Should we screen for hepatopulmonary syndrome in liver transplant candidates?

Hepatopulmonary syndrome (HPS) involves intrapulmonary vascular dilatation with resultant hypoxemia in patients with chronic liver disease. The only effective treatment is that of liver transplantation however, mortality is increased pretransplant and posttransplant in HPS patients with severe hypoxemia. The American Association for the Study of Liver Disease Practice Guidelines recommend that patients with HPS have an expedited referral and evaluation for liver transplantation. In addition, the United Network for Organ Sharing liver allocation policy supports Model for End-stage Liver Disease (MELD) exception points that would provide a patient a reasonable probability of being transplanted within 3 months if the partial pressure of oxygen (PaO2) is 60 mm Hg on room air. 2 This is important as the severity of HPS is not related to the severity of liver disease, and patients with severe HPS may have a very low model for end-stage liver disease score and not be otherwise eligible for transplant. Thus, identifying these patients has clinical implications. But how should we do this? In the current issue of Liver Transplantation, Roberts et al. describe the results of a cost-effectiveness analysis of screening for HPS in liver transplant candidates. The cost-effectiveness of a screening test depends on the prevalence of disease, the sensitivity of the test, and an effective intervention. Prevalence rates for HPS have ranged from 10 to 20% in patients being evaluated for liver transplantation. The authors used a “hypothetical” cohort of 50-year-old patients with cirrhosis presenting for initial liver transplant evaluation with 3 different screening strategies: no screening, screening with a dyspnea-fatigue index (questionnaire), and screening with pulse oximetry on room air. Arterial blood gases and contrast echocardiography were performed if the dyspnea-fatigue index was positive or, if the oxygen saturation was 97%. The authors found that the incremental cost-effectiveness ratio of screening with pulse oximetry (compared to no screening) was superior to that of the dyspnea-fatigue index (compared to pulse oximetry) ($6,867 vs. $55,900 per life-year gained). It is difficult to understand what this finding truly represents. The authors concluded that screening for HPS, especially with pulse oximetry is a cost-effective strategy that improves survival in transplant candidates. This is a robust conclusion from a cost-effectiveness analysis based on many assumptions and transition probabilities reflecting the “natural history” of the disease. The authors have created a model with 72% of HPS patients maintaining a PaO2 60 mm Hg from year to year. The data from the Mayo Clinic suggest that PaO2 declines approximately 5 mm Hg from year to year in the absence of liver transplantation. The assumptions in this modeling analysis, if incorrect, may lead to false conclusions, and we have no prospective evidence to suggest that screening for HPS with pulse oximetry improves survival. Do we really understand the natural history of HPS based on retrospective studies? It may be inappropriate to assign increased costs to the dyspnea-fatigue index, which when positive leads to further studies that may explain hypoxemia not related to HPS, such as the presence of pulmonary hypertension (portopulmonary hypertension), diastolic dysfunction, and cardiac/valvular heart disease. We are able to draw only so many conclusions from modeling types of analyses. What is real? We know that mortality is increased in patients with HPS who