Liver transplantation for acute-on-chronic liver failure / 器官移植

Acute-on-chronic liver failure (ACLF) is a specific category of liver failure, which is mainly characterized by rapid progression and multiple organ failure. At present, patients with ACLF are mainly given with systematic and comprehensive medical therapy to promote liver regeneration. However, liver transplantation is the only potentially curative treatment for patients who failed to respond to medical treatment and rapidly progress into multiple organ failure. Considering the differences of disease progression and clinical prognosis, and the shortage of donor liver in China, it is necessary to actively prevent the triggering factors of ACLF in patients with chronic liver diseases, screen out the recipients who are most likely to benefit from liver transplantation and deliver precision management during perioperative period of liver transplantation. In this article, the application of liver transplantation in ACLF was illustrated from the perspectives of accurate evaluation of ACLF, proper control of liver transplantation indications and meticulous perioperative management, aiming to optimize the therapeutic strategy of liver transplantation in patients with ACLF.

¿Es necesario inyectar inmunoglobulina (Ig anti-HB) como profilaxis en los contactos sexuales de pacientes con Hepatitis B?: síntesis rápida de evidencia / Is it necessary to inject immune globulin (Anti-HBc igg) as prophylaxis in sexual contacts of patients with Hepatitis B?: rapid evidence synthesis

ANTECEDENTES Y OBJETIVO Aproximadamente 240 millones de personas a nivel mundial están infectadas con Hepatitis B, mientras que más de 780 mil mueren cada año a causa de alguna complicación producto de esta enfermedad. En términos de vigilancia epidemiológica, al ser ésta una Enfermedad de Notificación Obligatoria (ENO), cada vez que se reporta un caso, se deben considerar medidas de profilaxis para los contactos que puedan contraer la enfermedad. De esta forma, recién nacidos de madres con Hepatitis B son vacunados, además de recibir Inmunoglobulina anti-Hepatitis B (Ig anti-HB), para prevenir la transmisión vertical de esta enfermedad, lo cual está incorporado en la guía clínica actual de tratamiento En este contexto en Departamento de Epidemiología solicita esta síntesis con el objetivo de conocer el efecto de aplicar Inmunoglobulina anti-Hepatitis B (Ig anti-HB) a contactos sexuales, de manera de evaluar su incorporación en la actualización de la circular de vigilancia epidemiológica para esta condición. METODOLOGÍA Se formuló una estrategia de búsqueda para ser utilizada en 10 bases de datos con el objetivo de identificar revisiones sistemáticas del tema. Al no encontrarse, se procedió a buscar estudios primarios que abordaran la pregunta estudiada. Se excluyeron los casos que consideraban exposiciones del personal de salud, transmisión vertical e inmunosupresión. Consultando al solicitante, se decidió excluir cualquier tipo de transmisión no sexual. RESULTADOS -La evidencia encontrada muestra que la Ig anti-HB no genera diferencia sobre el número de casos con HBsAg+, en comparación a Ig no específica. -La evidencia encontrada muestra que la Ig anti-HB no genera diferencia sobre el número de casos con anti-HBc+, en comparación a Ig no específica. -La evidencia encontrada muestra que la Ig anti-HB, en comparación a Ig no específica, reduce levemente el número de casos clínicos de Hepatitis B. -La calidad de la evidencia es incierta, puesto que este resumen no realiza una evaluación de ésta. -Se han notificado más de 5 000 casos de Hepatitis B entre 2001 y 2012, más del 80% en población masculina.

Evaluation of immunogenicity of an immune complexed hepatitis B vaccine / 中华微生物学和免疫学杂志

Objective To evaluate the immunogenicity of an immune complexed hepatitis B vac-cine ( HBsAg-HBIG immune complexes , IC) in mouse and cynomolgus monkeys by using recombinant hepa-titis B vaccine ( Saccharomyces cerevisiae, HBsAg) as the control .Methods BALB/c mice were vaccinated with single dose of IC and single dose of HBsAg respectively and then serum samples were collected at differ -ent time points for the detection of dynamic anti-HBs by using ELISA .The serum anti-HBs titers in BALB/c mice vaccinated with different immunization strategies were also analyzed .ELISPOT assay was performed to detect the numbers of IFN-γSFC and IFN-γpositive rate in splenocytes of BALB/c mice intramuscularly im-munized with IC, HBsAg or standard hepatitis B vaccine at 5μg/mouse.ED50 was measured to evaluate the stability of IC.Twelve cynomolgus monkeys were equally divided into two groups and immunized with high dose (100 μg) and low dose (20 μg) of IC respectively and then , serum anti-HBs levels at different time points were detected .Results The serum anti-HBs titers in IC immunized group at different time points were higher than those immunized with HBsAg .Moreover, the anti-HBs titer induced by two doses of IC reached a level comparable to that elicited by three doses of HBsAg .ELISPOT assay showed that both the numbers of IFN-γSFC and IFN-γpositive rate were the highest in IC immunized group as compared with those immunized with HBsAg and standard hepatitis B vaccine .IC had a lower ED50 than HBsAg, indicating a good long term stability .Cynomolgus monkeys immunized with high or low dose of IC produced high levels of anti-HBs titer during a long time period .Conclusion IC has a higher immunogenicity inducing both hu-moral immunity and cellular immunity as compared with HBsAg or standard hepatitis B vaccine .

Analysis of Clinical Characteristics and S Gene Mutation of Hepatitis B Virus (HBV) in Patients with Hepatitis B Surface Antigen RIA Negative and HBV DNA Positive / 대한진단검사의학회지

BACKGROUND: We investigated hepatitis B virus (HBV) infection cases, who were HBsAg negative by radioimmunoassay (RIA) and HBV DNA positive for their clinical characteristics, the S gene mutation of hepatitis B virus (HBV), and usefulness of other HBsAg immunoassay. METHODS: Among the patients requested for HBV DNA quantification, 16 patients positive in HBV DNA but negative in HBsAg RIA (BNIBT HBsAg Kit, China) were enrolled. The "a" determinant of HBV S gene was sequenced and clinical characteristics were reviewed. Additional HBsAg assay was performed using Architect HBsAg kit (Abbott laboratories, USA) employing chemiluminescent immunoassay method. RESULTS: Eleven of the 16 patients showed multiple mutations in the "a" determinant. These patients received liver transplantation several years ago and have been treated with hepatitis B immune globulin (HBIG) and antiviral drugs. G145R mutation was found in 8 patients and G145K, D144G, and D144A were also frequently found. Among 9 of the 11 patients tested for HBsAg by Architect HBsAg kit, 8 showed positive results. Among 4 of the remaining 5 patients, only 2 showed weak positive results (< or =1 IU/mL) in Architect HBsAg kit. CONCLUSIONS: HBV DNA-positive/HBsAg RIA-negative results were mostly observed in the patients treated with HBIG after liver transplantation, in whom HBIG escape mutations were found. Majority of these cases were positive in Architect HBsAg assay, and it is recommended to use other HBsAg immunoassay methods that are more sensitive than RIA in the detection limit as well as in the detection of escape mutant in hospitals performing liver transplantation.

Prevention of Hepatitis B Virus Reinfection after Liver Transplantation / 中华医院感染学杂志

OBJECTIVE To discuss the preventive methods of hepatitis B virus reinfection after liver transplantation. METHODS Eighty eight liver transplantation recipients with HBV-related end-stage liver diseases including chronic fulminant hepatitis B,end-stage liver cirrhosis and liver carcinoma were analyzed retrospectively,and were given lamivudine pre-transplantation to prevent hepatitis B virus reinfection.Post-transplantation medicines of lamivudine were administered in 3 cases;lamivudine and hepatitis B immunoglobulin(HBIg) in 85 cases.The follow-up criteria included serum HBV,HBV-DNA,liver biopsy,immunohistochemical study of liver biopsy specimens and clinical manifestations.All of patients were followed-up 6 months at least.RESULTS Two of the three cases who taken lamivudine developed reinfection,the little time is 6 months following liver transplantation.There were three of eighty five cases taken lamicudine and HBIg(small dosage) developed reinfection.CONCLUSIONS Liver transplantation is an effective treatment for HBV-related end-stage liver diseases.Given lamivudine at the pre-transplantation could reduce the levels of the HBV virus copies.Lamivudine and HBIg post-transplantation offer effective prevention against hepatitis B virus reinfection.

Efficacy of Hepatitis B Immune Globulin for Prevention of De Novo Hepatitis B in Living-related Liver Transplantation / 대한소아소화기영양학회지

PURPOSE: Hepatic allografts from donors with hepatitis B core antibody have been demonstrated to transmit hepatitis B virus (HBV) infection to recipients after liver transplantation (LT). The efficacy of hepatitis B immune globulin (HBIg) to prevent de novo hepatitis B was investigated by comparing active immunization in the early phase to HBIg monotherapy in the late phase of pediatric liver transplants at Samsung Medical Center. METHODS: Among pediatric liver transplants, from May, 1996 to June, 2002, 15 recipients who were hepatitis B surface antigen (HBsAg) (-) received an allograft from a donor with hepatitis B core antibody (HBcAb) (+). Except two who died from unrelated causes, eleven of 13 recipients were HBsAb (+), and 2 were naive (HBsAb(-), HBcAb(-)). All patients were vaccinated for HBV before LT. In the early phase (January, 1997~November, 1997, 3 patients), HBsAb (+) recipients received booster vaccination after LT. In the late phase (December, 1997~, 10 patients), all recipients were given booster vaccination and received HBIg therapy in order to maintain HBsAb titer greater than 200 IU/L. Lamivudine was given in one case because of severe side effect of HBIg. We retrospectively analyzed the effect of the preventive therapy for de novo hepatitis B through medical records. RESULTS: De novo hepatitis B developed in three of 13 recipients (23.1%). All of 3 patients who received active immunization in the early phase became HBsAg (+) at 7~19 months after transplantation. One of them was naive before LT and the other two were HBsAb (+). All of 10 recipients who were given HBIg in the late phase remained HBsAg (-) at 7~55 months' follow-up. CONCLUSION: Passive immunization with HBIg was effective for prevention of de novo hepatitis B in HBsAg (-) recipients of hepatic allografts from HBcAb (+) donors.

The Change of Anti-HBs Titer after Injection of HBIG and HBV in Newborn Delivered from HBsAg Carrier Mothers

PURPOSE: We studied prevention effects of vertical transmission of Hepatitis B with follow-up, through the change of Anti-HBs titers during 9 months after injection of Hepatitis B immunoglobulin (HBIG) and Hepatitis B vaccine (HBV) at birth in newborn delivered from Hepatitis antigen carrier mothers. METHODS: This study was performed on newborn delivered from HBsAg carrier mothers at Hae Sung Hospital from Feb. 1995 to May 1996. These newborn were injected intramuscularly with HBV and HBIG after evaluation of HBsAg and Anti-HBs titer directly at birth. Regular Hepatitis vaccination was given at 1 month, 6 months as well as HBsAg and Anti-HBs titer were evaluated at 24 hours, 1 month, 3 months, 6 months, and 9 months. RESULTS: The incidence of Hepatitis B carrier mothers is 5.6%, and newborn babies born to HBsAg carrier mothers showed HBsAg in 10.6%. In most newborn, Anti-HBs titer maintained in 100-1,000mIU/ml after injection of HBIG and HBV at birth, and mean Anti-HBs titer decreased a little at 1 month, but therafter increased gradually by regular Hepatitis vaccination. HBsAg positive newborn maintained mean HBsAg titers below 2 (S/N) until 9 months old after injection of HBIG and HBV. CONCLUSIONS: A screening test for Hepatitis B must be performed on all pregnant women, and that infants of Hepatitis B carrier mothers must be immunized by HBIG and HBV directly at birth.