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Abstract

Our observation that SBP-induced type-1 hepatorenal syndrome (HRS) occurs in the setting of a significant decrease in cardiac output and in the absence of significant changes in peripheral vascular resistance modifies the current concept of the pathogenesis of circulatory dysfunction in cirrhotic patients with SBP. Up to now, type-1 HRS in patients with SBP was considered to be caused by an accentuation of the arterial vasodilation and secondary activation of the endogenous vasoconstrictors systems already present in these patients (Hepatology 1996;23:164–176). Our study is compatible with an accentuation of arterial vasodilation because peripheral vascular resistance did not change in our patients despite an intense activation of the renin-angiotensin and sympathetic nervous systems. However, in addition to this, circulatory dysfunction and HRS was clearly associated to a decrease in cardiac function. Therefore, HRS associated to SBP occurs when there is simultaneous impairment of the 2 main factors influencing the effective arterial blood volume and arterial pressure, the cardiac output and the systemic vascular resistance. The mechanism of the decrease in cardiac function was not investigated in our patients, although it was likely related to a central hypovolemia because there were no changes in cardiopulmonary pressures despite the decrease in cardiac output. Our study offers a rational explanation for the findings of recent therapeutic investigations in patients with type-1 HRS. Reversal of type-1 HRS (normalization of serum creatinine) is frequently achieved when patients are treated by plasma volume expansion with albumin and vasoconstrictors (terlipressin or noradrenaline) (J Hepatol 2000;33:43–48, Acta Gastroenterol Belg 2001;64:15–19, Gastroenterology 2002;122:923–930, Hepatology 2002;36:941–948, Hepatology 2002;36:374–380) but not when infusion of albumin or vasoconstrictors are given alone (J Hepatol 2000;33:43–48). Plasma volume expansion with albumin increases cardiac preload and cardiac output and vasoconstrictors increase peripheral vascular resistance, thus correcting the 2 factors involved in the pathogenesis of HRS. The observation that infusion of albumin at the time of diagnosis of infection is highly effective in preventing renal failure in patients with SBP (N Engl J Med 1999;341:403–409) is consistent with the important role of the impairment in cardiac output in the pathogenesis of HRS in these patients. Circulatory dysfunction associated with SBP in our patients was associated with a marked increase in portal pressure. This observation also offers a rational explanation for the frequent association of acute bacterial infections with variceal bleeding refractory to therapy in cirrhosis (Hepatology 1998;27:1207–1212). Drs. Blendis and Wong considered albumin as an expensive treatment for patients with SBP. Of course, albumin is not cheap. However, it decreases hospital mortality by 66% in these patients (from 30% to 10%) (N Engl J Med 1999;341:403–409), and we are not aware of any treatment with such efficacy in decompensated cirrhosis.