Zespół wątrobowo-płucny – Etiologia i przyczyny

Zespół wątrobowo-płucny
Etiologia i przyczyny

Zespół wątrobowo-płucny (ZWP) to powikłanie zaawansowanych chorób wątroby, charakteryzujące się triadą: chorobą wątroby, wewnątrzpłucnymi rozszerzeniami naczyń oraz hipoksemią. Występuje u około 25% pacjentów z przewlekłą chorobą wątroby, choć częstość ta waha się od 4% do 47% w zależności od metod diagnostycznych. Patogeneza ZWP opiera się na rozszerzeniu naczyń płucnych, głównie pod wpływem nadmiernej produkcji tlenku azotu (NO) i innych wazodylatorów, co prowadzi do zaburzeń stosunku wentylacji do perfuzji, przecieków prawo-lewych i hipoksemii. Etiologia obejmuje nadciśnienie wrotne, marskość, zapalenie wątroby typu C, alkoholową chorobę wątroby oraz czynniki genetyczne, takie jak polimorfizmy genów angiogenezy i obniżone poziomy BMP9 i BMP10. Endotoksemia jelitowa i translokacja bakterii nasilają proces zapalny i produkcję mediatorów cytotoksycznych, m.in. TNF-α, co dodatkowo pogłębia zmiany naczyniowe.

Wprowadzenie do zespołu wątrobowo-płucnego

Zespół wątrobowo-płucny (ZWP, ang. Hepatopulmonary Syndrome, HPS) jest definiowany jako triada obejmująca: chorobę wątroby, nieprawidłowe utlenowanie tętnicze spowodowane wewnątrzpłucnymi rozszerzeniami naczyniowymi oraz hipoksemię.¹² To rzadkie powikłanie występuje u pacjentów z chorobami wątroby, szczególnie w zaawansowanym stadium, i charakteryzuje się poszerzeniem naczyń krwionośnych w płucach, co wpływa na zdolność przenoszenia tlenu do krwioobiegu.³

ZWP występuje u około 25% osób z przewlekłą chorobą wątroby, chociaż dane dotyczące częstości występowania są zróżnicowane i zależą od przyjętych kryteriów diagnostycznych, zastosowanych metod oraz badanej populacji. W badaniach szacuje się, że częstość występowania waha się od 4% do 47%.⁴⁵ W jednym z prospektywnych badań obejmującym 111 pacjentów z marskością wątroby, ZWP stwierdzono u 24% z nich przy zastosowaniu echokardiografii kontrastowej przezklatkowej, analizy gazów we krwi oraz badań czynności płuc.⁶

Przyczyny i czynniki patogenetyczne

Etiologia zespołu wątrobowo-płucnego jest złożona i nie została w pełni poznana. Jednak zidentyfikowano kilka głównych czynników przyczyniających się do jego rozwoju.

Zaburzenia wątrobowe i nadciśnienie wrotne

ZWP najczęściej wiąże się z nadciśnieniem wrotnym spowodowanym przewlekłą chorobą wątroby lub marskością. Jednakże nadciśnienie wrotne bez towarzyszącej choroby wątroby również może powodować ZWP.⁷ Ostra choroba wątroby, jak ostre zapalenie wątroby prowadzące do ostrej niewydolności wątroby, jest rzadką przyczyną ZWP.⁸⁹

Należy podkreślić, że obecność i nasilenie ZWP nie korelują z ciężkością choroby wątroby.¹⁰¹¹ ZWP może występować również u pacjentów z nadciśnieniem wrotnym bez marskości, takich jak przypadki zakrzepicy żyły wrotnej, guzkowego przerostu regeneracyjnego, wrodzonego zwłóknienia wątroby i zespołu Budda-Chiariego.¹²

Najczęstsze przyczyny ZWP obejmują:¹³

Marskość wątroby
Niealkoholową stłuszczeniową chorobę wątroby
Zapalenie wątroby typu C
Alkoholową chorobę wątroby
Zaburzenia genetyczne
Nowotwory wątroby
Choroby autoimmunologiczne

¹⁴

Rozszerzenie naczyń płucnych

Głównym mechanizmem patofizjologicznym w ZWP jest rozszerzenie naczyń płucnych, wynikające z zaburzenia równowagi między substancjami rozszerzającymi a zwężającymi naczynia krwionośne.¹⁵¹⁶ Badania autopsyjne u pacjentów z ZWP wykazały, że naczynia włosowate w płucach są znacznie poszerzone. Te rozszerzenia mogą wynikać z nadmiernej produkcji lub nieprawidłowego metabolizmu wątrobowego substancji rozszerzających naczynia (wazodylatorów) lub zmniejszonej produkcji czy wrażliwości na substancje zwężające naczynia (wazokonstryktory).¹⁷

Poszerzenie naczyń krwionośnych wpływa na ilość tlenu, który przechodzi z płuc do krwiobiegu, prowadząc do hipoksemii.¹⁸¹⁹ Ta dysfunkcja powoduje zaburzenia stosunku wentylacji do perfuzji, skrócenie czasu przejścia krwi przez płuca oraz powstanie przecieków prawo-lewych, co skutkuje niedotlenieniem.²⁰

Rola tlenku azotowego i innych mediatorów

Tlenek azotowy (NO) wyłonił się jako kluczowy czynnik powodujący rozszerzenie naczyń krwionośnych na poziomie naczyń płucnych.²¹ U pacjentów z marskością wątroby i ZWP poziom wydychanego NO wzrasta w porównaniu do pacjentów kontrolnych z marskością.²² Zmiany naczyniowe wywołane przez NO prawdopodobnie prowadzą do bardziej chronicznych zmian w strukturze naczyń krwionośnych, znanych jako przebudowa naczyniowa.²³

Proces uwalniania tlenku azotowego odbywa się poprzez kilka mechanizmów:²⁴

Translokacja bakterii jelitowych – zapalenie wywołane przez bakterie i materiał bakteryjny uciekający z jelita do krążenia krwi u pacjentów z marskością wątroby
Rekrutacja makrofagów do naczyń płucnych, gdzie produkowany jest tlenek azotowy
Aktywacja śródbłonkowej syntazy tlenku azotowego (eNOS) w płucach w odpowiedzi na zwiększoną produkcję endoteliny 1 (ET1) i pulmonalnej endoteliny B (ETB)

²⁵²⁶

Poza tlenkiem azotowym, inne mediatory zaangażowane w rozwój ZWP to:²⁷²⁸

Tlenek węgla (CO)
Czynnik martwicy nowotworów alfa (TNF-α)
Prostaglandyny
Wazoaktywny peptyd jelitowy
Kalcytonina
Glukagon
Substancja P
Przedsionkowy czynnik natriuretyczny

²⁹³⁰

Rola endotoksemii i translokacji bakteryjnej

Endotoksemia jelitowa towarzysząca marskości wątroby może być ważnym czynnikiem w rozwoju zespołu wątrobowo-płucnego.³¹ Nadciśnienie wrotne osłabia barierę śluzówki jelitowej z powodu zaburzeń drenażu.³² Translokacja bakterii i endotoksyn prowadzi do aktywacji makrofagów i monocytów w płucach, powodując gromadzenie się i/lub aktywację mediatorów cytotoksycznych i wazodylatacyjnych.³³

Nadmierna produkcja TNF-alfa spowodowana stymulacją komórek Kupffera przez endotoksyny poprzez szlak transdukcji sygnału kinazy aktywowanej mitogenami (MAPK) może być głównym mechanizmem pośredniczącym w patologicznych zmianach zespołu wątrobowo-płucnego.³⁴

Rola czynników genetycznych

Badania wykazały, że występowanie ZWP jest częstsze u osób posiadających gen białka chemoatraktanta monocytów-1 (MCP-1) 2518G.³⁵ Jednak dokładne znaczenie czynników genetycznych w rozwoju ZWP nie zostało jeszcze w pełni wyjaśnione. Ostatnie badania wskazują na możliwy związek z polimorfizmami genów zaangażowanych w regulację angiogenezy.³⁶

W niedawnym badaniu odkryto, że ZWP wiąże się z obniżonym poziomem białka morfogenetycznego kości 9 (BMP9) i BMP10 w porównaniu do pacjentów kontrolnych z zaawansowaną chorobą wątroby bez zespołu wątrobowo-płucnego. Niższe poziomy BMP9 były dodatkowo związane z cięższą postacią ZWP.³⁷

Mechanizmy patofizjologiczne

Zaburzenia wymiany gazowej

Hipoksemia w zespole wątrobowo-płucnym występuje głównie z powodu ograniczeń przemieszczania się tlenu z płuc do krwiobiegu oraz z powodu niedopasowania stosunku między powietrzem przechodzącym przez płuca a krwią wpływającą do płuc (niedopasowanie wentylacji do perfuzji), co jest spowodowane obecnością wewnątrzpłucnych rozszerzeń naczyniowych (IPVD).³⁸³⁹

Proponowane przyczyny hipoksemii to zmniejszona dyfuzja tlenu przez rozszerzone naczynia, w połączeniu ze skróconym czasem przejścia krwi przez płuca.⁴⁰ ZWP jest stanem niedopasowania wentylacji do perfuzji. Zwiększona perfuzja wtórna do rozszerzenia naczyń i powstawania obocznic w warunkach zachowanej wentylacji prowadzi do przecieku prawo-lewego krwi.⁴¹

Anatomiczne zmiany w naczyniach płucnych

Główną cechą patologiczną ZWP jest znaczne rozszerzenie przedwłośniczkowych i włośniczkowych naczyń płucnych, a także zwiększenie bezwzględnej liczby rozszerzonych naczyń. Dodatkowo, można obserwować niektóre opłucnowe i płucne połączenia tętniczo-żylne (prawdziwe przecieki).⁴²

ZWP można klasyfikować przy użyciu wzorców angiograficznych widocznych podczas arteriografii płucnej przeprowadzanej u pacjentów z ciężką depresją oddechową.⁴³ Rozszerzenia naczyniowe w ZWP są spowodowane zwiększoną produkcją lub nieprawidłowym metabolizmem wątrobowym wazodylatorów lub zmniejszoną produkcją wazokonstryktorów.⁴⁴

Specyficzne sytuacje kliniczne

ZWP u dzieci

ZWP jest rzadkim powikłaniem u dzieci, występującym u około 7% dzieci z atrezją dróg żółciowych, 20% z agenezją żyły wrotnej i 4% z zakrzepicą żyły wrotnej.⁴⁵ Podobnie jak u dorosłych, marskość wątroby nie jest wymogiem dla rozwoju ZWP u dzieci. Badania wykazały, że obecność krążenia obocznego wrotno-systemowego/żyły głównej dolnej (PS/IVC) jest czynnikiem ryzyka rozwoju ZWP u pacjentów z atrezją dróg żółciowych, choć mechanizm tej korelacji pozostaje nieznany.⁴⁶

ZWP a inne choroby płuc

ZWP może współistnieć z innymi chorobami układu oddechowego, które pogarszają wymianę gazową, w nawet do 30% przypadków.⁴⁷ Jednakże skojarzenie z chorobą śródmiąższową płuc (ILD) jest rzadko opisywane w literaturze. Współistnienie ZWP i ILD komplikuje proces diagnostyczny i może ograniczać opcje leczenia obu jednostek chorobowych.⁴⁸

Patogeneza tego skojarzenia nie jest znana, jednak choroby włóknieniowe płuc i marskość wątroby charakteryzują się obecnością uszkodzenia nabłonka/śródbłonka z nieprawidłowym bliznowaceniem, które prowadzi do fibroproliferacji i przebudowy tkanek, z udziałem kilku wspólnych cytokin prozapalnych i czynników wzrostu (TNF-α, IL-1, TGF-β i VEGF). Niedawne badanie wskazało na skrócenie telomerów jako jeden z możliwych zaangażowanych mechanizmów.⁴⁹

Implikacje kliniczne i prognostyczne

Zespół wątrobowo-płucny znacząco wpływa na rokowanie pacjentów z chorobami wątroby. Obecnie jedyną skuteczną i definitywnią metodą leczenia ZWP jest przeszczep wątroby.⁵⁰⁵¹ Po udanym przeszczepie wątroby, rozszerzenie naczyń w płucach i hipoksemia zaczynają się wycofywać. Powrót funkcji płucnej do normy zajmuje od sześciu do 12 miesięcy.⁵²

Pacjenci z marskością wątroby, którzy znajdują się na liście oczekujących na przeszczep wątroby, mają krótszy okres przeżycia, jeśli rozwiną ZWP.⁵³ Dla osób z marskością i ZWP średni czas przeżycia bez przeszczepu wątroby wynosi około dwóch lat.⁵⁴ Przyczyną zgonu u pacjentów z ZWP są zwykle powikłania związane z podstawową chorobą wątroby (np. niewydolność wątroby, niewydolność wielonarządowa z powodu sepsy, rak wątrobowokomórkowy, krwawienie z przewodu pokarmowego), a nie niewydolność oddechowa związana z ZWP.⁵⁵

Spontaniczna remisja ZWP bez leczenia jest mało prawdopodobna.⁵⁶ Z tego powodu zaleca się, aby u wszystkich pacjentów z marskością wątroby aktywnie poszukiwać objawów ZWP i nadawać im priorytet na liście oczekujących na przeszczep.⁵⁷

Podsumowanie

Zespół wątrobowo-płucny jest złożonym powikłaniem chorób wątroby, charakteryzującym się rozszerzeniem naczyń płucnych prowadzącym do hipoksemii. Główne przyczyny i mechanizmy patogenetyczne obejmują:

Nadciśnienie wrotne i przewlekłe choroby wątroby jako najczęstsze czynniki wyzwalające
Zaburzenie równowagi między substancjami rozszerzającymi a zwężającymi naczynia krwionośne
Kluczową rolę tlenku azotowego w rozszerzaniu naczyń płucnych
Endotoksemię i translokację bakteryjną jako czynniki przyczyniające się do aktywacji mediatorów zapalnych
Możliwy wpływ czynników genetycznych, w tym polimorfizmów genów związanych z angiogenezą

Zrozumienie przyczyn i mechanizmów ZWP ma kluczowe znaczenie dla opracowania skutecznych strategii diagnostycznych i terapeutycznych. Obecnie jedyną skuteczną metodą leczenia pozostaje przeszczep wątroby, który może prowadzić do całkowitego odwrócenia patologicznych zmian związanych z ZWP.⁵⁸⁵⁹

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Materiały źródłowe

#1 Hepatopulmonary syndrome in adults: Prevalence, causes, clinical manifestations, and diagnosis – UpToDate
https://www.uptodate.com/contents/hepatopulmonary-syndrome-in-adults-prevalence-causes-clinical-manifestations-and-diagnosis
Hepatopulmonary syndrome (HPS) is characterized by the triad of abnormal arterial oxygenation caused by intrapulmonary vascular dilatations (IPVDs) in the setting of liver disease, portal hypertension, or congenital portosystemic shunts. […] The prevalence, causes, clinical manifestations, and diagnostic evaluation of HPS are reviewed here. […] Estimates of the prevalence of HPS among patients with chronic liver disease range from 4 to 47 percent (on average one quarter), depending upon the diagnostic criteria, methods used, and population studied. […] In one prospective study of 111 patients with cirrhosis, HPS was reported in 24 percent when transthoracic contrast echocardiography, blood gas analysis, and pulmonary function testing were used for its detection. […] In another prospective study of patients with liver cirrhosis, 26 percent had HPS by similar criteria.
#2 Hepatopulmonary Syndrome: A Comprehensive Review
https://pmc.ncbi.nlm.nih.gov/articles/PMC11340781/
Hepatopulmonary syndrome (HPS) is defined by abnormally dilated blood vessels and shunts within the lungs, leading to impaired oxygen exchange. […] HPS is characterized by low blood oxygen levels along with portal hypertension, primarily caused by the dilation of small blood vessels within the lungs. […] The primary cause of HPS is believed to be pulmonary vascular dilatation, which arises from an imbalance between substances that promote vasodilation and those that induce vasoconstriction. […] In cirrhotic patients with HPS, exhaled NO levels increase compared to cirrhotic control patients. […] The prevalence of this condition is higher in individuals possessing the monocyte chemoattractant protein-1 (MCP-1) 2518G gene. […] The proposed cause of hypoxemia is reduced oxygen diffusion across the dilated vessels, coupled with a shortened intrapulmonary blood transit time.
#3 Hepatopulmonary Syndrome: Symptoms, Causes & Treatment
https://my.clevelandclinic.org/health/diseases/24190-hepatopulmonary-syndrome
Hepatopulmonary syndrome occurs in a small percentage of people with liver disease and/or portal hypertension. It causes the capillaries in your lungs to expand, which affects their ability to transfer oxygen into your blood. This causes hypoxemia (low blood oxygen levels). […] Hepatopulmonary syndrome is a rare complication of liver disease that causes low oxygen levels in your blood (hypoxemia). Hepato means of the liver, and pulmonary means of the lungs. Your liver and lungs are connected by blood vessels, which become dilated (widened) in advanced liver disease. The dilated blood vessels form shunts, irregular blood flow patterns that bypass the oxygenation process in your lungs. Dilated blood vessels (vasodilation) in your lungs and shunting lead to hypoxemia. […] Hepatopulmonary syndrome occurs in an estimated 25% of people with chronic liver disease. It can also occur with acute liver failure, but this is less common. Typically, cirrhosis of the liver leads to portal hypertension, which in some cases leads to hepatopulmonary syndrome. Less commonly, portal hypertension by other causes, such as blood clots, can also lead to hepatopulmonary syndrome.
#4 Hepatopulmonary syndrome in adults: Prevalence, causes, clinical manifestations, and diagnosis – UpToDate
https://www.uptodate.com/contents/hepatopulmonary-syndrome-in-adults-prevalence-causes-clinical-manifestations-and-diagnosis
Hepatopulmonary syndrome (HPS) is characterized by the triad of abnormal arterial oxygenation caused by intrapulmonary vascular dilatations (IPVDs) in the setting of liver disease, portal hypertension, or congenital portosystemic shunts. […] The prevalence, causes, clinical manifestations, and diagnostic evaluation of HPS are reviewed here. […] Estimates of the prevalence of HPS among patients with chronic liver disease range from 4 to 47 percent (on average one quarter), depending upon the diagnostic criteria, methods used, and population studied. […] In one prospective study of 111 patients with cirrhosis, HPS was reported in 24 percent when transthoracic contrast echocardiography, blood gas analysis, and pulmonary function testing were used for its detection. […] In another prospective study of patients with liver cirrhosis, 26 percent had HPS by similar criteria.
#5 Hepatopulmonary syndrome | PPT
https://www.slideshare.net/slideshow/hepatopulmonary-syndrome-242565537/242565537
Hepatopulmonary syndrome (HPS) is characterized by the triad of abnormal arterial oxygenation caused by intrapulmonary vascular dilatations (IPVDs) in the setting of liver disease, portal hypertension, or congenital portosystemic shunts. Its Prevalence varies depending on the diagnostic criteria, methods used, and population studied, so the estimate prevalence among patients with chronic liver disease ranges from 4 to 47 percent. […] E t i o l o g y Chronic liver diseases particularly with Portal hypertension Cryptogenic cirrhosis, Alcoholic cirrhosis, Postnecrotic cirrhosis Primary biliary cholangitis, Primary sclerosing cholangitis Chronic active hepatitis, Non-cirrhotic portal hypertension Alpha-1 antitrypsin deficiency Wilson’s disease, Sarcoidosis, Hemochromatosis, Biliary atresia Tyrosinemia, Gaucher disease Schistosomiasis, Short telomere syndrome Chronic granulomatous hepatitis Rarely associated with acute liver disease e.g Ischemic or Hypoxic Hepatitis, Acute hepatitis A.
#6 Hepatopulmonary syndrome in adults: Prevalence, causes, clinical manifestations, and diagnosis – UpToDate
https://www.uptodate.com/contents/hepatopulmonary-syndrome-in-adults-prevalence-causes-clinical-manifestations-and-diagnosis
Hepatopulmonary syndrome (HPS) is characterized by the triad of abnormal arterial oxygenation caused by intrapulmonary vascular dilatations (IPVDs) in the setting of liver disease, portal hypertension, or congenital portosystemic shunts. […] The prevalence, causes, clinical manifestations, and diagnostic evaluation of HPS are reviewed here. […] Estimates of the prevalence of HPS among patients with chronic liver disease range from 4 to 47 percent (on average one quarter), depending upon the diagnostic criteria, methods used, and population studied. […] In one prospective study of 111 patients with cirrhosis, HPS was reported in 24 percent when transthoracic contrast echocardiography, blood gas analysis, and pulmonary function testing were used for its detection. […] In another prospective study of patients with liver cirrhosis, 26 percent had HPS by similar criteria.
#7 Hepatopulmonary Syndrome – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK562169/
HPS is most commonly associated with portal hypertension due to chronic liver disease or cirrhosis. However, portal hypertension without underlying liver disease can also cause HPS. Acute liver disease, like acute hepatitis resulting in acute liver failure, is a rare cause of HPS. The presence and severity of HPS do not correlate with the severity of liver disease. […] Pulmonary vascular dilatation resulting from an imbalance between vasodilators and vasoconstrictors is thought to be the main cause of HPS. The exact mechanism of vasodilation is not precise, and multiple studies are ongoing to elucidate the exact mechanism.
#8 Hepatopulmonary Syndrome – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK562169/
HPS is most commonly associated with portal hypertension due to chronic liver disease or cirrhosis. However, portal hypertension without underlying liver disease can also cause HPS. Acute liver disease, like acute hepatitis resulting in acute liver failure, is a rare cause of HPS. The presence and severity of HPS do not correlate with the severity of liver disease. […] Pulmonary vascular dilatation resulting from an imbalance between vasodilators and vasoconstrictors is thought to be the main cause of HPS. The exact mechanism of vasodilation is not precise, and multiple studies are ongoing to elucidate the exact mechanism.
#9 Hepatopulmonary Syndrome: Symptoms, Causes & Treatment
https://my.clevelandclinic.org/health/diseases/24190-hepatopulmonary-syndrome
Hepatopulmonary syndrome occurs in a small percentage of people with liver disease and/or portal hypertension. It causes the capillaries in your lungs to expand, which affects their ability to transfer oxygen into your blood. This causes hypoxemia (low blood oxygen levels). […] Hepatopulmonary syndrome is a rare complication of liver disease that causes low oxygen levels in your blood (hypoxemia). Hepato means of the liver, and pulmonary means of the lungs. Your liver and lungs are connected by blood vessels, which become dilated (widened) in advanced liver disease. The dilated blood vessels form shunts, irregular blood flow patterns that bypass the oxygenation process in your lungs. Dilated blood vessels (vasodilation) in your lungs and shunting lead to hypoxemia. […] Hepatopulmonary syndrome occurs in an estimated 25% of people with chronic liver disease. It can also occur with acute liver failure, but this is less common. Typically, cirrhosis of the liver leads to portal hypertension, which in some cases leads to hepatopulmonary syndrome. Less commonly, portal hypertension by other causes, such as blood clots, can also lead to hepatopulmonary syndrome.
#10 Hepatopulmonary Syndrome – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK562169/
HPS is most commonly associated with portal hypertension due to chronic liver disease or cirrhosis. However, portal hypertension without underlying liver disease can also cause HPS. Acute liver disease, like acute hepatitis resulting in acute liver failure, is a rare cause of HPS. The presence and severity of HPS do not correlate with the severity of liver disease. […] Pulmonary vascular dilatation resulting from an imbalance between vasodilators and vasoconstrictors is thought to be the main cause of HPS. The exact mechanism of vasodilation is not precise, and multiple studies are ongoing to elucidate the exact mechanism.
#11 Hepatopulmonary Syndrome – OpenAnesthesia
https://www.openanesthesia.org/keywords/hepatopulmonary-syndrome/
Hepatopulmonary syndrome (HPS) is characterized by intrapulmonary vascular dilatations in the setting of portal hypertension, leading to right-to-left shunts and hypoxia. […] The severity of liver disease or portal hypertension does not predict the presence or severity of HPS. […] Endotoxemia and bacterial translocation leads to the activation of macrophages and monocytes in the lungs, causing the accumulation and/or activation of cytotoxic and vasodilatory mediators such as nitric oxide, tumor necrosis factor-alpha, carbon monoxide, and endothelin which contribute to the development of abnormal pulmonary vascular dilatation. […] HPS is a state of ventilation-perfusion mismatch. Increased perfusion secondary to vascular dilatation and collateralization in the setting of preserved ventilation results in the right-to-left shunting of blood. […] Liver transplantation is the only known cure for HPS.
#12 Hepatopulmonary syndrome – Past to present | Annals of Hepatology
https://www.elsevier.es/en-revista-annals-hepatology-16-articulo-hepatopulmonary-syndrome-past-present-S1665268119319180
Hepatopulmonary syndrome (HPS) is the one of the complication of liver cirrhosis with portal hypertension, irrespective of etiology, age and sex. […] The etiopathogenesis of this syndrome remains unknown. The most commonly accepted hypothesis postulates that there is inadequate synthesis or metabolism of pulmonary vasoactive substances such as nitric oxide, prostaglandins, vasoactive intestinal peptide, calcitonin, glucagon, substance P and atrial natriuretic factor, by the impaired liver leading to a functional vasodilatation of the pulmonary vasculature producing hypoxemia. […] HPS is found most commonly in the setting of cirrhosis, both less and advanced forms. […] HPS is also recognized in patients with portal hypertension in the absence of cirrhosis such as in portal vein thrombosis, nodular regenerative hyperplasia, congenital hepatic fibrosis and Budd-Chiari syndrome and also in the setting of acute and chronic hepatitis in the absence of portal hypertension.
#13 What Is Hepatopulmonary Syndrome?
https://www.icliniq.com/articles/respiratory-health/hepatopulmonary-syndrome
Hence, these nitric oxide-mediated changes in pulmonary blood vessel size result in structural changes in the blood vessels called vascular remodeling. […] Hepatopulmonary syndrome is caused by the dilation of blood vessels in the lungs, which reduces oxygen exchange. The exact cause is unknown, but it is thought to be caused by increased levels of nitric oxide and other substances in the blood due to liver diseases. […] Common causes include: Liver cirrhosis, Non-alcoholic fatty liver disease, Hepatitis C, Alcoholic liver disease, Genetic disorders, Liver tumors, Autoimmune diseases. […] Low oxygen levels can occur due to liver diseases. In hepatopulmonary syndrome, liver disease leads to the dilation of blood vessels in the lungs, impairs oxygen and carbon dioxide exchange, resulting in low oxygen levels in the blood.
#14 What Is Hepatopulmonary Syndrome?
https://www.icliniq.com/articles/respiratory-health/hepatopulmonary-syndrome
Hence, these nitric oxide-mediated changes in pulmonary blood vessel size result in structural changes in the blood vessels called vascular remodeling. […] Hepatopulmonary syndrome is caused by the dilation of blood vessels in the lungs, which reduces oxygen exchange. The exact cause is unknown, but it is thought to be caused by increased levels of nitric oxide and other substances in the blood due to liver diseases. […] Common causes include: Liver cirrhosis, Non-alcoholic fatty liver disease, Hepatitis C, Alcoholic liver disease, Genetic disorders, Liver tumors, Autoimmune diseases. […] Low oxygen levels can occur due to liver diseases. In hepatopulmonary syndrome, liver disease leads to the dilation of blood vessels in the lungs, impairs oxygen and carbon dioxide exchange, resulting in low oxygen levels in the blood.
#15 Hepatopulmonary Syndrome – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK562169/
HPS is most commonly associated with portal hypertension due to chronic liver disease or cirrhosis. However, portal hypertension without underlying liver disease can also cause HPS. Acute liver disease, like acute hepatitis resulting in acute liver failure, is a rare cause of HPS. The presence and severity of HPS do not correlate with the severity of liver disease. […] Pulmonary vascular dilatation resulting from an imbalance between vasodilators and vasoconstrictors is thought to be the main cause of HPS. The exact mechanism of vasodilation is not precise, and multiple studies are ongoing to elucidate the exact mechanism.
#16 Hepatopulmonary Syndrome: A Comprehensive Review
https://pmc.ncbi.nlm.nih.gov/articles/PMC11340781/
Hepatopulmonary syndrome (HPS) is defined by abnormally dilated blood vessels and shunts within the lungs, leading to impaired oxygen exchange. […] HPS is characterized by low blood oxygen levels along with portal hypertension, primarily caused by the dilation of small blood vessels within the lungs. […] The primary cause of HPS is believed to be pulmonary vascular dilatation, which arises from an imbalance between substances that promote vasodilation and those that induce vasoconstriction. […] In cirrhotic patients with HPS, exhaled NO levels increase compared to cirrhotic control patients. […] The prevalence of this condition is higher in individuals possessing the monocyte chemoattractant protein-1 (MCP-1) 2518G gene. […] The proposed cause of hypoxemia is reduced oxygen diffusion across the dilated vessels, coupled with a shortened intrapulmonary blood transit time.
#17 Hepatopulmonary Syndrome Management
https://icloudhospital.com/specialties/hepatopulmonary-syndrome-management
Hypoxemia in HPS is caused largely by limits in the passage of oxygen from the lungs into the circulation (diffusion limitation) and mismatching between air and blood moving through the lungs (ventilation-perfusion mismatch), both of which are induced by the presence of IPVDs. […] The etiology of HPS is unknown, as is why some people with liver illness develop Intrapulmonary vascular dilatations (IPVDs) whereas others do not. […] Autopsies of HPS patients revealed that the lungs’ capillaries are substantially swollen (dilated). These enlargements may be caused by excessive production or poor liver clearance of chemicals that relax blood vessels (vasodilators), or by reduced production or lack of sensitivity to a chemical typically produced by a healthy liver that induces blood vessels to contract (vasoconstrictor).
#18 Hepatopulmonary syndrome | UM Health-Sparrow
https://www.uofmhealthsparrow.org/departments-conditions/conditions/hepatopulmonary-syndrome
Hepatopulmonary syndrome is caused by blood vessels in the lungs expanding, also called dilating, and increasing in number. This condition affects the lungs of people who have advanced liver disease. […] Hepatopulmonary syndrome is caused when blood vessels in and around the lungs widen, also called dilate. This affects the amount of oxygen that moves from the lungs into the bloodstream. […] What causes this is not clear. And it’s not known why some people with liver disease develop hepatopulmonary syndrome while others do not.
#19 Hepatopulmonary syndrome – Augusta HealthSearchClose SearchSearch IconSearch IconClose Search IconMobile Menu IconMobile Menu Close IconInstagramFacebookTwitterYoutube
https://www.augustahealth.com/disease/hepatopulmonary-syndrome/
Hepatopulmonary syndrome is caused by blood vessels in the lungs expanding (dilating) and increasing in number, making it hard for red blood cells to properly absorb oxygen. […] Hepatopulmonary syndrome is caused when blood vessels in and around the lungs widen (dilate), which affects the amount of oxygen that moves from the lungs into the bloodstream. What causes this abnormality remains unclear, and itâs unknown why some people with liver disease develop hepatopulmonary syndrome while others do not.
#20 Hepatopulmonary syndrome – Wikipedia
https://en.wikipedia.org/wiki/Hepatopulmonary_syndrome
In medicine, hepatopulmonary syndrome is a syndrome of shortness of breath and hypoxemia (low oxygen levels in the blood of the arteries) caused by vasodilation (broadening of the blood vessels) in the lungs of patients with liver disease. […] The hepatopulmonary syndrome results from the formation of microscopic intrapulmonary arteriovenous dilatations in patients with both chronic, and far less commonly acute liver failure. […] The mechanism is unknown but is thought to be due to increased liver production or decreased liver clearance of vasodilators, possibly involving nitric oxide. […] The dilation of these blood vessels causes overperfusion relative to ventilation, leading to ventilation-perfusion mismatch and hypoxemia. […] Hepatopulmonary syndrome (HPS) consists of the triad of liver dysfunction, otherwise unexplained hypoxemia, and intrapulmonary vascular dilation (IPVD). […] Currently the only definitive treatment is liver transplantation. […] Alternative treatments such as supplemental oxygen or somatostatin to inhibit vasodilation remain anecdotal.
#21 Hepatopulmonary Syndrome Management
https://icloudhospital.com/specialties/hepatopulmonary-syndrome-management
It is apparent that nitric oxide (NO) has emerged as a key cause of blood vessel dilatation at the level of the pulmonary blood vessels (vasodilation). […] As our understanding of what causes HPS grows, it becomes clear that these NO-mediated changes in pulmonary blood vessel size likely culminate in a more chronic alteration in the structure of the blood vessels themselves, known as vascular remodeling. […] The fundamental cause of HPS is assumed to be pulmonary vascular dilatation caused by an imbalance between vasodilators and vasoconstrictors. […] Because of increased hepatic synthesis of endothelin 1 (ET1) and pulmonary endothelin B (ETB) in response to stress, pulmonary endothelial nitric oxide synthetase (eNOS) activation occurs in the lungs. […] In individuals with liver illness, intestinal bacteria translocation and endotoxemia cause a significant buildup of macrophages and monocytes in the lungs.
#22 Hepatopulmonary Syndrome: A Comprehensive Review
https://pmc.ncbi.nlm.nih.gov/articles/PMC11340781/
Hepatopulmonary syndrome (HPS) is defined by abnormally dilated blood vessels and shunts within the lungs, leading to impaired oxygen exchange. […] HPS is characterized by low blood oxygen levels along with portal hypertension, primarily caused by the dilation of small blood vessels within the lungs. […] The primary cause of HPS is believed to be pulmonary vascular dilatation, which arises from an imbalance between substances that promote vasodilation and those that induce vasoconstriction. […] In cirrhotic patients with HPS, exhaled NO levels increase compared to cirrhotic control patients. […] The prevalence of this condition is higher in individuals possessing the monocyte chemoattractant protein-1 (MCP-1) 2518G gene. […] The proposed cause of hypoxemia is reduced oxygen diffusion across the dilated vessels, coupled with a shortened intrapulmonary blood transit time.
#23 Hepatopulmonary Syndrome Management
https://icloudhospital.com/specialties/hepatopulmonary-syndrome-management
It is apparent that nitric oxide (NO) has emerged as a key cause of blood vessel dilatation at the level of the pulmonary blood vessels (vasodilation). […] As our understanding of what causes HPS grows, it becomes clear that these NO-mediated changes in pulmonary blood vessel size likely culminate in a more chronic alteration in the structure of the blood vessels themselves, known as vascular remodeling. […] The fundamental cause of HPS is assumed to be pulmonary vascular dilatation caused by an imbalance between vasodilators and vasoconstrictors. […] Because of increased hepatic synthesis of endothelin 1 (ET1) and pulmonary endothelin B (ETB) in response to stress, pulmonary endothelial nitric oxide synthetase (eNOS) activation occurs in the lungs. […] In individuals with liver illness, intestinal bacteria translocation and endotoxemia cause a significant buildup of macrophages and monocytes in the lungs.
#24 What Is Hepatopulmonary Syndrome?
https://www.icliniq.com/articles/respiratory-health/hepatopulmonary-syndrome
Autopsy reports in hepatopulmonary syndrome patients suggest that small blood vessels in the lungs are severely enlarged or dilated. These dilations are due to increased production or impaired liver clearance of chemicals that cause blood vessels to relax, or decreased production of chemicals causes blood vessels to contract. […] During this process, the release of nitric oxide (NO) at the level of pulmonary blood vessels is found to be a key factor in causing the dilation of blood vessels. […] The nitric oxide is released through several pathways, such as gut bacterial translocation -inflammation caused by bacteria and bacteria material escaping from the gut into the blood circulation in patients with cirrhosis. This results in the recruitment of macrophages to the pulmonary blood vessels, where nitric oxide is produced.
#25 What Is Hepatopulmonary Syndrome?
https://www.icliniq.com/articles/respiratory-health/hepatopulmonary-syndrome
Autopsy reports in hepatopulmonary syndrome patients suggest that small blood vessels in the lungs are severely enlarged or dilated. These dilations are due to increased production or impaired liver clearance of chemicals that cause blood vessels to relax, or decreased production of chemicals causes blood vessels to contract. […] During this process, the release of nitric oxide (NO) at the level of pulmonary blood vessels is found to be a key factor in causing the dilation of blood vessels. […] The nitric oxide is released through several pathways, such as gut bacterial translocation -inflammation caused by bacteria and bacteria material escaping from the gut into the blood circulation in patients with cirrhosis. This results in the recruitment of macrophages to the pulmonary blood vessels, where nitric oxide is produced.
#26 Hepatopulmonary Syndrome Management
https://icloudhospital.com/specialties/hepatopulmonary-syndrome-management
It is apparent that nitric oxide (NO) has emerged as a key cause of blood vessel dilatation at the level of the pulmonary blood vessels (vasodilation). […] As our understanding of what causes HPS grows, it becomes clear that these NO-mediated changes in pulmonary blood vessel size likely culminate in a more chronic alteration in the structure of the blood vessels themselves, known as vascular remodeling. […] The fundamental cause of HPS is assumed to be pulmonary vascular dilatation caused by an imbalance between vasodilators and vasoconstrictors. […] Because of increased hepatic synthesis of endothelin 1 (ET1) and pulmonary endothelin B (ETB) in response to stress, pulmonary endothelial nitric oxide synthetase (eNOS) activation occurs in the lungs. […] In individuals with liver illness, intestinal bacteria translocation and endotoxemia cause a significant buildup of macrophages and monocytes in the lungs.
#27 Hepatopulmonary syndrome: What we know and what we would like to know
https://www.wjgnet.com/1007-9327/full/v22/i25/5728.htm
Hepatopulmonary syndrome (HPS) is characterized by abnormalities in blood oxygenation caused by the presence of intrapulmonary vascular dilations (IPVD) in the context of liver disease, generally at a cirrhotic stage. […] The majority of the information about the etiopathogenesis of HPS has been obtained through experiments on animals. […] The main mediators involved in the onset of IPVD, which are fundamental to the pathogenesis of HPS, are nitric oxide (NO) and carbon monoxide (CO). […] Studies in animals keep leading to the discovery of new molecules which offer innovative perspectives in terms of the understanding of the etiopathogenesis of HPS and which could provide future targets for medical treatment of the syndrome. […] The principal abnormality which defines HPS is the dilatation of pre and post-capillary pulmonary vessels in the alveolar regions.
#28 Cirrhosis and hepatopulmonary syndrome
https://www.wjgnet.com/1007-9327/full/v20/i10/2586.htm
Hepatopulmonary syndrome (HPS) is characterized as a triad: liver disease, intrapulmonary vascular dilatation and arterial hypoxemia. HPS is reported to be present in 4% to 32% of adult patients with end-stage liver disease and in 9%-20% of children. The pathogenesis of HPS has not been clearly identified. Portal hypertension causes impairment in the perfusion of the bowel and increases the enteral translocation of Gram (-) bacteria and endotoxins. This stimulates the release of vasoactive mediators, such as tumor necrosis factor-alpha, heme oxygenase-derived carbon monoxide and nitric oxide. Genetic alterations have not been associated with this syndrome yet; however, cytokines and chemokines have been suggested to play a role. Recently, it was reported that cumulated monocytes lead to the activation of vascular endothelial growth factor-dependent signaling pathways and pulmonary angiogenesis, which plays an important role in HPS pathogenesis. At present, the most effective and only radical treatment is a liver transplant (LT). Cirrhotic patients who are on the waiting list for an LT have a shorter survival period if they develop HPS. Therefore, it is suggested that all cirrhotic cases should be followed closely for HPS and they should have priority in the waiting list.
#29 Hepatopulmonary syndrome: What we know and what we would like to know
https://www.wjgnet.com/1007-9327/full/v22/i25/5728.htm
Hepatopulmonary syndrome (HPS) is characterized by abnormalities in blood oxygenation caused by the presence of intrapulmonary vascular dilations (IPVD) in the context of liver disease, generally at a cirrhotic stage. […] The majority of the information about the etiopathogenesis of HPS has been obtained through experiments on animals. […] The main mediators involved in the onset of IPVD, which are fundamental to the pathogenesis of HPS, are nitric oxide (NO) and carbon monoxide (CO). […] Studies in animals keep leading to the discovery of new molecules which offer innovative perspectives in terms of the understanding of the etiopathogenesis of HPS and which could provide future targets for medical treatment of the syndrome. […] The principal abnormality which defines HPS is the dilatation of pre and post-capillary pulmonary vessels in the alveolar regions.
#30 Hepatopulmonary syndrome – Past to present | Annals of Hepatology
https://www.elsevier.es/en-revista-annals-hepatology-16-articulo-hepatopulmonary-syndrome-past-present-S1665268119319180
Hepatopulmonary syndrome (HPS) is the one of the complication of liver cirrhosis with portal hypertension, irrespective of etiology, age and sex. […] The etiopathogenesis of this syndrome remains unknown. The most commonly accepted hypothesis postulates that there is inadequate synthesis or metabolism of pulmonary vasoactive substances such as nitric oxide, prostaglandins, vasoactive intestinal peptide, calcitonin, glucagon, substance P and atrial natriuretic factor, by the impaired liver leading to a functional vasodilatation of the pulmonary vasculature producing hypoxemia. […] HPS is found most commonly in the setting of cirrhosis, both less and advanced forms. […] HPS is also recognized in patients with portal hypertension in the absence of cirrhosis such as in portal vein thrombosis, nodular regenerative hyperplasia, congenital hepatic fibrosis and Budd-Chiari syndrome and also in the setting of acute and chronic hepatitis in the absence of portal hypertension.
#31 Hepatopulmonary syndrome – Past to present | Annals of Hepatology
https://www.elsevier.es/en-revista-annals-hepatology-16-articulo-hepatopulmonary-syndrome-past-present-S1665268119319180
Intestinal endotoxemia accompanying cirrhosis may be an important factor in the development of hepatopulmonary syndrome. […] Overproduction of TNF-alpha due to endotoxin stimulation of Kupffer cells via mitogen-activated protein kinase (MAPK) signal transduction pathway may be a major mechanism mediating the pathologic alterations of hepatopulmonary syndrome.
#32
https://www.ijcasereportsandimages.com/archive/2017/002-2017-ijcri/CR-10759-02-2017-aravinda/ijcri-1075902201759-aravinda-full-text.php
Hepatopulmonary syndrome is characterized by arterial hypoxemia and pulmonary vascular dilatations. […] Diagnosis of hepatopulmonary syndrome was made through a constellation of findings in blood gas analysis, contrast echocardiography with biochemical and ultrasound evidence of liver disease applied to standard criteria; having excluded other possible causes. […] Hepatopulmonary syndrome should be suspected in any patient with liver disease and hypoxia. […] Aetiology of pulmonary vascular dilatation in cirrhosis is thought to relate to an increase in pulmonary NO by means of both endothelial and inducible NO synthase (eNOS and iNOS). […] An increased hepatic production of vasoconstrictor Endothelin-1 (ET-1) stimulates the production of ETB receptors in pulmonary microcirculation. […] Portal hypertension weakens intestinal mucosal barrier due to impaired drainage.
#33 Hepatopulmonary Syndrome – OpenAnesthesia
https://www.openanesthesia.org/keywords/hepatopulmonary-syndrome/
Hepatopulmonary syndrome (HPS) is characterized by intrapulmonary vascular dilatations in the setting of portal hypertension, leading to right-to-left shunts and hypoxia. […] The severity of liver disease or portal hypertension does not predict the presence or severity of HPS. […] Endotoxemia and bacterial translocation leads to the activation of macrophages and monocytes in the lungs, causing the accumulation and/or activation of cytotoxic and vasodilatory mediators such as nitric oxide, tumor necrosis factor-alpha, carbon monoxide, and endothelin which contribute to the development of abnormal pulmonary vascular dilatation. […] HPS is a state of ventilation-perfusion mismatch. Increased perfusion secondary to vascular dilatation and collateralization in the setting of preserved ventilation results in the right-to-left shunting of blood. […] Liver transplantation is the only known cure for HPS.
#34 Hepatopulmonary syndrome – Past to present | Annals of Hepatology
https://www.elsevier.es/en-revista-annals-hepatology-16-articulo-hepatopulmonary-syndrome-past-present-S1665268119319180
Intestinal endotoxemia accompanying cirrhosis may be an important factor in the development of hepatopulmonary syndrome. […] Overproduction of TNF-alpha due to endotoxin stimulation of Kupffer cells via mitogen-activated protein kinase (MAPK) signal transduction pathway may be a major mechanism mediating the pathologic alterations of hepatopulmonary syndrome.
#35 Hepatopulmonary Syndrome: A Comprehensive Review
https://pmc.ncbi.nlm.nih.gov/articles/PMC11340781/
Hepatopulmonary syndrome (HPS) is defined by abnormally dilated blood vessels and shunts within the lungs, leading to impaired oxygen exchange. […] HPS is characterized by low blood oxygen levels along with portal hypertension, primarily caused by the dilation of small blood vessels within the lungs. […] The primary cause of HPS is believed to be pulmonary vascular dilatation, which arises from an imbalance between substances that promote vasodilation and those that induce vasoconstriction. […] In cirrhotic patients with HPS, exhaled NO levels increase compared to cirrhotic control patients. […] The prevalence of this condition is higher in individuals possessing the monocyte chemoattractant protein-1 (MCP-1) 2518G gene. […] The proposed cause of hypoxemia is reduced oxygen diffusion across the dilated vessels, coupled with a shortened intrapulmonary blood transit time.
#36 Hepatopulmonary Syndrome | Abdominal Key
https://abdominalkey.com/hepatopulmonary-syndrome-2/
Hepatopulmonary syndrome is a condition that may be present in patients with liver disease. It is characterized by low levels of oxygen in the body. We think that the diseased liver is responsible for changes in the lungs that cause the low oxygen levels. […] The main pathological features of HPS are gross dilatation of the pulmonary pre-capillary and capillary vessels as well as an increase in the absolute number of dilated vessels. Additionally, some pleural and pulmonary arteriovenous communications (true shunts) may also be observed. […] Although the exact biological pathways that lead to the development of HPS need to be elucidated, a recent study found that polymorphisms in candidate genes involved in the regulation of angiogenesis was associated with a higher risk of HPS. […] Several lines of indirect evidence implicate NO and angiogenesis as likely contributors. Exhaled nitric oxide levels in patients with HPS are higher compared to those without HPS and these levels normalize after liver transplantation. […] Polymorphisms in genes associated with angiogenesis have now been linked to the presence of HPS.
#37 Hepatopulmonary Syndrome – Pulmonary Disorders – Merck Manual Professional Edition
https://www.merckmanuals.com/professional/pulmonary-disorders/pulmonary-hypertension/hepatopulmonary-syndrome
Hepatopulmonary syndrome results from the formation of microscopic intrapulmonary arteriovenous dilations in patients with chronic liver disease typically when complicated by portal hypertension. The mechanism is unknown but is thought to be due to increased hepatic production or decreased hepatic clearance of vasodilators. The vascular dilations cause overperfusion relative to ventilation, leading to hypoxemia, particularly because patients have an increased cardiac output resulting from systemic vasodilation. […] Hepatopulmonary syndrome is associated with reduced levels of bone morphogenetic protein 9 (BMP9) and BMP10 when compared to control patients with advanced liver disease without hepatopulmonary syndrome. Lower BMP9 levels were further associated with more severe hepatopulmonary syndrome.
#38 What Is Hepatopulmonary Syndrome?
https://www.icliniq.com/articles/respiratory-health/hepatopulmonary-syndrome
Hepatopulmonary syndrome is a rare lung complication associated with liver disease. This article illustrates the causes and management of this disease. […] Hepatopulmonary syndrome (HPS) is the common cause of respiratory insufficiency in patients with chronic liver disease. When the liver is not functioning properly, the blood vessels in the lungs may get dilated. The severity of this condition results in the failure of the lungs to effectively transfer oxygen to the body. This is referred to as hepatopulmonary syndrome. It is commonly seen in patients with scarring of the liver. […] The cause of hepatopulmonary syndrome is most commonly associated with portal hypertension due to chronic liver disease or cirrhosis. […] Hypoxemia in hepatopulmonary syndrome occurs commonly due to limitations to the movement of oxygen from the lungs into the bloodstream and also due to the mismatching ratio between air moving through the lungs and blood moving into the lungs (ventilation-perfusion mismatch) – Caused as a result of intrapulmonary vascular dilatation (IVPD).
#39 Hepatopulmonary Syndrome Management
https://icloudhospital.com/specialties/hepatopulmonary-syndrome-management
Hypoxemia in HPS is caused largely by limits in the passage of oxygen from the lungs into the circulation (diffusion limitation) and mismatching between air and blood moving through the lungs (ventilation-perfusion mismatch), both of which are induced by the presence of IPVDs. […] The etiology of HPS is unknown, as is why some people with liver illness develop Intrapulmonary vascular dilatations (IPVDs) whereas others do not. […] Autopsies of HPS patients revealed that the lungs’ capillaries are substantially swollen (dilated). These enlargements may be caused by excessive production or poor liver clearance of chemicals that relax blood vessels (vasodilators), or by reduced production or lack of sensitivity to a chemical typically produced by a healthy liver that induces blood vessels to contract (vasoconstrictor).
#40 Hepatopulmonary Syndrome: A Comprehensive Review
https://pmc.ncbi.nlm.nih.gov/articles/PMC11340781/
Hepatopulmonary syndrome (HPS) is defined by abnormally dilated blood vessels and shunts within the lungs, leading to impaired oxygen exchange. […] HPS is characterized by low blood oxygen levels along with portal hypertension, primarily caused by the dilation of small blood vessels within the lungs. […] The primary cause of HPS is believed to be pulmonary vascular dilatation, which arises from an imbalance between substances that promote vasodilation and those that induce vasoconstriction. […] In cirrhotic patients with HPS, exhaled NO levels increase compared to cirrhotic control patients. […] The prevalence of this condition is higher in individuals possessing the monocyte chemoattractant protein-1 (MCP-1) 2518G gene. […] The proposed cause of hypoxemia is reduced oxygen diffusion across the dilated vessels, coupled with a shortened intrapulmonary blood transit time.
#41 Hepatopulmonary Syndrome – OpenAnesthesia
https://www.openanesthesia.org/keywords/hepatopulmonary-syndrome/
Hepatopulmonary syndrome (HPS) is characterized by intrapulmonary vascular dilatations in the setting of portal hypertension, leading to right-to-left shunts and hypoxia. […] The severity of liver disease or portal hypertension does not predict the presence or severity of HPS. […] Endotoxemia and bacterial translocation leads to the activation of macrophages and monocytes in the lungs, causing the accumulation and/or activation of cytotoxic and vasodilatory mediators such as nitric oxide, tumor necrosis factor-alpha, carbon monoxide, and endothelin which contribute to the development of abnormal pulmonary vascular dilatation. […] HPS is a state of ventilation-perfusion mismatch. Increased perfusion secondary to vascular dilatation and collateralization in the setting of preserved ventilation results in the right-to-left shunting of blood. […] Liver transplantation is the only known cure for HPS.
#42 Hepatopulmonary Syndrome | Abdominal Key
https://abdominalkey.com/hepatopulmonary-syndrome-2/
Hepatopulmonary syndrome is a condition that may be present in patients with liver disease. It is characterized by low levels of oxygen in the body. We think that the diseased liver is responsible for changes in the lungs that cause the low oxygen levels. […] The main pathological features of HPS are gross dilatation of the pulmonary pre-capillary and capillary vessels as well as an increase in the absolute number of dilated vessels. Additionally, some pleural and pulmonary arteriovenous communications (true shunts) may also be observed. […] Although the exact biological pathways that lead to the development of HPS need to be elucidated, a recent study found that polymorphisms in candidate genes involved in the regulation of angiogenesis was associated with a higher risk of HPS. […] Several lines of indirect evidence implicate NO and angiogenesis as likely contributors. Exhaled nitric oxide levels in patients with HPS are higher compared to those without HPS and these levels normalize after liver transplantation. […] Polymorphisms in genes associated with angiogenesis have now been linked to the presence of HPS.
#43 Hepatopulmonary Syndrome: A Comprehensive Review
https://pmc.ncbi.nlm.nih.gov/articles/PMC11340781/
HPS can be classified using angiographic patterns seen when pulmonary arteriography is conducted in patients with severe respiratory depression. […] The only form of definitive treatment for HPS is a complete liver transplant, which leads to a total reversal of HPS maladaptive changes and provides the best overall long-term prognosis.
#44 Hepatopulmonary Syndrome – Pulmonary Disorders – Merck Manual Professional Edition
https://www.merckmanuals.com/professional/pulmonary-disorders/pulmonary-hypertension/hepatopulmonary-syndrome
Hepatopulmonary syndrome results from the formation of microscopic intrapulmonary arteriovenous dilations in patients with chronic liver disease typically when complicated by portal hypertension. The mechanism is unknown but is thought to be due to increased hepatic production or decreased hepatic clearance of vasodilators. The vascular dilations cause overperfusion relative to ventilation, leading to hypoxemia, particularly because patients have an increased cardiac output resulting from systemic vasodilation. […] Hepatopulmonary syndrome is associated with reduced levels of bone morphogenetic protein 9 (BMP9) and BMP10 when compared to control patients with advanced liver disease without hepatopulmonary syndrome. Lower BMP9 levels were further associated with more severe hepatopulmonary syndrome.
#45 Clinical outcomes and risk factors of hepatopulmonary syndrome in children | Scientific Reports
https://www.nature.com/articles/s41598-021-83785-x
The purpose of this study was to investigate the clinical outcomes of pediatric HPS and to identify the risk factors for HPS in children with biliary atresia in Korea. […] We found that PS/IVC was a risk factor for HPS in children with BA. Similar to our study, the presence of PS/IVC was more common in patients with HPS, and cirrhosis is not a requirement for the development of HPS in children. However, the mechanism of the correlation between PS/IVC and HPS is still unknown. […] The limitations of this study are the small number of patients and the application of two methods to diagnose intrapulmonary vasodilation. […] In conclusion, the prevalence of HPS in children with BA, portal vein agenesis, and portal vein thrombosis was 7%, 20%, and 4%, respectively. Only one of the total HPS patients died during the 10-year observation period, resulting in a 90% survival rate. Children with severe HPS showed excellent outcomes after LT. PS/IVC are a risk factor for the development of HPS in patients with BA.
#46 Clinical outcomes and risk factors of hepatopulmonary syndrome in children | Scientific Reports
https://www.nature.com/articles/s41598-021-83785-x
The purpose of this study was to investigate the clinical outcomes of pediatric HPS and to identify the risk factors for HPS in children with biliary atresia in Korea. […] We found that PS/IVC was a risk factor for HPS in children with BA. Similar to our study, the presence of PS/IVC was more common in patients with HPS, and cirrhosis is not a requirement for the development of HPS in children. However, the mechanism of the correlation between PS/IVC and HPS is still unknown. […] The limitations of this study are the small number of patients and the application of two methods to diagnose intrapulmonary vasodilation. […] In conclusion, the prevalence of HPS in children with BA, portal vein agenesis, and portal vein thrombosis was 7%, 20%, and 4%, respectively. Only one of the total HPS patients died during the 10-year observation period, resulting in a 90% survival rate. Children with severe HPS showed excellent outcomes after LT. PS/IVC are a risk factor for the development of HPS in patients with BA.
#47 Hepatopulmonary Syndrome and Diffuse Interstitial Lung Disease: An Unusual Combination | Archivos de BronconeumologÃa
https://www.archbronconeumol.org/en-hepatopulmonary-syndrome-diffuse-interstitial-lung-articulo-S1579212918303069
Hepatopulmonary syndrome (HPS) is characterized by a triad of impaired in arterial oxygenation caused by intrapulmonary vascular dilatations (IPVD) in the setting of advanced liver disease. The most common respiratory symptom is progressive dyspnea. Platypnea-orthodeoxia (increased dyspnea and reduced oxygen saturation in an orthostatic position) can occur in up to 25% of patients. Other signs suggestive of HPS are telangiectasia, nail clubbing, and peripheral cyanosis. Echocardiography with agitated saline contrast is the method most widely used for detecting and confirming IPVD. Liver transplantation (LT) is the current treatment of choice, since medical options have not demonstrated effectiveness. HPS has been reported to coexist with other respiratory diseases that worsen gas exchange in up to 30% of cases. However, the association with diffuse interstitial pulmonary disease (ILD) has been rarely reported in the literature. HPS in a patient with ILD complicates the diagnostic process and may limit the treatment options for both entities.
#48 Hepatopulmonary Syndrome and Diffuse Interstitial Lung Disease: An Unusual Combination | Archivos de BronconeumologÃa
https://www.archbronconeumol.org/en-hepatopulmonary-syndrome-diffuse-interstitial-lung-articulo-S1579212918303069
Hepatopulmonary syndrome (HPS) is characterized by a triad of impaired in arterial oxygenation caused by intrapulmonary vascular dilatations (IPVD) in the setting of advanced liver disease. The most common respiratory symptom is progressive dyspnea. Platypnea-orthodeoxia (increased dyspnea and reduced oxygen saturation in an orthostatic position) can occur in up to 25% of patients. Other signs suggestive of HPS are telangiectasia, nail clubbing, and peripheral cyanosis. Echocardiography with agitated saline contrast is the method most widely used for detecting and confirming IPVD. Liver transplantation (LT) is the current treatment of choice, since medical options have not demonstrated effectiveness. HPS has been reported to coexist with other respiratory diseases that worsen gas exchange in up to 30% of cases. However, the association with diffuse interstitial pulmonary disease (ILD) has been rarely reported in the literature. HPS in a patient with ILD complicates the diagnostic process and may limit the treatment options for both entities.
#49 Hepatopulmonary Syndrome and Diffuse Interstitial Lung Disease: An Unusual Combination | Archivos de BronconeumologÃa
https://www.archbronconeumol.org/en-hepatopulmonary-syndrome-diffuse-interstitial-lung-articulo-S1579212918303069
The pathogenesis of this association is unknown. However, fibrosing lung diseases and cirrhosis are characterized by the presence of epithelial/endothelial damage with abnormal scarring that leads to fibroproliferation and tissue remodeling, involving several common inflammatory cytokines and growth factors (TNF-, IL-1, TGF- and VEGF). A recent study pointed to telomere shortening as one of the possible mechanisms involved. […] In conclusion, the coexistence of HPS and ILD raises a number of difficulties in the diagnostic and therapeutic approach of both entities, and affects progress. Further studies are needed to explore the particularities of this association in order to be able to create strategies to improve prognosis.
#50 Hepatopulmonary Syndrome: A Comprehensive Review
https://pmc.ncbi.nlm.nih.gov/articles/PMC11340781/
HPS can be classified using angiographic patterns seen when pulmonary arteriography is conducted in patients with severe respiratory depression. […] The only form of definitive treatment for HPS is a complete liver transplant, which leads to a total reversal of HPS maladaptive changes and provides the best overall long-term prognosis.
#51 Hepatopulmonary Syndrome – OpenAnesthesia
https://www.openanesthesia.org/keywords/hepatopulmonary-syndrome/
Hepatopulmonary syndrome (HPS) is characterized by intrapulmonary vascular dilatations in the setting of portal hypertension, leading to right-to-left shunts and hypoxia. […] The severity of liver disease or portal hypertension does not predict the presence or severity of HPS. […] Endotoxemia and bacterial translocation leads to the activation of macrophages and monocytes in the lungs, causing the accumulation and/or activation of cytotoxic and vasodilatory mediators such as nitric oxide, tumor necrosis factor-alpha, carbon monoxide, and endothelin which contribute to the development of abnormal pulmonary vascular dilatation. […] HPS is a state of ventilation-perfusion mismatch. Increased perfusion secondary to vascular dilatation and collateralization in the setting of preserved ventilation results in the right-to-left shunting of blood. […] Liver transplantation is the only known cure for HPS.
#52 Hepatopulmonary Syndrome: Symptoms, Causes & Treatment
https://my.clevelandclinic.org/health/diseases/24190-hepatopulmonary-syndrome
Scientists aren’t sure exactly how portal hypertension causes dilation of the blood vessels in your lungs, though they have some ideas. They also don’t know why it only happens to some people and not others. It doesn’t seem to correlate with how advanced your liver disease is. They do know that vasodilation in your lungs causes hypoxemia. It causes an imbalance of blood flow relative to air ventilation. […] Liver transplantation is the only known cure for hepatopulmonary syndrome. After a successful liver transplant, vasodilation in your lungs and hypoxemia begin to reverse. It takes between six and 12 months for your pulmonary function to return to normal. However, not everyone qualifies for a liver transplant, and those who do often have to wait for one. This cure can be a race against time.
#53 Cirrhosis and hepatopulmonary syndrome
https://www.wjgnet.com/1007-9327/full/v20/i10/2586.htm
Hepatopulmonary syndrome (HPS) is characterized as a triad: liver disease, intrapulmonary vascular dilatation and arterial hypoxemia. HPS is reported to be present in 4% to 32% of adult patients with end-stage liver disease and in 9%-20% of children. The pathogenesis of HPS has not been clearly identified. Portal hypertension causes impairment in the perfusion of the bowel and increases the enteral translocation of Gram (-) bacteria and endotoxins. This stimulates the release of vasoactive mediators, such as tumor necrosis factor-alpha, heme oxygenase-derived carbon monoxide and nitric oxide. Genetic alterations have not been associated with this syndrome yet; however, cytokines and chemokines have been suggested to play a role. Recently, it was reported that cumulated monocytes lead to the activation of vascular endothelial growth factor-dependent signaling pathways and pulmonary angiogenesis, which plays an important role in HPS pathogenesis. At present, the most effective and only radical treatment is a liver transplant (LT). Cirrhotic patients who are on the waiting list for an LT have a shorter survival period if they develop HPS. Therefore, it is suggested that all cirrhotic cases should be followed closely for HPS and they should have priority in the waiting list.
#54 Hepatopulmonary Syndrome: Symptoms, Causes & Treatment
https://my.clevelandclinic.org/health/diseases/24190-hepatopulmonary-syndrome
If you have hepatopulmonary syndrome, you probably already have chronic liver disease. End-stage liver disease itself is eventually fatal without a liver transplant. Hepatopulmonary syndrome is just one of many side effects and complications that can come with it. Most people with hepatopulmonary syndrome don’t die from hypoxemia alone, but it does contribute to their overall decline. […] For those with cirrhosis and hepatopulmonary syndrome, the average is two years without a liver transplant.
#55 Hepatopulmonary syndrome in adults: Natural history, treatment, and outcomes – UpToDate
https://www.uptodate.com/contents/hepatopulmonary-syndrome-in-adults-natural-history-treatment-and-outcomes
Hepatopulmonary syndrome (HPS) is characterized by the triad of abnormal arterial oxygenation caused by intrapulmonary vascular dilatations in the setting of liver disease, portal hypertension, or congenital portosystemic shunts. […] The cause of death among patients with HPS tends to be multifactorial and related to complications of underlying liver disease (eg, hepatic failure, multisystem organ failure due to sepsis, hepatocellular cancer, gastrointestinal bleeding) rather than from HPS-related hypoxemic respiratory failure. […] Spontaneous resolution of HPS without treatment is unlikely.
#56 Hepatopulmonary syndrome in adults: Natural history, treatment, and outcomes – UpToDate
https://www.uptodate.com/contents/hepatopulmonary-syndrome-in-adults-natural-history-treatment-and-outcomes
Hepatopulmonary syndrome (HPS) is characterized by the triad of abnormal arterial oxygenation caused by intrapulmonary vascular dilatations in the setting of liver disease, portal hypertension, or congenital portosystemic shunts. […] The cause of death among patients with HPS tends to be multifactorial and related to complications of underlying liver disease (eg, hepatic failure, multisystem organ failure due to sepsis, hepatocellular cancer, gastrointestinal bleeding) rather than from HPS-related hypoxemic respiratory failure. […] Spontaneous resolution of HPS without treatment is unlikely.
#57 Cirrhosis and hepatopulmonary syndrome
https://www.wjgnet.com/1007-9327/full/v20/i10/2586.htm
Hepatopulmonary syndrome (HPS) is characterized as a triad: liver disease, intrapulmonary vascular dilatation and arterial hypoxemia. HPS is reported to be present in 4% to 32% of adult patients with end-stage liver disease and in 9%-20% of children. The pathogenesis of HPS has not been clearly identified. Portal hypertension causes impairment in the perfusion of the bowel and increases the enteral translocation of Gram (-) bacteria and endotoxins. This stimulates the release of vasoactive mediators, such as tumor necrosis factor-alpha, heme oxygenase-derived carbon monoxide and nitric oxide. Genetic alterations have not been associated with this syndrome yet; however, cytokines and chemokines have been suggested to play a role. Recently, it was reported that cumulated monocytes lead to the activation of vascular endothelial growth factor-dependent signaling pathways and pulmonary angiogenesis, which plays an important role in HPS pathogenesis. At present, the most effective and only radical treatment is a liver transplant (LT). Cirrhotic patients who are on the waiting list for an LT have a shorter survival period if they develop HPS. Therefore, it is suggested that all cirrhotic cases should be followed closely for HPS and they should have priority in the waiting list.
#58 Hepatopulmonary Syndrome: A Comprehensive Review
https://pmc.ncbi.nlm.nih.gov/articles/PMC11340781/
HPS can be classified using angiographic patterns seen when pulmonary arteriography is conducted in patients with severe respiratory depression. […] The only form of definitive treatment for HPS is a complete liver transplant, which leads to a total reversal of HPS maladaptive changes and provides the best overall long-term prognosis.
#59 Hepatopulmonary syndrome: What we know and what we would like to know
https://www.wjgnet.com/1007-9327/full/v22/i25/5728.htm
The prevalence of the syndrome has not been fully established since figures depend on the method employed for the diagnosis and the profile of the patients studied. […] In terms of diagnostic methodology, there are differences in the criteria of alteration of arterial oxygenation which define the syndrome. […] Different results are obtained depending on whether a contrast-enhanced echocardiography or macroaggregated albumin lung perfusion scan (99mTc-MAA) is used and if the echocardiography is transthoracic or transoesophageal. […] The prevalence of HPS in cirrhotic patients was found to be around 15%, while in patients listed for LT, figures have shown between 4% and 32%. […] The most widely studied treatment is LT. At the moment it is the only effective treatment for HPS and is proven to improve survival rates.