The hepatopulmonary syndrome (HPS) is characterized clinically by the triad of pulmonary vascular dilation, systemic hypoxemia and the setting of advanced liver disease^1–7). In 1956, a case report by Rydell and Hoffbauer⁸⁾ concerning a 17-year-old man with hypoxemia and juvenile cirrhosis provided the first clinical and postmortem documentation of what was to be later termed HPS by Knudsen and Kennedy in 1979⁷⁾. The postmortem study demonstrated both precapillary dilations and direct arteriovenous communications after vascular injections with a plastic vinyl acetate solution^9,10).

The definition of hypoxemia may vary, but several studies consider PaO₂ less than 70 mmHg in patients with liver disease as abnormal. An increased alveolar-arterial oxygen gradient (A-aDO₂: greater than 20 mmHg) represents a more sensitive but less practical measure of abnormal oxygenation. Patients with HPS frequently demonstrate oxygenation that become worse as one moves from the supine to standing position (orthodoxies) breathing either room air or 100% inspired oxygen. A poor correlation exists between PaO₂ determined while breathing room air and PaO₂ determined while breathing 100% oxygen; the latter may be of additional prognostic significance. Research studies using a multiple inert gas elimination technique (MIGET) have shown the hypoxemia of HPS to be a result of shunt, diffusion-perfusion defect and excess perfusion for a given ventilation (low V/Q)¹¹⁾.

Most studies about hepatopulmonary syndrome have focused on alcoholic liver disease^12–17). There is no clear data about the prevalence of HPS in postnecrotic liver cirrhosis by hepatitis B virus (HBV). And it is unclear how the presence of HPS relates to the clinical aspects of HBV induced liver cirrhosis. So this study was done to investigate the prevalence of HPS in poorly compensated postnecrotic liver cirrhosis by HBV and the correlation of HPS with clinical aspects of HBV induced poorly compensated postnecrotic liver cirrhosis.

Thirty-five patients were studied (13 women and 22 men: mean age, 53.1 ± 14.5 years) All patients were classified as Child’s C. (Child’s classification included assessment of total bilirubin, serum albumin, clinical ascites, nutrition and existence of encephalopathy; Child’s A classification represented minimal disease and Child’s C classification represented the most severe liver disease). The etiologies of liver diseases of all the patients were postnecrotic liver cirrhosis by hepative B virus.

The triad of liver disease, arterial hypoxemia and intrapulmonary vascular dilatation has defined an entity commonly referred to as the hepatopulmonary syndrome^{1,3,10–11,19,26)}. In the original description by Rydell and Hoffbauer⁴⁾, lung necropsy specimens studied using plastic vascular casts contained both precapillary/capillary dilatations and distinct anatomic arteriovenous communications which caused severe hypoxemia in the setting of chronic liver disease (juvenile cirrhosis)^14,16–18). Hepatopulmonary syndrome is becoming increasingly recognized as one of the most serious complications of chronic liver disease. Different workers have reported incidences of positive air-contrast echocardiography varying from 5 to 47%, and prevalence of HPS between 5 and 29%^3,14). Our present study, although small, suggested a relatively lower occurrence of this condition (17.1% positive intrapulmonary shunt, 5.7% hepatopulmonary syndrome) in the Korean population, among whom hepatitis B virus is the most common cause of cirrhosis (100% in the present study), compared with alcohol and hepatitis C virus in Western countries. The results from our study were similar to those from an Indian study that the prevalence of intrapulmonary shunting in hepatitis B virus induced liver cirrhosis was 8.9% but HPS with hypoxemia was only 6.7%²⁾. Further studies are required to determine if the prevalence of HPS varies with etiology of liver disease or with geographical and racial differences.

Advanced hepatic dysfunction, with associated hyperdynamic circulation, has been suggested as being the most probable setting for the development of HPS. However, the condition has also been found in cases of congenital hepatic fibrosis and portal vein thrombosis. This has given rise to the question of whether portal hypertension is a contributing factor^1,3). Moreover, if hepatic dysfunction was the only prerequisite, one would expect HPS to occur predominantly among Child’s class C cirrhosis. However, Abrams et al. found 15 of 25 cases of HPS (60%) had Child’s grade A, and only two had grade C³⁾. In this study, most of HPS cases were alcoholic liver cirrhosis and hepatitis C virus (HCV)-induced liver cirrhosis. A common bile duct legation rat model for hepatopulmonary syndrome has been developed and increased pulmonary endothelial nitric oxide syntheses activities and circulating endothelin-1 levels seem to correlate with vascular dilatation and oxygen abnormalities^19,26)

In the present study, all cases were HBV-induced Child’s grade C liver cirrhosis and the prevalence of HPS is 5.7%. In this small study, the prevalence of hepatopulmonay syndrome in patients with poorly compensated (Child C) postnecrotic liver cirrhosis by HBV was 5.7%. Two of 35 cases of cirrhosis (5.7%) had positive contrast echocardiography with hypoxemia (PO₂ <70 mmHg) and four of 35 case of cirrhosis (11.4%) were ‘subclinical’ cases (positive contrast echocardiography without hypoxemia). Our results suggested that “subclinical hepatopulmonary syndrome” exists and maybe there were some factors, still unknown, to determine definite hepatopulmonary syndrome (hypoxemia with positive contrast echocardiography) and subclinical hepatopulmonary syndrome. This study suggested that there was a wide clinical spectrum of hepatopulmonary syndrome. There was one report about association of esophageal varies and hepatopulmonary syndrome in liver cirrhosis²⁷⁾. But, in this study, there was no association of the grade of esophageal varies and hepatopulmonary syndrome. Cyanosis was the only reliable clinical indicator, and there was no clear relationship with the presence of spider angioma and hepatopulmonary syndrome. Further studies are required to determine if the prevalence of HPS and clinical manifestations of HPS varies with etiology or with geographical and racial differences.