Humans ; Hepatopulmonary Syndrome/surgery* ; Liver Transplantation/adverse effects* ; Extracorporeal Membrane Oxygenation/adverse effects* ; Postoperative Complications ; Patients

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.
Humans ; Carcinoma, Hepatocellular/pathology* ; Chemoembolization, Therapeutic ; Prospective Studies ; Liver Neoplasms/pathology* ; Prognosis ; Hepatopulmonary Syndrome/therapy* ; Prevalence ; Treatment Outcome ; Retrospective Studies

The present paper was aimed to study the role of spleen tyrosine kinase (Syk) in angiogenesis in hepatopulmonary syndrome (HPS) and the underlying mechanism. Sprague Dawley (SD) rats were randomly divided into three groups: sham operation group (sham group), common bile duct ligation (CBDL) 5-week group (5W group) and R788 intervention group (R788 group). HPS model was established by CBDL. Rats in R788 group were intraperitoneally injected with R788 (20 mg/kg) once daily to week 5 after CBDL operation. The protein expression levels and distribution of Syk, p-Erk1/2, and p-Akt in lung tissue were detected by Western blot and immunohistochemistry. Immunofluorescence staining was used to observe the location of Syk expression and the number of angiogenesis in lung tissue. The results showed that, compared with sham group, 5W group exhibited up-regulated protein expression level of Syk, increased phosphorylation levels of Erk1/2 and Akt, and increased number of pulmonary microvessels. Compared with 5W group, R788 group exhibited down-regulated protein expression level of Syk, decreased phosphorylation levels of Erk1/2 and Akt, and decreased number of pulmonary microvessels. These results suggest that Syk may promote pulmonary angiogenesis in HPS model rats by activating downstream Erk1/2 and Akt signaling pathways, which provides a theoretical basis and potential drug therapeutic targets for the clinical treatment of HPS.
Animals ; Disease Models, Animal ; Hepatopulmonary Syndrome ; Lung ; Rats ; Rats, Sprague-Dawley ; Syk Kinase

Hypothalamic obesity is often complicated in patients with craniopharyngioma due to hypothalamic damage by the tumor itself, treatment modalities, and associated multiple pituitary hormone deficiency. Hypothalamic obesity causes secondary diseases such as nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus (DM). We report a 19-year-old female who was diagnosed with craniopharyngioma, developed hypothalamic obesity after tumor resection, and progressed to hepatopulmonary syndrome. She manifested NAFLD 1 year after tumor resection. Two years later, the craniopharyngioma recurred, and she underwent a second resection. Three years after her second operation, she was diagnosed with type 2 DM, after which she did not visit the outpatient clinic for 2 years and then suddenly reappeared with a weight loss of 25.8 kg that had occurred over 21 months. One month later, she presented to the Emergency Department with dyspnea. Laboratory findings revealed liver dysfunction and hypoxia with increased alveolar artery oxygen gradient. Liver biopsy showed portal hypertension and micronodular cirrhosis. Echocardiography and a lung perfusion scan demonstrated a right to left shunt. She was finally diagnosed with hepatopulmonary syndrome and is currently awaiting a donor for liver transplantation. Patients surviving craniopharyngioma need to be followed up carefully to detect signs of hypothalamic obesity and monitored for the development of other comorbidities such as DM, NAFLD, and hepatopulmonary syndrome.
Ambulatory Care Facilities ; Anoxia ; Arteries ; Biopsy ; Comorbidity ; Craniopharyngioma* ; Diabetes Mellitus ; Dyspnea ; Echocardiography ; Emergency Service, Hospital ; Female ; Fibrosis ; Hepatopulmonary Syndrome* ; Humans ; Hypertension, Portal ; Hypothalamus ; Liver ; Liver Diseases ; Liver Transplantation ; Lung ; Non-alcoholic Fatty Liver Disease* ; Obesity* ; Oxygen ; Perfusion ; Tissue Donors ; Weight Loss ; Young Adult

Pulmonary arteriovenous fistula (PAVF) is a complication of the Glenn shunt. A 57-year-old tetralogy of Fallot (TOF) patient, who had undergone a Glenn shunt and TOF total correction, complained of dyspnea and cyanosis. PAVFs were present in the right lung, and right lung perfusion was nearly absent. After coil embolization, takedown of the Glenn shunt, and reconstruction of the right pulmonary artery, the patient's symptoms were relieved. Extrapulmonary radioisotope uptake caused by the PAVFs shown in lung perfusion scans decreased, and right lung perfusion increased gradually. Although the development and resolution of PAVFs after a Glenn shunt have been reported in the pediatric population, this may be the first report on this change in old age.
Arteriovenous Fistula* ; Cyanosis ; Dyspnea ; Embolization, Therapeutic ; Fontan Procedure ; Hepatopulmonary Syndrome ; Humans ; Lung ; Middle Aged* ; Perfusion ; Pulmonary Artery ; Tetralogy of Fallot*

OBJECTIVETo investigate the molecular mechanism of tumor necrosis factor-alpha (TNF-a) monoclonal antibody (McAb) in hepatopulmonary syndrome using a rat model.

METHODSSixty adult male Sprague-Dawley rats, weighing 250 ± 25 g, were randomized to a sham operation group, a common bile duct ligation (CBDL) group, or a CBDL+TNF-alphat McAb treatment group. The CBDL operation group was further divided into five subgroups, and the CBDL+TNF-alpha McAb treatment group was further divided into four subgroups. After the experimental period, all rats were sacrificed for excision of lung and liver tissues. Hematoxylin-eosin (HE) and Masson staining were performed to observe the extent of liver fibrosis,and HE staining was used to histopathologically assess changes in the lung tissue. Immunohistochemistry and western blotting were used to investigate the changes in expression levels of FAK, p-FAK and PTEN in lung.

RESULTSThe extent of inflammatory responses and fibrosis in the liver was significantly lower in the CBDL+TNF-alpha McAb treatment group as compared to those in the CBDL group. The inflammatory responses in the lung were also significantly lower in the CBDL+TNF-alpha McAb treatment group as compared to that in the CBDL group. The CBDL+TNF-alpha McAb treatment group also showed less extensive distribution of FAK and p-FAK protein in lung tissues,but more extensive distribution of PTEN protein.

CONCLUSIONFAK and PTEN are associated with hepatopulmonary syndrome in rats. The therapeutic effect of TNF-alpha McAb may involve modulation of the expression of FAK and PTEN.

Animals ; Antibodies, Monoclonal ; Blotting, Western ; Common Bile Duct ; Hepatopulmonary Syndrome ; Immunohistochemistry ; Ligation ; Liver Cirrhosis ; Lung ; Male ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha

OBJECTIVETo determine the changes in levels of D-dimer, prothrombin time (PT), fibrinogen (Fib), CD4 and CD8 in relation to hepatopulmonary syndrome (HPS) by using a rat model system and to assess the association with pathologic changes in lung.

METHODSForty male Sprague-Dawley rats were divided into equal groups for modeling of cirrhosis and HPS. The two groups were assessed by blood gas analysis, standard biochemical tests to measure D-dimer, PT, Fib, CD4 and CD8, and pathological examination of lung tissues.

RESULTSThe HPS rats showed significantly lower PaO2 than the cirrhosis rats (58.20+/-3.19 mmHg vs. 85.00+/-2.53 mmHg, P = 0.000). The HPS rats showed significantly higher levels of D-dimer, Fib and CD8 than the cirrhosis rats (0.39+/-0.09 mg/ml vs. 0.25+/-0.05 mg/ml, P = 0.000; 1.77+/-0.10 g/L vs. and 1.49+/-0.09 g/L, P = 0.010; 32.32+/-4.45/mm3 vs. 20.13+/-6.09/mm3, P = 0.014). The HPS rats showed significantly lower levels of PT, CD4 and CD4/CD8 than the cirrhosis rats (14.86+/-1.04 s vs. 16.23+/-0.75 s, P = 0.036; 20.45+/-3.86/mm3 vs. 26.75+/-5.32/mm3, P = 0.000; 0.64+/-0.09 vs. 1.32+/-0.13, P = 0.000). The lung tissues of the HPS rats showed microthrombosis in pulmonary vessels, which were not observed in lung tissues of the cirrhosis rats.

CONCLUSIONHPS-related differential levels of D-dimer, PT, Fib, CD4, CD8 and CD4/CD8 may represent a biomarker profile suggestive of incidence of thromboembolism in lung.

Animals ; CD4 Antigens ; metabolism ; CD4-CD8 Ratio ; CD8 Antigens ; metabolism ; Disease Models, Animal ; Fibrin Fibrinogen Degradation Products ; metabolism ; Fibrinogen ; metabolism ; Hepatopulmonary Syndrome ; blood ; Liver Cirrhosis ; blood ; Lung ; pathology ; Male ; Prothrombin Time ; Rats ; Rats, Sprague-Dawley

Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPHTN) are complications of portal hypertension and cirrhosis. Their pathophysiological mechanisms clearly differ. HPS is characterized by a defect in arterial oxygenation induced by pulmonary vascular dilatation. In contrast, PPHTN is predominantly due to excessive pulmonary vasoconstriction and vascular remodeling, but is rarely associated with hypoxia. We report a case of a patient who had both HPS and PPHTN at the time of presentation. HPS was aggravated after sildenafil administration for the treatment of PPHTN. We demonstrated increased amount of intrapulmonay shunt after sildenafil challenge by using agitated saline contrast transthoracic echocardiography.
Anoxia ; Dihydroergotamine ; Dilatation ; Echocardiography ; Fibrosis ; Hepatopulmonary Syndrome* ; Humans ; Hypertension* ; Hypertension, Portal ; Oxygen ; Vasoconstriction ; Sildenafil Citrate

Hepatopulmonary syndrome (HPS) is a serious complication of end-stage liver disease, which is characterized by hypoxia, intrapulmonary vascular dilatation, and liver cirrhosis. Liver transplantation (LT) is the only curative treatment modality for patients with HPS. However, morbidity and mortality after LT, especially in cases of severe HPS, remain high. This case report describes a patient with typical findings of an extracardiac pulmonary arteriovenous shunt on contrast-enhanced transesophageal echocardiography (TEE), and clubbing fingers, who had complete correction of HPS by deceased donor LT. The patient was a 16-year-old female who was born with biliary atresia and underwent porto-enterostomy on the 55th day after birth. She had been suffered from progressive liver failure with dyspnea, clubbing fingers, and cyanosis. Preoperative arterial blood gas analysis revealed severe hypoxia (arterial O2 tension of 54.5 mmHg and O2 saturation of 84.2%). Contrast-enhanced TEE revealed an extracardiac right-to-left shunt, which suggested an intrapulmonary arteriovenous shunt. The patient recovered successfully after LT, not only with respect to physical parameters but also for pychosocial activity, including school performance, during the 30-month follow-up period.
Adolescent ; Anoxia ; Arteriovenous Fistula/etiology ; Biliary Atresia/*diagnosis/etiology ; Cyanosis/complications ; Dyspnea/complications ; Echocardiography, Transesophageal ; End Stage Liver Disease/complications/*surgery ; Female ; Hepatic Artery/abnormalities ; Hepatopulmonary Syndrome/*diagnosis/ultrasonography ; Humans ; *Liver Transplantation ; Osteoarthropathy, Secondary Hypertrophic/complications

OBJECTIVETo explore the mechanism of tanshinol on alleviate the inflammatory injury of lung tissue in rat hepatopulmonary syndrome (HPS).

METHODSSD rats were randomly divided into normal control group (n = 8), hepatopulmonary syndrome (HPS) group (n = 11) and tanshinol intervention group (n = 9). HE staining was used to observe the histopathology changes of pulmonary and hepatic tissues, and to count the number of macrophages in lung tissues. The activity of alanine transferase (ALT) and concentrations of endotoxin, tumor necrosis factor-a (TNF-alpha) and homocystein (Hcy) in plasma were detected. The concentrations of TNF-alpha, nitric oxide (NO) and malondialdehyde (MDA) and the activity of inducible nitric oxide synthase (iNOS) in the lung tissues were measured, respectively.

RESULTSThickened alveolar septum and increased macrophages were observed in lungs in HPS rat. After administered with tanshinol, the pulmonary pathological changes were alleviated and the number of macrophages in lung tissue was decreased compared with HPS group. The activity of ALT and the concentrations of endotoxin, TNF-alpha and Hcy in plasma ,and TNF-alpha, iNOS, NO and MDA in lung tissue in HPS group were higher than those of normal control group; meanwhile, those tanshinol group were less those that of HPS group.

CONCLUSIONTanshinol may play an important role in delaying the development of HPS through protecting liver or directly antagonizing the effect of intestinal endotoxemia so as to alleviate the inflammatory reaction in lung tissue.

Alanine Transaminase ; metabolism ; Animals ; Caffeic Acids ; pharmacology ; Disease Models, Animal ; Endotoxins ; blood ; Hepatopulmonary Syndrome ; drug therapy ; pathology ; Homocysteine ; blood ; Liver ; drug effects ; pathology ; Lung ; drug effects ; pathology ; Macrophages ; drug effects ; pathology ; Male ; Malondialdehyde ; metabolism ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; blood