Hepatorenal syndrome type 1 and bacterial infection: A catastrophic association in patients with cirrhosis

T ype-1 hepatorenal syndrome (HRS) is a severe and frequently lethal complication of cirrhosis. It is characterized by a rapid deterioration of kidney function related to derangement of systemic hemodynamic with vasodilatation in the splanchnic bed, low blood pressure, insufficient cardiac output, and release of vasoconstrictors with renal ischemia. Patients at risk of developing HRS are those with decompensated cirrhosis and patients with compensated cirrhosis who develop a severe clinical deterioration, the so-called acute-on-chronic-liver-failure. In many cases a “trigger” can be identified such as gastrointestinal bleeding, alcohol, hepatotoxic drugs, or bacterial infections. Until recently, when a patient with cirrhosis developed renal dysfunction concomitant to a bacterial infection, the diagnostic work-up and treatment for HRS were postponed until antibiotic treatment was completed and only the renal failure persisted, despite resolution of infection, was called HRS. This strategy was based on the opinion that the pathogenesis of renal failure precipitated by bacterial infections was different from that of HRS precipitated by other triggers. This practice, however, delayed specific HRS treatment with vasopressin analogs. Accordingly, the International Ascites Club removed the recommendation and determined that the diagnosis (and treatment) of HRS could be made before the precipitating infection had resolved. We now know that bacterial infections are a frequent trigger of HRS, probably through a cytokine-mediated impairment of circulatory function, worsening effective hypovolemia. Accordingly, the administration of human albumin to patients with spontaneous bacterial peritonitis (SBP) was shown to decrease mortality from type-1 HRS. This result was not replicated in a trial performed in patients with cirrhosis with bacterial infections other than SBP, making it uncertain whether the recommendation to infuse albumin should be extended to all patients with bacterial infection. Therefore, a better understanding of the natural history of HRS associated with bacterial infections can lead to an improved therapeutic approach. Moreover, we need to ascertain whether the antibiotics empirically used to treat infections in patients with cirrhosis with normal renal function should be the same as that used in patients with infections associated with HRS. Finally, as the survival of patients with cirrhosis after infection-related HRS can be insufficient for liver transplantation, the new therapeutic strategies should ensure longer survivals. In this issue, Barreto et al. studied a cohort of 70 patients with cirrhosis with HRS associated with bacterial infections. Their study’s main objectives were to evaluate the renal response to antibiotic therapy, shortterm survival, and predictors of treatment failure and survival. The use of routinely recommended antibiotic therapy failed to resolve renal dysfunction in two-thirds of patients, suggesting that the mechanism of renal damage in such patients is more complex than that causing HRS in the absence of bacterial infections (Fig. 1), or that the efficacy of antibiotics is impaired by renal dysfunction. Unfortunately, the investigators did not report on whether doses and types of antibiotics were adjusted according to the loss of renal filtration capacity. The independent predictors of irreversible HRS were older age, Child-Pugh and Model for Endstage Liver Disease (MELD) scores, high bilirubin levels, and nosocomial infection. This confirms that the syndrome’s severity is predominantly due to the severity of the bacterial infection and to liver dysfunction, rather than to renal impairment. This suggests that the best results of treatment with terlipressin and albumin Abbreviations: HRS, hepatorenal syndrome; MELD, Model for Endstage Liver Disease; SBP, spontaneous bacterial peritonitis. Address reprint requests to: Francesco Salerno, M.D., Policlinico IRCCS San Donato, Via Morandi, 30, 20097 San Donato (MI), Italy. E-mail: francesco. salerno@unimi.it; fax: 10039-0252774462. Received August 16, 2013; accepted January 7, 2014. Copyright VC 2014 by the American Association for the Study of Liver Diseases. View this article online at wileyonlinelibrary.com. DOI 10.1002/hep.27015 Potential conflict of interest: Nothing to report.