A woman in her fifties with cirrhosis of the liver and postural dyspnoea

The patient was referred to a university hospital for workup for liver transplantation due to cirrhosis of the liver with refractory ascites and encephalopathy during her admission at the local hospital. She was known to have hypertension and type 2 diabetes, had no previous cardiac or pulmonary conditions, and had no prior history of smoking or exposure to dust with pulmonary toxicity. She had been diagnosed with non-alcoholic steatohepatitis (NASH), but the liver disease had been stable for four years before her condition deteriorated with over ten admissions in a one-year period. Earlier investigations with CT scanning of the liver and abdomen, as well as gastroscopy, had revealed oesophageal varices, portal hypertension and ascites. She had previously undergone assessment for transjugular intrahepatic portosystemic shunt (TIPS), but was rejected due to encephalopathy.

Three months before her referral for workup for liver transplantation, blood tests had found low platelet count, the lowest count being 50 × 10⁹/L (reference range 145–390 × 10⁹/L), and elevated transaminases with AST 77 U/L (<45) and ALT 54 U/L (<70). D-dimer was 12 mg/L (<0.5). At that time, findings of abdominal and pelvic CT scanning with contrast were negative with a query about portal vein thrombosis, although atypical location of thrombus masses were seen at the confluence of the inferior vena cava, common iliac vein and possibly also in the left internal iliac vein. No underlying malignant or myeloproliferative disease was found as a cause of the abnormal location of thrombi, and the FDG-PET scan was negative.

Treatment was initiated with low-dose subcutaneous dalteparin 5000 IU twice daily due to thrombocytopenia of 50 × 10⁹/L and bleeding diathesis. The dose of dalteparin was increased over a one-month period, after a rise in platelet count was observed. Due to low levels of antithrombin, antithrombin replacement therapy was added (Prothromplex 1 IU/kg).

Workup for liver transplantation took place for approximately two months and consisted of an MRI scan of the pancreas, CT scan of the abdomen, transthoracic echocardiography and gastroscopy, with no contraindications to transplantation being detected. Both pleural effusion and ascites contributed to her dyspnoea, but no further pulmonary assessment was carried out at that time because the dyspnoea improved after tapping and was assumed to be related to the fluid accumulation.

Two months after transplantation workup, she was admitted to hospital and accepted for transplantation. She had decompensated liver failure with jaundice. Biochemical tests found AST 65 U/L (<45), ALT 32 U/L (<70), bilirubin 24 mol/L (<25), albumin 32 g/L (36–45), INR 1.9 (0.8–1.2) and ammonia 87 mol/L (<35), as well as severe hyponatraemia of 128 mmol/L (137–145). Ascites was also detected, and tapping was performed. AST and ALT levels were near-normal, due to advanced decompensated liver cirrhosis and lack of synthesis. Her Child-Pugh score had deteriorated to B (9 points), and her MELD-Na score was 21. She was discharged, but was soon re-admitted to her local hospital due to a deteriorating general condition, decrease in oxygen saturation and recurrence of pleural effusion and ascites. She required care and nutrition, and was admitted until transplantation.

After five months of hospitalisation, expedited transplantation was requested due to serious progression of her disease. She had massive production of ascites and pleural effusion, and was therefore undergoing regular tapping and dewatering with diuretics. In addition, the patient required haemodiafiltration due to encephalopathy and serum ammonia of 217 µmol/L (<35). The patient was bed-bound, dependent on total parenteral nutrition and in a generally debilitated condition. She underwent thoracentesis a total of 14 times (> 1 L pleural fluid each time) and paracentesis six times (2.5–3.7 L each time). The pleural fluid was consistent with transudate (total pleural fluid protein <30 g/L and pleural LD <200 U/L). Findings of cytology were negative. She remained admitted to the local hospital while awaiting a suitable liver.

During the admission prior to liver transplantation, a decrease in peripheral oxygen saturation (SpO₂) was observed, measured on pulse oximetry as 70–80 % without supplemental oxygen, from her usual levels of 92–95 %. With oxygen supplementation of 2–3 L/min via nasal specs, SpO₂ rose to 90–95 %. The patient reported increasing shortness of breath when she stood upright, and it was observed that she had SpO₂ of 95 % with O₂ 3 L/min while lying down, but SpO₂ of 85 % with the same oxygen supplementation in a standing position. Arterial blood gas analysis with O₂ 3 L/min (standing) found pH 7.51 (7.35–7.45), pCO₂ 4.5 kPa (4.64–6.40), pO₂ 6.6 kPa (10.0–14.0 kPa) and SO₂ 85 %. She was therefore referred for echocardiography with queried hepatopulmonary syndrome with shunting or portopulmonary hypertension.

Transthoracic echocardiography (TTE) with and without agitated saline contrast (also referred to as bubble contrast) revealed normal dimensions of the left ventricle with good contraction and ejection fraction (EF) of 55 % with no significant valve defects. The right ventricle was dilated with good contraction, mild pulmonary hypertension and mild biatrial dilation. Agitated saline contrast echocardiography revealed a large atrial shunt with abundant passage of agitated saline contrast from the right to left side of the heart via the pulmonary veins after three consecutive heartbeats. This suggested a large intrapulmonary right-to-left shunt, consistent with intrapulmonary vascular dilation.

One month after the transplantation was expedited, the patient was diagnosed with hepatopulmonary syndrome. Since the patient had liver dysfunction with portal hypertension, unexplained hypoxaemia and intrapulmonary vascular dilation, it was concluded that she had the diagnostic triad of symptoms for hepatopulmonary syndrome. Dilation of the pulmonary capillaries in hepatopulmonary syndrome causes overperfusion relative to ventilation, leading to ventilation-perfusion mismatch and hypoxaemia.

While awaiting transplantation, the patient received primary treatment with supplemental oxygen for hepatopulmonary syndrome. After another three months, so a total of nine months after she was put on the transplantation list, the patient underwent transplantation without complications.