Response to pegylated interferon plus ribavirin among HIV/hepatitis C virus-coinfected patients with compensated liver cirrhosis.

BACKGROUND: The objective of this study was to determine the efficacy of pegylated interferon (peg-IFN) plus ribavirin (RBV) in human immunodeficiency virus (HIV)-infected patients with hepatitis C virus (HCV)-related compensated liver cirrhosis, as well as the predictors of response in these individuals. METHODS: All subjects enrolled in a prospective cohort of 841 HIV/HCV-coinfected patients who received peg-IFN and RBV and who had a liver biopsy or a liver stiffness measurement within the year before starting peg-IFN plus RBV were included in this study. The sustained virologic response (SVR) rate and predictors of SVR response were analyzed. RESULTS: A total of 629 patients were included in this study; 175 (28%) had cirrhosis. In an intention-to-treat analysis, 44 (25%) patients with cirrhosis and 177 (39%) without cirrhosis achieved SVR (P = .001). Among patients with cirrhosis, SVR was observed in 14%, 47%, and 30% of individuals with HCV genotypes 1, 2-3, and 4, respectively. Discontinuation of therapy owing to adverse events was observed in 30 (17%) individuals with cirrhosis and 37 (8%) subjects without cirrhosis (P = .001). CONCLUSIONS: The efficacy of peg-IFN plus RBV among HIV/HCV-coinfected patients with cirrhosis is lower than in those without cirrhosis, although this antiviral combination still leads to a substantial rate of SVR in those carrying HCV genotype 3. A higher rate of discontinuations of HCV therapy due to adverse events among cirrhotic patients could partially explain the differences in the SVR rate between both populations.

Hepatic steatosis and steatohepatitis in human immunodeficiency virus/hepatitis C virus-coinfected patients.

UNLABELLED: Hepatic steatosis (HS) is frequent in human immunodeficiency virus (HIV)- and hepatitis C virus (HCV)-coinfected patients. Antiretroviral therapy (ART) and metabolic alterations could induce HS. However, a protective effect of ART has been reported in a paired biopsy study. Thus, our aim was to examine the changes and predictors of HS progression among HIV/HCV-coinfected patients with sequential biopsies. We also evaluated the rates of steatohepatitis and factors associated thereof. HIV-infected patients with detectable serum HCV RNA, who underwent two biopsies, separated at least by 1 year, were included in this retrospective study. HS progression was defined as increase in one or more HS grades. The median (interquartile range) time between biopsies was 3.3 (2.0-5.2) years. Among 146 individuals, HS at baseline was observed in 86 (60%) patients and in 113 (77%) in the follow-up biopsy (P < 0.001). Progression of HS was observed in 60 (40%) patients. HS regressed in 11 (8%) patients. Factors associated with HS progression were changes in fasting plasma glucose (FPG) between biopsies (per 10 mg/dL increase; odds ratio [OR] [95% confidence interval; CI] = 1.4 [1.04-1.8]; P = 0.024) and cumulative use of dideoxynucleoside analogs (per year; OR [95% CI] = 1.5 [1.2-1.8]; P = 0.001). Persistent steatohepatitis or progression to steatohepatitis between biopsies was observed in 27 (18%) patients. Persistence of or progression to steatohepatitis was associated with progression ≥ 1 fibrosis stages between biopsies (OR [95% CI] = 2.4 [1.01-5.7]; P = 0.047). CONCLUSIONS: HS progresses frequently and regression is rarely observed in HIV/HCV-coinfected patients, including in those on ART. Cumulative exposure to dideoxynucleoside analogs and increases in FPG are related with HS progression. Stetatohepatitis is frequently observed in these patients and is linked to fibrosis progression.

Haemodynamic derangement in human immunodeficiency virus-infected patients with hepatitis C virus-related cirrhosis: the role of bacterial translocation.

BACKGROUND AND AIMS: Analysis of the influence of the effects of increased intestinal permeability on haemodynamic alterations in human immunodeficiency virus (HIV)-infected patients with decompensated hepatitis C virus (HCV)-related liver disease. METHODS: Forty HIV/HCV co-infected patients and 40 HCV mono-infected patients, 20 of them with compensated cirrhosis and 20 with a previous decompensation, and 20 healthy controls, were studied. Intestinal permeability was determined by serum levels of lipopolysaccharide-binding protein (LBP). Monocyte expression of toll-like receptor 4 (TLR-4), serum levels of interleukin (IL)-6 and soluble receptors of tumour necrosis factor (sTNFRI) were analysed. Cardiac index, systemic vascular resistance (SVR), plasma renin activity (PRA) and aldosterone concentration were also determined in cirrhotic patients. RESULTS: Serum levels of LBP, TLR-4, IL-6 and sTNFRI were significantly higher in HIV-HCV co-infected and HCV mono-infected patients with decompensated cirrhosis compared with those with compensated liver disease. Significantly lower values of SVR and higher values of cardiac index, PRA and aldosterone concentration were observed in patients with decompensated cirrhosis compared with those with compensated liver disease, particularly in those with elevated levels of IL-6. There were no significant differences between HIV/HCV co-infected and HCV mono-infected patients. CONCLUSIONS: Higher intestinal permeability and consequent macrophage activation is observed in patients with cirrhosis; this permeability is even higher in those with portal hypertension. Serum values of IL-6 are associated with the characteristic haemodynamic derangement observed in advanced phases of cirrhosis. HIV/HCV co-infected cirrhotic patients present inflammatory and systemic haemodynamic alterations similar to those observed in HCV mono-infected patients.

Natural history of compensated hepatitis C virus-related cirrhosis in HIV-infected patients.

OBJECTIVE: To provide information about the incidence and predictors of liver decompensation and death due to liver failure in human immunodeficiency virus (HIV)-infected patients with compensated hepatitis C virus (HCV)-related cirrhosis. METHODS: Prospective cohort study of 154 HIV-HCV-coinfected patients with a new diagnosis of Child-Pugh-Turcotte (CPT) class A compensated cirrhosis. We evaluated time from diagnosis to the first liver decompensation and death from liver disease, as well as predictors of these outcomes. RESULTS: Thirty-six patients (23.4%) developed liver decompensation. The incidence of liver decompensation was 6.40 cases per 100 person-years (95% confidence interval [CI], 4.18-9.38 cases per 100 person-years). Factors independently associated with liver decompensation were lack of HCV therapy (hazard ratio [HR], 3.38; 95% CI, 1.09-10.53; P = .035), baseline CD4 cell counts

Influence of concomitant antiretroviral therapy on the rate of sustained virological response to pegylated interferon plus ribavirin in hepatitis C virus/HIV-coinfected patients.

OBJECTIVES: To investigate whether concomitant antiretroviral therapy (ART) is a predictor of sustained virological response (SVR) in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients treated with pegylated interferon plus ribavirin. METHODS: Three hundred and ten HIV/HCV-coinfected patients on pegylated interferon plus ribavirin treatment, 258 of them with concurrent ART, were included in this retrospective multicentre study. The predictors of SVR were evaluated. RESULTS: SVR was shown by 114 (37%) subjects. HCV genotype 2 or 3, plasma HCV-RNA load lower than 600 000 IU/mL, an exposure to the therapy against HCV infection > or =80% of the planned dose and baseline CD4 cell counts higher than or equal to 300/mm(3) were predictors of SVR. Likewise, patients without ART and those receiving a combination including tenofovir or stavudine plus lamivudine plus a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) showed a higher SVR rate than the subjects who were on other ART strategies at baseline [44%, 44% and 29%, respectively; adjusted odd ratio (95% CI) for no ART = 1.96 (1.07-4.76), P = 0.025, and for ART including tenofovir or stavudine plus lamivudine plus a PI or a NNRTI = 2.08 (1.16-3.70), P = 0.014]. CONCLUSIONS: The ART strategy on starting therapy with pegylated interferon plus ribavirin is a predictor of SVR in HIV/HCV-coinfected patients. Subjects without ART and those receiving combinations of a PI or a NNRTI with a nucleos(t)ide backbone of tenofovir or stavudine plus lamivudine respond better than those who receive other regimens.

Natural history of compensated and decompensated HCV-related cirrhosis in HIV-infected patients: a prospective multicentre study.

OBJECTIVE: To define the course of HIV-HCV-coinfected patients with compensated and decompensated liver cirrhosis and to investigate the survival and the risk factors for death. PATIENTS AND METHODS: Ninety-two HIV-infected patients with HCV-related cirrhosis (50 of them without and 42 with previous decompensations) were prospectively followed up during a median period of 20 months. Clinical, biochemical, virological and immunological factors were analysed. Multivariate analyses were performed of those factors associated with decompensations and mortality. RESULTS: There were 168 readmissions due to liver-disease-related causes. A Child-Pugh index > or =6 in those without previous decompensations (hazard ratio [HR] 7.94, 95% confidence interval [CI] 1.59-39.58; P = 0.014), and Child-Pugh index > or =9 (HR 2.68, 95% CI 1.13-6.33; P = 0.003) and absence of HAART (HR 0.44, 95% CI 0.19-0.98; P = 0.048) in those with previous decompensations were independently associated with decompensation during the follow up. There were 27 deaths, 22 of them attributable to liver disease. Independent factors associated with liver-related mortality were a Child-Pugh index > or =9 (HR 6.24, 95% CI 2.31-16.85; P < 0.001), progression of Child-Pugh index during the follow up (HR 4.27, 95% CI 1.54-11.80; P = 0.008), more than one decompensation (HR 24.25, 95% CI 7.27-40.45; P < 0.001) and absence of HAART (HR 0.35, 95% CI 0.12-0.98; P = 0.002). CONCLUSIONS: Evolution from compensated to decompensated cirrhosis and death is influenced by markers of liver function and the absence of HAART. The importance of this last element must be adequately stressed.

Predictors of severe haematological toxicity secondary to pegylated interferon plus ribavirin treatment in HIV-HCV-coinfected patients.

BACKGROUND: Haematological adverse events related to pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy could affect the patients' quality of life; however, the risk factors for severe haematological toxicity associated with this therapy in patients coinfected with hepatitis C virus (HCV) and HIV are unclear. The objective of this study was to identify predictors of severe haematological toxicity among HIV-HCV-coinfected patients treated with PEG-IFN plus RBV. METHODS: This retrospective multicentric study included 237 HIV-HCV-coinfected patients on PEG-IFN plus RBV. Predictors of severe anaemia, neutropenia, thrombocytopenia and overall haematological toxicity were analyzed. RESULTS: Eighty (34%) individuals showed an episode of severe haematological toxicity. Severe anaemia, neutropenia and thrombocytopenia occurred in 32 (13%), 42 (18%) and 26 (11%) patients, respectively. In the multivariate analysis, zidovudine use (adjusted odds ratio [AOR] 3.3; 95% confidence interval [CI] 1.6-10; P = 0.001), baseline body weight < 65 kg (AOR 2.5; 95% CI 1.1-5; P = 0.024), cirrhosis (AOR 5; 95% CI 1.6-16.6; P = 0.006), PEG-IFN-alpha2a (AOR 2.7; 95% CI 1.1-6.6; P = 0.029) and pretreatment haemoglobin level < 14 g/dl (AOR 2.7; 95% CI 1.3-5.5; P = 0.005) were associated with any kind of severe haematological toxicity. Likewise, haemoglobin level < 13 g/dl, neutrophil counts < 2,500 cells/mm3 and platelet counts < 175,000 cells/mm3 were independent predictors of severe anaemia, neutropenia and thrombocytopenia, respectively. CONCLUSIONS: Zidovudine treatment, cirrhosis, baseline low body weight, use of PEG-IFN-alpha2a, and baseline haemoglobin level < 14 g/dl are predictors of overall severe haematological toxicity secondary to PEG-IFN plus RBV in HIV-infected individuals. Low pretreatment levels of each haematological series predict a significant decrease of their values during therapy.

Incidence of and risk factors for severe hepatotoxicity of nelfinavir-containing regimens among HIV-infected patients with chronic hepatitis C.

OBJECTIVES: To determine the incidence of and risk factors for severe hepatotoxicity of nelfinavir-containing regimens among human immunodeficiency virus/hepatitis C virus (HIV/HCV)-coinfected patients with known stage of liver fibrosis. METHODS: All HIV/HCV-coinfected patients were monitored for a period of 12 months after starting nelfinavir-containing regimens and, with an available liver biopsy, were included in a retrospective study. RESULTS: A total of 82 patients were included in the study. Nine (10.9%) HIV/HCV-coinfected patients showed an episode of severe hepatotoxicity during the study period. Eight (9.8%) individuals showed grade 3 or 4 change in levels of serum alanine aminotransferase and one subject presented with an event of decompensated liver cirrhosis. Six (18.2%) of 33 patients with advanced liver fibrosis and three (6%) of 49 individuals without advanced liver fibrosis showed an episode of severe hepatotoxicity (P = 0.1). In the multivariate analysis, only nevirapine use during nelfinavir therapy [adjusted odds ratio (AOR) 8.9; 95% confidence interval (CI), 1.4-54.1; P = 0.01] was independently associated with risk of development of severe liver toxicity. CONCLUSIONS: The incidence of severe hepatotoxicity of nelfinavir-containing regimens is low among HIV/HCV-coinfected patients with known stage of liver fibrosis. In addition, our findings show that concomitant nevirapine use is associated with an increased risk of severe hepatotoxicity in these subjects. Likewise, the proportion of severe liver toxicity tended to be higher in individuals with advanced liver fibrosis.

Incidence of and factors associated with hepatocellular carcinoma among hepatitis C virus and human immunodeficiency virus coinfected patients with decompensated cirrhosis.

We compared the incidence of and factors associated with hepatocellular carcinoma (HCC) among hepatitis C virus (HCV)-monoinfected subjects and human immunodeficiency virus (HIV)/HCV-coinfected individuals, both with decompensated cirrhosis. In a retrospective study, a cohort of 180 individuals with HIV coinfection and 1037 HCV-monoinfected patients with decompensated HCV-related cirrhosis from eight centres in Spain were analyzed. HCC was found in 234 (23%) HCV-monoinfected subjects and in four (2%) HIV-coinfected subjects (p<0.001). At the time of the first hepatic decompensation, 188 (17%) and 4 (2%) (p<0.001) patients in the former and in the latter group, respectively, showed HCC. Fifty-four (11%) patients without HCC at baseline developed such a disease during follow-up. There were no incident cases among the HIV-coinfected population. The density of incidence (95% IC) of HCC in HIV/HCV-coinfected and HCV-monoinfected patients was 0 (0-1.70) and 3.31 (2.70-4.64) cases per 100 person-years (p<0.001), respectively. Lack of HIV infection [adjusted odds risk (AOR) (95% IC)=16.7 (3.9-71.1)] and high alanine aminotransferase levels [AOR (95% IC)=2.5 (1.1-5)] were the only two independent predictors of the emergence of HCC. In the group of patients in whom the date of HCV infection could be estimated, the time elapsed until HCC diagnosis was shorter among HIV-coinfected subjects. The incidence of HCC in patients with HCV-related cirrhosis after the first hepatic decompensation is lower in HIV-coinfected patients. This is probably due to the fact that HIV infection shortens the survival of HCV-coinfected patients with end-stage liver disease to such an extent that HCC not had a chance to emerge.

Antiretroviral therapy based on protease inhibitors as a protective factor against liver fibrosis progression in patients with chronic hepatitis C.

Cohort studies have shown that highly active antiretroviral therapy (HAART) can improve liver-related mortality in HIV/hepatitis C virus (HCV)-coinfected patients. A reduction in the accelerated liver fibrosis progression observed in HIV infection induced by HAART could explain these findings. A few studies have assessed the impact of HAART on liver fibrosis, but with contradictory results. Therefore, we evaluated the associations between the use of different antiretroviral drug classes and HAART combinations, and liver fibrosis in HIV-infected patients with chronic hepatitis C. Six hundred and eighty-three HIV/HCV-coinfected patients, who underwent a liver biopsy and who had not received anti-HCV treatment were included. Age at HCV infection < 23years (adjusted odds ratio [AOR] = 0.7, 95% confidence interval [95% CI] = 0.3-0.9, P = 0.05) and protease inhibitor (PI)-based HAART versus no use of HAART (AOR = 0.5, 95% CI = 0.3-0.9, P = 0.01) were negatively associated with advanced fibrosis (> or = F3). PI-based HAART versus no use of HAART (AOR = 0.4, 95% CI = 0.2-0.7, P = 0.001) was negatively associated with fibrosis progression rate > or = 0.2 units/year and independently of age at HCV infection and CD4+ T-cell counts. Fifteen (17%) patients treated only with PIs and zidovudine plus lamivudine showed > or = F3, compared with 65 (37%) patients without HAART (P = 0.001). Forty (31%) patients on PI and stavudine plus lamivudine showed > or = F3 (P = 0.3, when compared with patients with no HAART). The use of PI-based HAART in HIV/HCV-coinfected patients is associated with less severe fibrosis and slower progression of fibrosis. The nucleoside analogue backbone in a HAART regimen may influence this association.

Modification of pro- and antiinflammatory cytokines and vascular-related molecules by tumor necrosis factor-a blockade in patients with rheumatoid arthritis.

OBJECTIVE: Analysis of serum concentrations and modifications of tumor necrosis factor-a (TNF-a), its soluble receptors (TNFR), interleukin 10 (IL-10), and vascular related molecules [soluble vascular cell adhesion molecule 1 (sVCAM-1), vascular endothelial growth factor (VEGF)] after therapy with methotrexate (MTX) and anti-TNF (infliximab) in patients with rheumatoid arthritis (RA). METHODS: Thirty-six patients with RA and 20 healthy controls were included. Patients had been orally taking a stable dose of MTX of at least 12.5 mg/week for a minimum of 6 months before inclusion in the study. Twenty-five patients had shown a clinical response to MTX (MTX Group). The other 11 had shown an unsatisfactory response and presented with active RA; they were selected for additional treatment with infliximab (MTX + IFM Group). Disease activity score (DAS28), hemoglobin concentration, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum levels of TNF-a, soluble TNFR, IL-10, sVCAM-1 and VEGF were determined at baseline and prior to every infusion of infliximab (3 mg/kg) at 2, 6, 14, 22, and 30 weeks. RESULTS: Although serum levels of TNF-a were similar in patients and controls, patients showed significantly higher concentrations of both soluble TNFR (sTNFR55 and sTNFR75), IL-10, sVCAM-1, and VEGF than healthy individuals. Significantly higher levels of sVCAM-1 and VEGF, but not of the other tested molecules, were detected in those with active disease. After infliximab treatment (MTX + IFM Group) there was a significant decrease in DAS28 and modified Health Assessment Questionnaire scores and ESR and CRP levels. Serum concentration of VEGF showed a significant decrease after infliximab, with levels comparable to those of patients with inactive RA, although VEGF continued to present higher values than in healthy controls. CONCLUSION: Increased levels of vascular related molecules sVCAM-1 and VEGF are serum markers of active RA. The absence of normalization of levels of these molecules in patients with inactive RA could be one of the reasons response to therapy is only temporary.

Implication of inflammation-related cytokines in the natural history of liver cirrhosis.

BACKGROUND/AIMS: Increased serum concentrations of pro-inflammatory cytokines have been detected in patients with liver cirrhosis. However, their role in the natural history of cirrhosis and portal hypertension, in the absence of infection, and the prognostic significance of inflammation-related cytokines have not been reported. Our objective was the analysis of the prognostic value of inflammation-related cytokines in cirrhotic patients. PATIENTS AND METHODS: Serum concentrations of tumor necrosis factor (TNF-alpha) and its soluble receptors I and II and interleukin 6 (IL-6), as well as mean blood pressure, plasma renin activity, aldosterone, vasopressin and norepinephrine concentrations were determined in 72 cirrhotic patients (Child-Pugh score: A 50%, B 33.3%, C 16.7%), without any evidence of infection, and in 25 healthy controls. Patients were followed up for a median of 35.9 (range 6-60) months. RESULTS: Increased concentrations of soluble TNF receptors were detected in cirrhotic patients when compared with healthy controls. TNF receptors and IL-6 concentrations were both significantly more elevated in advanced phases of cirrhosis (Child-Pugh score C vs B and vs A). Sixteen patients died as a related consequence of liver cirrhosis. Multivariant analysis demonstrated that Child-Pugh score, mean blood pressure and serum levels of TNF receptor I were associated with mortality. CONCLUSIONS: In addition to the classic factors implicated in mortality (Child-Pugh score and hemodynamic parameters), alterations in inflammation-related components are of prognostic significance in cirrhotic patients.

Antiphospholipid syndrome and asymptomatic carriers of antiphospholipid antibody: prospective analysis of 404 individuals.

OBJECTIVE: We carried out a prospective analysis of clinical and analytical findings in individuals with antiphospholipid antibodies (aPL). METHODS: We prospectively studied 404 individuals, classified in 2 groups: (1) patients with primary or secondary antiphospholipid syndrome (APS, n = 226); and (2) asymptomatic carriers of aPL (n = 178). Patients with APS and thrombosis were treated with dicumarin, and an international normalized ratio around 3.0 (range 2.5-3.5) was targeted. Asymptomatic carriers were not treated, but specific prophylaxis with low molecular weight heparin or aspirin was prescribed for the periods when individuals were at increased risk of thrombosis. Both groups of individuals were followed up at semester intervals for 36 months. RESULTS: Patients with APS presented with venous (n = 106, 46.9%) and/or arterial (n = 70. 31%) thrombosis or fetal loss (n = 58 out of 112 women of fertility age, 51.8%). At the time of the first thrombotic event, 50.0% of patients with APS had coincident risk factors for thrombosis (previous surgery and prolonged immobilization were significantly associated with venous thrombosis, and hypercholesterolemia and arterial hypertension with arterial thrombosis). Eighteen patients with APS died during the study period. Recurrence of thrombosis in patients with APS was linked to insufficient anticoagulation. During the followup, no episode of thrombosis was detected in any asymptomatic carrier. The proportion of subjects with aPL was similar in patients and in asymptomatic carriers. The proportion of subjects with aPL decreased during the followup, in both patients and carriers. CONCLUSION: Differences between patients and asymptomatic carriers with aPL are at least partially dependent on the proportion of coincident vascular risk factors. The decline in aPL during the followup defines a subgroup in which an anticoagulation suppression assay could be tried.

Progression of chronic hepatitis C to liver fibrosis and cirrhosis in patients coinfected with hepatitis C virus and human immunodeficiency virus.

To evaluate the factors associated with the evolution of chronic hepatitis C in human immunodeficiency virus (HIV)-infected patients, a cross-sectional analysis of 41 HIV-infected patients with chronic hepatitis C (known as "HIV-HCV [hepatitis C virus]-coinfected patients") and a control group of patients with chronic hepatitis C who did not have HIV infection (known as "non-HIV-infected patients") was performed. The association of histological variables with demographic parameters, HCV load and genotype, HIV load, CD4(+) T cell count, and response to highly active antiretroviral therapy (HAART) was evaluated. HIV-HCV-coinfected patients showed a significantly higher HCV load, more-advanced fibrosis, and a higher liver fibrosis progression rate (FPR) than did non-HIV-infected patients. A high HCV load and a low CD4(+) T cell count were associated with a higher FPR. The immune response induced by HAART did not influence this progression. In conclusion, HIV-HCV-infected patients, mainly such patients with a high HCV load and an immunodepressed state, have a higher FPR. An independent effect of the immune response to HAART was not evident.

Dilutional hyponatremia in patients with cirrhosis and ascites.

OBJECTIVES: To analyze the predisposing factors, modifications of vasoactive systems, and prognosis of patients with cirrhosis and hyponatremia. PATIENTS AND METHODS: Fifty-four patients with hyponatremia (serum sodium level of <130 mEq/L after 5 days of hyponatremic diet and no diuretic therapy). Twenty cirrhotic patients served as controls. We measured plasma renin activity and levels of plasma aldosterone, norepinephrine, and antidiuretic hormone. Follow-up identified the development of hepatorenal syndrome and death. RESULTS: A higher percentage of patients with hyponatremia had decreased liver size, higher levels of plasma renin activity, and higher serum concentrations of aldosterone and norepinephrine. Renal insufficiency was detected in 31 of them (57%). Precipitating factors (hemorrhage or infections) were detected in 27 patients (50%). Incidence of hepatorenal syndrome and death were higher in patients with spontaneous development of hyponatremia (n = 23 [85%] and n = 25 [93%], respectively) than in patients with precipitating factors (n = 15 [56%] and n = 12 [44%], respectively) and cirrhotic controls (n = 1 [5%] and n = 5 [25%], respectively) (P<.001). Results of multivariate analysis showed that Child-Pugh index, presence of hepatocarcinoma, and serum concentration of urea were associated with mortality. After excluding those patients with kidney failure at the time of admission, only Child-Pugh index and norepinephrine concentrations were independent predictors of mortality. CONCLUSIONS: Hyponatremia is an alteration in patients with advanced liver disease. Although survival is significantly reduced in patients with spontaneous development of hyponatremia, a reduced sodium concentration cannot be considered as a independent predictor of the risk for death.