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Luo SH, Zhang HF, Liu W, Chu JG, Chen JY. Comparison of clinical outcomes of transjugular intrahepatic portosystemic shunt for refractory ascites and recurrent nonrefractory ascites. World J Hepatol 2025; 17:100451. [PMID: 40027559 PMCID: PMC11866158 DOI: 10.4254/wjh.v17.i2.100451] [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: 08/16/2024] [Revised: 12/04/2024] [Accepted: 01/23/2025] [Indexed: 02/20/2025] Open
Abstract
BACKGROUND Transjugular intrahepatic portosystemic shunt (TIPS) has an important role in the therapy of complications of portal-hypertension-related ascites. Various guidelines now indicate that TIPS is indicated for refractory ascites (RA), but TIPS for recurrent nonrefractory ascites (RNRA) achieved better clinical results. AIM To compare the clinical outcomes of TIPS for RA and RNRA in patients with complications related to portal hypertension. METHODS There were 863 patients divided into two main categories who underwent TIPS between September 2016 and September 2021. In category 1, patients had ascites without cirrhotic gastrointestinal bleeding. The patients were divided into group A (RNRA, n = 183) and group B (RA, n = 217). In category 2, patients had ascites and cirrhotic gastrointestinal bleeding. The patients were divided into group C (RNRA, n = 328) and group D (RA, n = 135). The clinical outcomes were probability of total hepatic impairment, incidence of hepatic encephalopathy (HE) and mortality. RESULTS The symptoms of ascites disappeared or were relieved within 1 week in group A compared with group B (P = 0.032), and in group C compared with group D (P = 0.027). By the end of follow-up, there were significant differences in the rate of RA in group A compared with group B (P = 0.016), and in group C compared with group D (P = 0.012). The probability of total hepatic impairment was significantly different in group A compared with group B (P = 0.024), and in group C compared with group D (P = 0.019). The total incidence of HE was significantly different in group A compared with group B (P = 0.008), and in group C compared with group D (P = 0.004). The 6-month, and 1-, 2- and 3-year survival rates were significantly different between groups A and B (all P < 0.05), and between groups C and D (all P < 0.05). CONCLUSION TIPS has a good therapeutic effect on ascites related to cirrhotic portal hypertension, and early TIPS for RNRA can prolong survival, and prevent progression to RA.
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Affiliation(s)
- Shi-Hua Luo
- Department of Gastroenterology and Hepatology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang 330006, Jiangxi Province, China
| | - Hui-Fang Zhang
- Department of Gastroenterology and Hepatology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang 330006, Jiangxi Province, China
| | - Wei Liu
- Department of Gastroenterology, The First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
| | - Jian-Guo Chu
- Department of Gastroenterology, Air Force Medical Center of PLA, Beijing 100142, China
| | - Jian-Yong Chen
- Department of Gastroenterology and Hepatology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang 330006, Jiangxi Province, China.
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Cizmic A, Rahmanian PB, Gassa A, Kuhn E, Mader N, Wahlers T. Prognostic value of ascites in patients with liver cirrhosis undergoing cardiac surgery. J Cardiothorac Surg 2023; 18:302. [PMID: 37898812 PMCID: PMC10613375 DOI: 10.1186/s13019-023-02393-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 09/30/2023] [Indexed: 10/30/2023] Open
Abstract
INTRODUCTION Mild or moderate liver cirrhosis increases the risk of complications after cardiac surgery. Ascites is the most common complication associated with liver cirrhosis. However, the prognostic value of ascites on postoperative morbidity and mortality after cardiac surgery remains uninvestigated. METHODS A retrospective study included 69 patients with preoperatively diagnosed liver cirrhosis who underwent cardiac surgery between January 2009 and January 2018 at the Department of Cardiothoracic Surgery, University Hospital of Cologne, Germany. The patients were divided into ascites and non-ascites groups based on preoperatively diagnosed ascites. Thirty-day mortality, postoperative complications, length of stay, and blood transfusions were analyzed postoperatively. RESULTS Out of the total of 69 patients, 14 (21%) had preoperatively diagnosed ascites. Ascites group had more postoperative complications such as blood transfusions (packed red blood cells: 78.6% vs. 40.0%, p = 0.010; fresh frozen plasma: 57.1% vs. 29.1%, p = 0.049), acute kidney injury (78.6% vs. 45.5%, p = 0.027), longer ICU stay (8 vs. 3 days, p = 0.044) with prolonged mechanical ventilation (57.1% vs. 23.6%, p = 0.015) and tracheotomy (28.6% vs. 3.6%, p = 0.003). The 30-day mortality rate was significantly higher in the ascites group than in the non-ascites group (35.7% vs. 5.5%, p = 0.002). CONCLUSION Ascites should be implemented in preoperative risk score assessments in cirrhotic patients undergoing cardiac surgery. Preoperative treatment of ascites could reduce the negative impact of ascites on postoperative complications after cardiac surgery. However, this needs to be thoroughly investigated in prospective randomized clinical trials.
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Affiliation(s)
- Amila Cizmic
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
| | | | - Asmae Gassa
- Department of Cardiothoracic Surgery, University Hospital of Cologne, Cologne, Germany
| | - Elmar Kuhn
- Department of Cardiothoracic Surgery, University Hospital of Cologne, Cologne, Germany
| | - Navid Mader
- Department of Cardiothoracic Surgery, University Hospital of Cologne, Cologne, Germany
| | - Thorsten Wahlers
- Department of Cardiothoracic Surgery, University Hospital of Cologne, Cologne, Germany
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Wang P, Fu J, Jin P, Zeng J, Miao X, Wang H, Ma Y, Feng X. A soft, bioinspired artificial lymphatic system for interactive ascites transfer. Bioeng Transl Med 2023; 8:e10567. [PMID: 37693063 PMCID: PMC10486333 DOI: 10.1002/btm2.10567] [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: 08/23/2022] [Revised: 06/02/2023] [Accepted: 06/10/2023] [Indexed: 09/12/2023] Open
Abstract
Low-flow removal of refractory ascites is critical to treating cirrhosis and digestive system tumor, and thus, commercial ascites pump emerged lately. The rigid structure of clinically available pumps rises complication rate and lack of flow rate monitoring hinders early warning of abnormalities. Herein, a soft artificial system was proposed inspired by lymph for interactive ascites transfer with great biocompatibility. The implantable system is composed of pump cavity, valves and tubes, which are soft and flexible made by silica gel. Therefore, the system possesses similar modulus to tissues and can naturally fit surrounding tissues. The cavity with magnetic tablet embedded is driven by extracorporeal magnetic field. Subsequently, the system can drain ascites with a top speed of 23 mL min-1, much higher than that of natural lymphatic system and state-of-art devices. Moreover, integrated flexible sensors enable wireless, real-time flow rate monitoring, serving as proof of treatment adjustment, detection and locating of malfunction at early stage. The liver function of experimental objects was improved, and no severe complications occurred for 4 weeks, which proved its safety and benefit to treatment. This artificial lymphatic system can serve as a bridge to recovery and pave the way for further clinical research.
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Affiliation(s)
- Peng Wang
- AML, Department of Engineering MechanicsTsinghua UniversityBeijingChina
- Laboratory of Flexible Electronics TechnologyTsinghua UniversityBeijingChina
| | - Ji Fu
- Institute of Flexible Electronics Technology of THU JiaxingZhejiangChina
| | - Peng Jin
- AML, Department of Engineering MechanicsTsinghua UniversityBeijingChina
- Laboratory of Flexible Electronics TechnologyTsinghua UniversityBeijingChina
| | - Jin Zeng
- Institute of Flexible Electronics Technology of THU JiaxingZhejiangChina
| | - Xiaohui Miao
- Institute of Flexible Electronics Technology of THU JiaxingZhejiangChina
| | - Heling Wang
- Laboratory of Flexible Electronics TechnologyTsinghua UniversityBeijingChina
- Institute of Flexible Electronics Technology of THU JiaxingZhejiangChina
| | - Yinji Ma
- AML, Department of Engineering MechanicsTsinghua UniversityBeijingChina
- Laboratory of Flexible Electronics TechnologyTsinghua UniversityBeijingChina
| | - Xue Feng
- AML, Department of Engineering MechanicsTsinghua UniversityBeijingChina
- Laboratory of Flexible Electronics TechnologyTsinghua UniversityBeijingChina
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Wang X, Li Y, Sun M, Guo G, Yang W, Hui Y, Yu Z, Li C, Fan X, Wang B, Zhang J, Zhao X, Jiang K, Sun C. Visceral Adiposity Associates With Malnutrition Risk Determined by Royal Free Hospital-Nutritional Prioritizing Tool in Cirrhosis. Front Nutr 2021; 8:766350. [PMID: 34901116 PMCID: PMC8652121 DOI: 10.3389/fnut.2021.766350] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2021] [Accepted: 10/25/2021] [Indexed: 11/13/2022] Open
Abstract
Mounting evidence has suggested the clinical significance of body composition abnormalities in the context of cirrhosis. Herein, we aimed to investigate the association between visceral adiposity and malnutrition risk in 176 hospitalized patients with cirrhosis. The adiposity parameters were obtained by computed tomography (CT) as follows: total adipose tissue index (TATI), visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI), and visceral to subcutaneous adipose tissue area ratio (VSR). Malnutrition risk was screened using Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT). Visceral adiposity was determined given a higher VSR based on our previously established cutoffs. Multivariate analysis implicated that male gender (OR = 2.884, 95% CI: 1.360–6.115, p = 0.006), BMI (OR = 0.879, 95% CI: 0.812–0.951, P = 0.001), albumin (OR = 0.934, 95% CI: 0.882–0.989, P = 0.019), and visceral adiposity (OR = 3.413, 95% CI: 1.344–8.670, P = 0.010) were independent risk factors of malnutrition risk. No significant difference was observed regarding TATI, SATI, and VATI among patients with low or moderate and high risk of malnutrition. In contrast, the proportion of male patients embracing visceral adiposity was higher in high malnutrition risk group compared with that in low or moderate group (47.27 vs. 17.86%, p = 0.009). Moreover, this disparity was of borderline statistical significance in women (19.05 vs. 5.88%, p = 0.061). Assessing adipose tissue distribution might potentiate the estimation of malnutrition risk in cirrhotics. It is pivotal to recognize visceral adiposity and develop targeted therapeutic strategies.
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Affiliation(s)
- Xiaoyu Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Yifan Li
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Mingyu Sun
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Gaoyue Guo
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Wanting Yang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Yangyang Hui
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Zihan Yu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Chaoqun Li
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Department of Internal Medicine, Tianjin Hexi Hospital, Tianjin, China
| | - Xiaofei Fan
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Bangmao Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Jie Zhang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Xingliang Zhao
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Kui Jiang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China
| | - Chao Sun
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China.,Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Tianjin, China.,Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, Tianjin, China
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Kronborg TM, Ytting H, Hobolth L, Møller S, Kimer N. Novel Anti-inflammatory Treatments in Cirrhosis. A Literature-Based Study. Front Med (Lausanne) 2021; 8:718896. [PMID: 34631742 PMCID: PMC8495012 DOI: 10.3389/fmed.2021.718896] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 08/26/2021] [Indexed: 12/11/2022] Open
Abstract
Liver cirrhosis is a disease characterised by multiple complications and a poor prognosis. The prevalence is increasing worldwide. Chronic inflammation is ongoing in liver cirrhosis. No cure for the inflammation is available, and the current treatment of liver cirrhosis is only symptomatic. However, several different medical agents have been suggested as potential healing drugs. The majority are tested in rodents, but few human trials are effectuated. This review focuses on medical agents described in the literature with supposed alleviating and curing effects on liver cirrhosis. Twelve anti-inflammatory, five antioxidative, and three drugs with effects on gut microflora and the LPS pathway were found. Two drugs not categorised by the three former categories were found in addition. In total, 42 rodent studies and seven human trials were found. Promising effects of celecoxib, aspirin, curcumin, kahweol, pentoxifylline, diosmin, statins, emricasan, and silymarin were found in cirrhotic rodent models. Few indices of effects of etanercept, glycyrrhizin arginine salt, and mitoquinone were found. Faecal microbiota transplantation is in increasing searchlight with a supposed potential to alleviate cirrhosis. However, human trials are in demand to verify the findings in this review.
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Affiliation(s)
- Thit Mynster Kronborg
- Gastro Unit, Medical Division, Amager-Hvidovre University Hospital, Hvidovre, Denmark
| | - Henriette Ytting
- Gastro Unit, Medical Division, Amager-Hvidovre University Hospital, Hvidovre, Denmark
| | - Lise Hobolth
- Gastro Unit, Medical Division, Amager-Hvidovre University Hospital, Hvidovre, Denmark
| | - Søren Møller
- Department of Clinical Physiology and Nuclear Medicine 260, Center for Functional and Diagnostic Imaging and Research, Amager-Hvidovre Hospital, Hvidovre, Denmark.,Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Nina Kimer
- Gastro Unit, Medical Division, Amager-Hvidovre University Hospital, Hvidovre, Denmark.,Novo Nordisk Foundation Centre for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
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Mahiliavets EV, Bozhko YN, Mahiliavets ON. Use of laparocentesis in the treatment of ascites in patients with liver cirrhosis. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF BELARUS, MEDICAL SERIES 2021; 18:362-374. [DOI: 10.29235/1814-6023-2021-18-3-362-374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Ascites occurs in about 60 % of patients with cirrhosis within 10 years of diagnosis. Laparocentesis is the preferred first-line therapy in patients with cirrhosis and massive tense ascites, allowing more than 5–6 liters of ascitic fluid to be removed at one time. The search for informative prognostic factors and the development of a method for predicting unfavorable outcomes of repeated laparocenteses in patients with ascites are relevant to timely refer this contingent of patients to perform TIPS.The purpose of the study was to develop and evaluate the diagnostic significance of a model for determining the probability of unfavorable outcomes of laparocentesis in patients with ascites on the background of liver cirrhosis.The results of treatment of 99 patients with the ascitic syndrome associated with intrahepatic portal hypertension were studied. The multiple regression analysis using the binary response logit model was carried out to calculate the prediction models. The analysis of the treatment results of patients with liver cirrhosis and ascites by the laparocentesis method revealed a number of factors that influence the onset of an unfavorable outcome. 2 models with the inclusion of initial variables are the most promising for forecasting. Model A includes: patient weight, serum-ascites total protein gradient, hyponatremia; model B: MELD-Na score, serum-ascitic total protein gradient, patient weight. The developed prediction method is highly informative, effective, easily applicable, and can be widely used in clinical practice.The ability to predict an unfavorable outcome in patients with portal hypertension and ascites after laparocentesis allows for a personalized approach in the process of timely selection of more effective, but also more expensive treatment methods, such as TIPS, which will help us to increase the therapy effectiveness and the survival of this cohort of patients.
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Haep N, Florentino RM, Squires JE, Bell A, Soto-Gutierrez A. The Inside-Out of End-Stage Liver Disease: Hepatocytes are the Keystone. Semin Liver Dis 2021; 41:213-224. [PMID: 33992030 PMCID: PMC8996333 DOI: 10.1055/s-0041-1725023] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Chronic liver injury results in cirrhosis and end-stage liver disease (ESLD) which represents a leading cause of death worldwide, affecting people in their most productive years of life. Medical therapy can extend life, but the only definitive treatment is liver transplantation (LT). However, LT remains limited by access to quality donor organs and suboptimal long-term outcomes. The degeneration from healthy-functioning livers to cirrhosis and ESLD involves a dynamic process of hepatocyte damage, diminished hepatic function, and adaptation. However, the mechanisms responsible for deterioration of hepatocyte function and ultimately hepatic failure in man are poorly understood. We review the current understanding of cirrhosis and ESLD as a dynamic process and outline the current mechanisms associated with the development of hepatic failure from the clinical manifestations to energy adaptations, regeneration, and regulation of nuclear transcription factors. A new generation of therapeutics could target stabilization of hepatocyte differentiation and function to avoid the need for transplantation in patients with cirrhosis and ESLD.
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Affiliation(s)
- Nils Haep
- Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | | | - James E. Squires
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania,Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Aaron Bell
- Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania,Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Alejandro Soto-Gutierrez
- Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania,Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania
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The Presence of Ascites Affects the Predictive Value of HVPG on Early Rebleeding in Patients with Cirrhosis. Gastroenterol Res Pract 2020; 2020:1329857. [PMID: 33299405 PMCID: PMC7710417 DOI: 10.1155/2020/1329857] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2020] [Revised: 08/09/2020] [Accepted: 11/12/2020] [Indexed: 12/12/2022] Open
Abstract
Background and Aims Gastroesophageal variceal bleeding is a serious complication of portal hypertension in cirrhotic patients and could be predicted by hepatic venous pressure gradient (HVPG). However, whether the presence of ascites affects the prognostic value of HVPG for patients with acute variceal bleeding is still unknown. This retrospective study is aimed at investigating the influence of ascites on predictive performance of HVPG for early rebleeding in cirrhotic patients with acute variceal bleeding. Methods In this retrospective study, a total of 148 patients with cirrhosis hospitalized for acute variceal bleeding who underwent HVPG measurement and endoscopic variceal ligation (EVL) for the prevention of rebleeding were included. The receiver operating characteristic curve (ROC) and logistical regression method were employed to analyze the predictive performance of HVPG for early rebleeding. The locally weighted scatterplot smoothing approach was adopted to assess the monotonicity between bleeding risk and HVPG. Results A significantly higher HVPG level was observed in patients with early rebleeding compared to patients without rebleeding in the nonascites cohort. When using HVPG to predict early rebleeding, there was a lower area under curve in the ascites cohort compared to the nonascites cohort. HVPG was recognized as a risk factor for early rebleeding by a logistic regression model only in the nonascites cohort. An overall monotonicity in the trend of change in HVPG and risk for early rebleeding was observed in the nonascites cohort solely. Conclusion The predictive value of HVPG for early rebleeding in patients with cirrhosis that developed acute variceal bleeding is hindered by the presence of ascites.
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Henkel S, Vetterly C, Squires R, McKiernan P, Squires J. Pharmacological management of portal hypertension and its complications in children: lessons from adults and opportunities for the future. Expert Opin Pharmacother 2020; 22:291-304. [PMID: 33074032 DOI: 10.1080/14656566.2020.1825685] [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: 11/09/2022]
Abstract
INTRODUCTION Portal hypertension (PHT) and its complications in children are thought to be distinct from adult PHT in several areas, including the underlying bio-physiology of a child in which PHT develops, but also because of the pediatric-specific etiologies that drive disease progression. And yet pharmacologic approaches to PHT in children are mainly based on adult data, modified for pediatric practice. This reality has been driven by a lack of data specific to children. AREAS COVERED The authors discuss current therapeutic approaches to PHT in children, including management of acute gastrointestinal variceal bleed, pharmacotherapy in prophylaxis, and established and emerging therapies to combat systemic co-morbidities that result from PHT. The few areas where pediatric-specific data exist are highlighted and the many gaps in knowledge that remain unresolved are underscored. EXPERT OPINION Despite decades of experience, optimal management of pediatric PHT remains undefined. In large part, this can be directly linked to a lack of basic understanding related to the unique pathophysiology and natural history that defines PHT in children. As a result, meaningful research into the utility and effectiveness of pharmacotherapy in children with PHT remains in its infancy. Large, multi-center, prospective studies will be needed to begin to establish an infrastructure on which a pediatric-specific research agenda can be built.
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Affiliation(s)
- Sarah Henkel
- Division of Gastroenterology and Hepatology, UPMC Children's Hospital of Pittsburgh , Pittsburgh, PA
| | - Carol Vetterly
- Department of Pharmacy, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Pharmacy , Pittsburgh, PA
| | - Robert Squires
- Division of Gastroenterology and Hepatology, UPMC Children's Hospital of Pittsburgh , Pittsburgh, PA
| | - Patrick McKiernan
- Division of Gastroenterology and Hepatology, UPMC Children's Hospital of Pittsburgh , Pittsburgh, PA
| | - James Squires
- Division of Gastroenterology and Hepatology, UPMC Children's Hospital of Pittsburgh , Pittsburgh, PA
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Feng H, Wang X, Zhao T, Mao L, Hui Y, Fan X, Lin L, Zhao W, Jiang K, Wang B, Yu Q, Zhang J, Sun C. Myopenic obesity determined by visceral fat area strongly predicts long-term mortality in cirrhosis. Clin Nutr 2020; 40:1983-1989. [PMID: 32977996 DOI: 10.1016/j.clnu.2020.09.016] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 09/06/2020] [Accepted: 09/11/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND The impact of changes in body composition has proved to correlate with outcomes in cirrhosis, however, numerous issues remain elusive. The present study aimed to investigate the prognostic value of myopenic obesity (MO) on long-term mortality in cirrhosis. METHODS We retrospectively analyzed 200 patients with cirrhosis. Body composition parameters including skeletal muscle index (SMI) and visceral fat area (VFA) were estimated by computed tomography images at the third lumbar vertebra level. We defined MO as a low SMI (male: SMI < 46.96 cm2/m2 and female: SMI < 32.46 cm2/m2) with BMI ≥ 25 kg/m2 or VFA ≥ 100 cm2 according to our previous publication. Patients were categorized into one of four body composition groups in terms of the presence or absence of myopenia and obesity. RESULTS On the basis of VFA or BMI, the four group comparison demonstrated the prognosis was poor in MO, followed by myopenic/nonobesity (MN), nonmyopenic/obesity and nonmyopenic/nonobesity, in that order (log-rank test). Multivariate Cox analysis identified that MO (HR 2.498; 95% CI, 1.214-5.140; P = 0.013), MN (HR 2.763; 95% CI, 1.244-6.134; P = 0.013), age (HR 3.035; 95% CI, 1.904-4.839; P < 0.001), neutrophil-to-lymphocyte ratio (HR 1.142; 95% CI, 1.082-1.207; P < 0.001) and MELD (HR 1.140; 95% CI, 1.066-1.219; P = 0.001) were independently associated with 2-year mortality according to VFA classification. CONCLUSIONS MO was an independent predictor of higher long-term mortality in cirrhosis. Prevention strategies by reducing visceral fat obesity rather than BMI should be the optimal target for MO management.
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Affiliation(s)
- Hongjuan Feng
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China; Department of Nutriology, Tianjin Third Central Hospital, Jintang Road 83, Hedong District, Tianjin, 300170, China
| | - Xiaoyu Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154,Heping District, Tianjin, 300052, China
| | - Tianming Zhao
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154,Heping District, Tianjin, 300052, China
| | - Lihong Mao
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154,Heping District, Tianjin, 300052, China
| | - Yangyang Hui
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154,Heping District, Tianjin, 300052, China
| | - Xiaofei Fan
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154,Heping District, Tianjin, 300052, China
| | - Lin Lin
- Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, East Street 6, Tianjin Airport Economic Area, Tianjin, 300308, China
| | - Wei Zhao
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154,Heping District, Tianjin, 300052, China
| | - Kui Jiang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154,Heping District, Tianjin, 300052, China
| | - Bangmao Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154,Heping District, Tianjin, 300052, China
| | - Qingxiang Yu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154,Heping District, Tianjin, 300052, China.
| | - Jie Zhang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154,Heping District, Tianjin, 300052, China.
| | - Chao Sun
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154,Heping District, Tianjin, 300052, China; Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, East Street 6, Tianjin Airport Economic Area, Tianjin, 300308, China.
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11
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Spur cell anemia related to alcoholic liver cirrhosis managed without liver transplantation: a case report and literature review. Clin J Gastroenterol 2020; 13:882-890. [PMID: 32472376 PMCID: PMC7259740 DOI: 10.1007/s12328-020-01142-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Accepted: 05/20/2020] [Indexed: 11/13/2022]
Abstract
Spur cell anemia is an acquired hemolytic anemia associated with liver cirrhosis and is characterized by the presence of increased large red blood cells, which are covered with spike-like projections that vary in width, length, and distribution. A 26-year-old man was referred to our hospital presenting with jaundice, lower limb edema, and dyspnea. The patient was subsequently diagnosed with spur cell anemia related to alcoholic liver cirrhosis. Spur cell anemia is an independent predictor of mortality in liver cirrhosis and has been associated with extremely poor prognosis. The most effective treatment for spur cell anemia is liver transplantation. As seen in the literature, the treatment of spur cell anemia without liver transplantation is quite challenging. This report highlights the importance of management and treatment strategies, including control of fluid retention, blood transfusion, plasma diafiltration, and administration of diuretics. Our treatment strategies might be useful in patients who are not candidate of liver transplantation or patients waiting for liver transplantation.
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12
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Surgical technique for placement of the automated low flow ascites pump (Alfapump). Langenbecks Arch Surg 2020; 405:117-123. [DOI: 10.1007/s00423-019-01822-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Accepted: 09/02/2019] [Indexed: 12/20/2022]
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Garbuzenko DV, Arefyev NO. Current approaches to the management of patients with cirrhotic ascites. World J Gastroenterol 2019; 25:3738-3752. [PMID: 31391769 PMCID: PMC6676543 DOI: 10.3748/wjg.v25.i28.3738] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Revised: 05/09/2019] [Accepted: 06/25/2019] [Indexed: 02/06/2023] Open
Abstract
This review describes current approaches to the management of patients with cirrhotic ascites in relation to the severity of its clinical manifestations. The PubMed database, the Google Scholar retrieval system, the Cochrane Database of Systematic Reviews, and the reference lists from related articles were used to search for relevant publications. Articles corresponding to the aim of the review were selected for 1991-2018 using the keywords: "liver cirrhosis," "portal hypertension," "ascites," "pathogenesis," "diagnostics," and "treatment." Uncomplicated and refractory ascites in patients with cirrhosis were the inclusion criteria. The literature analysis has shown that despite the achievements of modern hepatology, the presence of ascites is associated with poor prognosis and high mortality. The key to successful management of patients with ascites may be the stratification of the risk of an adverse outcome and personalized therapy. Pathogenetically based approach to the choice of pharmacotherapy and optimization of minimally invasive methods of treatment may improve the quality of life and increase the survival rate of this category of patients.
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Affiliation(s)
| | - Nikolay Olegovich Arefyev
- Department of Pathological Anatomy and Forensic Medicine, South Ural State Medical University, Chelyabinsk 454092, Russia
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Zhao D, Zhang G, Wang M, Zhang C, Li J. Portal pressure gradient and serum albumin: A simple combined parameter associated with the appearance of ascites in decompensated cirrhosis treated with transjugular intrahepatic portosystemic shunt. Clin Mol Hepatol 2019; 25:210-217. [PMID: 30897897 PMCID: PMC6589851 DOI: 10.3350/cmh.2018.0083] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Accepted: 01/07/2019] [Indexed: 12/15/2022] Open
Abstract
Background/Aims In recent years, greater assessment accuracy after transjugular intrahepatic portosystemic shunt (TIPS) to ascertain prognosis has become important in decompensated cirrhosis due to portal hypertension. The aim of this study was to assess the ratio of the portal pressure gradient (PPG) pre-TIPS (pre-PPG) to albumin (PPA), which influence ascites formation in cirrhotic patients in the 6-months after TIPS placement, and is a metric introduced in our study. Methods This was a retrospective cohort study of 58 patients with decompensated cirrhosis admitted to an academic hospital for the purpose of TIPS placement. We collected the following data: demographics, laboratory measures, and PPG during the TIPS procedure. Then we analyzed the association between the above data and ascites formation postTIPS in cirrhosis patients. Results Twenty-two patients with ascites and 28 without ascites were evaluated. Univariate and binary logistic regression analysis were adjusted for the following variables: to determine prognosis; Child-Pugh scores, lymphocyte count, platelet count, hemoglobin level, albumin level and pre-PPG or PPA. The outcome showed that PPA was better than pre-PPG and albumin for predicting ascites according to area under receiver operating characteristic curves and a statistical model that also showed PPA’s influence 6-months post-TIPS. Conclusions The combined measurement of pre-PPG and albumin, defined as PPA, may provide a better way to predict post-TIPS ascites in decompensated cirrhosis, which underlines the need for a large clinical trial in the future.
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Affiliation(s)
- Dongmei Zhao
- Department of Infectious Disease, the First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Guobing Zhang
- Department of Interventional Radiology, the First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Mingquan Wang
- Department of Interventional Radiology, the First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Chaoxue Zhang
- Department of Ultrasound, the First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Jiabin Li
- Department of Infectious Disease, the First Affiliated Hospital of Anhui Medical University, Hefei, China
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Kockerling D, Nathwani R, Forlano R, Manousou P, Mullish BH, Dhar A. Current and future pharmacological therapies for managing cirrhosis and its complications. World J Gastroenterol 2019; 25:888-908. [PMID: 30833797 PMCID: PMC6397723 DOI: 10.3748/wjg.v25.i8.888] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Revised: 01/17/2019] [Accepted: 01/26/2019] [Indexed: 02/06/2023] Open
Abstract
Due to the restrictions of liver transplantation, complication-guided pharmacological therapy has become the mainstay of long-term management of cirrhosis. This article aims to provide a complete overview of pharmacotherapy options that may be commenced in the outpatient setting which are available for managing cirrhosis and its complications, together with discussion of current controversies and potential future directions. PubMed/Medline/Cochrane Library were electronically searched up to December 2018 to identify studies evaluating safety, efficacy and therapeutic mechanisms of pharmacological agents in cirrhotic adults and animal models of cirrhosis. Non-selective beta-blockers effectively reduce variceal re-bleeding risk in cirrhotic patients with moderate/large varices, but appear ineffective for primary prevention of variceal development and may compromise renal function and haemodynamic stability in advanced decompensation. Recent observational studies suggest protective, haemodynamically-independent effects of beta-blockers relating to reduced bacterial translocation. The gut-selective antibiotic rifaximin is effective for secondary prophylaxis of hepatic encephalopathy; recent small trials also indicate its potential superiority to norfloxacin for secondary prevention of spontaneous bacterial peritonitis. Diuretics remain the mainstay of uncomplicated ascites treatment, and early trials suggest alpha-adrenergic receptor agonists may improve diuretic response in refractory ascites. Vaptans have not demonstrated clinical effectiveness in treating refractory ascites and may cause detrimental complications. Despite initial hepatotoxicity concerns, safety of statin administration has been demonstrated in compensated cirrhosis. Furthermore, statins are suggested to have protective effects upon fibrosis progression, decompensation and mortality. Evidence as to whether proton pump inhibitors cause gut-liver-brain axis dysfunction is conflicting. Emerging evidence indicates that anticoagulation therapy reduces incidence and increases recanalisation rates of non-malignant portal vein thrombosis, and may impede hepatic fibrogenesis and decompensation. Pharmacotherapy for cirrhosis should be implemented in accordance with up-to-date guidelines and in conjunction with aetiology management, nutritional optimisation and patient education.
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Affiliation(s)
- David Kockerling
- Liver Unit/Division of Integrative Systems Medicine and Digestive Disease, Imperial College London, London W2 1NY, United Kingdom
| | - Rooshi Nathwani
- Liver Unit/Division of Integrative Systems Medicine and Digestive Disease, Imperial College London, London W2 1NY, United Kingdom
| | - Roberta Forlano
- Liver Unit/Division of Integrative Systems Medicine and Digestive Disease, Imperial College London, London W2 1NY, United Kingdom
| | - Pinelopi Manousou
- Liver Unit/Division of Integrative Systems Medicine and Digestive Disease, Imperial College London, London W2 1NY, United Kingdom
| | - Benjamin H Mullish
- Liver Unit/Division of Integrative Systems Medicine and Digestive Disease, Imperial College London, London W2 1NY, United Kingdom
| | - Ameet Dhar
- Liver Unit/Division of Integrative Systems Medicine and Digestive Disease, Imperial College London, London W2 1NY, United Kingdom
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16
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Abstract
Ascites, a common complication of liver cirrhosis, eventually becomes refractory to diuretic therapy and sodium restriction in ∼10% of patients. Multiple pathogenetic factors are involved in the development of refractory ascites, which ultimately lead to renal hypoperfusion and avid sodium retention. Therefore, renal dysfunction commonly accompanies refractory ascites. Management includes continuation of sodium restriction, which needs frequent reviews for adherence; and regular large volume paracentesis of 5 L or more with albumin infusions to prevent the development of paracentesis-induced circulatory dysfunction. In the appropriate patients with reasonable liver reserve, the insertion of a transjugular intrahepatic portosystemic stent shunt (TIPS) can be considered, especially if the patient is relatively young and has no previous hepatic encephalopathy or anatomical contraindications, and no past history of renal or cardiopulmonary disease. Response to TIPS with ascites clearance can lead to nutritional improvement. Devices such as an automated low-flow ascites pump may be available in the future for ascites treatment. Patients with refractory ascites and poor liver function and/or renal dysfunction, should be referred for liver transplant, as this will eliminate the portal hypertension and liver dysfunction. Renal dysfunction prior to liver transplant largely improves after transplant without affecting post-transplant survival.
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Affiliation(s)
- Danielle Adebayo
- Division of Gastroenterology, Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, ON, Canada. These authors contributed equally: Danielle Adebayo, Shuet Fong Neong
| | - Shuet Fong Neong
- Division of Gastroenterology, Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, ON, Canada. These authors contributed equally: Danielle Adebayo, Shuet Fong Neong
| | - Florence Wong
- Division of Gastroenterology, Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, ON, Canada. These authors contributed equally: Danielle Adebayo, Shuet Fong Neong
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Nishikawa H, Yoh K, Enomoto H, Ishii N, Iwata Y, Nakano C, Takata R, Nishimura T, Aizawa N, Sakai Y, Ikeda N, Hasegawa K, Takashima T, Iijima H, Nishiguchi S. Extracellular Water to Total Body Water Ratio in Viral Liver Diseases: A Study Using Bioimpedance Analysis. Nutrients 2018; 10:nu10081072. [PMID: 30103528 PMCID: PMC6115798 DOI: 10.3390/nu10081072] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Revised: 08/07/2018] [Accepted: 08/10/2018] [Indexed: 02/06/2023] Open
Abstract
Aims: To investigate the relationship between extracellular water to total body water ratio (ECW/TBW) in bioimpedance analysis (BIA) and clinical parameters in hepatitis viruses related to liver diseases. Methods: ECW/TBW was compared in patients with hepatitis B virus (HBV, n = 85) and hepatitis C virus (HCV, n = 440) related liver diseases. We also examined factors linked to mild to severe overhydrated state (ECW/TBW ≥0.4). Results: The median ECW/TBW in the HCV group was 0.388 (range, 0.365–0.433), while that in the HBV group was 0.381 (range, 0.363–0.425) (p < 0.0001). In all cases (n = 525), for predicting F3 or more, ECW/TBW yielded the area under the receiver operating characteristics (AUROC, 0.74912) and for predicting F4, ECW/TBW yielded the AUROC (0.75517). Multivariate analysis showed that age, prothrombin time, serum albumin, and alanine aminotransferase were significant factors linked to ECW/TBW ≥0.4. In patients with FIB-4 index <2, ECW/TBW in the HCV group was significantly higher than that in the HBV group (p = 0.0188), while in patients with 2 ≤ FIB-4 index <4 and FIB-4 index ≥4, the difference in the two groups did not reach significance. Conclusion: ECW/TBW can be different according to hepatitis viruses. Overhydrated status can easily occur in the HCV group even in the non-LC status compared with the HBV group.
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Affiliation(s)
- Hiroki Nishikawa
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
| | - Kazunori Yoh
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
| | - Hirayuki Enomoto
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
| | - Noriko Ishii
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
| | - Yoshinori Iwata
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
| | - Chikage Nakano
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
| | - Ryo Takata
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
| | - Takashi Nishimura
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
| | - Nobuhiro Aizawa
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
| | - Yoshiyuki Sakai
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
| | - Naoto Ikeda
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
| | - Kunihiro Hasegawa
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
| | - Tomoyuki Takashima
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
| | - Hiroko Iijima
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
| | - Shuhei Nishiguchi
- Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
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