Alberto Muñoz

Ciprofloxacin in primary prophylaxis of spontaneous bacterial peritonitis: A randomized, placebo-controlled study

BACKGROUND/AIMS Low protein concentration in ascitic fluid has been identified as a risk factor for spontaneous bacterial peritonitis (SBP). Until now, primary prophylaxis has not been recommended in these patients. The aim was to investigate the efficacy of long-term administration of ciprofloxacin to prevent SBP. METHODS One hundred cirrhotic patients with <1.5 g/dl of total protein in ascitic fluid were randomized prospectively, in a double blind fashion to receive ciprofloxacin 500 mg/day (n=50) or placebo (n=50) for 12 months. RESULTS Baseline data were similar in both groups. In the ciprofloxacin group, SBP occurred almost four times less frequently than in the placebo group but it was not statistically significant. The probability of survival at 12 months was significantly higher in patients receiving ciprofloxacin (86% versus 66%) (p<0.04). SBP and sepsis were the most frequent causes of death in the placebo group whereas gastrointestinal bleeding was responsible for the most deaths in the ciprofloxacin group. The probability of remaining free of bacterial infections was higher in patients receiving ciprofloxacin (80% versus 55%) (p=0.05). CONCLUSIONS Patients with cirrhosis and low protein concentration in ascitic fluid are candidates to receive long-term prophylaxis to reduce the risk of infections and improve survival.

Immune dysfunction in cirrhosis: Distinct cytokines phenotypes according to cirrhosis severity.

BACKGROUND/OBJECTIVES Cirrhosis associated immune dysfunction has been proposed to switch from a pro-inflammatory phenotype in stable cirrhosis to an immunodeficient one in patients with decompensated cirrhosis and acute-on-chronic liver failure. The aim of the present study was to compare serum cytokine levels between healthy patients, stable cirrhosis, and decompensated cirrhotic patients with and without development of acute-on-chronic liver failure (ACLF); and to explore whether any of the measured cytokines is associated with cirrhosis severity and prognosis in ACLF patients. METHODS Patients were enrolled from October 2013 to May 2014 in two hospitals located in Buenos Aires. Cirrhotic patients with an acute decompensating event were enrolled accordingly to the development of ACLF defined by the CANONIC study group. There were two control groups: healthy subjects (n=14) and stable cirrhotic patients (n=14). Demographic, clinical and biochemical data were obtained. Seventeen cytokines were measured using Bio-Plex Pro Human Cytokine 17-plex Assay. RESULTS Of the 49 decompensated cirrhotic patients enrolled, 18 (36.7%) developed ACLF. Leukocyte count, MELD score at admission, Clif-SOFA at admission and day 7 were significantly higher in the ACLF group (p=0.046, p<0.001, p<0.001, p<0.001 respectively) as well as short-term mortality (p<0.001) compared to stable and decompensated cirrhotic patients. In comparison with healthy controls, stable cirrhotic and decompensated cirrhotic patients showed increased levels of pro-inflammatory and anti-inflammatory cytokines: IL-6, IL-7, IL-8, IL-10, IL 12, and TNF-α. Decompensated cirrhotic patients with the development of ACLF showed a significant decrease of IL-7, IL-10, IL-12, TNF-α, MCP-1 and IFN-γ, but a sustained response of IL-6 and IL-8. When evaluating cirrhosis severity, IL-6 and IL-8 correlated positively with MELD score, whereas only IL-6 correlated positively with Clif-SOFA score at day 7; IL-2 correlated negatively with Clif-SOFA at admission. In comparison with all scores, leukocyte count showed positive correlation and IFN-γ negative correlation with disease severity. When evaluating survival, only MELD and Clif-SOFA scores had a significant association with mortality. CONCLUSIONS Pro-inflammatory cytokines and chemo-attractant elements are increased in cirrhosis in comparison with healthy subjects, and display higher values concomitantly with cirrhosis progression. However, in acute-on-chronic liver failure an opposite cytokine pattern that can be resumed as a combination of immune paresis and excessive inflammatory response was observed. Several pro-inflammatory cytokines (IL-2, IL-6, IL-8 and IFN-γ) showed correlation with disease severity; their utility as prognostic biomarkers needs to be further studied.

Patients with ascites have higher variceal pressure and wall tension than patients without ascites.

OBJECTIVE:It has been suggested that ascites is a risk factor for variceal bleeding. Recently, it has been demonstrated that total paracentesis decreases variceal pressure. However, no data are available showing the basal variceal pressure in patients with and without ascites.METHODS:We studied 76 cirrhotic patients, 49 with and 27 without ascites. Variceal pressure was measured by direct puncture. Variceal size, variceal pressure gradient, and variceal wall tension were also obtained.RESULTS:No demographic differences were observed between the groups. Child score was higher (9.7 ± 1.5 vs 7.8 ± 2.1, p < 0.001) and serum albumin lower (2.6 ± 0.6 vs 3.0 ± 0.7 mg %, p < 0.02) in ascitic than in nonascitic patients, respectively. Variceal pressure and variceal pressure gradient were significantly higher in patients with ascites than in those without ascites (25.0 ± 6 vs 20.4 ± 4.6 mm Hg, p < 0.001 and 18.75 ± 4.7 vs 13.70 ± 4.1 mm Hg, p < 0.0001, respectively). The variceal wall tension was significantly higher in patients with ascites (71.0 ± 25.1 mm Hg/mm) than in those without ascites (55.1 ± 22.1 mm Hg/mm, p < 0.03). No relationship was observed between variceal pressure gradient and liver function. Ascites patients included in Child-Pugh grade A+B presented a similar variceal pressure to Child C patients (18.5 ± 4.2 vs 19.3 ± 5.7 mm Hg, respectively, p = ns). In addition, no relationship was observed between variceal pressure gradient and etiology of cirrhosis.CONCLUSION:Our results demonstrate that patients with ascites have significantly higher variceal pressure and wall tension than patients without ascites. These results suggest that patients with ascites may be at risk for variceal bleeding.

Lidocaine and Monoethylglycinexylidide Serum Determinations to Analyze Liver Function of Cirrhotic Patients After Oral Administration

Our aim was to compare standard liver functiontests (serum bilirubin, serum albumin and prothrombinconcentration), with lidocaine andmonoethylglycinexylidide pharmacokinetic parameters,after oral lidocaine administration, to assess hepatic function ofcirrhotic individuals. Twenty-one consecutive cirrhoticpatients, nine consecutive acute hepatitis patients, andnine healthy individuals received oral lidocaine. Lidocaine and monoethylglycinexylidide serumconcentrations were determined by the TDx system.Cirrhotic patients had higher lidocaine and lowermonoethylglycinexylidide serum concentrations anddifferences in its pharmacokinetic variables, compared tocontrol and hepatitis groups (P < 0.05). Sensitivityof lidocaine serum determinations (100%) was greaterthan sensitivity of serum bilirubin (57%), serum albumin (62%), and prothrombin concentrations(43%) and monoethylglycinexylidide serum concentrations(57%) in differentiating cirrhotic individuals fromcontrols. In conclusion, after oral administration, lidocaine and monoethylglycinexylididepharmacokinetic parameters are significantly altered incirrhotic patients compared to normal and acutehepatitis subjects. Lidocaine pharmacokinetic parameterswould be better than those ofmonoethylglycinexylidide and standard liver functiontests in the evaluation of liver function of cirrhoticpatients.

Ombitasvir/paritaprevir/ritonavir/dasabuvir ± ribavirin is safe and effective in HCV-infected patients in a real-life cohort from Latin America

Information about the use of ombitasvir/paritaprevir/ritonavir/dasabuvir ± ribavirin (OBV/PTV/r/DSV ± RBV) in real‐clinical practice in Latin America is scarce. We aimed to confirm safety and effectiveness of OBV/PTV/r/DSV ± RBV therapy in real‐world setting. We analyzed a cohort of patients with genotype 1 infection treated with OBV/PTV/r/DSV ± RBV. Data on demographics, clinical features, safety, and virological response were retrospectively collected from 21 centers in Latin America. A total of 96 patients received OBV/PTV/r/DSV, associated with RBV in 68% of the cases. Most were genotype 1b (80%), 56 (58%) had cirrhosis, and 45 (47%) failed prior HCV treatment. Adverse events occurred in 62% of patients. The most common adverse events were pruritus (21%), hyperbilirubinemia (17%), and asthenia (17%). Five patients discontinued therapy prematurely due to hepatic decompensation, three of them were Child‐Pugh B at baseline and one patient died due to multi‐organ failure. Follow up HCV‐RNA 12 weeks after completion of therapy was evaluated in all the patients and sustained virologic response rate was 97%. No virologic breakthrough was detected. Our study confirms that OBV/PTV/r/DSV treatment is highly effective in patients with chronic HCV without cirrhosis or with Child‐Pugh A cirrhosis in non‐European populations. Adverse events were often mild and rarely led to treatment discontinuation except for patients with Child‐Pugh B cirrhosis or with previous history of hepatic decompensation. These results can support the development of public strategies to expand the access of OBV/PTV/r + DSV and other DAAs combinations in order to reduce the burden of HCV infection in our region.