M García González

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

Abstract 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 μg 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.

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.

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.

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 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.

[A prospective study about the usefulness of ultrasonographic monitoring after invasive liver procedures--liver biopsy and fine-needle aspiration (FNA)].

Objective: to determine the need to perform ultrasound scans to all patients after liver biopsy or fine-needle aspiration (FNA) in order to detect complications with or without symptoms. Material and methods: after liver biopsy or FNA using a regular protocol the patient is observed for 24 hours at the hospital, and all patients undergo an abdominal sonography at that time even in the absence of evident complications. Results: 298 liver biopsies and 98 FNAs were performed. There were complications in 37 patients (9.34%): 36 (9.09%) were minor complications such as pain, vasovagal episodes, or small bleeding, and 1 (0.25%) was a major complication with severe hemorrhage. Only 1 out of all 396 procedures had a complication detected by ultrasounds (intrahepatic hematoma) while the patient was asymptomatic. Conclusions: the low incidence of complications occurring without symptoms, and their favorable course suggest that routine ultrasonography is not necessary after these techniques, and that it should be only performed when a complication is suspected.

HCV-positive lymphoma after sustained virological response with direct-acting antiviral agents: The game is not over after HCV eradication

We read with interest the study published by Schiavinato A. et al entitled: “Polyclonal and monoclonal B lymphocytes response in HCVinfected patients treated with directacting antiviral agents”.1 There are extensive data supporting the association between hepatitis C virus (HCV) and Bcell nonHodgkin lymphoma (Bcell NHL), especially with marginal zone and diffuse large Bcell NHL subtypes. Antiviral treatment with interferonbased regimens has been shown to improve prognosis and can be curative in some cases of indolent lymphoma. However, there is scarce information evaluating the role of directacting antiviral agents (DAAs) in HCVpositive lymphomas, with only a few case series and recent casecontrol studies suggesting that its concomitant use with chemotherapy is safe and effective.2,3 Schiavinato et al assessed the effect of DAAs on peripheral blood lymphocytes using flow cytometry in 9 patients with HCVpositive lymphoma and 20 HCVinfected control patients. The study shows that treatment with DAAs is associated with a reduction in the Bcell compartment in most patients, but monoclonal cells persisted in 6 of the 9 patients 1 year after sustained virological response (SVR). In line with this finding, we report 2 cases of lowgrade Bcell NHL that appeared after SVR with DAAs. A 73yearold man with chronic HCV infection started a 12week course of sofosbuvir, ledipasvir (Harvoni®, Gilead Sciences Inc, Foster city, CA, USA) and ribavirin in April 2016 (Table 1). He achieved a 24week SVR without any adverse effects. In February 2017, he presented with marked asthenia, and a transabdominal ultrasound detected a heterogeneous and irregular mass in the epigastrium. A CT scan revealed a peripancreatic mass in touch with the tail and body of the pancreas compressing adjacent structures (Figure 1). An endoscopic ultrasoundguided fineneedle aspiration (FNA) and tissue flow cytometry confirmed the diagnosis of a lowgrade BCNHL of the marginal zone (Stage IIx). To date, he has achieved partial response after 4 cycles of bendamustine and rituximab. The second case is a 62yearold woman diagnosed with HCV infection in 2009, who started a 24week regimen of Harvoni® in May 2015 (Table 1). The treatment was well tolerated, and she achieved a 24week SVR. In December 2016, an abdominal ultrasound revealed a 2.8cm lymph node in the hepatic hilum. A CT scan showed multiple pathologic lymphadenopathies in the upper abdomen and retroperitoneum. Endoscopic ultrasoundguided FNA, flow cytometry and PET scan established the diagnosis of stage II lowgrade Bcell NHL. The patient is currently asymptomatic, with stable disease in radiologic imaging and is under close followup with a “watch and wait” approach. Based on some reports suggesting an increased risk of hepatocellular carcinoma recurrence, it has been hypothesized that HCV clearance with DAAs can affect the immune system in favour of tumour

Disminución de la agudeza visual

Resumen La disminucion de la agudeza visual es un sintoma comun a numerosas patologias oftalmologicas y neuro-oftalmologicas. El origen de la patologia puede localizarse en cualquier punto de la via visual que dirige el estimulo luminoso desde la superficie ocular al cortex occipital. Es fundamental realizar una anamnesis cuidadosa y una exploracion ocular sistematica para orientar el diagnostico y asi evitar exploraciones complementarias innecesarias. Algunas patologias que se acompanan de disminucion de la vision presentan un pronostico visual e incluso vital que depende de lo precoz que sea la instauracion del tratamiento adecuado; por tanto, deben ser identificadas y valoradas de forma urgente por oftalmologos y/o neurologos.

Protocolo diagnóstico del ojo rojo

Resumen La aparicion de un ojo rojo es una de las principales causas de consulta oftalmologica urgente. Dado que el ojo rojo es un signo comun en multiples patologias oculares, una exhaustiva y metodica exploracion de los signos y sintomas acompanantes nos permitira aproximarnos al diagnostico del proceso causal (conjuntivitis, patologia corneal, uveitis, glaucoma agudo, escleritis).