Characteristic haemodynamic changes of cirrhosis may influence the diagnosis of portopulmonary hypertension.

BACKGROUND & AIMS: Diagnosis of portopulmonary hypertension (POPH) is based on the presence of portal hypertension and the same haemodynamic criteria as pulmonary arterial hypertension (PAH). However, the typical hyperdynamic circulation of cirrhosis may have some impact on the diagnosis of POPH. The aim was to compare the haemodynamic pattern of the pulmonary circulation between cirrhotics and non-cirrhotics, including patients with PAH. PATIENTS AND METHODS: 600 patients with cirrhosis [male 77.5%, age 54 (47-60) years, Child A: 14.7%, B: 54.3%, C: 31%] received right heart catheterization. For comparison, 118 non-cirrhotic patients [male 60%, age 64 (53-65) years] with right heart catheterization and PCWP <20 mmHg were included. Both were divided into 3 groups, A: absence of pulmonary arterial hypertension; B or intermediate group: MPAP >25 mmHg, PVR 120-240 dyn s cm(-5) and PCWP <15 mmHg (or PCWP >15 mmHg with TPG ≥12 mmHg); C: pulmonary arterial hypertension (same criteria as B except PVR ≥240 dyn s cm(-5) ). RESULTS: Distribution of patients with cirrhosis was A 583, B 7 and C 10. Prevalence of POPH was 1.7%. Cirrhotics had lower SVR and greater CO than non-cirrhotics (P < 0.05). Interestingly, patients with cirrhosis without PAH (groups A and B) had lower PVR (P < 0.05) when comparing with non-cirrhotics, while no differences in PVR were observed in group C. However, mean TPG was greater in group C of cirrhotics [36.6 mmHg (12.2) vs. 27.1 mmHg (10.1); P = 0.034]. CONCLUSIONS: Patients with cirrhosis have lower PVR. TPG is greater in POPH than PAH. Characteristic haemodynamic changes of cirrhosis may influence the diagnosis of POPH.

Oral probiotic VSL#3 attenuates the circulatory disturbances of patients with cirrhosis and ascites.

BACKGROUND & AIMS: The modulation of gut flora constitutes a therapeutic tool in patients with liver disease, but some of its modalities require further investigation. Here, we evaluated the effects of probiotics on the hepatic and systemic haemodynamic alterations of advanced liver disease. METHODS: Seventeen patients with cirrhosis and ascites were prospectively included, five of whom abandoned this study prematurely. Hepatic and systemic haemodynamic evaluations were performed at baseline and after 6 weeks of receiving an oral VSL#3 probiotic preparation. Peripheral blood analyses included the evaluation of cytokines (TNF-alpha, IL-1beta, IL-6), bacterial translocation [bacterial DNA and lipopolysaccharide-binding protein (LBP)] and nitric oxide end-products (NOx). RESULTS: In 12 patients completing this study, the oral administration of VSL#3 resulted in reductions of the hepatic venous pressure gradient (HVPG, P < 0.001), cardiac index and heart rate (both P < 0.01) and in increases of the systemic vascular resistance (P < 0.05) and mean arterial pressure (P = 0.06). HVPG decreased at least 10% from baseline in eight patients (67%). Serum sodium increased in most patients (P < 0.01). All these changes were unrelated to the detection of bacterial DNA or to the levels of LBP, pro-inflammatory cytokines or NOx. No significant adverse effects were observed. CONCLUSION: Administration of the probiotic mixture VSL#3 improved the hepatic and systemic haemodynamics and serum sodium levels in patients with cirrhosis. Our results identify major effects of probiotics in liver disease and provide the rationale for assessing their therapeutic potential against the progression of portal hypertension and its complications in future clinical trials.