Favorable Outcomes of Liver Transplantation for Hepatopulmonary Syndrome.

BACKGROUND: Hepatopulmonary syndrome (HPS) is a pulmonary vascular complication of chronic liver disease, which develops insidiously as a result of chronic liver disease. The prognosis for untreated patients with HPS is extremely poor, and liver transplantation (LT) serves as the only effective means for treating this condition. Here, we performed a retrospective analysis to evaluate the efficacy of LT on the survival and long-term prognosis of patients with HPS. METHODS: Clinical data, including survival and postoperative efficacy, from patients with HPS from records as obtained over the period from January 1 to December 31, 2022. All records were from a waiting list for LT at the Beijing Friendship Hospital Affiliated with Capital Medical University. RESULTS: Among the 274 patients on the LT waiting list, 37 were diagnosed with HPS (13.50%) and were enrolled. Survival rates of patients with HPS receiving an LT were greater, whereas a statistically significant difference was obtained between patients with LT vs non-LT with moderate to severe HPS (P = .003). The overall time until death without LT was 4-72 days after their initial HPS diagnosis. Patients with HPS receiving an LT showed a significant improvement in the state of oxygenation after surgery (P = .001). CONCLUSION: Comprehensive preoperative screening of patients on the waiting list for LT is critical to identify those patients with HPS who would maximally benefit from LT. Survival rates of patients with moderate to severe HPS are significantly increased after LT, a procedure that should be performed as soon as possible in these patients with HPS.

Predictors of outcomes following liver transplant in hepatopulmonary syndrome: An OPTN database analysis.

Hepatopulmonary syndrome (HPS) is a type of pulmonary vascular disease occurring exclusively in those with underlying liver disease, associated with significant mortality in patients awaiting liver transplantation (LT). LT is curative in HPS, and these patients are granted Model for End Stage Liver Disease (MELD) exception points to expedite LT. The purpose of this study is to use multivariable competing risk Accelerated Failure Time models and propensity matching to examine the relationship between pre-LT hypoxemia and post-LT outcomes in HPS. We performed a retrospective cohort study of UNOS/OPTN database of all adult patients undergoing LT between January 1, 2006 and January 12, 2020. Pre-LT PaO2 was significantly associated with post-LT mortality in HPS, with each 1 mmHg increase in PaO2 significantly decreasing the risk of post-LT mortality (coefficient 0.039, HR = 0.95, p = 0.001). HPS patients with a pre-LT PaO2 < 54 mmHg demonstrated increased mortality following LT as compared to matched non-HPS cirrhotic patients. We conclude that HPS patients with a PaO2, 54 mmHg are at increased risk of post-LT mortality and may identify high-risk patients who would benefit from additional resources during LT, and that the effects of HPS MELD exception points to optimize post-LT outcomes should be continuously re-evaluated.

Improved survival in children with HPS: Experience from two high volume liver transplant centers across continents.

BACKGROUND: Severe HPS increases morbidity and mortality after LT in children. We reviewed the combined experience of LT for HPS in children from two LT centers in Europe and Asia. METHODS: All children with "proven" HPS as per ERS Task Force criteria (detailed in manuscript) who underwent LT were categorized into M (PaO2 ≥80 mmHg), Mo (PaO2  = 60-79 mmHg), S (50-59 mmHg), and VS (PaO2 <50 mmHg) HPS, based on room air PaO2 . RESULTS: Twenty-four children with HPS underwent 25 LT (one re-transplantation) at a median age of 8 years (IQR, 5-12), after a median duration of 8 (4-12) months following HPS diagnosis. Mechanical ventilation was required for a median of 3 (1.5-27) days after LT. Ten children had "S" post-operative hypoxemia, requiring iNO for a median of 5 (6-27) days. "VS" category patients had significantly prolonged invasive ventilation (median 35 vs. 3 and 1.5 days; p = .008), ICU stay (median 39 vs. 8 and 8 days; p = .007), and hospital stay (64 vs. 26.5 and 23 days; p < .001) when compared to "S" and "M/Mo" groups, respectively. The need for pre-transplant home oxygen therapy was the only factor predicting need for re-intubation. Patient and graft survival at 32 (17-98) months were 100% and 95.8%. All children ultimately had complete resolution of HPS. CONCLUSIONS: VS HPS is associated with longer duration of mechanical ventilation and hospital stay, which emphasizes the need for early LT in these children.

Pulmonary Abnormalities in Liver Disease: Relevance to Transplantation and Outcome.

Pulmonary disease in liver cirrhosis and portal hypertension (PH) constitutes a challenging clinical scenario and may have important implications with regard to prognosis, liver transplantation (LT) candidacy, and post-LT outcome. Pre-LT evaluation should include adequate screening for pulmonary diseases that may occur concomitantly with liver disease as well as for those that may arise as a complication of end-stage liver disease and PH, given that either may jeopardize safe LT and successful outcome. It is key to discriminate those patients who would benefit from LT, especially pulmonary disorders that have been reported to resolve post-LT and are considered "pulmonary indications" for transplant, from those who are at increased mortality risk and in whom LT is contraindicated. In conclusion, in this article, we review the impact of several pulmonary disorders, including cystic fibrosis, alpha 1-antitrypsin deficiency, hereditary hemorrhagic telangiectasia, sarcoidosis, coronavirus disease 2019, asthma, chronic obstructive pulmonary disease, pulmonary nodules, interstitial lung disease, hepatic hydrothorax, hepatopulmonary syndrome, and portopulmonary hypertension, on post-LT survival, as well as the reciprocal impact of LT on the evolution of lung function.

A high-dose rapamycin treatment alleviates hepatopulmonary syndrome in cirrhotic rats.

BACKGROUND: Rapamycin is a type of immunosuppressive agent that acts through inhibition of mammalian target of rapamycin (mTOR). Hepatopulmonary syndrome (HPS) is a lethal complication in cirrhotic patients. It is characterized by hypoxia and increased intrapulmonary shunts, in which pulmonary inflammation and angiogenesis play important roles. The current study aimed to evaluate the effect of rapamycin on HPS using the experimental model of common bile duct ligation (CBDL)-induced cirrhosis in rats. METHODS: The rats received low-dose (0.5 mg/kg), high-dose (2 mg/kg) rapamycin, or vehicle from the 15th to the 28th day post CBDL. Then the mortality rate, hemodynamics, biochemistry parameters, arterial blood gas and plasma levels of vascular endothelial growth factor (VEGF) and tumor necrosis factor (TNF)-α were evaluated on the 28th day post CBDL. Pulmonary histopathological stains were performed, and protein expression was examined. In parallel groups, the intrapulmonary shunts of CBDL rats were measured. RESULTS: Compared with the control, a high-dose rapamycin treatment decreased portal pressure and improved hypoxia in CBDL rats. It also reduced the plasma level of VEGF and TNF-α and decreased intrapulmonary shunts. Meanwhile, it ameliorated pulmonary inflammation and angiogenesis and downregulated the protein expression of mTOR, P70S6K, nuclear factor kappa B (NFκB), VEGF, and VEGF receptor 2. In contrast, low-dose rapamycin did not attenuate intrapulmonary shunts despite ameliorating portal hypertension. CONCLUSION: High-dose rapamycin ameliorates HPS in cirrhotic rats as evidenced by the alleviated hypoxia and decreased intrapulmonary shunts. Downregulation of the mTOR/P70S6K, NFκB, and VEGF signaling pathways might play a key role.

Current status of hepatopulmonary syndrome in liver transplantation in Japan: a Japanese multicenter analysis.

BACKGROUND: Hepatopulmonary syndrome (HPS) negatively affects the outcomes of deceased donor liver transplantation (LT). METHODS: We retrospectively reviewed the clinical records of patients with HPS who underwent LT and studied the impact of risk factors on clinical outcomes to determine strategies to overcome complications. Patients with symptoms of hypo-oxygenemia and a shunt ratio >15% on 99mTc-MAA lung perfusion scintigraphy were defined as having HPS. RESULTS: Forty-eight patients in 10 centers were enrolled. Diseases included biliary atresia, liver cirrhosis, non-alcoholic steatohepatitis, congenital hepatic fibrosis, and others. The length of ICU stay was 2-170 days. The respirator was used for 41.6% of patients on post-operative day (POD) 3 and 20.8% on POD 14. The patient survival rate was 87% at 1 year and 82% at 5 years. The causes of hospital mortality were sepsis, thrombotic microangiopathy, intracranial bleeding, pulmonary fibrosis, and transplant rejection. An amount of shunt ratio prior to LT was a significant risk factor for hospital mortality. Hypoxia from POD 3 to POD 14 was a risk factor for biliary stenosis. The shunt ratio of all surviving patients significantly improved. CONCLUSION: Although LT is feasible for patients with HPS, early transplantation and avoiding hypo-oxygenemia immediately after transplantation are important.

Acute Respiratory Failure and Pulmonary Complications in End-Stage Liver Disease.

Acute respiratory failure has a high mortality in patients with end-stage liver disease (ESLD). These patients may develop acute respiratory failure for reasons specific to advanced liver disease, including hepatopulmonary syndrome, portopulmonary hypertension, and hepatic hydrothorax. They may also develop respiratory complications due to conditions seen in the general intensive care unit population to which ESLD patients are at higher risk, including infection, volume overload, and the acute respiratory distress syndrome. Management of these patients is complicated and multifaceted, and a comprehensive understanding of the etiologies and treatment of acute respiratory failure is critical in this high-risk patient population. This article reviews current evidence surrounding the prevalence, management, and complications of the various etiologies of acute respiratory failure in ESLD patients.

Selective cyclooxygenase inhibition by SC-560 improves hepatopulmonary syndrome in cirrhotic rats.

OBJECTIVE: Hepatopulmonary syndrome (HPS) is characterized by hypoxia in patients with chronic liver disease. The mechanism of HPS includes pulmonary vasodilatation, inflammation, and angiogenesis. Prostaglandins synthesized by cyclooxygenases (COX) participate in vascular responsiveness, inflammation and angiogenesis, which can be modulated by COX inhibitors. We therefore evaluated the impact of COX inhibition in rats with common bile duct ligation (CBDL)-induced liver cirrhosis and HPS. METHODS: Cirrhotic rats were randomly allocated to receive non-selective COX inhibitor (indomethacin), selective COX-1 inhibitor (SC-560), or COX-2 inhibitor (celecoxib) for 14 days. After that, hemodynamic parameters, severity of hypoxia and intrapulmonary shunts, liver and renal biochemistry parameters, histological finding and protein expressions were evaluated. RESULTS: Non-selective COX inhibition by indomethacin improved hepatic fibrosis and pulmonary inflammation in cirrhotic rats with HPS. It also decreased mean arterial blood pressure, portal pressure, and alleviated hypoxia and intrapulmonary shunts. However, indomethacin increased mortality rate. In contrast, selective COX inhibitors neither affected hemodynamics nor increased mortality rate. Hypoxia was improved by SC-560 and celecoxib. In addition, SC-560 decreased intrapulmonary shunts, attenuated pulmonary inflammation and angiogenesis through down-regulating COX-, NFκB- and VEGF-mediated pathways. CONCLUSION: Selective COX-1 inhibitor ameliorated HPS by mitigating hypoxia and intrapulmonary shunts, which are related to anti-inflammation and anti-angiogenesis.

Isolated Intrapulmonary Vascular Dilatations and the Risk of Developing Hepatopulmonary Syndrome in Liver Transplant Candidates.

BACKGROUND: The natural history of intrapulmonary vascular dilations (IPVD) and their impact on patient outcomes in the setting of portal hypertension has only been described in small series. AIMS: To assess the development of hepatopulmonary síndrome (HPS) in patients with isolated IPVD and to evaluate outcomes of IPVD and HPS among patients evaluated for liver transplantation (LT). MATERIAL AND METHODS: Data from a prospective cohort of patients evaluated for LT with standardized screening for HPS were analyzed. IPVDs were defined as the presence of microbubbles in the left atrium > 3 cycles following right atrial opacification. HPS was defined as the presence of IPVD and hypoxemia (Alveolar-arterial gradient ≥ 15 mmHg) in the absence of concomitant cardiopulmonary disease. RESULTS: A total of 104 patients with negative contrast-enhanced echocardiogram (CE) were compared to 63 patients with IPVD and 63 patients with HPS. Only four patients were categorized as 'severe' HPS based on degree of hipoxemia (defined as PaO2 < 60 mmHg). Twenty IPVD patients were followed with ABG over a mean duration of 21 months (range 9-43), of whom 7 (35%) subsequently met HPS criteria. Overall unadjusted survival from the time of LT evaluation using multi-state survival models that accounted for pre- and post-LT time was not statistically different among the three groups (negative CE, IPVD, and HPS; p > 0.5). CONCLUSIONS: Patients with IPVD appear to have a substantial risk of developing oxygenation impairment over time and progress to HPS. In our cohort, survival in patients with HPS and isolated IPVD is not different when compared to those without IPVDs.

[Acute Liver Failure, Acute-On-Chronic Liver Failure, Hepatorenal Syndrome, Hepatopulmonary Syndrome and Portopulmonary Hypertension, Artificial Liver Support on the ICU]. / Akutes Leberversagen, akut-auf-chronisches Leberversagen, hepatorenales Syndrom, hepatopulmonales Syndrom und portopulmonale Hypertonie, Leberunterstützungsverfahren auf der Intensivstation.

Background Acute hepatic dysfunction in the form of acute liver failure (ALF) or acute-on-chronic liver failure (ACLF) is a disease with a high risk of mortality and requires interdisciplinary intensive care. Aim This article explains the nomenclature, pathophysiology, prognosis and possible treatment options of ALF and ACLF, including the possibilities of extracorporeal liver support therapy at the point of liver transplantation (LTx). Method Narrative review with a selective literature review and representative case studies. Results/Corner Points ALF and ACLF may have several causes and are associated with high mortality. The causes of ALF must be accurately diagnosed because targeted treatment options are available. Both ALF and ACLF may require a liver transplantation for the patient's survival. For ALF and ACLF there are different criteria for decision-making on liver transplantation and graft allocation. For extracorporeal liver support therapy, two methods have been established (MARS [molecuar adsorbent recirculating system] and FPSA [fractionated plasma separation and adsorption] Prometheus®). Both approaches may have the potential to increase the probability of survival of patients with ALF or ACLF. In some cases they can be used for bridging to liver transplantation, in individual cases also for primary poison elimination, e.g. after Amatoxin ingestion. Both methods are not suitable for long-term therapy. Conclusion Acute liver failure (ALF) and acute on chronic liver failure (ACLF) are serious diseases with a high risk of mortality. Affected patients should receive immediate interdisciplinary intensive care in a (tertiary) centre with the aim to clarify the cause of the disease as well as possible treatment options with respect to available extracorporeal liver support therapy and liver transplantation.

Biliary atresia: Indications and timing of liver transplantation and optimization of pretransplant care.

Biliary atresia (BA) is a progressive, fibro-obliterative disorder of the intrahepatic and extrahepatic bile ducts in infancy. The majority of affected children will eventually develop end-stage liver disease and require liver transplantation (LT). Indications for LT in BA include failed Kasai portoenterostomy, significant and recalcitrant malnutrition, recurrent cholangitis, and the progressive manifestations of portal hypertension. Extrahepatic complications of this disease, such as hepatopulmonary syndrome and portopulmonary hypertension, are also indications for LT. Optimal pretransplant management of these potentially life-threatening complications and maximizing nutrition and growth require the expertise of a multidisciplinary team with experience caring for BA. The timing of transplant for BA requires careful consideration of the potential risk of transplant versus the survival benefit at any given stage of disease. Children with BA often experience long wait times for transplant unless exception points are granted to reflect severity of disease. Family preparedness for this arduous process is therefore critical. Liver Transplantation 23:96-109 2017 AASLD.

Hepatopulmonary Syndrome: A Brief Review.

Hepatopulmonary syndrome (HPS) is a pulmonary complication of liver disease characterized by arterial hypoxemia. Mechanisms related to this event are diffusion-perfusion flaw, ventilation-perfusion (V/Q) mismatch, and direct arteriovenous shunts. Diagnosis of HPS is based on the presence of liver disease or portal hypertension, increased alveolar-arterial (A-a) PO2, and intrapulmonary vascular dilatations (IPVD). Lung transplantation (LT) remains the most effective therapy for HPS. In spite of its poor prognosis, we could improve the quality of life and survival rate of patients.

Prevalence, Severity, and Prognostic Effect of Hepatopulmonary Syndrome in Liver Transplant Candidates.

BACKGROUND: Hepatopulmonary syndrome (HPS) is commonly encountered in the setting of end-stage liver disease (ESLD). Past studies have reported conflicting results in terms of demonstrating an association between HPS and mortality. The aim of this study was to determine the prevalence of HPS in patients with ESLD referred for assessment of transplantation suitability. In addition, we investigated survival rates in the setting of HPS, with and without liver transplantation. MATERIAL AND METHODS: The medical records of 524 consecutive patients with ESLD evaluated for potential liver transplantation were retrospectively reviewed. HPS was defined by a reduced partial pressure of oxygen or an elevated alveolar-arterial oxygen gradient and the presence of intrapulmonary vascular dilatation on contrast-enhanced echocardiography. RESULTS: In total, 57 subjects (12%) fulfilled the diagnostic criteria of HPS; 88% of these had mild to moderate HPS. For patients with HPS, the overall survival rates at 1 and 3 years were 95% and 92%, respectively. Liver transplants were received by 245 patients (53%), 26 of whom had HPS. For transplant recipients with HPS, the overall survival rates at 1 and 3 years were 96% and 91%, respectively, compared to 85% and 80% in subjects without HPS. Post-transplantation survival in patients with and without HPS did not differ significantly (HR=0.489, 95% CI: 0.153-1.564; p=0.228). CONCLUSIONS: This study demonstrated a high prevalence of IPVD and HPS among patients who were potential candidates for liver transplantation. HPS was mild to moderate in the majority of those affected and had no significant effect on overall survival.

Intrapulmonary vascular dilatations are common in portopulmonary hypertension and may be associated with decreased survival.

Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH) are pulmonary vascular complications of portal hypertension with divergent clinicopathologic features and management. The presence of intrapulmonary vascular dilatations (IPVDs), detected by agitated saline contrast-enhanced transthoracic echocardiography (cTTE), is an essential feature of HPS but is not typically characteristic of POPH. Although IPVDs have been reported rarely in POPH, the prevalence and significance of this finding have not been systematically studied. We conducted a retrospective chart review of 80 consecutive patients diagnosed with POPH from January 1, 2002 to June 30, 2014 with documentation of cTTE findings, pulmonary hemodynamics, oxygenation, and survival. A total of 34 of the 80 patients (42%) underwent cTTE during initial diagnosis of POPH. IPVDs were detected in 20/34 patients (59%); intracardiac shunting was detected in 9/34 patients (26%; 4 also had IPVDs); and 9 patients (26%) had negative cTTE with no evidence of IPVD or intracardiac shunting. Patients with IPVD had decreased survival as compared to those without IPVD (P = 0.003), a trend that persisted after exclusion of liver transplant recipients (P = 0.07). The IPVD group had a trend toward higher Model for End-Stage Liver Disease score with and without incorporating sodium (MELD or MELD-Na; P = 0.05 for both). The right ventricular index of myocardial performance (RIMP) was lower in the IPVD group (median, 0.4 versus 0.6; P = 0.006). Patients with moderate or large IPVDs (n = 6) had worse oxygenation parameters (partial pressure of arterial oxygen, diffusing capacity of the lung for carbon monoxide, and alveolar-arterial oxygen gradient) as compared to the rest of the cohort. Unexpectedly, IPVDs were frequently documented in POPH and associated with decreased survival. To further understand this observation, we recommend screening for IVPD in all patients with POPH.

Clinical characteristics, predictors, and survival among patients with hepatopulmonary syndrome.

BACKGROUND: Hepatopulmonary syndrome (HPS) is a complication of advanced liver disease. The impact of HPS on survival is not clearly understood. MATERIAL AND METHODS: A prospective study was carried out at Department of Medicine, King Edward Medical University Lahore from June 2011 to May 2012. Patients with cirrhosis of liver were evaluated for presence of HPS with arterial blood gas analysis and saline bubble echocardiography. All patients were followed for 6 months for complications and mortality. Cox regression analysis was done to evaluate role of HPS on patient survival. RESULTS: 110 patients were included in the study. Twenty-nine patients (26%) had HPS. MELD score was significantly higher (p < 0.01) in patients with HPS (18.93 ± 3.51) as compared to that in patients without HPS (13.52 ± 3.3). Twenty two (75.9%) patients of Child class C, 5 (17.2%) patients of Child class B and 2 (6.9%) patients of Child class A had HPS (P 0.03). The clinical variables associated with presence of HPS were spider nevi, digital clubbing, dyspnea, and platypnea. HPS significantly increased mortality during six month follow up period (HR: 2.47, 95% CI: 1.10- 5.55). Child-Pugh and MELD scores were also associated with increased mortality. HPS was no longer associated with mortality when adjustment was done for age, gender, Child-Pugh, and MELD scores (HR: 0.44, 95% CI: 0.14-1.41). Both the Child-Pugh and MELD scores remained significantly associated with mortality in the multivariate survival analysis. CONCLUSIONS: HPS indicates advanced liver disease. HPS does not affect mortality when adjusted for severity of cirrhosis.

Prevalence and severity of hepatopulmonary syndrome and its influence on survival in cirrhotic patients evaluated for liver transplantation.

The prevalence of hepatopulmonary syndrome (HPS) and its influence on survival before and after liver transplantation (LT) remain controversial. Additionally, the chronology of post-LT reversibility is unclear. This study prospectively analyzed 316 patients with cirrhosis who were evaluated for LT in 2002-2007; 177 underwent LT at a single reference hospital. HPS was defined by a partial pressure of arterial oxygen (PaO2 ) <70 mmHg and/or an alveolar-arterial oxygen gradient (A-a PO2 ) ≥20 mmHg in the supine position and positive contrast echocardiography. The prevalence of HPS was 25.6% (81/316 patients), and most patients (92.6%) had mild or moderate HPS. High Child-Pugh scores and the presence of ascites were independently associated with HPS. Patients with and without HPS did not significantly differ in LT waiting list survival (mean 34.6 months vs. 41.6 months, respectively; log-rank, p = 0.13) or post-LT survival (mean 45 months vs. 47.6 months, respectively; log-rank, p = 0.62). HPS was reversed in all cases within 1 year after LT. One-fourth of the patients with cirrhosis who were evaluated for LT had HPS (mostly mild to moderate); the presence of HPS did not affect LT waiting list survival. HPS was always reversed after LT, and patient prognosis did not worsen.

The role of hemodynamic and vasoactive substances on hepatopulmonary syndrome.

BACKGROUND: Hepatopulmonary syndrome (HPS) is a chronic hepatic complication characterized by defect in arterial oxygenation induced by pulmonary vascular dilatation and vasoactive substances in the setting of chronic liver disease (CLD). This study is to investigate the abnormality of hemodynamic and vasoactive substances in hepatopulmonary syndrome. PATIENTS AND METHODS: From September 2007 to September 2012, 58 patients with HPS in the General Surgery Department and Transplantation Center of Renji Hospital were enrolled for the case-control study. HPS patients enrolled were referred to as group H, CLD without HPS to as group C and case controls to as group N. Hemodynamic parameters of the systemic and pulmonary circulations as well as vasoactive substances in the radial and pulmonary arteries were measured in all patients. Univariate and multiple regression analysis were performed afterwards. RESULTS: The mean pulmonary arterial pressure, pulmonary artery wedge pressure, systemic vascular resistance and pulmonary vascular resistance (PVR) in HPS patients were significantly lower than those in CLD patients without HPS (p < 0.05). The nitrite-to-nitrate ratio (NO2-/NO3-), endothelin-1 (ET-1) and tumor necrosis factor-α (TNF-α) in the radial and pulmonary arteries differed significantly among group H, group C and case controls (group N) separately (p < 0.05). The vasoactive intestinal peptide and 6-keto-prostaglandin-F1α in the radial and pulmonary arteries of group H were significantly higher than those in group N (p < 0.05). The NO2(-)/NO3(-) levels correlated negatively with PVR (r = -0.535, p < 0.05) and Endothelin-1 (r = -0.624, p < 0.05). CO (p < 0.05), CI (p < 0.05), SI (p < 0.05) and TNF-α (p < 0.05) level are considered significantly when performed with multiple regression analysis. CONCLUSIONS: The CO increases and PVR decreases in HPS patients. The abnormally elevated NO2-/NO3- level in the pulmonary circulation leads to pulmonary vasodilation. ET-1 may induce nitric oxide synthesis and correlated negatively with PVR in HPS. CO, CI, SI and TNF-α level are independent risk factors for HPS patients' survival.

Impact of the hepatopulmonary syndrome MELD exception policy on outcomes of patients after liver transplantation: an analysis of the UNOS database.

BACKGROUND & AIMS: Patients with hepatopulmonary syndrome (HPS) are prioritized for liver transplantation (given exception points) due to their high pre- and post-transplantation mortality. However, few studies have evaluated the outcomes of these patients. METHODS: We performed a retrospective cohort study using data submitted to the United Network for Organ Sharing in a study of the effects of room-air oxygenation on pre- and post-transplantation outcomes of patients with HPS. We identified thresholds associated with post-transplantation survival using cubic spline analysis and compared overall survival times of patients with and without HPS. RESULTS: From 2002 through 2012, nine hundred and seventy-three patients on the liver transplant waitlist received HPS exception points. There was no association between oxygenation and waitlist mortality among patients with HPS exception points. Transplant recipients with more severe hypoxemia had increased risk of death after liver transplantation. Rates of 3-year unadjusted post-transplantation survival were 84% for patients with PaO2 of 44.1-54.0 mm Hg vs 68% for those with PaO2 ≤ 44.0 mm Hg. In multivariable Cox models, transplant recipients with an initial room-air PaO2 ≤ 44.0 mm Hg had significant increases in post-transplantation mortality (hazard ratio = 1.58; 95% confidence interval [CI]: 1.15-2.18) compared with those with a PaO2 of 44.1-54.0 mm Hg. Overall mortality was significantly lower among waitlist candidates with HPS exception points than those without (hazard ratio = 0.82; 95% CI: 0.70-0.96), possibly because patients with HPS have a reduced risk of pre-transplantation mortality and similar rate of post-transplantation survival. CONCLUSIONS: Although there was no association between pre-transplantation oxygenation and waitlist survival in patients with HPS Model for End-Stage Liver Disease exception points, a pre-transplantation room-air PaO2 ≤ 44.0 mm Hg was associated with increased post-transplantation mortality. HPS Model for End-Stage Liver Disease exception patients had lower overall mortality compared with others awaiting liver transplantation, suggesting that the appropriateness of the HPS exception policy should be reassessed.

Defining and characterizing severe hypoxemia after liver transplantation in hepatopulmonary syndrome.

Hepatopulmonary syndrome is defined as a triad of liver disease, intrapulmonary vascular dilatations, and abnormal gas exchange, and it carries a poor prognosis. Liver transplantation is the only known cure for this syndrome. Severe hypoxemia in the early postoperative period has been reported to be a major complication and often leads to death in this population, but it has been poorly characterized. We sought to propose an objective definition for this complication and to describe its risk factors, incidence, and outcomes. We performed a systematic literature search and reviewed our single-center experience to characterize this complication. On the basis of the most commonly applied definition in 27 identified studies, we objectively defined severe postoperative hypoxemia as hypoxemia requiring a 100% fraction of inhaled oxygen to maintain a saturation ≥ 85% and out of proportion to any concurrent lung process. Nineteen of the 27 reports (70%) fulfilled this definition, as did 4 of the 21 patients (19%) at our center. We determined the prevalence and mortality of this complication from reports including 10 or more consecutive patients and providing sufficient postoperative details to determine whether this complication had occurred. In these reports, the prevalence of this complication was 12% (25/209). For the 11 cases with reported outcomes, the posttransplant mortality rate was 45% (5/11). There was a trend toward an increased risk of developing this complication in patients with very severe preoperative hypoxemia, defined as a partial pressure of arterial oxygen ≤ 50 mm Hg (8/41 with very severe hypoxemia versus 3/49 without severe hypoxemia, P = 0.053), and there was a significantly increased risk for patients with anatomic shunting ≥ 20% (7/25 with anatomic shunting ≥ 20% versus 1/25 without anatomic shunting ≥ 20%, P = 0.049). In conclusion, increased preoperative vigilance for this common complication is required among high-risk patients, and further research is required to identify the best management strategies.

Hepatopulmonary syndrome: favorable outcomes in the MELD exception era.

UNLABELLED: Hepatopulmonary syndrome (HPS) is a pulmonary vascular disorder occurring as a consequence of advanced liver disease, characterized by hypoxemia due to intrapulmonary vascular dilatations. HPS independently increases mortality, regardless of the cause or severity of liver disease. Liver transplantation (LT) improves survival in HPS. We present the largest consecutive series of HPS patients specifically addressing long-term survival relative to the degree of hypoxemia and the era in which LT was conducted. We evaluated 106 HPS patients at the Mayo Clinic from 1986 through 2010. Survival was assessed using Kaplan-Meier methodology. LT was accomplished in 49 HPS patients. Post-LT survival (1, 3, 5, and 10 years) did not differ between groups based on baseline partial pressure of arterial oxygen (PaO2 ) obtained at the time of HPS diagnosis. Improvements in overall survival at 1, 3, and 5 years post-LT in those HPS patients transplanted after January 1 2002 (n = 28) (92%, 88%, and 88%, respectively) as compared with those transplanted prior to that time (n = 21) (71%, 67%, and 67%, respectively) did not reach statistical significance (5-year P = 0.09). Model for Endstage Liver Disease (MELD) exception to facilitate LT was granted to 21 patients since January 1 2002 with post-LT survival of 19/21 patients and one wait-list death. CONCLUSION: Long-term outcome after LT in HPS is favorable, with a trend towards improved survival in the MELD exception era since 2002 as compared to earlier HPS transplants. Survival after LT was not associated with PaO2 levels at the time of HPS diagnosis. (HEPATOLOGY 2012).