[Effect of growth hormone supplementation on liver and lung function in patients with hypopituitarism].

To analyze the clinical features of patients with anterior hypopituitarism (HP) complicated with cirrhosis, and to explore the effects of growth hormone supplementation on liver and lung function. A total of 11 patients with HP complicated with cirrhosis admitted to Peking Union Medical College Hospital from January 2016 to December 2022 were included in the study, including 8 males and 3 females, aged [M(Q1, Q3)]31 (20, 37) years. There were 6 patients with pituitary stalk interruption syndrome, 4 patients after craniopharyngioma resection, and 1 patient after germinal cell tumor chemoradiotherapy. Cirrhosis appeared at [M(Q1, Q3)]7 (1, 16) years after the diagnosis of HP. There were 7 cases complicated with hepatopulmonary syndrome (HPS). The liver and lung function of 5 patients were improved significantly after the addition of growth hormone, and the arterial partial pressure of oxygen increased from (47±11) mmHg(1 mmHg=0.133 kPa) to (84±12) mmHg. Timely supplementation of growth hormone can improve the symptoms of fatty liver, cirrhosis and HPS, and postpone or even avoid the transplantation of liver and other organs.

Outcomes of liver transplantation for hepatopulmonary syndrome in patients with concomitant respiratory disease.

BACKGROUND & AIMS: Concomitant respiratory disease is a common finding in patients with hepatopulmonary syndrome (HPS). Among patients who underwent liver transplantation (LT) for HPS, we compared characteristics and outcome of patients with versus without concomitant respiratory disease. METHODS: This single center retrospective observational study included patients with HPS who underwent LT between 1999 and 2020. RESULTS: During the study period, 32 patients with HPS received a LT; nine (28%) with concomitant respiratory disease of whom one required a combined lung-liver transplantation. Patients with concomitant respiratory disease had higher PaCO2 (38 vs. 33 mm Hg, p = .031). The 30-day postoperative mortality was comparable, but the estimated cumulative probability of resolution of oxygen therapy after LT in HPS patients with versus those without concomitant respiratory disease was lower: 63% versus 91% at 12 months and 63% versus 100% at 18 months (HR 95% CI .140-.995, p = .040). In addition to the presence of concomitant respiratory disease (p = .040), history of smoking (p = .012), and high baseline 99mTcMAA shunt fraction (≥20%) (p = .050) were significantly associated with persistent need of oxygen therapy. The 5-year estimated cumulative probability of mortality in patients with concomitant respiratory disease was worse: 50% versus 23% (HR 95% CI .416-6.867, p = .463). CONCLUSIONS: The presence of a concomitant respiratory disease did not increase the short-term postoperative mortality after LT in patients with HPS. However, it resulted in a longer need for oxygen therapy.

[Budd-Chiari syndrome with hepatopulmonary syndrome: a case report and literature review].

Objective: To summarize the clinical features and prognosis of Budd-Chiari syndrome with hepatopulmonary syndrome (HPS) in children. Methods: The clinical data of a child who had Budd-Chiari syndrome with HPS treated at the Department of Pediatrics of the First Affiliated Hospital of Zhengzhou University in December 2016 was analyzed retrospectively. Taking "Budd-Chiari syndrome" and "hepatopulmonary syndrome" in Chinese or English as the keywords, literature was searched at CNKI, Wanfang, China Biomedical Literature Database and PubMed up to July 2023. Combined with this case, the clinical characteristics, diagnosis, treatment and prognosis of Budd-Chiari syndrome with HPS in children under the age of 18 were summarized. Results: A 13-year-old boy, presented with cyanosis and chest tightness after activities for 6 months, and yellow staining of the skin for 1 week. Physical examination at admission not only found mild yellow staining of the skin and sclera, but also found cyanosis of the lips, periocular skin, and extremities. Laboratory examination showed abnormal liver function with total bilirubin 53 µmol/L, direct bilirubin 14 µmol/L, and indirect bilirubin 39 µmol/L, and abnormal blood gas analysis with the partial pressure of oxygen of 54 mmHg (1 mmHg=0.133 kPa), the partial pressure of carbon dioxide of 31 mmHg, and the alveolar-arterial oxygen gradient of 57 mmHg. Hepatic vein-type Budd-Chiari syndrome, cirrhosis, and portal hypertension were indicated by abdominal CT venography. Contrast-enhanced transthoracic echocardiography (CE-TTE) was positive. After symptomatic and supportive treatment, this patient was discharged and received oxygen therapy outside the hospital. At follow-up until March 2023, there was no significant improvement in hypoxemia, accompanied by limited daily activities. Based on the literature, there were 3 reports in English while none in Chinese, 3 cases were reported. Among a total of 4 children, the chief complaints were dyspnea, cyanosis, or hypoxemia in 3 cases, and unknown in 1 case. There were 2 cases diagnosed with Budd-Chiari syndrome with HPS at the same time due to respiratory symptoms, and 2 cases developed HPS 1.5 years and 8.0 years after the diagnosis of Budd-Chiari syndrome respectively. CE-TTE was positive in 2 cases and pulmonary perfusion imaging was positive in 2 cases. Liver transplantation was performed in 2 cases and their respiratory function recovered well; 1 case received oxygen therapy, with no improvement in hypoxemia; 1 case was waiting for liver transplantation. Conclusions: The onset of Budd-Chiari syndrome with HPS is insidious. The most common clinical manifestations are dyspnea and cyanosis. It can reduce misdiagnosis to confirm intrapulmonary vascular dilatations with CE-TTE at an early stage. Liver transplantation is helpful in improving the prognosis.

[Pulmonary Complications in Patients with Liver Cirrhosis].

Portal hypertension is a clinical syndrome defined by an increased portal venous pressure. The most frequent cause of portal hypertension is liver cirrhosis, and many of the complications of cirrhosis, such as ascites and gastroesophageal variceal bleeding, are related to portal hypertension. Portal hypertension is a pathological condition caused by the accumulation of blood flow in the portal system. This blood flow retention reduces the effective circulation volume. To compensate for these changes, neurotransmitter hormone changes and metabolic abnormalities occur, which cause complications in organs other than the liver. A hepatic hydrothorax is fluid accumulation in the pleural space resulting from increased portal pressure. Hepatopulmonary syndrome and portopulmonary hypertension are the pulmonary complications in cirrhosis by deforming the vascular structure. Symptoms, such as dyspnea and hypoxia, affect the survival and the quality of life of patients. These lung complications are usually underestimated in the management of cirrhosis. This review briefly introduces the type of lung complications of cirrhosis.

Perioperative Extracorporeal Membrane Oxygenation Support for Acute Respiratory Distress Syndrome Aggravated by Hepatopulmonary Syndrome in Deceased Donor Liver Transplantation: A Case Report.

Background: Extracorporeal membrane oxygenation (ECMO) is an accommodation of the cardiopulmonary bypass technique that can support gas exchange and hemodynamic stability. It is used as a salvage maneuver in patients with life-threatening respiratory or cardiac failure that does not respond to conventional treatment. There are few case reports of successful perioperative use of ECMO, especially preoperatively, in liver transplantation (LT). Here, we report an experience of successful anesthetic management in deceased donor liver transplantation (DDLT) by applying perioperative veno-venous (VV) ECMO support in the setting of acute respiratory distress syndrome (ARDS) aggravated by hepatopulmonary syndrome (HPS). Case: A 25-year-old female (156.0 cm, 65.0 kg), without any underlying disease, was referred to our emergency department for decreased mentality. Based on imaging and laboratory tests, she was diagnosed with acute liver failure of unknown cause combined with severe ARDS aggravated by HPS. Since the patient faced life-threatening hypoxemia with a failure of conventional ventilation maneuvers, preoperative VV ECMO was initiated and maintained during the operation. The patient remained hemodynamically stable throughout DDLT, and ARDS showed gradual improvement after the administration of VV ECMO. As ARDS improved, the patient's condition alleviated, and VV ECMO was weaned on postoperative day 6. Conclusions: This case demonstrates that VV ECMO may be a useful therapeutic option not only during the intraoperative and postoperative periods but also in the preoperative period for patients with liver failure combined with reversible respiratory failure.

Macitentan treatment of portopulmonary hypertension with hepatopulmonary syndrome: a case report and literature review.

Pulmonary arterial hypertension-targeted therapies in portopulmonary hypertension (PoPH) are scarce, let alone for patients with chronic liver failure (CLF) and hepatopulmonary syndrome (HPS). A 48-year male was admitted to the hospital because of cirrhosis for 18 years, systemic oedema, and chest distress after exercise for 1 week. He was diagnosed with CLF, PoPH, and HPS. After 7 weeks of macitentan treatment, the patient's activity tolerance, pulmonary artery systolic pressure, arterial partial pressure of oxygen (PaO2 ), cTNI, and NT-proBNP changes indicated gradual recovery, without hepatic safety concerns. This case indicated that administering macitentan in patients diagnosed as PoPH (with CLF and HPS) may be efficient and safe enough in a clinical setting.

Short Telomere Syndrome presenting with pulmonary fibrosis, liver cirrhosis and hepatopulmonary syndrome: a case report.

BACKGROUND: Idiopathic pulmonary fibrosis is thought to result from aberrant post-injury activation of epithelial cells leading to fibroblast proliferation and activation. A number of genetic aetiologies have been implicated in this disease process, including, among others, the short telomere syndromes. Short telomere syndromes follow an autosomal dominant pattern of inheritance resulting in shortened telomere length, which consequently leads to accelerated cell death. Organs with rapid cell turnover are most affected. CASE PRESENTATION: We describe a case of a 53-year-old man with a chief complaint of cough and dyspnea on exertion. His presentation was otherwise significant for features of accelerated aging, including a history of osteoporosis and early greying, and a family history of pulmonary fibrosis in his father. Pulmonary function testing revealed a restrictive pattern with severely reduced diffusion capacity and high resolution CT of the chest showed diffuse lung disease with mild fibrosis, in pattern suggesting an alternative diagnosis to IPF. Biopsy of the lung was in keeping with chronic fibrosing interstitial pneumonia. Imaging of the abdomen showed splenomegaly, hepatic cirrhosis and portal hypertension. Transthoracic contrast echocardiogram showed intrapulmonary shunting consistent with hepatopulmonary syndrome. Given the constellation of early aging, idiopathic pulmonary fibrosis, cryptogenic cirrhosis and a family history of pulmonary fibrosis in this patient, the Short Telomere Syndrome was suspected. Peripheral blood was sent for Flow-cytometry FISH, which demonstrated granulocyte telomere length below the 10th percentile for the patient's age, consistent with a diagnosis of Short Telomere Syndrome in this clinical context. Targeted genetic testing of mutations known to be associated with short telomere was negative though it was acknowledged that the full spectrum of disease-causing mutations remains unknown. Given the extensive fibrosis on biopsy and his progressive hypoxemia he was treated with mycophenolate and prednisone. Ultimately, he developed progressive respiratory failure and underwent double lung and concurrent liver transplant 18 months after the initial diagnosis was made. CONCLUSIONS: Short Telomere Syndrome is a rare cause of end stage organ disease and testing lacks sensitivity making diagnosis challenging. Organ transplant is still the mainstay of treatment. Nevertheless, disease identification is important because of implications for family member screening and the possibility of future treatment options.

A novel mutation in TRMT5 associated with idiopathic non-cirrhotic portal hypertension and hepatopulmonary syndrome: Case report of two siblings.

Non-cirrhotic portal hypertension (NCPH) is a rare clinical entity in children. Familial clusters of idiopathic non-cirrhotic portal hypertension (INCPH) were previously reported in cases with deoxyguanosine kinase (DGOUK) and potassium calcium-activated channel subfamily N member 3 (KCNN3) mutations. Herein, we report two siblings who had a novel mutation in mitochondrial tRNA methyltransferase 5 (TRMT5) gene and presented with hepatopulmonary syndrome and later diagnosed as INCPH. Autosomal recessive inheritance of this mutation may suggest a role of TRMT5 mutations in the development of NCPH. Screening of TRMT5 mutations could be considered when familial INCPH is suspected.

Impact of hepatopulmonary syndrome in liver transplantation candidates and the role of angiogenesis.

BACKGROUND: Hepatopulmonary syndrome affects 10-30% of patients with cirrhosis and portal hypertension. We evaluated the serum angiogenic profile of hepatopulmonary syndrome and assessed the clinical impact of hepatopulmonary syndrome in patients evaluated for liver transplantation. METHODS: The Pulmonary Vascular Complications of Liver Disease 2 study was a multicentre, prospective cohort study of adults undergoing their first liver transplantation evaluation. Hepatopulmonary syndrome was defined as an alveolar-arterial oxygen gradient ≥15 mmHg (≥20 mmHg if age >64 years), positive contrast-enhanced transthoracic echocardiography and absence of lung disease. RESULTS: We included 85 patients with hepatopulmonary syndrome and 146 patients without hepatopulmonary syndrome. Patients with hepatopulmonary syndrome had more complications of portal hypertension and slightly higher Model for End-Stage Liver Disease-Na score compared to those without hepatopulmonary syndrome (median (interquartile range) 15 (12-19) versus 14 (10-17), p=0.006). Hepatopulmonary syndrome patients had significantly lower 6-min walk distance and worse functional class. Hepatopulmonary syndrome patients had higher circulating angiopoietin 2, Tie2, tenascin C, tyrosine protein kinase Kit (c-Kit), vascular cell adhesion molecule 1 and von Willebrand factor levels, and lower E-selectin levels. Patients with hepatopulmonary syndrome had an increased risk of death (hazard ratio 1.80, 95% CI 1.03-3.16, p=0.04), which persisted despite adjustment for covariates (hazard ratio 1.79, 95% CI 1.02-3.15, p=0.04). This association did not vary based on levels of oxygenation, reflecting the severity of hepatopulmonary syndrome. CONCLUSION: Hepatopulmonary syndrome was associated with a profile of abnormal systemic angiogenesis, worse exercise and functional capacity, and an overall increased risk of death.

[Hepatopulmonary syndrome: a rare manifestation of cirrhosis in patient with diencephalic obesity and nonalcoholic fatty liver disease after surgery for craniopharyngioma].

We describe a 15-year girl, who developed panhypopituitarism and diencephalic obesity after surgical excision of craniopharyngioma, followed by nonalcoholic fatty liver disease and cirrhosis 5 years after surgery. Cirrhosis in this case manifested by hypoxia due to hepatopulmonary syndrome, and despite cure of craniopharyngioma by surgery and radiosurgery treatment and adequate hormonal substitution therapy patient died 9 years after surgery. Growth hormone substitutional therapy in patients with hypopituitarism, and steatohepatitis may decrease liver triglyceride accumulation and prevent end-stage liver disease.

Impact of Liver Transplantation on Carbon Monoxide Production as Measured by Arterial Carboxyhemoglobin Levels in Cirrhotic Patients with and without Hepatopulmonary Syndrome.

BACKGROUND Hepatic dysfunction is associated with increased production of carbon monoxide. End-stage liver disease patients with hepatopulmonary syndrome (HPS) have been shown to have higher blood carbon monoxide levels than those without HPS. The impact of liver transplantation on blood carbon monoxide levels is currently unknown. We assessed the impact of liver transplantation on blood carbon monoxide and whether this is affected by HPS. MATERIAL AND METHODS Eligible liver transplant recipients had room air arterial blood gas testing performed before and after liver transplantation. The carboxyhemoglobin fraction was obtained from arterial co-oximetry and used as a surrogate for carboxyhemoglobin production. Mean arterial carboxyhemoglobin fraction before transplantation was compared to that after transplantation. Mean absolute and median relative pre- to post-transplant within-patient change in carboxyhemoglobin fraction was compared between those with and without HPS. RESULTS Thirty-nine transplanted cirrhotic patients were analyzed, of whom 14 (36%) met criteria for hepatopulmonary syndrome. The mean pre-transplant carboxyhemoglobin fraction was higher than the post-transplant fraction (2.6 vs 1.8, difference 0.8 [95% CI 0.4-1.2]; P value 0.0002). Of the 14 patients with HPS, 11 (79%) experienced a decrease in their carboxyhemoglobin fraction after liver transplantation; among the 25 patients without HPS, 16 (64%) experienced such a decrease (P=0.48). Neither the absolute nor relative within-patient pre- to post-transplant change in carboxyhemoglobin fraction was significantly different between patients with and without HPS. CONCLUSIONS Blood carbon monoxide levels decreased significantly in cirrhotic patients following liver transplantation, but HPS did not affect the magnitude of this change.

Anesthetic Management Using Low Fraction of Inspiratory Oxygen for Living Donor Liver Transplantation in a Patient With Hepatopulmonary Syndrome Complicated by Interstitial Pneumonia: A Case Report.

BACKGROUND: Hepatopulmonary syndrome frequently complicates end-stage liver disease. It causes hypoxemia and requires oxygen administration. Additionally, interstitial pneumonia causes hypoxemia; however, it is known to be aggravated by high-concentration oxygen administration. CASE PRESENTATION: A 71-year-old woman with hepatopulmonary syndrome and interstitial pneumonia underwent living donor liver transplantation, requiring conflicting management in terms of the inspiratory oxygen concentration. We achieved a low intraoperative fraction of inspiratory oxygen by increasing the cardiac output with intravenous catecholamines. As a result, the transplanted liver functioned well postoperatively, and the patient was discharged without exacerbation of the interstitial pneumonia. CONCLUSION: We suggest that patients with hepatopulmonary syndrome complicated with interstitial pneumonia can undergo successful living donor liver transplantation without the use of high inspiratory oxygen concentration by using catecholamines to maintain a high mixed venous oxygen saturation.

First presentation of portal hypertension complicated by hepatopulmonary syndrome.

Hepatopulmonary syndrome (HPS) is a serious complication of chronic liver disease, characterised by portal hypertension and arterial hypoxaemia due to intrapulmonary vascular dilatation. We report an unusual case in which a 27-year-old man had a first presentation of portal hypertension and cirrhosis complicated by HPS. This patient presented with progressive dyspnoea on exertion and deterioration in mobility, with a type 1 respiratory failure and increased oxygen demand. A bubble echocardiogram showed a possible right-to-left shunt, CT aortogram displayed evidence of portal hypertension and cirrhosis, and liver biopsy findings were consistent with alpha-1 antitrypsin deficiency. The patient's increased oxygen demand was subsequently treated with continuous positive airway pressure before he was discharged with 8 L home oxygen. With no current established medical therapy for HPS, the patient was assessed for liver transplantation and a decision was made in favour of this.

Hepatopulmonary Syndrome and Multiple Arteriovenous Fistulas in a Child with Niemann-Pick Disease.

Background: Niemann-Pick disease (NPD) is caused by abnormal storage of sphingomyelin. NPD may affect the pulmonary system and cause hypoxia. In the present case, both hepatopulmonary syndrome (HPS) and pulmonary arteriovenous fistulas (PAVFs) developed in a child with NPD and were successfully treated with repeated embolization. Case Presentation: We have reported the case of a 16-year-old-girl with NPD who suffered severe hypoxia, dyspnea, fatigue, had multiple PAVFs, and was diagnosed with type 2 HPS. To improve oxygenation, 10 PAVFs were embolized. She needed re-embolization after 9 months because of hypoxia redevelopment. Conclusions: Pulmonary involvement, HPS, and/or PAVFs could be responsible for hypoxemia in patients with NPD, who should, therefore, be investigated for HPS and PAVFs. Embolization could be beneficial. Some patients may need repeated embolization.

Hepatopulmonary Syndrome and Portopulmonary Hypertension: Management in Liver Transplantation in the Horizon 2020.

Hepatopulmonary syndrome (HPS) is characterized by intrapulmonary microvasculature dilatation that causes intrapulmonary shunting and leads to a gas exchange abnormality in the presence of liver diseases, which is the most common cause of respiratory insufficiency in these patients. HPS doubles the risk of death, and liver transplantation (LT) is the only curative therapeutic option so it should be considered in patients with severe HPS, with excellent survival rates post-LT. However, pretransplant Pao2 <45 mm Hg has been associated with an increase in post-transplant morbidity and mortality, but it does not imply a contraindication for LT. The resolution of HPS usually occurs within 6 months post-LT, but it can take 1 year. Portopulmonary hypertension (PoPH) is defined as pulmonary arterial hypertension (PAH) that develops in the setting of portal hypertension with or without liver disease in the absence of other causes of PAH. The prevalence of PoPH is 5% to 10% among liver transplant (LT) candidates. The impact of LT on PoPH is unpredictable. Therefore, despite conferring a high morbidity and mortality, PoPH itself is not an indication for liver transplantation. It may be considered a contraindication for LT in severe cases.

Platypnoea and orthodeoxia in the hepatopulmonary syndrome.

A 71-year-old female patient with alcohol-induced cirrhosis presented with symptoms of dyspnoea. Previous extensive investigations had detected no apparent cause. Platypnoea and orthodeoxia were observed. A bubble echocardiogram revealed significant intracardiac shunting and a diagnosis of hepatopulmonary syndrome was made. The patient was discharged on home oxygen and referred for liver transplantation.

Hepatopulmonary syndrome has low prevalence of pulmonary vascular abnormalities on chest computed tomography.

PURPOSE: Hepatopulmonary syndrome (HPS) is defined as an arterial oxygenation defect induced by intrapulmonary vascular dilatations associated with hepatic disease. This study aimed to assess the prevalence of type 1 and 2 pulmonary vascular abnormalities on chest computed tomography (CT) in patients with cirrhosis and HPS and to characterize intra- and interobserver reliability. MATERIALS AND METHODS: Two thoracic radiologists retrospectively evaluated chest CT scans from 38 cirrhosis patients with HPS. They classified the pulmonary vascular abnormalities as type 1 (multiple dilated distal pulmonary arteries), type 2(nodular dilatation or individual pulmonary arterial malformation), or absence of abnormality. Furthermore, they measured the diameters of the central pulmonary arteries and subsegmental pulmonary arteries and bronchi. We analyzed the prevalence, intraobserver reliability, and interobserver reliability of abnormal CT findings related to HPS, and the correlation of these findings with partial arterial oxygen pressure (PaO2). RESULTS: The overall prevalence of pulmonary vascular abnormalities was 28.9% (95% confidence intervals: 15.4%, 45.9%). Moreover, 26.3% of patients had type 1 abnormality (13.4%, 43.1%) and 2.6% of patients had type 2 abnormality (0.0%, 13.8%). The intraobserver reliability kappa value was 0.666 (0.40, 0.91) and the interobserver kappa value was 0.443 (0.12, 0.77). There was no correlation between pulmonary vascular abnormalities on CT and PaO2 values. CONCLUSIONS: The prevalence of pulmonary vascular abnormalities on chest CT of patients with cirrhosis and HPS is low and not correlated with PaO2. These findings question the usefulness of chest CT for the evaluation of patients with cirrhosis and HPS.