576 European Journal of Gastroenterology & Hepatology 2014, Vol 26 No 5
Between 1 January 2012 and 30 June 2012, a total of 26 consecutive patients who were diagnosed with BCS and first admitted to our department were eligible for this study. However, one patient with concomitant hepatocellular carcinoma was excluded. Thus, 25 patients were finally included. According to the location of occlusion, BCS was classified as pure hepatic vein occlusion (n = 4), pure inferior vena cava occlusion (n = 0), and combined occlusion of hepatic vein and inferior vena cava (n = 21). Demographic data (male: 14; female: 11; mean±SD of age: 35.7±13.2) and laboratory tests are shown in Supplementary Table 1. The results of thrombotic risk factors are presented in Table 1. The JAK2 V617F mutation, the JAK2 exon 12 mutation, and the MPL W515 L/K mutation were negative in all patients. Neither factor II G20210A mutation nor the factor V Leiden mutation was found in any patient. One patient was diagnosed with paroxysmal nocturnal hemoglobinuria because of both CD55 and CD59 deficiencies on granulocytes. Serum erythropoietin level below the reference range was not found in any patients. The heterozygous and the homozygous MTHFR mutation were found in 14 and four patients, respectively. Anticardiolipin IgG antibodies were negative in all patients.
13 Dignass A, Van Assche G, Lindsay JO, Le´mann M, So¨derholm J, Colombel JF, et al. The second European evidence-based Consensus on the diagnosis and management of Crohn’s disease: current management. J Crohns Colitis 2010; 4:28–62.
Prevalence of thrombotic risk factors in Chinese Budd–Chiari syndrome patients: results of a prospective validation study Xingshun Qi, Feifei Wu, Daiming Fan and Guohong Han, Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China Correspondence to Guohong Han, MD, Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, No. 27 Changle West Road, Xi’an 710032, China Tel: + 86 29 8477 1537; fax: + 86 29 8253 9041; e-mail: [email protected] Received 6 January 2014 Accepted 9 January 2014
Thrombotic risk factors, such as myeloproliferative neoplasms, factor V Leiden mutation, prothrombin G20210A mutation, paroxysmal nocturnal hemoglobinuria, etc., are common in western patients with Budd–Chiari syndrome (BCS) [1,2]. However, recent observational studies have shown that these risk factors are rarely observed in Chinese BCS patients [3–5]. More recently, this discrepancy has been further confirmed by other studies [6,7]. However, considering that the current evidence is limited, a prospective study has been carried out to further validate these previous findings. Table 1
Initials W.G.G. H.Z.G. N.X. G.K.P. D.C.P. Z.C.X. F.A.B. W.Q.E. H.Y.Z. H.X.Y. D.Y.L. G.X.Q. C.X. Z.Y.K. Z.L.W. Y.X.Q. G.L.X. L.H.Y. L.M.E. R.Y.L. W.Z.F. L.T.T. X.Y.Q. K.Q.L. X.F.X.
Collectively, the results of the prospective validation study were almost consistent with those of our previous work. These findings suggested that the etiological distribution of BCS should be different between western countries and China, and the pathogenesis of BCS in
Results of thrombotic risk factors in 25 Chinese Budd–Chiari syndrome patients MPL JAK2 JAK2 W515 V617F exon 12 L/K Sex Age Type mutation mutation mutation M M M M M M M F F F F M M M M M F F F F F M F F M
47 38 22 45 40 30 53 60 57 27 38 20 35 50 18 36 18 23 38 41 39 50 35 23 10
Com Com Com HV HV Com Com Com Com Com Com HV HV Com Com Com Com Com Com Com Com Com Com Com Com
Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg
NA Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg
NA Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg
Factor II G20210A mutation
Factor V Leiden G1691A mutation
MTHFR C667T mutation
CD55 on erythrocytes (%)
CD55 on granulocytes (%)
CD59 on erythrocytes (%)
CD59 on granulocytes (%)
EPO
ACA
Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg
Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg
NA Hetero Homo Homo Neg Homo Hetero Neg Hetero Neg Neg Hetero Neg Hetero Hetero Hetero Hetero Hetero Neg Hetero Hetero Hetero Hetero Homo Hetero
95.68 99.61 99.72 99.47 99.2 99.40 99.52 98.88 99.34 98.75 99.51 99.01 98.67 98.96 99.21 98.94 99.5 99.49 98.95 99.04 99.6 98.72 99.41 99.68 97.66
52.33 99.79 99.28 99.89 99.97 99.93 99.99 99.99 99.99 99.67 99.89 99.65 99.94 99.4 99.95 99.96 99.87 99.97 99.91 99.77 99.6 99.82 99.69 99.83 99.77
92.43 99.99 99.98 99.99 99.96 99.93 99.98 99.98 99.89 99.95 99.95 99.96 99.96 99.88 99.98 99.99 99.98 99.83 99.99 99.97 99.1 99.96 99.88 99.98 99.78
75.99 99.79 95.66 97.01 99.62 99.92 99.4 99.97 99.95 99.27 99.74 99.48 99.87 99.92 99.95 99.96 99.84 99.97 99.6 99.68 99.9 99.74 99.06 99.78 97.52
NA 18.6 6.52 24.6 23.9 6.72 57.7 8.33 27.8 62.4 87.9 279.43 4.71 20.4 73.8 56.6 186 13.1 14.3 29.5 25.6 9.64 43.3 123 35.5
Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg
Serum erythropoietin levels’ reference range is 3.70–29.50 mIU/ml. The CD55 or the CD59 deficiency is considered if the proportion of erythrocytes or granulocytes with normal expression of CD55 or CD59 is less than 90%. ACA, anticardiolipin IgG antibodies; Com, combined obstruction of hepatic vein and inferior vena cava; EPO, serum erythropoietin level; F, female; Hetero, heterozygous 677C/T genotype; Homo, homozygous 677TT genotype; HV, hepatic vein; M, male; MTHFR, 5,10-methylenetetrahydrofolate reductase; Neg, negative.
All supplementary digital content is available directly from the corresponding author.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Letter to the Editor 577
Chinese patients should be explored in future. However, the potential limitation of this study is that it has only a small number of BCS patients enrolled prospectively during a 6-month period, which might require external validity. Certainly, it is often difficult to obtain a larger sample size from a single center during a relatively short period, given the rarity of this disease. Ideally, a nationwide epidemiological study should be carried out to evaluate the prevalence of thrombotic risk factors in Chinese BCS patients.
Acknowledgements Conflicts of interest
There are no conflicts of interest.
References 1 2
3
4
5
6
7
Valla DC. Primary Budd–Chiari syndrome. J Hepatol 2009; 50:195–203. Seijo S, Plessier A, Hoekstra J, Dell’era A, Mandair D, Rifai K, et al. Good long-term outcome of Budd–Chiari syndrome with a step-wise management. Hepatology 2013; 57:1962–1968. Qi X, Wu F, Ren W, He C, Yin Z, Niu J, et al. Thrombotic risk factors in Chinese Budd–Chiari syndrome patients. An observational study with a systematic review of the literature. Thromb Haemost 2013; 109:878–884. Qi X, Zhang C, Han G, Zhang W, He C, Yin Z, et al. Prevalence of paroxysmal nocturnal hemoglobinuria in Chinese patients with Budd–Chiari syndrome or portal vein thrombosis. J Gastroenterol Hepatol 2013; 28:148–152. Qi X, He C, Han G, Yin Z, Wu F, Zhang Q, et al. Prevalence of the JAK2 V617F mutation in Chinese patients with Budd–Chiari syndrome and portal vein thrombosis: a prospective study. J Gastroenterol Hepatol 2012; 27:1036–1043. Wang H, Sun G, Zhang P, Zhang J, Gui E, Zu M, et al. JAK2 V617F mutation and 46/1 haplotype in Chinese Budd–Chiari syndrome patients. J Gastroenterol Hepatol 2014; 29:208–214. Cheng D, Xu H, Lu ZJ, Hua R, Qiu H, Du H, et al. Clinical features and etiology of Budd–Chiari syndrome in Chinese patients: a single-center study. J Gastroenterol Hepatol 2013; 28:1061–1067.
Sorafenib for the treatment of recurrent hepatocellular carcinoma after liver transplantation: does mTOR inhibitors association augment toxicity? Giovanni Perricone, Andrea Mancuso, Luca S. Belli, Chiara Mazzarelli and Claudio Zavaglia, Hepatology and Gastroenterology Unit, Niguarda Ca’ Granda Hospital, Piazza Ospedale Maggiore 3, Milan, Italy Correspondence to Giovanni Perricone, MD, Hepatology and Gastroenterology Unit, Niguarda Ca’ Granda Hospital, Piazza Ospedale Maggiore 3, 20162 Milan, Italy Table 1
Tel: + 39 026 444 4454; fax: + 39 026 444 2895; e-mails: [email protected], [email protected] Received 30 January 2014 Accepted 31 January 2014
Although sorafenib has shown a survival benefit in cirrhotics with advanced hepatocellular carcinoma (HCC), its efficacy and safety in the post-liver transplantation (LT) setting have scarcely been studied. Few retrospective cohort studies have been published so far. Recently, Sposito et al. [1] compared the outcome of 15 patients with HCC recurrence after LT treated with sorafenib with 24 historical controls who received best supportive care. The median survival from the start of treatment was 10.6 months for the sorafenib group compared with 2.2 months in the control group. No severe adverse event was registered. In the same setting, Staufer et al. [2] observed grade 3–4 adverse events in 92% of 13 patients (nine treated with mTOR inhibitors). Sorafenib was discontinued in 77%. We have already published data in 11 patients treated with sorafenib, with or without everolimus, for recurrent HCC after LT [3]. The median survival from the start of treatment was 5 months. One patient died because of massive gastrointestinal bleeding [4]. Adverse events or intolerance motivated sorafenib withdrawal in 36% and dose reduction in 91%. From July 2010 to July 2013, we treated four additional patients with sorafenib, in association with everolimus (Table 1). The maximum daily tolerated dose of sorafenib was 400 mg. The median treatment duration was 111 days (range 77–144 days). Grade 2 adverse events occurred in two patients. Grade 3 cholestasis occurred in another patient. The last patient was hospitalized for severe diarrhea 4 months after starting sorafenib. He started to complain of diarrhea 2 weeks after starting treatment. After reduction of sorafenib to 400 mg daily, intermittent diarrhea persisted but the patient’s condition improved. He had stable disease at computed tomographic scan performed 3 months after the start of treatment. During hospitalization, grade 3 diarrhea associated with
Main characteristics of four patients with recurrent hepatocellular carcinoma after liver transplantation treated with sorafenib
Patient Age/sex Time to recurrence (months) Localization of recurrence Baseline serum a-fetoprotein (ng/ml) Immune suppression Maximum sorafenib dose (mg/day) Duration of treatment with sorafenib (days) Adverse events (grades 3–4) Best tumor response Outcome Survival after OLT (days) Survival after sorafenib start (days)
1
2
3
4
56/F 3 Lung 217 EVR 400 183 Noa Progression Dead 628 532
56/M 31 Liver, bone 1210 TAC-EVR 400 77 Grade 3 cholestasis Progression Dead 1431 488
53/M 46 Liver, lung, peritoneum 2 EVR 400 78 Nob Progression Alive 1501 104
50/M 15 Liver, lung 4 EVR 400 144 Grade 3 diarrhea Stable disease Dead 978 161
EVR, everolimus; F, female; M, male; OLT, orthotopic liver transplantation; TAC, tacrolimus. a Grade 2 fatigue and cholestasis. b Grade 2 fatigue, urticaria, and hand–foot skin reaction; grade 1 fever and weight loss.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Between 1 January 2012 and 30 June 2012, a total of 26 consecutive patients who were diagnosed with BCS and first admitted to our department were eligible for this study. However, one patient with concomitant hepatocellular carcinoma was excluded. Thus, 25 patients were finally included. According to the location of occlusion, BCS was classified as pure hepatic vein occlusion (n = 4), pure inferior vena cava occlusion (n = 0), and combined occlusion of hepatic vein and inferior vena cava (n = 21). Demographic data (male: 14; female: 11; mean±SD of age: 35.7±13.2) and laboratory tests are shown in Supplementary Table 1. The results of thrombotic risk factors are presented in Table 1. The JAK2 V617F mutation, the JAK2 exon 12 mutation, and the MPL W515 L/K mutation were negative in all patients. Neither factor II G20210A mutation nor the factor V Leiden mutation was found in any patient. One patient was diagnosed with paroxysmal nocturnal hemoglobinuria because of both CD55 and CD59 deficiencies on granulocytes. Serum erythropoietin level below the reference range was not found in any patients. The heterozygous and the homozygous MTHFR mutation were found in 14 and four patients, respectively. Anticardiolipin IgG antibodies were negative in all patients.
13 Dignass A, Van Assche G, Lindsay JO, Le´mann M, So¨derholm J, Colombel JF, et al. The second European evidence-based Consensus on the diagnosis and management of Crohn’s disease: current management. J Crohns Colitis 2010; 4:28–62.
Prevalence of thrombotic risk factors in Chinese Budd–Chiari syndrome patients: results of a prospective validation study Xingshun Qi, Feifei Wu, Daiming Fan and Guohong Han, Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China Correspondence to Guohong Han, MD, Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, No. 27 Changle West Road, Xi’an 710032, China Tel: + 86 29 8477 1537; fax: + 86 29 8253 9041; e-mail: [email protected] Received 6 January 2014 Accepted 9 January 2014
Thrombotic risk factors, such as myeloproliferative neoplasms, factor V Leiden mutation, prothrombin G20210A mutation, paroxysmal nocturnal hemoglobinuria, etc., are common in western patients with Budd–Chiari syndrome (BCS) [1,2]. However, recent observational studies have shown that these risk factors are rarely observed in Chinese BCS patients [3–5]. More recently, this discrepancy has been further confirmed by other studies [6,7]. However, considering that the current evidence is limited, a prospective study has been carried out to further validate these previous findings. Table 1
Initials W.G.G. H.Z.G. N.X. G.K.P. D.C.P. Z.C.X. F.A.B. W.Q.E. H.Y.Z. H.X.Y. D.Y.L. G.X.Q. C.X. Z.Y.K. Z.L.W. Y.X.Q. G.L.X. L.H.Y. L.M.E. R.Y.L. W.Z.F. L.T.T. X.Y.Q. K.Q.L. X.F.X.
Collectively, the results of the prospective validation study were almost consistent with those of our previous work. These findings suggested that the etiological distribution of BCS should be different between western countries and China, and the pathogenesis of BCS in
Results of thrombotic risk factors in 25 Chinese Budd–Chiari syndrome patients MPL JAK2 JAK2 W515 V617F exon 12 L/K Sex Age Type mutation mutation mutation M M M M M M M F F F F M M M M M F F F F F M F F M
47 38 22 45 40 30 53 60 57 27 38 20 35 50 18 36 18 23 38 41 39 50 35 23 10
Com Com Com HV HV Com Com Com Com Com Com HV HV Com Com Com Com Com Com Com Com Com Com Com Com
Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg
NA Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg
NA Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg
Factor II G20210A mutation
Factor V Leiden G1691A mutation
MTHFR C667T mutation
CD55 on erythrocytes (%)
CD55 on granulocytes (%)
CD59 on erythrocytes (%)
CD59 on granulocytes (%)
EPO
ACA
Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg
Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg
NA Hetero Homo Homo Neg Homo Hetero Neg Hetero Neg Neg Hetero Neg Hetero Hetero Hetero Hetero Hetero Neg Hetero Hetero Hetero Hetero Homo Hetero
95.68 99.61 99.72 99.47 99.2 99.40 99.52 98.88 99.34 98.75 99.51 99.01 98.67 98.96 99.21 98.94 99.5 99.49 98.95 99.04 99.6 98.72 99.41 99.68 97.66
52.33 99.79 99.28 99.89 99.97 99.93 99.99 99.99 99.99 99.67 99.89 99.65 99.94 99.4 99.95 99.96 99.87 99.97 99.91 99.77 99.6 99.82 99.69 99.83 99.77
92.43 99.99 99.98 99.99 99.96 99.93 99.98 99.98 99.89 99.95 99.95 99.96 99.96 99.88 99.98 99.99 99.98 99.83 99.99 99.97 99.1 99.96 99.88 99.98 99.78
75.99 99.79 95.66 97.01 99.62 99.92 99.4 99.97 99.95 99.27 99.74 99.48 99.87 99.92 99.95 99.96 99.84 99.97 99.6 99.68 99.9 99.74 99.06 99.78 97.52
NA 18.6 6.52 24.6 23.9 6.72 57.7 8.33 27.8 62.4 87.9 279.43 4.71 20.4 73.8 56.6 186 13.1 14.3 29.5 25.6 9.64 43.3 123 35.5
Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg
Serum erythropoietin levels’ reference range is 3.70–29.50 mIU/ml. The CD55 or the CD59 deficiency is considered if the proportion of erythrocytes or granulocytes with normal expression of CD55 or CD59 is less than 90%. ACA, anticardiolipin IgG antibodies; Com, combined obstruction of hepatic vein and inferior vena cava; EPO, serum erythropoietin level; F, female; Hetero, heterozygous 677C/T genotype; Homo, homozygous 677TT genotype; HV, hepatic vein; M, male; MTHFR, 5,10-methylenetetrahydrofolate reductase; Neg, negative.
All supplementary digital content is available directly from the corresponding author.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Letter to the Editor 577
Chinese patients should be explored in future. However, the potential limitation of this study is that it has only a small number of BCS patients enrolled prospectively during a 6-month period, which might require external validity. Certainly, it is often difficult to obtain a larger sample size from a single center during a relatively short period, given the rarity of this disease. Ideally, a nationwide epidemiological study should be carried out to evaluate the prevalence of thrombotic risk factors in Chinese BCS patients.
Acknowledgements Conflicts of interest
There are no conflicts of interest.
References 1 2
3
4
5
6
7
Valla DC. Primary Budd–Chiari syndrome. J Hepatol 2009; 50:195–203. Seijo S, Plessier A, Hoekstra J, Dell’era A, Mandair D, Rifai K, et al. Good long-term outcome of Budd–Chiari syndrome with a step-wise management. Hepatology 2013; 57:1962–1968. Qi X, Wu F, Ren W, He C, Yin Z, Niu J, et al. Thrombotic risk factors in Chinese Budd–Chiari syndrome patients. An observational study with a systematic review of the literature. Thromb Haemost 2013; 109:878–884. Qi X, Zhang C, Han G, Zhang W, He C, Yin Z, et al. Prevalence of paroxysmal nocturnal hemoglobinuria in Chinese patients with Budd–Chiari syndrome or portal vein thrombosis. J Gastroenterol Hepatol 2013; 28:148–152. Qi X, He C, Han G, Yin Z, Wu F, Zhang Q, et al. Prevalence of the JAK2 V617F mutation in Chinese patients with Budd–Chiari syndrome and portal vein thrombosis: a prospective study. J Gastroenterol Hepatol 2012; 27:1036–1043. Wang H, Sun G, Zhang P, Zhang J, Gui E, Zu M, et al. JAK2 V617F mutation and 46/1 haplotype in Chinese Budd–Chiari syndrome patients. J Gastroenterol Hepatol 2014; 29:208–214. Cheng D, Xu H, Lu ZJ, Hua R, Qiu H, Du H, et al. Clinical features and etiology of Budd–Chiari syndrome in Chinese patients: a single-center study. J Gastroenterol Hepatol 2013; 28:1061–1067.
Sorafenib for the treatment of recurrent hepatocellular carcinoma after liver transplantation: does mTOR inhibitors association augment toxicity? Giovanni Perricone, Andrea Mancuso, Luca S. Belli, Chiara Mazzarelli and Claudio Zavaglia, Hepatology and Gastroenterology Unit, Niguarda Ca’ Granda Hospital, Piazza Ospedale Maggiore 3, Milan, Italy Correspondence to Giovanni Perricone, MD, Hepatology and Gastroenterology Unit, Niguarda Ca’ Granda Hospital, Piazza Ospedale Maggiore 3, 20162 Milan, Italy Table 1
Tel: + 39 026 444 4454; fax: + 39 026 444 2895; e-mails: [email protected], [email protected] Received 30 January 2014 Accepted 31 January 2014
Although sorafenib has shown a survival benefit in cirrhotics with advanced hepatocellular carcinoma (HCC), its efficacy and safety in the post-liver transplantation (LT) setting have scarcely been studied. Few retrospective cohort studies have been published so far. Recently, Sposito et al. [1] compared the outcome of 15 patients with HCC recurrence after LT treated with sorafenib with 24 historical controls who received best supportive care. The median survival from the start of treatment was 10.6 months for the sorafenib group compared with 2.2 months in the control group. No severe adverse event was registered. In the same setting, Staufer et al. [2] observed grade 3–4 adverse events in 92% of 13 patients (nine treated with mTOR inhibitors). Sorafenib was discontinued in 77%. We have already published data in 11 patients treated with sorafenib, with or without everolimus, for recurrent HCC after LT [3]. The median survival from the start of treatment was 5 months. One patient died because of massive gastrointestinal bleeding [4]. Adverse events or intolerance motivated sorafenib withdrawal in 36% and dose reduction in 91%. From July 2010 to July 2013, we treated four additional patients with sorafenib, in association with everolimus (Table 1). The maximum daily tolerated dose of sorafenib was 400 mg. The median treatment duration was 111 days (range 77–144 days). Grade 2 adverse events occurred in two patients. Grade 3 cholestasis occurred in another patient. The last patient was hospitalized for severe diarrhea 4 months after starting sorafenib. He started to complain of diarrhea 2 weeks after starting treatment. After reduction of sorafenib to 400 mg daily, intermittent diarrhea persisted but the patient’s condition improved. He had stable disease at computed tomographic scan performed 3 months after the start of treatment. During hospitalization, grade 3 diarrhea associated with
Main characteristics of four patients with recurrent hepatocellular carcinoma after liver transplantation treated with sorafenib
Patient Age/sex Time to recurrence (months) Localization of recurrence Baseline serum a-fetoprotein (ng/ml) Immune suppression Maximum sorafenib dose (mg/day) Duration of treatment with sorafenib (days) Adverse events (grades 3–4) Best tumor response Outcome Survival after OLT (days) Survival after sorafenib start (days)
1
2
3
4
56/F 3 Lung 217 EVR 400 183 Noa Progression Dead 628 532
56/M 31 Liver, bone 1210 TAC-EVR 400 77 Grade 3 cholestasis Progression Dead 1431 488
53/M 46 Liver, lung, peritoneum 2 EVR 400 78 Nob Progression Alive 1501 104
50/M 15 Liver, lung 4 EVR 400 144 Grade 3 diarrhea Stable disease Dead 978 161
EVR, everolimus; F, female; M, male; OLT, orthotopic liver transplantation; TAC, tacrolimus. a Grade 2 fatigue and cholestasis. b Grade 2 fatigue, urticaria, and hand–foot skin reaction; grade 1 fever and weight loss.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
