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Huang YJ, Wang JS, Chen CH, Chang CH, Liao SC, Lee SW, Peng YC, Lee TY, Li TC. Predictive factors and clinical outcomes in decompensated non-cirrhotic chronic hepatitis B patients treated with entecavir or tenofovir disoproxil fumarate. J Formos Med Assoc 2025:S0929-6646(25)00222-0. [PMID: 40360345 DOI: 10.1016/j.jfma.2025.05.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2024] [Revised: 04/03/2025] [Accepted: 05/08/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND & AIMS Little is known about the short-term and long-term outcomes of non-cirrhotic chronic hepatitis B (CHB) patients who experience hepatic decompensation. Therefore, this study aimed to investigate the clinical outcomes of decompensated non-cirrhotic CHB patients. METHODS We conducted a retrospective study and enrolled a total of 304 decompensated non-cirrhotic CHB patients. Cox regression model was used to analyze factors associated with all-cause mortality. Additionally, the incidence of HBsAg seroclearance and its associated factors were estimated by the competing risk analysis. RESULTS The median follow-up time was 4.36 years (IQR 1.04-7.16). Out of the total enrolled patients, 63 (20.72 %) patients either died or underwent liver transplantation, and 14 patients achieved HBsAg seroclearance. Risk factors associated with 1-month, 3-month, and long-term all-cause mortality were the presence of ascites and hepatic encephalopathy, baseline HBV DNA levels, and MELD scores. The cumulative incidence of HBsAg seroclearance was 1.78 %, 3.72 %, 4.25 %, 5.68 %, 5.68 %, 8.28 %, and 8.28 % at the 1-year, 2-year, 3-year, 4-year, 5-year, 6-year, and 7-year follow-up, respectively. Independent predictors for HBsAg seroclearance were baseline alanine aminotransferase (ALT)≧ 25 times upper limit of normal (subdistribution hazard ratio [sHR] = 5.97; 95 %CI, 1.82-19.63; p = 0.0032) and HBV DNA <5 log10 IU/ml (sHR = 4.43; 95 %CI, 1.55-12.63; p = 0.0054). CONCLUSIONS The presence of ascites and hepatic encephalopathy, baseline HBV DNA levels, and MELD scores were associated with short-term and long-term all-cause mortality. Additionally, lower HBV DNA levels and higher ALT levels at baseline were independently predictive of sequential HBsAg seroclearance.
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Affiliation(s)
- Yi-Jie Huang
- Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan; Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Jun-Sing Wang
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Cheng-Hsu Chen
- Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Life Science, Tunghai University, Taichung, Taiwan
| | - Chung-Hsin Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Szu-Chia Liao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Shou-Wu Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Yen-Chun Peng
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Teng-Yu Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Tsai-Chung Li
- Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan; Department of Audiology and Speech-Language Pathology, College of Medical and Health Sciences, Asia University, Taichung, Taiwan.
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2
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Brennan PN, MacMillan M, Manship T, Moroni F, Glover A, Troland D, MacPherson I, Graham C, Aird R, Semple SIK, Morris DM, Fraser AR, Pass C, McGowan NWA, Turner ML, Manson L, Lachlan NJ, Dillon JF, Kilpatrick AM, Campbell JDM, Fallowfield JA, Forbes SJ. Autologous macrophage therapy for liver cirrhosis: a phase 2 open-label randomized controlled trial. Nat Med 2025; 31:979-987. [PMID: 39794616 PMCID: PMC11922741 DOI: 10.1038/s41591-024-03406-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Accepted: 11/11/2024] [Indexed: 01/13/2025]
Abstract
Cirrhosis is a major cause of morbidity and mortality; however, there are no approved therapies except orthotopic liver transplantation. Preclinical studies showed that bone-marrow-derived macrophage injections reduce inflammation, resolve fibrosis and stimulate liver regeneration. In a multicenter, open-label, parallel-group, phase 2 randomized controlled trial ( ISRCTN10368050 ) in n = 51 adult patients with compensated cirrhosis and Model for End-Stage Liver Disease (MELD) score ≥10 and ≤17, we evaluated the efficacy of autologous monocyte-derived macrophage therapy (n = 27) compared to standard medical care (n = 24). The primary endpoint was the difference in baseline to day 90 change in MELD score (ΔMELD) between treatment and control groups (ΔΔMELD). Secondary endpoints included adverse clinical outcomes, non-invasive fibrosis biomarkers and health-related quality of life (HRQoL) at 90 d, 180 d and 360 d. The ΔΔMELD between day 0 and day 90 in the treatment group compared to controls was -0.87 (95% confidence interval: -1.79, 0.0; P = 0.06); therefore, the primary endpoint was not met. During 360-d follow-up, five of 24 participants in the control group developed a total of 10 severe adverse events, four of which were liver related, and three deaths (two liver related), whereas no liver-related severe adverse events or deaths occurred in the treatment group. Although no differences were observed in biomarkers or HRQoL, exploratory analysis showed anti-inflammatory serum cytokine profiles after macrophage infusion. This study reinforces the safety and potential efficacy of macrophage therapy in cirrhosis, supporting further investigation.
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Affiliation(s)
- Paul N Brennan
- Division of Molecular and Clinical Medicine, University of Dundee, Dundee, UK
- Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK
| | - Mark MacMillan
- Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK
| | - Thomas Manship
- Edinburgh Transplant Centre, Royal Infirmary of Edinburgh, Edinburgh, UK
| | | | - Alison Glover
- Scottish National Blood Transfusion Service (SNBTS), Edinburgh, UK
| | - Debbie Troland
- Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK
| | - Iain MacPherson
- Division of Molecular and Clinical Medicine, University of Dundee, Dundee, UK
| | - Catriona Graham
- Wellcome Trust Clinical Research Facility, University of Edinburgh, Edinburgh, UK
| | - Rhona Aird
- Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK
| | - Scott I K Semple
- Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
| | - David M Morris
- Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
| | | | - Chloe Pass
- Scottish National Blood Transfusion Service (SNBTS), Edinburgh, UK
| | - Neil W A McGowan
- Scottish National Blood Transfusion Service (SNBTS), Edinburgh, UK
| | - Marc L Turner
- Scottish National Blood Transfusion Service (SNBTS), Edinburgh, UK
| | - Lynn Manson
- Scottish National Blood Transfusion Service (SNBTS), Edinburgh, UK
| | | | - John F Dillon
- Division of Molecular and Clinical Medicine, University of Dundee, Dundee, UK
| | - Alastair M Kilpatrick
- Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK
| | | | - Jonathan A Fallowfield
- Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK
| | - Stuart J Forbes
- Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK.
- Edinburgh Transplant Centre, Royal Infirmary of Edinburgh, Edinburgh, UK.
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3
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Huang YJ, Wang JS, Chen CH, Lee SW, Chang CH, Liao SC, Peng YC, Lee TY, Li TC. Determinants of outcomes in patients with hepatitis B virus-decompensated cirrhosis. Sci Rep 2025; 15:562. [PMID: 39747298 PMCID: PMC11696113 DOI: 10.1038/s41598-024-84413-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2024] [Accepted: 12/23/2024] [Indexed: 01/04/2025] Open
Abstract
The role of pre-treatment HBV DNA levels on the prognosis of hepatitis B virus-related decompensated cirrhosis is unclear. This study investigated the effects of pre-treatment HBV DNA and other determinants on short-term and long-term survival of chronic hepatitis B (CHB) patients with decompensated cirrhosis. A total of 278 cirrhotic decompensated CHB patients treated with entecavir or tenofovir disoproxil fumarate were retrospectively enrolled. Cox regression models were used to analyze factors associated with all-cause mortality. The median follow-up time was 17 months (IQR2.17-58.94), during which 132 patients (47.4%) either died or underwent liver transplantation. The cumulative incidence of all-cause mortality was 16%, 29%, 34%, 39%, and 51% at the 1-month, 3-month, 6-month, 1-year, and 5-year follow-ups, respectively. Risk factors associated with 3-month all-cause mortality were age, presence of ascites and hepatic encephalopathy, baseline hepatitis flares, pre-treatment HBV DNA levels, and MELD scores. In the subgroup analysis, for 3-month all-cause mortality, significant associations of age, baseline hepatitis flares, and MELD scores with pre-treatment HBV DNA levels were observed (p for interaction were 0.005, 0.032, and 0.030, respectively). Risk factors associated with 5-year all-cause mortality were age, the presence of ascites and hepatic encephalopathy, and MELD scores. Liver functional reserve and age played a critical role in the prognosis of CHB patients with decompensated cirrhosis. Pre-treatment HBV DNA levels had an impact on short-term all-cause mortality, but not on long-term all-cause mortality.
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Affiliation(s)
- Yi-Jie Huang
- Department of Public Health, College of Public Health, China Medical University, No. 100, Sec. 1, Jingmao Rd., Beitun Dist., Taichung, 406040, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Jun-Sing Wang
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Cheng-Hsu Chen
- Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Life Science, Tunghai University, Taichung, Taiwan
| | - Shou-Wu Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Chung-Hsin Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Szu-Chia Liao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Yen-Chun Peng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Teng-Yu Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Tsai-Chung Li
- Department of Public Health, College of Public Health, China Medical University, No. 100, Sec. 1, Jingmao Rd., Beitun Dist., Taichung, 406040, Taiwan.
- Department of Audiology and Speech-Language Pathology, College of Medical and Health Science, Asia University, Taichung, Taiwan.
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Gupta VF, Benvenuti T, Ronald J, Cline BC, Befera NT, Martin JG, Pabon-Ramos WM, Sag AA, Smith TP, Suhocki PV, Kim CY. Long term impact of transjugular intrahepatic portosystemic shunt (TIPS) creation on hepatic morphology. Clin Imaging 2024; 110:110142. [PMID: 38696997 DOI: 10.1016/j.clinimag.2024.110142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 03/03/2024] [Accepted: 04/01/2024] [Indexed: 05/04/2024]
Abstract
PURPOSE The purpose of this study was to evaluate long-term morphologic changes occurring in the liver after TIPS creation with correlation with hepatic function to gain insight on the physiologic impact of TIPS on the liver. METHODS This retrospective study included patients who underwent TIPS creation between 2005 and 2022 and had contrasted CT or MRI studies prior to and between 1 and 2 years post procedure. Strict exclusion criteria were applied to avoid confounding. Parenchymal volume and vessel measurements were assessed on the pre- and post-TIPS CT or MRI and MELD scores calculated. RESULTS Of 580 patients undergoing TIPS creation, 65 patients (mean age, 55 years; 36 males) had pre-TIPS and post-TIPS imaging meeting inclusion criteria at median 16.5 months. After TIPS, the mean MELD score increased (12.9 to 15.4; p = 0.008) and total liver volume decreased (1730 to 1432 mL; p < 0.001). However, the magnitude of volume change did not correlate with MELD change. Neither portosystemic gradient nor TIPS laterality correlated with total or lobar hepatic volume changes or MELD changes. The main portal vein diameter increased (15.0 to 18.7 mm; p < 0.001). Thrombosis of the hepatic vein used for TIPS creation resulted in a mean increase in MELD of +4.1 compared to -2.1 in patients who had a patent and normal hepatic vein (p = 0.007). CONCLUSIONS Given lack of correlation between portosystemic gradient, hepatic atrophy, hepatic function, and TIPS laterality, the alterations in portal flow dynamics after TIPS may not be impactful to hepatic function. However, hepatic vein patency after TIPS correlated with improved hepatic function.
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Affiliation(s)
| | | | - James Ronald
- Division of Interventional Radiology, Department of Radiology, Duke University Medical Center, Durham, NC, USA
| | - Brendan C Cline
- Division of Interventional Radiology, Department of Radiology, Duke University Medical Center, Durham, NC, USA
| | - Nicholas T Befera
- Division of Interventional Radiology, Department of Radiology, Duke University Medical Center, Durham, NC, USA
| | - Jonathan G Martin
- Division of Interventional Radiology, Department of Radiology, Duke University Medical Center, Durham, NC, USA
| | - Waleska M Pabon-Ramos
- Division of Interventional Radiology, Department of Radiology, Duke University Medical Center, Durham, NC, USA
| | - Alan A Sag
- Division of Interventional Radiology, Department of Radiology, Duke University Medical Center, Durham, NC, USA
| | - Tony P Smith
- Division of Interventional Radiology, Department of Radiology, Duke University Medical Center, Durham, NC, USA
| | - Paul V Suhocki
- Division of Interventional Radiology, Department of Radiology, Duke University Medical Center, Durham, NC, USA
| | - Charles Y Kim
- Division of Interventional Radiology, Department of Radiology, Duke University Medical Center, Durham, NC, USA.
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5
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Kirichenko A, Uemura T, Liang Y, Hasan S, Abel S, Renz P, Shamsesfandabadi P, Carpenter J, Yin Y, Thai N. Stereotactic Body Radiation Therapy (SBRT) for Hepatocellular Carcinoma (HCC) With Single Photon Emission Computed Tomography (SPECT) Functional Treatment Planning in Patients With Advanced Hepatic Cirrhosis. Adv Radiat Oncol 2024; 9:101367. [PMID: 38405302 PMCID: PMC10885583 DOI: 10.1016/j.adro.2023.101367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Accepted: 08/19/2023] [Indexed: 02/27/2024] Open
Abstract
Purpose We report on the feasibility and outcomes of liver stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) with single-photon emission computed tomography (SPECT) functional treatment planning in patients with Child-Pugh (CP) B/C cirrhosis. Methods and Materials Liver SPECT with 99mTc-sulfur colloid was coregistered to treatment planning computed tomography (CT) for the guided avoidance of functional hepatic parenchyma during SBRT. Functional liver volumes (FLVs) obtained from SPECT were compared with anatomic liver volumes defined on the planning CT. Radiation dose constraints were adapted exclusively to FLV. Local control, toxicity, and survival were reported with at least 6 months of radiographic follow-up. Pre- and posttransplant outcomes were analyzed in a subset of patients who completed SBRT as a bridge to liver transplant. Model of End-Stage Liver Disease was used to score hepatic function before and after SBRT completion. Results With a median follow-up of 32 months, 45 patients (58 lesions) with HCC and CP-B/C cirrhosis received SBRT to a median dose of 45 Gy (3-5 fractions). FLV loss (34%, P < .001) was observed in all patients, and the functional and anatomic liver volumes matched well in a control group of noncirrhotic/non-HCC patients. Despite marked functional parenchyma retraction, the amount of FLV on SPECT exposed to the threshold irradiation was significantly less than the CT liver volumes (P < .001) because of the optimized beam placement during dosimetry planning. Twenty-three patients (51%) successfully completed orthotopic liver transplant, with a median time to transplant of 9.2 months. With 91% in-field local control, the overall 2-year survival was 65% (90% after the orthotopic liver transplant), with no incidence of radiation-induced liver disease observed within 3 to 4 months or accelerated CP class migration from B to C within the first 6 months post-SBRT. Mean Model of End-Stage Liver Disease-Na score was not significantly elevated at 3-month intervals after SBRT completion. Conclusions Functional treatment planning with 99mTc sulfur colloid SPECT/CT allows identification and avoidance of functional hepatic parenchyma in patients with CP-B/C cirrhosis, leading to low toxicity and satisfactory transplant outcomes.
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Affiliation(s)
- Alexander Kirichenko
- Division of Radiation Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, Pennsylvania
| | - Tadahiro Uemura
- Division of Abdominal Transplantation and Hepato-Biliary Surgery, Allegheny General Hospital, Pittsburgh, Pennsylvania
| | - Yun Liang
- Division of Radiation Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, Pennsylvania
| | | | - Steven Abel
- Division of Radiation Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, Pennsylvania
| | - Paul Renz
- Division of Radiation Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, Pennsylvania
| | - Parisa Shamsesfandabadi
- Division of Radiation Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, Pennsylvania
| | - Jennifer Carpenter
- Division of Abdominal Transplantation and Hepato-Biliary Surgery, Allegheny General Hospital, Pittsburgh, Pennsylvania
| | - Yue Yin
- Allegheny-Singer Research Institute, Biostatistics, Allegheny Health Network, Pittsburgh, Pennsylvania
| | - Ngoc Thai
- Division of Abdominal Transplantation and Hepato-Biliary Surgery, Allegheny General Hospital, Pittsburgh, Pennsylvania
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Zhang W, Jin P, Liu J, Wu Y, Wang R, Zhang Y, Shen Y, Zhang M, Bai X, Fung J, Liang T. Dynamic evaluation based on acute-on-chronic liver failure predicts survival of patients after liver transplantation: a cohort study. Int J Surg 2023; 109:3117-3125. [PMID: 37498133 PMCID: PMC10583902 DOI: 10.1097/js9.0000000000000596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Accepted: 06/26/2023] [Indexed: 07/28/2023]
Abstract
BACKGROUND AND AIMS Dynamic evaluation of critically ill patients is the key to predicting their outcomes. Most scores based on the Model for End-stage Liver Disease (MELD) and acute-on-chronic liver failure (ACLF) utilize point-in-time assessment. This study mainly aimed to investigate the impact of dynamic clinical course change on post-liver transplantation (LT) survival. METHODS This study included 637 adults (overall cohort) with benign end-stage liver diseases. The authors compared the MELD scores and our ACLF-based dynamic evaluation scores. Patients enrolled or transplanted with ACLF-3 were defined as the ACLF-3 cohort ( n =158). The primary outcome was 1-year mortality. ΔMELD and ΔCLIF-OF (Chronic Liver Failure-Organ Failure) represented the respective dynamic changes in liver transplant function. Discrimination was assessed using the area under the curve. A Cox regression analysis identified independent risk factors for specific organ failure and 1-year mortality. RESULTS Patients were grouped into three groups: the deterioration group (D), the stable group (S), and the improvement group (I). The deterioration group (ΔCLIF-OF ≥2) was more likely to receive national liver allocation ( P =0.012) but experienced longer cold ischemia time ( P =0.006) than other groups. The area under the curves for ΔCLIF-OF were 0.752 for the entire cohort and 0.767 for ACLF-3 cohorts, both superior to ΔMELD ( P <0.001 for both). Compared to the improvement group, the 1-year mortality hazard ratios (HR) of the deterioration group were 12.57 (6.72-23.48) for the overall cohort and 7.00 (3.73-13.09) for the ACLF-3 cohort. Extrahepatic organs subscore change (HR=1.783 (1.266-2.512) for neurologic; 1.653 (1.205-2.269) for circulation; 1.906 (1.324-2.743) for respiration; 1.473 (1.097-1.976) for renal) were key to transplantation outcomes in the ACLF-3 cohort. CLIF-OF at LT (HR=1.193), ΔCLIF-OF (HR=1.354), and cold ischemia time (HR=1.077) were independent risk factors of mortality for the overall cohort, while ΔCLIF-OF (HR=1.384) was the only independent risk factor for the ACLF-3 cohort. Non-ACLF-3 patients showed a higher survival rate than patients with ACLF-3 in all groups ( P =0.002 for I, P =0.005 for S, and P =0.001 for D). CONCLUSION This was the first ACLF-based dynamic evaluation study. ΔCLIF-OF was a more powerful predictor of post-LT mortality than ΔMELD. Extrahepatic organ failures were core risk factors for ACLF-3 patients. CLIF-OF at LT, ΔCLIF-OF, and cold ischemia time were independent risk factors for post-LT mortality. Patients with a worse baseline condition and a deteriorating clinical course had the worst prognosis. Dynamic evaluation was important in risk stratification and recipient selection.
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Affiliation(s)
- Wei Zhang
- Department of Hepatobiliary and Pancreatic Surgery
- Liver Transplant Center
| | - Pingbo Jin
- Department of Hepatobiliary and Pancreatic Surgery
- Liver Transplant Center
| | - Junfang Liu
- Department of Hepatobiliary and Pancreatic Surgery
- Liver Transplant Center
| | - Yue Wu
- Department of Hepatobiliary and Pancreatic Surgery
- Liver Transplant Center
| | | | - Yuntao Zhang
- Department of Hepatobiliary and Pancreatic Surgery
- Liver Transplant Center
| | - Yan Shen
- Department of Hepatobiliary and Pancreatic Surgery
- Liver Transplant Center
| | - Min Zhang
- Department of Hepatobiliary and Pancreatic Surgery
- Liver Transplant Center
| | - Xueli Bai
- Department of Hepatobiliary and Pancreatic Surgery
- Liver Transplant Center
| | - John Fung
- Transplantation Institute, Department of Surgery, University of Chicago, Chicago, Illinois, USA
| | - Tingbo Liang
- Department of Hepatobiliary and Pancreatic Surgery
- Liver Transplant Center
- Key Lab of Combined Multi-organ Transplantation of the Ministry of Health
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China
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7
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Wang C, Yao J, Niu H, Yang C, Liu J, Bai Y, Ju S, Xiong B. Dynamic changes in liver function after transjugular intrahepatic portosystemic shunt in patients with cirrhosis. J Interv Med 2022; 5:207-212. [DOI: 10.1016/j.jimed.2022.09.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 08/26/2022] [Accepted: 09/05/2022] [Indexed: 10/14/2022] Open
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8
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Nazir N, Abbas S, Nasir H, Hussain I. Electrochemical sensing of limonene using thiol capped gold nanoparticles and its detection in the real breath sample of a cirrhotic patient. J Electroanal Chem (Lausanne) 2022. [DOI: 10.1016/j.jelechem.2021.115977] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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9
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Acar Ş, Akyıldız M, Gürakar A, Tokat Y, Dayangaç M. Delta MELD as a predictor of early outcome in adult-to-adult living donor liver transplantation. TURKISH JOURNAL OF GASTROENTEROLOGY 2020; 31:782-789. [PMID: 33361041 DOI: 10.5152/tjg.2020.18761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
BACKGROUND/AIMS An increased post-operative mortality risk has been reported among patients who undergo living donor liver transplantation (LDLT) with higher model for end-stage liver disease (MELD) scores. In this study, we investigated the effect of MELD score reduction on post-operative outcomes in patients with a high MELD (≥20) score by pre-transplant management. MATERIALS AND METHODS We retrospectively analyzed 386 LDLT cases, and patients were divided into low-MELD (<20, n=293) vs. high-MELD (≥20, n=93) groups according to their MELD score at the time of index hospitalization. Patients in the high-MELD group were managed specifically according to a treatment algorithm in an effort to decrease the MELD score. Patients in the high-MELD group were further divided into 2 subgroups: (1) responders (n=34) to pre-transplant treatment with subsequent reduction of the MELD score by a minimum of 1 point vs. (2) non-responders (n=59), whose MELD score remained unchanged or further increased on the day of LDLT. Responders vs. non-responders were compared according to etiology, demographics, and survival.
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Affiliation(s)
- Şencan Acar
- Department of Gastroenterology and Hepatology, Section of Transplant Hepatology, Johns Hopkins University School of Medicine Baltimore, MD, USA;Department of Gastroenterology and Organ Transplantation Center, Sakarya University School of Medicine, Sakarya, Turkey
| | - Murat Akyıldız
- Department of Gastroenterology and Organ Transplantation Center, Koc University School of Medicine, İstanbul, Turkey
| | - Ahmet Gürakar
- Department of Gastroenterology and Hepatology, Section of Transplant Hepatology, Johns Hopkins University School of Medicine Baltimore, MD, USA
| | - Yaman Tokat
- Department of General Surgery and Liver Transplantation Unit, Florence Nightingale Hospital, Istanbul Bilim University, İstanbul, Turkey
| | - Murat Dayangaç
- Department of General Surgery and Liver Transplantation Unit, Medipol Mega University Hospital, İstanbul, Turkey
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10
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Gong N, Jia C, Huang H, Liu J, Huang X, Wan Q. Predictors of Mortality During Initial Liver Transplant Hospitalization and Investigation of Causes of Death. Ann Transplant 2020; 25:e926020. [PMID: 33273447 PMCID: PMC7722774 DOI: 10.12659/aot.926020] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Accepted: 09/02/2020] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Liver transplant (LT) remains a life-saving procedure with a high mortality rate. The present study investigated the causes of death and sought to identify predictive factors of mortality during the initial LT hospitalization. MATERIAL AND METHODS We retrieved data on first-time adult recipients who underwent LT between November 2017 and October 2019 receiving grafts from donation after citizen's death. The risk factors for mortality during the initial LT hospitalization were confirmed by univariate analysis. We also analyzed the causes of death. RESULTS We enrolled 103 recipients, including 86 males and 17 females, with a mean age of 47.7 years. Thirty-eight (36.9%) recipients were labeled as non-cholestatic cirrhosis-related indications. Approximately 8% of all recipients had diabetes prior to LT. Induction therapy was used in 11 (10.7%) recipients, along with maintenance therapy. The median model for end-stage liver disease score at LT was 32.4 (21.4-38.4). The in-hospital mortality rate of LT recipients was 6.8% (7/103), and infections were responsible for most of the deaths (6/7). The 1 remaining death resulted from primary graft failure. Univariate analysis showed recipients with postoperative pneumonia (p2 mg/dL, and alanine transaminase on day 1 after LT >1800 µmol/L (all P<0.001) were much more likely to die. CONCLUSIONS In-hospital mortality of LT recipients was high, due in large part to infections. Acute hepatic necrosis, prolonged post-transplant ICU stays, certain types of postoperative infections, and postoperative liver and kidney dysfunction were potential risk factors for in-hospital mortality of LT recipients.
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Affiliation(s)
- Ni Gong
- Department of General Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China
| | - Chao Jia
- Department of Intensive Care Unit, Qingdao Municipal Hospital Group, Qingdao University, Qingdao, Shandong, P.R. China
| | - He Huang
- Hunan International Travel Health Care Center, Changsha, Hunan, P.R. China
| | - Jing Liu
- Department of Transplant Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China
| | - XueTing Huang
- Department of Transplant Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China
| | - QiQuan Wan
- Department of Transplant Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China
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11
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Abstract
Risk scoring for patients with cirrhosis has evolved greatly over the past several decades. However, patients with low Model for End-Stage Liver Disease-Sodium scores still suffer from liver-related morbidity and mortality. Unfortunately, it is not clear which of these low Model for End-Stage Liver Disease-Sodium score patients would benefit from earlier consideration of liver transplantation. This article reviews the literature of risk prediction in patients with cirrhosis, identifies which patients may benefit from earlier interventions, such as transplantation, and proposes directions for future research.
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12
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Mahgoub S, Armstrong MJ, Ferguson JW. Editorial: current challenges in predicting mortality in patients with cirrhosis and refractory ascites. Aliment Pharmacol Ther 2020; 52:885-886. [PMID: 32852822 DOI: 10.1111/apt.15982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Sara Mahgoub
- Liver Unit, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Matthew J Armstrong
- Liver Unit, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.,Institute of Immunology and Immunotherapy, National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Centre (BRC), University of Birmingham, Birmingham, UK
| | - James W Ferguson
- Liver Unit, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.,Institute of Immunology and Immunotherapy, National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Centre (BRC), University of Birmingham, Birmingham, UK
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13
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Yip TCF, Lee HW, Wong VWS, Wong GLH, Tse YK, Lui GCY, Ahn SH, Chan HLY. Factors associated with improvement in MELD score after antiviral treatment in patients with chronic hepatitis B. J Gastroenterol Hepatol 2020; 35:1610-1618. [PMID: 32032974 DOI: 10.1111/jgh.15007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Revised: 02/05/2020] [Accepted: 02/05/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS Improvement in Model for End-Stage Liver Disease (MELD) score during antiviral treatment is associated with reduced hepatic decompensation and death in patients with chronic hepatitis B (CHB)-related cirrhosis. We aimed to identify factors associated with transplant-free survival and on-treatment MELD score improvement. METHODS We identified patients with CHB-related cirrhosis and MELD score ≥ 15 at the start of entecavir and/or tenofovir disoproxil fumarate treatment between 2005 and 2017. The primary endpoint was transplant-free survival at month 6. The secondary endpoints at month 6 were transplant-free survival with > 5-point improvement in MELD score and transplant-free survival with MELD score < 15. RESULTS Of 999 cirrhotic CHB patients, 605 (60.6%) achieved transplant-free survival at month 6. Proportion of transplant-free survival at month 6 stabilized at 10% in patients with high MELD. Patients who achieved transplant-free survival at month 6 were younger, had lower MELD score, lower alanine aminotransferase (ALT), and higher albumin at baseline. Of 605 patients with transplant-free survival, 276 (45.6%) achieved > 5-point improvement in MELD score; 183 (30.2%) had 1-point to 5-point improvement in MELD score; 146 (24.1%) had no improvement or a worsened MELD score. Also, 321 (53.1%) patients with transplant-free survival had a MELD score < 15 at month 6. CONCLUSION On top of lower MELD score, patients with CHB-related cirrhosis who are younger, have higher albumin, and lower ALT are more likely to achieve transplant-free survival after 6 months of antiviral treatment.
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Affiliation(s)
- Terry Cheuk-Fung Yip
- Faculty of Medicine, Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Hye Won Lee
- Faculty of Medicine, Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Vincent Wai-Sun Wong
- Faculty of Medicine, Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Grace Lai-Hung Wong
- Faculty of Medicine, Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Yee-Kit Tse
- Faculty of Medicine, Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Grace Chung-Yan Lui
- Faculty of Medicine, Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Henry Lik-Yuen Chan
- Faculty of Medicine, Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong
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14
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Akturk OM, Çakir M. Red Cell Distribution Width as a Predictor of Malignancy in Patients Who Underwent Upper Gastrointestinal System Endoscopy. Int J Appl Basic Med Res 2020; 10:200-204. [PMID: 33088744 PMCID: PMC7534711 DOI: 10.4103/ijabmr.ijabmr_329_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Revised: 05/25/2020] [Accepted: 06/18/2020] [Indexed: 11/04/2022] Open
Abstract
Introduction Red cell distribution width (RDW) has predictive properties in different benign and malignant diseases. Aim Our aim was to evaluate the predictive value of RDW for malignant gastric lesions by upper gastrointestinal screening. Materials and Methods Data of 91 male patients (Group A) who underwent upper gastrointestinal endoscopy and subsequent surgery for gastric malignancy and age-matched 91 healthy male patients (Group B) with benign disorders were reviewed in this retrospective cohort study. The pathology reports, laboratory parameters, and demographics of the patients were recorded for comparison. Receiver operating characteristic curves were plotted for RDW, and a threshold for prediction of malignancy was calculated. Results The average age of the patients with gastric cancer was 62 (interquartile range [IQR]: 53-70) years. The difference in RDW levels between Group A and Group B was found to be significant: 14.40% (IQR: 13.40-16.40) versus 13.10% (IQR: 12.55-13.50) for the malignant and benign groups, respectively, P = 0.000. The area under the curve was 0.81 (95% confidence interval [CI]: 0.76-0.86), P = 0.000. For the threshold of 13.45%, the positive predictive value (PPV) for malignancy was found to be 69.15 (95% CI: 61.77-75.67) and negative predictive value (NPV) was 70.45 (95% CI: 62.60-77.26). Conclusion RDW was found to have a PPV for malignancy in nearly two-thirds of the patients and had a similar NPV.
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Affiliation(s)
- Okan Murat Akturk
- Department of Surgery, Haseki Training and Research Hospital, İstanbul, Turkey
| | - Mikail Çakir
- Department of Surgery, Haseki Training and Research Hospital, İstanbul, Turkey
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15
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16
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Brock GN, Washburn K, Marvin MR. Use of rapid Model for End-Stage Liver Disease (MELD) increases for liver transplant registrant prioritization after MELD-Na and Share 35, an evaluation using data from the United Network for Organ Sharing. PLoS One 2019; 14:e0223053. [PMID: 31581270 PMCID: PMC6776460 DOI: 10.1371/journal.pone.0223053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Accepted: 09/12/2019] [Indexed: 11/20/2022] Open
Abstract
The Model for End-Stage Liver Disease (MELD) score has been successfully used to prioritize patients on the United States liver transplant waiting list since its adoption in 2002. The United Network for Organ Sharing (UNOS)/Organ Procurement Transplantation Network (OPTN) allocation policy has evolved over the years, and notable recent changes include Share 35, inclusion of serum sodium in the MELD score, and a ‘delay and cap’ policy for hepatocellular carcinoma (HCC) patients. We explored the potential of a registrant’s change in 30-day MELD scores (ΔMELD30) to improve allocation both before and after these policy changes. Current MELD and ΔMELD30 were evaluated using cause-specific hazards models for waitlist dropout based on US liver transplant registrants added to the waitlist between 06/30/2003 and 6/30/2013. Two composite scores were constructed and then evaluated on UNOS data spanning the current policy era (01/02/2016 to 09/07/2018). Predictive accuracy was evaluated using the C-index for model discrimination and by comparing observed and predicted waitlist dropout probabilities for model calibration. After the change to MELD-Na, increased dropout associated with ΔMELD30 jumps is no longer evident at MELD scores below 30. However, the adoption of Share 35 has potentially resulted in discrepancies in waitlist dropout for patients with sharp MELD increases at higher MELD scores. Use of the ΔMELD30 to add additional points or serve as a potential tiebreaker for patients with rapid deterioration may extend the benefit of Share 35 to better include those in most critical need.
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Affiliation(s)
- Guy N. Brock
- Department of Biomedical Informatics and Center for Biostatistics, College of Medicine, The Ohio State University, Columbus, OH, United States of America
- Department of Surgery, Division of Transplantation Surgery, Wexner Medical Center, The Ohio State University, Columbus, OH, United States of America
- Center for Surgical Health Assessment, Research and Policy (SHARP), Wexner Medical Center, The Ohio State University, Columbus, OH, United States of America
- * E-mail:
| | - Kenneth Washburn
- Department of Surgery, Division of Transplantation Surgery, Wexner Medical Center, The Ohio State University, Columbus, OH, United States of America
| | - Michael R. Marvin
- Department of Transplantation and Liver Surgery, Geisinger Medical Center, Danville, PA, United States of America
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17
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Moroni F, Dwyer BJ, Graham C, Pass C, Bailey L, Ritchie L, Mitchell D, Glover A, Laurie A, Doig S, Hargreaves E, Fraser AR, Turner ML, Campbell JDM, McGowan NWA, Barry J, Moore JK, Hayes PC, Leeming DJ, Nielsen MJ, Musa K, Fallowfield JA, Forbes SJ. Safety profile of autologous macrophage therapy for liver cirrhosis. Nat Med 2019; 25:1560-1565. [PMID: 31591593 DOI: 10.1038/s41591-019-0599-8] [Citation(s) in RCA: 144] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2019] [Accepted: 08/29/2019] [Indexed: 01/26/2023]
Abstract
Therapies to reduce liver fibrosis and stimulate organ regeneration are urgently needed. We conducted a first-in-human, phase 1 dose-escalation trial of autologous macrophage therapy in nine adults with cirrhosis and a Model for End-Stage Liver Disease (MELD) score of 10-16 (ISRCTN 10368050). Groups of three participants received a single peripheral infusion of 107, 108 or up to 109 cells. Leukapheresis and macrophage infusion were well tolerated with no transfusion reactions, dose-limiting toxicities or macrophage activation syndrome. All participants were alive and transplant-free at one year, with only one clinical event recorded, the occurrence of minimal ascites. The primary outcomes of safety and feasibility were met. This study informs and provides a rationale for efficacy studies in cirrhosis and other fibrotic diseases.
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Affiliation(s)
- Francesca Moroni
- MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK
| | - Benjamin J Dwyer
- MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK
| | - Catriona Graham
- Edinburgh Clinical Research Facility, University of Edinburgh, Edinburgh, UK
| | - Chloe Pass
- Tissues, Cells and Advanced Therapeutics, Scottish National Blood Transfusion Service (SNBTS), Edinburgh, UK
| | - Laura Bailey
- Tissues, Cells and Advanced Therapeutics, Scottish National Blood Transfusion Service (SNBTS), Edinburgh, UK
| | - Lisa Ritchie
- Tissues, Cells and Advanced Therapeutics, Scottish National Blood Transfusion Service (SNBTS), Edinburgh, UK
| | - Donna Mitchell
- Tissues, Cells and Advanced Therapeutics, Scottish National Blood Transfusion Service (SNBTS), Edinburgh, UK
| | - Alison Glover
- Tissues, Cells and Advanced Therapeutics, Scottish National Blood Transfusion Service (SNBTS), Edinburgh, UK
| | - Audrey Laurie
- Tissues, Cells and Advanced Therapeutics, Scottish National Blood Transfusion Service (SNBTS), Edinburgh, UK
| | - Stuart Doig
- Tissues, Cells and Advanced Therapeutics, Scottish National Blood Transfusion Service (SNBTS), Edinburgh, UK
| | - Emily Hargreaves
- Tissues, Cells and Advanced Therapeutics, Scottish National Blood Transfusion Service (SNBTS), Edinburgh, UK
| | - Alasdair R Fraser
- Tissues, Cells and Advanced Therapeutics, Scottish National Blood Transfusion Service (SNBTS), Edinburgh, UK
| | - Marc L Turner
- Tissues, Cells and Advanced Therapeutics, Scottish National Blood Transfusion Service (SNBTS), Edinburgh, UK
| | - John D M Campbell
- Tissues, Cells and Advanced Therapeutics, Scottish National Blood Transfusion Service (SNBTS), Edinburgh, UK
| | - Neil W A McGowan
- Tissues, Cells and Advanced Therapeutics, Scottish National Blood Transfusion Service (SNBTS), Edinburgh, UK
| | - Jacqueline Barry
- Cell and Gene Therapy Catapult, 12th Floor Tower Wing, Guy's Hospital, Great Maze Pond, London, UK
| | - Joanna K Moore
- MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK
| | - Peter C Hayes
- Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK
| | - Diana J Leeming
- Nordic Bioscience, Fibrosis Biology and Biomarkers, Herlev, Denmark
| | - Mette J Nielsen
- Nordic Bioscience, Fibrosis Biology and Biomarkers, Herlev, Denmark
| | - Kishwar Musa
- Nordic Bioscience, Fibrosis Biology and Biomarkers, Herlev, Denmark
| | | | - Stuart J Forbes
- MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK.
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18
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Intra arterial treatment of hepatocellular carcinoma: Comparison of MELD score variations between radio-embolization and chemo-embolization. Diagn Interv Imaging 2019; 100:689-697. [PMID: 31281074 DOI: 10.1016/j.diii.2019.05.006] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Revised: 05/14/2019] [Accepted: 05/23/2019] [Indexed: 01/15/2023]
Abstract
PURPOSE The purpose of this study was to assess liver function deterioration, as assessed using the model for end-stage liver disease (MELD) score variations, following transarterial chemo-embolization (TACE) versus selective internal radiation therapy (SIRT) in patients with unresectable unilobar hepatocellular carcinomas (HCC). PATIENTS AND METHODS We retrospectively evaluated all patients who underwent a single conventional TACE or SIRT procedure in our department from May 2013 to May 2018 for unilobar unresectable HCC. A total of 86 patients (76 men, 20 women; mean age, 65.5 years) were included. There were 63 patients in the TACE group [56 men, 7 women; mean age, 65.1±9.6 (SD) years] and 23 patients in the SIRT group [20 men, 3 women; mean age, 70±9.2 (SD) years]. Delta MELD, defined as post treatment minus pre-treatment MELD score, was considered for liver function deterioration and compared between patients who underwent single lobar treatment of SIRT versus TACE. RESULTS Patients in SIRT group had significant higher tumor burden, alpha-fetoprotein serum level, and rates of macroscopic vessel invasion. Mean pre-treatment MELD scores did not differ between TACE [mean, 8.41±1.71 (SD); range: 7.24-9.24] and SIRT groups [mean, 8.36±1.74 (SD); range: 7.07-9.21] (P=0.896) as well as Child-Pugh class and albumin-bilirubin (ALBI) grade distribution. However, following treatment, mean DeltaMELD was greater in TACE group (mean, 0.83±1.83 [SD]; range: -0.30--1.31) than in SIRT group (mean, -0.13±1.06 [SD]; range: -0.49-0.32) (P=0.021). At multivariate analysis, SIRT treatment was independently associated with a lower DeltaMELD score than TACE (R=-0.955 [-1.68; -0.406]; P=0.017;). CONCLUSION Whereas performed in patients with higher tumor burden, SIRT resulted in lower degrees of liver function worsening as assessed using MELD score variations.
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19
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Cholankeril G, Li AA, Dennis BB, Gadiparthi C, Kim D, Toll AE, Maliakkal BJ, Satapathy SK, Nair S, Ahmed A. Pre-Operative Delta-MELD is an Independent Predictor of Higher Mortality following Liver Transplantation. Sci Rep 2019; 9:8312. [PMID: 31165776 PMCID: PMC6549161 DOI: 10.1038/s41598-019-44814-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Accepted: 05/14/2019] [Indexed: 12/13/2022] Open
Abstract
Clinical decompensation immediately prior to liver transplantation may affect post-liver transplant (LT) outcomes. Using the serial Model for End-Stage Liver Disease (MELD) scores recorded in the United Network for Organ Sharing national registry (2010-2017), we analyzed post-LT mortality among adult LT recipients based on the degree of fluctuation in MELD score during the 30-day period prior to LT surgery. Delta-MELD (D-MELD) was defined as recipient MELD score at LT minus lowest MELD score within the preceding 30 days. Impact of D-MELD as a continuous and categorical variable (D-MELD 0-4, 5-10, >10) on early, 30-day post-LT mortality was assessed. Overall, a total of 12,785 LT recipients were analyzed, of which 8,862 (67.9%) had a pre-operative D-MELD 0-4; 2,574 (20.1%) with a D-MELD 5-10; and 1,529 (12.0%) with a D-MELD > 10. One-point incremental increase in pre-operative D-MELD (adjusted HR, 1.07, 95% CI: 1.04-1.10) was associated with higher 30-day post-LT mortality. Moreover, pre-operative D-MELD > 10 was associated with nearly a two-fold increased risk for 30-day post-LT mortality (adjusted HR, 1.89, 95% CI: 1.30-2.77) compared to D-MELD 0-4. The increased risk of pre-LT mortality associated with severity of clinical decompensation assessed by the magnitude of pre-operative D-MELD persists in the early post-LT period.
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Affiliation(s)
- George Cholankeril
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Andrew A Li
- Department of Internal Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Brittany B Dennis
- Department of Medicine, Saint George's Hospital, University of London, London, UK
| | - Chiranjeevi Gadiparthi
- Division of Gastroenterology and Hepatology, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Alice E Toll
- Department of Research, United Network for Organ Sharing, Richmond, VA, USA
| | - Benedict J Maliakkal
- Division of Gastroenterology and Hepatology, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Sanjaya K Satapathy
- Division of Gastroenterology and Hepatology, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Satheesh Nair
- Division of Gastroenterology and Hepatology, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA.
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20
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Smalley HK, Anand N, Buczek D, Buczek N, Lin T, Rajore T, Wacker M, Basavaraju SV, Gurbaxani BM, Hammett T, Keskinocak P, Sokol J, Kuehnert MJ. A mathematical model to describe survival among liver recipients from deceased donors with risk of transmitting infectious encephalitis pathogens. Transpl Infect Dis 2019; 21:e13115. [PMID: 31102550 DOI: 10.1111/tid.13115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Revised: 04/08/2019] [Accepted: 05/12/2019] [Indexed: 11/30/2022]
Abstract
BACKGROUND Between 2002 and 2013, the organs of 13 deceased donors with infectious encephalitis were transplanted, causing infections in 23 recipients. As a consequence, organs from donors showing symptoms of encephalitis (increased probability of infectious encephalitis (IPIE) organs) might be declined. We had previously characterized the risk of IPIE organs using data available to most transplant teams and not requiring special diagnostic tests. If the probability of infection is low, the benefits of a transplant from a donor with suspected infectious encephalitis might outweigh the risk and could be lifesaving for some transplant candidates. METHODS Using organ transplant data and Cox Proportional Hazards models, we determined liver donor and recipient characteristics predictive of post-transplant or waitlist survival and generated 5-year survival probability curves. We also calculated expected waiting times for an organ offer based on transplant candidate characteristics. Using a limited set of actual cases of infectious encephalitis transmission via transplant, we estimated post-transplant survival curves given an organ from an IPIE donor. RESULTS 54% (1256) of patients registered from 2002-2006 who died or were removed from the waiting list because of deteriorated condition within 1 year could have had an at least marginal estimated benefit by accepting an IPIE liver with some probability of infection, with the odds increasing to 86% of patients if the probability of infection was low (5% or less). Additionally, 54% (1252) were removed from the waiting list prior to their estimated waiting time for a non-IPIE liver and could have benefited from an IPIE liver. CONCLUSION Improved allocation and utilization of IPIE livers could be achieved by evaluating the patient-specific trade-offs between (a) accepting an IPIE liver and (b) remaining on the waitlist and accepting a non-IPIE liver after the estimated waiting time.
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Affiliation(s)
- Hannah K Smalley
- H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, Georgia
| | - Nishi Anand
- H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, Georgia
| | - Dylan Buczek
- H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, Georgia
| | - Nicholas Buczek
- H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, Georgia
| | - Timothy Lin
- H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, Georgia
| | - Tanay Rajore
- H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, Georgia
| | - Muriel Wacker
- H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, Georgia
| | - Sridhar V Basavaraju
- Office of Blood, Organ, and Other Tissue Safety, Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Brian M Gurbaxani
- H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, Georgia.,Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Teresa Hammett
- National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Pinar Keskinocak
- H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, Georgia.,Center for Health and Humanitarian Systems, Georgia Institute of Technology, Atlanta, Georgia
| | - Joel Sokol
- H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, Georgia
| | - Matthew J Kuehnert
- Office of Blood, Organ, and Other Tissue Safety, Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
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21
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Lin W, Zhang J, Liu X, Liu H, He J, Li M, Zhang S, Zhang Y, Chen H, Zhang C, Wu W, Jin C, Lee SS, Duan Z. A Dynamic Model for Predicting Outcome in Patients with HBV Related Acute-On-Chronic Liver Failure. Ann Hepatol 2019; 17:392-402. [PMID: 29735787 DOI: 10.5604/01.3001.0011.7383] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM Accurately predicting the prognosis of individual patient is crucial in the management of ACLF. We aimed to establish a specific prognostic model for HBV-related ACLF patients treated with nucleoside analog (NA). MATERIAL AND METHODS We prospectively collected 205 ACLF cases diagnosed according to the APASL criteria. A dynamic prognostic model based on APASL criteria was established and validated. To demonstrate that the model is also applicable to those within EASL criteria, we divided the patients into two groups: met APASL criteria only (group A, n = 123); met both APASL and EASL criteria (group B, n = 82). Its prognostic accuracy was also compared with chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score in group B. RESULTS The model is: R = 0.94 x Bilirubin + 0.53 x evolution of Bilirubin - 0.45 x PT-A - 0.22 x evolution in PT-A -0.1 x PLT + 10 x anti-HBe. The area under receiver operating characteristic curve (AUC) of the model for predicting 90-day mortality was 0.86, which was significantly higher than that of model for end stage liver disease(MELD), MELD-Na, CLIF-SOFA, ΔMELD (7d) and ΔMELD-Na (7d), ΔCLIF- SOFA(7d) (all p < 0.01). The AUC of our model in the validation group was 0.79 which was superior to MELD (0.45) CLIF-SOFA (0.53) score in group B patients (p < 0.01). CONCLUSION In conclusion, the model was superior to the conventional methods in predicting the outcomes of patients with HBV related ACLF treated with NA. It is the first description of a novel prognostic model using consecutive data in patients with HBV-induced acute-on-chronic liver failure (ACLF) treated by nucleoside analogs.
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Affiliation(s)
- Wei Lin
- Beijing Youan Hospital, Capital Medical University, China. Collaborative Innovation Center of Infectious diseases
| | - Jing Zhang
- Beijing Youan Hospital, Capital Medical University, China. Collaborative Innovation Center of Infectious diseases
| | - Xiaohui Liu
- Beijing Youan Hospital, Capital Medical University, China. Collaborative Innovation Center of Infectious diseases
| | | | - Jinqiu He
- Infectious Diseases Hospital Affliated to Nanchang Univeristy, China
| | - Ming Li
- The Second People's Hospital of Fuyang, China
| | - Shuqin Zhang
- Hepatobilary Hospital of Jilin Province, China. The First Affiliated Hospital of Xinjiang Medical University, China
| | | | - Hong Chen
- The First Hospital of Lanzhou University, China
| | | | - Wenfang Wu
- The School of Biomedical Engineering, Capital Medical University, China
| | - Chenggang Jin
- School of Social Development Public Policy, Beijing Normal University, China
| | | | - Zhongping Duan
- Beijing Youan Hospital, Capital Medical University, China. Collaborative Innovation Center of Infectious diseases
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Hsieh YC, Lee KC, Wang YW, Yang YY, Hou MC, Huo TI, Lin HC. Correlation and prognostic accuracy between noninvasive liver fibrosismarkers and portal pressure in cirrhosis: Role of ALBI score. PLoS One 2018; 13:e0208903. [PMID: 30540824 PMCID: PMC6291250 DOI: 10.1371/journal.pone.0208903] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2018] [Accepted: 11/27/2018] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND The role of noninvasive liver fibrosis markers which were developed to evaluate the severity of chronic liver disease remains unclear in cirrhosis. AIMS To evaluate the correlation between noninvasive markers and hemodynamic parameters and their prognostic performance in cirrhotic patients. METHODS A total of 242 cirrhotic patients undergoing hemodynamic study were analyzed. The correlations between noninvasive models, including FIB-4, aspartate aminotransferase to platelet ratio index, cirrhosis discriminant score, Lok index, Goteborg University Cirrhosis Index, and albumin-bilirubin (ALBI) score and hemodynamic parameters were investigated, along with their predictive accuracy for short- and long-term survival. RESULTS There was a significant correlation between all noninvasive markers and hepatic venous pressure gradient (HVPG), and ALBI score had the best correlation (r = 0.307, p<0.001). For the prediction of 3-month and 6-month mortality, serum sodium (sNa) levels had the highest area under curve (AUC; 0.799 and 0.818, respectively) among all parameters, and ALBI score showed the best performance (AUC = 0.691 and 0.740, respectively) compared with other 5 noninvasive models. Of 159 patients with low MELD scores (<14), high ALBI score (>-1.4) and low sNa (<135 mmol/L) predicted early mortality. In the Cox multivariate model, ALBI, MELD, HVPG and sNa were independent predictors of long-term survival. CONCLUSIONS Among noninvasive markers, ALBI score is best correlated with HVPG and associated with short-term outcome in cirrhotic patients. A high ALBI score and low sNa identify high-risk patients with low MELD scores. High MELD, HVPG, ALBI and low sNa levels are independent predictors of survival. Independent studies are required to confirm our findings.
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Affiliation(s)
- Yun-Cheng Hsieh
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Kuei-Chuan Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Ying-Wen Wang
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Ying-Ying Yang
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Teh-Ia Huo
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan
- * E-mail: (TH); (MCL)
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
- * E-mail: (TH); (MCL)
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Nafady HA, Hassan TA, Ahmed LA, Waheeb MA. The role of red cell distribution width as a noninvasive index for predicting liver cell failure and portal hypertension in cirrhotic patients. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2018. [DOI: 10.4103/ejim.ejim_52_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Model for End-Stage Liver Disease and Sodium Velocity Predicts Overall Survival in Nonmetastatic Hepatocellular Carcinoma Patients. Can J Gastroenterol Hepatol 2018; 2018:5681979. [PMID: 30533403 PMCID: PMC6247644 DOI: 10.1155/2018/5681979] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Revised: 10/07/2018] [Accepted: 10/21/2018] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND & AIMS The significance of short-term changes in model for end-stage liver disease and Sodium (MELD-Na) following hepatocellular carcinoma (HCC) diagnosis is unknown. In this report, we explore the value of the rate of short-term changes in MELD-Na as an independent predictor of mortality in patients with nonmetastatic HCC. METHODS We reviewed a cohort of patients diagnosed with nonmetastatic HCC at our institution between 2001 and 2011. We evaluated potential predictors of overall survival, including baseline MELD-Na and the change in MELD-Na over 90 days. We explored survival times of cohorts grouped by baseline MELD-Na and the change in MELD-Na. RESULTS 182 patients met eligibility criteria. With a median follow-up of 21 months for surviving patients, 110 deaths were observed (60%). Median MELD-Na at the time of diagnosis was 9.7 (IQR 7.5 to 13.9). The median changes in percentage of MELD-Na over 90 days were an increase of 9% (IQR -4% to 55%). Multivariable Cox proportional hazards modeling demonstrated that both baseline MELD-Na (HR=1.07 per unit increase, 95% CI 1.03 to 1.11, p<0.001) and changes in MELD-Na exceeding 40% (HR=3.69, 95% CI 2.39 to 5.69, p<0.001) were independently associated with increased mortality risk. Median survival among patients whose changes in MELD-Na were greater than 40% was 4.5 months, and median survival among the 131 other patients was 25.8 months (p<0.001). CONCLUSIONS We identified a subset of HCC patients who have extremely poor prognosis by incorporating the rate of short-term change in MELD-Na to baseline MELD-Na score.
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Yip TCF, Chan HLY, Tse YK, Lam KLY, Lui GCY, Wong VWS, Wong GLH. On-Treatment Improvement of MELD Score Reduces Death and Hepatic Events in Patients With Hepatitis B-Related Cirrhosis. Am J Gastroenterol 2018; 113:1629-1638. [PMID: 30315283 DOI: 10.1038/s41395-018-0247-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Accepted: 07/18/2018] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Antiviral treatment modifies the natural history of chronic hepatitis B (CHB)-related cirrhosis as reflected by improving Model for End-Stage Liver Disease (MELD) score over time. We evaluated the impact of on-treatment change of MELD score on clinical outcomes in patients with CHB-related cirrhosis. METHODS Cirrhotic CHB patients who received entecavir and/or tenofovir disoproxil fumarate for at least 6 months in Hong Kong between 2005 and 2016 were identified. The primary outcome was all-cause mortality; secondary outcomes were hepatocellular carcinoma (HCC), and hepatic events including ascites, spontaneous bacterial peritonitis, variceal bleeding, hepatorenal syndrome, hepatic encephalopathy, and liver transplantation. RESULTS We identified 1743 cirrhotic CHB patients. Their mean MELD score decreased from 12.3 ± 5.5 at baseline to 11.0 ± 4.7 at month 6. At a median (interquartile range) follow-up of 3.9 (1.9-6.0) years, 290 (16.6%) patients died; 201 (11.5%) developed HCC. Among 1140 patients without prior hepatic events, 150 (13.2%) developed hepatic events. Among 464 patients with baseline MELD score ≥15, the 6-year cumulative mortality was 72.8, 36.7, and 23.1% for unchanged or increased MELD score, 1-5 point improvement in MELD score, and >5 point improvement in MELD score at month 6, respectively (log-rank test, P < 0.001); the corresponding 6-year cumulative incidence of hepatic events was 52.7, 30.5, and 23.9% in the three subgroups (Gray's test, P = 0.004). Patients with MELD score <15 at month 6 had lower risk of mortality and hepatic events (all P < 0.001). CONCLUSIONS On-treatment improvement of MELD score correlates with reduced risk of mortality and hepatic events in cirrhotic CHB patients.
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Affiliation(s)
- Terry Cheuk-Fung Yip
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China. State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China. State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Henry Lik-Yuen Chan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China. State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China. State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China. State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Yee-Kit Tse
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China. State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China. State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Kelvin Long-Yan Lam
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China. State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China. State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Grace Chung-Yan Lui
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China. State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Vincent Wai-Sun Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China. State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China. State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China. State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Grace Lai-Hung Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China. State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China. State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China. State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
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Xue R, Meng Q, Dong J, Li J, Yao Q, Zhu Y, Yu H. Clinical performance of stem cell therapy in patients with acute-on-chronic liver failure: a systematic review and meta-analysis. J Transl Med 2018; 16:126. [PMID: 29747694 PMCID: PMC5946490 DOI: 10.1186/s12967-018-1464-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2018] [Accepted: 03/27/2018] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Stem cell therapy has been applied in the treatment of acute-on-chronic liver failure (ACLF). However, its clinical efficiency is still debatable. The aim of this systematic review and meta-analysis is to evaluate the clinical efficiency of stem cell therapy in the treatment of ACLF. METHODS The Cochrane Library, OVID, EMBASE, and PUBMED were searched to December 2017. Both randomized and non-randomized studies, assessing stem cell therapy in patients with ACLF, were included. The outcome measures were total bilirubin (TBIL), alanine transaminase (ALT), international normalized ratio (INR), albumin (ALB), and the model for end-stage liver disease (MELD) score. The quality of evidence was assessed by GRADEpro. RESULTS Four randomized controlled trials and six non-randomized controlled trials were included. The TBIL levels significantly decreased at 1-, 3-, 12-month after the stem cell therapy (p = 0.0008; p = 0.04; p = 0.007). The ALT levels decreased significantly compared with the control group in the short-term (p < 0.00001). There was no obvious change in the INR level compared with the control groups (p = 0.64). The ALB levels increased markedly as compared with the control groups (p < 0.0001). The significant difference can be found in MELD score between stem cell therapy and control groups (p = 0.008). Further subgroup analysis for 3-month clinical performance according to the stem cell types have also been performed. CONCLUSION This study suggests that the clinical outcomes of stem cell therapy were satisfied in patients with ACLF in the short-term. MSCs may be better than BM-MNCs in the stem cells transplantation of ACLF. However, more attention should focus on clinical trials in large-volume centers.
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Affiliation(s)
- Ran Xue
- Department of Critical Care Medicine of Liver Disease, Beijing You-An Hospital, Capital Medical University, No. 8, Xi tou tiao, You an men wai Street, Feng tai District, Beijing, 100069 People’s Republic of China
| | - Qinghua Meng
- Department of Critical Care Medicine of Liver Disease, Beijing You-An Hospital, Capital Medical University, No. 8, Xi tou tiao, You an men wai Street, Feng tai District, Beijing, 100069 People’s Republic of China
| | - Jinling Dong
- Department of Critical Care Medicine of Liver Disease, Beijing You-An Hospital, Capital Medical University, No. 8, Xi tou tiao, You an men wai Street, Feng tai District, Beijing, 100069 People’s Republic of China
| | - Juan Li
- Department of Critical Care Medicine of Liver Disease, Beijing You-An Hospital, Capital Medical University, No. 8, Xi tou tiao, You an men wai Street, Feng tai District, Beijing, 100069 People’s Republic of China
| | - Qinwei Yao
- Department of Critical Care Medicine of Liver Disease, Beijing You-An Hospital, Capital Medical University, No. 8, Xi tou tiao, You an men wai Street, Feng tai District, Beijing, 100069 People’s Republic of China
| | - Yueke Zhu
- Department of Critical Care Medicine of Liver Disease, Beijing You-An Hospital, Capital Medical University, No. 8, Xi tou tiao, You an men wai Street, Feng tai District, Beijing, 100069 People’s Republic of China
| | - Hongwei Yu
- Department of Critical Care Medicine of Liver Disease, Beijing You-An Hospital, Capital Medical University, No. 8, Xi tou tiao, You an men wai Street, Feng tai District, Beijing, 100069 People’s Republic of China
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Correale M, Tarantino N, Petrucci R, Tricarico L, Laonigro I, Di Biase M, Brunetti ND. Liver disease and heart failure: Back and forth. Eur J Intern Med 2018; 48:25-34. [PMID: 29100896 DOI: 10.1016/j.ejim.2017.10.016] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Revised: 10/04/2017] [Accepted: 10/23/2017] [Indexed: 12/18/2022]
Abstract
In their clinical practice, physicians can face heart diseases (chronic or acute heart failure) affecting the liver and liver diseases affecting the heart. Systemic diseases can also affect both heart and liver. Therefore, it is crucial in clinical practice to identify complex interactions between heart and liver, in order to provide the best treatment for both. In this review, we sought to summarize principal evidence explaining the mechanisms and supporting the existence of this complicate cross-talk between heart and liver. Hepatic involvement after heart failure, its pathophysiology, clinical presentation (congestive and ischemic hepatopathy), laboratory and echocardiographic prognostic markers are discussed; likewise, hepatic diseases influencing cardiac function (cirrhotic cardiomyopathy). Several clinical conditions (congenital, metabolic and infectious causes) possibly affecting simultaneously liver and heart have been also discussed. Cardiovascular drug therapy may present important side effects on the liver and hepato-biliary drug therapy on heart and vessels; post-transplantation immunosuppressive drugs may show reciprocal cardio-hepatotoxicity. A heart-liver axis is drafted by inflammatory reactants from the heart and the liver, and liver acts a source of energy substrates for the heart.
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Affiliation(s)
| | - Nicola Tarantino
- Department of Medical & Surgical Sciences, University of Foggia, Italy.
| | - Rossella Petrucci
- Department of Medical & Surgical Sciences, University of Foggia, Italy.
| | - Lucia Tricarico
- Department of Medical & Surgical Sciences, University of Foggia, Italy.
| | - Irma Laonigro
- Ospedali Riuniti University Hospital, Foggia, Italy.
| | - Matteo Di Biase
- Department of Medical & Surgical Sciences, University of Foggia, Italy.
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Xue R, Duan Z, Liu H, Chen L, Yu H, Ren M, Zhu Y, Jin C, Han T, Gao Z, Meng Q. A novel dynamic model for predicting outcome in patients with hepatitis B virus related acute-on-chronic liver failure. Oncotarget 2017; 8:108970-108980. [PMID: 29312583 PMCID: PMC5752496 DOI: 10.18632/oncotarget.22447] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2017] [Accepted: 10/27/2017] [Indexed: 12/11/2022] Open
Abstract
AIM It is challenging to predict the outcome of patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) through existing prognostic models. Our aim was to establish a novel dynamic model to improve the predictive efficiency of 30-day mortality in HBV-ACLF patients. METHODS 305 patients who were diagnosed as HBV-ACLF (derivation cohort, n=211; validation cohort, n=94) were included in this study. The HBV-ACLF dynamic (HBV-ACLFD) model was constructed based on the daily levels of predictive variables in 7 days after diagnosis combined with baseline risk factors by multivariate logistic regression analysis. The HBV-ACLFD model was compared with the Child-Turcotte-Pugh (CTP) score, end-stage liver disease (MELD) score, and MELD within corporation of serum sodium (MELD-Na) score by the area under the receiver-operating characteristic curves (AUROC). RESULTS The HBV-ACLFD model demonstrated excellent discrimination with AUROC of 0.848 in the derivation cohort and of 0.813 in the validation cohort (p=0.620). The performance of the HBV-ACLFD model appeared to be superior to MELD score, MELD-Na score and CTP score (P<0.0001). CONCLUSION The HBV-ACLFD model can accurately predict 30-day mortality in patients with HBV-ACLF, which is helpful to select appropriate clinical procedures, so as to relieve the social and economic burden.
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Affiliation(s)
- Ran Xue
- Department of Critical Care Medicine of Liver Disease, Beijing You-An Hospital, Capital Medical University, Beijing, China
| | - Zhonghui Duan
- Department of Critical Care Medicine of Liver Disease, Beijing You-An Hospital, Capital Medical University, Beijing, China
| | - Haixia Liu
- Department of Critical Care Medicine of Liver Disease, Beijing You-An Hospital, Capital Medical University, Beijing, China
| | - Li Chen
- Georgia Prevention Institute, Medical College of Georgia, Augusta University, Augusta, GA, USA
| | - Hongwei Yu
- Department of Critical Care Medicine of Liver Disease, Beijing You-An Hospital, Capital Medical University, Beijing, China
| | - Meixin Ren
- Department of Critical Care Medicine of Liver Disease, Beijing You-An Hospital, Capital Medical University, Beijing, China
| | - Yueke Zhu
- Department of Critical Care Medicine of Liver Disease, Beijing You-An Hospital, Capital Medical University, Beijing, China
| | - Chenggang Jin
- The School of Social Development and Public Policy, Beijing Normal University, Beijing, China
| | - Tao Han
- Department of Hepatology, Tianjin Third Central Hospital of Tianjin Medical University, Tianjin, China
| | - Zhiliang Gao
- Department of Infectious Diseases, The Third Affiliated Hospital, Zhongshan University, Guangzhou, China
| | - Qinghua Meng
- Department of Critical Care Medicine of Liver Disease, Beijing You-An Hospital, Capital Medical University, Beijing, China
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Utility of post-liver transplantation MELD and delta MELD in predicting early and late mortality. Eur J Gastroenterol Hepatol 2017; 29:1424-1427. [PMID: 28957872 DOI: 10.1097/meg.0000000000000957] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION The performance of early post-liver transplantation (post-LT) model for end-stage liver disease (MELD) or even its dynamic changes over time (ΔMELD) in predicting the mortality after LT is still controversial. AIM The aim of this study was to assess the ability of absolute and ΔMELD calculated at days 7 and 30 after LT to predict 1- and 5-year mortality. PATIENTS AND METHODS Data of 209 consecutive patients who underwent LT in two centers were reviewed. Patients who received LT for hepatocellular carcinoma were excluded, as well as those who did not survive for at least 1 month. MELD and [INCREMENT]MELD were calculated for each patient at 7 and 30 days after LT. RESULTS One hundred fifty-six patients were included, mostly male [104 (66.7%)] with a mean age of 51.9±8.8 years. The main indications for transplantation were decompensated hepatitis C virus-related liver cirrhosis [138 (88.5%)] and hepatitis C and B virus co-infection [10 (6.4%)]. Grafts were obtained from 104 living donors and 52 deceased donors. Survival at 1 and 5 years was 89.7 and 85.9%, respectively, with a mean survival of 52.3±1.5 months. In univariate analysis, both absolute and ΔMELD at postoperative days 7 and 30 significantly predicted 1- and 5-year post-LT mortality. In multivariate analysis, MELD at postoperative day 30 was significantly associated with 1- (odds ratio: 1.24, 95% confidence interval: 1.14-1.35, P<0.0001) and 5-year mortality (odds ratio: 1.23, 95% confidence interval: 1.14-1.33, P<0.0001). The area under the curve for MELD at 30 days post-LT in the prediction of mortality was 0.823 (P=0.01) at 1 year and 0.812 (P<0.001) at 5 years. A cutoff of post-LT day 30 MELD less than 10 could predict mortality with a sensitivity and specificity of 90 and 68.1% at 1 year and 81.3 and 69.7% at 5 years, respectively. CONCLUSION Failure of the MELD score to decline over the first postoperative month to less than 10 is a significant predictor of both early and late post-LT mortality.
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Machicao VI. Model for End-Stage Liver Disease-Sodium Score: The Evolution in the Prioritization of Liver Transplantation. Clin Liver Dis 2017; 21:275-287. [PMID: 28364813 DOI: 10.1016/j.cld.2016.12.014] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The adoption of the model of end-stage liver disease (MELD) score as surrogate marker of liver disease severity has been the greatest change in liver allocation. Since its implementation, waiting time has lost significance. The MELD score calculation was later modified to reflect the contribution of hyponatremia in the estimation of mortality risk. However, the MELD score does not capture accurately the risk of mortality of patients with hepatocellular carcinoma (HCC). Therefore the arbitrary assignment of MELD points has been used for HCC patients. The current allocation system still prioritizes transplantation in HCC patients.
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Affiliation(s)
- Victor Ilich Machicao
- Division of Gastroenterology, Hepatology and Nutrition, McGovern Medical School, University of Texas Health Science Center at Houston, 6400 Fannin Street, MSB 4.234, Houston, TX 77030, USA.
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Chen RC, Cai YJ, Wu JM, Wang XD, Song M, Wang YQ, Zheng MH, Chen YP, Lin Z, Shi KQ. Usefulness of albumin-bilirubin grade for evaluation of long-term prognosis for hepatitis B-related cirrhosis. J Viral Hepat 2017; 24:238-245. [PMID: 27862671 DOI: 10.1111/jvh.12638] [Citation(s) in RCA: 66] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2016] [Accepted: 10/12/2016] [Indexed: 01/27/2023]
Abstract
Long-term prognosis varies widely among patients with hepatitis B virus (HBV)-related liver cirrhosis. Our study aimed to investigate the applicability of albumin-bilirubin (ALBI), Child-Pugh and model for end-stage liver disease (MELD) scores to the long-term prognosis prediction of HBV-related cirrhosis. Patients diagnosed with HBV-associated cirrhosis from the First Affiliated Hospital of Wenzhou Medical University between January 2010 and December 2015 were enrolled in this study. The patients were followed up every 3 months. The prognostic performance of ALBI in long-term outcome prediction for HBV-related cirrhosis was compared with Child-Pugh and MELD scores using time-dependent receiver operating characteristic curve (tdROC) and decision curve analysis. A total of 806 patients were included in our study with 275 (34.1%) deceased during the follow-up. Multivariate Cox regression analysis showed that ALBI grade was an independent predictor associated with mortality. The tdROC analysis showed that ALBI score (0.787, 0.830 and 0.833) was superior to MELD (0.693, P=.003; 0.717, P<.001; 0.744, P<.001) and Child-Pugh score (0.641, P<.001; 0.649, P<.001; 0.657, P<.001) for predicting 1-year, 2-year and 3-year mortality. Additionally, decision curves also got the similar results. In addition, patients with lower ALBI score had a longer life expectancy, even among patients within the same Child-Pugh class. Thus, ALBI score was effective in predicting the long-term prognosis for patients with HBV-related cirrhosis and more accurate than Child-Pugh and MELD scores.
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Affiliation(s)
- R-C Chen
- Department of Liver Diseases, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Y-J Cai
- Department of Liver Diseases, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - J-M Wu
- Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - X-D Wang
- Department of Liver Diseases, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - M Song
- Department of Liver Diseases, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Y-Q Wang
- Department of Liver Diseases, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - M-H Zheng
- Department of Liver Diseases, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Y-P Chen
- Department of Liver Diseases, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Z Lin
- Department of Liver Diseases, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - K Q Shi
- Department of Liver Diseases, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
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Pannu AK, Bhalla A, Rao C, Singh C. Delta model for end-stage liver disease and delta clinical prognostic indicator as predictors of mortality in patients with viral acute liver failure. Int J Crit Illn Inj Sci 2017; 7:252-255. [PMID: 29291180 PMCID: PMC5737069 DOI: 10.4103/ijciis.ijciis_122_16] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Objective: The objective of the study is to compare the model for end-stage liver disease (MELD) with clinical prognostic indicators (CPI) specifically the change in these parameters after 48 h of admission in predicting the mortality in patients with acute liver failure (ALF) due to acute viral hepatitis. Materials and Methods: An open label, investigator-initiated prospective study was conducted that included 41 patients with acute viral hepatitis with ALF. The cases were followed prospectively till death or discharge. The MELD and CPI were calculated at admission and 48 h of admission. Results: Patients having no change or worsening in CPI score, i.e., delta CPI more negative had a higher mortality over the next 48 h compared to patients having an improvement in their respective CPI score. Delta CPI predicted adverse outcome better than the presence of any three CPI on admission (P = 0.019). Patients having no change or a worsening in MELD score, i.e., delta MELD more negative, had a higher mortality in the next 48 h compared to the patients having improvement in their respective MELD score. However, MELD >33 on admission was superior to delta MELD in predicting the adverse outcome (P = 0.019). Conclusion: Among the patients with ALF due to viral hepatitis, delta CPI was found to be superior to delta MELD in predicting the adverse outcome in patients with viral ALF (P < 0.0001).
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Affiliation(s)
- Ashok Kumar Pannu
- Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ashish Bhalla
- Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Chelapati Rao
- Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Charanpreet Singh
- Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Phase Angle Bioelectrical Impedance Analysis (BIA) as a Biomarker Tool for Liver Disease. BIOMARKERS IN DISEASE: METHODS, DISCOVERIES AND APPLICATIONS 2017. [DOI: 10.1007/978-94-007-7675-3_43] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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Mao W, Sun Q, Fan J, Lin S, Ye B. AST to Platelet Ratio Index Predicts Mortality in Hospitalized Patients With Hepatitis B-Related Decompensated Cirrhosis. Medicine (Baltimore) 2016; 95:e2946. [PMID: 26945406 PMCID: PMC4782890 DOI: 10.1097/md.0000000000002946] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Aspartate aminotransferase to platelet ratio index (APRI) has originally been considered as a noninvasive marker for detecting hepatic fibrosis in patients with chronic hepatitis B and C. APRI has been used for predicting liver-related mortality in patients with chronic hepatitis C virus infection or alcoholic liver disease. However, whether APRI could be useful for predicting mortality in chronic hepatitis B virus (HBV) infection remains unevaluated. This study aims to address this knowledge gap. A total of 193 hospitalized chronic HBV-infected patients (cirrhosis, n = 100; noncirrhosis, n = 93) and 88 healthy subjects were retrospectively enrolled. All patients were followed up for 4 months. Mortality that occurred within 90 days of hospital stay was compared among patients with different APRI. APRI predictive value was evaluated by univariate and multivariate regression embedded in a Cox proportional hazards model. APRI varied significantly in our cohort (range, 0.16-10.00). Elevated APRI was associated with increased severity of liver disease and 3-month mortality in hospitalized patients with HBV-related cirrhosis. Multivariate analysis demonstrated that APRI (odds ratio: 1.456, P < 0.001) and the model for end-stage liver disease score (odds ratio: 1.194, P < 0.001) were 2 independent markers for predicting mortality. APRI is a simple marker that may serve as an additional predictor of 3-month mortality in hospitalized patients with HBV-related decompensated cirrhosis.
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Affiliation(s)
- Weilin Mao
- From the Department of Clinical Laboratory, The First Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang (WM, JF, SL, BY) and Department of Urology, The Sixth Affiliated Hospital of Xinjiang Medical University, Xinjiang (S-QQ), China
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Peng Y, Qi X, Guo X. Child-Pugh Versus MELD Score for the Assessment of Prognosis in Liver Cirrhosis: A Systematic Review and Meta-Analysis of Observational Studies. Medicine (Baltimore) 2016; 95:e2877. [PMID: 26937922 PMCID: PMC4779019 DOI: 10.1097/md.0000000000002877] [Citation(s) in RCA: 334] [Impact Index Per Article: 37.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2015] [Revised: 01/07/2016] [Accepted: 01/29/2016] [Indexed: 02/06/2023] Open
Abstract
Child-Pugh and MELD scores have been widely used for the assessment of prognosis in liver cirrhosis. A systematic review and meta-analysis aimed to compare the discriminative ability of Child-Pugh versus MELD score to assess the prognosis of cirrhotic patients.PubMed and EMBASE databases were searched. The statistical results were summarized from every individual study. The summary areas under receiver operating characteristic curves, sensitivities, specificities, positive and negative likelihood ratios, and diagnostic odds ratios were also calculated.Of the 1095 papers initially identified, 119 were eligible for the systematic review. Study population was heterogeneous among studies. They included 269 comparisons, of which 44 favored MELD score, 16 favored Child-Pugh score, 99 did not find any significant difference between them, and 110 did not report the statistical significance. Forty-two papers were further included in the meta-analysis. In patients with acute-on-chronic liver failure, Child-Pugh score had a higher sensitivity and a lower specificity than MELD score. In patients admitted to ICU, MELD score had a smaller negative likelihood ratio and a higher sensitivity than Child-Pugh score. In patients undergoing surgery, Child-Pugh score had a higher specificity than MELD score. In other subgroup analyses, Child-Pugh and MELD scores had statistically similar discriminative abilities or could not be compared due to the presence of significant diagnostic threshold effects.Although Child-Pugh and MELD scores had similar prognostic values in most of cases, their benefits might be heterogeneous in some specific conditions. The indications for Child-Pugh and MELD scores should be further identified.
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Affiliation(s)
- Ying Peng
- From the Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang (YP, XQ, XG); and Postgraduate College, Dalian Medical University, Dalian, China (YP)
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Marroni CA, Miranda D, Boemeke L, Fernandes SA. Phase Angle Bioelectrical Impedance Analysis (BIA) as a Biomarker Tool for Liver Disease. BIOMARKERS IN DISEASE: METHODS, DISCOVERIES AND APPLICATIONS 2016:1-18. [DOI: 10.1007/978-94-007-7742-2_43-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/06/2023]
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Kim TY, Lee JG, Sohn JH, Kim JY, Kim SM, Kim J, Jeong WK. Hepatic Venous Pressure Gradient Predicts Long-Term Mortality in Patients with Decompensated Cirrhosis. Yonsei Med J 2016; 57:138-45. [PMID: 26632394 PMCID: PMC4696945 DOI: 10.3349/ymj.2016.57.1.138] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2014] [Revised: 02/03/2015] [Accepted: 03/04/2015] [Indexed: 01/06/2023] Open
Abstract
PURPOSE The present study aimed to investigate the role of hepatic venous pressure gradient (HVPG) for prediction of long-term mortality in patients with decompensated cirrhosis. MATERIALS AND METHODS Clinical data from 97 non-critically-ill cirrhotic patients with HVPG measurements were retrospectively and consecutively collected between 2009 and 2012. Patients were classified according to clinical stages and presence of ascites. The prognostic accuracy of HVPG for death, survival curves, and hazard ratios were analyzed. RESULTS During a median follow-up of 24 (interquartile range, 13-36) months, 22 patients (22.7%) died. The area under the receiver operating characteristics curves of HVPG for predicting 1-year, 2-year, and overall mortality were 0.801, 0.737, and 0.687, respectively (all p<0.01). The best cut-off value of HVPG for predicting long-term overall mortality in all patients was 17 mm Hg. The mortality rates at 1 and 2 years were 8.9% and 19.2%, respectively: 1.9% and 11.9% with HVPG ≤17 mm Hg and 16.2% and 29.4% with HVPG >17 mm Hg, respectively (p=0.015). In the ascites group, the mortality rates at 1 and 2 years were 3.9% and 17.6% with HVPG ≤17 mm Hg and 17.5% and 35.2% with HVPG >17 mm Hg, respectively (p=0.044). Regarding the risk factors for mortality, both HVPG and model for end-stage liver disease were positively related with long-term mortality in all patients. Particularly, for the patients with ascites, both prothrombin time and HVPG were independent risk factors for predicting poor outcomes. CONCLUSION HVPG is useful for predicting the long-term mortality in patients with decompensated cirrhosis, especially in the presence of ascites.
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Affiliation(s)
- Tae Yeob Kim
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Jae Gon Lee
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Joo Hyun Sohn
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea.
| | - Ji Yeoun Kim
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Sun Min Kim
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Jinoo Kim
- Department of Radiology, Ajou University Hospital, Ajou University College of Medicine, Suwon, Korea
| | - Woo Kyoung Jeong
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Ramanathan S, Khandelwal N, Kalra N, Bhatia A, Dhiman RK, Duseja AK, Chawla YK. Correlation of HVPG level with ctp score, MELD Score, ascites, size of varices, and etiology in cirrhotic patients. Saudi J Gastroenterol 2016; 22:109-15. [PMID: 26997216 PMCID: PMC4817293 DOI: 10.4103/1319-3767.164185] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND/AIM This study intends to determine the correlation of a patient's hepatic venous pressure gradient (HVPG) measurement with six factors: Child-Turcotte-Pugh (CTP) score, model for end-stage liver disease (MELD) score, presence of ascites, size of varices, presence of variceal bleeding, and an etiology of cirrhosis. The study also aims to identify the predictors of higher HVPG measurements that can indirectly affect the prognosis of cirrhotic patients. PATIENTS AND METHODS Thirty patients diagnosed with cirrhosis were enrolled prospectively and each patient's HVPG level was measured by the transjugular catheterization of the right or middle hepatic vein. The wedged hepatic venous pressure (WHVP) and free hepatic venous pressure (FHVP) were measured using a 7F balloon catheter. The HVPG level was calculated as the difference between the WHVP and FHVP measurements. RESULTS The mean HVPG level was higher in alcoholic than in nonalcoholic cirrhosis (19.5 ± 7.3 vs 15.2 ± 4.5 mm Hg, P = 0.13). The mean HVPG was also higher in bleeders compared with nonbleeders (18.5 ± 5.3 vs 10.7 ± 3.1 mmHg, P = 0.001). Patients with varices had a higher mean HVPG level than those without varices (17.4 ± 5.8 vs 11.7 ± 3.9 mmHg, P = 0.04). The difference among the three categories of varices (small, large, and no varices) was statistically significant (P = 0.03). In addition, the mean HVPG level was higher in patients with ascites than in those without ascites (18.7 ± 4.7 vs 11 ± 5.3 mmHg, P = 0.002), and it was significantly higher in patients in CTP class C (21.8 ± 5.5 mmHg) as compared with those in CTP class B (16.9 ± 2.9 mmHg) and CTP class A (10.5 ± 4.1 mmHg; P ≤ 0.001). CONCLUSION HVPG levels were significantly higher in patients in CTP class C as compared with those in CTP classes A and B, thereby indicating that an HVPG measurement correlates with severity of liver disease. A high HVPG level signifies more severe liver disease and can predict the major complications of cirrhosis.
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Affiliation(s)
- Subramaniam Ramanathan
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, Haryana and Punjab, India
| | - Niranjan Khandelwal
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, Haryana and Punjab, India
| | - Naveen Kalra
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, Haryana and Punjab, India,Address for correspondence: Dr. Naveen Kalra, Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, Haryana and Punjab, India. E-mail:
| | - Anmol Bhatia
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, Haryana and Punjab, India
| | - Radha K. Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, Haryana and Punjab, India
| | - Ajay K. Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, Haryana and Punjab, India
| | - Yogesh K. Chawla
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, Haryana and Punjab, India
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Mao W, Hu Y, Lou Y, Dou J, Zou L. Immature platelet fraction values predict recovery of platelet counts following liver transplantation. Clin Res Hepatol Gastroenterol 2015; 39:469-74. [PMID: 25592682 DOI: 10.1016/j.clinre.2014.11.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2014] [Revised: 11/03/2014] [Accepted: 11/14/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND Thrombocytopenia after orthotopic liver transplantation (OLT) is a well-recognized and prevalent early postoperative complication. In the current study, we assessed the clinical utility of the immature platelet fraction (expressed as a percent of total platelets, IPF %) to predict platelet count recovery following OLT. METHODS We analyzed the changes in peripheral platelet counts, IPF values, and liver function before OLT, and 21 days after transplantation in 30 patients with liver cirrhosis. All patients were followed up for at least six months. RESULTS The nadir in the peripheral platelet counts most commonly occurred on the 5th day after post-transplant. Platelets counts gradually rose again to exceed pre-transplant levels by the 3rd to 4th day after the IPF % reached its peak. CONCLUSION The IPF % increased prior to the elevation of platelet counts in patients with OLT suggesting that the IPF % may reflect production of platelets. These findings suggest IPF% could be useful as a predictor of platelet recovery in patients with OLT.
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Affiliation(s)
- Weilin Mao
- Department of Clinical Laboratory, The First Affiliated Hospital, College of Medicine, Zhejiang University, #79, Qingchun Road, Hangzhou, Zhejiang Province 310003, China
| | - Ying Hu
- Department of Clinical Laboratory, The First Affiliated Hospital, College of Medicine, Zhejiang University, #79, Qingchun Road, Hangzhou, Zhejiang Province 310003, China
| | - Yufeng Lou
- Department of Clinical Laboratory, The First Affiliated Hospital, College of Medicine, Zhejiang University, #79, Qingchun Road, Hangzhou, Zhejiang Province 310003, China
| | - Jiufeng Dou
- Department of Clinical Laboratory, The First Affiliated Hospital, College of Medicine, Zhejiang University, #79, Qingchun Road, Hangzhou, Zhejiang Province 310003, China
| | - Lingli Zou
- Department of Clinical Laboratory, Naval Convalescent Zone of Hangzhou Sanatorium, Nanjing Military Region, Zhejiang 310002, China.
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Gelu-Simeon M, Bayan T, Ostos M, Boufassa F, Teicher E, Steyaert JM, Bertucci I, Anty R, Pageaux GP, Meyer L, Duclos-Vallée JC. MELD Score Kinetics in Decompensated HIV+/HCV+ Patients: A Useful Prognostic Tool (ANRS HC EP 25 PRETHEVIC Cohort Study). Medicine (Baltimore) 2015; 94:e1239. [PMID: 26222860 PMCID: PMC4554127 DOI: 10.1097/md.0000000000001239] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
To assess prognostic factors for survival and describe Model for End-Stage liver disease (MELD) dynamics in human immunodeficiency virus+/hepatitis C virus+ (HIV+/HCV+) patients after an initial episode of hepatic decompensation.An HIV+/HCV+ cohort of patients experiencing an initial decompensation episode within the year preceding enrollment were followed prospectively. Clinical and biological data were collected every 3 months. Predictors for survival were identified using Kaplan-Meier curves and Cox models. A 2-slope-mixed linear model was used to estimate MELD score changes as a function of survival.Sixty seven patients were included in 32 centers between 2009 and 2012 (72% male; median age: 48 years [interquartile ratio (IQR):45-52], median follow-up: 22.4 months [range: 0.5-65.3]). Overall survival rates were 86%, 78%, and 59% at 6, 12, and 24 months, respectively. Under multivariate analysis, the MELD score at initial decompensation was predictive of survival, adjusted for age, type of decompensation, baseline CD4 counts, and further decompensation during follow-up as a time-dependent variable. The adjusted hazard ratio of death was 1.32 for a score 3 points higher (95% CI: [1.06-1.63], P = 0.012). MELD score kinetics within the 6 months after initial decompensation differed significantly between non-deceased and deceased patients, with a decreased (-0.49/month; P = 0.016), versus a flat (+0.06/month, P = 0.753) mean change in score.MELD is an effective tool to predict survival in HIV+/HCV+ patients with decompensated cirrhosis. A non-decreasing MELD score within 6 months following this initial decompensation episode may benefit from privileged access to liver transplantation in this poor prognosis population.
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Affiliation(s)
- Moana Gelu-Simeon
- From the AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire (MG-S, MO, ET, J-CD-V); DHU Hepatinov, Villejuif (MG-S, MO, ET, J-CD-V); Inserm, UMR 1018 CESP, Centre de Recherche en Epidémiologie et Santé des Populations (TB, FB, LM); Université Paris-Sud, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre (TB, FB, LM, J-CD-V); École Polytechnique, Laboratoire d'Informatique (LIX), Palaiseau (J-MS); ANRS, Agence Nationale de Recherches sur le Sida et les hépatites virales, Paris (IB); Inserm, UMR 1193, Villejuif (J-CD-V); AP-HP Hôpital de Bicêtre, Service de Médecine Interne, Immunologie Clinique et Maladies Infectieuses, Le Kremlin-Bicêtre (ET); Centre Hospitalier Universitaire de Nice - Hôpital de l'Archet, Service d'Hépato-gastroentérologie, Nice (RA); Université de Nice-Sophia-Antipolis, Faculté de Médecine (RA); Inserm, Unité 1065, Nice (RA); Centre Hospitalier Régional Universitaire de Montpellier - Hôpital Saint-Eloi, Service d'Hépato-Gastroentérologie et Transplantation (G-PP); Université Montpellier 1, Faculté de Médecine, Montpellier (G-PP); CHU de Pointe-à-Pitre, Service d'Hépato-Gastro-Entérologie, Pointe-à-Pitre Cedex, Guadeloupe (MG-S); Institut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement and Travail (IRSET), Rennes (MG-S); and AP-HP Hôpital Bicêtre, Service de Santé Publique, Le Kremlin-Bicêtre, France (LM)
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Red cell distribution width to platelet ratio, a useful indicator of liver fibrosis in chronic hepatitis patients. Hepatol Int 2015; 9:454-60. [PMID: 26088296 DOI: 10.1007/s12072-015-9638-9] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2015] [Accepted: 05/11/2015] [Indexed: 12/28/2022]
Abstract
AIMS We investigated the correlation between the red cell distribution width (RDW) and RDW-to-platelet ratio (RPR) with the degree of inflammation and fibrosis in chronic hepatitis patients with different etiologies and in native and transplanted liver. METHODS Between 2010 and 2013, patients from the MedStar Washington Hospital Center and Georgetown University Hospital with chronic hepatitis B, chronic hepatitis C, alcoholic hepatitis, and primary biliary cirrhosis who had a biopsy of the liver done in this time period were included. The correlation among the RDW, RPR, and model for end-stage liver disease (MELD) score with the degree of liver inflammation, fibrosis, and cirrhosis in separate groups of native and transplanted liver was calculated. RESULTS A total of 152 cases with native liver and 70 cases with transplanted liver were included. The majority of patients had hepatitis C in both groups. None of the investigated variables showed significant correlation with the degree of inflammation in either group. The strongest correlation with the degree of fibrosis in the native liver group was for the RPR with 0.51 (p < 0.001) and then the RDW and MELD with 0.34 (p < 0.001) and 0.31 (p < 0.001), respectively. In the transplanted liver group, none of the variables showed significant correlation with the degree of fibrosis. The receiver-operator curve showed that only the RDW and RPR in the native liver group, with areas under the curve of 0.770 and 0.684, respectively, have significantly positive association with the risk of cirrhosis. In the transplanted group, none of the predictors were associated with risk of cirrhosis. In the native liver group, a cutoff value of 0.088 in the RPR led to 82.7% sensitivity and 61.0% specificity to predict cirrhosis. CONCLUSION The RPR can be a strong predictor of the degree of fibrosis and cirrhosis in patients with chronic hepatitis and native liver. It shows higher accuracy compared to the RDW and MELD score. However, its use in predicting inflammation is limited.
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Massie AB, Luo X, Alejo JL, Poon AK, Cameron AM, Segev DL. Higher Mortality in registrants with sudden model for end-stage liver disease increase: Disadvantaged by the current allocation policy. Liver Transpl 2015; 21:683-9. [PMID: 25762287 DOI: 10.1002/lt.24102] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2014] [Accepted: 02/16/2015] [Indexed: 12/31/2022]
Abstract
Liver allocation is based on current Model for End-Stage Liver Disease (MELD) scores, with priority in the case of a tie being given to those waiting the longest with a given MELD score. We hypothesized that this priority might not reflect risk: registrants whose MELD score has recently increased receive lower priority but might have higher wait-list mortality. We studied wait-list and posttransplant mortality in 69,643 adult registrants from 2002 to 2013. By likelihood maximization, we empirically defined a MELD spike as a MELD increase ≥ 30% over the previous 7 days. At any given time, only 0.6% of wait-list patients experienced a spike; however, these patients accounted for 25% of all wait-list deaths. Registrants who reached a given MELD score after a spike had higher wait-list mortality in the ensuing 7 days than those with the same resulting MELD score who did not spike, but they had no difference in posttransplant mortality. The spike-associated wait-list mortality increase was highest for registrants with medium MELD scores: specifically, 2.3-fold higher (spike versus no spike) for a MELD score of 10, 4.0-fold higher for a MELD score of 20, and 2.5-fold higher for a MELD score of 30. A model incorporating the MELD score and spikes predicted wait-list mortality risk much better than a model incorporating only the MELD score. Registrants with a sudden MELD increase have a higher risk of short-term wait-list mortality than is indicated by their current MELD score but have no increased risk of posttransplant mortality; allocation policy should be adjusted accordingly.
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Affiliation(s)
- Allan B Massie
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD
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King A, Barton D, Beard HA, Than N, Moore J, Corbett C, Thomas J, Guo K, Guha I, Hollyman D, Stocken D, Yap C, Fox R, Forbes SJ, Newsome PN. REpeated AutoLogous Infusions of STem cells In Cirrhosis (REALISTIC): a multicentre, phase II, open-label, randomised controlled trial of repeated autologous infusions of granulocyte colony-stimulating factor (GCSF) mobilised CD133+ bone marrow stem cells in patients with cirrhosis. A study protocol for a randomised controlled trial. BMJ Open 2015; 5:e007700. [PMID: 25795699 PMCID: PMC4368910 DOI: 10.1136/bmjopen-2015-007700] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION Liver disease mortality and morbidity are rapidly rising and liver transplantation is limited by organ availability. Small scale human studies have shown that stem cell therapy is safe and feasible and has suggested clinical benefit. No published studies have yet examined the effect of stem cell therapy in a randomised controlled trial and evaluated the effect of repeated therapy. METHODS AND ANALYSIS Patients with liver cirrhosis will be randomised to one of three trial groups: group 1: Control group, Standard conservative management; group 2 treatment: granulocyte colony-stimulating factor (G-CSF; lenograstim) 15 µg/kg body weight daily on days 1-5; group 3 treatment: G-CSF 15 µg/kg body weight daily on days 1-5 followed by leukapheresis, isolation and aliquoting of CD133+ cells. Patients will receive an infusion of freshly isolated CD133+ cells immediately and frozen doses at days 30 and 60 via peripheral vein (0.2×10(6) cells/kg for each of the three doses). Primary objective is to demonstrate an improvement in the severity of liver disease over 3 months using either G-CSF alone or G-CSF followed by repeated infusions of haematopoietic stem cells compared with standard conservative management. The trial is powered to answer two hypotheses of each treatment compared to control but not powered to detect smaller expected differences between the two treatment groups. As such, the overall α=0.05 for the trial is split equally between the two hypotheses. Conventionally, to detect a relevant standardised effect size of 0.8 point reduction in Model for End-stage Liver Disease score using two-sided α=0.05(overall α=0.1 split equally between the two hypotheses) and 80% power requires 27 participants to be randomised per group (81 participants in total). ETHICS AND DISSEMINATION The trial is registered at Current Controlled Trials on 18 November 2009 (ISRCTN number 91288089, EuDRACT number 2009-010335-41). The findings of this trial will be disseminated to patients and through peer-reviewed publications and international presentations.
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Affiliation(s)
- A King
- NIHR Centre for Liver Research and Biomedical Research Unit, University of Birmingham, Birmingham, UK Liver Unit, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK
| | - D Barton
- NIHR Liver BRU Clinical trials group (EDD), CRUK clinical trials unit, University of Birmingham, Birmingham, UK
| | - H A Beard
- NIHR Centre for Liver Research and Biomedical Research Unit, University of Birmingham, Birmingham, UK Cellular and Molecular Therapies, NHS Blood and Transplant, Birmingham, UK
| | - N Than
- NIHR Centre for Liver Research and Biomedical Research Unit, University of Birmingham, Birmingham, UK
| | - J Moore
- MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK
| | - C Corbett
- NIHR Centre for Liver Research and Biomedical Research Unit, University of Birmingham, Birmingham, UK
| | - J Thomas
- MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK
| | - K Guo
- NIHR Centre for Liver Research and Biomedical Research Unit, University of Birmingham, Birmingham, UK
| | - I Guha
- National Institute for Health Research Biomedical Research Unit in Gastrointestinal and Liver Diseases at Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - D Hollyman
- Cellular and Molecular Therapies, NHS Blood and Transplant, Birmingham, UK
| | - D Stocken
- Newcastle Clinical Trial Unit, Institute of Health and Society, Newcastle University, Newcastle, UK
| | - C Yap
- NIHR Liver BRU Clinical trials group (EDD), CRUK clinical trials unit, University of Birmingham, Birmingham, UK
| | - R Fox
- NIHR Liver BRU Clinical trials group (EDD), CRUK clinical trials unit, University of Birmingham, Birmingham, UK
| | - S J Forbes
- MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK
| | - P N Newsome
- NIHR Centre for Liver Research and Biomedical Research Unit, University of Birmingham, Birmingham, UK Liver Unit, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK
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Hsieh YC, Lee KC, Yang YY, Huo TI, Huang YH, Lin HC. Interleukin-1 receptor antagonist correlates with hepatic venous pressure gradient and predicts occurrence of overall complications and bacterial infections in patients with cirrhosis. Hepatol Res 2015; 45:294-304. [PMID: 24826996 DOI: 10.1111/hepr.12355] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2014] [Revised: 04/11/2014] [Accepted: 05/07/2014] [Indexed: 12/12/2022]
Abstract
AIM The plasma levels of interleukin (IL)-1α, IL-1β and IL-1 receptor antagonist (IL-1Ra) are increased in cirrhotic patients. We aimed to investigate whether these cytokines correlate with hepatic venous pressure gradient (HVPG), the severity of liver cirrhosis and complications of cirrhosis. METHODS Sixty-three cirrhotic patients that underwent hemodynamic studies in Taipei Veterans General hospital were enrolled retrospectively. Plasma levels of IL-1α, IL-1β, IL-1Ra and endotoxin were assessed by enzyme-linked immunosorbent assay. Plasma obtained from 11 healthy subjects served as normal controls. RESULTS Plasma levels of IL-1α, IL-1β and IL-1Ra were increased in cirrhotic patients compared with controls. IL-1Ra levels significantly correlated with plasma endotoxin levels, Child-Pugh scores, Model of End-Stage Liver Disease (MELD) scores and HVPG. On multivariate analysis, higher IL-1Ra levels (≥760 pg/mL) predicted the occurrence of portal hypertension-related complications and the development of bacterial infections independently of the MELD scores and portal pressure. Furthermore, higher IL-1Ra levels also predicted the survival in patients without hepatocellular carcinoma. CONCLUSION The plasma IL-1Ra level correlates with HVPG. Additionally, it may predict the occurrence of portal hypertension-related complications and bacterial infections in cirrhotic patients and the survival in patients without hepatocellular carcinoma.
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Affiliation(s)
- Yun-Cheng Hsieh
- Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
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Peng YF, Zhang ZX, Cao W, Meng CR, Xu SS, Zhang Q. The association between red blood cell distribution width and acute pancreatitis associated lung injury in patients with acute pancreatitis. Open Med (Wars) 2015; 10:176-179. [PMID: 28352692 PMCID: PMC5152967 DOI: 10.1515/med-2015-0028] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2014] [Accepted: 01/15/2015] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Red blood cell distribution width (RDW) that describes red blood cell volume heterogeneity is a common laboratory test. Our aim was to focus on the association between RDW and acute pancreatitis associated lung injury (APALI). METHODOLOGY A total of 152 acute pancreatitis (AP) patients who conformed to the criteria were included in this study. The demographic data, medical histories and laboratory measures was obtained from each patient on admission, further, the medical histories and biological data were analyzed, retrospectively. RESULTS Increased RDW at admission was observed in patients with APALI compared with the non-APALI groups. Our results exhibited that RDW was an independent risk factor for APALI after adjusting leukocyte, neutrophil percentage, random blood glucose (RBG), total bilirubin (TB) and total bile acid (TBA) (Crude model) (OR=2.671;CI 95% 1.145-6.230; P=0.023), further adjustment based on Crude model for sex and age did not attenuate the significantly high risk of APALI in patients with AP, RWD still remained a roles as an independent risk factor for APALI (OR=2.653;CI95 % 1.123-6.138; P=0.026). CONCLUSIONS Our study demonstrate that RDW at admission is associated with APALI and should be considered as an underlying risk factor of APALI.
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Affiliation(s)
- You-Fan Peng
- Laboratory Medicine Diagnostic Centre, The First Affiliated Hospital, Xin Jiang Medical University, Xinjiang Urumqi, China
| | - Zhao-Xia Zhang
- Laboratory Medicine Diagnostic Centre, The First Affiliated Hospital, Xin Jiang Medical University, Xinjiang Urumqi, China
| | - Wei Cao
- Hemopathy Research Center, The First Affiliated Hospital, Xin Jiang Medical University, Xinjiang Urumqi, China
| | - Cun-Ren Meng
- Laboratory Medicine Diagnostic Centre, The First Affiliated Hospital, Xin Jiang Medical University, Xinjiang Urumqi, China
| | - Shen-Sheng Xu
- Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang Urumqi, China
| | - Qiong Zhang
- Laboratory Medicine Diagnostic Centre, The First Affiliated Hospital, Xin Jiang Medical University, No.1-137, Liyushan Road, Xin'shi Region, Urumqi. XinJiang, China, 830011, Phone:15022960879, Telephone:0991-4361446
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Mould DR, Walz AC, Lave T, Gibbs JP, Frame B. Developing Exposure/Response Models for Anticancer Drug Treatment: Special Considerations. CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY 2015. [PMID: 26225225 PMCID: PMC4369756 DOI: 10.1002/psp4.16] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Anticancer agents often have a narrow therapeutic index (TI), requiring precise dosing to ensure sufficient exposure for clinical activity while minimizing toxicity. These agents frequently have complex pharmacology, and combination therapy may cause schedule-specific effects and interactions. We review anticancer drug development, showing how integration of modeling and simulation throughout development can inform anticancer dose selection, potentially improving the late-phase success rate. This article has a companion article in Clinical Pharmacology & Therapeutics with practical examples.
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Affiliation(s)
- D R Mould
- Projections Research Phoenixville, Pennsylvania, USA
| | - A-C Walz
- Roche Pharma Research and Early Development, Modeling & Simulation, Pharmaceutical Sciences, Roche Innovation Center Basel F. Hoffmann-La Roche, Basel, Switzerland
| | - T Lave
- Roche Pharma Research and Early Development, Modeling & Simulation, Pharmaceutical Sciences, Roche Innovation Center Basel F. Hoffmann-La Roche, Basel, Switzerland
| | - J P Gibbs
- Amgen Thousand Oaks, California, USA
| | - B Frame
- Projections Research Phoenixville, Pennsylvania, USA
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Comparison between accuracy of different scoring systems in prediction of liver cirrhosis-related complications. EGYPTIAN LIVER JOURNAL 2015. [DOI: 10.1097/01.elx.0000459079.56315.44] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Red cell distribution width is associated with presence, stage, and grade in patients with renal cell carcinoma. DISEASE MARKERS 2014; 2014:860419. [PMID: 25580051 PMCID: PMC4280806 DOI: 10.1155/2014/860419] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/29/2014] [Revised: 11/08/2014] [Accepted: 12/01/2014] [Indexed: 12/18/2022]
Abstract
It has been reported that red blood cell width (RDW) is a marker associated with the presence and adverse outcomes of various diseases. However, no data are available on the correlation of RDW with presence, stage, and grade in patients with renal cell carcinoma (RCC) yet. By retrospectively analyzing clinical and laboratory data at baseline of histologically confirmed RCC cases and controls, the present study demonstrated that the RDW values were significantly higher in patients with RCC than those in controls, and the baseline RDW value was independently associated with the presence of RCC. Besides, the data revealed a positive association between RCC stage and grade and the level of RDW. These findings may have important clinical implications due to future application using a RDW value in predicting RCC.
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Schaubel DE, Zhang H, Kalbfleisch JD, Shu X. Semiparametric methods for survival analysis of case-control data subject to dependent censoring. CAN J STAT 2014. [DOI: 10.1002/cjs.11218] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Affiliation(s)
| | - Hui Zhang
- U.S. Food and Drug Administration; Silver Spring MD USA
| | | | - Xu Shu
- Department of Biostatistics; University of Michigan; Ann Arbor MI USA
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