Adefovir en el tratamiento de la infección por virus B / Adefovir therapy in hepatitis B virus infection

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Variability of MELD score during the year before liver transplantation.

Model for end-stage liver disease (MELD) score is a good parameter to establish the patient survival before liver transplantation and give priority to the sickest patients. The aim of this study was to evaluate the variability and potential regression of MELD score during the months before liver transplant. From the 350 patients waitlisted for transplantation, we evaluated the 124 patients who had enough blood tests during 12 months before the final event (transplantation, death, removal from list due to improvement or worsening). We considered month 12 as the final event and blood tests from 0, 3, 6, and 12 months were analyzed. MELD score was calculated and compared using ANOVA for repeated measures test. To determine variability of MELD and its components, intraclass correlation coefficient (ICC) was calculated for 0, 3, and 6 months. The degree of constancy was defined by proximity of ICC to 1. Two groups by initial MELD (< or =17 or >17) were considered. Patient data are: mean age, 53 +/- 9 years; sex: 70% men, etiology, 28% hepatitis C, 11% alcohol and hepatitis C, 16% alcohol, 28% hepatocellular carcinoma, 6% hepatitis B, 11% others; Initial Child-score, 8.5 +/- 2.0; Initial MELD score, 15.2 +/- 4.9; mean time on waiting list, 8.1 +/- 5.7 months. MELD score from 6 and 12 months was significantly higher than the initial one. The most constant parameter was creatinine (ICC:0.89); bilirubin (ICC:0.58) and INR (ICC:0.59) were the most variable ones. MELD score ICC was 0.79. In only one patient did MELD score decrease 5 points below the initial one. For initial MELD < or = 17 and >17, variability was lower in the former. In conclusion, MELD became significantly higher 6 months after the basal determination. This score is reliable as it does not tend to decrease in time. In high MELD scores (>17), 3-month survival was lower and variability greater so that more careful follow-up and prioritizing are needed.

[Intestinal transplantation in adults: present situation and future prospects]. / Trasplante intestinal del adulto. Situación actual y perspectivas de futuro.

Intestinal transplantation is becoming more firmly established as a treatment for intestinal failure in patients whose home parenteral nutrition regimens have caused serious side effects. Outcomes have improved spectacularly over recent years thanks to the refinement of surgical techniques and the introduction of new immunosuppressants, and also to greater experience in anesthetic and postoperative management of intestinal transplant patients. The main causes of high morbidity and mortality continue to be sepsis and acute rejection of the graft. Both graft and patient survival have improved with the advent of the immunosuppressant regimens based on Tacrolimus, although survival rates are still far below those reported for other solid organ transplants. The first intestinal transplant performed in Spain took place in July 2002 in our hospital and the results were promising. Given this new challenge for anesthesiologists, we decided to review current trends in the perioperative management of patients receiving isolated intestinal transplants, the main complications that arise, treatment strategies, and future prospects.

Trasplante intestinal del adulto. Situación actual y perspectivas de futuro / Intestinal transplantation in adults: present situation and future prospects

El trasplante de intestino se está consolidando como tratamiento del fallo intestinal para aquellos pacientes en régimen de nutrición parenteral domiciliaria que desarrollan efectos colaterales severos. A lo largo de los últimos años los resultados han mejorado espectacularmente gracias al refinamiento de las técnicas quirúrgicas y a la aparición de nuevos fármacos inmunosupresores, así como a una mayor experiencia en el manejo anestésico y postoperatorio de estos pacientes. Los principales responsables de la alta morbilidad y mortalidad siguen siendo la sepsis y el rechazo agudo. La introducción del tacrolimus como inmunosupresor de base ha permitido mejorar las tasas de supervivencia del injerto y del paciente, todavía lejos de los resultados en el trasplante de otros órganos sólidos. En julio de 2002 se realizó en nuestro hospital el primer trasplante de intestino aislado en un adulto en España con resultados esperanzadores. Ante este nuevo reto para nuestra especialidad hemos querido revisar las tendencias actuales en el manejo perioperatorio de estos pacientes, sus complicaciones más importantes, el tratamiento y las nuevas perspectivas de futuro (AU)

Analysis of hepatitis C viral quasispecies in liver transplantation.

The hepatitis C virus (HCV) is an RNA virus that replicates with a high rate of mutation, especially in the hypervariable region 1 (HVR-1). Continuous viral mutations lead to a mixed and changing populations of mutants, called quasispecies. The nature of the HCV quasispecies may have implications for viral persistence and pathogenies. Studies with liver transplant patients suggest a relationship between the degree of immunosuppression and the complexity of the quasispecies. This study evaluated whether immunosuppressive therapy modifies the evolution of HCV quasispecies among liver transplant recipients compared with immunocompetent HCV patients. Two groups were studied: 11 patients who underwent OLT for HCV-related cirrhosis and 10 control group patients. Two serum samples from each patient were obtained to analyze the HCV HVR1 region by RT-PCR. SSCP analysis failed to show statistically significant differences in the number of quasispecies at basal and final time points or at pretransplant versus posttransplant (7.3+/-2 vs 6.7+/-3 in control patients, respectively, and 4.4+/-2 vs 4.1+/-1 in transplanted patients, respectively). No significant difference was observed between missing or new variants in the control (2.8+/-2 vs 2.3+/-2, respectively) or transplanted group (2.5+/-2 vs 2.2+/-1, respectively). Upon sequence analysis, the genetic complexity was significantly lower among samples after OLT in transplanted patients (0.057+/-0.04 [pretransplant] vs 0.035+/-0.02 [posttransplant]; P=.048). However, no significant differences were found among control patients in basal versus final samples (0.04+/-0.03 vs 0.066+/-0.04, respectively). Our findings seem to demonstrate that viral quasispecies diversity is lower among patients receiving a liver transplant.

Use of adefovir in the treatment of the chronic hepatitis B virus infection with resistance to lamivudine.

Current therapies for the treatment of chronic hepatitis B virus (HBV) infection do not eliminate viral replication once therapy is stopped, resulting in a rapid rebound of viremia in a majority of patients. Prolonged therapy results in emergence of resistant virus, which is a major clinical concern. The appearance of resistant HBV is associated with decreased seroconversion rates as well as worse liver histology. Adefovir dipivoxil, a nucleotide analogue with potent antiviral activity against HBV and human immunodeficiency virus (HIV), has shown in vivo and in vitro to have activity against lamivudine-resistant HBV. We present a series of 6 patients with chronic HBV infection and lamivudine-resistant HBV treated with adefovir dipivoxil. The viremia decreased in all patients; in 4 of them, serum HBV DNA was negative by chain reaction (PCR) in a mean period of 10 months from beginning of treatment. Resistance to adefovir after 12 months of treatment has not been detected. Alanine aminotransferase (ALT) levels decreased in all patients and, at this moment, 5 of 6 patients present normal levels. There were no toxic side effects due to adefovir treatment. The data confirm that adefovir treatment has efficacy against HBV lamivudine-resistant forms.

Use of combined treatment of hepatitis B immune globulin and lamivudine as prevention of hepatitis B virus recurrence in liver allograft.

Antiviral prophylaxis with lamivudine appears to reduce hepatitis B virus (HBV) infection after liver transplantation, although recurrence of infection occurs in at least 20% of the patients because of the development of drug resistance. Treatment for HBV reinfection with lamivudine pretransplantation and posttransplantation together with hepatitis B immunoglobulin could abolish recurrence of HBV infections following liver transplantation. We report the experience at our center in which lamivudine has been used in combination with low doses of immunoglobulin. Lamivudine (100 mg/d) was administered to liver transplant candidates for at least 4 weeks before transplantation and was continued posttransplantation indefinitely. Immunoglobulin was administered intramuscularly (10,000 IU at time of liver transplantation; 1,000 IU for 1 week; 1,000 IU weekly the first month; and 1,000 IU monthly thereafter). Lamivudine and low-dose immunoglobulin administration prevents posttransplantation recurrence of hepatitis B with 100% efficiency; it is well tolerated and is less cost-effective than high-dose immunoglobulin regimens.

Prophylaxis of recurrent hepatitis B virus by vaccination after liver transplant: preliminary results.

Liver transplantation for chronic HBV-induced cirrhosis is associated with a high rate of recurrence and poor long-term survival. Prolonged and combined prophylaxis with hepatitis B immunoglobulin (HBIg) and lamivudine has been demonstrated to prevent HBV recurrence, but its lifelong administration is highly expensive. An alternative strategy may be the use of an HBV vaccine after liver transplantation. Herein we report the results of administration of a reinforced recombinant HBV vaccine to liver transplant recipients. Twelve patients transplanted for HBV-related liver disease and treated with HBIg for at least 24 months were administered HBV vaccine (40 microg administered intramuscularly and repeated 1 and 2 months thereafter) 2 months after beginning the last HBIg dose. The response rate to HBV vaccination was 75% (9/12 patients). Serum titers of anti-HBs were considered to be protective when they reached levels >10 IU/L. Responding patients were followed for a median of 43+/-22.5 months; during this period none of the responders showed evidence of HBV recurrence. These results suggest that vaccine administration after liver transplant may avoid HBV recurrence allowing HBIg withdrawal. However, future studies are necessary to define an optimal schedule.

Fibrin-glue sealed liver biopsy in patients with a liver transplantation or in liver transplantation waiting list: preliminary results.

Liver biopsy is frequently necessary for candidate evaluation or histologic follow-up of transplanted livers. Although generally considered to be safe, it carries a risk of complications in up to 0.5% of cases; hemorrhage being the most important. It can present as an asymptomatic intra- or perihepatic hematoma or result in overt hemorrhage of variable intensity. Patients with deranged hemostasis or on antiaggregant therapy are at high-risk for hemorrhagic complications. Percutaneous liver biopsy may be contraindicated if hemostasis is profoundly disordered. Safety values are not well defined: arbitrary limits are 60% prothrombin activity and 60,000 platelets per mm3. Patients with more altered values are candidates for alternative techniques, such as transjugular biopsy. Another option is the so-called plugged percutaneous liver biopsy, which uses direct injection of a plugging material into the biopsy tract. Different materials have been used: Tissucol, absorbable gelatin sponge, or hemostasis coils. We communicate our experience with Tissucol (fibrin glue) plugging in 30 percutaneous liver biopsies on 16 patients after liver transplantation with prothrombin activity <60%, platelet count <60,000 per mm3, or both. Only two complications were observed. Plugged liver biopsy is an efficient and relatively safe procedure in patients with impaired hemostasis; it can be performed even when transjugular biopsy is not available.

Prevention of de novo hepatitis B infection in liver allograft recipients with previous hepatitis B infection or hepatitis B vaccination.

OBJECTIVES: To assess de novo hepatitis B virus (HBV) transmission from liver donors with HBV serum markers (HBM) to their recipients and the need for HBV vaccination before liver transplantation. METHODS: A total of 108 orthotopic liver transplantations for nonviral disease and the risk of developing de novo hepatitis B based on HBMs before transplantation have been studied. Of the 108 patients, 94 met the study criteria and were divided into two groups: 27 who had HBMs before transplantation (from past infection or by previous vaccination) and 67 who had no HBM. Development of de novo hepatitis B was determined by analytical, serological, and histological parameters. RESULTS: No case (0%) of de novo hepatitis B was detected in the pretransplantation HBM group, whereas there were 10 cases (14.5%) in the other group (p < 0.005). CONCLUSIONS: The presence of pretransplantation HBM in liver transplant recipients protects these patients against the development of de novo hepatitis B. This is especially important considering that there is a high prevalence of donors with positive hepatitis B core antibody (especially in some countries), and that these donors transmit HBV infection to recipients without HBM in a significant number of cases. Thus, vaccination against HBV in patients who are candidates for liver transplantation is fundamental to avoid cases of de novo hepatitis B.

[Risk of hepatitis B virus transmission from hepatitis B core antibody-positive liver donors]. / Riesgo de transmisión del virus de la hepatitis B de donantes de hígado anti-HBc positivos.

BACKGROUND: To study the hepatitis B virus (HBV) transmission from donors HBsAg-/AntiHBc+ to liver transplant recipients. PATIENTS AND METHOD: We studied retrospectively the HBV serological markers in 43 donors from our center and also the serological condition of the 41 recipients. The HBV serological markers were analyzed by ELISA and HBV DNA was detected by hybridation assays. RESULTS: 13 donors samples showed some HBV serological markers: 6 anti-HBc and anti- HBs (13.9%), 4 anti-HBc (9%) and 3 anti- HBs (6.9%). There were no cases of hepatitis B among liver recipients from donors with negative serological markers. Among the 13 recipients with HBV serological markers, 9 were followed during 39 (SD 17) months. The 5 recipients with no HBV markers, who received an anti- HBc+ with or without anti- HBs (100%) developed hepatitis B. The two liver recipients with anti-HBs solely, did not developed infection (0%). Of the 41 recipients, 15 had some HBV markers before transplant and two of them received an anti-HBc+ and did not develop the infection (0%). CONCLUSIONS: In our study, the prevalence of serological HBV infection in donors and recipients was of 30.2 and 31.7%, respectively. Anti-HBc with or without anti-HBs donors transmitted the HBV infection in all the cases (100%) to the susceptible recipients. The presence of anti-HBs in recipients protected these against the infection. Only the anti-HBs positive donors did not trasmit the HBV infection.

[Hereditary hemorrhagic telangiectasia with liver involvement]. / Telangiectasia hemorrágica hereditaria con afectación hepática.

Rendu-Osler-Weber syndrome, or hereditary hemorrhagic telangiectasia, is characterized by vascular alterations that tend to hemorrhage. We present a 56-year-old woman, with a diagnosis of chronic liver disease of unknown origin 15 years earlier, who came to our hospital as a liver transplantation candidate following hemorrhage due to esophageal varices. Rendu-Osler-Weber syndrome can affect the liver in several ways although vascular alterations can be distinguished from those produced in the liver parenchyma. The different types of vascular alterations in the liver may manifest as as telangiectasias, angiomas, aneurysms of the hepatic artery and fistulae between different vessels. This syndrome may also produce alterations in the liver parenchyma although the exact pathogenic mechanisms are unknown. There are three main forms of treatment: embolization of the branches of the hepatic artery, ligature of the hepatic artery and liver transplantation.

[Toxic cholestatic hepatitis due to phenytoin]. / Hepatitis tóxica colestásica por fenitoína.

We report the case of a 51-years-old female who was prophylactically treated with diphenylhydantoin after surgery of an intracranial aneurysm. Twenty-four days after beginning the treatment, a general syndrome appeared, in addition to a diffuse cutaneous exanthema. Four days later, a cholestatic syndrome, compatible with "toxic cholestatic acute hepatitis", was developed. The suppression of the drug, was followed by rapid clinical improvement and gradual normalization of transaminases values, although biochemical cholestasis persisted for months.

[Prevalence and significance of the C virus antibody in chronic hepatopathy not related to B virus in alcoholics]. / Prevalencia y significado del anticuerpo al virus C en hepatopatía crónica de alcohólicos no relacionada al virus B.

The presence of antibody to the hepatitis C virus was determined in 254 alcoholic patients with non-B chronic hepatitis and a titre of antinuclear antibodies of 1/40 or lower. Alcoholic hepatitis was present in 12 patients, steatohepatitis in 20, active chronic hepatitis in 22, cirrhosis in 181, and hepatocarcinoma in 19. Twenty patients had previously received blood transfusion alone or during surgery, 49 had undergone previous surgery without transfusion, a clinical episode of hepatitis could be traced in 14, 4 patients were drug addicts, 41 had received blood transfusion after the diagnosis was made, and 128 presented with alcoholism alone. Anti-hepatitis C antibody was found in 20 out of 2,000 blood donors (1%) in our hospital. Anti-hepatitis C antibody was found in 87 patients (34.2%) in our series, a figure unaltered by past medical history. Patients with anti-HC antibody had higher levels of AST, ALT, total proteins, gamma-globulin, and IgG. The incidence of active chronic hepatitis was higher among patients with anti-HC antibody, whereas the incidence of steatohepatitis was higher among patients without anti-HC. Regarding findings on liver biopsy, the incidence of anti-HC was significantly higher (p less than 0.001) among patients with active chronic hepatitis (72.7%) than in any other group; no significant differences were found between patients with cirrhosis (33.3%), hepatocarcinoma (31.5%), steatohepatitis (15%), or alcoholic hepatitis (16.7%). Among HBsAg-negative patients, the incidence of anti-HC was similar between those with (39.7%) and without other serum markers of HB (32.9%).(ABSTRACT TRUNCATED AT 250 WORDS)

[Prevalence of hepatitis C virus antibody in chronic HBsAg-negative non alcoholic hepatopathy]. / Prevalencia del anticuerpo al virus de hepatitis C en la hepatopatía crónica no alcohólica HBsAg negativa.

The presence of antibody to hepatitis C virus was determined in 316 HBsAg-negative patients with non-alcoholic chronic hepatitis who did not receive any blood transfusion once the diagnosis was made. A titre of antinuclear antibodies of 1/40 or lower was found in 18 patients. Persistent chronic hepatitis was present in 21 patients, active chronic hepatitis in 145, hepatic cirrhosis in 128, and hepatocarcinoma in 22 patients. One hundred and three patients had previously received blood transfusion, 76 had undergone previous surgery without transfusion, a clinical episode of hepatitis could be traced in 14, 13 patients were drug addicts (all of them HIV negative), 1 patient had received multiples injections, another had been treated with acupuncture, and 108 patients were free of any of the above. Anti-HCV was present in 76.6% of patients; a significantly higher proportion (87.4%) was found among patients who had received blood transfusion than in patients with previous surgery (72.4%) (p = 0.012), clinical hepatitis (57.1%), or without previous hepatic disease (70.3%) (p = 0.003). The incidence of anti-HCV was lower among cirrhotics (70.3%) than in patients with active chronic hepatitis (84.1%) (p = 0.006); in contrast, previous blood transfusion was significantly higher (p = 0.001) among the latter (40.7%) than in cirrhotics (21.9%). The incidence of anti-HCV was similar among patients with (78.6%) and without (75.8%) type B infection. Our results suggest that infection with virus C may account for a high proportion of non-alcoholic non-B chronic hepatitis.

[Solitary ulcer of the rectum]. / Ulcera solitaria del recto.

In our center solitary ulcer of the rectum has a low incidence. There has been only one case in more than 13,000 distal endoscopic studies performed in the last ten years. Its rarity, and its possible confusion with other pathologies of the distal colon motivated our interest in this disease. The clinical and diagnostic features and therapeutic attitude in solitary rectal ulcer are remarked.

[Intestinal angiodysplasia: a presentation of 7 cases and review of the literature]. / Angiodisplasia intestinal: presentación de siete casos y revisión de la literatura.

Seven cases of intestinal angiodysplasia that required surgery for hemostatic control are presented, with a review of their clinical, endoscopic, arteriographic and histologic features. The average age of presentation was 52.43 years, there was a predominance in women, and the principal clinical manifestation was recurrent rectal hemorrhage. The most common location was the cecum and ascendant colon. Arteriographic diagnosis was achieved in only two patients.