Development and validation of a new prognostic score for hepatitis B virus-related acute-on-chronic liver failure.

BACKGROUND & AIMS: Early determination of the prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is important to guide clinical management and decrease mortality. The aim of this study was to develop a new simplified prognostic score to accurately predict outcomes in patients with HBV-ACLF. METHODS: Prospective clinical data from 2,409 hospitalized patients with acute deterioration of HBV-related chronic liver disease were used to develop a new prognostic score that was validated in an external group. RESULTS: A total of 954 enrolled patients with HBV-ACLF were diagnosed based on the Chinese Group on the Study of Severe Hepatitis B-ACLF (COSSH-ACLF) criteria. Six predictive factors were significantly related to 28-day mortality and constituted a new prognostic score (=1.649×ln(international normalized ratio)+0.457×hepatic encephalopathy score+0.425×ln(neutrophil)+0.396×ln(total bilirubin)+0.576×ln(serum urea)+0.033×age). The C-indices of the new score for 28-/90-day mortality (0.826/0.809) were significantly higher than those of 4 other scores (COSSH-ACLF, 0.793/0.784; CLIF-C ACLF, 0.792/0.770; MELD, 0.731/0.727; MELD-Na, 0.730/0.726; all p <0.05). The prediction error rates of the new score for 28-day mortality were significantly lower than those of the 4 other scores: COSSH-ACLF (15.9%), CLIF-C ACLF (16.3%), MELD (35.3%) and MELD-Na (35.6%). The probability density function evaluation and risk stratification of the new score also showed the highest predictive values for mortality. These results were then validated in an external cohort. CONCLUSION: A new prognostic score based on 6 predictors, without an assessment of organ failure, can accurately predict short-term mortality in patients with HBV-ACLF and might be used to guide clinical management. LAY SUMMARY: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a complex syndrome that is associated with a high short-term mortality rate. We developed a simplified prognostic score for patients suffering from this condition based on a prospective multicentre cohort. This new score had better predictive ability than 4 other commonly used scores.

Hepatitis B and Delta: clinical aspects of patients in the Brazilian Western Amazonia / Hepatitis B y Delta: aspectos clínicos de pacientes en el Amazonas brasileño Occidental / Hepatite B e Delta: aspectos clínicos de pacientes na Amazônia Ocidental brasileira

ABSTRACT Objective: to analyze clinical, serological, biochemical and hematological aspects in patients infected with the hepatitis B (HBV) and Delta (HDV) viruses. Method: cross-sectional, descriptive and retrospective study, performed with patients chronically infected with HBV and superinfected with HDV. Results: among the 112 patients selected, 74% were monoinfected with HBV (Group HBV) and 26% were superinfected with HDV (Group HBV+HDV). There was no difference in gender distribution. The average age was 36 years with standard deviation of ±12 years. The symptoms and signs presented a higher proportion in Group HBV+HDV (p=0.001). In both groups, most patients had non-reactive AgHBe. The records of biochemical and hematologic changes showed highest proportion in Group VHB+VHD Group (p<0.05). Conclusion: the study found that patients were in clinical stages of the disease different from those in the initial examination for monitoring their chronic condition. The clinical profile suggests greater severity of liver disease among the patients superinfected with HDV.

RESUMEN Objetivo: Analizar los aspectos clínicos, serológicos, bioquímicos y hematológicos de pacientes infectados por el virus de las hepatitis B (VHB) y Delta (VHD). Método: Se trata de un estudio transversal, descriptivo, retrospectivo, realizado entre pacientes crónicos infectados de VHB y sobre infectados de VHD. Resultados: Entre los 112 pacientes seleccionados, el 74% estaba mono infectado por VHB (Grupo VHB) y el 26%, sobre infectado por VHD (Grupo VHB+VHD). No se encontró diferencia en la distribución por género. La edad promedio era 36 años, con desviación típica de ±12 años. Los síntomas y signos sobresalían en mayor proporción en el grupo VHB+VHD (p=0,001). Para ambos grupos, la mayoría de los pacientes estaba con AgHBe no reactivo. El registro de alteraciones bioquímicas y hematológicas atribuyó proporción más grande al grupo VHB+VHD (p<0,05). Conclusión: El estudio demostró que los pacientes, en la consulta inicial para el seguimiento de la condición crónica, estaban en diferentes estadios clínicos de la enfermedad. El perfil clínico sugiere que la gravedad de la enfermedad hepática es mayor entre pacientes sobre infectados de VHD.

RESUMO Objetivo: Analisar aspectos clínicos, sorológicos, bioquímicos e hematológicos entre pacientes infectados por vírus das hepatites B (VHB) e Delta (VHD). Método: Estudo transversal, descritivo, retrospectivo, realizado com pacientes cronicamente infectados por VHB e superinfectados por VHD. Resultados: Entre os 112 pacientes selecionados, 74% estavam monoinfectados por VHB (Grupo VHB) e 26% superinfectados por VHD (Grupo VHB+VHD). Não houve diferença na distribuição por gênero. A idade média foi de 36 anos, com desvio padrão de ±12 anos. Os sintomas e sinais apresentaram maior proporção no grupo VHB+VHD (p=0,001). Para ambos os grupos, a maioria dos pacientes estava com AgHBe não reagente. O registro de alterações bioquímicas e hematológicas apresentou maior proporção no grupo VHB+VHD (p<0,05). Conclusão: O estudo revelou que os pacientes estavam em diferentes estágios clínicos da doença na consulta inicial para acompanhamento de condição crônica. O perfil clínico sugere maior gravidade da doença hepática entre os pacientes superinfectados por VHD.

Hepatitis B and Delta: clinical aspects of patients in the Brazilian Western Amazonia.

OBJECTIVE: to analyze clinical, serological, biochemical and hematological aspects in patients infected with the hepatitis B (HBV) and Delta (HDV) viruses. METHOD: cross-sectional, descriptive and retrospective study, performed with patients chronically infected with HBV and superinfected with HDV. RESULTS: among the 112 patients selected, 74% were monoinfected with HBV (Group HBV) and 26% were superinfected with HDV (Group HBV+HDV). There was no difference in gender distribution. The average age was 36 years with standard deviation of ±12 years. The symptoms and signs presented a higher proportion in Group HBV+HDV (p=0.001). In both groups, most patients had non-reactive AgHBe. The records of biochemical and hematologic changes showed highest proportion in Group VHB+VHD Group (p<0.05). CONCLUSION: the study found that patients were in clinical stages of the disease different from those in the initial examination for monitoring their chronic condition. The clinical profile suggests greater severity of liver disease among the patients superinfected with HDV.

New horizons in hepatitis B and C in the older adult.

Hepatitis C (HCV) and hepatitis B (HBV), are blood-borne viruses that can cause acute hepatitis; but are clinically relevant because chronic infection is associated with development of cirrhosis and hepatocellular carcinoma. Both these viruses are becoming more common in the older population, due to the ageing of generations exposed to the risk factors associated with infection; intravenous drug use, multiple sexual partners and men who have sex with men. This review will cover the natural history and epidemiology of these infections as well as the revolution in drug therapy that now allows cure of HCV infection and complete control of HBV infection.

Classification and sensitivity analysis of the transmission dynamic of hepatitis B.

BACKGROUND: Hepatitis B infection caused by the hepatitis B virus is one of the most serious viral infections and a global health problem. In the transmission of hepatitis B infection, three different phases, i.e. acute infected, chronically infected, and carrier individuals, play important roles. Carrier individuals are especially significant, because they do not exhibit any symptoms and are able to transmit the infection. Here we assessed the transmissibility associated with different infection stages of hepatitis B and generated an epidemic model. METHODS: To demonstrate the transmission dynamic of hepatitis B, we investigate an epidemic model by dividing the infectious class into three subclasses, namely acute infected, chronically infected, and carrier individuals with both horizontal and vertical transmission. RESULTS: Numerical results and sensitivity analysis of some important parameters are presented to show that the proportion of births without successful vaccination, perinatally infected individuals, and direct contact rate are highest risk factors for the spread of hepatitis B in the community. CONCLUSION: Our work provides a coherent platform for studying the full dynamics of hepatitis B and an effective direction for theoretical work.

Chronic hepatitis B and D: prognosis according to Child-Pugh score.

OBJECTIVE:: compare chronic hepatitis B patients to those superinfected with hepatitis D virus, according to Child-Pugh score regarding disease severity. METHOD:: retrospective descriptive study, performed with 59 patients followed in the ambulatory, of which 22 (37.3%) were chronically infected with hepatitis B virus (Group HBV) and 37 (62.7%) superinfected with Delta virus (Group HBV+HDV); variables of sex, age and items of Child-Pugh score were collected by consulting medical records. RESULTS:: out of the patients, 57.6% were male, with a mean age of 30.5 years. Score A, which indicates lesser severity, was found in 100% of group HBV and 78.4% of group HBV+HDV. Score B, which indicates greater severity, was found only in group HBV+HDV in 21.6% of the patients. CONCLUSION:: by means of the Child-Pugh score, it was observed that patients with superinfection by HDV tended to present a worse prognosis. OBJETIVO:: comparar os pacientes com hepatite B crônica com superinfectados pelo vírus D segundo escore de Child-Pugh quanto à gravidade da doença. MÉTODO:: estudo descritivo retrospectivo, realizado com 59 pacientes acompanhados em ambulatório, sendo 22 (37,3%) cronicamente infectados pelo vírus da hepatite B (Grupo VHB) e 37 (62,7%) com superinfecção por vírus Delta (Grupo VHB+VHD); foram coletadas variáveis quanto ao sexo, idade e referentes ao escore de Child-Pugh por meio de consulta a prontuários. RESULTADOS:: entre os pacientes 57,6% era do sexo masculino, com idade média de 30,5 anos. O escore A, que indica menor gravidade, foi encontrado em 100% do grupo VHB e 78,4% do grupo VHB+VHD. O escore B, que indica maior gravidade, foi encontrado apenas no grupo VHB+VHD em 21,6% dos pacientes. CONCLUSÃO:: por meio do escore de Child-Pugh, observou-se que os pacientes com superinfecção por VHD tendem a apresentar pior prognóstico.

Chronic hepatitis B and D: prognosis according to Child-Pugh score / Hepatitis crónicas B y D: pronóstico según escore Child-Pugh / Hepatites crônicas B e D: prognóstico segundo escore Child-Pugh

ABSTRACT Objective: compare chronic hepatitis B patients to those superinfected with hepatitis D virus, according to Child-Pugh score regarding disease severity. Method: retrospective descriptive study, performed with 59 patients followed in the ambulatory, of which 22 (37.3%) were chronically infected with hepatitis B virus (Group HBV) and 37 (62.7%) superinfected with Delta virus (Group HBV+HDV); variables of sex, age and items of Child-Pugh score were collected by consulting medical records. Results: out of the patients, 57.6% were male, with a mean age of 30.5 years. Score A, which indicates lesser severity, was found in 100% of group HBV and 78.4% of group HBV+HDV. Score B, which indicates greater severity, was found only in group HBV+HDV in 21.6% of the patients. Conclusion: by means of the Child-Pugh score, it was observed that patients with superinfection by HDV tended to present a worse prognosis.

RESUMEN Objetivo: comparar los pacientes con hepatitis B crónica con superinfectados por el virus D según escore de Child-Pugh cuanto a la gravedad de la enfermedad. Método: estudio descriptivo retrospectivo, realizado con 59 pacientes acompañados en ambulatorio, siendo 22 (37,3%) crónicamente infectados por el virus de hepatitis B (Grupo VHB) y 37 (62,7%) con superinfección por virus Delta (Grupo VHB+VHD); fueron colectadas variables cuanto al sexo, edad y referentes al escore de Child-Pugh por medio de consulta a prontuarios. Resultados: entre los pacientes 57,6% era de varones, con edad media de 30,5 años. El escore A, que indica menor gravedad, fue encontrado en 100% del grupo VHB y 78,4% del grupo VHB+VHD. El escore B, que indica mayor gravedad, fue encontrado apenas en el grupo VHB+VHD en 21,6% de los pacientes. Conclusión: por medio del escore de Child-Pugh, se observó que los pacientes con superinfección por VHD tienden a presentar peor pronóstico.

RESUMO Objetivo: comparar os pacientes com hepatite B crônica com superinfectados pelo vírus D segundo escore de Child-Pugh quanto à gravidade da doença. Método: estudo descritivo retrospectivo, realizado com 59 pacientes acompanhados em ambulatório, sendo 22 (37,3%) cronicamente infectados pelo vírus da hepatite B (Grupo VHB) e 37 (62,7%) com superinfecção por vírus Delta (Grupo VHB+VHD); foram coletadas variáveis quanto ao sexo, idade e referentes ao escore de Child-Pugh por meio de consulta a prontuários. Resultados: entre os pacientes 57,6% era do sexo masculino, com idade média de 30,5 anos. O escore A, que indica menor gravidade, foi encontrado em 100% do grupo VHB e 78,4% do grupo VHB+VHD. O escore B, que indica maior gravidade, foi encontrado apenas no grupo VHB+VHD em 21,6% dos pacientes. Conclusão: por meio do escore de Child-Pugh, observou-se que os pacientes com superinfecção por VHD tendem a apresentar pior prognóstico.

Virus de la hepatitis B e infección por VIH/SIDA en niños / Hepatitis b and HIV/AIDS infection in children

La infección por VIH/SIDA en niños ha aumentado a nivel mundial y en nuestro medio no es la excepción, aunque desde hace muchos años se ha cambiado la historia natural de la enfermedad utilizando la terapia antirretroviral altamente efectiva (HAART). La manera más frecuente de transmisión del Virus de la Hepatitis B (VHB) son contactos con sangre o fluidos y a través de actividad sexual. La infección por VIH/SIDA es una enfermedad viral progresiva caracterizada por el desarreglo inmune. La infección concurrente de VIH con VHB y hepatitis C (VHC) se asocia con incremento en la severidad y empeora el pronóstico de la enfermedad hepática.

HIV/AIDS in children has increased worldwide and in our environment is no exception, although for many years has changed the natural history of disease using highly effective antiretroviral therapy (HAART). The most frequent way of transmission of Hepatitis B Virus (HBV) is contact with blood or body fluids and by sexual activity. HIV/AIDS is a viral disease characterized by progressive immune disorder. HIV concurrent infection with HBV and hepatitis C virus (HCV) is associated with increased severity and worsens the prognosis of liver disease.

Actualización sobre hepatitis B / Upgrade in hepatitis B

El virus de la hepatitis B (VHB), es un virus DNA, el cual tiene varios antígenos, como el antígeno de superficie, y antígeno core. Colombia, es un país de baja endemicidad, sin embargo, en la Sierra Nevada de Santa Marta, está endemicidad es alta. El VHB tiene como una de sus complicaciones la hipertensión porta. En general, el VHB no atraviesa la placenta, por lo que la infección es rara in utero. Son pocos los pacientes que se presentan con HB y falla hepática fulminante y por lo tanto, son pocos los antivirales que han sido utilizados, con muy poca experiencia.

The hepatitis B virus (HBV) is a DNA virus, which has several antigens such as surface antigen and core antigen. Colombia is a country of low endemicity, however, in the Sierra Nevada of Santa Marta, is endemic is high. HBVis one of the complications of portal hypertension. In general, HBV does not cross the placenta, so the infection is rare in utero. Few patients who present with HB and fulminant hepatic failure and therefore, few antiviral drugs that have been u s e d , wi t h v e r y l i t t l e e x p e r i e n c e.

Grabbing the rice straw: health information seeking in Chinese immigrants in the United States.

Chinese immigrants in the United States experience a higher incidence of cancers of the oral cavity, pharynx, stomach, and liver and higher rates of tuberculosis and hepatitis B virus than other U.S. immigrant groups. Because of language and cultural barriers, many do not seek the health information they need, resulting in delayed diagnosis and inability to effectively manage health problems. The purpose of this study was to identify the cultural beliefs and meanings influencing the utilization behaviors and perceptions of how this group finds and uses the health information they need. Using an explorative qualitative descriptive design, 24 Chinese immigrants in two urban centers in the northwestern part of the United States were interviewed about their beliefs and perceptions of health information. Results revealed many challenges that served as barriers to health promotion, indicating that health care providers need to respond to the needs of this population with increased thoughtfulness and culturally relevant practices.

[Analysis of clinical features and virological characteristics in patients infected with three different HBV subgenotypes].

OBJECTIVE: To investigate the clinical characteristics and the pattern of precore and core promoter mutations of hepatitis B virus (HBV) subgenotypes Ba, C1 and C2. METHODS: A cohort of 151 patients with chronic HBV infection in Guangdong province of China was enrolled in this study. HBV subgenotypes were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Precore and core promoter mutations were analysed using nucleotide sequencing. RESULTS: Of the 151 patients, 80, 51 and 20 were infected with subgenotypes Ba, C1 and C2 respectively. No significant differences were found in HBeAg positivity and liver functional indexes among these three subgenotypes when age and sex were matched. Virologically, HBV/Ba showed the highest frequency of A1896 mutation but the lowest frequency of T1762/A1764 mutation. HBV/C1 was associated with the highest tendency to develop T1762/A1764 mutation, but the lowest prevalence of A1896 mutation. HBV/C2 was associated with an intermediate tendency to develop A1896 and T1762/A1764 mutations. CONCLUSION: Different mutation patterns in precore and core promoter regions are responsible for HBeAg-negative HBV infections among different subgenotypes.

Analysis of hepatitis B surface antigen mutations in Mongolia: molecular epidemiology and implications for mass vaccination.

Although the potential significance of hepatitis B surface antigen (HBsAg) mutants for failure of immunization has been studied in some endemic countries, whether the "a" determinant variants are responsible for vaccine failure in Mongolia remains unknown. Fifty-nine HBsAg-positive children (age: 8.8 +/- 0.9 years) who had been observed during the nationwide survey of vaccinated cohorts conducted in 2004 were subjected to molecular analyses of hepatitis B virus (HBV). Partial S gene sequences encoding amino acids (aa) 40-171 of HBsAg were determined in 57 children (96.6%) who had detectable HBV DNA. Phylogenetic analysis of the S gene sequences revealed that genotype D accounted for 93.0% and genotype A for 5.3%. Only one child (1.7%) had HBVs of genotypes A and D. HBsAg mutations were found in 17 (29.8%) children ranging from 1 to 4 aa per subject (mean +/- SD, 1.6 +/- 0.9 aa). Pro127Thr and Thr118Ala were the most common substitutions, which occurred in 6 (10.5%) and 3 (5.3%) subjects, respectively; none had Gly145Arg. There were no significant associations in the prevalence of HBsAg mutations with age, sex, residential area, or vaccination status against hepatitis B. Analysis of the deduced amino acid sequence of the entire preS1/preS2/S gene revealed that eight genotype D isolates and one genotype A isolate were quite similar to previously-reported wild-type isolates, suggesting that they are essentially wild-type, but not vaccine-induced mutants. In conclusion, the results demonstrate that hepatitis B surface gene mutants do not play a significant role in vaccination failure in Mongolia.

[Distribution of HBV genotypes in the Czech population--pilot study]. / Distribuce genotypu HBV v ceské populaci--pilotní studie.

A compact structure of the hepatitis B virus genome does not provide much space for development of mutations capable of further replication. In spite of that, 7 genotypes have been described so far. Discovery of the hepatitis B virus (HBV) genome diversity led to a range of further questions. Individual genotypes are subjects of investigation these days as for the pattern of disease transmission, course of disease, and consequences of an infection. The aim of this pilot study was to describe genotype distribution in the infected population of the Czech Republic. Moreover, epidemiological and clinical characteristics were monitored in our sample. We studied a group of 65 patients with positive HBsAg from which 48 samples of patients were genotyped. PCR (polymerase chain reaction) method was used in order to amplify S region of the HBV genome. Direct sequencing of PCR products was used, this is the most accurate method for genotype identification. A relatively uniform genotypic distribution was identified within the study population--only 2 genotypes, A and D, were found. Genotype A was identified in 35 (73%) patients and genotype D in 13 (27%) patients. No statistically significant association between the particular genotype and epidemiological and clinical parameters was proved in this pilot study. This study brings basic information on genotype distribution. A possible proof of correlation with clinical and epidemiological characteristics will require examination of a larger sample of patients.

Hepatitis B genotypes correlate with tumor recurrence after curative resection of hepatocellular carcinoma.

BACKGROUND AND AIMS: Hepatitis B virus (HBV) genotype C is associated with the development of hepatocellular carcinoma (HCC), compared with genotype B. This study aims to investigate whether HBV genotypes influence the clinicopathologic features and long-term prognosis of patients after curative resection of HCC. METHODS: Stored serum samples from 62 patients with HBV-related HCC were tested for HBV genotype using a molecular method. RESULTS: Sixty of 62 patients (96.8%) undergoing curative resection of HCC were infected with genotype B or C. Concomitant cirrhosis was encountered more frequently in patients with genotype C. During a mean follow-up period of 26.3 +/- 9.8 months, patients with genotype B had a lower overall tumor recurrence rate than those with genotype C (22% vs. 46%; P = 0.04). Stepwise multiple Cox proportional hazards regression analysis showed that multiplicity of tumor (hazard ratio, 6.84; 95% confidence interval [CI], 1.45-32.2; P = 0.02) was associated with tumor recurrence, whereas genotype C and age were associated with borderline significance (P = 0.06). Stratified analysis showed that genotype C was still associated with tumor recurrence in cirrhotic patients with borderline significance by univariate analysis (hazard ratio, 3.8; 95% CI, 0.84-17.6; P = 0.07). However, cumulative 2-year survival rates were similar between patients with genotype B and C (92% vs. 85%; P = 0.23). CONCLUSIONS: Our data suggest that patients with HCC with genotype C have a greater tumor recurrence rate after curative resection of HCC compared with those with genotype B. Prolonged follow-up is needed to clarify the impact of HBV genotype on postoperative outcome.

Analysis of the complete genome of subgroup A' hepatitis B virus isolates from South Africa.

A phylogenetic analysis is presented of six complete and seven pre-S1/S2/S gene sequences of hepatitis B virus (HBV) isolates from South Africa. Five of the full-length sequences and all of the pre-S2/S sequences have been previously reported. Four of the six complete genomes and three of the five incomplete sequences clustered with subgroup A', a unique segment of genotype A of HBV previously identified in 60% of South African isolates using analysis of the pre-S2/S region alone. This separation was also evident when the polymerase open reading frame was analysed, but not on analysis of either the X or pre-core/core genes. Amino acids were identified in the pre-S1 and polymerase regions specific to subgroup A'. In common with genotype D, 10 of 11 genotype A South African isolates had an 11 amino acid deletion in the amino end of the pre-S1 region. This deletion is also found in hepadnaviruses from non-human primates.