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Chen S, Shen C, Tian Y, Peng Y, Hu J, Xie H, Yin P. Physiologically based pharmacokinetic modeling and simulation of topiramate in populations with renal and hepatic impairment and considerations for drug-drug interactions. CPT Pharmacometrics Syst Pharmacol 2025; 14:510-522. [PMID: 39676284 PMCID: PMC11919257 DOI: 10.1002/psp4.13292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 10/27/2024] [Accepted: 11/25/2024] [Indexed: 12/17/2024] Open
Abstract
Topiramate (TPM) is a broad-spectrum antiepileptic drug (AED) commonly prescribed for approved and off-label uses. Routine monitoring is suggested for clinical usage of TPM in special population due to its broad side effect profile. Therefore, it is crucial to further explore its pharmacokinetic characteristics. Physio-chemical properties of TPM were initially determined from online database and further optimized while establishing the PBPK model for healthy adults using the PK-Sim software. The model was then extrapolated to patients with renal impairment and patients who were hepatically impaired. A drug-drug interaction (DDI) model was also built to simulate plasma TPM concentrations while concomitantly used with carbamazepine (CBZ). The goodness-of-fit method and average fold error (AFE) method were used to compare the differences between predicted and observed values to assess the accuracy of the PBPK model. Almost all of the predicted concentration fell within twofold error range of corresponding observed concentrations. The AFE ratio of predicted to observed values of Cmax and AUC0-inf was all within 0.5 and 2. It is recommended that the doses be reduced to 70%, 50%, and 40% of the healthy adult dose for the chronic kidney disease (CKD) stage 3, stage 4, and stage 5 patients, respectively, and reduced to ~70%, and 35% for the Child-Pugh-B, and Child-Pugh C scored patient with hepatic impairment, respectively. If TPM is co-administered with CBZ, increasing TPM doses to 150%-175% of the monotherapy dose is recommended according to model simulation.
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Affiliation(s)
- Shuqing Chen
- Department of Epidemiology and Biostatistics, School Public HealthTongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Chaozhuang Shen
- Anhui Provincial Center for Drug Clinical EvaluationYijishan Hospital of Wannan Medical CollegeWuhuAnhuiChina
| | - Yuchen Tian
- Department of Epidemiology and Biostatistics, School Public HealthTongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Yuhe Peng
- Department of Epidemiology and Biostatistics, School Public HealthTongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Jing Hu
- Department of Epidemiology and Biostatistics, School Public HealthTongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Haitang Xie
- Anhui Provincial Center for Drug Clinical EvaluationYijishan Hospital of Wannan Medical CollegeWuhuAnhuiChina
| | - Ping Yin
- Department of Epidemiology and Biostatistics, School Public HealthTongji Medical College, Huazhong University of Science and TechnologyWuhanChina
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Li Y, Shao W, Wang X, Geng K, Wang W, Liu Z, Chen Y, Shen C, Xie H. Physiologically based pharmacokinetic model of brivaracetam to predict the exposure and dose exploration in hepatic impairment and elderly populations. J Pharm Sci 2024; 113:3286-3296. [PMID: 39243975 DOI: 10.1016/j.xphs.2024.08.022] [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: 06/19/2024] [Revised: 08/20/2024] [Accepted: 08/20/2024] [Indexed: 09/09/2024]
Abstract
Brivaracetam (BRV) is a new third-generation antiseizure medication for the treatment of focal epileptic seizures. Its use has been increasing among epileptic populations in recent years, but pharmacokinetic (PK) behavior may change in hepatic impairment and the elderly populations. Due to ethical constraints, clinical trials are difficult to conduct and data are limited. This study used PK-Sim® to develop a physiologically based pharmacokinetic (PBPK) model for adults and extrapolate it to hepatic impairment and the elderly populations. The model was evaluated with clinical PK data, and dosage explorations were conducted. For the adult population with mild hepatic impairment, the dose is recommended to be adjusted to 70 % of the recommended dose, and to 60 % for moderate and severe hepatic impairment. For the elderly population with mild hepatic impairment under 80 years old, it is recommended that the dose be adjusted to 60 % of the recommended dose and to 50 % for moderate and severe conditions. The elderly population with hepatic impairment over 80 years old is adjusted to 50 % of the recommended dose for all stages. Healthy elderly do not need to adjust. The BRV PBPK model was successfully developed, studying exposure in hepatic impairment and elderly populations and optimizing dosing regimens.
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Affiliation(s)
- Yiming Li
- Anhui Provincial Center for Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu 241001, Anhui, PR China; Wannan Medical College, No. 22, Wenchang West Road, Yijiang District, Wuhu 241002, PR China
| | - Wenxin Shao
- Department of Pharmacy, The First People's Hospital of Yibin, No. 65, Wenxing Street, Yinbin 644000, PR China
| | - Xingwen Wang
- Anhui Provincial Center for Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu 241001, Anhui, PR China; Wannan Medical College, No. 22, Wenchang West Road, Yijiang District, Wuhu 241002, PR China
| | - Kuo Geng
- Anhui Provincial Center for Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu 241001, Anhui, PR China; Wannan Medical College, No. 22, Wenchang West Road, Yijiang District, Wuhu 241002, PR China
| | - Wenhui Wang
- Anhui Provincial Center for Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu 241001, Anhui, PR China; Wannan Medical College, No. 22, Wenchang West Road, Yijiang District, Wuhu 241002, PR China
| | - Zhiwei Liu
- Anhui Provincial Center for Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu 241001, Anhui, PR China; Wannan Medical College, No. 22, Wenchang West Road, Yijiang District, Wuhu 241002, PR China
| | - Youjun Chen
- Anhui Provincial Center for Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu 241001, Anhui, PR China; Wannan Medical College, No. 22, Wenchang West Road, Yijiang District, Wuhu 241002, PR China
| | - Chaozhuang Shen
- Department of Clinical Pharmacy and Pharmacy Administration, West China school of Pharmacy, Sichuan University, Chengdu 610064, PR China
| | - Haitang Xie
- Anhui Provincial Center for Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu 241001, Anhui, PR China.
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Swaroop S, Vaishnav M, Arora U, Biswas S, Aggarwal A, Sarkar S, Khanna P, Elhence A, Kumar R, Goel A, Shalimar. Etiological Spectrum of Cirrhosis in India: A Systematic Review and Meta-analysis. J Clin Exp Hepatol 2024; 14:101291. [PMID: 38544766 PMCID: PMC10964076 DOI: 10.1016/j.jceh.2023.10.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Accepted: 10/01/2023] [Indexed: 06/24/2024] Open
Abstract
BACKGROUND Cirrhosis is a significant cause of morbidity and mortality globally and in India. This systematic review and meta-analysis aimed to ascertain the etiological spectrum and changing trends of cirrhosis in India. METHODS We searched electronic databases, including Pubmed/Medline, Scopus, and Embase. We included original studies that reported the etiology of cirrhosis in the Indian population. RESULTS We included 158 studies (adults: 147, children: 11). The overall pooled estimate of alcohol as a cause of cirrhosis in adults was 43.2% (95% confidence interval (CI) 39.8-46.6%; I2 = 97.8%), followed by nonalcoholic fatty liver disease (NAFLD)/cryptogenic in 14.4%, 95% CI (11.7-17.3%; I2 = 98.4%), hepatitis B virus (HBV) in 11.5%, 95% CI (9.8-13.3%; I2 = 96.6%), and hepatitis C virus (HCV) in 6.2%, 95% CI (4.8-7.8%; I2 = 97.2%) of the included patients. The most common cause of cirrhosis in all zones was alcohol-related. Comparison of etiologies over time revealed a reduction in the viral hepatitis-related and an increase in the proportion of alcohol-related and NAFLD/cryptogenic-related cirrhosis. The overall pooled estimates of various etiologies in children were: HBV in 10.7%, 95% CI (4.6-18.7%; I2 = 91.0%), NAFLD/Cryptogenic in 22.3%, 95% CI (9.0-39.2%; I2 = 96.7%), and HCV in 2.0%, 95% CI (0.0-8.5%; I2 = 94.6%). CONCLUSIONS Alcohol is the most common etiology of cirrhosis in adults in India. The proportions of alcohol and NAFLD-related cirrhosis are increasing, and those of viral hepatitis-related cirrhosis are reducing. The results of our meta-analysis will help formulate health policies and the allocation of resources.
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Affiliation(s)
- Shekhar Swaroop
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Manas Vaishnav
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Umang Arora
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Sagnik Biswas
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Arnav Aggarwal
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Soumya Sarkar
- Department of Anaesthesia, All India Institute of Medical Sciences, Kalyani, West Bengal, India
| | - Puneet Khanna
- Department of Anaesthesia, Pain Medicine and Critical Care, All India Institute of Medical Sciences, New Delhi, India
| | - Anshuman Elhence
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, Bihar, India
| | - Amit Goel
- Department of Hepatology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
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Chau P, Yoon JS, Moses D, Pather N. A systematic review and meta-analysis of portal vein morphometry in pediatric and adult populations: Drawing the line between normal and abnormal findings. Eur J Radiol 2023; 168:111016. [PMID: 37742371 DOI: 10.1016/j.ejrad.2023.111016] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 07/13/2023] [Accepted: 07/26/2023] [Indexed: 09/26/2023]
Abstract
PURPOSE The morphometry of the hepatic portal vein is of clinical importance, particularly in pre-operative assessments, surgical management, and diagnoses of liver conditions. This systematic review and meta-analysis aimed to characterize the morphometry of the normal portal vein in both pediatric and adult patients. METHODS The study, conducted using the PRISMA guidelines and registered with PROSPERO, utilized the MEDLINE, EMBASE, SCOPUS and Web of Science databases up to May 2020, and updated to May 2023. All studies reporting extractable data on diameter, length, and cross-sectional area (CSA) of the main, left, and right portal veins (PV, LPV, RPV, respectively) were included. The AQUA Tool was used to assess the quality of the included studies. Data analysis included subgroup analyses based on geographical location, sex, age, and imaging modality. RESULTS A total of 122 studies with 11,637 subjects were eligible for inclusion. Overall, the pooled mean diameter of the PV (PVD) was 10.09 mm (95% CI: 9.56-10.62). Significant differences in diameter were found between pediatric (6.60 mm; 95% CI: 5.38-7.82) and adult (10.72 mm; 95% CI: 10.25-11.19) subjects. Additionally, there was a significantly larger PVD measurement from computed tomography (CT) than other imaging modalities: CT, 13.28 mm (95% CI: 11.71-14.84); magnetic resonance imaging (MRI), 10.50 mm (95% CI: 9.35-11.66) and ultrasound (US), 9.81 mm (95% CI: 9.47-10.16). The mean diameters of the LPV and RPV were 8.27 mm (95% CI: 6.78-9.77) and 8.33 mm (95% CI: 6.70-9.95), respectively. Mean PV length in adults is 48.63 mm (95% CI: 35.63-61.64). Mean CSA of the PV was 1.09 cm2. CONCLUSIONS The study obtained aim to improve the understanding of portal vein anatomy, especially with relevance to surgical interventions of the liver in both pediatric and adult patients. Measurements from ultrasound imaging closely approximates the generated pooled PVD mean for pediatric and adult patients. CT imaging, however, significantly exceeded the established 13 mm threshold for adults. For pediatric patients, a threshold of 8 mm is proposed as a diagnostic upper limit for a normal PVD. Although not significant, the PVD decreased from the portal confluence towards its bifurcation.
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Affiliation(s)
- Patrick Chau
- Department of Anatomy, School of Biomedical Sciences, Faculty of Medicine and Health, UNSW Sydney, Sydney, Australia
| | - Ji Soo Yoon
- Department of Anatomy, School of Biomedical Sciences, Faculty of Medicine and Health, UNSW Sydney, Sydney, Australia
| | - Daniel Moses
- Department of Radiology, Prince of Wales Hospital, Sydney, Australia
| | - Nalini Pather
- Department of Anatomy, School of Biomedical Sciences, Faculty of Medicine and Health, UNSW Sydney, Sydney, Australia; Academy of Medical Education, Medical School, Faculty of Medicine, University of Queensland, Australia; Medical Education, Faculty of Medicine and Health, UNSW Sydney, Sydney, Australia.
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Shen C, Shao W, Wang W, Sun H, Wang X, Geng K, Wang X, Xie H. Physiologically based pharmacokinetic modeling of levetiracetam to predict the exposure in hepatic and renal impairment and elderly populations. CPT Pharmacometrics Syst Pharmacol 2023; 12:1001-1015. [PMID: 37170680 PMCID: PMC10349187 DOI: 10.1002/psp4.12971] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Revised: 04/06/2023] [Accepted: 04/10/2023] [Indexed: 05/13/2023] Open
Abstract
Levetiracetam (LEV) is an anti-epileptic drug approved for use in various populations. The pharmacokinetic (PK) behavior of LEV may be altered in the elderly and patients with renal and hepatic impairment. Thus, dosage adjustment is required. This study was conducted to investigate how the physiologically-based PK (PBPK) model describes the PKs of LEV in adult and elderly populations, as well as to predict the PKs of LEV in patients with renal and hepatic impairment in both populations. The whole-body PBPK models were developed using the reported physicochemical properties of LEV and clinical data. The models were validated using data from clinical studies with different dose ranges and different routes and intervals of administration. The fit performance of the models was assessed by comparing predicted and observed blood concentration data and PK parameters. It is recommended that the doses be reduced to ~70%, 60%, and 45% of the adult dose for the mild, moderate, and severe renal impairment populations and ~95%, 80%, and 57% of the adult dose for the Child Pugh-A (CP-A), Child Pugh-B (CP-B), and Child Pugh-C (CP-C) hepatic impairment populations, respectively. No dose adjustment is required for the healthy elderly population, but dose reduction is required for the elderly with organ dysfunction accordingly, on a scale similar to that of adults. A PBPK model of LEV was successfully developed to optimize dosing regimens for special populations.
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Affiliation(s)
- Chaozhuang Shen
- Anhui Provincial Center for Drug Clinical EvaluationYijishan Hospital of Wannan Medical CollegeWuhuAnhuiChina
| | - Wenxin Shao
- Anhui Provincial Center for Drug Clinical EvaluationYijishan Hospital of Wannan Medical CollegeWuhuAnhuiChina
| | - Wenhui Wang
- Anhui Provincial Center for Drug Clinical EvaluationYijishan Hospital of Wannan Medical CollegeWuhuAnhuiChina
| | - Hua Sun
- Anhui Provincial Center for Drug Clinical EvaluationYijishan Hospital of Wannan Medical CollegeWuhuAnhuiChina
| | - Xiaohu Wang
- Anhui Provincial Center for Drug Clinical EvaluationYijishan Hospital of Wannan Medical CollegeWuhuAnhuiChina
| | - Kuo Geng
- Anhui Provincial Center for Drug Clinical EvaluationYijishan Hospital of Wannan Medical CollegeWuhuAnhuiChina
| | - Xingwen Wang
- Anhui Provincial Center for Drug Clinical EvaluationYijishan Hospital of Wannan Medical CollegeWuhuAnhuiChina
| | - Haitang Xie
- Anhui Provincial Center for Drug Clinical EvaluationYijishan Hospital of Wannan Medical CollegeWuhuAnhuiChina
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Kageyama K, Yamamoto A, Jogo A, Sohgawa E, Izuta S, Himoto D, Kakimi A, Kita R, Miki Y. Identification of reversed portal flow on 4DCT and of factors contributing to reversed portal flow in patients with liver cirrhosis and portosystemic shunt before interventional radiology procedures. Hepatol Res 2023; 53:228-237. [PMID: 36356950 DOI: 10.1111/hepr.13855] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2022] [Revised: 10/26/2022] [Accepted: 10/31/2022] [Indexed: 11/12/2022]
Abstract
AIM Patients with liver cirrhosis and portosystemic shunt occasionally develop reversed portal flow in the portal venous system. The factors contributing to reversed portal flow in these patients remain unclear. The aim of this study was to identify factors contributing to reversed portal flow in patients with portosystemic shunts based on four-dimensional computed tomography (4DCT), which visualized flow dynamics in the portal venous system. METHODS Data from 34 consecutive patients with portosystemic shunts who had undergone 4DCT before interventional radiology procedures were retrospectively investigated in this study. Uni- and multivariate analyses were performed to identify factors contributing to reversed portal flow. RESULTS Flow dynamics could be visualized on 4DCT in 32 of the 34 patients. Fifteen patients had forward portal flow; 17 had reversed portal flow. The main portal, splenic, and superior mesenteric veins displayed reversed portal flow in five, 12, and five vessels, respectively. Portosystemic shunt originating from splenic and superior mesenteric veins, worse albumin-bilirubin score, and small main portal vein diameter were significant factors contributing to reversed portal flow in both univariate (p = 0.049, p = 0.027, and p = 0.002) and multivariate (odds ratio [OR] 6.345, p = 0.012; OR 4.279, p = 0.039; and OR 5.516, p = 0.019) analyses. CONCLUSIONS The reversed portal flow was visualized on 4DCT. Portosystemic shunt originating distant to the liver, worse albumin-bilirubin score, and small diameter of the main portal vein were factors contributing to reversed flow in the portal venous system.
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Affiliation(s)
- Ken Kageyama
- Department of Diagnostic and Interventional Radiology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Akira Yamamoto
- Department of Diagnostic and Interventional Radiology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Atsushi Jogo
- Department of Diagnostic and Interventional Radiology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Etsuji Sohgawa
- Department of Diagnostic and Interventional Radiology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Shinichiro Izuta
- Department of Central Radiology, Osaka Metropolitan University Hospital, Osaka, Japan
| | - Daisuke Himoto
- Department of Central Radiology, Osaka Metropolitan University Hospital, Osaka, Japan
| | - Akihiko Kakimi
- Department of Central Radiology, Osaka Metropolitan University Hospital, Osaka, Japan
| | - Ryuichi Kita
- Department of Hepatology, Osaka Red Cross Hospital, Osaka, Japan
| | - Yukio Miki
- Department of Diagnostic and Interventional Radiology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
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Chang NW, Wang HK, Liu CS, Loong CC, Lai YC, Chiou HJ, Chou YH. First-Pass Arrival Interval of Ultrasound Contrast Medium in the Hepatic Artery and Portal Vein as a Marker for Assessment of Liver Transplant Recipients. Transplant Proc 2021; 53:2329-2334. [PMID: 34446308 DOI: 10.1016/j.transproceed.2021.07.050] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 07/22/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND This study measures the first-pass arrival times in the hepatic artery and portal vein of the transplanted liver using contrast-enhanced ultrasound (CEUS) and assess its correlation with graft performance in the early posttransplant period. METHODS This study evaluated 35 liver transplant recipients who underwent CEUS examination within 1 month of transplant surgery. CEUS under contrast-specific harmonic imaging mode were recorded for 60 seconds immediately after intravenous administration of microbubble ultrasound contrast medium (Sonazoid, GE Healthcare, Oslo, Norway). The recorded video clips were reviewed by 2 readers to determine the first-pass arrival times in the hepatic artery and portal vein, and the difference between the 2 was defined as the arterial-portal arrival interval (APAI). Laboratory data on the same date of CEUS examination were collected as indicators to correlate with APAI. RESULTS The intra- and inter-rater reliability for APAI measurement were excellent, with intraclass correlation coefficients > .95. The mean APAI was 4.5 ± 1.8 seconds (range, 2.0-10.5 seconds). The APAI was positively correlated with the serum total bilirubin level (r = 0.357, P = .035) and negatively correlated with the platelet count (r = -0.354, P = .037). At the 5 second cutoff point, a total serum bilirubin of >8 mg/dL was reported in 5 of 11 patients (45.4%) with APAI of >5 seconds and in only 3 of 24 patients (12.5%) with APAI of <5 seconds (P < .05). CONCLUSIONS The APAI is a quantitative marker that links the hemodynamics and the clinical status of the liver graft.
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Affiliation(s)
- Nai-Wen Chang
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Hsin-Kai Wang
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
| | - Chin-Su Liu
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Transplantation Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Pediatric Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Che-Chuan Loong
- Division of Transplantation Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Chen Lai
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Hong-Jen Chiou
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yi-Hong Chou
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Medical Imaging and Radiological Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan; Department of Radiology, Yee Zen General Hospital, Taoyuan, Taiwan
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Kageyama K, Yamamoto A, Jogo A, Izuta S, Himoto D, Kakimi A, Sohgawa E, Miki Y. Visualization of flow dynamics in the portal circulation using 320-detector-row computed tomography: a feasibility study. Eur Radiol Exp 2021; 5:1. [PMID: 33432529 PMCID: PMC7801554 DOI: 10.1186/s41747-020-00197-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Accepted: 11/26/2020] [Indexed: 11/21/2022] Open
Abstract
Multidetector row computed tomography (CT) scanners perform dynamic scanning and have a wide scan range. Time-resolved three-dimensional CT (i.e., 4D CT) has recently enabled visualization of flow in neurovascular vessels. We hypothesized that 4D CT technology would be a useful and non-invasive method for visualizing the flow dynamics of the portal circulation. The aim of this study was to evaluate the technical feasibility of 4D CT for visualizing flow dynamics in the portal circulation using 320-detector-row CT. 4D CT images of 18 consecutive patients with portal circulation including gastrorenal shunt were retrospectively evaluated for their ability to generate flow dynamics of the portal circulation. Flow dynamics could be visualized by 4D CT in 68 of the 72 vessels in the portal vein, splenic vein, superior mesenteric vein, and gastrorenal shunt. Flow direction could not be identified in four vessels, all of them being superior mesenteric veins. Flow direction was recognized on 4D CT in the 68 vessels of the portal circulation. A preliminary validation study revealed that flow direction of all 19 vessels in the portal circulation had concordance between 4D CT and color Doppler ultrasound. 4D CT could visualize flow dynamics of the portal circulation.
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Affiliation(s)
- Ken Kageyama
- Department of Diagnostic and Interventional Radiology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
| | - Akira Yamamoto
- Department of Diagnostic and Interventional Radiology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan
| | - Atsushi Jogo
- Department of Diagnostic and Interventional Radiology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan
| | - Shinichiro Izuta
- Department of Central Radiology, Osaka City University Hospital, 1-5-7 Asahi-machi, Abeno-ku, Osaka, 545-8586, Japan
| | - Daisuke Himoto
- Department of Central Radiology, Osaka City University Hospital, 1-5-7 Asahi-machi, Abeno-ku, Osaka, 545-8586, Japan
| | - Akihiko Kakimi
- Department of Central Radiology, Osaka City University Hospital, 1-5-7 Asahi-machi, Abeno-ku, Osaka, 545-8586, Japan
| | - Etsuji Sohgawa
- Department of Diagnostic and Interventional Radiology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan
| | - Yukio Miki
- Department of Diagnostic and Interventional Radiology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan
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Willmann S, Coboeken K, Kapsa S, Thelen K, Mundhenke M, Fischer K, Hügl B, Mück W. Applications of Physiologically Based Pharmacokinetic Modeling of Rivaroxaban-Renal and Hepatic Impairment and Drug-Drug Interaction Potential. J Clin Pharmacol 2021; 61:656-665. [PMID: 33205449 PMCID: PMC8048900 DOI: 10.1002/jcph.1784] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Accepted: 11/09/2020] [Indexed: 02/06/2023]
Abstract
The non–vitamin K antagonist oral anticoagulant rivaroxaban is used in several thromboembolic disorders. Rivaroxaban is eliminated via both metabolic degradation and renal elimination as unchanged drug. Therefore, renal and hepatic impairment may reduce rivaroxaban clearance, and medications inhibiting these clearance pathways could lead to drug‐drug interactions. This physiologically based pharmacokinetic (PBPK) study investigated the pharmacokinetic behavior of rivaroxaban in clinical situations where drug clearance is impaired. A PBPK model was developed using mass balance and bioavailability data from adults and qualified using clinically observed data. Renal and hepatic impairment were simulated by adjusting disease‐specific parameters, and concomitant drug use was simulated by varying enzyme activity in virtual populations (n = 1000) and compared with pharmacokinetic predictions in virtual healthy populations and clinical observations. Rivaroxaban doses of 10 mg or 20 mg were used. Mild to moderate renal impairment had a minor effect on area under the concentration‐time curve and maximum plasma concentration of rivaroxaban, whereas severe renal impairment caused a more pronounced increase in these parameters vs normal renal function. Area under the concentration‐time curve and maximum plasma concentration increased with severity of hepatic impairment. These effects were smaller in the simulations compared with clinical observations. AUC and Cmax increased with the strength of cytochrome P450 3A4 and P‐glycoprotein inhibitors in simulations and clinical observations. This PBPK model can be useful for estimating the effects of impaired drug clearance on rivaroxaban pharmacokinetics. Identifying other factors that affect the pharmacokinetics of rivaroxaban could facilitate the development of models that approximate real‐world pharmacokinetics more accurately.
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Affiliation(s)
| | | | - Stefanie Kapsa
- Clinical Pharmacokinetics Cardiovascular, Bayer AG, Wuppertal, Germany
| | - Kirstin Thelen
- Clinical Pharmacokinetics Cardiovascular, Bayer AG, Wuppertal, Germany
| | - Markus Mundhenke
- Medical Affairs Cardiovascular, Bayer Vital GmbH, Leverkusen, Germany
| | | | - Burkhard Hügl
- Clinic for Cardiology and Rhythmology, Marienhaus Klinikum St Elisabeth Neuwied, Neuwied, Germany
| | - Wolfgang Mück
- Clinical Pharmacokinetics Cardiovascular, Bayer AG, Wuppertal, Germany
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Marsousi N, Desmeules JA, Rudaz S, Daali Y. Usefulness of PBPK Modeling in Incorporation of Clinical Conditions in Personalized Medicine. J Pharm Sci 2017; 106:2380-2391. [DOI: 10.1016/j.xphs.2017.04.035] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2017] [Revised: 04/06/2017] [Accepted: 04/07/2017] [Indexed: 12/14/2022]
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Bildgebende Darstellung viszeraler Gefäße. Internist (Berl) 2017; 58:775-786. [DOI: 10.1007/s00108-017-0286-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Maruyama H, Kobayashi K, Kiyono S, Ogasawara S, Suzuki E, Ooka Y, Chiba T, Yamaguchi T. Compensating effect of minor portal hypertension on the muscle mass loss-related poor prognosis in cirrhosis. Int J Med Sci 2017; 14:804-810. [PMID: 28824317 PMCID: PMC5562187 DOI: 10.7150/ijms.19847] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2017] [Accepted: 06/18/2017] [Indexed: 12/24/2022] Open
Abstract
Background: To examine the influence of the severity of portal hemodynamic abnormality on the prognosis of cirrhosis with respect to the muscle mass loss (MML). Methods: The study involved a subgroup analysis in 98 cirrhosis patients (63.5 ± 11.8 years) who prospectively underwent both Doppler ultrasound and hepatic venous catheterization. The prognostic influence of MML diagnosed by computed tomography using the L3 skeletal muscle index was evaluated (median observation period, 32.7 months). Results: The cumulative survival rate showed difference between patients with MML (n = 34; 82.2%/1year, 41.2%/3years and 36.1%/5years) and those without (n = 64; 92.1%/1year, 74.9%/3years and 69.4%/5years; P = 0.005). When divided with respect to the portal velocity, the survival rate showed differences between patients with and without MML in the cohort < 12.8 cm/s (n=52, p=0.009) and ≥ 12.8 cm/s (n=44, p=0.041). The survival rate also showed differences between patients with MML (n = 24; 78.8%/1year, 40.6%/3years and 34.8%/5years) and those without (n = 45; 91.1%/1year, 71.3%/3years and 63.1%/5years; P = 0.008) in the cohort with hepatic venous pressure gradient (HVPG) > 12 mmHg. However, in the cohort with HVPG ≤ 12 mmHg, survival rate showed no difference between patients with MML (n=10; 100%/1year, 61.9%/3years and 61.9%/5years) and those without (n=19; 93.8%/1year, 71.2%/3years and 59.4%/5years; p = 0.493) Conclusion: Lower HVPG has a compensating effect on the MML-induced poor prognosis of cirrhosis. Care should be taken in the evaluation of the influence of MML in consideration of the severity of portal hypertension.
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Affiliation(s)
- Hitoshi Maruyama
- Department of Gastroenterology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670, Japan
| | - Kazufumi Kobayashi
- Department of Gastroenterology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670, Japan
| | - Soichiro Kiyono
- Department of Gastroenterology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670, Japan
| | - Sadahisa Ogasawara
- Department of Gastroenterology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670, Japan
| | - Eichiro Suzuki
- Department of Gastroenterology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670, Japan
| | - Yoshihiko Ooka
- Department of Gastroenterology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670, Japan
| | - Tetsuhiro Chiba
- Department of Gastroenterology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670, Japan
| | - Tadashi Yamaguchi
- Department of Research Center for Frontier Medical Engineering, Chiba University, 1-33, Yayoicho, Inage-ku, Chiba, 263-8522, Japan
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Kondo T, Maruyama H, Sekimoto T, Shimada T, Takahashi M, Okugawa H, Yokosuka O. Impact of portal hemodynamics on Doppler ultrasonography for predicting decompensation and long-term outcomes in patients with cirrhosis. Scand J Gastroenterol 2016; 51:236-44. [PMID: 26357874 DOI: 10.3109/00365521.2015.1081275] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Significance of portal hemodynamics for non-invasive marker of cirrhosis remains unclear. The aim was to determine the value of portal hemodynamics on Doppler ultrasound for predicting decompensation and prognosis in cirrhosis. METHODS This retrospective study comprised 236 cirrhotic patients (132 males, 104 females; age 63.7 ± 11.3 years; 110 compensated, 126 decompensated). Clinical data, including Doppler findings, were analyzed with respect to decompensation and prognosis. The median follow-up period was 33.2 months (0.1-95.4). RESULTS Fifty-three patients developed clinical decompensation, 13 patients received liver transplantation, and 71 died. Higher model for end-stage liver disease score (p < 0.001) at baseline was the significant factor for the presence of decompensation. Higher alanine transaminase (p = 0.020), lower albumin (p = 0.002) and lower mean velocity in the portal trunk (p = 0.038) were significant factors for developing decompensation (best cut-off value: Alanine transaminase > 31 IU/L, albumin < 3.6 g/dL, and portal trunk < 12.8 cm/s). The cumulative incidence of decompensation was higher in patients with portal trunk < 12.8 cm/s (22.5% at 1 year, 71.2% at 5 years) than those without (6.9% at 1 year, 35.4% at 5 years; p < 0.001). The significant prognostic factors were hepatocellular carcinoma (p = 0.036) and lower albumin (p = 0.008) for compensated patients, and reversed portal flow (p = 0.028), overt ascites (p < 0.001), and higher bilirubin (p < 0.001) for decompensated patients. CONCLUSION Portal hemodynamics offer a non-invasive marker for decompensation and prognosis of cirrhosis, suggesting a future direction for practical management.
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Affiliation(s)
- Takayuki Kondo
- a Department of Gastroenterology and Nephrology , Chiba University Graduate School of Medicine , Chuou-ku , Chiba , Japan
| | - Hitoshi Maruyama
- a Department of Gastroenterology and Nephrology , Chiba University Graduate School of Medicine , Chuou-ku , Chiba , Japan
| | - Tadashi Sekimoto
- a Department of Gastroenterology and Nephrology , Chiba University Graduate School of Medicine , Chuou-ku , Chiba , Japan
| | - Taro Shimada
- a Department of Gastroenterology and Nephrology , Chiba University Graduate School of Medicine , Chuou-ku , Chiba , Japan
| | - Masanori Takahashi
- a Department of Gastroenterology and Nephrology , Chiba University Graduate School of Medicine , Chuou-ku , Chiba , Japan
| | - Hidehiro Okugawa
- a Department of Gastroenterology and Nephrology , Chiba University Graduate School of Medicine , Chuou-ku , Chiba , Japan
| | - Osamu Yokosuka
- a Department of Gastroenterology and Nephrology , Chiba University Graduate School of Medicine , Chuou-ku , Chiba , Japan
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Sah VK, Wang L, Min X, Rizal R, Feng Z, Ke Z, Deng M, Li L, Li H. Human schistosomiasis: A diagnostic imaging focused review of a neglected disease. ACTA ACUST UNITED AC 2015. [DOI: 10.1016/j.jrid.2015.11.007] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Elwir S, Hal H, Veith J, Schreibman I, Kadry Z, Riley T. Radiographical findings in patients with liver cirrhosis and hepatic encephalopathy. Gastroenterol Rep (Oxf) 2015; 4:221-5. [PMID: 26463277 PMCID: PMC4976681 DOI: 10.1093/gastro/gov049] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2015] [Accepted: 08/23/2015] [Indexed: 01/28/2023] Open
Abstract
Background and aims: Hepatic encephalopathy is a common complication encountered in patients with liver cirrhosis. Hepatic encephalopathy is not reflected in the current liver transplant allocation system. Correlation was sought between hepatic encephalopathy with findings detected on radiographic imaging studies and the patient’s clinical profile. Methods: A retrospective analysis was conducted of patients with cirrhosis, who presented for liver transplant evaluation in 2009 and 2010. Patients with hepatocellular carcinoma, ejection fraction less than 60% and who had a TIPS (transjugular intrahepatic portosystemic shunting) procedure or who did not complete the evaluation were excluded. Statistical analysis was performed and variables found to be significant on univariate analysis (P < 0.05) were analysed by a multivariate logistic regression model. Results: A total of 117 patients met the inclusion criteria and were divided into a hepatic encephalopathy group (n = 58) and a control group (n = 59). Univariate analysis found that a smaller portal vein diameter, smaller liver antero-posterior diameter, liver nodularity and use of diuretics or centrally acting medications showed significant correlation with hepatic encephalopathy. This association was confirmed for smaller portal vein, use of diuretics and centrally acting medications in the multivariate analysis. Conclusion: A decrease in portal vein diameter was associated with increased risk of encephalopathy. Identifying patients with smaller portal vein diameter may warrant screening for encephalopathy by more advanced psychometric testing, and more aggressive control of constipation and other factors that may precipitate encephalopathy.
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Affiliation(s)
- Saleh Elwir
- Department of Internal Medicine, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania (PA), USA
| | - Hassan Hal
- Department of Radiology, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA
| | - Joshua Veith
- Penn State Milton S. Hershey Medical Center and School of Medicine, Hershey, PA, USA
| | - Ian Schreibman
- Division of Gastroenterology and Hepatology, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA
| | - Zakiyah Kadry
- Division of Transplant Surgery, Penn State Milton S. Hershey Medical Center, Hershey PA, USA
| | - Thomas Riley
- Division of Gastroenterology and Hepatology, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA
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Landgraf BR, Johnson KM, Roldán-Alzate A, Francois CJ, Wieben O, Reeder SB. Effect of temporal resolution on 4D flow MRI in the portal circulation. J Magn Reson Imaging 2013; 39:819-26. [PMID: 24395121 DOI: 10.1002/jmri.24233] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2012] [Accepted: 04/30/2013] [Indexed: 12/12/2022] Open
Abstract
PURPOSE To demonstrate the use of temporal averaging with radial 4D flow magnetic resonance imaging (MRI) to reduce scan time for quantification and visualization of flow in the portal circulation. This study compared phase-contrast MR angiography, 3D flow visualization, and flow quantification of portal venous hemodynamics of time-averaged vs. time-resolved reconstructions. MATERIALS AND METHODS Time-resolved 3D radial ("4D") phase contrast data were acquired from 44 subjects (15 volunteers, 29 cirrhosis patients) at 3T. Images were reconstructed as a fully sampled time-resolved reconstruction and multiple time-averaged reconstructions using a variable number of acquired projections to simulate different scan times. Images from each reconstruction were evaluated to compare the quality of anatomical and hemodynamic visualization. RESULTS Time-averaged reconstructions outperformed time-resolved reconstructions for flow quantification (3.9 ± 3.1% error vs. 5.2 ± 4.4% error), average streamline length (47 ± 7 mm vs. 34 ± 15 mm), and visualization quality (average grading = 3.7 ± 0.5 vs. 2.2 ± 0.9). In addition, excellent visualization quality was achieved using fewer acquired projections. CONCLUSION Reductions in scan time can be achieved through time-averaging while still providing excellent visualization and quantification in the portal circulation. Scan time reduction of up to 70%-80% was possible for high-quality assessment, translating into a reduction in scan time from 10-12 minutes to ∼3-4 minutes.
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Doppler parameters of hepatic and renal hemodynamics in patients with liver cirrhosis. Int J Nephrol 2012; 2012:961654. [PMID: 22811907 PMCID: PMC3397178 DOI: 10.1155/2012/961654] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2012] [Revised: 03/25/2012] [Accepted: 04/24/2012] [Indexed: 01/04/2023] Open
Abstract
Introduction. There are limited studies on simultaneous evaluation of liver and renal blood flow using Doppler methods. We evaluated and compared the changes of liver and renal Doppler US parameters in patients with liver cirrhosis according to the degree of liver disease. Material and Methods. We assessed a large spectrum of liver and renal Doppler US parameters in 67 patients with liver cirrhosis. Results. Significant differences between Child's classes or score, as well as MELD score, were observed in all investigated intrarenal blood flow Doppler US parameters, except renal artery peak systolic velocity, but only in some of the hepatic ones. The deviations of renal Doppler US parameters were also related with the complications of liver cirrhosis, as well as serum urea and creatinine levels. There was relationship between Doppler US parameters of hepatic artery and the corresponding renal artery Doppler US parameters. The changes of Doppler US parameters were age independent. Conclusion. Our results show, renal Doppler US parameters correlate with the severity and complications of liver cirrhosis. Because of dynamic deviations of renal Doppler US parameters with advance of liver cirrhosis, we recommend Doppler US of renal artery as a part of follow up of these patients.
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Shateri K, Mohammadi A, Moloudi F, Nosair E, Ghasemi-Rad M. Correlation Between Sonographic Portal Vein Diameter and Flow Velocity With the Clinical Scoring Systems MELD and CTP in Cirrhotic Patients: Is There a Relationship? Gastroenterology Res 2012; 5:112-119. [PMID: 38952407 PMCID: PMC11216000 DOI: 10.4021/gr369w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/23/2012] [Indexed: 07/03/2024] Open
Abstract
Background Liver cirrhosis is defined as a chronic disease of the liver with destruction of the hepatic parenchymal cells. The aim of the current study was to investigate the correlation between sonographic portal vein diameter (PVD) as well as portal flow velocity (PFV) with the clinical scoring systems; CTP and MELD in cirrhotic patients. Methods In this cross sectional study, convenience sampling enrolled 108 patients, diagnosed with liver cirrhosis. Blood samples were taken and all patients subsequently underwent Doppler sonography to determine mean portal vein velocity and diameter. Results All 108 patients (66 males and 42 females) were enrolled in study. The mean age (± SD) was 50.9 ± 17.6 years (range 13 - 85). The results of the present work revealed weak +ve correlation between MELD and CHILD scores (r = 0.629; P = 0.01). Moreover, the mean PVD showed a little or no +ve correlation with both MELD and CHILD scores (r = 0.216, P = 0.05) and (r = 0.241, P = 0.05) respectively. However, the mean PFV showed no statistical significant relationship with MELD score (P = 0.41). Conclusion Sonographic portal vein parameters cannot be a substitute for clinical grading and staging of cirrhosis; and we cannot propose it as a single acceptable diagnostic indicator in grading liver cirrhosis with accuracy.
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Affiliation(s)
- Kamran Shateri
- Department of Gastroenterology, Urmia University of Medical Sciences, Urmia, Iran
| | - Afshin Mohammadi
- Department of Radiology, Urmia University of Medical Sciences, Urmia, Iran
| | - Farzad Moloudi
- Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran
| | - Emad Nosair
- Sharjah University, UAE; and Ain Shams University, Egypt
| | - Mohammad Ghasemi-Rad
- Genius and Talented Student Organization, Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran
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Mittal P, Gupta R, Mittal G, Kalia V. Association between portal vein color Doppler findings and the severity of disease in cirrhotic patients with portal hypertension. IRANIAN JOURNAL OF RADIOLOGY 2011; 8:211-7. [PMID: 23329943 PMCID: PMC3522358 DOI: 10.5812/iranjradiol.4489] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/02/2010] [Revised: 08/08/2011] [Accepted: 08/23/2011] [Indexed: 11/16/2022]
Abstract
BACKGROUND Doppler ultrasound is the accepted gold standard for assessing direction of flow in the portal vein (PV). Moreover, it is non-invasive; therefore, it is well accepted by the patients and does not interfere with flow hemodynamics. OBJECTIVES The present study was aimed to evaluate the association between color Doppler findings and the severity of portal hypertension in patients with cirrhosis. PATIENTS AND METHODS The study group included 50 patients referred for ultrasound (US) evaluation over a period of six months from March to August, 2007. The patients were divided into three groups (Child' A, B and C) based on Child Pugh classification. The direction of flow in the main portal vein (hepatopetal or nonhepatopetal) and peak venous velocity (PVV) in the main portal vein were measured and correlated with the presence or absence of ascites, splenomegaly, splenic and esophageal varices (assessed by Doppler US). These findings were correlated with clinical features and laboratory findings (using Child Pugh's criteria). RESULTS There was significant association between the decrease of peak portal venous velocity (PVV) and the increase in Child Pugh score. Hepatofugal flow was seen only in patients with more advanced disease. There was also significant association between PVV and splenic varices and ascites, while PVV was not affected by the presence or absence of esophageal varices or splenomegaly. Presence of a recanalized umbilical vein (UV) was associated with increased PVV even in advanced disease. CONCLUSIONS Color Doppler is an excellent modality for detecting and characterizing the complex hemodynamics of portal hypertension in cirrhosis and they correlate with the clinical stage of disease.
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Affiliation(s)
- Puneet Mittal
- Department of Radiodiagnosis, Punjab Institute of Medical Sciences, Jalandhar, India
- Corresponding author: Puneet Mittal, Department of Radiodiagnosis, Punjab Institute of Medical Sciences, 448, Opp. Singla Memorial Hospital, PremBasti, Sangrur, Punjab 148001, India. Tel.: +91-1672231086, Fax: +91-1812480736, E-mail:
| | - Ranjana Gupta
- Department of Radiodiagnosis, Punjab Institute of Medical Sciences, Jalandhar, India
| | - Gaurav Mittal
- Department of Medicine, Punjab Institute of Medical Sciences, Jalandhar, India
| | - Vishal Kalia
- Department of Radiodiagnosis, Dayanad Medical College and Hospital, Ludhiana, India
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El-Shabrawi MHF, El-Raziky M, Sheiba M, El-Karaksy HM, El-Raziky M, Hassanin F, Ramadan A. Value of duplex Doppler ultrasonography in non-invasive assessment of children with chronic liver disease. World J Gastroenterol 2010; 16:6139-6144. [PMID: 21182231 PMCID: PMC3012578 DOI: 10.3748/wjg.v16.i48.6139] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2010] [Revised: 09/13/2010] [Accepted: 09/20/2010] [Indexed: 02/06/2023] Open
Abstract
AIM to investigate the value of duplex Doppler ultrasonography (US) in the assessment of the hemodynamics of the portal and hepatic veins in a cohort of children with chronic liver disease (CLD) and to detect any relationship between the US changes, etiology and severity (or stage) of CLD. METHODS we prospectively enrolled 25 children with biopsy-proven CLD. Thirteen had cirrhosis (aged 8.9 ± 2.0 years) and 12 had chronic hepatitis (aged 9.3 ± 2.3 years). Gray scale and color-coded duplex Doppler US were performed for all, as well as 30 healthy age and sex-matched controls. Findings were correlated with clinical, laboratory and histopathological characteristics. RESULTS prominent caudate lobe was detected in 100% of cirrhotics, but none of the chronic hepatitis or controls. Thickened lesser omentum and loss of the triphasic waveform of the hepatic vein were present in 69.2% and 53.8% of cirrhotics vs 33.3% and 8.3% of chronic hepatitis respectively. Portal vein flow velocity was significantly lower (P < 0.0001) and the congestion index was significantly higher (P < 0.005) in both patient groups compared to controls. Child-Pugh's staging showed a positive correlation with both abnormal hepatic vein waveform and direction of portal blood flow; and a negative correlation with both hepatic and portal vein flow velocities. No correlation with the etiology of CLD could be detected. CONCLUSION duplex Doppler added to grayscale US can detect significant morphologic and portal hemodynamic changes that correlate with the severity (stage) of CLD, but not with etiology.
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Xingjiang W, Weiwei D, Jianmin C, Jianming H, Jieshou L. Functional Hepatic Flow Can Predict the Hepatic Reserve Function in Surgical Cirrhotic Patients. J INVEST SURG 2009; 22:178-82. [DOI: 10.1080/08941930802713076] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
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Edginton AN, Willmann S. Physiology-based simulations of a pathological condition: prediction of pharmacokinetics in patients with liver cirrhosis. Clin Pharmacokinet 2009; 47:743-52. [PMID: 18840029 DOI: 10.2165/00003088-200847110-00005] [Citation(s) in RCA: 123] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND Liver cirrhosis is a progressive disease characterized by loss of functional hepatocytes with concomitant connective tissue and nodule formation in the liver. The morphological and physiological changes associated with the disease substantially affect drug pharmacokinetics. Whole-body physiologically based pharmacokinetic (WB-PBPK) modelling is a predictive technique that quantitatively relates the pharmacokinetic parameters of a drug to such (patho-)physiological conditions. OBJECTIVE To extend an existing WB-PBPK model, based on the physiological changes associated with liver cirrhosis, which allows for prediction of drug pharmacokinetics in patients with liver cirrhosis. METHODS The literature was searched for quantitative measures of the physiological changes associated with the presence of Child-Pugh class A through C liver cirrhosis. The parameters that were included were the organ blood flows, cardiac index, plasma binding protein concentrations, haematocrit, functional liver volume, hepatic enzymatic activity and glomerular filtration rate. Predictions of pharmacokinetic profiles and parameters were compared with literature data for the model compounds alfentanil, lidocaine (lignocaine), theophylline and levetiracetam. RESULTS The predicted versus observed plasma concentration-time profiles for alfentanil and lidocaine were similar, such that the pharmacokinetic changes associated with Child-Pugh class A, B and C liver cirrhosis were adequately described. The theophylline elimination half-life was greatly increased in Child-Pugh class B and C patients compared with controls, as predicted by the model. Levetiracetam urinary excretion was consistently reduced with disease progression and very closely resembled observed values. CONCLUSION Consideration of the physiological differences between healthy individuals and patients with liver cirrhosis was important for the simulation of drug pharmacokinetics in this compromised group. The WB-PBPK model was altered to incorporate these physiological differences with the result of adequate simulation of drug pharmacokinetics. The information provided in this study will allow other researchers to further validate this liver cirrhosis model within a WB-PBPK model.
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Affiliation(s)
- Andrea N Edginton
- Competence Center Systems Biology, Bayer Technology Services GmbH, Leverkusen, Germany.
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Erdogmus B, Tamer A, Buyukkaya R, Yazici B, Buyukkaya A, Korkut E, Alcelik A, Korkmaz U. Portal vein hemodynamics in patients with non-alcoholic fatty liver disease. TOHOKU J EXP MED 2008; 215:89-93. [PMID: 18509239 DOI: 10.1620/tjem.215.89] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Paralleling the rise in the incidence of obesity and diabetes worldwide, nonalcoholic fatty liver disease (NAFLD) is being increasingly recognized as one of the major causes of chronic liver disease. Doppler sonography is used as a diagnostic method in the non-invasive assessment of the hemodynamics of hepatic vascular flow in liver diseases. We investigated the effects of fatty infiltration in the liver on the Doppler flow hemodynamics of the portal vein. Doppler sonography of the liver and portal vein was performed in 60 subjects with NAFLD and 20 healthy volunteers (control). The patients were grouped into mild (grade 1), moderate (grade 2), and severe (grade 3) according to sonographic appearance of hepatosteatosis (n = 20 for each group). The vein pulsatility index (VPI), mean flow velocity (MFV), peak maximum velocity (V(max)), and peak minimum velocity (V(min)) of the portal vein were significantly lower in patients with NAFLD than those of the controls (p < 0.001). The VPI was 0.20 in the patients and 0.31 in the control. The MFV was 12.3 cm/sec in the patients and 16.5 cm/sec in the control group. The portal vein flow was found to be decreased as the grade of fatty infiltration increased for VPI (r = -0.946, p < 0.001), MFV (r = -0.951, p < 0.001). The alteration in Doppler waveform pattern of portal vein with fatty liver population suggests reduced vascular compliance in the liver.
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Affiliation(s)
- Besir Erdogmus
- Department of Radiology, Duzce University, Medical School, Duzce, Turkey.
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Balci A, Karazincir S, Sumbas H, Oter Y, Egilmez E, Inandi T. Effects of diffuse fatty infiltration of the liver on portal vein flow hemodynamics. JOURNAL OF CLINICAL ULTRASOUND : JCU 2008; 36:134-140. [PMID: 18196595 DOI: 10.1002/jcu.20440] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
PURPOSE To investigate the effects of various degrees of diffuse fatty infiltration of the liver on portal vein blood flow with Doppler sonography. METHODS One hundred forty subjects were examined with color and spectral Doppler sonography. The subjects were divided into 4 groups of 35 subjects each according to the degree (normal, grade 1, grade 2 and grade 3) of hepatic fatty infiltration assessed on gray-scale images. The portal vein pulsatility index (VPI) and time-averaged mean flow velocity (MFV) were calculated for each subject. VPI was calculated as (peak maximum velocity - peak minimum velocity) / peak maximum velocity. RESULTS VPI and MFV values were, respectively, 0.32 +/- 0.06 and 16.8 +/- 2.6 cm/second in the normal group, 0.27 +/- 0.07 and 14.2 +/- 2.2 cm/second in the group with grade 1 fatty infiltration, 0.22 +/- 0.06 and 12.2 +/- 1.8 cm/second in the group with grade 2 fatty infiltration, and 0.18 +/- 0.04 and 10.8 +/- 1.5 cm/second in the group with grade 3 fatty infiltration. There was a negative inverse correlation between the grade of fatty infiltration and both VPI (f = 55.3, p < 0.001) and MFV (f = 43.9, p < 0.001). CONCLUSION The pulsatility index and mean velocity of the portal vein blood flow decrease as the severity of fatty infiltration increases.
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Affiliation(s)
- Ali Balci
- Department of Radiology, Mustafa Kemal University Faculty of Medicine, Bağriyanik Mh. Uğur Mumcu Cad., 31100 Antakya, Hatay, Turkey
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Zardi EM, Uwechie V, Gentilucci UV, Dobrina A, Petitti T, Laghi V, Picardi A, Afeltra A. Portal diameter in the diagnosis of esophageal varices in 266 cirrhotic patients: which role? ULTRASOUND IN MEDICINE & BIOLOGY 2007; 33:506-511. [PMID: 17337112 DOI: 10.1016/j.ultrasmedbio.2006.10.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/30/2006] [Revised: 09/19/2006] [Accepted: 10/05/2006] [Indexed: 05/14/2023]
Abstract
The aim was to evaluate the predictability of portal diameter (PD) in the diagnosis of esophageal varices (EV) and of large size EV (F3EV) in a large series of patients with cirrhosis. Two-hundred sixty-six persons with cirrhosis (M:F = 153:113; mean age 65.4 +/- 10 y) were studied by abdominal sonography and upper endoscopy. Portal hypertensive gastropathy (PHG) was found in 16.1% and EV was found in 60.9% of patients. Only Child's class (B vs. A: OR 3.4, p < 0.0001; C vs. A: OR 10.3, p < 0.0001; C vs. B: OR 3.1, p = 0.01) and age (OR 1.04, p = 0.03) were independent predictors of EV, whereas PD was not (p = 0.4). Child's class and age were also the only independent predictors of F3EV. Mean PD showed a slight and not significant increase in PHG patients compared with patients with negative endoscopy, a reduction in F1EV patients and then a progressive increase in F2EV and F3EV patients. Patients with PD <12 mm showed a significantly higher prevalence of F1-F2EV (p < 0.05) and a near-significant lower prevalence of endoscopies negative for EV (p = 0.06) than patients with 12 < or = PD < or = 13 mm. PD was not able to predict EV or F3EV in a large series of patients with cirrhosis. The oscillatory trend of PD, proceeding from patients with negative endoscopy to F3EV patients, seems to indicate that EV may unload portal pressure in the initial phases of portal hypertension.
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Tchambaz L, Schlatter C, Jakob M, Krähenbühl A, Wolf P, Krähenbühl S. Dose adaptation of antineoplastic drugs in patients with liver disease. Drug Saf 2006; 29:509-22. [PMID: 16752933 DOI: 10.2165/00002018-200629060-00004] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Dose adaptation for liver disease is important in patients treated with antineoplastic drugs because of the high prevalence of impaired liver function in this population and the dose-dependent, frequently serious adverse effects of these drugs. We classified the antineoplastic drugs marketed in Switzerland at the end of 2004 according to their bioavailability and/or hepatic extraction to predict their kinetic behaviour in patients with decreased liver function. This prediction was compared with kinetic studies carried out with these drugs in patients with liver disease. The studies were identified by a structured, computer-based literature search. Of the 69 drugs identified, 52 had a predominant extrarenal (in most cases hepatic) metabolism and/or excretion. For 49 drugs, hepatic extraction could be calculated and/or bioavailability data were available, allowing classification according to hepatic extraction. For 18 drugs, kinetic studies have been reported in patients with impaired liver function, with the findings generally resulting in quantitative recommendations for adaptation of the dosage. In particular, recommendations are precise for 16 drugs excreted by the bile (e.g. doxorubicin and derivatives and vinca alkaloids). Validation studies comparing such recommendations with kinetics and/or dynamics of antineoplastic drugs in patients with decreased liver function have not been published. We conclude that there are currently not enough data for safe use of cyctostatics in patients with liver disease. Pharmaceutical companies should be urged to provide kinetic data (especially hepatic extraction data) for the classification of such drugs and to conduct kinetic studies for drugs with primarily hepatic metabolism in patients with impaired liver function to allow quantitative advice to be given for dose adaptation.
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Affiliation(s)
- Lydia Tchambaz
- Division of Clinical Pharmacology & Toxicology, University Hopsital, Basel, Switzerland
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Chen XR, Li GM, Wang JR, Chen JJ. [Portal hemodynamics in patients with different syndromes of cirrhosis]. ACTA ACUST UNITED AC 2005; 2:178-81. [PMID: 15339437 DOI: 10.3736/jcim20040307] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
OBJECTIVE To explore the relationship between the portal hemodynamics or the indices of liver fibrosis and the liver function score in patients with different traditional Chinese medical syndromes of liver cirrhosis. METHODS One hundred and forty-seven cases of liver cirrhosis with different syndromes were included in the study. Diameters and blood flow velocities of the portal vein and splenic vein were tested by color Doppler sonarography. The indices of liver function (TBIL, ALT, AST, Alb, Glb, PTA) and the indices of hepatic fibrosis (HA, PC-III, LN, VI-C) were tested. RESULTS The diameters of portal vein in liver cirrhosis patients with different syndromes (internal accumulation of of damp-heat, stagnation of liver-qi, superabundance of dampness due to spleen-asthenia, asthenia of liver and kidney yin, asthenia of spleen and kidney yang, blood stasis) were not significantly different. The blood flow velocities and flow volumes of portal vein in patients with the blood stasis syndrome and the internal accumulation of damp-heat syndrome were significantly different (P < 0.05). The diameter of splenic vein in patients with the internal accumulation of damp-heat syndrome was significantly different to that of the asthenia of liver and kidney yin syndrome, or the blood stasis syndrome, or the asthenia of spleen and kidney yang syndrome, respectively (P < 0.05 or P < 0.01). The blood flow velocity of splenic vein in patients with the blood stasis syndrome or the asthenia of spleen and kidney yang syndrome was significantly different to that of the internal accumulation of damp-heat syndrome, or the stagnation of liver-qi syndrome, or the asthenia of liver and kidney yin syndrome, respectively (P < 0.01). The blood flow volume of splenic vein in patients with the internal accumulation of damp-heat syndrome was significantly different to that of the asthenia of liver and kidney yin syndrome, or the asthenia of spleen and kidney yang syndrome, or the blood stasis syndrome, respectively (P < 0.01). The liver cirrhosis indices HA and PC-III in patients with the asthenia of liver and kidney yin syndrome were significantly different to those of the internal accumulation of damp-heat syndrome (P < 0.05). In Child-Pugh classification, the incidence of Child-Pugh C was the highest in the asthenia of spleen and kidney yang syndrome, while the incidence of Child-Pugh A was the highest in the stagnation of liver qi syndrome. CONCLUSION The changes of portal vein dynamics in liver cirrhosis patients with the asthenia of liver and kidney yin syndrome, or the asthenia of spleen and kidney yang syndrome, or the blood stasis syndrome are significantly different to those of the internal accumulation of damp-heat syndrome and the stagnation of liver-qi syndrome.
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Affiliation(s)
- Xiao-Rong Chen
- Department of Integrated Traditional Chinese and Western Medicine, Shanghai Municipal Infectious Disease Hospital, Shanghai 200083, China.
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Kitamura H, Kobayashi C. Impairment of change in diameter of the hepatic portion of the inferior vena cava: a sonographic sign of liver fibrosis or cirrhosis. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2005; 24:355-361. [PMID: 15723848 DOI: 10.7863/jum.2005.24.3.355] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
OBJECTIVE We propose a new sonographic technique for detecting parenchymal stiffness of the liver. This technique measures the physiologic change in the diameter of the hepatic inferior vena cava (IVC). The hepatic portion of the IVC is extensively attached to the hepatic parenchyma so that changes in diameter of the venous lumen could not occur without changes in the shape of the surrounding parenchyma. Therefore, increased parenchymal stiffness due to cirrhosis or fibrosis may result in an impaired change in venous diameter. METHODS Thirty patients with histologically proven cirrhosis and 30 patients with normal livers were examined. A commercial ultrasound system was used in conjunction with a convex probe at a center frequency of 4.0 MHz. The major axis of the IVC was measured during normal breathing. The patients were then requested to take a deep breath to produce negative intrathoracic pressure, and the same measurement as that during normal breathing was repeated immediately. RESULTS In the normal liver group, the maximal diameter of the vena cava was 2.35 +/- 0.34 cm (mean +/- SD), and this was reduced by 1.30 +/- 0.67 cm (range, 0.4-2.85 cm) during deep inspiration. In the cirrhotic patient group, the maximal diameter was 1.74 +/- 0.35 cm, and this was reduced by 0.03 +/- 0.09 cm (range, 0.0-0.4 cm) (P < .0001). CONCLUSIONS The physiologic change in the diameter of the hepatic portion of the IVC enhanced by deep respiration may reflect the stiffness of hepatic parenchyma.
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Affiliation(s)
- Hiroshi Kitamura
- Department of Surgery, National Hospital Organization Chushin Matsumoto National Hospital, 811 Kotobuki-toyooka, Matsumoto, Nagano 3900021, Japan.
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Shi BM, Wang XY, Mu QL, Wu TH, Xu J. Value of portal hemodynamics and hypersplenism in cirrhosis staging. World J Gastroenterol 2005; 11:708-711. [PMID: 15655827 PMCID: PMC4250744 DOI: 10.3748/wjg.v11.i5.708] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2004] [Revised: 03/02/2004] [Accepted: 07/11/2004] [Indexed: 02/06/2023] Open
Abstract
AIM To determine the correlation between portal hemodynamics and spleen function among different grades of cirrhosis and verify its significance in cirrhosis staging. METHODS The portal and splenic vein hemodynamics and spleen size were investigated by ultrasonography in consecutive 38 cirrhotic patients with cirrhosis (Child's grades A to C) and 20 normal controls. The differences were compared in portal vein diameter and flow velocity between patients with and without ascites and between patients with mild and severe esophageal varices. The correlation between peripheral blood cell counts and Child's grades was also determined. RESULTS The portal flow velocity and volume were significantly lower in patients with Child's C (12.25+/-1.67 cm/s vs 788.59+/-234 mm/min, respectively) cirrhosis compared to controls (19.55+/-3.28 cm/s vs 1254.03+/-410 mm/min, respectively) and those with Child's A (18.5+/-3.02 cm/s vs 1358.48+/-384 mm/min, respectively) and Child's B (16.0+/-3.89 cm/s vs 1142.23+/-390 mm/min, respectively) cirrhosis. Patients with ascites had much lower portal flow velocity and volume (13.0+/-1.72 cm/s vs 1078+/-533 mm/min) than those without ascites (18.6+/-2.60 cm/s vs 1394+/-354 mm/min). There was no statistical difference between patients with mild and severe esophageal varices. The portal vein diameter was not significantly different among the above groups. There were significant differences in splenic vein diameter, flow velocity and white blood cell count, but not in spleen size, red blood cell and platelet counts among the various grades of cirrhosis. The spleen size was negatively correlated with red blood cell and platelet counts (r = -0.620 and r = -0.8.34, respectively). CONCLUSION An optimal system that includes parameters representing the portal hemodynamics and spleen function should be proposed for cirrhosis staging.
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Affiliation(s)
- Bao-Min Shi
- Department of General Surgery, Shandong Provincial Hospital, Clinical College of Shandong University, 324 Jingwu Road, Jinan 250021, Shandong Province, China.
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Nakanishi S, Shiraki K, Yamamoto K, Koyama M, Kimura N, Nakano T. Hemodynamics in the portal vein evaluated by pulse wave Doppler ultrasonography in patients with chronic hepatitis C treated with interferon. World J Gastroenterol 2005; 11:396-9. [PMID: 15637752 PMCID: PMC4205346 DOI: 10.3748/wjg.v11.i3.396] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To employ pulse wave Doppler ultrasonography to evaluate the changes in portal blood flow velocity in patients with chronic hepatitis C (CHC) receiving interferon (IFN) treatment.
METHODS: The subjects in this study were 14 patients (13 men and 1 woman) with CHC who received IFN treatment. Portal blood flow velocity was measured in the vessels at the porta hepatis at four time points: before IFN administration (pre-IFN), 2 wk after the start of administration (wk 2), 24 wk after the start of administration (wk 24, i.e., the end of IFN administration), and 24 wk after the end of administration (wk 48).
RESULTS: The patients with CHC in whom IFN treatment resulted in complete elimination or effective elimination of viruses showed a significant increase in portal blood flow velocity at the end of IFN treatment compared with that before IFN treatment. In contrast, when IFN was ineffective, no significant increase in portal blood flow velocity was observed at wk 24 or 48 compared with the pre-IFN value. In addition, the patients with CHC in whom IFN was ineffective showed significantly lower portal blood flow velocity values than control subjects at all measurement time points.
CONCLUSION: Pulse wave Doppler ultrasonography is a noninvasive and easily performed method for evaluating the effects of IFN treatment in patients with CHC. This technique is useful for measuring portal blood flow velocity before and 24 wk after IFN administration in order to evaluate the changes over time, thus assessing the effectiveness of IFN treatment.
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Affiliation(s)
- Shigeo Nakanishi
- First Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie 514-8507, Japan
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Duvoux C, Radier C, Roudot-Thoraval F, Maille F, Anglade MC, Van Nhieu JT, Rosa I, Hospitel S, Abd-Alsamad I, Sitruk V, Seror O, Ziol M, Blondon H, Dhumeaux D, Richardet JP. Low-grade steatosis and major changes in portal flow as new prognostic factors in steroid-treated alcoholic hepatitis. Hepatology 2004; 40:1370-8. [PMID: 15565651 DOI: 10.1002/hep.20475] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The aim of this study was to assess the prevalence and prognostic value of major alterations of portal flow in patients with steroid-treated alcoholic hepatitis. Fifty patients with severe, histologically proven alcoholic hepatitis were enrolled. Clinical data, liver test results, and hepatic Doppler ultrasound findings were collected at inclusion and at month 2. Patients were followed for 1 year or until death. Major changes in portal flow were defined as reversed or alternating flow in the portal trunk and/or in intrahepatic portal branches. Changes in portal flow were observed in 24 (48.0%) of 50 and 17 (39.5%) of 43 patients at inclusion and month 2, respectively. Univariate analysis showed that age older than 50 years, steatosis less than 20% on initial liver biopsy, presence of major changes in portal flow, Child-Turcotte-Pugh score higher than 12, factor V level higher than 45%, and hepatofugal splenic blood flow were associated with a lower 1-year survival. Cox regression analysis showed that steatosis < 20% (relative hazard [RH] = 9.3, P = .0009) and major changes in portal flow (RH = 3.1, P = .04), were independently associated with poor survival. In conclusion, major changes in portal flow are frequent in patients with severe alcoholic hepatitis. Altered portal flow and steatosis < 20% are new prognostic factors in steroid-treated alcoholic hepatitis and must be taken into account in patient management.
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Affiliation(s)
- Christophe Duvoux
- Service d'Hépatologie et de Gastroentérologie, Unité de Transplantation Hépatique and INSERM U581, Créteil, France.
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Abstract
AIM: To evaluate hepatic reserve function by investigating the change of functional hepatic flow and total hepatic flow in cirrhotic patients with portal hypertension.
METHODS: HPLC method was employed for the determination of concentration of D-sorbitol in human plasma and urine. The functional hepatic flow (FHF) and total hepatic flow (THF) were determined by means of modified hepatic clearance of D-sorbitol combined with duplex doppler color sonography in 20 patients with cirrhosis and 10 healthy volunteers.
RESULTS: FHF, evaluated by means of the D-sorbitol clearance, was significantly reduced in patients with cirrhosis in comparison to controls (764.74 ± 167.91 vs 1 195.04 ± 242.97 mL/min, P < 0.01). While THF was significantly increased in patients with cirrhosis in comparison to controls (1 605.23 ± 279.99 vs 1 256.12 ± 198.34 mL/min, P < 0.01). Portal blood flow and hepatic artery flow all were increased in cirrhosis compared to controls (P < 0.05 and P < 0.01). D-sorbitol total clearance was significantly reduced in cirrhosis compared to control (P < 0.01), while D-sorbitol renal clearance was significantly increased in cirrhosis (P < 0.05). In controls FHF was similar to THF (1 195.05 ± 242.97 vs 1 256.12 ± 198.34 mL/min, P = 0.636), while FHF was significantly reduced compared with THF in cirrhosis (764.74 ± 167.91 vs 1 605.23 ± 279.99 mL/min, P < 0.01).
CONCLUSION: Our method that combined modified hepatic clearance of D-sorbitol with duplex doppler color sonography is effective in the measurement of FHF and THF. FHF can be used to estimate hepatic reserve function.
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Affiliation(s)
- Zheng Pan
- Research Institute of General Surgery, Nanjing General Hospital of Nanjing Command, No.305, Eastern Road of Zhongshan, Nanjing 210002, Jiangsu Province, China.
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O'Donohue J, Ng C, Catnach S, Farrant P, Williams R. Diagnostic value of Doppler assessment of the hepatic and portal vessels and ultrasound of the spleen in liver disease. Eur J Gastroenterol Hepatol 2004; 16:147-55. [PMID: 15075987 DOI: 10.1097/00042737-200402000-00005] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES To investigate the clinical utility and the intra-observer and inter-observer variability of Doppler ultrasound assessment of the hepatic and portal vessels along with measurement of spleen size in the diagnosis of chronic liver disease and cirrhosis. METHODS AND MATERIALS Ultrasound measurements of portal vein diameter (PVD), portal vein velocity (PVV), hepatic arterial resistance index (HARI), hepatic vein profile (HVP), and spleen size were obtained in 49 controls and 45 patients with liver disease (23 with primary biliary cirrhosis, 22 with hepatitis C) by two experienced observers, who each performed three blinded measurements of each variable. Control values were derived from normal hospital workers. Percutaneous liver biopsies in 41 of the patients showed cirrhosis (14 patients), moderate/severe fibrosis (13 patients), and early disease (14 patients). RESULTS Seventy-one percent of cirrhotic patients had splenomegaly (> 13.6 cm). The spleen size was significantly larger in cirrhotics (16.0 cm) than in non-cirrhotics (13.0 cm, P < 0.009) and healthy controls (10.7 cm, P < 0.00005), and was the only independent predictor of cirrhosis, with a threshold of 15 cm predicting cirrhosis with a specificity of 98%, positive predictive value of 93%, sensitivity of 57% and negative predictive value of 80%. HVP was abnormal in 76.9% of cirrhotics, 57.7% of non-cirrhotics and 2.1% of controls (P < 0.04). However, the mean PVV, PVD and HARI were no different between controls and patients or between cirrhotic and non-cirrhotic liver disease. There was significant inter-observer variability for PVV, but intra-observer and inter-observer variability was acceptable for the other measurements. CONCLUSIONS Splenomegaly size and abnormal HVP are useful predictors of chronic liver disease and cirrhosis, and both can be measured reliably and reproducibly. However, Doppler measurements of PVV, PVD and HARI are not useful in distinguishing patients with chronic liver disease from normal controls.
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Affiliation(s)
- John O'Donohue
- Institute of Liver Studies, King's College Hospital, London, UK. john.o'
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Kutlu R, Karaman I, Akbulut A, Baysal T, Sigirci A, Alkan A, Aladag M, Seckin Y, Saraç K. Quantitative Doppler evaluation of the splenoportal venous system in various stages of cirrhosis: differences between right and left portal veins. JOURNAL OF CLINICAL ULTRASOUND : JCU 2002; 30:537-543. [PMID: 12404519 DOI: 10.1002/jcu.10114] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
PURPOSE The purpose of our study was to evaluate the relationship between the splenoportal hemodynamics in patients with cirrhosis and the stage of the disease. METHODS Patients with cirrhosis were grouped according to modified Child-Pugh scoring into stages A, B, and C of cirrhosis. A control group of healthy volunteers was included. After gastroenterologic clinical and laboratory examinations, all participants underwent a splenoportal Doppler sonographic evaluation in which the vessels' diameter, area, and blood flow velocity were measured and blood flow rate and the congestion index in the splenoportal venous system were calculated. RESULTS Seventy-five patients with cirrhosis (25 women and 50 men) were enrolled; the control group consisted of 30 healthy volunteers (15 women and 15 men) with no liver disease. The mean age (+/- standard deviation) of the patients was 54.4 +/- 14.8 years (range, 13-80 years) and of the control subjects was 47.3 +/- 14.5 years (range, 18-72 years). No significant differences in vessel diameter, blood flow velocity, and blood flow rate were found in the main and left portal veins between the study group and the control group. In the right portal vein, we found decreases in the vessel diameter, blood flow velocity, and blood flow rate, and in the splenic vein, we found increases in vessel diameter and blood flow rate. The congestion index was increased in the main portal and splenic veins but was unchanged in the left portal vein. CONCLUSIONS Although our data indicate that there is no difference in Doppler sonographic parameters of the main portal vein according to Child-Pugh scores, the hemodynamic differences between the left and right branches of the portal vein may be clinically useful in patients with cirrhosis.
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Affiliation(s)
- Ramazan Kutlu
- Department of Radiology, Turgut Ozal Medical Center, Inonu University School of Medicine, Elazig Yolu, Kampus, 44100 Malatya, Turkey
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Barakat M. Portal vein pulsatility and spectral width changes in patients with portal hypertension: relation to the severity of liver disease. Br J Radiol 2002; 75:417-21. [PMID: 12036834 DOI: 10.1259/bjr.75.893.750417] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Using Doppler ultrasound in patients with chronic liver disease (CLD) and portal hypertension, portal vein pulsatility pattern and spectral width changes were assessed and evaluated in relation to the severity of liver disease as determined according to the Child-Pugh score. The pulsatility index (PI) was significantly lower in CLD patients (mean+/-SD: 0.23+/-0.08) compared with healthy subjects (0.39+/-0.1) (p<0.001) and lower in Child-Pugh class C compared with Child-Pugh class A patients (0.21+/-0.07 vs 0.25+/-0.08, respectively) (p<0.05). The spectral width index was significantly higher in CLD patients vs healthy subjects (0.91+/-0.16 vs 0.60+/-0.12, respectively) (p<0.001). The difference was also noted in the early stage (Child-Pugh A patients) when compared with healthy subjects (0.88+/-0.17). In conclusion, portal vein pulsatility and spectral width indices can reflect the early haemodynamic changes in CLD patients. These changes become more pronounced with the progression of liver disease.
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Affiliation(s)
- M Barakat
- Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Assiut University, Assiut, Egypt
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Tingze H, Jiexiong F, Wenying L, Hong T, Yunman T, Fuyu L, Xiaoping J, Fukang W, Xuedong W, Yuan L. Triplex operation for children with extrahepatic portal hypertension. J Pediatr Surg 2002; 37:605-9. [PMID: 11912519 DOI: 10.1053/jpsu.2002.31618] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
BACKGROUND/PURPOSE How to deal with the vexatious problem of esophageal and gastric varices secondary to extrahepatic portal hypertension has been discussed extensively among pediatric surgeons around the world. The aim of this study is to evaluate the effect of triplex operation (splenopneumopexy, portal azygous devascularization, and ligation of splenic artery) for children with portal hypertension in the author's hospital. METHODS From March 1993 to November 1998, 7 children with extrahepatic portal hypertension were admitted to the author's hospital to undergo triplex operation. The diagnoses of these patients were confirmed by gastroscopy, barium meal, and Doppler ultrasonography. The number of white blood cells and platelets and the hepatic function were checked before and after operation. And the free portal pressures (FPP) were checked before and after the ligation of the splenic artery. All patients underwent follow-up for 1 to 7 years (mean, 4.6 years). The episodes of upper gastrointestinal bleeding were recorded. The degree of varices of distal esophagus and proximal stomach were assessed by barium meal and gastroscopy. The diameters of the spleenic and portal vein were obtained by B ultrasonography. The portopulmonary shunt and portal blood flow were evaluated by color Doppler flow image (CDFI). The indices of hemorheology such as hematocrit, viscosity of whole blood and plasma, and the indexes of deformability and aggregability of red blood cells were obtained through viscometer (R-20 Seerle, Beijing, China). RESULTS There was no operative mortality in this group. Postoperatively, hemorrhage from the esophagus and gastric varices was completely controlled. Although the diameter of spleen reduced progressively, no patient's spleen recovered to normal during the follow-up period. The degree of varices was mitigated, and the FPP was decreased significantly to 34.48 +/- 5.71 cm H(2)O from the preoperative 42.62 +/- 6.72 cm H(2)O (P <.05). The rate of portal flow also was decreased. The direction of portal vein was bidirection (one part was away from the liver and the other was toward the liver). The numbers of white blood cells and platelets were increased. The viscosities of whole blood and hematocrit also were increased after operation. CONCLUSION The triplex operation is an effective procedure for the control of hemorrhage from varices in children with extrahepatic portal hypertension.
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Affiliation(s)
- Hu Tingze
- Department of Pediatric Surgery and Ultrasonography, Huaxi Hospital, Sichuan University, Chengdu, China
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Sereno S, Toccaceli F, Russo V, Iacomi F, Zardi EM, Laghi V. Doppler sonography measurement of portal blood flow velocity after glucagon injection in patients with chronic HCV infection. ULTRASOUND IN MEDICINE & BIOLOGY 2001; 27:723-726. [PMID: 11397536 DOI: 10.1016/s0301-5629(01)00347-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/23/2023]
Abstract
Doppler sonography measurement of portal flow velocity (PFV) after glucagon injection was performed in 45 patients with chronic hepatitis C virus (HCV) infection. Patients were divided into three groups: group 1 = no or mild liver fibrosis; group 2 = moderate to severe liver fibrosis, and group 3 = liver cirrhosis. All patients were examined using a Doppler ultrasound (US) multipurpose equipment and a convex 3.5-MHz probe, 10 min before (baseline), as well as 5 and 10 min after, IV administration of 1 mg of glucagon chloride. No significant differences were found in mean baseline PFV among group 1 (19.4 +/- 2.4 cm/s), group 2 (20.1 +/- 3.6 cm/s) and group 3 (17.5 +/- 3.7 cm/s). Five minutes after glucagon injection, all three groups showed significantly increased values of mean PFV (25.6 +/- 4.8, 23.7 +/- 4.0 and 19.5 +/- 5.0 cm/s, respectively; p < 0.05 vs. baseline). The mean increase of PFV above baseline was significantly higher in group 1 (7.9 +/- 3.7 cm/s) than in group 2 (4.5 +/- 3.9 cm/s) (p < 0.05) or in group 3 (2.7 +/- 2.3 cm/s) (p < 0.05). A significant inverse correlation was found between individual values of fibrosis score and of individual increase of PFV. In patients with chronic HCV infection, Doppler sonography measurement of PFV after glucagon injection could be useful in assessing the severity of liver histological damage.
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Affiliation(s)
- S Sereno
- Department of Infectious and Tropical Diseases, University La Sapienza, Rome, Italy
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von Herbay A, Frieling T, Häussinger D. Color Doppler sonographic evaluation of spontaneous portosystemic shunts and inversion of portal venous flow in patients with cirrhosis. JOURNAL OF CLINICAL ULTRASOUND : JCU 2000; 28:332-339. [PMID: 10934332 DOI: 10.1002/1097-0096(200009)28:7<332::aid-jcu3>3.0.co;2-9] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/23/2023]
Abstract
PURPOSE The aim of the study was to evaluate the usefulness of color Doppler sonography in the detection of spontaneous portosystemic shunts and abnormal blood flow direction in the portal vein in patients with cirrhosis. METHODS Patients were 67 men and 42 women (mean age, 53 +/- 14 years) with cirrhosis confirmed by liver biopsy. All patients underwent abdominal gray-scale and color Doppler sonographic evaluations to detect the presence of spontaneous portosystemic shunts and to analyze portal vein blood flow direction. RESULTS Spontaneous portosystemic shunts were found in 41 patients (38%), most often as splenorenal shunts (21%) and patent umbilical veins (14%). Less frequent were gastric collaterals, gallbladder varices, collaterals to thrombotic portal veins, mesoiliac shunts, and portorenal shunts to the right kidney. The presence of shunts was associated with that of esophageal varices (p < 0.01), ascites (p < 0.01), and inversion of portal flow (p < 0. 001) but not with splenomegaly. The direction of portal venous flow was normal (hepatopetal) in 80 patients (73%), hepatofugal in 10 (9%), and bidirectional in 7 (6%); 12 patients (11%) had partial portal vein thrombosis. CONCLUSIONS Portosystemic shunts and the direction of portal venous flow are important features in the sonographic diagnosis of portal hypertension.
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Affiliation(s)
- A von Herbay
- Department of Gastroenterology, University of Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf, Germany
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39
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Kuriyama S, Yamazaki M, Mitoro A, Tsujimoto T, Kikukawa M, Tsujinoue H, Nakatani T, Toyokawa Y, Yoshiji H, Fukui H. Hepatocellular carcinoma in an orthotopic mouse model metastasizes intrahepatically in cirrhotic but not in normal liver. Int J Cancer 1999; 80:471-6. [PMID: 9935192 DOI: 10.1002/(sici)1097-0215(19990129)80:3<471::aid-ijc22>3.0.co;2-4] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Prognosis of hepatocellular carcinoma (HCC) still remains poor mainly because of intrahepatic metastasis. In the majority of cases, HCC is found in conjunction with liver cirrhosis. It is, therefore, of great importance to investigate the invasive and metastatic behavior of HCC in cirrhotic liver. To examine this, a liver cirrhosis model was produced by injecting thioacetamide i.p. into mice. Murine HCC cells were labeled with the fluorescent carbocyanine dye, DiI, and implanted directly under the capsule of cirrhotic and normal livers of syngeneic mice. DiI-labeled HCC cells in the liver were observed under fluorescent and confocal microscopy. Histological analysis of cirrhotic and normal livers revealed that implanted HCC cells migrated to and invaded the adjacent periportal regions, but not the adjacent centrolobular areas. This characteristic behavior of HCC was more evident in cirrhotic liver than in normal liver. Furthermore, intrahepatic metastasis to unimplanted hepatic lobes was observed in cirrhotic liver as early as 7 days after implantation, while it was not detected in normal liver even 4 weeks later. Thus, an orthotopic animal model for HCC with cirrhosis described here may be suitable for investigating the invasive and metastatic behavior of HCC. Importantly, labeling tumor cells with a fluorescent dye before orthotopic implantation may be a convenient and useful method to investigate the invasive and metastatic behavior of various types of cancer.
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Affiliation(s)
- S Kuriyama
- Third Department of Internal Medicine, Nara Medical University, Japan
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Sagarad SV, Chawla YK, Dhiman RK. Portal hemodynamics after large-volume paracentesis in patients with liver cirrhosis and tense ascites. Dig Dis Sci 1998; 43:2470-2. [PMID: 9824136 DOI: 10.1023/a:1026638316826] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
Large-volume paracentesis with a plasma expander has been extensively evaluated and shown to be an effective and safe therapy. While hepatic and systemic hemodynamics have been studied extensively, there is little information on portal hemodynamics by duplex Doppler. Portal vein diameter, portal flow velocity, and portal blood flow were measured with duplex Doppler in 11 cirrhotic patients before and 24 hr after large volume paracentesis. There were no significant changes in the portal vein diameter (9.88+/-2.62 mm vs 10.09+/-2.73 mm), portal flow velocity (10.65+/-2.60 vs 10.01+/-2.58 cm/sec), and portal blood flow (488+/-288.9 vs 502+/-73.38 ml/min), before and 24 hr after large-volume paracentesis. Thus, significant changes in portal hemodynamics do not occur after large-volume paracentesis.
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Affiliation(s)
- S V Sagarad
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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