Outcomes of Orthotopic Liver Transplantation in Non-malignant End-stage Liver Diseases Y. Sirivatanauksorn, N. Kongkaewpaisan, A. Pongpaibul, S. Limsrichamrern, P. Mahawithitwong, P. Kositamongkol, C. Tovikkai, and S. Asavakarn ABSTRACT Background. Orthotopic liver transplantation (OLT) is an effective treatment for patients who have end-stage liver disease. The aim of this study is to compare outcomes of OLT in fulminant hepatic failure (FHF) and non-fulminant hepatic failure (non-FHF) patients. Methods. A retrospective review of adult patients who underwent OLT for nonmalignant end-stage liver diseases between 2002 and 2011 at Siriraj Hospital was performed. All explanted liver histopathology results were reviewed. The clinical factors and overall results of OLT were analyzed. Results. Of the 137 patients, 72 patients had non-malignant diagnoses. Eleven patients were diagnosed with FHF, whereas 61 patients were in the non-FHF group. The most common indication for liver transplantation was chronic viral hepatitis. One- and 5-year survival rates (95% confidence interval) in the FHF group were 91% (51%e99%) and 91% (51%e99%), respectively, whereas those in the non-FHF group were 74% (61% e83%) and 66% (52%e77%), respectively. Multivariate cox regression analysis revealed no statistically significant difference of survival between both groups (P ¼ .34). Conclusions. The post-OLT outcomes in non-malignant patients were comparable between FHF and non-FHF groups in terms of survival. OLT remains the only therapeutic option for the FHF patients.
O
RTHOTOPIC liver transplantation (OLT) is an effective and standard treatment for patients who have end-stage liver diseases, both chronic liver cirrhosis and acute liver failure [1e4], with reported 5-year survival rates of up to 70% [2,5,6]. In fulminant liver failure, liver function rapidly deteriorates due to abrupt onset of extensive damage of liver cells. This condition has various causes and can occur in patients with or without pre-existing liver disease. With fully supportive therapy, some patients who have fulminant hepatic failure (FHF) do not improve and the mortality rate is still high. Therefore, OLT is a potential therapy. Nevertheless, the procedure itself might be associated with high morbidity and mortality in the perioperative period. The aim of this study is to evaluate the etiologies of nonmalignant end-stage liver diseases from explanted liver and to compare outcomes of OLT for patients with FHF and non-fulminant hepatic failure (non-FHF) at Siriraj Hospital. 0041-1345/14/$esee front matter http://dx.doi.org/10.1016/j.transproceed.2014.02.026 778
METHODS A retrospective review of adult patients who underwent OLT for non-malignant end-stage liver diseases from January 2002 to December 2011 at Siriraj Hospital, Bangkok, Thailand, was performed. A pathologist (AP) retrospectively reviewed all explanted liver histopathology slides, and patients with an explant pathologic diagnosis of hepatocellular carcinoma were excluded from the
From the HepatoPancreatoBiliary and Transplant Surgery Unit, Division of General Surgery, Department of Surgery (Y.S., N.K., S.L., P.M., P.K., C.T., S.A.), and the Department of Pathology (A.P.), Siriraj Organ Transplantation Center, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand. Supported by the Siriraj Grant for Research Development. Address reprint requests to Yongyut Sirivatanauksorn, Division of General Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, 2 Prannok Road, Bangkoknoi, Bangkok 10700, Thailand. E-mail: [email protected] ª 2014 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 46, 778e781 (2014)
LIVER TRANSPLANTATION OUTCOMES study. The preoperative and perioperative clinical factors and postoperative outcomes of liver transplantation were reviewed. Parameters were compared using the t test or Fisher’s exact test, where appropriate. Survival rates were estimated using the KaplanMeier method and compared with the log-rank test. Multivariate Cox regression analysis was used to evaluate the effect of FHF on survival. Demographic (age, sex, blood group), preoperative (waiting time model for end-stage liver disease [MELD] score, diabetes, hypertension, chronic kidney disease), and perioperative (operative time and estimated blood loss) factors were included in the multivariate Cox regression analysis. A P value of less than .05 was considered significant. Statistical analysis was performed with Stata version 11.1 (StataCorp, Tex, United States).
RESULTS
During January 2002 and December 2011, 137 adult OLTs were performed at Siriraj Hospital. Sixty-five patients were diagnosed with hepatocellular carcinoma and were excluded from the study. Pathology revealed non-malignant related conditions in 72 patients, which were divided into two groups, FHF (11 patients) and non-FHF (61 patients), according to the urgency status of transplantation. Indications for OLT
The indications for OLT for both groups in this study are shown in Table 1. In the FHF group, the indications were acute flare up of hepatitis B virus (64%), cryptogenic cirrhosis (18%), acute Wilson’s disease (9%) and druginduced hepatitis (9%). In the non-FHF group, more than half of the patients were diagnosed with chronic viral hepatitis, hepatitis C (30%), hepatitis B (21%), and hepatitis B and hepatitis C co-infection (2%).
779 Table 1. Indications for Liver Transplantation in Non-malignant End-stage Liver Diseases Indications
Chronic hepatitis B Chronic hepatitis C Alcoholic liver disease Cryptogenic cirrhosis Primary biliary cirrhosis Biliary atresia Non-alcoholic steatotic hepatitis Primary sclerosing cholangitis Wilson’s disease Hemochromatosis Calori’s disease Late hepatic artery thrombosis (retransplantation) Co-infection (hepatitis B and C) Drug-induced Total
FHF Group
Non-FHF Group
Total
7 e e 2 e e e e 1 e e e
13 18 10 4 4 3 2 2 1 1 1 1
20 18 10 6 4 3 2 2 2 1 1 1
e 1 11
1 e 61
1 1 72
Patient Survival
Overall 30-day, 1-year, and 5-year patient survival rates (95% confidence interval) were 85% (74%e91%), 76% (65%e85%), and 70% (58%e80%), respectively. In the FHF group, 30-day, 1-year, and 5-year survival rates were all 91% (51%e99%), whereas the corresponding numbers in the non-FHF group were 84% (72%e91%), 74% (61% e83%), and 66% (52%e77%), respectively (Fig 1). Survival rates between the two groups were not statistically different (log-rank test, P ¼ .14). Multivariate Cox regression analysis also found that FHF did not have an impact on post-transplantation survival (hazard ratio ¼ 0.33, P ¼ .34; Table 3).
Preoperative and Perioperative Clinical Factors
In the whole cohort, the mean age of recipients was 49.9 years. The recipients in the FHF were slightly younger (46.6 vs 50.4 years). Overall, 63% of the recipients were male and 37% were female. In the FHF group, 82% were male and 18% were female, whereas those in the non-FHF group were 59% male and 41% female (Table 2). Comparing between both groups, two parameters that reached statistical significance were waiting times and average MELD score. Mean waiting times for the FHF group was significantly shorter than those in non-FHF group (5 days vs 251 days). With the urgency for OLT, the average MELD score in FHF group was also significantly higher than those in non-FHF group (39 vs 22). FHF patients tended to stay longer in intensive care (5.8 days vs 2.9 days), but it was not statistically significant. Recipients’ comorbidities (diabetes, hypertension, and chronic kidney disease), operative time, estimated blood loss, and length of hospital stay between both groups were not significantly different (Table 2). In addition, there were 57% waitlist dropouts in both groups because of the low number of donors in Thailand.
Causes of Death
Twenty-one patients (29%) died during the follow-up period. The causes of death in both groups are shown in Table 2. Preoperative and Perioperative Clinical Parameters in FHF and Non-FHF Groups* Parameters
FHF
Non-FHF
P Value
Number Age (y) Male recipients (%) Waiting time (d) MELD score Diabetes mellitus (%) Hypertension (%) Chronic kidney disease (%) Operative time (min) Estimated blood loss (mL) Length of hospital stay (d) Intensive care stay (d) Waitlist dropout (%)
11 46.6 (12.1) 9 (81.8) 4.6 (2.7) 38.5 (8.7) 2 (18.2) 0 (0.0) 0 (0.0) 261 (54) 2,736 (2,225) 25.9 (29.8) 5.8 (12.1) 57
61 50.4 (10.6) 36 (59.0) 251.3 (363.1) 22.4 (9.2) 21 (34.4) 7 (11.5) 5 (8.2) 304 (81) 4,685 (4,671) 21.2 (21.8) 2.9 (2.7) 57
e .29 .19 .03
O
RTHOTOPIC liver transplantation (OLT) is an effective and standard treatment for patients who have end-stage liver diseases, both chronic liver cirrhosis and acute liver failure [1e4], with reported 5-year survival rates of up to 70% [2,5,6]. In fulminant liver failure, liver function rapidly deteriorates due to abrupt onset of extensive damage of liver cells. This condition has various causes and can occur in patients with or without pre-existing liver disease. With fully supportive therapy, some patients who have fulminant hepatic failure (FHF) do not improve and the mortality rate is still high. Therefore, OLT is a potential therapy. Nevertheless, the procedure itself might be associated with high morbidity and mortality in the perioperative period. The aim of this study is to evaluate the etiologies of nonmalignant end-stage liver diseases from explanted liver and to compare outcomes of OLT for patients with FHF and non-fulminant hepatic failure (non-FHF) at Siriraj Hospital. 0041-1345/14/$esee front matter http://dx.doi.org/10.1016/j.transproceed.2014.02.026 778
METHODS A retrospective review of adult patients who underwent OLT for non-malignant end-stage liver diseases from January 2002 to December 2011 at Siriraj Hospital, Bangkok, Thailand, was performed. A pathologist (AP) retrospectively reviewed all explanted liver histopathology slides, and patients with an explant pathologic diagnosis of hepatocellular carcinoma were excluded from the
From the HepatoPancreatoBiliary and Transplant Surgery Unit, Division of General Surgery, Department of Surgery (Y.S., N.K., S.L., P.M., P.K., C.T., S.A.), and the Department of Pathology (A.P.), Siriraj Organ Transplantation Center, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand. Supported by the Siriraj Grant for Research Development. Address reprint requests to Yongyut Sirivatanauksorn, Division of General Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, 2 Prannok Road, Bangkoknoi, Bangkok 10700, Thailand. E-mail: [email protected] ª 2014 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 46, 778e781 (2014)
LIVER TRANSPLANTATION OUTCOMES study. The preoperative and perioperative clinical factors and postoperative outcomes of liver transplantation were reviewed. Parameters were compared using the t test or Fisher’s exact test, where appropriate. Survival rates were estimated using the KaplanMeier method and compared with the log-rank test. Multivariate Cox regression analysis was used to evaluate the effect of FHF on survival. Demographic (age, sex, blood group), preoperative (waiting time model for end-stage liver disease [MELD] score, diabetes, hypertension, chronic kidney disease), and perioperative (operative time and estimated blood loss) factors were included in the multivariate Cox regression analysis. A P value of less than .05 was considered significant. Statistical analysis was performed with Stata version 11.1 (StataCorp, Tex, United States).
RESULTS
During January 2002 and December 2011, 137 adult OLTs were performed at Siriraj Hospital. Sixty-five patients were diagnosed with hepatocellular carcinoma and were excluded from the study. Pathology revealed non-malignant related conditions in 72 patients, which were divided into two groups, FHF (11 patients) and non-FHF (61 patients), according to the urgency status of transplantation. Indications for OLT
The indications for OLT for both groups in this study are shown in Table 1. In the FHF group, the indications were acute flare up of hepatitis B virus (64%), cryptogenic cirrhosis (18%), acute Wilson’s disease (9%) and druginduced hepatitis (9%). In the non-FHF group, more than half of the patients were diagnosed with chronic viral hepatitis, hepatitis C (30%), hepatitis B (21%), and hepatitis B and hepatitis C co-infection (2%).
779 Table 1. Indications for Liver Transplantation in Non-malignant End-stage Liver Diseases Indications
Chronic hepatitis B Chronic hepatitis C Alcoholic liver disease Cryptogenic cirrhosis Primary biliary cirrhosis Biliary atresia Non-alcoholic steatotic hepatitis Primary sclerosing cholangitis Wilson’s disease Hemochromatosis Calori’s disease Late hepatic artery thrombosis (retransplantation) Co-infection (hepatitis B and C) Drug-induced Total
FHF Group
Non-FHF Group
Total
7 e e 2 e e e e 1 e e e
13 18 10 4 4 3 2 2 1 1 1 1
20 18 10 6 4 3 2 2 2 1 1 1
e 1 11
1 e 61
1 1 72
Patient Survival
Overall 30-day, 1-year, and 5-year patient survival rates (95% confidence interval) were 85% (74%e91%), 76% (65%e85%), and 70% (58%e80%), respectively. In the FHF group, 30-day, 1-year, and 5-year survival rates were all 91% (51%e99%), whereas the corresponding numbers in the non-FHF group were 84% (72%e91%), 74% (61% e83%), and 66% (52%e77%), respectively (Fig 1). Survival rates between the two groups were not statistically different (log-rank test, P ¼ .14). Multivariate Cox regression analysis also found that FHF did not have an impact on post-transplantation survival (hazard ratio ¼ 0.33, P ¼ .34; Table 3).
Preoperative and Perioperative Clinical Factors
In the whole cohort, the mean age of recipients was 49.9 years. The recipients in the FHF were slightly younger (46.6 vs 50.4 years). Overall, 63% of the recipients were male and 37% were female. In the FHF group, 82% were male and 18% were female, whereas those in the non-FHF group were 59% male and 41% female (Table 2). Comparing between both groups, two parameters that reached statistical significance were waiting times and average MELD score. Mean waiting times for the FHF group was significantly shorter than those in non-FHF group (5 days vs 251 days). With the urgency for OLT, the average MELD score in FHF group was also significantly higher than those in non-FHF group (39 vs 22). FHF patients tended to stay longer in intensive care (5.8 days vs 2.9 days), but it was not statistically significant. Recipients’ comorbidities (diabetes, hypertension, and chronic kidney disease), operative time, estimated blood loss, and length of hospital stay between both groups were not significantly different (Table 2). In addition, there were 57% waitlist dropouts in both groups because of the low number of donors in Thailand.
Causes of Death
Twenty-one patients (29%) died during the follow-up period. The causes of death in both groups are shown in Table 2. Preoperative and Perioperative Clinical Parameters in FHF and Non-FHF Groups* Parameters
FHF
Non-FHF
P Value
Number Age (y) Male recipients (%) Waiting time (d) MELD score Diabetes mellitus (%) Hypertension (%) Chronic kidney disease (%) Operative time (min) Estimated blood loss (mL) Length of hospital stay (d) Intensive care stay (d) Waitlist dropout (%)
11 46.6 (12.1) 9 (81.8) 4.6 (2.7) 38.5 (8.7) 2 (18.2) 0 (0.0) 0 (0.0) 261 (54) 2,736 (2,225) 25.9 (29.8) 5.8 (12.1) 57
61 50.4 (10.6) 36 (59.0) 251.3 (363.1) 22.4 (9.2) 21 (34.4) 7 (11.5) 5 (8.2) 304 (81) 4,685 (4,671) 21.2 (21.8) 2.9 (2.7) 57
e .29 .19 .03
