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Prevalence and prognostic impact of Hepatopulmonary syndrome in patients with unresectable hepatocellular carcinoma undergoing transarterial chemoembolization: a prospective cohort study

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Chinese Medical Journal 2022年第17期135卷 2043-2048页

作者： He Zhao Jiaywei Tsauo Xiaowu Zhang Huaiyuan Ma Ningna Weng Zhengqiang Yang Xiao Li Department of Interventional Therapy National Cancer Center/National Clinical Research Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBejing 100021China Department of Gastroenterology West China HospitalSichuan UniversityChengduSichuan 610041China

Background::To determine the prevalence and prognostic impact of Hepatopulmonary syndrome(HPS)in patients with unresectable hepatocellular carcinoma(HCC)undergoing transarterial chemoembolization(TACE).Methods::Fifty-four patients with unresectable HCC undergoing TACE between December 2014 and December 2015 were prospectively screened for HPS and were followed up for a maximum of 2 years or until the end of this prospective study.Results::Nineteen of the 54(35.2%)patients were considered to have HPS,including one(5.3%)with severe HPS,nine(47.4%)with moderate HPS,and nine(47.4%)with mild HPS.The median overall survival(OS)was 10.1(95%confidence interval[CI],3.9–16.3)months for patients with HPS and 15.1(95%CI,7.3–22.9)months for patients without HPS,which is not a significant difference(P=0.100).The median progression-free survival was also not significantly different between patients with and without HPS(5.2[95%CI,0–12.8]vs.8.4[95%CI,3.6–13.1]months;P=0.537).In the multivariable Cox regression analyses,carbon monoxide diffusing capacity(hazard ratio[HR]=1.033[95%CI,1.003–1.064];P=0.028)and Child-Pugh class(HR=1.815[95%CI,1.011–3.260];P=0.046)were identified to be the independent prognostic factors of OS.Conclusion::Mild or moderate HPS is common in patients with unresectable HCC undergoing TACE,but it does not seem to have a significant prognostic impact.

关键词： Hepatocellular carcinoma Hepatopulmonary syndrome Chemoembolization Therapeutic Prognosis Prevalence

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Clinical characteristics of Hepatopulmonary syndrome and hepatorenal syndrome and associated therapeutic potential of transjugular intrahepatic portosystemic shunt

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iLIVER 2023年第1期2卷 67-72页

作者： Haoyu Wang Fuquan Liu Peking University the 9th Clinical Medical College Shijitan Hospital Beijing 100038China

Hepatorenal syndrome(HRS)and Hepatopulmonary syndrome(HPS)are two serious complications of liver disease,causing damage not only to the liver but also to the kidneys,lungs,and heart.HRS and HPS affect the patient's circulatory and respiratory systems,with poor prognosis and high mortality in clinical practice.There is a lack of effective treatment other than liver transplantation.Transjugular intrahepatic portosystemic shunt(TIPS)is an effective tool to prolong the survival of patients with advanced liver disease and is mainly used to treat portal hypertension and ascites because it can effectively reduce portal pressure.Studies on the treatment of both of these complications with TIPS are limited and deserve further study because the therapeutic effects of TIPS have the potential to improve the prognosis of severe liver disease.This article reviews the clinical features of HRS and HPS,the consequences of these syndromes,and the potential mechanistic effects after TIPS intervention.

关键词： Hepatopulmonary syndrome Hepatorenal syndrome Transjugular intrahepatic portosystemic shunt

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Growth hormone ameliorates Hepatopulmonary syndrome and nonalcoholic steatohepatitis secondary to hypopituitarism in a child:A case report

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World Journal of Clinical Cases 2022年第18期10卷 6211-6217页

作者： Xiao-Yuan Zhang Ke Yuan Yan-Lan Fang Chun-Lin Wang Department of Pediatrics The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina

BACKGROUND Craniopharyngioma is a benign tumor that usually develops in children;however,it is located in the center and close to sensitive structures,such as the pituitary gland and hypothalamus.As the hypothalamus plays a crucial role in the homeostasis of anterior pituitary hormone synthesis,damage to the hypothalamus leads to multiple pituitary hormone deficiencies and non-alcoholic fatty liver disease,including Hepatopulmonary syndrome(HPS).HPS has limited treatment and poor prognosis.CASE SUMMARY A girl aged 13 years and 6 mo underwent surgery for craniopharyngioma 6 years prior.Right craniotomy was performed with total resection via the corpus callosum approach,and the tumor at the base was approximately 3.5 cm×3.5 cm×4.0 cm.At 1 year postoperatively,she exhibited abdominal distension and weakness,and the laboratory tests revealed fatty liver disease.Thereafter,she had not visited the outpatient clinic for 2 years.Two years ago,she developed decreased activity endurance,severe cyanosis,chest tightness,wheezing,and intermittent and recurrent low fever after mild physical labor.Hepatobiliary ultrasonography,liver biopsy,and contrast echocardiography of the right heart showed cirrhosis and multiple pituitary hormone deficiencies,indicating HPS.After 1 year of treatment with recombinant human growth hormone,the liver function and oxygenation improved;she did not undergo liver transplantation.CONCLUSION Craniopharyngioma surgery can easily cause hypopituitarism,which can lead to nonalcoholic steatohepatitis and HPS in children.Early growth hormone therapy is important to improve the prognosis of these diseases.

关键词： Craniopharyngioma Nonalcoholic fatty liver disease Hypopituitarism Hepatopulmonary syndrome Growth hormone Children Case report

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Serum Soluble Vascular Endothelial Growth Factor Receptor 1 as a Potential Biomarker of Hepatopulmonary syndrome

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Journal of Clinical and Translational Hepatology 2023年第5期11卷 1150-1160页

作者： Yu-Jie Li Xian-Feng Wu Dan-Dan Wang Peng Li Hao Liang Xiao-Yan Hu Jia-Qi Gan Yi-Zhu Sun Jun-Hong Li Jun Li Xin Shu Ai-Lin Song Chun-Yong Yang Zhi-Yong Yang Wei-Feng Yu Li-Qun Yang Xiao-Bo Wang Karine Belguise Zheng-Yuan Xia Bin Yi Department of Anesthesiology Southwest HospitalThird Military Medical University(Army Medical University)ChongqingChina Department of Anesthesiology Sichuan Academy of Medical Sciences&Sichuan Provincial People’s HospitalChengduSichuanChina Department of Anesthesiology Renji Hospital Affiliated to Shanghai Jiao Tong UniversityShanghaiChina LBCMCP Centre de Biologie Intégrative(CBI)Universitéde ToulouseCNRSUPSToulouseFrance Department of Anesthesiology Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina

Background and Aims:The results of basic research implicate the vascular endothelial growth factor(VEGF)family as a potential target of Hepatopulmonary syndrome(HPS).However,the negative results of anti-angiogenetic therapy in clinical studies have highlighted the need for markers for HPS.Therefore,we aimed to determine whether VEGF family members and their receptors can be potential biomarkers for HPS through clinical and experimental studies.Methods:Clinically,patients with chronic liver disease from two medical centers were enrolled and examined for HPS.Patients were divided into HPS,intrapulmonary vascular dilation[positive contrast-enhanced echocardiography(CEE)and normal oxygenation]and CEE-negative groups.Baseline information and perioperative clinical data were compared between HPS and non-HPS patients.Serum levels of VEGF family members and their receptors were measured.In parallel,HPS rats were established by common bile duct ligation.Liver,lung and serum samples were collected for the evaluation of pathophysiologic changes,as well as the expression levels of the above factors.Results:In HPS rats,all VEGF family members and their receptors underwent significant changes;however,only soluble VEGFR1(sFlt-1)and the sFlt-1/placental growth factor(PLGF)ratio were changed in almost the same manner as those in HPS patients.Furthermore,through feature selection and internal and external validation,sFlt-1 and the sFlt-1/PLGF ratio were identified as the most important variables to distinguish HPS from non-HPS patients.Conclusions:Our results from animal and human studies indicate that sFlt-1 and the sFlt-1/PLGF ratio in serum are potential markers for HPS.

关键词： Chronic liver disease Hepatopulmonary syndrome Placental growth factor Pathological pulmonary angiogenesis sFlt-1/PLGF ratio

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Hepatopulmonary syndrome and Liver Transplantation:A Recent Review of the Literature

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Journal of Clinical and Translational Hepatology 2016年第1期4卷 47-53页

作者： Caglar Cosarderelioglu Arif M.Cosar Merve Gurakar Nabil N.Dagher Ahmet Gurakar Johns Hopkins University School of Medicine Department of Gastroenterology/Hepatology Baltimore MD USA Virginia Commonwealth University School of Medicine Richmond VA USA Johns Hopkins University School of Medicine Department of Surgery/Liver Transplant Baltimore MD USA

A severe and common pulmonary vascular complication of liver disease is Hepatopulmonary syndrome (HPS).It is a triad of liver dysfunction and/or portal hypertension,intrapulmonary vascular dilatations,and increased alveolar-arterial oxygen gradient.Prevalence varies according to various study groups from 4%-47%.While the most common presenting symptom of HPS is dyspnea,it is usually asymptomatic,and thus all liver transplant candidates should be screened for its presence.Pulse oximetry is a useful screening method,but arterial blood gas examination is the gold standard.If there is an abnormal P (A-a)O2 gradient,microbubble transthoracic echocardiography should be done for diagnosis.Outcome is unpredictable,and there is currently no effective medical therapy.The only effective therapy is considered to be liver transplantation.Complete resolution of HPS after liver transplantation is seen within a year in most HPS patients.

关键词： Hepatopulmonary syndrome Pulmonary complications of cirrhosis Liver transplantation

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Progress in investigating the pathogenesis of Hepatopulmonary syndrome

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Hepatobiliary & Pancreatic Diseases International 2010年第4期9卷 355-360页

作者： Zhang, Zhao-Jie Yang, Chang-Qing Tongji Univ Sch Med Tongji Hosp Div Gastroenterol Shanghai 200065 Peoples R China Tongji Univ Sch Med Tongji Hosp Inst Digest Dis Shanghai 200065 Peoples R China

BACKGROUND: The pathogenesis of Hepatopulmonary syndrome is complicated and remains unknown. This review aims to provide an updated knowledge about the pathogenesis of the syndrome. DATA SOURCES: Five medical databases, MEDLINE, Science-Direct, OVID, Springer Link, and Wiley Inter Science were searched for articles on 'Hepatopulmonary syndrome', 'cirrhosis', 'angiogenesis', 'intestinal endotoxemia', 'nitric oxide', 'carbon monoxide', and other related subjects. RESULTS: Currently, imbalance between vasodilation and vasoconstriction, intestinal bacterial translocation, intestinal endotoxemia, and activation of the lung monocyte/macrophage system may play important roles in the pathogenesis of Hepatopulmonary syndrome. Recent studies found that angiogenesis is also an important factor in the pathogenesis of experimental Hepatopulmonary syndrome. CONCLUSION: Angiogenesis inhibition may be a potential approach for the treatment of Hepatopulmonary syndrome in the future.

关键词： Hepatopulmonary syndrome cirrhosis pathogenesis angiogenesis intestinal endotoxemia nitric oxide carbon monoxide

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New therapeutic strategy with extracorporeal membrane oxygenation for refractory Hepatopulmonary syndrome after liver transplant: A case report

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World Journal of Transplantation 2024年第1期14卷 210-214页

作者： Belinda Sánchez Pérez María Pérez Reyes Jose Aranda Narvaez Julio Santoyo Villalba Jose Antonio Perez Daga Claudia Sanchez-Gonzalez Julio Santoyo-Santoyo Hepatobiliary and Trasplantation Unit General and Digestive Surgery DepartmentUniversity Regional HospitalMalaga 29010Spain Department of General and Digestive Surgery Regional University Hospital of MalagaMalaga 29010Spain

BACKGROUND Due to the lack of published literature about treatment of refractory Hepatopulmonary syndrome(HPS)after liver transplant(LT),this case adds information and experience on this issue along with a treatment with positive outcomes.HPS is a complication of end-stage liver disease,with a 10%-30%incidence in cirrhotic patients.LT can reverse the physiopathology of this process and restore normal oxygenation.However,in some cases,refractory hypoxemia persists,and extracorporeal membrane oxygenation(ECMO)can be used as a rescue therapy with good results.CASE SUMMARY A 59-year-old patient with alcohol-related liver cirrhosis and portal hypertension was included in the LT waiting list for HPS.He had good liver function(Model for End-Stage Liver Disease score 12,Child-Pugh class B7).He had pulmonary fibrosis and a mild restrictive respiratory pattern with a basal oxygen saturation of 82%.The macroaggregated albumin test result was>30.Spirometry demonstrated a forced expiratory volume in one second(FEV1)of 78%,forced vital capacity(FVC)of 74%,FEV1/FVC ratio of 81%,diffusion capacity for carbon monoxide of 42%,and carbon monoxide transfer coefficient of 57%.He required domiciliary oxygen at 2 L/min(16 h/d).The patient was admitted to the intensive care unit(ICU)and extubated in the first 24 h,needing high-flow therapy and non-invasive ventilation and inhaled nitric oxide afterwards.Reintubation was needed after 72 h.Due to the non-response to supportive therapies,installation of ECMO was decided with progressive recovery after 9 d.Extubation was possible on the tenth day,maintaining a high-flow nasal cannula and de-escalating to conventional oxygen therapy after 48 h.He was discharged from ICU on postoperative day(POD)20 with a 90%-92%oxygen saturation.Steroid recycling was needed twice for acute rejection.The patient was discharged from hospital on POD 27 with no symptoms,with an 89%-90%oxygen saturation.CONCLUSION Due to the favorable results observed,ECMO could become the central axis of treatment of HPS and ref

关键词： Liver transplantation Hepatopulmonary syndrome Refractory hypoxemia Treatment Extracorporeal membrane oxygenation Case report

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Prospective evaluation of postoperative outcome after liver transplantation in Hepatopulmonary syndrome patients

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Chinese Medical Journal 2009年第21期122卷 2598-2602页

作者： YI Hui-min WANG Gen-shu YI Shu-hong YANG Yang CAI Chang-jie CHEN Gui-hua Liver Transplantation Center Third Affiliated Hospital of Sun Yat-sen University Guangzhou Guangdong 510630 China

Background Only a few reviews of small case series and individual case reports including a relatively small number of adult patients undergoing liver transplantation for Hepatopulmonary syndrome （HPS） are available, and there has been no prospective evaluation of the long-term outcome of HPS patients after orthotopic liver transplantation （OLT）. The aim of this study was to determine the frequency of HPS in OLT patients with chronic end-stage liver-disease, and the short-term and long-term postoperative outcome of HPS patients after OLT. Methods This prospective study included 31 HPS and 30 control, non-HPS patients. The preoperative conditions were similar between the two groups. Twenty-six of 31 HPS patients and all of the non-HPS patients underwent OLT. Standardized methods, such as arterial blood gas at room air and ^99m-technetium macroaggregated albumin （^99mTc MAA） lung and brain perfusion scanning were performed for the diagnosis of HPS. Patients were followed after OLT. Results The incidence of HPS in OLT patients was 9.3% [26/279]. Hypoxemia in HPS was obviously improved with a normalized shunt of ^99mTC MAA in the lungs after OLT. The immediate postoperative survival rate [within 28 days after OLT） of HPS was 76.9% （20/26）. The one year survival was 61.5% （16/26） and four-year survival was 57.7% （15/26）; much higher than HPS patients without OLT （0）. But high postoperative morbidity and mortality were observed in HPS patients whose death occurred within 3 months of OLT due to complications summarized in this study. Conclusions Liver transplantation was an effective treatment for HPS. But the postoperative mortality rate following OLT in HPS patients was still much higher than that of patients without HPS.

关键词： Hepatopulmonary syndrome liver transplantation survival mortality

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Clinical Significance of a Myeloperoxidase Gene Polymorphism and Inducible Nitric Oxide Synthase Expression in Cirrhotic Patients with Hepatopulmonary syndrome

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2010年第4期30卷 437-442页

作者：王燕颖王文多张艳霞赵欣杨东亮 Department of Gastroenterology Heilongjiang Provincial Hospital Department of Infectious Disease Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

The clinical significance of a myeloperoxidase (MPO) gene polymorphism and inducible nitric oxide synthase (iNOS) expression in cirrhotic patients with Hepatopulmonary syndrome (HPS) was explored. Enrolled subjects were divided into three groups according to their disease/health conditions: the HPS group (cirrhotic patients with HPS; n=63), the non-HPS group (cirrhotic patients without HPS; n=182), and the control group (healthy subjects without liver disease; n=35). The distribution of the MPO–463 G/A genotype and its relationship with iNOS expression in a typical cell block from ascitic fluid were detected by immunohistochemistry and polymerase chain reaction-restricted fragment length polymorphism analysis (PCR-RFLP). In the HPS group, the partial pressure of oxygen in blood and ascitic fluid was significantly decreased (8.95±1.58 kPa and 6.81±0.95 kPa, respectively; both P<0.01), while the partial pressure of carbon dioxide significantly increased (4.62±0.20 kPa and 5.92±0.45 kPa, respectively; P<0.01). MPO and iNOS levels were significantly increased in the HPS group as compared with the non-HPS group. These increases were even more remarkable in ascitic fluid (41.36±11.62 and 13.23±4.81 μg/L; 10.27± 3.20 and 4.95±1.12 μg/L) than in blood (16.66±5.24 and 4.87±1.73 μg/L; 5.79±2.31 and 2.35±0.84 μg/L). The distribution of the MPO genotypes GG, GA, and AA were 76.2%, 22.2% and 1.6% in the HPS group, and 57.7%, 37.9% and 4.4% in the non-HPS group (P<0.05). The expression of iNOS was significantly higher in patients with the G alleles (G/G and G/A) (61.54%, 48/78) than in patients with A alleles (G/A and A/A) (38.46%, 30/78) (P<0.01). It was suggested that the expression levels of iNOS and MPO were correlated with HPS-induced hypoxemia. The MPO-463 G/A mutation might be a protective factor that prevents the development of HPS. The MPO might be involved in the regulation of iNOS expression. In humans, MPO pathways, the iNOS/NO system, and their interaction might have an impact on the occurrence and development of

关键词： Hepatopulmonary syndrome myeloperoxidase inducible nitric oxide synthase polymorphism

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Growth hormone cocktail improves Hepatopulmonary syndrome secondary to hypopituitarism:A case report

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World Journal of Clinical Cases 2021年第18期9卷 4852-4858页

作者： Wen Ji Min Nie Jiang-Feng Mao Hong-Bing Zhang Xi Wang Xue-Yan Wu Department of Endocrinology Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Endocrinology Peking Union Medical College HospitalBeijing 100730China Department of Physiology Collaborative Innovation Center for Cancer MedicineInstitute of Basic Medical Sciences and School of Basic MedicineBeijing 100005China

BACKGROUND Metabolic associated fatty liver disease frequently occurs in patients with hypopituitarism and growth hormone(GH)deficiency.Some patients may develop to Hepatopulmonary syndrome(HPS).HPS has a poor prognosis and liver transplantation is regarded as the only approach to cure it.CASE SUMMARY A 29-year-old man presented with progressive dyspnea for 1 mo.At the age of 10 years,he was diagnosed with panhypopituitarism associated with pituitary stalk interruption syndrome.Levothyroxine and hydrocortisone were given since then.To achieve ideal height,he received GH treatment for 5 years.The patient had an oxygen saturation of 78%and a partial pressure of arterial oxygen of 37 mmHg with an alveolar–arterial oxygen gradient of 70.2 mmHg.Abdominal ultrasonography showed liver cirrhosis and an enlarged spleen.Perfusion lung scan demonstrated intrapulmonary arteriovenous right-to-left shunt.HPS(very severe)was our primary consideration.His hormonal evaluation revealed GH deficiency and hypogonadotropic hypogonadism when thyroid hormone,cortisol,and desmopressin were administrated.After adding with long-acting recombinant human GH and testosterone for 14 mo,his liver function and hypoxemia were improved and his progressive liver fibrosis was stabilized.He was off the waiting list of liver transplantation.CONCLUSION Clinicians should screen HPS patients'anterior pituitary function as early as possible and treat them primarily with GH cocktail accordingly.

关键词： Hepatopulmonary syndrome Testosterone Growth hormone Intrapulmonary shunt Insulin-like growth factor Case report

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