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Zheng L, Wu G, Lin J, Li H, Zhang C, Zhao Z, Chen M, Wu Z, Luo G, Fan Q, Qi X, Huo H, Sun L, Luo M. A novel noninvasive assessment of portal pressure from computational biofluid mechanics in patients with portal hypertension. Trials 2025; 26:167. [PMID: 40400007 PMCID: PMC12093596 DOI: 10.1186/s13063-025-08818-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 03/17/2025] [Indexed: 05/23/2025] Open
Abstract
BACKGROUND AND AIMS To introduce and assess a novel method for portal pressure measurement based on biofluid mechanics in portal hypertensive patients undergoing surgery. METHODS The research was a multi-center, retrospective study, conducted on patients who underwent surgery and measurement of free portal pressure (FPP). There were 118 patients included and 21 patients excluded due to the failure or poor results of Doppler ultrasound, and 97 patients were screened. We used patients' CT images, Doppler ultrasound results of the portal system, blood density and viscosity to reconstruct their portal system and simulate its internal blood flow. According to the patient's physical property, geometry, and boundary conditions, the Navier-Stokes equations were solved by FLUENT software, and virtual free portal pressure (vFPP) was calculated. Finally, the Bland-Altman Limits of Agreement, intraclass correlation coefficient (ICC), and the Lin's concordance correlation coefficient were performed to evaluate the numerical correlation between the vFPP and FPP. RESULTS All patients enrolled in this study underwent the surgery, and the FPP of patients was measured during the surgery, with a mean FPP of 22.8 ± 3.3 mmHg (range: 13-33 mmHg). Meanwhile, according to computational biofluid mechanics, all patients' vFPP was calculated. Then, we further explored whether there was a close relationship between vFPP and FPP in the whole population. For the analysis of Bland-Altman Limits of Agreement, the mean value of difference was - 0.1569 (95% CI: - 0.4305 to 0.1167); lower limit of agreement: - 2.8176 (95% CI: - 3.2868 to - 2.3484); upper limit of agreement: 2.5038 (95% CI: 2.0346 to 2.9730). The ICC was 0.9215 (95% CI: 0.8848 to 0.9468). Furthermore, the Lin's concordance correlation coefficient showed a numerical correlation between the vFPP and FPP, which was 0.9205 (95% CI: 0.8840 to 0.9459). All these results confirmed that our vFPP model could provide an accurate prediction of FPP in patients. CONCLUSIONS The vFPP of patients calculated by computational biofluid mechanics was significantly correlated with the FPP of portal hypertensive patients, which would be a novel, non-invasive, and accurate method for the assessment of portal pressure in surgical patients.
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Affiliation(s)
- Lei Zheng
- Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People's Republic of China
| | - Guangbo Wu
- Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People's Republic of China
| | - Jiayun Lin
- Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People's Republic of China
| | - Hongjie Li
- Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People's Republic of China
| | - Chihao Zhang
- Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People's Republic of China
| | - Zhifeng Zhao
- Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People's Republic of China
| | - Min Chen
- Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People's Republic of China
| | - Zhenghao Wu
- Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People's Republic of China
| | - Guqing Luo
- Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People's Republic of China
| | - Qiang Fan
- Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People's Republic of China
| | - Xiaoliang Qi
- Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People's Republic of China
| | - Haizhong Huo
- Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People's Republic of China.
| | - Longci Sun
- Department of Gastrointestinal Surgery, Shanghai Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, People's Republic of China.
| | - Meng Luo
- Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People's Republic of China.
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Zhu Y, Chen J, Chen C, Tang R, Xu J, Shi S, Yu X. Deciphering mechanical cues in the microenvironment: from non-malignant settings to tumor progression. Biomark Res 2025; 13:11. [PMID: 39849659 PMCID: PMC11755887 DOI: 10.1186/s40364-025-00727-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Accepted: 01/05/2025] [Indexed: 01/25/2025] Open
Abstract
The tumor microenvironment functions as a dynamic and intricate ecosystem, comprising a diverse array of cellular and non-cellular components that precisely orchestrate pivotal tumor behaviors, including invasion, metastasis, and drug resistance. While unraveling the intricate interplay between the tumor microenvironment and tumor behaviors represents a tremendous challenge, recent research illuminates a crucial biological phenomenon known as cellular mechanotransduction. Within the microenvironment, mechanical cues like tensile stress, shear stress, and stiffness play a pivotal role by activating mechanosensitive effectors such as PIEZO proteins, integrins, and Yes-associated protein. This activation initiates cascades of intrinsic signaling pathways, effectively linking the physical properties of tissues to their physiological and pathophysiological processes like morphogenesis, regeneration, and immunity. This mechanistic insight offers a novel perspective on how the mechanical cues within the tumor microenvironment impact tumor behaviors. While the intricacies of the mechanical tumor microenvironment are yet to be fully elucidated, it exhibits distinct physical attributes from non-malignant tissues, including elevated solid stresses, interstitial hypertension, augmented matrix stiffness, and enhanced viscoelasticity. These traits exert notable influences on tumor progression and treatment responses, enriching our comprehension of the multifaceted nature of the microenvironment. Through this innovative review, we aim to provide a new lens to decipher the mechanical attributes within the tumor microenvironment from non-malignant contexts, broadening our knowledge on how these factors promote or inhibit tumor behaviors, and thus offering valuable insights to identify potential targets for anti-tumor strategies.
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Affiliation(s)
- Yicheng Zhu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Shanghai Key Laboratory of Precision Medicine for Pancreatic Cancer, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Jiaoshun Chen
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Shanghai Key Laboratory of Precision Medicine for Pancreatic Cancer, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Chen Chen
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Shanghai Key Laboratory of Precision Medicine for Pancreatic Cancer, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Rong Tang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Shanghai Key Laboratory of Precision Medicine for Pancreatic Cancer, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Jin Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China
- Shanghai Key Laboratory of Precision Medicine for Pancreatic Cancer, Shanghai, 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China
| | - Si Shi
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China.
- Shanghai Key Laboratory of Precision Medicine for Pancreatic Cancer, Shanghai, 200032, China.
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China.
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China.
- Shanghai Key Laboratory of Precision Medicine for Pancreatic Cancer, Shanghai, 200032, China.
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China.
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Vashishtha C, Sarin SK. Bleeding Complications of Portal Hypertension. Clin Liver Dis 2024; 28:483-501. [PMID: 38945639 DOI: 10.1016/j.cld.2024.03.006] [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] [Indexed: 07/02/2024]
Abstract
In portal hypertension, acute variceal bleed is the cause of 2/3rd of all upper gastrointestinal bleeding episodes. It is a life-threatening emergency in patients with cirrhosis. Nonselective beta-blockers by decreasing the hepatic venous pressure gradient are the mainstay of medical therapy for the prevention of variceal bleeding and rebleeding. Evaluation of the severity of bleed, hemodynamic resuscitation, prophylactic antibiotic, and intravenous splanchnic vasoconstrictors should precede the endoscopy procedure. Endoscopic band ligation is the recommended endotherapy. Rescue transjugular intrahepatic port-systemic shunt (TIPS) is recommended for variceal bleed refractory to endotherapy. In patients with a high risk of failure of combined pharmacologic and endoscopic therapy, pre-emptive TIPS may improve the outcome. For gastric varices, "Sarin classification" is universally applied as it is simple and has therapeutic implication. For IGV1 and GOV2, injection cyanoacrylate glue is considered the endotherapy of choice. Endoscopic ultrasound is a useful modality in the management of gastric varices.
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Affiliation(s)
- Chitranshu Vashishtha
- Department of Hepatology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi 110070, India
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi 110070, India.
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Hu Y, Duan S, Zhang Y, Hao L, Wang S, Xue F, Zhang K, Zhu Y, Zhang L. Feasibility and safety of ultrasound-guided percutaneous transhepatic measurement of portal venous pressure. PLoS One 2024; 19:e0305725. [PMID: 39028708 PMCID: PMC11259298 DOI: 10.1371/journal.pone.0305725] [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: 12/04/2023] [Accepted: 06/03/2024] [Indexed: 07/21/2024] Open
Abstract
BACKGROUND AND OBJECTIVE The measurement of portal venous pressure (PVP) has been extensively studied, primarily through indirect methods. However, the potential of ultrasound-guided percutaneous transhepatic PVP measurement as a direct method has been largely unexplored. This study aimed to investigate the accuracy, safety, and feasibility of this approach. METHODS In vitro, the experiment aimed to select a needle that could accurately transmit pressure, had a small inner diameter and was suitable for liver puncture, and performed on 20 healthy New Zealand white rabbits. An ultrasound-guided percutaneous transhepatic portal vein puncture was undertaken to measure PVP. Additionally, free hepatic venous pressure (FHVP) and wedged hepatic venous pressure (WHVP) were measured under digital subtraction angiography (DSA). The correlation between the two methods was assessed. Enroll study participants from October 18, 2023 to November 11, 2023 with written informed consent. Five patients were measured the PVP under ultrasound guidance before surgery to determine the feasibility of this measurement method. RESULTS There was no significant difference in the results obtained using 9 different types of needles (P > 0.05). This demonstrated a great repeatability (P < 0.05). The 22G chiba needle with small inner diameter, allowing for accurate pressure transmission and suitable for liver puncture, was utilized for percutaneous transhepatic PVP measurement. There were positive correlations between PVP and HVPG (r = 0.881), PVP and WHVP (r = 0.709), HVPG and WHVP (r = 0.729), IVCP and FHVP (r = 0.572). The PVP was accurately and safely measured in 5 patients with segmental hepatectomy. No complications could be identified during postoperative ultrasound. CONCLUSION Percutaneous transhepatic portal venous puncture under ultrasound guidance is accurate, safe and feasible to measure portal venous pressure. CLINICAL TRIAL REGISTRATION NUMBER This study has been registered in the Chinese Clinical Trial Registry with registration number ChiCTR2300076751.
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Affiliation(s)
- Yanshan Hu
- Zhengzhou University People’s Hospital, Zhengzhou, China
- Henan Engineering Technology Center of Ultrasonic Molecular Imaging and Nanotechnology, Zhengzhou, Henan Province, China
| | - Shaobo Duan
- Zhengzhou University People’s Hospital, Zhengzhou, China
- Henan Engineering Technology Center of Ultrasonic Molecular Imaging and Nanotechnology, Zhengzhou, Henan Province, China
- Department of Health Management, Henan Provincial People’s Hospital, Zhengzhou, Henan Province, China
| | - Ye Zhang
- Department of Health Management, Henan Provincial People’s Hospital, Zhengzhou, Henan Province, China
| | - Liuwei Hao
- Department of Health Management, Henan Provincial People’s Hospital, Zhengzhou, Henan Province, China
| | - Shuaiyang Wang
- Department of Health Management, Henan Provincial People’s Hospital, Zhengzhou, Henan Province, China
| | - Fei Xue
- Department of Hepatobiliary Surgery, Henan Provincial People’s Hospital, Zhengzhou, Henan Province, China
| | - Kewei Zhang
- Department of Vascular Surgery, Henan Provincial People’s Hospital, Zhengzhou, Henan Province, China
| | - Yadong Zhu
- Department of Vascular Surgery, Henan Provincial People’s Hospital, Zhengzhou, Henan Province, China
| | - Lianzhong Zhang
- Zhengzhou University People’s Hospital, Zhengzhou, China
- Henan Engineering Technology Center of Ultrasonic Molecular Imaging and Nanotechnology, Zhengzhou, Henan Province, China
- Department of Ultrasound, Henan Provincial People’s Hospital, Zhengzhou, Henan Province, China
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Madir A, Grgurevic I, Tsochatzis EA, Pinzani M. Portal hypertension in patients with nonalcoholic fatty liver disease: Current knowledge and challenges. World J Gastroenterol 2024; 30:290-307. [PMID: 38313235 PMCID: PMC10835535 DOI: 10.3748/wjg.v30.i4.290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Revised: 12/19/2023] [Accepted: 01/08/2024] [Indexed: 01/26/2024] Open
Abstract
Portal hypertension (PH) has traditionally been observed as a consequence of significant fibrosis and cirrhosis in advanced non-alcoholic fatty liver disease (NAFLD). However, recent studies have provided evidence that PH may develop in earlier stages of NAFLD, suggesting that there are additional pathogenetic mechanisms at work in addition to liver fibrosis. The early development of PH in NAFLD is associated with hepatocellular lipid accumulation and ballooning, leading to the compression of liver sinusoids. External compression and intra-luminal obstacles cause mechanical forces such as strain, shear stress and elevated hydrostatic pressure that in turn activate mechanotransduction pathways, resulting in endothelial dysfunction and the development of fibrosis. The spatial distribution of histological and functional changes in the periportal and perisinusoidal areas of the liver lobule are considered responsible for the pre-sinusoidal component of PH in patients with NAFLD. Thus, current diagnostic methods such as hepatic venous pressure gradient (HVPG) measurement tend to underestimate portal pressure (PP) in NAFLD patients, who might decompensate below the HVPG threshold of 10 mmHg, which is traditionally considered the most relevant indicator of clinically significant portal hypertension (CSPH). This creates further challenges in finding a reliable diagnostic method to stratify the prognostic risk in this population of patients. In theory, the measurement of the portal pressure gradient guided by endoscopic ultrasound might overcome the limitations of HVPG measurement by avoiding the influence of the pre-sinusoidal component, but more investigations are needed to test its clinical utility for this indication. Liver and spleen stiffness measurement in combination with platelet count is currently the best-validated non-invasive approach for diagnosing CSPH and varices needing treatment. Lifestyle change remains the cornerstone of the treatment of PH in NAFLD, together with correcting the components of metabolic syndrome, using nonselective beta blockers, whereas emerging candidate drugs require more robust confirmation from clinical trials.
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Affiliation(s)
- Anita Madir
- Department of Gastroenterology, Hepatology and Clinical Nutrition, University Hospital Dubrava, Zagreb 10000, Croatia
| | - Ivica Grgurevic
- Department of Gastroenterology, Hepatology and Clinical Nutrition, University Hospital Dubrava, Zagreb 10000, Croatia
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb 10000, Croatia
| | - Emmanuel A Tsochatzis
- UCL Institute for Liver and Digestive Health, Royal Free Hospital and University College London, London NW3 2PF, United Kingdom
| | - Massimo Pinzani
- UCL Institute for Liver and Digestive Health, Royal Free Hospital and University College London, London NW3 2PF, United Kingdom
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Liu S, Ma J, Chen P, Liu S, Guo Y, Tan M, Guo X, Feng Y, Wang Q, Li W, Yang C, Gao B, Hua Y, Liu N, Song H, He R, Wang R, Gao Q, Liu C, Qi X. Novel serum biomarker of Golgi protein 73 for the diagnosis of clinically significant portal hypertension in patients with compensated cirrhosis. J Med Virol 2024; 96:e29380. [PMID: 38235849 DOI: 10.1002/jmv.29380] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Revised: 12/17/2023] [Accepted: 12/28/2023] [Indexed: 01/19/2024]
Abstract
Hepatic venous pressure gradient (HVPG) is the gold standard for evaluating clinically significant portal hypertension (CSPH). However, reliable noninvasive methods are limited. Our study aims to investigate the diagnostic value of serum Golgi protein 73 (GP73) for CSPH in patients with compensated cirrhosis. The study enrolled 262 consecutive patients with compensated cirrhosis from three centers in China from February 2021 to September 2023, who underwent both serum GP73 tests and HVPG measurements. CSPH was defined as HVPG ≥ 10 mmHg. Diagnostic accuracy was evaluated using the areas under the receiver operating characteristic curve (AUC). The prevalence of CSPH was 56.9% (n = 149). There were significant differences between the CSPH and non-CSPH groups in the median serum GP73 level (126.8 vs. 73.1 ng/mL, p < 0.001). GP73 level showed a significant positive linear correlation with HVPG (r = 0.459, p < 0.001). The AUC for the diagnosis of CSPH using serum GP73 alone was 0.75 (95% confidence interval [CI] 0.68-0.81). Multivariate logistic regression analysis determined that the levels of GP73, platelets and international normalized ratio were independently associated with CSPH. The combination of these three markers was termed "IP73" score with an AUC value of 0.85 (95% CI 0.80-0.89) for CSPH. Using 0 as a cut-off value, the specificity and sensitivity of IP73 score were 77.9% and 81.9%, respectively. The IP73 score offers a novel, simple and noninvasive method of assessing CSPH in patients with compensated cirrhosis. A cut-off value of the IP73 score at 0 can distinguish patients with or without CSPH.
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Affiliation(s)
- Shanghao Liu
- Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
- Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing, China
| | - Jianzhong Ma
- Department of General Surgery, The Third People's Hospital of Taiyuan, Taiyuan, China
| | - Ping Chen
- Department of infectious diseases, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, China
| | - Shirong Liu
- Department of Infectious Diseases, Qufu People's Hospital, Qufu, China
| | - Ying Guo
- Department of Hepatology, The Third People's Hospital of Taiyuan, Taiyuan, China
| | - Mingjie Tan
- Department of Gastrointestinal and Hepatology, Beijing You'An Hospital, Capital Medical University, Beijing, China
| | - Xiaoqing Guo
- Department of Hepatology, The Third People's Hospital of Taiyuan, Taiyuan, China
| | - Yinong Feng
- Department of Hepatology, The Third People's Hospital of Taiyuan, Taiyuan, China
| | - Qinghui Wang
- Department of Hepatology, The Third People's Hospital of Taiyuan, Taiyuan, China
| | - Wenhua Li
- Department of Hepatology, The Third People's Hospital of Taiyuan, Taiyuan, China
| | - Chengchen Yang
- College of Medicine, Zhejiang University, Hangzhou, China
| | - Bo Gao
- Medical Laboratory, Qufu People's Hospital, Qufu, China
| | - Yongli Hua
- Department of Hepatology, The Third People's Hospital of Taiyuan, Taiyuan, China
| | - Ning Liu
- Department of Infectious Diseases, Qufu People's Hospital, Qufu, China
| | - Haolin Song
- College of Medicine, Zhejiang University, Hangzhou, China
| | - Ruiling He
- The First Clinical Medical College of Lanzhou University, Lanzhou, China
| | - Ruiying Wang
- The First Clinical Medical College of Lanzhou University, Lanzhou, China
| | - Qi Gao
- Beijing Key Laboratory of POCT for Bioemergency and Clinic (No. BZ0329); Beijing Hotgen Biotechnology Inc., Beijing, China
| | - Chuan Liu
- Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
- Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing, China
| | - Xiaolong Qi
- Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
- Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing, China
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Sathawane A, Khobragade H, Pal S. Correlation of Hepatic Venous Pressure Gradient Level With Clinical and Endoscopic Parameters in Decompensated Chronic Liver Disease. Cureus 2023; 15:e51154. [PMID: 38283456 PMCID: PMC10811441 DOI: 10.7759/cureus.51154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Accepted: 12/27/2023] [Indexed: 01/30/2024] Open
Abstract
BACKGROUND The amount of liver fibrosis usually correlates with portal pressure, which is measured as the hepatic venous pressure gradient (HVPG). The fact that portal pressure significantly decreases after treatment may increase cirrhotic patients' long-term survival suggests that measuring HVPG may offer specific information for outcome prediction. The study thus seeks to determine the relationship between the level of the HVPG and endoscopic and clinical parameters in decompensated chronic liver disease (CLD). METHODOLOGY Thirty patients with CLD were studied and subjected to serum creatinine, total bilirubin, serum sodium, serum albumin, prothrombin time (PT), international normalized ratio (INR), esophagogastroduodenoscopy (upper gastrointestinal (UGI) endoscopy), and transjugular or transfemoral catheterization for HVPG measurement, and Child-Turcotte-Pugh (CTP) score and Model for End-Stage Liver Disease (MELD) score were calculated. RESULTS The results indicates a strong positive connection between MELD and HVPG, which is statistically significant (r=0.754; p<0.001). Similarly, CTP and HVPG also exhibit a significant positive association (r=0.793; p<0.001) suggesting a link between the severity of liver disease. Additionally, the moderate positive correlation for encephalopathy has a significant value (r=0.584; p=0.001), while the weak positive correlations for serum bilirubin, INR, and HVPG have non-significant values (r=0.244; p=0.194, and r=0.375; p=0.041, respectively). A strong negative connection between serum albumin and HVPG was also found (r=0.546; p=0.005) suggesting a relationship between worsening liver function. CONCLUSION In patients with decompensated CLD, the severity of the CLD as measured by the CTP and MELD score corresponds with HVPG, and higher HVPG associated with severe CLD and severe ascites, large varices, and variceal hemorrhage. Higher HVPG in cirrhotic patients also suggests the existence of sequelae, such as varices, severe ascites, and severe hepatic encephalopathy, although HVPG has little bearing on the underlying cause.
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Affiliation(s)
- Amol Sathawane
- Gastroenterology, Rabindranath Tagore International Institute of Cardiac Sciences, Kolkata, IND
| | - Harshal Khobragade
- Medicine, Rabindranath Tagore International Institute of Cardiac Sciences, Kolkata, IND
| | - Sandip Pal
- Gastroenterology, Rabindranath Tagore International Institute of Cardiac Sciences, Kolkata, IND
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Chooklin S, Chuklin S. Methods for assessing portal hypertension. EMERGENCY MEDICINE 2023; 19:393-401. [DOI: 10.22141/2224-0586.19.6.2023.1618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Abstract
Many researchers and clinicians have taken the value of hepatic venous pressure gradient (HVPG) as an essential prognostic factor in subjects with chronic liver diseases. HVPG ≥ 10 mmHg indicates the presence of clinically significant portal hypertension, the main predictor of the risk of variceal bleeding, hepatic decompensation, and mortality. However, HVPG measurement is invasive and requires high expertise, so its routine use outside tertiary care centers or clinical trials is limited. Clinically significant portal hypertension also might be detected using non-invasive options such as ultrasonography, elastography, magnetic resonance imaging, and indices derived from laboratory parameters. Our review aims to present the feasibility and applicability of HVPG in modern clinical practice in patients with liver cirrhosis, including invasive and non-invasive methods, based on literary sources from the MEDLINE database.
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Richards SM, Guo F, Zou H, Nigsch F, Baiges A, Pachori A, Zhang Y, Lens S, Pitts R, Finkel N, Loureiro J, Mongeon D, Ma S, Watkins M, Polus F, Albillos A, Tellez L, Martinez-González J, Bañares R, Turon F, Ferrusquía-Acosta J, Perez-Campuzano V, Magaz M, Forns X, Badman M, Sailer AW, Ukomadu C, Hernández-Gea V, Garcia-Pagán JC. Non-invasive candidate protein signature predicts hepatic venous pressure gradient reduction in cirrhotic patients after sustained virologic response. Liver Int 2023; 43:1984-1994. [PMID: 37443448 DOI: 10.1111/liv.15657] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Revised: 06/02/2023] [Accepted: 06/12/2023] [Indexed: 07/15/2023]
Abstract
BACKGROUND AND AIMS A reduction in hepatic venous pressure gradient (HVPG) is the most accurate marker for assessing the severity of portal hypertension and the effectiveness of intervention treatments. This study aimed to evaluate the prognostic potential of blood-based proteomic biomarkers in predicting HVPG response amongst cirrhotic patients with portal hypertension due to Hepatitis C virus (HCV) and had achieved sustained virologic response (SVR). METHODS The study comprised 59 patients from two cohorts. Patients underwent paired HVPG (pretreatment and after SVR), liver stiffness (LSM), and enhanced liver fibrosis scores (ELF) measurements, as well as proteomics-based profiling on serum samples using SomaScan® at baseline (BL) and after SVR (EOS). Machine learning with feature selection (Caret, Random Forest and RPART) methods were performed to determine the proteins capable of classifying HVPG responders. Model performance was evaluated using AUROC (pROC R package). RESULTS Patients were stratified by a change in HVPG (EOS vs. BL) into responders (greater than 20% decline in HVPG from BL, or <10 mmHg at EOS with >10 mmHg at BL) and non-responders. LSM and ELF decreased markedly after SVR but did not correlate with HVPG response. SomaScan (SomaLogic, Inc., Boulder, CO) analysis revealed a substantial shift in the peripheral proteome composition, reflected by 82 significantly differentially abundant proteins. Twelve proteins accurately distinguished responders from non-responders, with an AUROC of .86, sensitivity of 83%, specificity of 83%, accuracy of 83%, PPV of 83%, and NPV of 83%. CONCLUSIONS A combined non-invasive soluble protein signature was identified, capable of accurately predicting HVPG response in HCV liver cirrhosis patients after achieving SVR.
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Affiliation(s)
| | - Fang Guo
- Novartis Institutes for Biomedical Research, East Hannover, New Jersey, USA
| | - Heng Zou
- Novartis Institutes for Biomedical Research, East Hannover, New Jersey, USA
| | - Florian Nigsch
- Novartis Institutes of Biomedical Research, Basel, Switzerland
| | - Anna Baiges
- Barcelona Hepatic Hemodynamic Laboratory, Barcelona Health Care Provider of the European Reference Network on Rare Liver, Barcelona, Spain
- CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas), Barcelona, Spain
- Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Departament de Medicina. Facultat de Medicina i Ciències de la Salut. Universitat de Barcelona., Barcelona, Spain
| | - Alok Pachori
- Novartis Institutes for Biomedical Research, East Hannover, New Jersey, USA
| | - Yiming Zhang
- Novartis Institutes for Biomedical Research, East Hannover, New Jersey, USA
| | - Sabela Lens
- CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas), Barcelona, Spain
- Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Departament de Medicina. Facultat de Medicina i Ciències de la Salut. Universitat de Barcelona., Barcelona, Spain
| | - Rebecca Pitts
- Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, USA
| | - Nancy Finkel
- Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, USA
| | - Joseph Loureiro
- Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, USA
| | - Dale Mongeon
- Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, USA
| | - Shenglin Ma
- Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, USA
| | - Mollie Watkins
- Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, USA
| | - Florine Polus
- Novartis Institutes of Biomedical Research, Basel, Switzerland
| | - Agustin Albillos
- CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas), Barcelona, Spain
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
| | - Luis Tellez
- CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas), Barcelona, Spain
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
| | - Javier Martinez-González
- CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas), Barcelona, Spain
- Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
| | - Rafael Bañares
- CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas), Barcelona, Spain
- Hospital General Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Madrid, Spain
| | - Fanny Turon
- Barcelona Hepatic Hemodynamic Laboratory, Barcelona Health Care Provider of the European Reference Network on Rare Liver, Barcelona, Spain
- CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas), Barcelona, Spain
- Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Departament de Medicina. Facultat de Medicina i Ciències de la Salut. Universitat de Barcelona., Barcelona, Spain
| | - José Ferrusquía-Acosta
- Barcelona Hepatic Hemodynamic Laboratory, Barcelona Health Care Provider of the European Reference Network on Rare Liver, Barcelona, Spain
| | - Valeria Perez-Campuzano
- Barcelona Hepatic Hemodynamic Laboratory, Barcelona Health Care Provider of the European Reference Network on Rare Liver, Barcelona, Spain
- CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas), Barcelona, Spain
- Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Departament de Medicina. Facultat de Medicina i Ciències de la Salut. Universitat de Barcelona., Barcelona, Spain
| | - Marta Magaz
- Barcelona Hepatic Hemodynamic Laboratory, Barcelona Health Care Provider of the European Reference Network on Rare Liver, Barcelona, Spain
- CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas), Barcelona, Spain
- Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Departament de Medicina. Facultat de Medicina i Ciències de la Salut. Universitat de Barcelona., Barcelona, Spain
| | - Xavier Forns
- CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas), Barcelona, Spain
- Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Departament de Medicina. Facultat de Medicina i Ciències de la Salut. Universitat de Barcelona., Barcelona, Spain
| | - Michael Badman
- Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, USA
| | | | - Chinweike Ukomadu
- Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, USA
| | - Virginia Hernández-Gea
- Barcelona Hepatic Hemodynamic Laboratory, Barcelona Health Care Provider of the European Reference Network on Rare Liver, Barcelona, Spain
- CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas), Barcelona, Spain
- Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Departament de Medicina. Facultat de Medicina i Ciències de la Salut. Universitat de Barcelona., Barcelona, Spain
| | - Juan Carlos Garcia-Pagán
- Barcelona Hepatic Hemodynamic Laboratory, Barcelona Health Care Provider of the European Reference Network on Rare Liver, Barcelona, Spain
- CIBEREHD (Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas), Barcelona, Spain
- Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Departament de Medicina. Facultat de Medicina i Ciències de la Salut. Universitat de Barcelona., Barcelona, Spain
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Di X, Gao X, Peng L, Ai J, Jin X, Qi S, Li H, Wang K, Luo D. Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets. Signal Transduct Target Ther 2023; 8:282. [PMID: 37518181 PMCID: PMC10387486 DOI: 10.1038/s41392-023-01501-9] [Citation(s) in RCA: 140] [Impact Index Per Article: 70.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Revised: 05/10/2023] [Accepted: 05/11/2023] [Indexed: 08/01/2023] Open
Abstract
Cellular mechanotransduction, a critical regulator of numerous biological processes, is the conversion from mechanical signals to biochemical signals regarding cell activities and metabolism. Typical mechanical cues in organisms include hydrostatic pressure, fluid shear stress, tensile force, extracellular matrix stiffness or tissue elasticity, and extracellular fluid viscosity. Mechanotransduction has been expected to trigger multiple biological processes, such as embryonic development, tissue repair and regeneration. However, prolonged excessive mechanical stimulation can result in pathological processes, such as multi-organ fibrosis, tumorigenesis, and cancer immunotherapy resistance. Although the associations between mechanical cues and normal tissue homeostasis or diseases have been identified, the regulatory mechanisms among different mechanical cues are not yet comprehensively illustrated, and no effective therapies are currently available targeting mechanical cue-related signaling. This review systematically summarizes the characteristics and regulatory mechanisms of typical mechanical cues in normal conditions and diseases with the updated evidence. The key effectors responding to mechanical stimulations are listed, such as Piezo channels, integrins, Yes-associated protein (YAP) /transcriptional coactivator with PDZ-binding motif (TAZ), and transient receptor potential vanilloid 4 (TRPV4). We also reviewed the key signaling pathways, therapeutic targets and cutting-edge clinical applications of diseases related to mechanical cues.
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Affiliation(s)
- Xingpeng Di
- Department of Urology and Institute of Urology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, P.R. China
| | - Xiaoshuai Gao
- Department of Urology and Institute of Urology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, P.R. China
| | - Liao Peng
- Department of Urology and Institute of Urology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, P.R. China
| | - Jianzhong Ai
- Department of Urology and Institute of Urology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, P.R. China
| | - Xi Jin
- Department of Urology and Institute of Urology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, P.R. China
| | - Shiqian Qi
- Department of Urology and Institute of Urology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, P.R. China
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, P.R. China
| | - Hong Li
- Department of Urology and Institute of Urology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, P.R. China
| | - Kunjie Wang
- Department of Urology and Institute of Urology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, P.R. China.
| | - Deyi Luo
- Department of Urology and Institute of Urology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, P.R. China.
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11
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Wei J, Hu Y, Yu J, Yin C, Chen G, Jin L. Predictive value of hepatic venous pressure gradient and efficacy and significance of early PTVE for gastrointestinal bleeding after TACE for liver cancer. J Cancer Res Ther 2022; 18:1967-1972. [PMID: 36647957 DOI: 10.4103/jcrt.jcrt_331_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Aims To investigate the predictive value of hepatic venous pressure gradient (HVPG) and the efficacy and significance of early percutaneous transhepatic varices embolization (PTVE) for gastrointestinal bleeding after transcatheter arterial chemoembolization (TACE) for liver cancer. Methods and Materials This retrospective study enrolled 60 patients diagnosed with stage B or stage C liver cancer, according to the Barcelona Clinic Liver Cancer (BCLC) staging system, between December 2019 and October 2021. TACE and HVPG measurement (>16 mmHg or >20 mmHg) were performed on all 60 patients, who were randomized into control and experimental (PTVE) groups. All patients were followed up for 12 months. Statistical Analysis Used SPSS 20.0 software was used for data analysis. The two groups were compared with respect to the initial occurrence time of hemorrhage after TACE, recurrence time of hemorrhage, liver function, TACE frequency, TACE type, and tumor control. Results The initial hemorrhage rates at one, three, six, and 12 months after TACE were 3.2%, 12.9%, 22.6%, and 48.4%, respectively, in the control group (n = 31) and 0%, 0%, 3.4%, and 10.3%, respectively, in the PTVE group (n = 29). Differences between the groups in terms of initial hemorrhage rate at six and 12 months postoperatively were significant (P < 0.05). The recurrence rates of hemorrhage at one, three, six, and 12 months after TACE were 11.1%, 22.2%, 22.2%, and 33.3%, respectively, in 27 patients in the control group. In eight patients in the PTVE group, the corresponding rates were 0%, 0%, 0%, and 25.0%. The differences between the groups in the recurrence rate of hemorrhage at the four time points were significant (P < 0.05). At six months postoperatively, liver function recovery and remission were noted in eight (25.8%) and 18 (66.7%) patients, respectively, in the control group; these events were noted in 10 (34.5%) and 19 patients (65.5%), respectively, in the PTVE group, and the difference between the groups was not significant (P > 0.05). In the control group, TACE was performed for a total of 94 times on 31 patients within 12 months, including conventional transcatheter arterial chemoembolization (C-TACE, 75.5%) and the drug-eluting bead TACE (DEB-TACE, 24.5%); the objective response rate (ORR) was 39.3%. In the PTVE group, TACE was performed for a total of 151 times on 29 patients within 12 months, with an average of 5.21 times on each patient, including the C-TACE (57.6%) and DEB-TACE (42.4%); the ORR was 60.1%. Differences in TACE frequency, proportion of C-TACE/DEB-TACE, and ORR were significant between the two groups (P < 0.05). Conclusion HVPG can accurately evaluate gastrointestinal bleeding after TACE in patients with liver cancer. Early PTVE can significantly lower the risk of gastrointestinal bleeding and help TACE control tumor progression in patients with an HVPG >16 mmHg or >20 mmHg.
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Affiliation(s)
- Jian Wei
- Department of Interventional Radiography, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yuefeng Hu
- Department of Interventional Radiography, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Jianan Yu
- Department of Interventional Radiography, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Chao Yin
- Department of Interventional Radiography, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Guang Chen
- Department of Interventional Radiography, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Long Jin
- Department of Interventional Radiography, Beijing Friendship Hospital, Capital Medical University, Beijing, China
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12
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Li N, Zhang X, Zhou J, Li W, Shu X, Wu Y, Long M. Multiscale biomechanics and mechanotransduction from liver fibrosis to cancer. Adv Drug Deliv Rev 2022; 188:114448. [PMID: 35820602 DOI: 10.1016/j.addr.2022.114448] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 05/08/2022] [Accepted: 07/06/2022] [Indexed: 02/06/2023]
Abstract
A growing body of multiscale biomechanical studies has been proposed to highlight the mechanical cues in the development of hepatic fibrosis and cancer. At the cellular level, changes in mechanical microenvironment induce phenotypic and functional alterations of hepatic cells, initiating a positive feedback loop that promotes liver fibrogenesis and hepatocarcinogenesis. Tumor mechanical microenvironment of hepatocellular carcinoma facilitates tumor cell growth and metastasis, and hinders the drug delivery and immunotherapy. At the molecular level, mechanical forces are sensed and transmitted into hepatic cells via allosteric activation of mechanoreceptors on the cell membrane, leading to the activation of various mechanotransduction pathways including integrin and YAP signaling and then regulating cell function. Thus, the application of mechanomedicine concept in the treatment of liver diseases is promising for rational design and cell-specific delivery of therapeutic drugs. This review mainly discusses the correlation between biomechanical cues and liver diseases from the viewpoint of mechanobiology.
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Affiliation(s)
- Ning Li
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory), and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China; School of Engineering Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Xiaoyu Zhang
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory), and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China; School of Engineering Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Jin Zhou
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory), and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China
| | - Wang Li
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory), and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China; School of Engineering Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Xinyu Shu
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory), and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China; School of Engineering Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Yi Wu
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory), and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China; School of Engineering Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Mian Long
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory), and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China; School of Engineering Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
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13
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Benítez C. Pressure Measurements Under Pressure: Simplifying the Diagnosis of Clinically Significant Portal Hypertension. Dig Dis Sci 2022; 67:2711-2713. [PMID: 34739622 DOI: 10.1007/s10620-021-07283-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/06/2021] [Indexed: 12/09/2022]
Affiliation(s)
- Carlos Benítez
- Liver Transplant Unit, Gastroenterology Department, Hospital Clínico de la Pontificia Universidad Católica de Chile, Diagonal Paraguay 362, 8330077, Santiago, Chile.
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14
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Evaluation of hepatic hemodynamics (hepatic venous pressure gradient) during right heart catheterization: a comprehensive review. Curr Probl Cardiol 2022; 47:101278. [DOI: 10.1016/j.cpcardiol.2022.101278] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 05/30/2022] [Indexed: 01/01/2023]
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15
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Bai W, Al-Karaghouli M, Stach J, Sung S, Matheson GJ, Abraldes JG. Test-Retest Reliability and Consistency of HVPG and Impact on Trial Design: A Study in 289 Patients from 20 Randomized Controlled Trials. Hepatology 2021; 74:3301-3315. [PMID: 34181770 DOI: 10.1002/hep.32033] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 06/10/2021] [Accepted: 06/24/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS Portal hypertension (PH) is a major driver for cirrhosis complications. Portal pressure is estimated in practice by the HVPG. The assessment of HVPG changes has been used for drug development in PH. This study aimed at quantifying the test-retest reliability and consistency of HVPG in the specific context of randomized controlled trials (RCTs) for the treatment of PH in cirrhosis and its impact on power calculations for trial design. APPROACH AND RESULTS We conducted a search of published RCTs in patients with cirrhosis reporting individual patient-level data of HVPG at baseline and after an intervention, which included a placebo or an untreated control arm. Baseline and follow-up HVPGs in the control groups were extracted after digitizing the plots. We assessed reliability and consistency and the potential impact of study characteristics. We retrieved a total of 289 before and after HVPG measurements in the placebo/untreated groups from 20 RCTs. The time span between the two HVPG measurements ranged between 20 minutes and 730 days. Pre-/post-HVPG variability was lower in studies including only compensated patients; therefore, modeled sample size calculations for trials in compensated cirrhosis were lower than for decompensated cirrhosis. A higher proportion of alcohol-associated cirrhosis and unicentric trials was associated with lower differences between baseline and follow-up measurements. The smallest detectable difference in an individual was 26% and 30% in compensated and decompensated patients, respectively. CONCLUSIONS The test-retest reliability of HVPG is overall excellent. Within-individual variance was higher in studies including higher proportions of decompensated patients. These findings should be taken into account when performing power analysis for trials based on the effects on HVPG or when considering HVPG as a tool to guide therapy of PH.
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Affiliation(s)
- Wayne Bai
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, AB, Canada
| | - Mustafa Al-Karaghouli
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, AB, Canada
| | - Jesse Stach
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, AB, Canada.,Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB, Canada
| | - Shuen Sung
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, AB, Canada
| | - Granville J Matheson
- Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY.,Department of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet and Stockholm County Council, Stockholm, Sweden
| | - Juan G Abraldes
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, AB, Canada
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16
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Dao M, MacDonald I, Asaro RJ. Erythrocyte flow through the interendothelial slits of the splenic venous sinus. Biomech Model Mechanobiol 2021; 20:2227-2245. [PMID: 34535857 DOI: 10.1007/s10237-021-01503-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Accepted: 07/12/2021] [Indexed: 10/20/2022]
Abstract
The flow patterns of red blood cells through the spleen are intimately linked to clearance of senescent RBCs, with clearance principally occurring within the open flow through the red pulp and slits of the venous sinus system that exists in humans, rats, and dogs. Passage through interendothelial slits (IESs) of the sinus has been shown by MacDonald et al. (Microvasc Res 33:118-134, 1987) to be mediated by the caliber, i.e., slit opening width, of these slits. IES caliber within a given slit of a given sinus section has been shown to operate in an asynchronous manner. Here, we describe a model and simulation results that demonstrate how the supporting forces exerted on the sinus by the reticular meshwork of the red pulp, combined with asymmetrical contractility of stress fibers within the endothelial cells comprising the sinus, describe this vital and intriguing behavior. These results shed light on the function of the sinus slits in species such as humans, rats, and dogs that possess sinusoidal sinuses. Instead of assuming a passive mechanical filtering mechanism of the IESs, our proposed model provides a mechanically consistent explanation for the dynamically modulated IES opening/filtering mechanism observed in vivo. The overall perspective provided is also consistent with the view that IES passage serves as a self-protective mechanism in RBC vesiculation and inclusion removal.
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Affiliation(s)
- Ming Dao
- Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
| | - Ian MacDonald
- Department of Medical Biophysics, Schulich School of Medicine and Dentistry Western University, London, ON, Canada
| | - R J Asaro
- Department of Structural Engineering, University of California, San Diego, La Jolla, CA, 92093, USA.
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17
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Danielsen KV, Hove JD, Nabilou P, Yin M, Chen J, Zhao M, Kallemose T, Teisner AS, Siebner HR, Ehman RL, Møller S, Bendtsen F. Using MR elastography to assess portal hypertension and response to beta-blockers in patients with cirrhosis. Liver Int 2021; 41:2149-2158. [PMID: 34060714 PMCID: PMC8373798 DOI: 10.1111/liv.14981] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 05/18/2021] [Accepted: 05/27/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND MR elastography can determine organ-related stiffness, which reflects the degree of fibrosis. Liver stiffness increases in cirrhosis, and stiffness increases further post-prandially due to increased portal blood in-flow. Non-selective beta-blockers (NSBB) reduce the portal venous inflow, but their effect on liver and spleen stiffness are disputed. AIMS To assess whether MR elastography of the liver or spleen reflects the severity of cirrhosis, whether treatment with NSBB changes liver and spleen stiffness and whether changes in stiffness can predict the effect of NSBB on portal pressure. METHODS Fifty-two patients with cirrhosis underwent liver vein catheterization and two-dimensional (2D) MR elastography on separate days. Thirty-six of the patients had a hepatic venous pressure gradient (HVPG) of ≥12 mmHg and were tested prior to, and after, intravenous infusion of NSBB using HVPG measurement and MR elastography. RESULTS HVPG showed a strong, positive, linear relationship with liver stiffness (r2 = 0.92; P < .001) and spleen stiffness (r2 = 0.94; P < .001). The cut-off points for identifying patients with a HVPG ≥ 12 mmHg were 7.7 kPa for liver stiffness (sensitivity 0.78, specificity 0.64) and 10.5 kPa for spleen stiffness (sensitivity 0.8, specificity 0.79). Intravenous administration of NSBB significantly decreased spleen stiffness by 6.9% (CI: 3.5-10.4, P < .001), but NSBB had no consistent effect on liver stiffness. However, changes in spleen stiffness were not related to the HVPG response (P = .75). CONCLUSIONS Two-dimensional MR elastographic estimation of liver or spleen stiffness reflects the degree of portal hypertension in patients with liver cirrhosis, but changes in stiffness after NSBB do not predict the effect on HVPG.
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Affiliation(s)
- Karen Vagner Danielsen
- Centre of Gastroenterology, Medical division, Copenhagen University Hospital Hvidovre, Denmark,Dept. Clinical Physiology and Nuclear Medicine, Centre of Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Jens Dahlgaard Hove
- Dept. of Cardiology, Copenhagen University Hospital Hvidovre, Denmark,Institute of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen
| | - Puria Nabilou
- Centre of Gastroenterology, Medical division, Copenhagen University Hospital Hvidovre, Denmark
| | - Meng Yin
- Dept. of Radiology, Mayo Clinic, Rochester, cx USA
| | - Jun Chen
- Dept. of Radiology, Mayo Clinic, Rochester, cx USA
| | - Mirabella Zhao
- Centre of Gastroenterology, Medical division, Copenhagen University Hospital Hvidovre, Denmark
| | - Thomas Kallemose
- Clinical Research Department. Copenhagen University Hospital Hvidovre, Denmark
| | - Ane Søgaard Teisner
- Centre of Gastroenterology, Medical division, Copenhagen University Hospital Herlev, Denmark
| | - Hartwig Roman Siebner
- Institute of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen,Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | | | - Søren Møller
- Dept. Clinical Physiology and Nuclear Medicine, Centre of Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark,Institute of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen
| | - Flemming Bendtsen
- Centre of Gastroenterology, Medical division, Copenhagen University Hospital Hvidovre, Denmark,Institute of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen
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18
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Gonzalo Bada N, Suárez Parga JM, Hernández Cabrero T, Ponce Dorrego D, Zarauza Soto Y, Abadía Barnó M, Olveira Martín A, Novo Torres J, Rodríguez Díaz R, Fernández Rodríguez L, Mora Sanz P, Froilán Torres C. Hemodynamic changes after endoscopic variceal ligation: a cohort study. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2021; 112:456-461. [PMID: 32450703 DOI: 10.17235/reed.2020.6656/2019] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
BACKGROUND there is controversy about the need to maintain vasoconstrictor treatment after adequate haemostasis is achieved through endoscopic band ligation (EBL) in bleeding esophageal varices (BEV). Measuring a "before and after urgent-EBL" hepatic venous pressure gradient (HVPG) in acute variceal hemorrhage is very difficult. Thus, the goal of this study was to determine hemodynamic variations after an EBL session. A "before" HVPG (PRE) was performed and another one 24 hours "after-ligation" (POST), in cirrhotic patients undergoing endoscopic band ligation as BEV prophylaxis. PATIENTS AND METHODS this was a single-center, cohort, prospective study. Patients followed a program of repeated sessions of EBL until eradication of their varices and underwent a basal hepatic venous pressure gradient (PRE HVPG), without changing their usual treatment with beta-blockers. Subsequently, an endoscopic ligation session was performed, following the clinical practices guidelines. A second pressure measurement (POST HVPG) was taken 24 hours after the endoscopic treatment. RESULTS 30 patients were included. PRE and POST HVPG median results were 16.5 mmHg (14-20) and 19.5 mmHg (17-21), respectively, with a significant increase after the procedure (p < 0.001). Percentage variations in portal pressure, based on the baseline gradient values (12, 16 and 20 mmHg), were higher for patients with a lower basal HVPG versus a higher HVPG for any of the categories compared (p = 0.087, p = 0.016 and p < 0.001, respectively). In our series, 36.7 % of patients showed a ≥ 20 % gradient increase after ligation. CONCLUSION endoscopic band ligation causes an increase in portal pressure, at least for a transitional period, determined by the hepatic venous pressure gradient.
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Veldhuijzen van Zanten D, Buganza E, Abraldes JG. The Role of Hepatic Venous Pressure Gradient in the Management of Cirrhosis. Clin Liver Dis 2021; 25:327-343. [PMID: 33838853 DOI: 10.1016/j.cld.2021.01.002] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Quantifying the degree of portal hypertension provides useful information to estimate prognosis and to evaluate new therapies for portal hypertension. This quantification is done in clinical practice with the measurement of the hepatic venous pressure gradient. This article addresses the applications of measuring portal pressure in cirrhosis, including the differential diagnosis of portal hypertension; estimation of prognosis in cirrhosis, including preoperative evaluation before hepatic and extrahepatic surgery; assessment of the response to drug therapy (mainly in the context of drug development); and assessing the regression of portal hypertension syndrome.
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Affiliation(s)
- Daniel Veldhuijzen van Zanten
- Department of Medicine, University of Alberta, 13-103 Clinical Sciences Building, 11350-83 Avenue, Edmonton, Alberta T6G 2G3, Canada
| | - Elizabeth Buganza
- Division of Gastroenterology, Zeidler Ledcor Centre, University of Alberta, 8540 112 St NW, Edmonton, Alberta T6G 2X8, Canada
| | - Juan G Abraldes
- Division of Gastroenterology, University of Alberta, 8540 112 St NW, 1-38 Zeidler Ledcor Centre, Edmonton, Alberta T6G 2X8, Canada.
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20
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Fortea JI, Puente Á, Cuadrado A, Huelin P, Pellón R, González Sánchez FJ, Mayorga M, Cagigal ML, García Carrera I, Cobreros M, Crespo J, Fábrega E. Congestive Hepatopathy. Int J Mol Sci 2020; 21:ijms21249420. [PMID: 33321947 PMCID: PMC7764741 DOI: 10.3390/ijms21249420] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 11/20/2020] [Accepted: 12/04/2020] [Indexed: 12/15/2022] Open
Abstract
Liver disease resulting from heart failure (HF) has generally been referred as “cardiac hepatopathy”. One of its main forms is congestive hepatopathy (CH), which results from passive venous congestion in the setting of chronic right-sided HF. The current spectrum of CH differs from earlier reports with HF, due to ischemic cardiomyopathy and congenital heart disease having surpassed rheumatic valvular disease. The chronic passive congestion leads to sinusoidal hypertension, centrilobular fibrosis, and ultimately, cirrhosis (“cardiac cirrhosis”) and hepatocellular carcinoma after several decades of ongoing injury. Contrary to primary liver diseases, in CH, inflammation seems to play no role in the progression of liver fibrosis, bridging fibrosis occurs between central veins to produce a “reversed lobulation” pattern and the performance of non-invasive diagnostic tests of liver fibrosis is poor. Although the clinical picture and prognosis is usually dominated by the underlying heart condition, the improved long-term survival of cardiac patients due to advances in medical and surgical treatments are responsible for the increased number of liver complications in this setting. Eventually, liver disease could become as clinically relevant as cardiac disease and further complicate its management.
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Affiliation(s)
- José Ignacio Fortea
- Gastroenterology and Hepatology Department, University Hospital Marqués de Valdecilla, 39008 Santander, Spain; (Á.P.); (A.C.); (P.H.); (I.G.C.); (M.C.); (J.C.); (E.F.)
- Group of Clinical and Translational Research in Digestive Diseases, Health Research Institute Marqués de Valdecilla (IDIVAL), 39011 Santander, Spain
- Biomedical Research Networking Center in Hepatic and Digestive Diseases (CIBERehd), 28029 Madrid, Spain
- Correspondence: or ; Tel./Fax: +34-(94)-220-2520 (ext. 72929)
| | - Ángela Puente
- Gastroenterology and Hepatology Department, University Hospital Marqués de Valdecilla, 39008 Santander, Spain; (Á.P.); (A.C.); (P.H.); (I.G.C.); (M.C.); (J.C.); (E.F.)
- Group of Clinical and Translational Research in Digestive Diseases, Health Research Institute Marqués de Valdecilla (IDIVAL), 39011 Santander, Spain
- Biomedical Research Networking Center in Hepatic and Digestive Diseases (CIBERehd), 28029 Madrid, Spain
| | - Antonio Cuadrado
- Gastroenterology and Hepatology Department, University Hospital Marqués de Valdecilla, 39008 Santander, Spain; (Á.P.); (A.C.); (P.H.); (I.G.C.); (M.C.); (J.C.); (E.F.)
- Group of Clinical and Translational Research in Digestive Diseases, Health Research Institute Marqués de Valdecilla (IDIVAL), 39011 Santander, Spain
- Biomedical Research Networking Center in Hepatic and Digestive Diseases (CIBERehd), 28029 Madrid, Spain
| | - Patricia Huelin
- Gastroenterology and Hepatology Department, University Hospital Marqués de Valdecilla, 39008 Santander, Spain; (Á.P.); (A.C.); (P.H.); (I.G.C.); (M.C.); (J.C.); (E.F.)
- Group of Clinical and Translational Research in Digestive Diseases, Health Research Institute Marqués de Valdecilla (IDIVAL), 39011 Santander, Spain
- Biomedical Research Networking Center in Hepatic and Digestive Diseases (CIBERehd), 28029 Madrid, Spain
| | - Raúl Pellón
- Radiology Department, University Hospital Marqués de Valdecilla, 39008 Santander, Spain; (R.P.); (F.J.G.S.)
| | | | - Marta Mayorga
- Pathological Anatomy Service, University Hospital Marqués de Valdecilla, 39008 Santander, Spain; (M.M.); (M.L.C.)
| | - María Luisa Cagigal
- Pathological Anatomy Service, University Hospital Marqués de Valdecilla, 39008 Santander, Spain; (M.M.); (M.L.C.)
| | - Inés García Carrera
- Gastroenterology and Hepatology Department, University Hospital Marqués de Valdecilla, 39008 Santander, Spain; (Á.P.); (A.C.); (P.H.); (I.G.C.); (M.C.); (J.C.); (E.F.)
| | - Marina Cobreros
- Gastroenterology and Hepatology Department, University Hospital Marqués de Valdecilla, 39008 Santander, Spain; (Á.P.); (A.C.); (P.H.); (I.G.C.); (M.C.); (J.C.); (E.F.)
| | - Javier Crespo
- Gastroenterology and Hepatology Department, University Hospital Marqués de Valdecilla, 39008 Santander, Spain; (Á.P.); (A.C.); (P.H.); (I.G.C.); (M.C.); (J.C.); (E.F.)
- Group of Clinical and Translational Research in Digestive Diseases, Health Research Institute Marqués de Valdecilla (IDIVAL), 39011 Santander, Spain
- Biomedical Research Networking Center in Hepatic and Digestive Diseases (CIBERehd), 28029 Madrid, Spain
| | - Emilio Fábrega
- Gastroenterology and Hepatology Department, University Hospital Marqués de Valdecilla, 39008 Santander, Spain; (Á.P.); (A.C.); (P.H.); (I.G.C.); (M.C.); (J.C.); (E.F.)
- Group of Clinical and Translational Research in Digestive Diseases, Health Research Institute Marqués de Valdecilla (IDIVAL), 39011 Santander, Spain
- Biomedical Research Networking Center in Hepatic and Digestive Diseases (CIBERehd), 28029 Madrid, Spain
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Wang SF, Huang YT, Huang CH, Chang SH, Lin CY. Fibrosis index predicts variceal bleeding and reduces need for nonselective beta-blocker in compensated cirrhosis with initial small esophageal varices without red-color sign. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:1223. [PMID: 33178755 PMCID: PMC7607085 DOI: 10.21037/atm-20-2444] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Accepted: 08/07/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Various non-invasive markers predicting hepatic fibrosis are poor predictors of esophageal variceal bleeding (EVB). Elastography performs well but resource-limited. Controversy for small EV prevention also exists. We aim to investigate if a non-invasive marker could predict subsequent EVB within 1 and 2 years in patients with compensated liver cirrhosis (CLC), initial small EV without red-color sign (RCS), without use of non-selective beta-blockers (NSBB) and endoscopic variceal ligation (EVL). This marker would also be tested if it could help reduce use of NSBB, thereby avoiding potential side effects and saving medical costs. METHODS In this retrospective cohort study, 6,803 CLC patients fulfilling the inclusion-exclusion criteria were enrolled between 2001 and 2018, and were followed-up for 1 year, 2 years. The primary outcomes were subsequent EVB within 1 and 2 years of enrollment. Another 281 CLC patients with NSBB use were compared for additional outcome analysis. RESULTS In total, 539 patients and 710 patients experienced EVB within 1 year and 2 years, respectively. The fibrosis index (FI) with cut-off value of 3.95 showed a negative predictive value (NPV) of 94.3% and an area under receiver operating characteristic (AUROC) of 62.95% for predicting subsequent EVB within 1 year. The EVB and mortality of patients with FI <3.95 and not taking NSBB were significantly lower than those of the other 3 groups. Similar results were demonstrated within 2 years. CONCLUSIONS In CLC patients with initial small EV and no RCS, low FI scores showed a high NPV and moderate AUROC in predicting subsequent EVB and mortalities, signifying clinically non-significant portal hypertension. Patients with low FI scores and not taking NSBB had significantly lowest EVB and mortality. The medical cost savings for cutting NSBB in these patients would be estimated at least $3 million per year in the U.S. Further randomized control trial study needed to validate this screening tool.
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Affiliation(s)
- Sheng-Fu Wang
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan
| | - Yu-Tung Huang
- Center for Big Data Analytics and Statistics, Department of Medical Research and Development, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan
| | - Chien-Hao Huang
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan
- Center for Big Data Analytics and Statistics, Department of Medical Research and Development, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan
- School of Medicine, College of Medicine, Chang-Gung University, Taoyuan
- Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan
| | - Shang-Hung Chang
- Center for Big Data Analytics and Statistics, Department of Medical Research and Development, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan
- School of Medicine, College of Medicine, Chang-Gung University, Taoyuan
- Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan
| | - Chun-Yen Lin
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan
- School of Medicine, College of Medicine, Chang-Gung University, Taoyuan
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22
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Zhang Y, Wang Z, Yue ZD, Zhao HW, Wang L, Fan ZH, Wu YF, He FL, Liu FQ. Accurate ultrasonography-based portal pressure assessment in patients with hepatocellular carcinoma. World J Gastrointest Oncol 2020; 12:931-941. [PMID: 32879669 PMCID: PMC7443839 DOI: 10.4251/wjgo.v12.i8.931] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Revised: 05/08/2020] [Accepted: 07/01/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Portal pressure is of great significance in the treatment of hepatocellular carcinoma (HCC), but direct measurement is complicated and costly; thus, non-invasive measurement methods are urgently needed.
AIM To investigate whether ultrasonography (US)-based portal pressure assessment could replace invasive transjugular measurement.
METHODS A cohort of 102 patients with HCC was selected (mean age: 54 ± 13 years, male/female: 65/37). Pre-operative US parameters were assessed by two independent investigators, and multivariate logistic analysis and linear regression analysis were conducted to develop a predictive formula for the portal pressure gradient (PPG). The estimated PPG predictors were compared with the transjugular PPG measurements. Validation was conducted on another cohort of 20 non-surgical patients.
RESULTS The mean PPG was 17.32 ± 1.97 mmHg. Univariate analysis identified the association of the following four parameters with PPG: Spleen volume, portal vein diameter, portal vein velocity (PVV), and portal blood flow (PBF). Multiple linear regression analysis was performed, and the predictive formula using the PVV and PBF was as follows: PPG score = 19.336 - 0.312 × PVV (cm/s) + 0.001 × PBF (mL/min). The PPG score was confirmed to have good accuracy with an area under the curve (AUC) of 0.75 (0.68-0.81) in training patients. The formula was also accurate in the validation patients with an AUC of 0.820 (0.53-0.83).
CONCLUSION The formula based on ultrasonographic Doppler flow parameters shows a significant correlation with invasive PPG and, if further confirmed by prospective validation, may replace the invasive transjugular assessment.
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Affiliation(s)
- Yu Zhang
- Department of Interventional Therapy, Peking University Ninth School of Clinical Medicine, Beijing Shijitan Hospital and Capital Medical University, Beijing 100038, China
| | - Zhong Wang
- Department of Interventional Therapy, Peking University Ninth School of Clinical Medicine, Beijing Shijitan Hospital and Capital Medical University, Beijing 100038, China
| | - Zhen-Dong Yue
- Department of Interventional Therapy, Peking University Ninth School of Clinical Medicine, Beijing Shijitan Hospital and Capital Medical University, Beijing 100038, China
| | - Hong-Wei Zhao
- Department of Interventional Therapy, Peking University Ninth School of Clinical Medicine, Beijing Shijitan Hospital and Capital Medical University, Beijing 100038, China
| | - Lei Wang
- Department of Interventional Therapy, Peking University Ninth School of Clinical Medicine, Beijing Shijitan Hospital and Capital Medical University, Beijing 100038, China
| | - Zhen-Hua Fan
- Department of Interventional Therapy, Peking University Ninth School of Clinical Medicine, Beijing Shijitan Hospital and Capital Medical University, Beijing 100038, China
| | - Yi-Fan Wu
- Department of Interventional Therapy, Peking University Ninth School of Clinical Medicine, Beijing Shijitan Hospital and Capital Medical University, Beijing 100038, China
| | - Fu-Liang He
- Department of Interventional Therapy, Peking University Ninth School of Clinical Medicine, Beijing Shijitan Hospital and Capital Medical University, Beijing 100038, China
| | - Fu-Quan Liu
- Department of Interventional Therapy, Peking University Ninth School of Clinical Medicine, Beijing Shijitan Hospital and Capital Medical University, Beijing 100038, China
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Ryou M, Stylopoulos N, Baffy G. Nonalcoholic fatty liver disease and portal hypertension. EXPLORATION OF MEDICINE 2020; 1:149-169. [PMID: 32685936 DOI: 10.37349/emed.2020.00011] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a substantial and growing problem worldwide and has become the second most common indication for liver transplantation as it may progress to cirrhosis and develop complications from portal hypertension primarily caused by advanced fibrosis and erratic tissue remodeling. However, elevated portal venous pressure has also been detected in experimental models of fatty liver and in human NAFLD when fibrosis is far less advanced and cirrhosis is absent. Early increases in intrahepatic vascular resistance may contribute to the progression of liver disease. Specific pathophenotypes linked to the development of portal hypertension in NAFLD include hepatocellular lipid accumulation and ballooning injury, capillarization of liver sinusoidal endothelial cells, enhanced contractility of hepatic stellate cells, activation of Kupffer cells and pro-inflammatory pathways, adhesion and entrapment of recruited leukocytes, microthrombosis, angiogenesis and perisinusoidal fibrosis. These pathological events are amplified in NAFLD by concomitant visceral obesity, insulin resistance, type 2 diabetes and dysbiosis, promoting aberrant interactions with adipose tissue, skeletal muscle and gut microbiota. Measurement of the hepatic venous pressure gradient by retrograde insertion of a balloon-tipped central vein catheter is the current reference method for predicting outcomes of cirrhosis associated with clinically significant portal hypertension and guiding interventions. This invasive technique is rarely considered in the absence of cirrhosis where currently available clinical, imaging and laboratory correlates of portal hypertension may not reflect early changes in liver hemodynamics. Availability of less invasive but sufficiently sensitive methods for the assessment of portal venous pressure in NAFLD remains therefore an unmet need. Recent efforts to develop new biomarkers and endoscopy-based approaches such as endoscopic ultrasound-guided measurement of portal pressure gradient may help achieve this goal. In addition, cellular and molecular targets are being identified to guide emerging therapies in the prevention and management of portal hypertension.
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Affiliation(s)
- Marvin Ryou
- Department of Medicine, Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Nicholas Stylopoulos
- Division of Endocrinology, Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA.,The Broad Institute of MIT and Harvard, Cambridge MA
| | - Gyorgy Baffy
- Department of Medicine, Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.,Department of Medicine, VA Boston Healthcare System, Harvard Medical School, Boston, MA
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24
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Comment on “Somatostatin as Inflow Modulator in Liver-transplant Recipients With Severe Portal Hypertension: A Randomized Trial”. Ann Surg 2019; 270:e95-e96. [PMID: 31567356 DOI: 10.1097/sla.0000000000003350] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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25
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Abstract
Idiopathic portal hypertension (IPH) and extrahepatic portal venous obstruction (EHPVO) are prototype noncirrhotic causes of portal hypertension (PHT), characterized by normal hepatic venous pressure gradient, variceal bleeds, and moderate to massive splenomegaly with preserved liver synthetic functions. Infections, toxins, and immunologic, prothrombotic and genetic disorders are possible causes in IPH, whereas prothrombotic and local factors around the portal vein lead to EHPVO. Growth failure, portal biliopathy, and minimal hepatic encephalopathy are long-term concerns in EHPVO. Surgical shunts and transjugular intrahepatic portosystemic shunt resolve the complications secondary to PHT. Meso-Rex shunt is now the standard-of-care surgery in children with EHPVO.
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Affiliation(s)
- Rajeev Khanna
- Department of Pediatric Hepatology, Institute of Liver & Biliary Sciences (ILBS), D-1, Vasant Kunj, New Delhi 110 070, India
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver & Biliary Sciences (ILBS), D-1, Vasant Kunj, New Delhi 110 070, India.
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26
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Kasztelan-Szczerbinska B, Cichoz-Lach H. Refractory ascites-the contemporary view on pathogenesis and therapy. PeerJ 2019; 7:e7855. [PMID: 31637125 PMCID: PMC6798865 DOI: 10.7717/peerj.7855] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Accepted: 09/09/2019] [Indexed: 12/14/2022] Open
Abstract
Refractory ascites (RA) refers to ascites that cannot be mobilized or that has an early recurrence that cannot be prevented by medical therapy. Every year, 5-10% of patients with liver cirrhosis and with an accumulation of fluid in the peritoneal cavity develop RA while undergoing standard treatment (low sodium diet and diuretic dose up to 400 mg/day of spironolactone and 160 mg/day of furosemide). Liver cirrhosis accounts for marked alterations in the splanchnic and systemic hemodynamics, causing hypovolemia and arterial hypotension. The consequent activation of renin-angiotensin and sympathetic systems and increased renal sodium re-absorption occurs during the course of the disease. Cirrhotic patients with RA have poor prognoses and are at risk of developing serious complications. Different treatment options are available, but only liver transplantation may improve the survival of such patients.
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Affiliation(s)
| | - Halina Cichoz-Lach
- Department of Gastroenterology with Endoscopy Unit, Medical University of Lublin, Poland
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27
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Vogt JC, Nishimura RA, Newman DB. Middle-aged Man With Exertional Dyspnea and Neck Fullness. JAMA Cardiol 2019; 4:1045-1046. [DOI: 10.1001/jamacardio.2019.1677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Affiliation(s)
- Joshua C. Vogt
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota
| | - Rick A. Nishimura
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota
| | - D. Brian Newman
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota
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28
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Abadía M, Montes ML, Ponce D, Froilán C, Romero M, Poza J, Hernández T, Fernández-Martos R, Olveira A, on behalf of the “La Paz Portal Hypertension” Study Group Investigators. Management of betablocked patients after sustained virological response in hepatitis C cirrhosis. World J Gastroenterol 2019; 25:2665-2674. [PMID: 31210717 PMCID: PMC6558437 DOI: 10.3748/wjg.v25.i21.2665] [Citation(s) in RCA: 3] [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: 02/16/2019] [Revised: 03/13/2019] [Accepted: 03/25/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Current guidelines do not address the post–sustained virological response management of patients with baseline hepatitis C virus (HCV) cirrhosis and oesophageal varices taking betablockers as primary or secondary prophylaxis of variceal bleeding. We hypothesized that in some of these patients portal hypertension drops below the bleeding threshold after sustained virological response, making definitive discontinuation of the betablockers a safe option.
AIM To assess the evolution of portal hypertension, associated factors, non-invasive assessment, and risk of stopping betablockers in this population.
METHODS Inclusion criteria were age > 18 years, HCV cirrhosis (diagnosed by liver biopsy or transient elastography > 14 kPa), sustained virological response after direct-acting antivirals, and baseline oesophageal varices under stable, long-term treatment with betablockers as primary or secondary bleeding prophylaxis. Main exclusion criteria were prehepatic portal hypertension, isolated gastric varices, and concomitant liver disease. Blood tests, transient elastography, and upper gastrointestinal endoscopy were performed. Hepatic venous pressure gradient (HVPG) was measured five days after stopping betablockers. Betablockers could be stopped permanently if gradient was < 12 mmHg, at the discretion of the attending physician.
RESULTS Sample comprised 33 patients under treatment with propranolol or carvedilol: median age 64 years, men 54.5%, median Model for End-Stage Liver Disease (MELD) score 9, Child-Pugh score A 77%, median platelets 77.000 × 103/µL, median albumin 3.9 g/dL, median baseline transient elastography 24.8 kPa, 88% of patients received primary prophylaxis. Median time from end of antivirals to gradient was 67 wk. Venous pressure gradient was < 12 mmHg in 13 patients (39.4%). In univariate analysis the only associated factor was a MELD score decrease from baseline. On endoscopy, variceal size regressed in 19/27 patients (70%), although gradient was ≥ 12 mmHg in 12/19 patients. The elastography area under receiver operating characteristic for HVPG ≥ 12 mmHg was 0.62. Betablockers were stopped permanently in 10/13 patients with gradient < 12 mmHg, with no bleeding episodes after a median follow-up of 68 wk.
CONCLUSION Portal hypertension dropped below the bleeding threshold in 39% of patients more than one year after antiviral treatment. Endoscopy and transient elastography are inaccurate for reliable detection of this change. Stopping betablockers permanently seems uneventful in patients with a gradient < 12 mmHg.
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Affiliation(s)
- Marta Abadía
- Servicio de Aparato Digestivo, Hospital Universitario La Paz, Madrid 28046, Spain
| | - María Luisa Montes
- Unidad VIH, Servicio de Medicina Interna, Hospital Universitario La Paz, Madrid 28046, Spain
| | - Dolores Ponce
- Servicio de Radiología, Hospital Universitario La Paz, Madrid 28046, Spain
| | - Consuelo Froilán
- Servicio de Aparato Digestivo, Hospital Universitario La Paz, Madrid 28046, Spain
| | - Miriam Romero
- Servicio de Aparato Digestivo, Hospital Universitario La Paz, Madrid 28046, Spain
| | - Joaquín Poza
- Servicio de Aparato Digestivo, Hospital Universitario La Paz, Madrid 28046, Spain
| | - Teresa Hernández
- Servicio de Radiología, Hospital Universitario La Paz, Madrid 28046, Spain
| | | | - Antonio Olveira
- Servicio de Aparato Digestivo, Hospital Universitario La Paz, Madrid 28046, Spain
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Mandorfer M, Hernández-Gea V, Reiberger T, García-Pagán JC. Hepatic Venous Pressure Gradient Response in Non-Selective Beta-Blocker Treatment—Is It Worth Measuring? ACTA ACUST UNITED AC 2019. [DOI: 10.1007/s11901-019-00469-x] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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30
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Baffy G. Potential mechanisms linking gut microbiota and portal hypertension. Liver Int 2019; 39:598-609. [PMID: 30312513 DOI: 10.1111/liv.13986] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Revised: 10/01/2018] [Accepted: 10/04/2018] [Indexed: 12/11/2022]
Abstract
Gut microbiota is the largest collection of commensal micro-organisms in the human body, engaged in reciprocal cellular and molecular interactions with the liver. This mutually beneficial relationship may break down and result in dysbiosis, associated with disease phenotypes. Altered composition and function of gut microbiota has been implicated in the pathobiology of nonalcoholic fatty liver disease (NAFLD), a prevalent condition linked to obesity, insulin resistance and endothelial dysfunction. NAFLD may progress to cirrhosis and portal hypertension, which is the result of increased intrahepatic vascular resistance and altered splanchnic circulation. Gut microbiota may contribute to rising portal pressure from the earliest stages of NAFLD, although the significance of these changes remains unclear. NAFLD has been linked to lower microbial diversity and weakened intestinal barrier, exposing the host to bacterial components and stimulating pathways of immune defence and inflammation. Moreover, disrupted host-microbial metabolic interplay alters bile acid signalling and the release of vasoregulatory gasotransmitters. These perturbations become prominent in cirrhosis, increasing the risk of clinically significant portal hypertension and leading to bacterial translocation, sepsis and acute-on-chronic liver failure. Better understanding of the gut-liver axis and identification of novel microbial molecular targets may yield specific strategies in the prevention and management of portal hypertension.
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Affiliation(s)
- Gyorgy Baffy
- Department of Medicine, VA Boston Healthcare System and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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Salman MA, Mansour DA, Balamoun HA, Elbarmelgi MY, Hadad KEE, Abo Taleb ME, Salman A. Portal venous pressure as a predictor of mortality in cirrhotic patients undergoing emergency surgery. Asian J Surg 2019; 42:338-342. [PMID: 30316666 DOI: 10.1016/j.asjsur.2018.09.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2018] [Revised: 09/03/2018] [Accepted: 09/17/2018] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVE Emergency surgery is a risk factor for mortality in cirrhotic patients. Portal hypertension is an essential feature of decompensated cirrhosis. This study aimed to assess the value of portal venous pressure (PVP) measurement in prediction of 1-month mortality in cirrhotic patients undergoing emergency laparotomy. METHODS This prospective study included 121 adults with liver cirrhosis subjected to an emergency laparotomy. Child-Turcotte-Pugh (CTP) score and model for end-stage liver disease (MELD) score were used for preoperative patient evaluation. PVP was measured directly at the beginning of surgery. Portal hypertension (PHT) is diagnosed when PVP is greater than 12 mmHg. The primary outcome measure was the risk of mortality within one month after surgery. RESULTS PVP ranged from 5 to 27 mmHg; 82 patients (67.8%) had PHT. Fifty-five patients (45.5%) died within 1 month. Mortality was significantly associated with increasing CTP Class, MELD score and PHT (p < 0.001 for all). PHT predicts mortality with a sensitivity of 83.6% and specificity of 92.8%. PHT was the only independent predictor of mortality (OR: 23.0, 95%CI: 8.9-59.4). CONCLUSION In patients with liver cirrhosis, emergency laparotomy carries a substantial risk of mortality within one month. Portal hypertension is an independent predictor of risk of mortality in these patients.
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Affiliation(s)
| | - Doaa Ahmed Mansour
- General Surgery Department, Kasralainy School of Medicine, Cairo University, Egypt.
| | - Hany Armia Balamoun
- General Surgery Department, Kasralainy School of Medicine, Cairo University, Egypt.
| | | | | | | | - Ahmed Salman
- Internal Medicine Department, Kasralainy School of Medicine, Cairo University, Egypt.
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Reiberger T, Bucsics T, Paternostro R, Pfisterer N, Riedl F, Mandorfer M. Small Esophageal Varices in Patients with Cirrhosis-Should We Treat Them? CURRENT HEPATOLOGY REPORTS 2018; 17:301-315. [PMID: 30546995 PMCID: PMC6267385 DOI: 10.1007/s11901-018-0420-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
PURPOSE OF REVIEW The natural history and classification systems of small varices (≤ 5 mm in diameter) in cirrhotic patients with portal hypertension are summarized. Studies that assessed the course of and therapeutic intervention for small varices are discussed. RECENT FINDINGS Current non-invasive methods show suboptimal sensitivity to detect small varices in patients with cirrhosis. Next to etiological therapy, hepatic venous pressure gradient (HVPG)-guided non-selective betablocker or carvedilol treatment has shown to impact on natural history of small varices. SUMMARY The main therapeutic focus in cirrhotic patients with small varices is the cure of the underlying etiology. The optimal management of small varices should include measurement of HVPG. A pharmacological decrease in HVPG by non-selective betablocker therapy of ≥ 10% reduces the risk of progression to large varices, first variceal bleeding, and hepatic decompensation. If HVPG is not available, we would recommend carvedilol 12.5 mg q.d. for treatment of small varices in compensated patients without severe ascites. Only if small esophageal varices (EV) are not treated or in hemodynamic non-responders, follow-up endoscopies should be performed in 1-2 years of intervals considering the activity of liver disease or if hepatic decompensation occurs.
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Affiliation(s)
- Thomas Reiberger
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
- Division of Gastroenterology & Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Theresa Bucsics
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
- Division of Gastroenterology & Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Rafael Paternostro
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
- Division of Gastroenterology & Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Nikolaus Pfisterer
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
- Division of Gastroenterology & Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Division of Gastroenterology, Krankenanstalt Rudolfstiftung, Vienna, Austria
| | - Florian Riedl
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
- Division of Gastroenterology & Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Division of Gastroenterology, Medicine II, Universitätsklinikum St. Pölten, St. Pölten, Austria
| | - Mattias Mandorfer
- Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
- Division of Gastroenterology & Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
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The Mexican consensus on the treatment of hepatitis C. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2018. [DOI: 10.1016/j.rgmxen.2017.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022] Open
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Aiza-Haddad I, Ballesteros-Amozurrutia A, Borjas-Almaguer OD, Castillo-Barradas M, Castro-Narro G, Chávez-Tapia N, Chirino-Sprung RA, Cisneros-Garza L, Dehesa-Violante M, Flores-Calderón J, Flores-Gaxiola A, García-Juárez I, González-Huezo MS, González-Moreno EI, Higuera-de la Tijera F, Kershenobich-Stalnikowitz D, López-Méndez E, Malé-Velázquez R, Marín-López E, Mata-Marín JA, Méndez-Sánchez N, Monreal-Robles R, Moreno-Alcántar R, Muñoz-Espinosa L, Navarro-Alvarez S, Pavia-Ruz N, Pérez-Ríos AM, Poo-Ramírez JL, Rizo-Robles MT, Sánchez-Ávila JF, Sandoval-Salas R, Torre A, Torres-Ibarra R, Trejo-Estrada R, Velarde-Ruiz Velasco JA, Wolpert-Barraza E, Bosques-Padilla F. The Mexican consensus on the treatment of hepatitis C. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2018; 83:275-324. [PMID: 29803325 DOI: 10.1016/j.rgmx.2017.11.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/08/2017] [Revised: 10/17/2017] [Accepted: 11/02/2017] [Indexed: 12/12/2022]
Abstract
The aim of the Mexican Consensus on the Treatment of HepatitisC was to develop clinical practice guidelines applicable to Mexico. The expert opinion of specialists in the following areas was taken into account: gastroenterology, infectious diseases, and hepatology. A search of the medical literature was carried out on the MEDLINE, EMBASE, and CENTRAL databases through keywords related to hepatitisC treatment. The quality of evidence was subsequently evaluated using the GRADE system and the consensus statements were formulated. The statements were then voted upon, using the modified Delphi system, and reviewed and corrected by a panel of 34 voting participants. Finally, the level of agreement was classified for each statement. The present guidelines provide recommendations with an emphasis on the new direct-acting antivirals, to facilitate their use in clinical practice. Each case must be individualized according to the comorbidities involved and patient management must always be multidisciplinary.
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Affiliation(s)
| | | | - O D Borjas-Almaguer
- Hospital Universitario «Dr. José Eleuterio González», Monterrey, Nuevo León, México
| | | | - G Castro-Narro
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | | | | | - L Cisneros-Garza
- Centro de Enfermedades Hepáticas del Hospital San José, Monterrey, Nuevo León, México
| | | | - J Flores-Calderón
- Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Ciudad de México, México
| | | | - I García-Juárez
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | | | - E I González-Moreno
- Hospital Universitario «Dr. José Eleuterio González», Monterrey, Nuevo León, México
| | | | | | - E López-Méndez
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - R Malé-Velázquez
- Instituto de Salud Digestiva y Hepática, Guadalajara, Jalisco, México
| | | | - J A Mata-Marín
- Hospital de Infectología del Centro Médico Nacional «La Raza», Ciudad de México, México
| | | | - R Monreal-Robles
- Hospital Universitario «Dr. José Eleuterio González», Monterrey, Nuevo León, México
| | | | - L Muñoz-Espinosa
- Hospital Universitario «Dr. José Eleuterio González», Monterrey, Nuevo León, México
| | | | - N Pavia-Ruz
- Hospital Infantil de México «Federico Gómez», Ciudad de México, México
| | - A M Pérez-Ríos
- Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, México
| | - J L Poo-Ramírez
- Clínica San Jerónimo de Salud Hepática y Digestiva, Ciudad de México, México
| | | | - J F Sánchez-Ávila
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | | | - A Torre
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
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Eshmuminov D, Leoni F, Schneider MA, Becker D, Muller X, Onder C, Hefti M, Schuler MJ, Dutkowski P, Graf R, Rudolf von Rohr P, Clavien PA, Bautista Borrego L. Perfusion settings and additives in liver normothermic machine perfusion with red blood cells as oxygen carrier. A systematic review of human and porcine perfusion protocols. Transpl Int 2018; 31:956-969. [PMID: 29928775 DOI: 10.1111/tri.13306] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Revised: 06/10/2018] [Accepted: 06/18/2018] [Indexed: 12/30/2022]
Abstract
Liver machine perfusion (MP) at normothermic temperature (NMP) is a promising way to preserve and evaluate extended criteria donor livers. Currently, no consensus exists in methodology and perfusion protocols. Here, the authors performed a systematic literature search to identify human and porcine studies reporting on liver NMP with red blood cells. A qualitative synthesis was performed concerning technical aspects of MP, fluid composition, gas supply, and liver positioning. Thirty-seven publications including 11 human and 26 porcine studies were considered for qualitative synthesis. Control mode, pressure, flow, perfusate additives, and targeted blood gas parameters varied across human as well as porcine studies. For future analyses, it is advisable to report flow adjusted to liver weight and exact pressure parameters including mean, systolic, and diastolic pressure. Parenteral nutrition and insulin addition was common. Parenteral nutrition included amino acids and/or glucose without lipids. Taurocholic acid derivatives were used as bile flow promoters. However, short-term human NMP without taurocholic acid derivatives seems to be possible. This finding is relevant due to the lack of clinical grade bile salts. Near physiological oxygen tension in the perfusate is doable by adjusting gas flows, while blood gas parameters regulation needs more detailed description.
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Affiliation(s)
- Dilmurodjon Eshmuminov
- Department of Surgery, Swiss HPB and Transplantation Center, University Hospital Zurich, Zurich, Switzerland
| | - Filippo Leoni
- Department of Surgery, Swiss HPB and Transplantation Center, University Hospital Zurich, Zurich, Switzerland
| | - Marcel André Schneider
- Department of Surgery, Swiss HPB and Transplantation Center, University Hospital Zurich, Zurich, Switzerland
| | - Dustin Becker
- Wyss Zurich - ETH Zurich/University of Zurich, Zurich, Switzerland
| | - Xavier Muller
- Department of Surgery, Swiss HPB and Transplantation Center, University Hospital Zurich, Zurich, Switzerland
| | - Christopher Onder
- Institute for Dynamic Systems and Control, ETH Zurich, Zurich, Switzerland
| | - Max Hefti
- Wyss Zurich - ETH Zurich/University of Zurich, Zurich, Switzerland
| | - Martin J Schuler
- Wyss Zurich - ETH Zurich/University of Zurich, Zurich, Switzerland
| | - Philipp Dutkowski
- Department of Surgery, Swiss HPB and Transplantation Center, University Hospital Zurich, Zurich, Switzerland
| | - Rolf Graf
- Department of Surgery, Swiss HPB and Transplantation Center, University Hospital Zurich, Zurich, Switzerland
| | | | - Pierre-Alain Clavien
- Department of Surgery, Swiss HPB and Transplantation Center, University Hospital Zurich, Zurich, Switzerland
| | - Lucia Bautista Borrego
- Department of Surgery, Swiss HPB and Transplantation Center, University Hospital Zurich, Zurich, Switzerland
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Origins of Portal Hypertension in Nonalcoholic Fatty Liver Disease. Dig Dis Sci 2018; 63:563-576. [PMID: 29368124 DOI: 10.1007/s10620-017-4903-5] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Accepted: 12/26/2017] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) advanced to cirrhosis is often complicated by clinically significant portal hypertension, which is primarily caused by increased intrahepatic vascular resistance. Liver fibrosis has been identified as a critical determinant of this process. However, there is evidence that portal venous pressure may begin to rise in the earliest stages of NAFLD when fibrosis is far less advanced or absent. The biological and clinical significance of these early changes in sinusoidal homeostasis remains unclear. Experimental and human observations indicate that sinusoidal space restriction due to hepatocellular lipid accumulation and ballooning may impair sinusoidal flow and generate shear stress, increasingly disrupting sinusoidal microcirculation. Sinusoidal endothelial cells, hepatic stellate cells, and Kupffer cells are key partners of hepatocytes affected by NAFLD in promoting endothelial dysfunction through enhanced contractility, capillarization, adhesion and entrapment of blood cells, extracellular matrix deposition, and neovascularization. These biomechanical and rheological changes are aggravated by a dysfunctional gut-liver axis and splanchnic vasoregulation, culminating in fibrosis and clinically significant portal hypertension. We may speculate that increased portal venous pressure is an essential element of the pathogenesis across the entire spectrum of NAFLD. Improved methods of noninvasive portal venous pressure monitoring will hopefully give new insights into the pathobiology of NAFLD and help efforts to identify patients at increased risk for adverse outcomes. In addition, novel drug candidates targeting reversible components of aberrant sinusoidal circulation may prevent progression in NAFLD.
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Tseng Y, Ma L, Luo T, Zeng X, Li N, Wei Y, Zhou J, Li F, Chen S. Non-invasive predictive model for hepatic venous pressure gradient based on a 3-dimensional computed tomography volume rendering technology. Exp Ther Med 2018; 15:3329-3335. [PMID: 29545851 PMCID: PMC5841049 DOI: 10.3892/etm.2018.5816] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2017] [Accepted: 11/17/2017] [Indexed: 12/14/2022] Open
Abstract
Portal hypertension secondary to liver cirrhosis may cause a number of life-threatening complications. The rupture of gastroesophageal varices is associated with a high mortality rate of 15–30%. Hepatic venous pressure gradient (HVPG) is an accurate reflection of disease severity, however this can only be assessed via an invasive interventional procedure. The aim of the present study was to explore a non-invasive method based on 3D computed tomography (CT) volume rendering technology to accurately predict HVPG. A total of 77 patients diagnosed with liver cirrhosis underwent HVPG examination in the present study and the appropriate clinical and radiological data were retrospectively reviewed. A 3D liver and spleen volume rendering was constructed for volume measurements. All non-invasive parameters were tested using univariate analysis and the resulting variables that were statistically significant (P<0.20) were used in the multivariate linear regression model. The HVPG predictive model was as follows: HVPG = 18.726 - 0.324 (albumin) + 1.57 (aminotransferase-to-platelet ratio index) + 0.004 (liver volume) (multivariate regression analysis, P=0.006). The corresponding area under receiver operating characteristic curve to identify clinically significant portal hypertension defined as HVPG ≥10 mmHg was 0.810 (95% confidence interval; 0.705–0.891), with an optimal cut-off value of 12.84, yielding a sensitivity of 80.36% a specificity of 76.19%. The results of the present study indicate that 3D CT volume rendering technology may have the potential to be used for non-invasive prediction of HVPG.
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Affiliation(s)
- Yujen Tseng
- Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
| | - Lili Ma
- Department of Endoscopy, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
| | - Tiancheng Luo
- Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
| | - Xiaoqing Zeng
- Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
| | - Na Li
- Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
| | - Yichao Wei
- Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
| | - Ji Zhou
- Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
| | - Feng Li
- Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
| | - Shiyao Chen
- Department of Gastroenterology, Endoscopy Center, Evidence-Based Medicine Center, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
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Pelegrina A, Martí J, Miquel R, Ferrer J, Hernández-Gea V, Diaz A, Nadal C, García-Valdecasas JC, Fuster J. Changes of liver hemodynamic and elastography parameters in patients with colorectal liver metastases receiving preoperative chemotherapy: "a note of caution". World J Surg Oncol 2017; 15:224. [PMID: 29246174 PMCID: PMC5732417 DOI: 10.1186/s12957-017-1290-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Accepted: 12/05/2017] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND New systemic chemotherapy agents have improved prognosis in patients with colorectal liver metastases (CLM), but some of them damage the liver parenchyma and ultimately increase postoperative morbidity and mortality after liver resection. The aims of our study were to determine the degree of hemodynamic and pathological liver injury in CLM patients receiving preoperative chemotherapy and to identify an association between these injuries and postoperative complications after liver resection. METHODS This is a prospective descriptive study of patients with CLM receiving preoperative chemotherapy before curative liver resection from November 2013 to June 2014. All patients had preoperative elastography and hepatic hemodynamic evaluation. We analyzed clinical preoperative data and postoperative outcomes after grouping the patients by chemotherapy type, development of sinusoidal obstructive syndrome (SOS), and development of major complications. RESULTS Eleven from the 20 patients included in the study received preoperative oxaliplatin-based chemotherapy (OBC). Nine patients had SOS at pathological analysis and five patients developed major complications. Patients receiving preoperative OBC had higher values of hepatic venous pressure gradient (HVPG) and developed more SOS and major complications. Patients developing SOS had higher values of HVPG and developed more major complications. Patients with major complications had higher values of HVPG, and patients with a HVPG of 5 mmHg or greater had more major complications than those under 5 mmHg (20 vs 80%, p = 0.005). CONCLUSIONS OBC and SOS impair liver hemodynamics in CLM patients. An increase in major complications after liver resection in these patients develops at subclinical HVPG levels.
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Affiliation(s)
- Amalia Pelegrina
- Liver Surgery and Transplant Unit, Department of Surgery, Institut de Malalties Digestives i Metabòliques Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Josep Martí
- Liver Surgery and Transplant Unit, Department of Surgery, Institut de Malalties Digestives i Metabòliques Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Rosa Miquel
- Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Madrid, Spain.,Department of Pathology, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain.,Institute of Liver Studies King's College Hospital, Denmark Hill, SE5 9RS, UK
| | - Joana Ferrer
- Liver Surgery and Transplant Unit, Department of Surgery, Institut de Malalties Digestives i Metabòliques Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain.,Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Madrid, Spain
| | - Virginia Hernández-Gea
- Barcelona Hemodynamics Laboratory, Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, University of Barcelona, Barcelona, Spain.,Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Madrid, Spain
| | - Alba Diaz
- Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Madrid, Spain.,Department of Pathology, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Cristina Nadal
- Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Madrid, Spain.,Institut de Malalties Hemato-Oncológiques Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Juan Carlos García-Valdecasas
- Liver Surgery and Transplant Unit, Department of Surgery, Institut de Malalties Digestives i Metabòliques Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain.,Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Madrid, Spain
| | - Josep Fuster
- Liver Surgery and Transplant Unit, Department of Surgery, Institut de Malalties Digestives i Metabòliques Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain. .,Network for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Madrid, Spain.
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Austrian consensus guidelines on the management and treatment of portal hypertension (Billroth III). Wien Klin Wochenschr 2017; 129:135-158. [PMID: 29063233 PMCID: PMC5674135 DOI: 10.1007/s00508-017-1262-3] [Citation(s) in RCA: 100] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2017] [Accepted: 08/22/2017] [Indexed: 12/14/2022]
Abstract
The Billroth III guidelines were developed during a consensus meeting of the Austrian Society of Gastroenterology and Hepatology (ÖGGH) and the Austrian Society of Interventional Radiology (ÖGIR) held on 18 February 2017 in Vienna. Based on international guidelines and considering recent landmark studies, the Billroth III recommendations aim to help physicians in guiding diagnostic and therapeutic strategies in patients with portal hypertension.
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EUS-guided intrahepatic portosystemic shunt with direct portal pressure measurements: a novel alternative to transjugular intrahepatic portosystemic shunting. Gastrointest Endosc 2017; 85:243-247. [PMID: 27468858 PMCID: PMC5287288 DOI: 10.1016/j.gie.2016.07.041] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2016] [Accepted: 07/01/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Transjugular intrahepatic portosystemic shunting involves the creation of a low-resistance channel between the portal vein (PV) and the hepatic vein (HV), and is routinely performed under angiography. The aims were to evaluate (1) safety and technical feasibility; (2) procedural duration; and (3) subjective workload assessment of EUS-guided intrahepatic portosystemic shunt (EIPS). METHODS Five Yorkshire pigs were used in the study. The HV or inferior vena cava (IVC) was identified using a linear-array echoendoscope and accessed with a 19-G FNA needle preloaded with a digital pressure wire. Mean pressure was recorded. The needle was advanced into the PV, where pressure measurements were again taken, and ultimately exchanged over a guidewire. A lumen-apposing metal stent was deployed under EUS and fluoroscopic guidance, with distal and proximal ends positioned inside the PV and HV (IVC), respectively. Dilation was performed, and pressure measurements repeated. The National Aeronautics and Space Administration (NASA) Task Load Index (TLI) was scored. Animals survived 2 weeks before necropsy. RESULTS EIPS was successful in 5 out of 5 pigs. Mean time required for EUS identification, needle access, pressure measurement, and stent placement was 43 (31-55) minutes. NASA TLI scores revealed moderate workload. Mean baseline pressure measurements were PV 7.0 (5-9) and HV/IVC 5.0 (3-7) mm Hg and PV 6.3 (5-7) and HV/IVC 6.0 (4-7) mm Hg after. All animals survived 2 weeks. No bleeding was seen on necropsy. CONCLUSIONS This study demonstrates the technical feasibility of EIPS using LAMS, with direct portal pressure measurement, in a survival model. In addition, the procedure was performed quickly with moderate technical demand.
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Mandorfer M, Reiberger T. Beta blockers and cirrhosis, 2016. Dig Liver Dis 2017; 49:3-10. [PMID: 27717792 DOI: 10.1016/j.dld.2016.09.013] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2016] [Revised: 09/09/2016] [Accepted: 09/19/2016] [Indexed: 12/11/2022]
Abstract
To date, non-selective beta blockers (NSBBs) are a cornerstone in the treatment of portal hypertension. During the last years, our understanding of the potential benefits of early initiation of NSBB treatment, their effects beyond the prevention of variceal bleeding (i.e., their non-hemodyamic effects), as well as potential detrimental effects in patients with advanced disease has continuously evolved. In addition, we have learned that not all NSBBs are equal. Due to its additional anti-α1-adrenergic activity, carvedilol has been shown to be more potent in decreasing portal pressure, but might lead to more pronounced decreases in systemic arterial pressure, when compared to conventional NSBBs. It might be particularly beneficial in 'early' portal hypertension, when potential detrimental effects on systemic hemodynamics are less critical. In contrast, there is increasing evidence that the use of carvedilol or high NSBB doses should be carefully scrutinized in patients with severe or refractory ascites. Our review summarizes the current knowledge on the use of NSBBs for preventing variceal bleeding and other decompensating events and provides guidance for their safe use in hemodynamically 'vulnerable' patient populations. Finally, we also highlight areas for further research.
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Affiliation(s)
- Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Austria.
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Austria
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Mandorfer M, Kozbial K, Schwabl P, Freissmuth C, Schwarzer R, Stern R, Chromy D, Stättermayer AF, Reiberger T, Beinhardt S, Sieghart W, Trauner M, Hofer H, Ferlitsch A, Ferenci P, Peck-Radosavljevic M. Sustained virologic response to interferon-free therapies ameliorates HCV-induced portal hypertension. J Hepatol 2016; 65:692-699. [PMID: 27242316 DOI: 10.1016/j.jhep.2016.05.027] [Citation(s) in RCA: 240] [Impact Index Per Article: 26.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2016] [Revised: 05/17/2016] [Accepted: 05/19/2016] [Indexed: 12/04/2022]
Abstract
BACKGROUND & AIMS We aimed to investigate the impact of sustained virologic response (SVR) to interferon (IFN)-free therapies on portal hypertension in patients with paired hepatic venous pressure gradient (HVPG) measurements. METHODS One hundred and four patients with portal hypertension (HVPG ⩾6mmHg) who underwent HVPG and liver stiffness measurement before IFN-free therapy (baseline [BL]) were retrospectively studied. Among 100 patients who achieved SVR, 60 patients underwent HVPG and transient elastography (TE) after antiviral therapy (follow-up [FU]). RESULTS SVR to IFN-free therapies significantly decreased HVPG across all BL HVPG strata: 6-9mmHg (BL: 7.37±0.28 vs. FU: 5.11±0.38mmHg; -2.26±0.42mmHg; p<0.001), 10-15mmHg (BL: 12.2±0.4 vs. FU: 8.91±0.62mmHg; -3.29±0.59mmHg; p<0.001) and ⩾16mmHg (BL: 19.4±0.73 vs. FU: 17.1±1.21mmHg; -2.3±0.89mmHg; p=0.018). In the subgroup of patients with BL HVPG of 6-9mmHg, HVPG normalized (<6mmHg) in 63% (12/19) of patients, while no patient progressed to ⩾10mmHg. Among patients with BL HVPG ⩾10mmHg, a clinically relevant HVPG decrease ⩾10% was observed in 63% (26/41); 24% (10/41) had a FU HVPG <10mmHg. Patients with Child-Pugh stage B were less likely to have a HVPG decrease (hazard ratio [HR]: 0.103; 95% confidence interval [CI]: 0.02-0.514; p=0.006), when compared to Child-Pugh A patients. In the subgroup of patients with BL CSPH, the relative change in liver stiffness (per %; HR: 0.972; 95% CI: 0.945-0.999; p=0.044) was a predictor of a HVPG decrease ⩾10%. The area under the receiver operating characteristic curve for the diagnosis of FU CSPH by FU liver stiffness was 0.931 (95% CI: 0.865-0.997). CONCLUSIONS SVR to IFN-free therapies might ameliorate portal hypertension across all BL HVPG strata. However, changes in HVPG seemed to be more heterogeneous among patients with BL HVPG of ⩾16mmHg and a HVPG decrease was less likely in patients with more advanced liver dysfunction. TE might be useful for the non-invasive evaluation of portal hypertension after SVR. LAY SUMMARY We investigated the impact of curing hepatitis C using novel interferon-free treatments on portal hypertension, which drives the development of liver-related complications and mortality. Cure of hepatitis C decreased portal pressure, but a decrease was less likely among patients with more pronounced hepatic dysfunction. Transient elastography, which is commonly used for the non-invasive staging of liver disease, might identify patients without clinically significant portal hypertension after successful treatment.
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Affiliation(s)
- Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Karin Kozbial
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Philipp Schwabl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Clarissa Freissmuth
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Rémy Schwarzer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Rafael Stern
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - David Chromy
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Albert Friedrich Stättermayer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Sandra Beinhardt
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Wolfgang Sieghart
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Harald Hofer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Arnulf Ferlitsch
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Peter Ferenci
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Markus Peck-Radosavljevic
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria.
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Mandorfer M, Reiberger T. Nonselective beta blockers in patients with ascites: implications of a nationwide study. Liver Int 2016; 36:1255-7. [PMID: 27507252 DOI: 10.1111/liv.13147] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Affiliation(s)
- Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Lab, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna Hepatic Hemodynamic Lab, Vienna, Austria
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Schulman AR, Thompson CC, Ryou M. EUS-guided portal pressure measurement using a digital pressure wire with real-time remote display: a novel, minimally invasive technique for direct measurement in an animal model. Gastrointest Endosc 2016; 83:817-20. [PMID: 26684600 PMCID: PMC4849408 DOI: 10.1016/j.gie.2015.11.038] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2015] [Accepted: 11/25/2015] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Hepatic venous pressure gradient (HVPG) currently serves as a surrogate for portal pressure measurement but has many limitations. We developed a novel technique for rapid and direct portal pressure measurements using a digital pressure wire delivered through an EUS-guided 22-gauge FNA needle. Our aims were to evaluate (1) the short-term safety and technical feasibility, (2) procedural duration and subjective workload assessment, and (3) accuracy compared with a transjugular criterion standard approach. METHODS The subjects were Yorkshire pigs, weighing 40 to 55 kg. The portal vein was identified by using a linear array echoendoscope and accessed with a commercially available 22-gauge FNA needle preloaded with a digital pressure wire. Access was confirmed by portal venography. Mean digital pressure measurements were recorded over 30 to 60 seconds, and the National Aeronautics and Space Administration Task Load Index was scored. The control measurements were conventional transjugular catheterization with a balloon occlusion catheter to obtain free and wedged hepatic pressures, with subsequent HVPG calculation. RESULTS The total time required for EUS identification and needle access of the portal vein, venography, and digital pressure measurement was less than 5 minutes in 5 of 5 pigs. The National Aeronautics and Space Administration Task Load Index scores revealed a low subjective workload. Baseline portal pressure measurements via EUS ranged from 5 mm Hg to 10 mm Hg (mean, 6.4 mm Hg). HVPG measurements were consistently ±1 mm Hg of portal pressure. CONCLUSIONS This study is the first report of direct EUS-guided portal pressure measurements by using a digital pressure wire. This method is routinely performed in minutes and provides real-time pressure tracings via wireless transmission. This novel approach for direct portal pressure measurement has the potential to replace traditional indirect HVPG measurements.
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Affiliation(s)
- Allison R. Schulman
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital, Boston, Massachusetts, USA
| | - Christopher C. Thompson
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital, Boston, Massachusetts, USA,Harvard Medical School, Boston, Massachusetts, USA
| | - Marvin Ryou
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital, Boston, Massachusetts, USA,Harvard Medical School, Boston, Massachusetts, USA
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Abstract
HCV coinfection has emerged as a major cause of non-AIDS-related morbidity and mortality in HIV-positive patients. As a consequence of the availability of modern combined antiretroviral therapy regimens, for optimally managed HIV/HCV-coinfected patients, the rates of liver fibrosis progression and the risk of liver-related events are increasingly similar to those of HCV-monoinfected patients. Moreover, our understanding of modulators of liver disease progression has greatly improved. In addition to immune status, endocrine, metabolic, genetic and viral factors are closely interrelated and might be important determinants of liver disease progression. In the last decade, a variety of serologic and radiographic tests for noninvasive liver disease staging have been extensively validated and are commonly used in HIV/HCV-coinfected patients. Sustained virologic response prevents end-stage liver disease, hepatocellular carcinoma, and death, with an even greater effect size in HIV-positive compared to HIV-negative patients. As interferon-free regimens achieve comparable rates of sustained virologic response in HIV-negative and HIV-positive patients, HIV/HCV-coinfected patients should from now on be referred to as a special, rather than a difficult-to-treat, population. Our comprehensive review covers all relevant aspects of HIV/HCV coinfection. Beginning with the changing epidemiology, it also provides new insights into the natural history of this condition and gives an overview on non-invasive techniques for the staging of liver disease. Furthermore, it outlines current recommendations for the treatment of acute hepatitis C and summarizes the unprecedented advances in the field of chronic hepatitis C therapy.
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