Shorter hepatitis B immunoglobulin administration is not associated to hepatitis B virus recurrence when receiving combined prophylaxis after liver transplantation.

BACKGROUND & AIMS: The combination of hepatitis B immunoglobulin and a nucleos(t)ide analogues has markedly reduced the rate of hepatitis B virus recurrence after liver transplantation; however, the optimal duration of hepatitis B immunoglobulin has not been clarified. This lack of consensus perpetuates the use of different strategies. The aim of this study was to evaluate the risk factors associated to hepatitis B virus recurrence after liver transplantation in a large cohort of patients under different hepatitis B immunoglobulin regimens. METHODS: Retrospective multicentre analysis of hepatitis B virus-related liver transplantation recipients receiving combined prophylaxis (hepatitis B immunoglobulin + nucleos(t)ide analogues). The strategy of short-term hepatitis B immunoglobulin was compared to lifelong administration. Hepatitis B virus recurrence was defined as positive HBsAg after liver transplantation. RESULTS: Three hundred and thirty-eight patients were analysed. After a median follow-up period of 72 months, 37 patients (11%) developed hepatitis B virus recurrence. Hepatocellular carcinoma recurrence and lamivudine resistance after liver transplantation were the only factors independently associated to hepatitis B virus recurrence (HR 5.4 [2.3-12] and 9.3 [4.2-20] respectively P < .001). HBsAg reappearance after hepatitis B virus recurrence was transient (16 patients), persistent (15) or alternant (6). The hepatitis B immunoglobulin regimen did not have an impact on the rate or evolution of hepatitis B virus recurrence. Overall, patient survival was good and not influenced by hepatitis B virus recurrence (82% at 5 years). Fulminant liver failure, hepatitis C coinfection or hepatocellular carcinoma at liver transplantation were independent risk factors for lower survival. CONCLUSIONS: Liver transplantation is an effective treatment for hepatitis B virus-related liver disease. Since the introduction of combined prophylaxis the rate of hepatitis B virus recurrence is very low. However, lifelong hepatitis B immunoglobulin administration does not seem necessary to reduce hepatitis B virus recurrence.

Exploring the influence of baseline rheumatoid factor levels on TNF inhibitor retention rate in patients with rheumatoid arthritis: a multicentre and retrospective study.

OBJECTIVE: To assess whether the retention rate of certolizumab pegol (CZP) was longer than that of other tumour necrosis factor inhibitors (TNFi) based on baseline rheumatoid factor (RF) levels. METHODS: Longitudinal, retrospective and multicentre study including patients with RA who were treated with any TNFi (monoclonal antibodies (mAB), etanercept (ETA) or CZP). Log-rank test and Cox regressions were conducted to evaluate the retention rate in the three groups according to the level of RF, with the third quartile of the baseline levels used as cut-off: <200 (

Hyponatremia in patients treated with terlipressin for severe gastrointestinal bleeding due to portal hypertension.

UNLABELLED: Terlipressin is frequently used in acute variceal bleeding due to its powerful effect on vasopressin V1 receptors. Although terlipressin is also a partial agonist of renal vasopressin V2 receptors, its effects on serum sodium concentration have not been specifically investigated. To examine the effects of terlipressin on serum sodium concentration in patients with acute portal-hypertensive bleeding, 58 consecutive patients with severe portal-hypertensive bleeding treated with terlipressin were investigated. In the whole population, serum sodium decreased from 134.9 ± 6.6 mEq/L to 130.5 ± 7.7 mEq/L (P = 0.002). Thirty-nine patients (67%) had a decrease in serum sodium ≥ 5 mEq/L during treatment: in 18 patients (31%), between 5 and 10 mEq/L and in 21 patients (36%), greater than 10 mEq/L. In this latter group, serum sodium decreased from 137.2 ± 5 to 120.5 ± 5 mEq/L (P < 0.001). In multivariate analysis, the reduction in serum sodium was related to baseline serum sodium and Model for End-Stage Liver Disease (MELD) score; patients with low MELD and normal or near-normal baseline serum sodium had the highest risk of hyponatremia. Serum sodium returned to baseline values in most patients shortly after cessation of therapy. Three of the 21 patients with marked reduction in serum sodium developed neurological manifestations, including osmotic demyelination syndrome in one patient due to a rapid recovery of serum sodium (serum sodium in these three patients decreased from 135, 130, and 136 to 117, 114, and 109 mEq/L, respectively). CONCLUSION: An acute reduction in serum sodium concentration is common during treatment with terlipressin for severe portal-hypertensive bleeding. It develops rapidly after start of therapy, may be severe in some patients and is associated with neurological complications, and is usually reversible after terlipressin withdrawal.

Paracetamol in therapeutic dosages and acute liver injury: causality assessment in a prospective case series.

BACKGROUND: Acute liver injury (ALI) induced by paracetamol overdose is a well known cause of emergency hospital admission and death. However, there is debate regarding the risk of ALI after therapeutic dosages of the drug.The aim is to describe the characteristics of patients admitted to hospital with jaundice who had previous exposure to therapeutic doses of paracetamol. An assessment of the causality role of paracetamol was performed in each case. METHODS: Based on the evaluation of prospectively gathered cases of ALI with detailed clinical information, thirty-two cases of ALI in non-alcoholic patients exposed to therapeutic doses of paracetamol were identified. Two authors assessed all drug exposures by using the CIOMS/RUCAM scale. Each case was classified into one of five categories based on the causality score for paracetamol. RESULTS: In four cases the role of paracetamol was judged to be unrelated, in two unlikely, and these were excluded from evaluation. In seven of the remaining 26 cases, the RUCAM score associated with paracetamol was higher than that associated with other concomitant medications. The estimated incidence of ALI related to the use of paracetamol in therapeutic dosages was 0.4 per million inhabitants older than 15 years of age and per year (99%CI, 0.2-0.8) and of 10 per million paracetamol users-year (95% CI 4.3-19.4). CONCLUSIONS: Our results indicate that paracetamol in therapeutic dosages may be considered in the causality assessment in non-alcoholic patients with liver injury, even if the estimated incidence of ALI related to paracetamol appears to be low.

[Intrasinus renal hilium approach, EUREKA time for spanish urological surgical anatomy.] / Vía intrasinusal de abordaje al hilio renal, un momento E U R E K A de la investigación anatómica quirúrgica urológica española.

Historical research has allowed us to reviewand document the author of the first description of the intrasinusal route for access to the renal hilum as astrategy for accessing kidney stones through the bibliography. This new route described and published by M. Serés represented a paradigm shift in open surgery for kidney stones. We want to highlight that the Spanish urological anatomical-surgical investigation with the investigations of Manuel Serés, meant a singular contribution and of enormous importance for the History of International Urology, whose value we must claim with its indisputable and reliable references.

La investigación histórica nos ha permitido revisar y mostrar documentalmente por la bibliografía el autor de la primera descripción de la via intrasinusal para el acceso al hilio renal como estrategia de accesoa la litiasis renal. Esta nueva via descrita y publicada por M. Serés supuso un cambio de paradigma en la cirugía abierta de la litiasis renal. Queremos resaltar que la investigación anatomo-quirúrgica urológica española con las investigaciones de Manuel Serés, significó una aportación singular y de enorme trascendencia para la Historia de la Urología Internacional, cuyo valor debemos reivindicar con sus referencias indiscutibles y fehacientes.

Treatment of resistant pruritus from cholestasis with albumin dialysis: combined analysis of patients from three centers.

BACKGROUND & AIMS: Albumin dialysis using molecular adsorbent recirculating system (MARS) is a new procedure for treating resistant pruritus from cholestasis, but it is usually published as a case report or a short series. Therefore, we analyzed patients with resistant pruritus treated with MARS from three centers, to assess the changes on pruritus and the indices of cholestasis. METHODS: Twenty patients (12 female, mean age: 51+/-3.4 years) with chronic cholestatic liver disease or chronic liver-graft rejection were evaluated. The severity of pruritus was assessed using a visual analogue scale (VAS) before and after treatment, and 30 days thereafter. Liver tests, including total bilirubin, alkaline phosphatase, gamma-glutamyl-transferase, cholesterol, triglycerides, and total bile acid were also determined, as well as the number of sessions and the coupled procedure (dialysis or perfusion). RESULTS: Albumin dialysis resulted in a decrease of pruritus (VAS: from 70.2+/-4.8 to 20.1+/-4.2, p<0.001), which partially resumed after 30 days (38.7+/-6.6). VAS decreased by 72% immediately after treatment and by 51% after 1 month. Pruritus decreased in all but one patient. MARS resulted in a significant bile acid decrease of 41% after treatment and by 37% after 1 month. The effect of MARS on pruritus and markers of cholestasis was similar in patients with different diseases and was independent of the coupled procedure. The improvement of pruritus in individuals was positive in 75% of patients. No major adverse effects were observed. CONCLUSIONS: Albumin dialysis using MARS is an effective procedure for managing resistant pruritus in most patients with chronic cholestasis and graft rejection.

[The volume of urological knowledge in the last 25 years.] / El "volumen" del saber urológico en el último cuarto de siglo.

Few specialties have gone through as many transitions in the last decades as Urology. Progressive physiology advances in several disease have become part of the urological knowledge. Laparoscopic surgery and ESWL (Extracorporeal Shock Wave Lithotripsy) wave have completely turn upside down the whole management of disease. The current text provides a back to the future sigh into Urology.

Pocas especialidades médicas y quirúrgicas han experimentado en las últimas décadas tantos y tan significativos avances terapéuticos como la Urología. Además de progresos en los conocimientos fisiopatológicos de las distintas enfermedades que conforman el corpus del saber Urológico. La cirugía laparoscópica y las ondas de choque extracorpóreas han revolucionado la especialidad en su totalidad, provocando cambios de paradigma tanto en las indicaciones terapéuticas como en la interpretación de algunos procesos patológicos. Aportamos unas reflexiones desde una mirada retrospectiva.

Albumin dialysis improves hepatic encephalopathy and decreases circulating phenolic aromatic amino acids in patients with alcoholic hepatitis and severe liver failure.

INTRODUCTION: The aim of this study was to assess the effects of albumin dialysis on hepatic encephalopathy and circulating levels of amino acids in severe alcoholic hepatitis. METHODS: The study was carried out in nine patients with severe alcoholic hepatitis and four with primary biliary cirrhosis treated with the molecular adsorbent recirculating system. Besides standard liver function tests, circulating levels of ammonia, total, branched chain and aromatic amino acids, the presence and severity of hepatic encephalopathy, and number connection test were measured before and after each treatment. RESULTS: There were eight episodes of encephalopathy in patients with alcoholic hepatitis. Albumin dialysis was associated with significant improvement in encephalopathy (p = 0.02), and a decrease in total amino acid levels (2490 +/- 152 microM to 2229 +/- 114 microM, p < 0.001). Moreover, the Fischer's ratio, which was significantly lower in patients with alcoholic hepatitis (1.32 +/- 0.08) than in controls (3.20 +/- 0.16), increased by 17% after albumin dialysis (p < 0.02) because of a significant decrease in phenolic aromatic amino acids (193 +/- 17 microM to 165 +/- 9 microM, p = 0.04). No differences were observed in circulating ammonia. Changes in phenolic aromatic amino acids and the Fischer's ratio were more prominent in patients with encephalopathy and higher bilirubin removal. Albumin dialysis did not significantly affect the amino acid profile in the controls. CONCLUSIONS: Albumin dialysis results in a significant decrease in circulating phenolic aromatic amino acids and improvement of hepatic encephalopathy in patients with severe liver failure.

Adherence to Lamivudine after an early withdrawal of hepatitis B immune globulin plays an important role in the long-term prevention of hepatitis B virus recurrence.

Lamivudine combined with hepatitis B immune globulin (HBIg) is the standard of care for preventing the recurrence hepatitis B virus after liver transplant. To determine the risk of hepatitis B virus (HBV) recurrence after early withdrawal of HBIg in patients receiving lamivudine maintenance therapy, 20 patients receiving a course of HBIg and lamivudine after transplantation and long-term maintenance therapy with lamivudine and 9 patients receiving HBIg and lamivudine indefinitely were analyzed. The survival rate was 90% after a mean follow-up of 83 months. The HBV recurrence rate was 14% with a mean period of 91 months free from HBV recurrence. Both groups had similar HBV recurrence rates, 15% for the combination and 11% for lamivudine alone. Four patients, 3 of whom were noncompliant with therapy, experienced posttransplant HBV recurrence. Patients who adhere to long-term prophylaxis with lamivudine after early withdrawal of HBIg have a low risk of HBV recurrence, similar to those who receive combination prophylaxis.

Hyperlactatemia in patients with non-acetaminophen-related acute liver failure.

AIM: To characterize hyperlactatemia in patients with non-acetaminophen acute liver failure (ALF) in an attempt to clarify the mechanisms implicated and the role as a prognosis factor. METHODS: In the setting of liver transplantation, 63 consecutive patients with non-acetaminophen acute liver failure were studied in relation to tissue oxygenation, hemodynamic and metabolic parameters. Before and after transplantation, the number of infected patients and outcome were registered. RESULTS: Acute ALF showed higher levels of lactate than subacute ALF (5.4+/- 1 mmol/L versus 2.2+/- 0.6 mmol/L, P=0.01). Oxygenation parameters were within the normal range. Lactate levels showed good correlation with respiratory quotient (r=0.759, P< 0.005), mean glucose administration (r=0.664, P=0.01) and encephalopathy (r=0.698, P=0.02), but not with splanchnic arteriovenous difference in PCO2, pH and the presence of infection (P=0.1). Portal vein lactate was higher (P< 0.05) than arterial and mixed venous lactate, suggesting its production of hyperlactatemia in the intestine and spleen. The presence of infection was an independent predictor of survival. CONCLUSION: Hyperlactatemia is not a prognosis factor due to byproduct of the overall acceleration in glycolysis.

Early Introduction of Subcutaneous Hepatitis B Immunoglobulin Following Liver Transplantation for Hepatitis B Virus Infection: A Prospective, Multicenter Study.

BACKGROUND: Subcutaneous administration of hepatitis B immunoglobulin (HBIg) is effective in preventing hepatitis B virus (HBV) recurrence after liver transplantation, but early conversion to subcutaneous administration is undocumented. METHODS: In a prospective study, patients transplanted for terminal liver disease due to HBV infection who were HBV DNA-negative at transplant were switched by week 3 posttransplantation from intravenous to subcutaneous HBIg (500 or 1000 IU weekly or fortnightly, adjusted according to serum anti-HBs trough level) if they were HBsAg- and HBV-DNA negative at time of switch. All patients concomitantly received nucleos(t)ide analogue antiviral therapy. Primary endpoint was failure rate by month 6, defined as serum anti-HBs of 100 IU/L or less or HBV reinfection despite serum anti-HBs greater than 100 IU/L. RESULTS: Of 49 patients treated, 47 (95.9%) continued treatment until month 6. All patients achieved administration by a caregiver or self-injection by week 14. No treatment failures occurred. Mean anti-HBs declined progressively to month 6, plateauing at a protective titer of approximately 290 IU/L. All patients tested for HBV DNA remained negative (45/45). Only 1 adverse event (mild injection site hematoma) was assessed as treatment-related. CONCLUSIONS: Introduction of subcutaneous HBIg administration by week 3 posttransplantation, combined with HBV virostatic prophylaxis, is effective and convenient for preventing HBV recurrence.

Insertion (8;11) in a renal oncocytoma with multifocal transformation to chromophobe renal cell carcinoma.

We report the case of a 43-year-old male with multiple tumor foci showing microscopic features of chromophobe renal carcinoma (ChRCC) arising in an oncocytoma. Conventional cytogenetics of fresh tumor cells and fluorescence in situ hybridization (FISH) revealed the following abnormal karyotype: 46,XY,der(8)ins(8;11)(p?;q13),der(11)ins(8;11)inv(11)(q12?p15) with CCND1 (11q13) rearrangement. To our knowledge, chromosome 8 has not been reported as a partner involved in structural rearrangements of 11q13 in oncocytomas. FISH in paraffin tissue sections revealed a rearrangement of CCND1 (11q13) in the oncocytoma cells. The multiple foci of chromophobe carcinoma presented multiple copies of CCND1, suggesting that they represented a transformation from oncocytoma into ChRCC. There was immunohistochemical overexpression of CCND1 in both oncocytoma and chromophobe carcinoma cells. In this case, the correlation of the microscopic findings with changes in CCND1 gene associated to CCND1 overexpression in both components suggest that the ChRCC would have originated from the preexisting oncocytoma. It is not possible to detect, by cytogenetic techniques alone, if the ChRCC component have also the CCND1 rearrangement in addition to the detected polysomy. FISH techniques on paraffin tissue sections may help to identify genetic aberrations such as CCND1 rearrangement in order to establish a diagnosis of oncocytoma.

Entecavir has high efficacy and safety in white patients with chronic hepatitis B and comorbidities.

OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of entecavir monotherapy in nucleos(t)ide-naive chronic hepatitis B patients and to analyse the influence of the comorbidity burden on therapy outcome. METHODS: We retrospectively analysed data from 237 nucleos(t)ide-naive chronic hepatitis B white patients treated with entecavir (0.5 mg/day) at 23 Spanish centres. For the efficacy and safety analyses, patients were grouped according to their baseline comorbidities. RESULTS: The mean age of the cohort was 43 years (range: 19-82 years); 73% were male, 83% were white, and 33% were hepatitis B e antigen (HBeAg) positive. At baseline, the median hepatitis B virus DNA level was 6.20 log10 IU/ml. Of the patients, 18% had cirrhosis, 9.7% had diabetes, 16.3% had hypertension, and 15.7% had obesity; 13.4% of patients had more than one comorbid condition. Virological and biochemical responses at month 36 were obtained independently of the patients' baseline comorbid condition. Of 10 HBeAg-positive patients who discontinued treatment after HBeAg seroconversion, those who had not also cleared HBsAg (six) experienced virological recurrence in a median 5.6 months. There were no treatment discontinuations due to adverse events. Three patients were diagnosed with hepatocellular carcinoma at months 12, 30 and 54, and six experienced hepatic decompensation during follow-up. The median serum creatinine levels did not increase after 36 months of treatment, even in patients with comorbidities. CONCLUSION: Entecavir is safe, well tolerated, and highly effective, even in patients with comorbid condition(s). Discontinuation of treatment in patients who have not been cleared of HBsAg may lead to virological recurrence.

Use of primary human liver cells originating from discarded grafts in a bioreactor for liver support therapy and the prospects of culturing adult liver stem cells in bioreactors: a morphologic study.

INTRODUCTION: The development of a bioreactor providing a three-dimensional network of interwoven capillary membranes with integrated oxygenation and decentralized mass exchange enables the culture of primary human liver cells from discarded donor organs for extracorporeal liver support. METHODS: Primary liver cells were isolated from 54 discarded organs (donor age 56.7+/-13.2 years). Between 2.8x10(10) and 6.4x10(10) parenchymal cells (PC) were cocultured with nonparenchymal cells (NPC) of the same organ in bioreactors (n=36). The metabolic activity of the cells was regularly determined during culture. The cell morphology and ultrastructure were investigated after culture periods of 1 to 5 weeks. RESULTS: Cell metabolism was maintained over at least 3 weeks after a phase of adaptation lasting 2 to 3 days. Through the use of transmission electron microscopy and immunohistochemistry, it was demonstrated that PC and NPC spontaneously formed tissue-like structures. Vascular cavities (CD 31 immunoreactivity [IR]) and bile duct-like channels (CK 19 IR), both exhibiting proliferation activity (Ki-67 IR), were regularly distributed. Some of the bile duct-like channels showed similarities to the Canals of Hering found in the natural liver. Cells expressing morphologic and antigenic characteristics of adult liver stem cells (CD 34 IR and c-kit IR) and areas with cells that showed both hepatocyte and biliary characteristics were detected. CONCLUSION: The results show that primary human liver cells obtained from discarded donor organs recover and can be maintained in bioreactors for clinical liver support therapy. In addition, initial observations on adult liver stem-cell culture in bioreactors are presented.