient without any previous liver disease. It often is associated with multiple organ failure. Until recently, the mortality rate ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
Transplantation Proceedings, 47, 709e717 (2015)
FHF was close to 80% [5]; however, with aggressive medical therapy, intensive care monitoring, and the advent of liver transplantation (LT), survival rates have improved considerably [6]. Nevertheless, LT is a rare treatment option for acute hepatitis and thus the outcomes are not well understood. Funding: Korea Healthcare Technology R&D Project, Ministry for Health and Welfare, Republic of Korea (grant A102065). *Address correspondence to Jung Pyo Lee, MD, PhD, Assistant Professor, Department of Internal Medicine, Seoul National University Boramae Medical Center, 425 Sindaebang 2-dong, Dongjak-gu, Seoul 156-707, Republic of Korea. E-mail: [email protected] 0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2014.10.057
709
710
PARK, GWAK, KIM ET AL
1940 adult patients underwent LT between 2005 and 2012
147 patients, pretransplant AKI
• 37 patients: Prerenal failure • 1 patient: Nephrotoxic renal failure • 13 patients: Parenchymal renal disease (HBGN, DN, ATN)
96 patients
20 patients, HAV group
Fig 1. Flow diagram of the study protocol. Abbreviations: HBGN, hepatitis B virus associated glomerulonephritis; DN, diabetic nephropathy; ATN, acute tubular necrosis.
Acute kidney injury (AKI) is a frequent complication in the setting of fulminant viral hepatitis [7]. Hepatorenal syndrome (HRS) is the most common cause of AKI in endstage liver disease, with LT as the treatment of choice [8e10]. However, AKI due to fulminant hepatitis A has shown several different renal manifestations compared with HRS regarding to high urinary sodium, hematuria, and proteinuria [11,12]. Furthermore, clinical outcomes after LT in patients with fulminant HA with AKI have not been thoroughly investigated. We aimed to investigate the outcomes of LT in patients with AKI in fulminant HA compared with patients undergoing LT for HRS due to other causes. METHODS Study Population This study was performed as a retrospective multicenter study. We reviewed 1,940 consecutive adult (age >18 y) Korean patients who underwent LT at Samsung Medical Center, Seoul National University Hospital, and Yonsei University Severance Hospital from 2005 to 2012. We focused on patients with AKI in acute hepatitis A, and HRS due to other causes. Twenty patients with acute hepatitis A who underwent LT because of FHF with AKI (HAV group) were compared with 76 (HRS group) patients who underwent LT because of HRS due to other causes, including 17 fulminant cases. Patients who did not fulfill HRS criteria in the HRS group and those who had prerenal, nephrotoxic renal failure in the HAV group were excluded.
76 patients, HRS group
17 patients, Fulminant
59 patients, Non-fulminant
This study was approved by the institutional Review Boards of Samsung Medical Center, Seoul National University Hospital, and Yonsei University Severance Hospital. All clinical investigations were conducted in accordance with the guidelines of the 2000 Declaration of Helsinki. Informed consents were obtained from all donors and recipients before transplantation.
Definition of FHF and AKI The definition of FHF was based on the American Association for the Study of Liver Diseases practice guidelines for the management of acute liver failure, update 2011, and included the following: evidence of coagulation abnormality, usually a prothrombin time (PT)/INR 1.5, and any degree of mental alteration (encephalopathy) in a patient without preexisting cirrhosis and with an illness of .999
7 (100.0) 0 (0.0) 0 (0.0) 6 (85.7)
8 (88.9) 1 (11.1) 0 (0.0) 5 (50.0)
6 (66.7) 3 (33.3) 2 (28.6)
7 (63.6) 4 (36.4) 5 (55.6)
.286
.654 .989 .342 .015 .246 .381 .777 .985
4.2 20.6 12.3 3.4 9.2 3.6 2,580.3 2,309.8
2.6 13.6 2.9 0.3 2.8 1.4 2,721.7 1,448.0
Not Recovered (n ¼ 11)
4.8 20.6 11.2 3.1 13.4 4.3 3,400.8 2,288.6
2.9 12.5 2.2 0.3 10.2 2.0 8,161.6 3,055.3
P Value
.304 >.999
Abbreviations as in Table 1.
may be due to recipient age (younger in the HAV group), because multivariate analysis revealed that this difference was not statistically significant after adjustment for age. The main message we can obtain is that if the recipient survives the peritransplantation period, his or her renal function will improve. And it will improve better if the kidney was not damaged before the insult. We performed subgroup analysis to identify any differences between recipients who did and did not recover from AKI in the HAV group; the former had better pretransplantation liver function than the latter regarding Child-Pugh score and serum albumin. Preoperative MELD and Child-Pugh scores have been shown to be related to recovery from HRS, post-transplantation hemodialysis, and early acute renal failure [29e31]. Alessandria et al reported HRS type and MELD score to be independent prognostic factors in patients with HRS [31]. Yet there was scant evidence that liver function would predict renal prognosis in patients with acute HA. Our results are valuable in light of the fact that there are no reports about post-transplantation renal outcome in patients with acute HA and AKI. But the present study has several limitations. First, it was a retrospective study; a prospective design would make the results more meaningful. Second,
sample size was relatively small, although we did perform a multicenter study. Third, we used creatinine-based eGFR to assess renal function. Although creatinine-based calculation is still the most commonly used method for estimation of GFR, creatinine and creatinine-based methods have been shown to be of limited value as predictors of GFR in cirrhotic patients [32,33]. Therefore, assessing eGFR in cirrhotic patients using any formula has limitations, even though several earlier studies with similar design also used the MDRD formula [34e37]. Ideally, either inulin clearance or isotopic clearance is necessary for assessing the true measure of GFR [38]. In conclusion, patients with acute HA and AKI are sicker perioperatively compared with patients with FHF and HRS from other causes. Postoperative long-term prognosis, especially regarding renal function, may be better in patients with acute HA and AKI. Better pre-transplantation liver function may contribute to recovery of kidney function after transplantation.
REFERENCES [1] Zikos D, Grewal KS, Craig K, Cheng JC, Peterson DR, Fisher KA. Nephrotic syndrome and acute renal failure associated with hepatitis A virus infection. Am J Gastroenterol 1995;90:295e8.
LT IN FULMINANT HEPATITIS A WITH ACUTE KIDNEY INJURY
717
[2] Jeong SH, Lee HS. Hepatitis A: clinical manifestations and management. Intervirology 2010;53:15e9. [3] Lemon SM, Shapiro CN. The value of immunization against hepatitis A. Infect Agents Dis 1994;3:38e49. [4] Shin SJ, Kim JH. The characteristics of acute kidney injury complicated in acute hepatitis A. Scand J Infect Dis 2009;41:869e72. [5] Rakela J, Lange SM, Ludwig J, Baldus WP. Fulminant hepatitis: Mayo Clinic experience with 34 cases. Mayo Clin Proc 1985;60:289e92. [6] Ostapowicz G, Fontana RJ, Schiodt FV, Larson A, Davern TJ, Han SH, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med 2002;137:947e54. [7] di Belgiojoso GB, Ferrario F, Landriani N. Virus-related glomerular diseases: histological and clinical aspects. J Nephrol 2002;15:469e79. [8] Garcia-Tsao G, Parikh CR, Viola A. Acute kidney injury in cirrhosis. Hepatology 2008;48:2064e77. [9] O’Leary JG, Lepe R, Davis GL. Indications for liver transplantation. Gastroenterology 2008;134:1764e76. [10] Lee JP, Kwon HY, Park JI, Yi NJ, Suh KS, Lee HW, et al. Clinical outcomes of patients with hepatorenal syndrome after living donor liver transplantation. Liver Transpl 2012;18:1237e44. [11] Jung YJ, Kim W, Jeong JB, Kim BG, Lee KL, Oh KH, et al. Clinical features of acute renal failure associated with hepatitis A virus infection. J Viral Hepat 2010;17:611e7. [12] Vaboe AL, Leh S, Forslund T. Interstitial nephritis, acute renal failure in a patient with nonfulminant hepatitis A infection. Clin Nephrol 2002;57:149e53. [13] Larsen K. Creatinine assay by a reaction-kinetic principle. Clin Chim Acta 1972;41:209e17. [14] Arroyo V, Gines P, Gerbes AL, Dudley FJ, Gentilini P, Laffi G, et al. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. International Ascites Club. Hepatology 1996;23:164e76. [15] Cuthbert JA. Hepatitis A: old and new. Clin Microbiol Rev 2001;14:38e58. [16] Tong MJ, el-Farra NS, Grew MI. Clinical manifestations of hepatitis A: recent experience in a community teaching hospital. J Infect Dis 1995;171(Suppl 1):S15e8. [17] Wilkinson SP, Davies MH, Portmann B, Williams R. Renal failure in otherwise uncomplicated acute viral hepatitis. Br Med J 1978;2:338e41. [18] Song KS, Kim MJ, Jang CS, Jung HS, Lee HH, Kwon OS, et al. [Clinical features of acute viral hepatitis A complicated with acute renal failure]. Korean J Hepatol 2007;13:166e73. In Korean. [19] Kim SH, Yoon HE, Kim YK, Kim JY, Choi BS, Choi YJ, et al. Acute hepatitis Aeassociated acute renal failure in adults. Nephron Clin Pract 2008;109:c127e32. [20] Kim HW, Yu MH, Lee JH, Chang JW, Yang WS, Kim SB, et al. Experiences with acute kidney injury complicating nonfulminant hepatitis A. Nephrology (Carlton) 2008;13:451e8. [21] Choi HK, Song YG, Han SH, Ku NS, Jeong SJ, Baek JH, et al. Clinical features and outcomes of acute kidney injury among patients with acute hepatitis A. J Clin Virol 2011;52:192e7. [22] Cho SY, Choi SH, Park JH, Chung JW. Initial laboratory predictors of severe hepatitis and acute kidney injury in patients with acute hepatitis A. Diagn Microbiol Infect Dis 2011;69:400e4.
[23] Xu X, Ling Q, Zhang M, Gao F, He Z, You J, et al. Outcome of patients with hepatorenal syndrome type 1 after liver transplantation: Hangzhou experience. Transplantation 2009;87: 1514e9. [24] Giusto M, Berenguer M, Merkel C, Aguilera V, Rubin A, Ginanni Corradini S, et al. Chronic kidney disease after liver transplantation: pretransplantation risk factors and predictors during follow-up. Transplantation 2013;95:1148e53. [25] Gonwa TA, Klintmalm GB, Levy M, Jennings LS, Goldstein RM, Husberg BS. Impact of pretransplant renal function on survival after liver transplantation. Transplantation 1995;59: 361e5. [26] le Moine O. Hepatorenal syndromedoutcome after liver transplantation. Nephrol Dial Transplant 1998;13:20e2. [27] Lee JP, Heo NJ, Joo KW, Yi NJ, Suh KS, Moon KC, et al. Risk factors for consequent kidney impairment and differential impact of liver transplantation on renal function. Nephrol Dial Transplant 2010;25:2772e85. [28] Cohen AJ, Stegall MD, Rosen CB, Wiesner RH, Leung N, Kremers WK, et al. Chronic renal dysfunction late after liver transplantation. Liver Transpl 2002;8:916e21. [29] Cabezuelo JB, Ramirez P, Rios A, Acosta F, Torres D, Sansano T, et al. Risk factors of acute renal failure after liver transplantation. Kidney Int 2006;69:1073e80. [30] Sanchez EQ, Gonwa TA, Levy MF, Goldstein RM, Mai ML, Hays SR, et al. Preoperative and perioperative predictors of the need for renal replacement therapy after orthotopic liver transplantation. Transplantation 2004;78:1048e54. [31] Alessandria C, Ozdogan O, Guevara M, Restuccia T, Jimenez W, Arroyo V, et al. MELD score and clinical type predict prognosis in hepatorenal syndrome: relevance to liver transplantation. Hepatology 2005;41:1282e9. [32] Caregaro L, Menon F, Angeli P, Amodio P, Merkel C, Bortoluzzi A, et al. Limitations of serum creatinine level and creatinine clearance as filtration markers in cirrhosis. Arch Intern Med 1994;154:201e5. [33] Papadakis MA, Arieff AI. Unpredictability of clinical evaluation of renal function in cirrhosis. Prospective study. Am J Med 1987;82:945e52. [34] Ojo AO, Held PJ, Port FK, Wolfe RA, Leichtman AB, Young EW, et al. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med 2003;349:931e40. [35] Pawarode A, Fine DM, Thuluvath PJ. Independent risk factors and natural history of renal dysfunction in liver transplant recipients. Liver Transpl 2003;9:741e7. [36] Kim DY, Lim C, Parasuraman R, Raoufi M, Yoshida A, Arenas J, et al. Renal disease burden following liver transplantation. Transplant Proc 2006;38:3663e5. [37] Cicinnati VR, Yu Z, Klein CG, Sotiropoulos GC, Saner F, Malago M, et al. Clinical trial: switch to combined mycophenolate mofetil and minimal dose calcineurin inhibitor in stable liver transplant patientsdassessment of renal and allograft function, cardiovascular risk factors and immune monitoring. Aliment Pharmacol Ther 2007;26:1195e208. [38] Poge U, Gerhardt T, Stoffel-Wagner B, Klehr HU, Sauerbruch T, Woitas RP. Calculation of glomerular filtration rate based on cystatin C in cirrhotic patients. Nephrol Dial Transplant 2006;21:660e4.
ABSTRACT Background. Liver transplantation (LT) is the treatment of choice for hepatorenal syndrome (HRS). Recently, acute kidney injury (AKI) due to acute hepatitis A (HA) is increasing, but the outcome of LT is not well established. We investigated the outcomes of LT in patients with AKI due to acute HA compared with those of patients with HRS due to other causes. Methods. We investigated the outcomes of LT in 20 patients with AKI associated with acute HA (HAV group) compared with 76 patients with hepatorenal syndrome (HRS) due to other causes (HRS group) at 3 Korea centers. Results. Preoperative mean prothrombin time and serum creatinine level were higher in the HAV group than in the HRS group. But mean total bilirubin level was lower in the HAV group. There was no difference in Model for End-Stage Liver Disease scores. Posttransplantation patient and graft survival rates were similar between the 2 groups. More patients in the HAV group needed post-transplantation hemodialysis than in the HRS group (65.0% vs 38.2%; P ¼ .043). However, post-transplantation estimated glomerular filtration rate was significantly higher in the HAV group after post-transplantation month 2 (P < .05). Conclusions. Peri-transplantation kidney function of the HAV group was poorer than that of HRS group. However, post-transplantation long-term renal outcome could be better in the HAV group.
A
CUTE hepatitis A (HA) is one of the most common infectious diseases worldwide, with a clinical spectrum ranging from asymptomatic to fulminant hepatitis, which occurs in 50 mmol, in a patient without any previous liver disease. It often is associated with multiple organ failure. Until recently, the mortality rate ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
Transplantation Proceedings, 47, 709e717 (2015)
FHF was close to 80% [5]; however, with aggressive medical therapy, intensive care monitoring, and the advent of liver transplantation (LT), survival rates have improved considerably [6]. Nevertheless, LT is a rare treatment option for acute hepatitis and thus the outcomes are not well understood. Funding: Korea Healthcare Technology R&D Project, Ministry for Health and Welfare, Republic of Korea (grant A102065). *Address correspondence to Jung Pyo Lee, MD, PhD, Assistant Professor, Department of Internal Medicine, Seoul National University Boramae Medical Center, 425 Sindaebang 2-dong, Dongjak-gu, Seoul 156-707, Republic of Korea. E-mail: [email protected] 0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2014.10.057
709
710
PARK, GWAK, KIM ET AL
1940 adult patients underwent LT between 2005 and 2012
147 patients, pretransplant AKI
• 37 patients: Prerenal failure • 1 patient: Nephrotoxic renal failure • 13 patients: Parenchymal renal disease (HBGN, DN, ATN)
96 patients
20 patients, HAV group
Fig 1. Flow diagram of the study protocol. Abbreviations: HBGN, hepatitis B virus associated glomerulonephritis; DN, diabetic nephropathy; ATN, acute tubular necrosis.
Acute kidney injury (AKI) is a frequent complication in the setting of fulminant viral hepatitis [7]. Hepatorenal syndrome (HRS) is the most common cause of AKI in endstage liver disease, with LT as the treatment of choice [8e10]. However, AKI due to fulminant hepatitis A has shown several different renal manifestations compared with HRS regarding to high urinary sodium, hematuria, and proteinuria [11,12]. Furthermore, clinical outcomes after LT in patients with fulminant HA with AKI have not been thoroughly investigated. We aimed to investigate the outcomes of LT in patients with AKI in fulminant HA compared with patients undergoing LT for HRS due to other causes. METHODS Study Population This study was performed as a retrospective multicenter study. We reviewed 1,940 consecutive adult (age >18 y) Korean patients who underwent LT at Samsung Medical Center, Seoul National University Hospital, and Yonsei University Severance Hospital from 2005 to 2012. We focused on patients with AKI in acute hepatitis A, and HRS due to other causes. Twenty patients with acute hepatitis A who underwent LT because of FHF with AKI (HAV group) were compared with 76 (HRS group) patients who underwent LT because of HRS due to other causes, including 17 fulminant cases. Patients who did not fulfill HRS criteria in the HRS group and those who had prerenal, nephrotoxic renal failure in the HAV group were excluded.
76 patients, HRS group
17 patients, Fulminant
59 patients, Non-fulminant
This study was approved by the institutional Review Boards of Samsung Medical Center, Seoul National University Hospital, and Yonsei University Severance Hospital. All clinical investigations were conducted in accordance with the guidelines of the 2000 Declaration of Helsinki. Informed consents were obtained from all donors and recipients before transplantation.
Definition of FHF and AKI The definition of FHF was based on the American Association for the Study of Liver Diseases practice guidelines for the management of acute liver failure, update 2011, and included the following: evidence of coagulation abnormality, usually a prothrombin time (PT)/INR 1.5, and any degree of mental alteration (encephalopathy) in a patient without preexisting cirrhosis and with an illness of .999
7 (100.0) 0 (0.0) 0 (0.0) 6 (85.7)
8 (88.9) 1 (11.1) 0 (0.0) 5 (50.0)
6 (66.7) 3 (33.3) 2 (28.6)
7 (63.6) 4 (36.4) 5 (55.6)
.286
.654 .989 .342 .015 .246 .381 .777 .985
4.2 20.6 12.3 3.4 9.2 3.6 2,580.3 2,309.8
2.6 13.6 2.9 0.3 2.8 1.4 2,721.7 1,448.0
Not Recovered (n ¼ 11)
4.8 20.6 11.2 3.1 13.4 4.3 3,400.8 2,288.6
2.9 12.5 2.2 0.3 10.2 2.0 8,161.6 3,055.3
P Value
.304 >.999
Abbreviations as in Table 1.
may be due to recipient age (younger in the HAV group), because multivariate analysis revealed that this difference was not statistically significant after adjustment for age. The main message we can obtain is that if the recipient survives the peritransplantation period, his or her renal function will improve. And it will improve better if the kidney was not damaged before the insult. We performed subgroup analysis to identify any differences between recipients who did and did not recover from AKI in the HAV group; the former had better pretransplantation liver function than the latter regarding Child-Pugh score and serum albumin. Preoperative MELD and Child-Pugh scores have been shown to be related to recovery from HRS, post-transplantation hemodialysis, and early acute renal failure [29e31]. Alessandria et al reported HRS type and MELD score to be independent prognostic factors in patients with HRS [31]. Yet there was scant evidence that liver function would predict renal prognosis in patients with acute HA. Our results are valuable in light of the fact that there are no reports about post-transplantation renal outcome in patients with acute HA and AKI. But the present study has several limitations. First, it was a retrospective study; a prospective design would make the results more meaningful. Second,
sample size was relatively small, although we did perform a multicenter study. Third, we used creatinine-based eGFR to assess renal function. Although creatinine-based calculation is still the most commonly used method for estimation of GFR, creatinine and creatinine-based methods have been shown to be of limited value as predictors of GFR in cirrhotic patients [32,33]. Therefore, assessing eGFR in cirrhotic patients using any formula has limitations, even though several earlier studies with similar design also used the MDRD formula [34e37]. Ideally, either inulin clearance or isotopic clearance is necessary for assessing the true measure of GFR [38]. In conclusion, patients with acute HA and AKI are sicker perioperatively compared with patients with FHF and HRS from other causes. Postoperative long-term prognosis, especially regarding renal function, may be better in patients with acute HA and AKI. Better pre-transplantation liver function may contribute to recovery of kidney function after transplantation.
REFERENCES [1] Zikos D, Grewal KS, Craig K, Cheng JC, Peterson DR, Fisher KA. Nephrotic syndrome and acute renal failure associated with hepatitis A virus infection. Am J Gastroenterol 1995;90:295e8.
LT IN FULMINANT HEPATITIS A WITH ACUTE KIDNEY INJURY
717
[2] Jeong SH, Lee HS. Hepatitis A: clinical manifestations and management. Intervirology 2010;53:15e9. [3] Lemon SM, Shapiro CN. The value of immunization against hepatitis A. Infect Agents Dis 1994;3:38e49. [4] Shin SJ, Kim JH. The characteristics of acute kidney injury complicated in acute hepatitis A. Scand J Infect Dis 2009;41:869e72. [5] Rakela J, Lange SM, Ludwig J, Baldus WP. Fulminant hepatitis: Mayo Clinic experience with 34 cases. Mayo Clin Proc 1985;60:289e92. [6] Ostapowicz G, Fontana RJ, Schiodt FV, Larson A, Davern TJ, Han SH, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med 2002;137:947e54. [7] di Belgiojoso GB, Ferrario F, Landriani N. Virus-related glomerular diseases: histological and clinical aspects. J Nephrol 2002;15:469e79. [8] Garcia-Tsao G, Parikh CR, Viola A. Acute kidney injury in cirrhosis. Hepatology 2008;48:2064e77. [9] O’Leary JG, Lepe R, Davis GL. Indications for liver transplantation. Gastroenterology 2008;134:1764e76. [10] Lee JP, Kwon HY, Park JI, Yi NJ, Suh KS, Lee HW, et al. Clinical outcomes of patients with hepatorenal syndrome after living donor liver transplantation. Liver Transpl 2012;18:1237e44. [11] Jung YJ, Kim W, Jeong JB, Kim BG, Lee KL, Oh KH, et al. Clinical features of acute renal failure associated with hepatitis A virus infection. J Viral Hepat 2010;17:611e7. [12] Vaboe AL, Leh S, Forslund T. Interstitial nephritis, acute renal failure in a patient with nonfulminant hepatitis A infection. Clin Nephrol 2002;57:149e53. [13] Larsen K. Creatinine assay by a reaction-kinetic principle. Clin Chim Acta 1972;41:209e17. [14] Arroyo V, Gines P, Gerbes AL, Dudley FJ, Gentilini P, Laffi G, et al. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. International Ascites Club. Hepatology 1996;23:164e76. [15] Cuthbert JA. Hepatitis A: old and new. Clin Microbiol Rev 2001;14:38e58. [16] Tong MJ, el-Farra NS, Grew MI. Clinical manifestations of hepatitis A: recent experience in a community teaching hospital. J Infect Dis 1995;171(Suppl 1):S15e8. [17] Wilkinson SP, Davies MH, Portmann B, Williams R. Renal failure in otherwise uncomplicated acute viral hepatitis. Br Med J 1978;2:338e41. [18] Song KS, Kim MJ, Jang CS, Jung HS, Lee HH, Kwon OS, et al. [Clinical features of acute viral hepatitis A complicated with acute renal failure]. Korean J Hepatol 2007;13:166e73. In Korean. [19] Kim SH, Yoon HE, Kim YK, Kim JY, Choi BS, Choi YJ, et al. Acute hepatitis Aeassociated acute renal failure in adults. Nephron Clin Pract 2008;109:c127e32. [20] Kim HW, Yu MH, Lee JH, Chang JW, Yang WS, Kim SB, et al. Experiences with acute kidney injury complicating nonfulminant hepatitis A. Nephrology (Carlton) 2008;13:451e8. [21] Choi HK, Song YG, Han SH, Ku NS, Jeong SJ, Baek JH, et al. Clinical features and outcomes of acute kidney injury among patients with acute hepatitis A. J Clin Virol 2011;52:192e7. [22] Cho SY, Choi SH, Park JH, Chung JW. Initial laboratory predictors of severe hepatitis and acute kidney injury in patients with acute hepatitis A. Diagn Microbiol Infect Dis 2011;69:400e4.
[23] Xu X, Ling Q, Zhang M, Gao F, He Z, You J, et al. Outcome of patients with hepatorenal syndrome type 1 after liver transplantation: Hangzhou experience. Transplantation 2009;87: 1514e9. [24] Giusto M, Berenguer M, Merkel C, Aguilera V, Rubin A, Ginanni Corradini S, et al. Chronic kidney disease after liver transplantation: pretransplantation risk factors and predictors during follow-up. Transplantation 2013;95:1148e53. [25] Gonwa TA, Klintmalm GB, Levy M, Jennings LS, Goldstein RM, Husberg BS. Impact of pretransplant renal function on survival after liver transplantation. Transplantation 1995;59: 361e5. [26] le Moine O. Hepatorenal syndromedoutcome after liver transplantation. Nephrol Dial Transplant 1998;13:20e2. [27] Lee JP, Heo NJ, Joo KW, Yi NJ, Suh KS, Moon KC, et al. Risk factors for consequent kidney impairment and differential impact of liver transplantation on renal function. Nephrol Dial Transplant 2010;25:2772e85. [28] Cohen AJ, Stegall MD, Rosen CB, Wiesner RH, Leung N, Kremers WK, et al. Chronic renal dysfunction late after liver transplantation. Liver Transpl 2002;8:916e21. [29] Cabezuelo JB, Ramirez P, Rios A, Acosta F, Torres D, Sansano T, et al. Risk factors of acute renal failure after liver transplantation. Kidney Int 2006;69:1073e80. [30] Sanchez EQ, Gonwa TA, Levy MF, Goldstein RM, Mai ML, Hays SR, et al. Preoperative and perioperative predictors of the need for renal replacement therapy after orthotopic liver transplantation. Transplantation 2004;78:1048e54. [31] Alessandria C, Ozdogan O, Guevara M, Restuccia T, Jimenez W, Arroyo V, et al. MELD score and clinical type predict prognosis in hepatorenal syndrome: relevance to liver transplantation. Hepatology 2005;41:1282e9. [32] Caregaro L, Menon F, Angeli P, Amodio P, Merkel C, Bortoluzzi A, et al. Limitations of serum creatinine level and creatinine clearance as filtration markers in cirrhosis. Arch Intern Med 1994;154:201e5. [33] Papadakis MA, Arieff AI. Unpredictability of clinical evaluation of renal function in cirrhosis. Prospective study. Am J Med 1987;82:945e52. [34] Ojo AO, Held PJ, Port FK, Wolfe RA, Leichtman AB, Young EW, et al. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med 2003;349:931e40. [35] Pawarode A, Fine DM, Thuluvath PJ. Independent risk factors and natural history of renal dysfunction in liver transplant recipients. Liver Transpl 2003;9:741e7. [36] Kim DY, Lim C, Parasuraman R, Raoufi M, Yoshida A, Arenas J, et al. Renal disease burden following liver transplantation. Transplant Proc 2006;38:3663e5. [37] Cicinnati VR, Yu Z, Klein CG, Sotiropoulos GC, Saner F, Malago M, et al. Clinical trial: switch to combined mycophenolate mofetil and minimal dose calcineurin inhibitor in stable liver transplant patientsdassessment of renal and allograft function, cardiovascular risk factors and immune monitoring. Aliment Pharmacol Ther 2007;26:1195e208. [38] Poge U, Gerhardt T, Stoffel-Wagner B, Klehr HU, Sauerbruch T, Woitas RP. Calculation of glomerular filtration rate based on cystatin C in cirrhotic patients. Nephrol Dial Transplant 2006;21:660e4.
