Long-term clearance of hepatitis C virus following interferon α-2b or peginterferon α-2b, alone or in combination with ribavirin.

Sustained virologic response (SVR) is the standard measure for evaluating response to therapy in patients with chronic hepatitis C (CHC). The aim of this study was to prospectively assess the durability of SVR in the pivotal studies of peginterferon (PEG-IFN) α-2b or IFN α-2b. We conducted two phase 3b long-term follow-up studies of patients previously treated for CHC in eight prospective randomized studies of IFN α-2b and/or PEG-IFN α-2b. Patients who achieved SVR [undetectable hepatitis C virus (HCV) RNA 24 weeks after completion of treatment] were eligible for inclusion in these follow-up studies. In total, 636 patients with SVR following treatment with IFN α-2b and 366 with SVR following treatment with PEG-IFN α-2b were enrolled. Definite relapse (quantifiable serum HCV RNA with no subsequent undetectable HCV RNA) was reported in six patients treated with IFN α-2b and three patients treated with PEG-IFN α-2b. Based on these relapses, the point estimate for the likelihood of maintaining response after 5 years was 99.2% [95% confidence interval (CI), 98.1-99.7%] for IFN α-2b and 99.4% (95% CI, 97.7-99.9%) for PEG-IFN α-2b. Successful treatment of hepatitis C with PEG-IFN α-2b or IFN α-2b leads to clinical cure of hepatitis C in the vast majority of cases.

Initial immunosuppression with or without basiliximab: a comparative study.

BACKGROUND: Following liver transplantation, acute kidney injury (AKI) and chronic kidney disease occur in 20%-50% and 30%-90% of patients, respectively. Basiliximab, a chimeric monoclonal antibody, is highly effective to prevent rejection in organ transplant recipients, particularly among patients with renal dysfunction who benefit from delayed introduction of calcineurin inhibitors. OBJECTIVE: The objective of this study was to measure the immunosuppressive effect of basiliximab and its impact on renal failure, lengths of hospital and intensive care unit (ICU) stays and prevalence of infection. METHODS: From January 2010 through December 2011, we performed a controlled, nonrandomized study comparing two different immunosuppressive regimens: Group I, 36 transplantation on 34 patients, tacrolimus and corticosteroids de novo with mycophenolate mofetil in cases of renal failure; and Group II, 33 transplantation in 33 patients, corticosteriods and mycophenolate mofetil de novo with basiliximab on day 0 and day 4, and inception of tacrolimus on day 3. RESULTS: Basiliximab patients (Group II) showed a significantly lower incidence of renal failure requiring replacement therapy (3.03% vs 25%; P = .014). The incidence of acute cellular rejection episodes treated with corticosteriod boluses was also significantly lower (3.03% vs 25%; P = .014). Bacterial, fungal, and cytomegalovirus infection rates were lower in Group II, although the differences were not significant. Similarly, Group II patients had an insignificantly shorter average stay in the hospital (25.9 vs 40.06 days) and the ICU (5.9 vs 8.17 days). CONCLUSIONS: Basiliximab administration with delayed introduction of calcineurin inhibitors may be an effective strategy to reduce post-liver transplantation AKI requiring renal replacement therapy.

Case report of splenic artery steal syndrome: demonstration of portal hyperflow mechanism by anatomic variant of the splenic artery and correlation with Doppler rates.

We report the case of a liver transplant recipient who developed a "splenic artery steal syndrome" (SASS) successfully treated by partial splenic embolization (PSE). Interestingly, because the patient presented an anatomic variant of the splenic artery (SA) originating from the superior mesenteric artery (SMA), improvement was observed in hepatic artery (HA) flow following PSE that could only be explained by decreased portal perfusion and not by the derivation from the SA.

[Study of the nutritional status of elders in Cantabria]. / Estudio del estado nutricional de los ancianos de Cantabria.

INTRODUCTION: Population ageing is a main concern under the biosanitary point of view. AIM: To assess the nutritional status of people 65 year-old and older in Cantabria (Spain) METHOD: A total of 1605 persons were studied by means of the MNA (Mini Nutritional Assessment); a) by primary care (59.9% in the unit, and 4.7% at home) and, b) in nursing homes (35.4%). RESULTS: Nutritional score (NS) was 23.4 ± 4.1 for women and 24.4 ± 4 in males (p < 0.001). We emphasize the fact that 22.3% of people studied in the nursing homes were malnourished or at risk of malnutrition, compared with 14.2% of those studied at the unit, and only 3.3% of the home visited elders. The correlation between the value of the NS and the subjective estimation of nutrition status showed a high value (0.65). We emphasize the negative correlation (-0.53) between BNI value and the incidence of skin lesions. CONCLUSION: Our results highlight the importance of identifying malnutrition or its risk in elders in order to prevent the negative consequences of this deficiency.

Estudio del estado nutricional de los ancianos de Cantabria / Study of the nutritional status of elders in Cantabria

Introducción: El envejecimiento de la población representa uno de los retos más importantes desde el punto de vista biosanitario Objetivo: Valorar el estado nutricional de las personas de 65 y más años de Cantabria. Métodos: Un total de 1605 personas fueron evaluadas por medio del MNA; a) en atención primaria (59,9% en la consulta y 4,7% en domicilios) y, b) en residencias de ancianos (35,4%).Resultados: La puntuación nutricional (PN) obtenida de la suma de los ítems del MNA fue 23,4 ± 4,1 para las mujeres y 24,4 ± 4 en los varones (p < 0,001). Destaca el hecho de que el 22,3% de las personas estudiadas en residencias está malnutrida o en riesgo de malnutrición, frente al 14,2% de las que acuden a consulta, y sólo el3,3% de las estudiadas en su domicilio. La correlación entre los valores de la PN y la apreciación subjetiva del estado de nutrición mostró un valor elevado (0,65). Destacamos la correlación negativa (-0,53) entre los valores del IMC y la incidencia de lesiones cutáneas. Conclusiones: Nuestros resultados indican la importancia de la identificación de la desnutrición o su riesgo, en personas mayores, por las consecuencias negativas que presenta este estado carencial (AU)

Introduction: Population ageing is a main concern under the biosanitary point of view. Aim: To assess the nutritional status of people 65 year old and older in Cantabria (Spain) Method: A total of 1605 persons were studied by means of the MNA (Mini Nutritional Assessment); a) by primary care (59.9% in the unit, and 4.7% at home) and, b) in nursing homes (35.4%).Results: Nutritional score (NS) was 23.4 ± 4.1 for women and 24.4 ± 4 in males (p < 0.001). We emphasize the fact that 22.3% of people studied in the nursing homes were malnourished or at risk of malnutrition, compared with 14.2% of those studied at the unit, and only 3.3% of the home visited elders. The correlation between the value of the NS and the subjective estimation of nutrition status showed a high value (0.65).We emphasize the negative correlation (-0.53) between BNI value and the incidence of skin lesions. Conclusion: Our results highlight the importance of identifying malnutrition or its risk in elders in order to prevent the negative consequences of this deficiency (AU)

Hepatitis C virus sensitivity to combined antiviral therapy in liver transplant versus immunocompetent patients.

Recurrent hepatitis C virus (HCV) after orthotopic liver transplantation (OLT) frequently causes allograft failure, because viral aggressiveness has been shown to be increased among immunosuppressed patients. Several studies have reported lower efficacy of antiviral therapy after OLT associated with worse tolerability. The aim of this study was to compare the logarithmic falls in viral loads at 4 and 12 weeks of treatment with pegylated interferon alpha and ribavirin among OLT versus immunocompetent patients. OLT patients (group 1) were recruited from 3 Spanish centers. Two age- and sex-matched controls (group 2) were randomly assigned to each case. We excluded coinfection with human immunodeficiency virus or hepatitis B or cholestatic hepatitis. Among group 1 (n = 66) were 72.7% men with an overall mean age of 52.7 +/- 10.1 years; 90.9% were genotype 1. The mean baseline viral load was 6.0 +/- 0.6 log10 IU/mL, and 19% of patients had cirrhosis. Among group 2 (n = 132) were 72.7% men with an overall mean age of 50.1 +/- 10.1 years; 92.4% were genotype 1. The mean baseline viral load was 5.9 +/- 0.5 log10 IU/mL, and 17% of patients had cirrhosis. There were no significant differences in patient characteristics between the 2 groups. The logarithmic falls in viral loads at 4 weeks of treatment were similar in groups 1 and 2: 2.3 +/- 2.1 vs 2.4 +/- 1.9 log10 IU/mL (P = .49); they were also similar at 12 weeks of treatment: 3.9 +/- 1.9 vs 3.7 +/- 2.4 log10 IU/mL (P = .66). In conclusion, in our study HCV sensitivity to combined antiviral therapy was the same among transplant versus immunocompetent patients.

Severe sirolimus-related inflammatory state anemia in an HIV+ liver transplant patient with calcineurin inhibitor renal insufficiency: a case report.

Although multifactorial anemia is common following orthotopic liver transplantation (OLT), the late introduction of sirolimus (SRL) has been associated with high rates of anemia, whose pathogenic mechanisms have not been fully studied. Herein we have described a case of severe anemia in an HIV+ OLT patient who was switched from calcineurin inhibitors (CNI) to SRL due to severe nephrotoxicity. After 22 weeks of SRL, hemoglobin levels dropped 4 g/dL to a nadir of 6.5 g/dL. After discarding other causes for anemia, we concluded that it displayed the features of anemia of a chronic inflammatory state (ACIS): decreased mean corpuscular volume (MCV), low serum iron despite high ferritinemia, and elevated fibrinogen and C-reactive protein (CRP) levels. SRL trough levels were never above the therapeutic range. After blood transfusions and erythropoietin (EPO) use, SRL was maintained within the lower range of therapeutic levels, with significant improvement in renal function. As described among kidney transplant recipients, SRL-related anemia in this HIV+ patient with CNI nephrotoxicity after OLT showed features of ACIS. Blood transfusions and EPO use allowed SRL maintenance.

Encefalopatía hepática secundaria a la existencia de un shunt portosistémico tratada satisfactoriamente mediante radiología intervencionista / Hepatic encephalopathy secondary to porto-systemic shunt satisfactorily treated with interventionist radiology

La encefalopatía hepática es un estado reversible de alteraciónen la función cognitiva, que puede ocurrir en pacientes con enfermedadhepática aguda o crónica o shunts porto-sistémicos, en elque puede aparecer cualquiera de los signos neurológicos o psiquiátricosconocidos. Las sustancias nitrogenadas procedentes dela digestión intestinal alcanzan el cerebro sin la depuración que suponesu paso por el hígado, debido a las derivaciones porto-sistémicas,y dan lugar a los signos característicos de la encefalopatíahepática. A continuación presentamos dos casos clínicos de pacientescon shunt porto-sistémicos, diagnosticados de encefalopatíahepática crónica recurrente refractaria al tratamiento médicoconvencional, tratados satisfactoriamente con embolización de dichoshunt mediante técnicas de radiología intervencionista

Hepatic encephalopathy is a reversible state of altered cognitionthat may occur in patients with acute or chronic liver diseaseor porto-systemic shunt, and in which known neurological or psychiatricsigns may develop. Nitrogenated substances from intestinaldigestion reach the brain without being cleared by their passagethrough the liver due to the presence of porto-systemicshunt. We report two cases of patients with porto-systemic shuntdiagnosed with recurrent chronic hepatic encephalopathy refractoryto conventional medical treatment. They were satisfactorilytreated with shunt embolization using interventionist radiologytechniques

Clinical trial: pharmacodynamics and pharmacokinetics of re-treatment with fixed-dose induction of peginterferon alpha-2a in hepatitis C virus genotype 1 true non-responder patients.

BACKGROUND: Patients infected with hepatitis C virus genotype 1 who are true non-responders to previous therapy suffer from a very difficult-to-cure disease. New approaches to treatment are necessary. AIM: To explore the efficacy, pharmacokinetics and safety of fixed-dose induction with peginterferon alpha-2a and ribavirin in this difficult-to-cure population. METHODS: Seventy-five hepatitis C virus genotype 1 true non-responder patients to a previous interferon-based combination regimen were randomised to receive peginterferon alpha-2a 360, 270 or 180 microg/week for 12 weeks, followed by 180 microg/week for 36 weeks, in combination with ribavirin (1000/1200 mg/day). Peginterferon alpha-2a concentration was measured throughout the study. RESULTS: Sustained virological response rates were 38%, 30% and 18%, in the 360, 270 and 180 microg/week groups, respectively (relapse rates: 25%, 50% and 64%, respectively). The area under the serum concentration-time curve of peginterferon alpha-2a from 0-12 weeks increased in a dose-dependent manner (P < 0.0001) and was associated with the sustained virological response (odds ratio: 1.35; 95% CI: 0.89, 2.06). The three regimens were equally well tolerated. CONCLUSION: Fixed-dose induction of peginterferon alpha-2a resulted in increased drug exposure and improved the likelihood of achieving a cure, without compromising safety in hepatitis C virus genotype 1 true non-responder patients.

[Hepatic encephalopathy secondary to porto-systemic shunt satisfactorily treated with interventionist radiology]. / Encefalopatía hepática secundaria a la existencia de un shunt portosistémico tratada satisfactoriamente mediante radiología intervencionista.

Hepatic encephalopathy is a reversible state of altered cognition that may occur in patients with acute or chronic liver disease or porto-systemic shunt, and in which known neurological or psychiatric signs may develop. Nitrogenated substances from intestinal digestion reach the brain without being cleared by their passage through the liver due to the presence of porto-systemic shunt. We report two cases of patients with porto-systemic shunt diagnosed with recurrent chronic hepatic encephalopathy refractory to conventional medical treatment. They were satisfactorily treated with shunt embolization using interventionist radiology techniques.

Hepatocarcinoma y trasplante hepático / Hepatocellular carcinoma and liver transplantation

No disponible

Hepatitis C virus recurrence after liver transplantation: influence of immunosuppressive regimens on viral load and liver histology.

Cyclosporine has recently been reported to produce in vitro suppression of hepatitis C virus replication driven by blockade of cyclophilins, an effect not shown for tacrolimus. However, the clinical consequence of this in vitro finding have not been well studied in vivo. We compared viral load and fibrosis in transplanted patients receiving monotherapy with tacrolimus or cyclosporine. Patients with recurrent hepatitis C after transplantation were selected from two tertiary centers with the following inclusion criteria: monotherapy with tacrolimus or cyclosporine for more than 12 months before viral load measurement, no antiviral treatment, corticosteroids stopped within 12 months after transplantation. HIV, hepatitis B, and active infection by cytomegalovirus were excluded. Patient characteristics, viral load, and fibrosis were compared by univariate analysis between the cyclosporine and tacrolimus groups. Significant variables, viral load, and fibrosis were included in a multivariate model. Sixty-six patients were included, 46 on tacrolimus and 20 on cyclosporine. Fifty-six were male, and the mean age was 55.3 +/- 10.1 years. Fibrosis (Ishak score) was 3.9 +/- 1.9 in the cyclosporine group and 2.7 +/- 1.9 in the tacrolimus group (P = .019). Viral load (log(10)IU/mL) was 5.8 +/- 0.5 and 5.9 +/- 0.5, respectively (P = .7) and time since liver transplantation was 95.3 +/- 47.7 and 41.1 +/- 16.8 months (P = .0001). In the multivariate model, viral load (P = .65) and fibrosis (P = .24) were not significantly different and only time since transplantation remained significant (P = .0001). In conclusion, viral load was not different in patients with tacrolimus as compared with cyclosporine, and the lower fibrosis observed in the cyclosporine group lacked significance when considered together with time since liver transplantation.

Scarce influence of corticosteroid boluses on long-term viral load and liver histology in transplanted patients with recurrent hepatitis C.

Corticosteroid boluses, which are the treatment for acute rejection episodes, have been shown to produce transient increases in viremia. However, their effect on long-term viral load, histological activity index (HAI), and fibrosis has not been well established. The aim of our study was to compare late viral load, HAI, and fibrosis in patients with versus without steroid boluses in the immediate posttransplant period. We analyzed patients transplanted due to hepatitis C virus. Inclusion criteria were: no change in immunosuppression (cyclosporine or tacrolimus with/without mycophenolate); no steroids in the previous 4 months; no antiviral treatment; liver biopsy and viral load determination >12 months after transplantation. Exclusion criteria were HIV, hepatitis B, and active cytomegalovirus infection. Nonparametric tests were used to compare viral load, HAI, and fibrosis (Ishak-score) among patients who received steroid boluses for an acute rejection episode (group 1) versus those who did not (group 2). Among the 48 selected patients were 38 men with the overall mean age of the entire group of 55.6 +/- 10.9 years. The mean period from liver transplantation was 53.25 +/- 33.4 months. Thirty-four (70.1%) were treated with tacrolimus and the rest, cyclosporine. Eleven (22.9%) had and 37 (77.1%) had not received corticosteroid boluses. The viral load was similar in groups 1 and 2 (5.74 +/- 0.54 vs 5.98 +/- 0.53 Log(10) IU per mL, P = .32). Fibrosis was also similar (2.5 +/- 1.6 vs 2.2 +/- 1.7, P = .56). However, HAI was higher in group 1 (7.5 +/- 1.7 vs 6.0 +/- 1.7, P = .026). In conclusion, although long-term viral load was similar in patients who had versus had not received one cycle of steroid boluses, the HAI was significantly higher in the former cohort, but had not resulted in greater fibrosis during the study follow-up.

Hepatitis C recurrence after liver transplantation: Viral and histologic response to full-dose PEG-interferon and ribavirin.

Hepatitis C recurrence after liver transplantation (LT) is universal, and frequently leads to cirrhosis and death. The aim of our study was to assess the efficacy and safety of 48-weeks of full-dose peg-interferon-alpha-2a (n = 4) or alpha-2b (n = 51) plus ribavirin (>11 mg/kg/day) in a multicentric cohort of 55 patients > or =12 months after LT. All subjects had histologically proven HCV recurrence, excluding severe cholestatic recurrence. Mean age was 54.3 +/- 9.7, 77% male, 90.9% genotype 1, 32.7% cirrhotics. All but 5 patients received monotherapy with tacrolimus (54.5%), cyclosporine (30.7%) or mycophenolate mofetil (5.5%). The rates of end-of-treatment response and sustained virological response (SVR) were 66.7% and 43.6%, respectively. Low baseline HCV-RNA (p = 0.005) and a length from LT to therapy between 2-4 years (p = 0.011) were predictors of SVR. The lack of achieving a viral load decrease > or =1-log10 at week 4 and/or 2-log10 at week 12 was 100% predictive of failure. The most frequent side effects were neutropenia (76,4%), anemia (60%) and infectious complications (30.9%). Toxicity led to peg-interferon withdrawal in 16 (29%) subjects. In 15 patients with post-treatment biopsy, the histological activity index was significantly improved (p = 0.006), whereas fibrosis did not change (p = 0.14). Three patients died (cholangitis, hepatic artery thrombosis and lung cancer). In conclusion, HCV therapy after LT was very effective, although it led to a significant rate of toxicity.

Viral kinetics and early prediction of nonresponse to peg-IFN-alpha-2b plus ribavirin in HCV genotypes 1/4 according to HIV serostatus.

To evaluate, among 70 hepatitis C virus (HCV)-monoinfected and 36 human immunodeficiency virus (HIV)-coinfected naïve patients with genotypes 1/4 receiving weight-adjusted pegylated interferon-alpha-2b/ribavirin, viral kinetics and the feasibility to predict treatment failure measuring early HCV-RNA decreases. HCV-RNA was assessed at baseline, weeks 4, 12 and 24. Receiver operating characteristic (ROC) curves were calculated to determine the most sensitive cut-off values of viral decrease at week 4 predicting treatment failure. Baseline predictors of failure were evaluated by univariate and multivariate analyses. Despite similar baseline HCV-RNA (5.75 vs 5.72 log(10)IU/ml, P = 0.6), HCV monoinfection led to significantly lower HCV-RNA values at weeks 4 (3.7 vs 4.3 log(10)IU/ml, P = 0.01), 12 (2.3 vs 3.5 log(10)IU/ml, P = 0.01) and 24 (1.4 vs 3.3 log(10)IU/ml, P = 0.001) and a higher rates of viral clearance at weeks 24 (60%vs 36%, P = 0.02), 48 (46%vs 25%, P = 0.03) and 72 (37%vs 17%). The lack of achieving an HCV-RNA decrease of at least 1 log(10) at week 4 was highly predictive of treatment failure for HCV-monoinfected patients (Se 100%, Sp 50%, positive predictive value (PPV) 57%, negative predictive value (NPV) 100%, ROC curve area, 0.86 [95% confidence interval (CI) 0.77-0.95], but not for HCV/HIV-coinfected patients (cut-off, 0 log(10), Se 100%, Sp 27%, PPV 21%, NPV 100%, ROC curve area, 0.71 (95% CI 0.49-0.93). HIV coinfection was independently associated with failure (odds ratio 2.95, 95% CI 1.08-8.04, P = 0.01). Thus the magnitude of HCV-RNA decreases at week 4 correlated with treatment response. Significant differences in viral kinetics and cut-off values predicting nonresponse suggest a slower HCV clearance rate in HIV coinfection, which was independently associated with treatment failure.