Portopulmonary Hypertension -A Little More Data

A recent study (E Echocahrd-Dugelay et al. JPGN 2015; 61: 346-54, editorial 268-9) provides a little more data on the rare condition of portopulmonary hypertension (POPH). Untreated POPH can lead to right-sided heart failure and death; a prompt diagnosis improves the chance for responding to treatment.

In brief, the authors reviewed their experience with 14 patients that were diagnosed with POPH between 1983-2009. The authors also reviewed the literature for a total of 98 patients.


  • 0.5% of children with portal hypertension had POPH
  • 0.9% of children with end-stage liver disease awaiting liver transplantation had POPH
  • Congenital portosystemic shunts (CPSS) appeared to be a risk factor for POPH and were noted in 3 of their 14 cases as well as 22 of 98 cases overall.
  • In treated patients (n=42), five-year survival was noted to be 80%. Treatment included vasodilator therapy, closure of CPSS, or liver transplantation.
  • Hepatopulmonary syndrome (with hypoxemia) may precede POPH; this was reported in 6 of the 98 patients in this report

Dr. Ronald Sokol’s commentary noted that guidelines for timing/frequency of pulse oximetry testing and formal echocardiographic screening are needed but “challenging given the present body of evidence.”  He recommends screening all pediatric liver transplantation candidates who have cirrhosis and portal hypertension with pulse oximetry and echocardiography as well as those with clinical features of POPH (eg. syncope, shortness of breath, dyspnea).  For other patient populations, it remains unclear.

Bottomline (from the authors): “Detection of POPH at an early stage requires systematic screening at regular intervals by echocardiography in children with all causes of portal hypertension.” Unanswered questions:

  • how much portal hypertension is needed to merit screening?
  • how often should screening take place?

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Pulmonary Complications Associated with Chronic Liver Disease

A useful review of “pulmonary complications in chronic liver disease” (Hepatology 2014; 59: 1627-37) has been published.

The main topics included hepatopulmonary syndrome (HPS) , portopulmonary hypertension (POPH), and hepatic hydrothorax (HH).

A few of the key points:

HPS is most common of these conditions and is identified in 5-30% of cirrhosis patients.  It is identified with abnormal oxygenation (screening with pulse ox <96%) due to intrapulmonary vascular dilatations. There is no established medical therapy.  It is reversible with liver transplantation.

The hallmark of POPH is the development of pulmonary arterial hypertension associated with portal hypertension.  It occurs in 5-10% of cirrhosis patients and often presents as dyspnea on exertion/fatigue.  There are numerous pharmacologic treatments that may be useful, include the following:

  • prostacyclin analogs like epoprostenol
  • endothelin receptor antagonists like boesentan
  • phosphodiesterase-5 inhibitors like sildenafil, vardenafil, and tadalafil

Severe POPH is a relative contraindication for liver transplantation.

HH is a transudative pleural effusion seen in 5-10% of cirrhosis patients. Initial management includes salt restriction and diuretics.  Transjugular intrahepatic portosystemic shunt and thoracentesis are second-line options.  Liver transplantation is curative.

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.



Expert advice on portal hypertension

A consensus report on portal hypertension has helpful advice on a broad range of management issues and should be kept in mind as a handy reference (Pediatr Transplantation 2012; 16: 426-37).  The report is concise and full of bullet points.  It is based on a meeting of pediatric experts to modify adult guidelines (Baveno V) for pediatrics.

In many instances, the experts indicate that there is not enough pediatric data. Specific subjects include the following (along with some points):

  • Treatment options for portal hypertension -consider screening for varices if thrombocytopenia and splenomegaly.  ‘No indication to use beta-blockers to prevent varices.’
  • Prevention of first bleeding episode -in the presence of varices (grade II or III), variceal ligation reasonable in selected children and/or within context of defined research protocols. Grade I varices can be flattened with insufflation, and grade III varices are confluent around circumference of esophagus (per Japanese Research Society for Portal HTN analysis)
  • Role of hepatic venous pressure gradient measurement (HVPG) -‘panel was undecided as to whether HVPG measurements in children’ should be ‘part of specialized clinical practice or’ a research tool.
  • Blood volume restitution -suggests use of platelets in cases of bleeding with profound thrombocytopenia (<20,000).
  • Antibiotic prophylaxis -unclear whether empiric antibiotics in children are needed in the presence of variceal bleeding.
  • Management of treatment failures -can retry endoscopy and if fails, consider transjugular intrahepatic portosystemic shunting (TIPS)
  • Management of gastric varices -only case reports in children, thus no evidence-based recommendations.
  • Prevention of rebleeding -variceal ligation (EVL) preferred in patients with cirrhosis.  EVL should be performed every 2-4 weeks up to five sessions to eradicate varices after 1st bleed.
  • Treatment of portal vein obstruction -diagnosis, natural history, anticoagulation, use of MesoRex bypass procedure, associated portal biliopathy -diagnosis and treatment.  With regard to MesoRex, ‘controversy exists as to the appropriateness of ..this procedure in an asymptomatic child.’ Surveillance endoscopy may assist in decision-making.
  • Hypersplenism with portal vein obstruction-in the presence of platelet count <50,000 and portal vein obstruction, strong consideration should be given to MesoRex procedure.
  • Portopulmonary hypertension and hepatopulmonary syndrome -important to monitor oxygen saturation in patients with portal vein obstruction/other causes of portal hypertension. If <97%, additional investigation may be needed.  Portopulmonary hypertension is best characterized with cardiac catheterization and hepatopulmonary syndrome with saline echocardiography.
  • Other topics: Prevention of hepatic encephalopathy, managing bleeding episodes, endoscopic treatment

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Portopulmonary Hypertension

A useful update: Liver Transpl 2012; 18: 881-91.

Definition: When pulmonary artery hypertension (PAH), mean pulmonary artery pressure (MPAP) ≥ 25 mm Hg, occurs in the setting of of portal hypertension and no alternative cause of the PAH exists (eg, collagen vascular disease, congenital heart disease, or certain drugs), it is known as portopulmonary hypertension (POPH).

  • Mild POPH: MPAP < 35 mm Hg
  • Moderate POPH: MPAP ≥ 35 mm Hg & <45 mm Hg
  • Severe POPH:  MPAP ≥ 45 mm Hg

Patients with moderate POPH and severe POPH, if not improved with medical therapy, have high mortality rates and these are generally considered contraindications for liver transplantation.

POPH is associated with high pulmonary vascular resistance ≥ 240 dyn(sec)(cm¯5 ) and with  pulmonary wedge pressure < 15 mm Hg.

Difference between POPH and hepatopulmonary syndrome:

From the following link: Portopulmonary hypertension and hepatopulmonary syndrome “Abnormal intrapulmonary vascular dilatation, the hallmark of hepatopulmonary syndrome, can cause profound hypoxaemia that can be very difficult to treat. By contrast, portopulmonary hypertension results from excessive pulmonary vasoconstriction and vascular remodelling that eventually leads to right-heart failure.”

Pathophysiology: unclear.  Most but not all cases are associated with cirrhosis.

Frequency: 6-8% of cirrhotic patients.

Diagnosis: while dyspnea may be present, routine screening with echocardiography is part of liver transplantation evaluation.

Prognosis: retrospective study from Mayo clinic (n=74, 1994-2007) noted 5-hr survival of 14% for untreated patients, 45% treated with vasodilators, and 67% who underwent liver transplantation.

Treatments: Table 6 in article.

  • PDE5 Inhibitors (oral): Tadalfil, Sildenafil
  • Endothelin Receptor antagonists (oral): Ambrisentan, Bosentan
  • Prostacyclins (IV): EPO, Trepostinil
  • Prostacyclins (Inhalation): Iloprost , Tyvaso
  • Liver transplantation: 79 patients with LT for POPH 2007-2011

Beta-blockers may have adverse effect.

Noncirrhotic POPH: Worldwide, infection with Schistosoma mansion is likely the most common reason; severe disease may occur in 10% of the 200 million people who are infected.  When noncirrhotic POPH occurs without cirrhosis or Schistosoma mansion, this requires a high degree of clinical suspicion as well as awareness of this disorder.

Additional references:

**Hepatology 2008; 48: 13, 196. POPH: pulmonary arterial htn associated w portal htn:

  • -resting pulm artery pressure > 25mmHg
  • -pulm capillary wedge pressure <15mmHg
  • -pulm vascular resistance >240dynes(s)(cm to -5)
  • -measure c trans thoracic echocardiography
  • -female sex, autoimmune dz were risk factors
  • -avg age associated was 53yrs whereas idiopathic PAH avg age is 36yrs

**NEJM 2008; 358: 2378. Review. Hepatopulmonary Syndrome – New England Journal of Medicine  Hepatopulmonary syndrome, a separate but related condition characterized by hypoxemic respiratory insufficiency due to increased intrapulmonary shunting
**Liver Tx 2007; 13: 680. Hepatopulmonary syndrome experience at CHOA