Who is the arch-criminal in the development of hepatopulmonary syndrome?

December 19, 2007

The hepatopulmonary syndrome (HPS) develops when an arterial oxygenation deficiency occurs due to intra-pulmonary vascular dilatations that are often associated with severe hepatic disease. HPS occurs in 15-20% of patients with liver cirrhosis undergoing evaluation for orthotopic liver transplantation. Recent studies support that the presence of HPS significantly increases mortality in cirrhosis, particularly in those with decompensated liver disease.

One of the characteristics of HPS is intra-pulmonary vascular dilatation. The intra-pulmonary vascular dilatation severely affects pulmonary gas exchange, and consequently leads to hypoxia and raised mortality of cirrhotic patients. The present research hotspots focus mainly on clarifying the pathogenesis of HPS, particularly in exploring the mechanism of intra-pulmonary vascular dilatation.

Dr. Hui-Ying Zhang et al. developed a rat model characteristic of cirrhosis and HPS that can be non-invasively induced by multiple pathogenic factors including high fat diet, alcohol, cholesterol, corn flour and CCl4 and demonstrated a significantly increased level of lipopolysaccharide (LPS) in plasma is closely related to the decreased blood oxygen content and intra-pulmonary vascular dilatation. And they further characterized the relation between the progeression and severity of HPS and the degree of hepatic dysfunction, and explored how intestinal endotoxemia (IETM) affects the intra-pulmonary vascular dilatation.

In the research, Dr. Zhang et al. dynamically observed typical histological changes in both liver and lung and found that the progression and severity of HPS were closely associated with increased plasma LPS level, and that there was a paralleling deterioration between the lung function and the hepatic function in the cirrhotic rats. This indicated that HPS is interrelated with underlying liver disease and supported their hypothesis that hepatic pathological alteration is a substantial basis for the development of HPS in cirrhotic rats.

On the other hand , they also observed and found that dynamic alterations of plasma endotoxin were closely associated with increased expression of eNOS, iNOS, HO-1 and increased number of capillaries, which demonstrated that eNOS, iNOS and HO-1 were involved in increased NO and CO production in the lung. The elevated NO resulted preferably from iNOS of pulmonary macrophages and, to a lesser extent, from eNOS in the lung of cirrhotic rats. Both NO and CO are involved in pulmonary vascular abnormalities, and pulmonary macrophages play a role to HPS. They also found that the exhibition of pulmonary vascular abnormalities was not only in vascular dilatation but also in increased number. The results suggest that both NOS/NO and HO-1/CO pathways are contributor to the development of HPS, and that IETM plays a leading role in the development of HPS in the cirrhotic rats.

More interesting, they observed and found a mutual inhibition between NOS/NO and HO-1/CO pathways by using respective inhibitors, and consequently demonstrated that NOS/NO and HO-1/CO pathways may be interrelated in pathogenesis of intra-pulmonary vascular abnormalities in the development of HPS.

In conclusion, it is IETM that is the arch-criminal in the development of hepatopulmonary syndrome. Therefore, the strategy directed against LPS will certainly be effective in the prevention and treatment of HPS.
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To view the paper, visit http://www.wjgnet.com/1007-9327/13/6385.asp.

World Journal of Gastroenterology

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