Differences in the incidence and clinical evolution of early neurotoxicity after liver transplantation based on tacrolimus formulation used in the immunosuppressive induction protocol.

INTRODUCTION: Posttransplant early calcineurin inhibitor (CNI)-induced neurotoxicity (ECIIN) was related to high CNI levels, among other factors. Minimizing exposure could modify its incidence or clinical evolution. OBJECTIVE: To compare the incidence, predisposing factors, and clinical evolution of ECIIN after immunosuppressive induction with low-dose tacrolimus-MR (Advagraf) or conventional dose tacrolimus (Prograf). PATIENTS AND METHODS: We matched 71 patients treated with an immunosuppression induction schedule with basiliximab and low doses of Advagraf (cases group) 1:1 by recipient age and indication for liver transplantation (OLT) with patients treated with a conventional tacrolimus regimen (control group). Baseline characteristics, liver and kidney function, operative technical characteristics, kidney function, and C0 tacrolimus levels at several time points after liver OLT were analyzed. RESULTS: There were 31 cases of ECIIN (21%), 14 in the cases group (20%) and 17 in the control group (24%; P < .001). The incidence of ECIIN was higher in alcoholic liver disease (odds ratio [OR], 8.2; 95% CI, 2.3-28.6; P < .001) and past history of encephalopathy (OR, 2.6; 95% CI, 1.16-5.9; P < .02). Among cases, the incidence of ECIIN was higher when encephalopathy signs were present at time of transplantation (36% vs 12%; P < .001). Control of ECIIN required a switch to cyclosporine therapy in all those in the cases group, whereas this was only needed for 9 cases in the control group (47%; P < .001). CONCLUSION: In this study, although the incidence rate of neurotoxicity induced by Advagraf was lower than the induced by Prograf, it did not respond to routine treatment and required a significantly higher rate of switch to cyclosporine for its control.

Late recurrence of hepatocellular carcinoma after liver transplantation: is an active surveillance for recurrence needed?

INTRODUCTION: Liver transplantation (OLT) is considered the most efficient therapeutic option for patients with liver cirrhosis and early stage hepatocellular carcinoma (HCC) in terms of overall survival and recurrence rates, when restrictive selection criteria are applied. Nevertheless, tumor recurrence may occur in 3.5% to 21% of recipients. It usually occurs within 2 years following OLT, having a major negative impact on prognosis. The efficacy of active posttransplantation surveillance for recurrence has not been demonstrated, due to the poor prognosis of recipients with recurrences. AIM: To analyze the clinical, pathological, and prognostic consequences of late recurrence (>5 years after OLT). METHOD: We analyzed the clinical records of 165 HCC patients including 142 males of overall mean age of 58 ± 6.9 years who underwent OLT between July 1994 and August 2011. RESULTS: Overall survival was 84%, 76%, 66.8%, and 57% at 1, 3, 5, and 10 years, respectively. Tumor recurrence, which was observed in 18 (10.9%) recipients, was a major predictive factor for survival: its rates were 72.2%, 53.3%, 26.7%, and 10% at 1, 3, 5, and 10 years, respectively. HCC recurrence was detected in 77.8% of patients within the first 3 years after OLT. Three recipients (100% males, aged 54-60 years) showed late recurrences after 7, 9, and 10 years. In only one case were Milan criteria surpassed after the examination of explanted liver; no vascular invasion was detected in any case. Recurrence sites were peritoneal, intrahepatic, and subcutaneous abdominal wall tissue. In all cases, immunosuppression was switched from a calcineurin-inhibitor to a mammalian target of rapamycin inhibitor. We surgically resected the extrahepatic recurrences. The remaining recipient was treated with transarterial chemoembolization with doxorubicin-eluting beads and sorafenib. Prognosis after diagnosis of recurrence was poor with median a survival of 278 days (range, 114-704). CONCLUSIONS: Global survival, recurrence rate, and pattern of recurrence were similar to previously reported data. Nevertheless, in three patients recurrence was diagnosed >5 years after OLT. Although recurrence was limited and surgically removed in two cases, disease-free survival was poor. Thus, prolonged active surveillance for HCC recurrence beyond 5 years after OLT may be not useful to provide a survival benefit for these patients.

Viral and host factors related with histopathologic activity in patients with chronic hepatitis B and moderate or intermittently elevated alanine aminotransferase levels.

OBJECTIVE: viral and host factors are related with progression of pathological lesion in chronic hepatitis B. We analyzed these factors in patients with moderate or intermittently elevated ALT levels, and its threshold that determinate significant histological activity. PATIENTS AND METHODS: retrospective analyses of viral and host parameters in 89 consecutive chronic hepatitis B patients biopsied because of moderate or intermittently elevated ALT levels [1-2 x ULN (ULN = 39 IU/ml)] and/or DNA-HBV > 2 x 10³ IU/ml in AntiHBe+ patients. It was analyzed age, gender, ALT levels, HBeAg, viral load and genotype. It was considered advanced histological lesion a Knodell Score (KS) > 7 and histological lesion indicating treatment, lobular inflammation ≥2 or fibrosis ≥2 according to Scheuer Classification. RESULTS: KS > 7 and histological lesion indicating treatment was found in 47.8 and 60.7% respectively. It was observed relationship between age, male gender, ALT levels and viral load with histological damage (p < 0.05). Frequency of advanced lesion indicating treatment was upper in patients with ALT levels > ULN (69.1 vs. 47.1%, p = 0.04). There were not significant upper frequencies of advanced lesion when a cut-off of 40 years or DNA-HBV > 2 x 10³ IU/ml viral load or serological status HBeAg was considerate. Histological activity was lesser in genotype D patients than those infected with others genotypes (p < 0.05). CONCLUSION: upper frequency of advanced histological lesion in chronic hepatitis B patients with moderate or intermittently elevated ALT levels make recommended liver biopsy, independent of viral load and serological status HBeAg. Other factors like age, gender or genotype can help to indicate biopsy in individual cases.

Influencia de factores virales y del huésped en la actividad histológica en pacientes con hepatitis crónica por virus de la hepatitis B y elevación moderada o intermitente de alanina aminotransferasa / No disponible

Objetivo: analizar factores virales y del huésped relacionados con actividad histológica en un subgrupo de pacientes con hepatitis crónica B y elevación intermitente o moderada de alanina aminotransferasa (ALT), y el umbral que determine daño histológico indicativo de tratamiento. Pacientes y métodos: análisis retrospectivo de parámetros virales y del huésped en 89 pacientes con hepatitis crónica B biopsiados consecutivamente por elevación intermitente o moderada de ALT [1-2 x USN (USN = 39 UI/ml)]. Fueron analizados edad, sexo, ALT, HBeAg, carga viral y genotipo. Se consideró como lesion histológica avanzada un Índice de Knodell (IK) > 7, e indicativa de tratamiento la inflamación lobulillar ≥ 2 o fibrosis ≥ 2 según la clasificación de Scheuer. Resultados: existió un IK > 7 y lesión indicativa de tratamiento en 47,8 y 60,7%, respectivamente. La edad, sexo varón, ALT y carga viral se relacionaron con lesión avanzada (p < 0,05). La frecuencia de lesión indicativa de tratamiento fue mayor en pacientes con ALT > USN (69,1 vs. 47,1%, p = 0,04). La frecuencia de lesión avanzada no fue significativamente mayor cuando se consideraron como puntos de corte la edad de 40 años o ADNVHB > 2 x 103 UI/ml o positividad de HBeAg. Se observó menor actividad histológica en pacientes con genotipo D respecto a aquellos infectados con otros genotipos (p < 0,05). Conclusión: una mayor frecuencia de lesión avanzada en pacientes con hepatitis crónica B y elevación intermitente o moderada de ALT hacen recomendable la biopsia hepática independientemente de la carga viral y positividad de HBeAg. Factores como la edad, sexo o genotipo pueden ayudar de forma individual a dicha indicación(AU)

Objective: viral and host factors are related with progression of pathological lesion in chronic hepatitis B. We analyzed these factors in patients with moderate or intermittently elevated ALT levels, and its threshold that determinate significant histological activity. Patients and methods: retrospective analyses of viral and host parameters in 89 consecutive chronic hepatitis B patients biopsied because of moderate or intermittently elevated ALT levels [1-2 x ULN (ULN = 39 IU/ml)] and/or DNA-HBV > 2 x 103 IU/ml in AntiHBe+ patients. It was analyzed age, gender, ALT levels, HBeAg, viral load and genotype. It was considered advanced histological lesion a Knodell Score (KS) > 7 and histological lesion indicating treatment, lobular inflammation ≥ 2 or fibrosis ≥ 2 according to Scheuer Classification. Results: KS > 7 and histological lesion indicating treatment was found in 47.8 and 60.7% respectively. It was observed relationship between age, male gender, ALT levels and viral load with histological damage (p < 0.05). Frequency of advanced lesion indicating treatment was upper in patients with ALT levels > ULN (69.1 vs. 47.1%, p = 0.04). There were not significant upper frequencies of advanced lesion when a cut-off of 40 years or DNAHBV > 2 x 103 IU/ml viral load or serological status HBeAg was considerate. Histological activity was lesser in genotype D patients than those infected with others genotypes (p < 0.05). Conclusion: upper frequency of advanced histological lesion in chronic hepatitis B patients with moderate or intermittently elevated ALT levels make recommended liver biopsy, independent of viral load and serological status HBeAg. Other factors like age, gender or genotype can help to indicate biopsy in individual cases(AU)

Valganciclovir-induced leukopenia in liver transplant recipients: influence of concomitant use of mycophenolate mofetil.

INTRODUCTION: An increased incidence and magnitude of leukopenia during concomitant treatment with valganciclovir (VGC) and mycophenolate mofetil (MMF) has been reported. OBJECTIVE: To evalute the incidence and severity of leukopenia and neutropenia among liver recipients treated with VGC and related factors. PATIENTS AND METHODS: Retrospective analysis of clinical and analytical data related to leukopenia (<3000 leukocytes/mm(3)) and neutropenia (<900 neutrophils/mm(3)) in liver transplant patients who were treated with VGC from 2003 to 2007. We examined the influence of concomitant administration of MMF and development of subsequent infections. RESULTS: Among 209 liver transplants, 40 treatments with VGC were prescribed in 37 patients (17.7%), 12 of which (30%) were associated with MMF. The patients has an average age of 49.7 +/- 12.7, body mass index (BMI) of 27.28 +/- 5.17, and Model for End-stage Liver Disease Score (MELD) 12.45 +/- 7.5. The daily average dose of VGC was 1440 +/- 446.5 mg and MMF, 1454.5 +/- 350.3 mg. We observed a decrease of 30% in initial leukocyte count (5353.7 +/- 2706.6) and 40% in neutrophil count (3600 +/- 2182.1). With no relationship to total dose or BMI-adjusted dose of VGC nor concomitant administration of MMF. The initial leukocyte count was significantly lower (4411 +/- 1930 vs 6206 +/- 3053; P = .03) and underwent a main drop (2344.7 +/- 1974.3 vs 898.1 +/- 2435.6; P = .04) when leukopenia developed. In the induced neutropenia group, previous leukocyte count (3797.1 +/- 1223.9 vs 5683.9 +/- 2829.3; P = .01), MELD (18.7 +/- 8.8 vs 11.1 +/- 6.6; P = .01), and the creatinine pretreatment (1.44 +/- 0.4 vs 1.09 +/- 0.3; P = .01) were significantly different. Subsequent infections induced by the leukopenia were not observed. CONCLUSIONS: In our series, the concomitant use of VGC and MMF was not associated with a greater incidence of leukopenia and/or neutropenia than VGC administration alone. Previous leukocyte count was associated with them. MELD and renal dysfunction are factors related to severe neutropenia. Leukopenia was not associated with a greater incidence of infections.

Poliquistosis hepática / Polycystic liver disease

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Síndrome de Budd-Chiari en una paciente con trombocitemia esencial y portadora de la mutación G20210A en el gen de la protrombina / No disponible

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[The autoimmune hepatitis-primary biliary cirrhosis overlap syndrome: a case report]. / Síndrome overlap hepatitis autoinmune-cirrosis biliar primaria: a propósito de un caso.

The autoimmune hepatitis-primary biliary cirrhosis overlap syndrome is an entity characterized by clinical, analytical, immunological and histological manifestations of both entities. We present the case of a 26-year-old woman with a serious acute hepatitis that fulfills the diagnostic criteria of the overlap syndrome and that showed a satisfactory response to oral corticoid therapy.

Síndrome overlap hepatitis autoinmune-cirrosis biliar primaria: a propósito de un caso / The autoinmune hepatitis-primary biliary cirrhosis overlap syndrome: a case report

El síndrome overlap hepatitis autoinmune- cirrosis biliar primaria es una entidad caracterizada por manifestaciones clínicas, analíticas, inmunológicas e histológicas de ambas entidades. Presentamos el caso de una mujer de 26 años con una hepatitis aguda grave que cumple los criterios diagnósticos del síndrome de superposición y que respondió de forma satisfactoria al tratamiento con corticoides orales

The autoinmune hepatitis-primary biliary cirrhosis overlap syndrome is an entity characterized by clinical, analytical, immunological and histological manifestations of both entities. We present the case of a 26-year-old woman with a serious acute hepatitis that fulfills the diagnostic criteria of the overlap syndrome and that showed a satisfactory response to oral corticoid therapy

[Epidermiology of alcohol withdrawal syndrome. Mortality and factors of poor prognostic]. / Epidemiología del síndrome de abstinencia alcohólica. Mortalidad y factores de mal pronóstico.

INTRODUCTION: Patients with alcoholism and alcohol withdrawal syndrome (AWS) have a worse prognostic. METHODS: We have performed a retrospective analysis of the hospital discharges in with diagnosis include AWS from 1 of January of 1997 to the 31 of December of 2002. RESULTS: We identified 924 hospital stays with 2.4% of mortality (1.6% in Internal Medicine). Mortality is associated with greater age (57 years +/-15 vs. 49+/- 13, p < 0.005), with the diagnostic of hepatic cirrhosis (6.2 vs. 1.8%, p < 0.005), bacteraemia (10 vs. 1.8%, p < 0.001) and respiratory infection (9.6 vs. 1.8%, p < 0,001), with a lower mortality when AWS was secondary diagnosis (1.2 vs. 4.2%, p < 0.005). In multivariant analysis were associated with more mortality age (OR 1.03), hepatic cirrhosis (OR 3.4), bacteriemia (OR 4.5) and respiratory infection (OR 3.6). CONCLUSION: Alcohol withdrawal syndrome mortality could to benefit from treatment in an Internal Medicine Service.

Epidemiología del síndrome de abstinencia alcohólica. Mortalidad y factores de mal pronóstico / Epidemiology of alcohol withdrawal syndrome. Mortality factors of poor prognostic

Introducción: El alcoholismo y la aparición del síndrome de abstinencia alcohólica (SAA) condicionan un peor pronóstico en los pacientes que lo presentan. Métodos: Se recogieron las características epidemiológicas, evolución y mortalidad de todos los casos diagnosticados de SAA en el Complexo Hospitalario de Santiago durante los años 1997 al 2002. Resultados: Se identificaron 924 casos con una mortalidad del 2,4% (1,6% en Medicina Interna). La mortalidad se asoció con mayor edad (57 años ± 15 vs. 49± 13, p < 0,005), y con los diagnósticos de cirrosis hepática (6,2 vs. 1,8%, p < 0,005), bacteriemia (10 vs. 1,8%, p < 0,001) e infección respiratoria (9,6 vs. 1,8%, p < 0,001), con una mortalidad menor cuando el SAA fue diagnóstico secundario (1,2 vs. 4,2%, p < 0,005). En el análisis multivariante se asociaron a mayor mortalidad la edad (OR 1,03), la cirrosis hepática (OR 3,4), la bacteriemia (OR 4,5) y la infección respiratoria (OR 3,6). Conclusión: La mortalidad asociada al síndrome de abstinencia podría beneficiarse de la centralización del tratamiento en el Servicio de Medicina Interna

Introduction: Patients with alcoholism and alcohol withdrawal syndrome (AWS) have a worse prognostic. Methods: We have performed a retrospective analysis of the hospital discharges in with diagnosis include AWS from 1 of January of 1997 to the 31 of December of 2002. Results: We identified 924 hospital stays with 2.4% of mortality (1.6% in Internal Medicine). Mortality is associated with greater age (57 years ±15 vs. 49± 13, p < 0.005), with the diagnostic of hepatic cirrhosis (6.2 vs. 1.8%, p < 0.005), bacteraemia (10 vs. 1.8%, p < 0.001) and respiratory infection (9.6 vs. 1.8%, p < 0,001), with a lower mortality when AWS was secondary diagnosis (1.2 vs. 4.2%, p < 0.005). In multivariant analysis were associated with more mortality age (OR 1.03), hepatic cirrhosis (OR 3.4), bacteriemia (OR 4.5) and respiratory infection (OR 3.6). Conclusion: Alcohol withdrawal syndrome mortality could to benefit from treatment in an Internal Medicine Service

Enfermedad celiaca del adulto / Adult coeliac disease

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Circadian variability of blood pressure in liver transplant recipients without antihypertensive therapy.

Hypertension is a frequent cardiovascular risk factor in liver transplant recipients. The usefulness of ambulatory blood pressure monitoring (ABPM) in these patients is unknown. This study was aimed at evaluating the circadian rhythms of blood pressure in liver allograft recipients. In 53 liver transplant patients blood pressure was measured with the Spacelabs device program. No patient received antihypertensive therapy for at least 15 days beforehand. Clinical blood pressure measurement showed 26 patients to be hypertensive. Of these, ABPM verified the diagnosis in 23. Overall, 72% of the patients were hypertensive, and 39.5% showed a nondipper pattern. Diastolic hypertension was more frequent than systolic hypertension. No differences were found in renal function, immunosuppressive therapy, or corticosteroids.

[De novo hepatitis B with anti-HBc negative in a liver transplant recipient [corrected]]. / Hepatitis B de novo con anticuerpo frente al HBcAg negativo en un trasplantado hepático.

De novo hepatitis B was diagnosed in a 47-year-old man 15 months after liver transplantation for end-stage alcoholic cirrhosis. Serum antibodies to hepatitis B core antigen (anti-HBc) were negative, and remained undetectable over 20 months of follow-up. The possible causes of negative serum anti-HBc despite of active hepatitis B virus infection are reviewed. Immunosuppression may underlie this phenomenon in similar cases.

[Late-onset Wilsons disease]. / Enfermedad de Wilson de manifestación tardía.

A 58-year old male with a past history of psychiatric disorders was studied for a persistent serum transaminase increase. Low serum ceruloplasmin level (lower than 3 mg/dL), increased urinary copper excretion, and increased liver tissue copper concentration (1050 mcg/g dry weight) confirmed the diagnosis of Wilsons disease. Slit lamp examination did not show Kayser-Fleischer rings. D-penicilamin therapy was followed by serum transaminase normalization. Similar late-onset cases of Wilsons disease are exceptional, but confirm the clinical heterogeneity of the disease.

Enfermedad de Wilson de manifestación tardía / Late-onset Wilson's disease

Un varón de 58 años con antecedente de trastornos psiquiátricos fue estudiado por elevación persistente de transaminasas. Se estableció el diagnóstico de enfermedad de Wilson en base a una ceruloplasmina sérica baja (menor de 3 mg/dL), una excreción urinaria de cobre aumentada y una concentración hepática de cobre aumentada (1050 mcg por gramo de tejido seco). No se observó anillo de Kayser-Fleischer en el estudio con lámpara de hendidura. Fue tratado con D-penicilamina, con normalización progresiva de las transaminasas. Los casos similares de enfermedad de Wilson de manifestación tardía son excepcionales, pero confirman la heterogeneidad clínica de la enfermedad. (AU)

[Complications and yield of percutaneous liver biopsy with ultrasonographic marking]. / Complicaciones y rendimiento de la biopsia hepática percutánea con marcado ecográfico.

OBJECTIVES: To describe the complications and the diagnostic yield of percutaneous liver biopsies performed under ultrasonographic control in an Internal Medicine department. PATIENTS AND METHODS: A total of 750 percutaneous liver biopsies were performed at the Internal Medicine department of our institution during the 1995-2001 time period. The Menghini technique was employed previous ultrasonographic marking of the puncture site was performed by the same physicians who performed the biopsy. Major and minor complications as well as the diagnostic yield (obtention of diagnostic hepatic tissue) of the technique were recorded. RESULTS: No deaths occurred in our series. Two patients (0.3%) had major complications presenting as liver subcapsular hematoma with hemoperitoneum which resolved with conservative measures. One of them was a male patient with acute leukemia and the other was a woman on antiaggregant therapy. Eight patients (1.1%) had minor complications (vasovagal syncope), all of them young males. In three cases no adequate material for diagnosis was obtained (technique yield 99.6%). CONCLUSIONS: In our series, percutaneous liver biopsy with ultrasonographic marking is a diagnostic technique associated with a low rate of severe complications and with a high diagnostic yield. The use of ultrasonographic marking by the same physicians performed the biopsy does not involve a longer time or increased cost of the technique, provides more safety in the procedure and has a low morbidity rate. This procedure could be used on a routine basis for all percutaneous liver biopsies.