Ultra-sensitive procalcitonin may help rule out bacterial infections in patients with cirrhosis.

BACKGROUND: Bacterial infections are frequent complications in patients with cirrhosis. Since they are associated with poor outcomes, antibiotics are frequently over-prescribed. Surrogate markers of bacterial infections, like procalcitonin, are needed to better discriminate between infected and not infected patients. AIMS: To evaluated the diagnostic accuracy of an ultra-sensitive procalcitonin assay for the diagnosis of bacterial infections in patients with cirrhosis. MATERIAL AND METHODS: In a single-center prospective study, we determined the basal levels of procalcitonin in 106 episodes of admissions to the emergency department in 84 cirrhotic patients. Patients were classified as infected or not infected by two independent hepatologists blinded to the procalcitonin result. RESULTS: The prevalence of bacterial infection was 28% (29 episodes). The median procalcitonin was significantly higher in the infected group than in the not infected group (0.45 vs. 0.061 ng/mL, p < 0.001). The diagnostic accuracy of procalcitonin for bacterial infection estimated by the ROC curve was 0.95 (CI: 95%, 0.91-0.99). When selecting a cutoff value of 0.098 ng/mL a sensitivity of 97% and a negative predictive value 98% were found. CONCLUSIONS: The use of an ultra-sensitive procalcitonin assay identifies patients with cirrhosis at very low risk of bacterial infections.

Efficacy and safety of long term entecavir in chronic hepatitis B treatment naïve patients in clinical practice.

BACKGROUND AND AIMS: Entecavir (ETV) is effective and safe in patients with chronic hepatitis B in the short term, but its long term efficacy and safety has not been established. MATERIAL AND METHODS: We evaluated HBV DNA clearance, HBeAg/antiHBe and HBsAg/antiHBs seroconversion rates in HBeAg-positive and negative NUC naïve HBV patients treated with ETV for more than 6 months, and predictors of response. RESULTS: A hundred and sixty nine consecutive patients were treated with ETV for a median of 181 weeks. 61% were HBeAg positive, 23% were cirrhotics, and mean HBV-DNA levels were 6,88 ± 1,74 log10 IU/mL. Overall, 156 (92%) patients became HBV DNA undetectable, 92 (88%) HBeAg positive and 64 (98%) HBeAg negative patients. Seventy four (71%) patients cleared HBeAg after a median of 48 weeks of treatment, 23 (14%) patients cleared HBsAg (19 HBeAg positive and 4 HBeAg negative, p 0.025) after a median of 96 weeks of treatment, and 22 (13%) patients developed protective titers of anti-HBs. At the end of the study, 35 (20%) patients had discontinued therapy: 33 HBeAg positive and 2 HBeAg negative; 9 of them (26%) developed virological relapse after a median of 48 weeks of stopping treatment. None of the patients had primary non response and one patient developed breakthrough. Two patients developed HCC, three underwent liver transplantation and 3 deaths were attributable to liver-related events. No serious adverse events were reported. CONCLUSION: Long term ETV treatment showed high virological response rates, and a favorable safety profile for NUC-naive HBeAg-positive and negative patients treated in clinical practice.

Genetic variation in interleukin-28B predicts SVR in hepatitis C genotype 1 Argentine patients treated with PEG IFN and ribavirin.

BACKGROUND AND AIMS: Genetic variations in the interleukin 28B (IL28B) gene have been associated with viral response to PEG-interferon-α/ribavirin (PR) therapy in hepatitis C virus (HCV) genotype 1 infected patients from North America, Europe and Asia. The importance of these IL28B variants for Argentine patients remains unknown. MATERIAL AND METHODS: IL28B host genotypes (rs8099917 and rs12979860) were determined in a population of Argentine patients with European ancestry. Results were analyzed looking for their association with sustained virologic response (SVR) to PR therapy and compared with other baseline hosts' biochemical, histological and virological predictors of response. RESULTS: We studied 102 patients, 60% were men, and 40% of them were rs8099917 TT and 18% rs12979860 CC. Mean baseline serum HCV RNA was 1.673.092 IU/mL and mean F score was: 2.10 ± 1.18 (21% cirrhotic). SVR rate was higher in rs8099917 TT genotypes (55%) when compared to GT/GG (25%) (p = 0.002) and in rs1512979860 CC (64%) than in CT/TT (30%) (p = 0.004). The univariate analysis showed that rs8099917 TT (OR 3.7; 95 %CI 1.5-8.7; p = 0.002), rs12979860 CC (OR 4.6; 95%CI 1.5-13.7; p = 0.006), low viral load (OR 4.6; 95% CI 1.7-12.6; p = 0.002) and F0-2 (OR 8.5; 95% CI 2.3-30.6; p = 0.001) were significantly associated with SVR. In the multivariate analysis, rs12979860 CC, rs8099917 TT, viral load < 400.000 IU/mL and F0-2 were associated with SVR rates (p = 0.029, p = 0.012, p = 0.013 and p = 0.004, respectively). CONCLUSION: IL28B host genotypes should be added to baseline predictors of response to PR therapy in Latin American patients with European ancestry.

Short and long term outcome of kidney transplanted patients with chronic viral hepatitis B and C.

INTRODUCTION: Liver disease related to chronic viral hepatitis is a major cause of morbidity and mortality in renal transplant patients. There is no agreement upon the influence of chronic hepatitis B (HBV) and hepatitis C (HCV) infection in patient and graft survival. AIMS: The aim of the study was to evaluate the influence of HBV and HCV on patient and graft short and long term survival, in the patients transplanted at our institution. MATERIALS AND METHODS: We evaluated the influence of antiHCV and HBsAg status (positive vs. negative); sex; age (> 49 years vs. < 49 years at transplantation); time on dialysis (> 3 vs. < 3 years); acute rejection; kind of graft (deceased vs. living donor, and kidney versus kidney and pancreas); number of transplantations; use of induction immunosuppression; and maintenance immunosuppression treatment (comparing the traditional triple therapy containing azathioprine, cyclosporine and prednisone vs. newer regimens which include tacrolimus, mycophenolate mofetil, sirolimus, etc) on the survival, long term and within the first month of transplantation, of the graft and the patients transplanted in our Institution between January 1991 and August 2009. RESULTS: We included 542 patients, 60% males. median age of 42.03 years (SD 13.06 years). 180 patients (33%) were antiHCV positive and 23 (4%) were HBsAg positive. AntiHCV positive, traditional triple therapy and acute rejection were associated with diminished graft survival. Older age, antiHCV positive, HBsAg positive, deceased donor, kidney-pancreas transplantation and traditional triple therapy were associated with diminished patient survival. Traditional triple therapy was associated with diminished one month graft survival; and older age and antiHCV positive were associated with diminished one month patient survival. CONCLUSION: In our experience, antiHCV positive status was associated with diminished long term patient and graft survival, and diminished six month graft survival; and HBsAg positive was associated with diminished patient survival.

Imatinib-induced fatal acute liver failure.

Imatinib mesylate is a drug that has been approved for treatment of chronic myeloid leukemia (CML) in blast crisis, accelerated or chronic phase, and also for advanced gastrointestinal stromal tumors. Severe hepatic toxicity and three deaths from hepatic failure have been reported. We report the case of a 51-year-old woman who was admitted to our institution with severe acute hepatitis. She was diagnosed with CML and began treatment with imatinib mesylate at a dose of 400 mg/d. Five months after beginning treatment, she developed severe hepatitis associated with coagulopathy, and was admitted to our institution. She had been consuming acetaminophen 500-1000 mg/d after the onset of symptoms. She had a progressive increase in bilirubin level and a marked decrease of clotting factor V. Five days after admission, grade II encephalopathy developed and she was referred for liver transplantation. Her clinical condition progressively deteriorated, and 48 h after being referred for transplantation she suffered a cardiac arrest and died. This report adds concern about the possibility of imatinib-mesylate-induced hepatotoxicity and liver failure, particularly in the case of concomitant use with acetaminophen. Liver function tests should be carefully monitored during treatment and, with the appearance of any elevation of liver function tests, treatment should be discontinued.

Central hypothyroidism and hypophysitis during treatment of chronic hepatitis C with pegylated interferon alpha and ribavirin.

Thyroid dysfunction is a known complication of interferon treatment in patients with hepatitis C virus (HCV) infection. Other uncommon endocrine complications have been reported during the treatment of viral hepatitis with IFN-alpha, such as hypopituitarism. A 54-year-old female patient with chronic hepatitis C began treatment with pegylated (PEG)-IFN-alpha 2a 180 mug/week plus ribavirin 1,000 mg/day. At week 20 of treatment, her routine laboratory control showed low levels of thyroid-stimulating hormone (TSH) and free serum thyroxine. This was confirmed at week 24, and other laboratory values showed low levels of adrenocorticotrophic hormone (ACTH). A T1-weighted magnetic resonance imaging scan demonstrated high intensity of the anterior pituitary gland and enhancement after intravenous administration of gadolinium. Hypophysitis with hypothalamic-pituitary dysfunction and secondary or central hypothyroidism was diagnosed on the basis of the clinical features, endocrinological assessment, immunological markers and imaging studies. Twenty-four weeks after stopping treatment, HCV RNA was negative by polymerase chain reaction and alanine aminotransferase values were below the upper limits of normal, and ACTH and thyroid values remained within the reference values. This is the first report of central hypothyroidism and hypophysitis during treatment with PEG-IFN-alpha plus ribavirin, and may be included in the potential list of side effects of the combination treatment.

Chylous ascites as the main manifestation of left ventricular dysfunction: a case report.

BACKGROUND: Ascites is one of the most common complications of liver diseases, even though in 15% of the cases it is related to extrahepatic diseases; 3% are of cardiac nature and they appear associated with signs and symptoms of heart failure. CASE PRESENTATION: A 70 year old man was admitted with more than one year history of abdominal distension and a weight gain of 10 kilograms. He is asymptomatic and walks 2000-3000 meters a day without angor or dyspnea. The physical examination shows moderate abdominal distension, with no hepatosplenomegaly or edema, and there is mild jugular vein distension. The studies performed (complete laboratory work up, paracentesis, liver biopsy, echocardiogram, intrahepatic pressure measurements, etc.) showed a chylous ascites related to portal hypertension, and left ventricular dysfunction was the only probable cause found. CONCLUSION: Asymptomatic heart dysfunction can mimic liver disease and should be kept in mind as a cause of chylous ascites.

HBsAg as predictor of outcome in renal transplant patients.

Chronic liver infections related to hepatitis B and C viruses are a common problem in renal transplant patients with a prevalence of 1.5 to 50% in different countries. There is no uniform agreement regarding their influence on the incidence of acute rejection, graft outcome and survival of renal transplant patients. We retrospectively evaluated the influence of antiHBc, antiHCV and HBsAg positive status; gender; age over 50 years of age at the time of transplantation; pre and postransplantation alaninaminotransferase (ALT) elevation; acute rejection; type of graft; number of transplants; and maintenance and induction immunosuppression treatment on the incidence of acute rejection and both graft and patient survival in the population transplanted in our center between 1991 and 1998. The univariate analysis showed that antiHCV, HBsAg and antiHBc status, more than one renal transplant and one or more episodes of acute rejection were associated with diminished graft survival; and being over the age of 50 at the time of transplantation was also associated with diminished patient survival. In the multivariate analysis HBsAg positive and one or more episodes of rejection were associated with a diminished graft survival, and none of the variables studied was associated with diminished patient survival. In conclusion antiHCV and HBsAg positive status was associated with an increased risk of losing the transplanted kidney, and HBsAg positivity was associated with an increased risk of death, but this was not a statistically significant association.

HBsAg as predictor of outcome in renal transplant patients

Las hepatitis virales crónicas causadas por los virus B y C son un problema común en los pacientes trasplantados renales. No hay un consenso en cuanto a su influencia en la evolucíon del injerto y la sobrevida de los pacientes trasplantados renales. Evaluamos en forma retrospectiva la influencia de la positividad de antiHBc, antiHCV y HBsAg; sexo; edad mayor de 50 años al momento del trasplante; elevación de la alaninaminotransferasa en el período pre y postrasplante; rechazo agudo; tipo de injerto; número de trasplantes; y tratamiento inmunosupresor en la sobrevida del injerto renal y del paciente en los pacientes trasplantados en nuestro centro entre 1991 y 1998. El análisis univariado mostró que la presencia de antiHBc, anti HCV y HBsAg, más de un trasplante renal y uno o más episodios de rechazo agudo se asociaron con una disminución en la sobrevida de los pacientes. El análisis multivariado mostró que la presencia de positividad para HBsAg y uno o más episodios de rechazo agudo se asociaron con una disminución en la sobrevida del injerto, y ninguna de las variables se asoció con una disminución en la sobrevida de los pacientes. En conclusión: la presencia de antiHCV y HBsAg se asoció con un mayor riesgo de muerte, aunque esto no fue estadísticamente significativo.

HBsAg as predictor of outcome in renal transplant patients

Las hepatitis virales crónicas causadas por los virus B y C son un problema común en los pacientes trasplantados renales. No hay un consenso en cuanto a su influencia en la evolucíon del injerto y la sobrevida de los pacientes trasplantados renales. Evaluamos en forma retrospectiva la influencia de la positividad de antiHBc, antiHCV y HBsAg; sexo; edad mayor de 50 años al momento del trasplante; elevación de la alaninaminotransferasa en el período pre y postrasplante; rechazo agudo; tipo de injerto; número de trasplantes; y tratamiento inmunosupresor en la sobrevida del injerto renal y del paciente en los pacientes trasplantados en nuestro centro entre 1991 y 1998. El análisis univariado mostró que la presencia de antiHBc, anti HCV y HBsAg, más de un trasplante renal y uno o más episodios de rechazo agudo se asociaron con una disminución en la sobrevida de los pacientes. El análisis multivariado mostró que la presencia de positividad para HBsAg y uno o más episodios de rechazo agudo se asociaron con una disminución en la sobrevida del injerto, y ninguna de las variables se asoció con una disminución en la sobrevida de los pacientes. En conclusión: la presencia de antiHCV y HBsAg se asoció con un mayor riesgo de muerte, aunque esto no fue estadísticamente significativo. (AU)

HBsAg as predictor of outcome in renal transplant patients.

Chronic liver infections related to hepatitis B and C viruses are a common problem in renal transplant patients with a prevalence of 1.5 to 50

in different countries. There is no uniform agreement regarding their influence on the incidence of acute rejection, graft outcome and survival of renal transplant patients. We retrospectively evaluated the influence of antiHBc, antiHCV and HBsAg positive status; gender; age over 50 years of age at the time of transplantation; pre and postransplantation alaninaminotransferase (ALT) elevation; acute rejection; type of graft; number of transplants; and maintenance and induction immunosuppression treatment on the incidence of acute rejection and both graft and patient survival in the population transplanted in our center between 1991 and 1998. The univariate analysis showed that antiHCV, HBsAg and antiHBc status, more than one renal transplant and one or more episodes of acute rejection were associated with diminished graft survival; and being over the age of 50 at the time of transplantation was also associated with diminished patient survival. In the multivariate analysis HBsAg positive and one or more episodes of rejection were associated with a diminished graft survival, and none of the variables studied was associated with diminished patient survival. In conclusion antiHCV and HBsAg positive status was associated with an increased risk of losing the transplanted kidney, and HBsAg positivity was associated with an increased risk of death, but this was not a statistically significant association.

Descompensación aguda fatal como forma de presentación de un hepatocarcinoma en un trasplantado renal con hepatitis crónica B y C asintomática / Fatal acute hepatic failure with hepatocarcinoma presentation in a patient with renal transplant with asymptomatic chronic B and C hepatitis

El hepatocarcinoma es un tumor primario que complica las hepatopatopatías crónicas y se asocia con cirrosis en el 80-90 por ciento de los casos. Un paciente trasplantado renal portador de una hepatitis crónica B y C es internado por presentar deterioro del estado general, deterioro de la función renal asociado a aumento de las transaminasas y de la fosfatasa alcalina con niveles muy elevados de a-fetoproteína. Desarrolló deterioro de la función renal, ascitis y peritonitis bacteriana espontánea. La TAC mostraba múltiples masas hepáticas. El paciente falleció 17 días después de comenzados los síntomas con encefalopatía hepática. Una biopsia postmortem confirmó el diagnóstico de cirrosis y hepatocarcinoma. Este reporte, como así algunos otros, nos muestra la evolución acelerada de las hepatopatías virales crónicas en los pacientes trasplantados renales y abre el interrogante sobre la conveniencia del trasplante renal y el adecuado seguimiento en los pacientes con hepatitis virales crónicas.

Descompensación aguda fatal como forma de presentación de un hepatocarcinoma en un trasplantado renal con hepatitis crónica B y C asintomática / Fatal acute hepatic failure with hepatocarcinoma presentation in a patient with renal transplant with asymptomatic chronic B and C hepatitis

El hepatocarcinoma es un tumor primario que complica las hepatopatopatías crónicas y se asocia con cirrosis en el 80-90 por ciento de los casos. Un paciente trasplantado renal portador de una hepatitis crónica B y C es internado por presentar deterioro del estado general, deterioro de la función renal asociado a aumento de las transaminasas y de la fosfatasa alcalina con niveles muy elevados de a-fetoproteína. Desarrolló deterioro de la función renal, ascitis y peritonitis bacteriana espontánea. La TAC mostraba múltiples masas hepáticas. El paciente falleció 17 días después de comenzados los síntomas con encefalopatía hepática. Una biopsia postmortem confirmó el diagnóstico de cirrosis y hepatocarcinoma. Este reporte, como así algunos otros, nos muestra la evolución acelerada de las hepatopatías virales crónicas en los pacientes trasplantados renales y abre el interrogante sobre la conveniencia del trasplante renal y el adecuado seguimiento en los pacientes con hepatitis virales crónicas. (AU)