Predictors of HBeAg seroconversion after long-term nucleos(t)ide analogues treatment for chronic hepatitis B: a multicenter study in real clinical setting

ABSTRACT Aims: To evaluate the HBeAg seroconversion rate in real clinical setting and explore its predictors in long-term nucleos(t)ide analogues (NAs) treatment for chronic hepatitis B (CHB). Methods: 251 patients were recruited from January 2001 to September 2009 in four hospitals in Hebei province, China, for this retrospective study. Clinical and laboratory data before and after treatment with lamivudine (LAM, 100 mg daily), adefovir (ADV, 10 mg daily), telbivudine (LDT, 600 mg daily), entecavir (ETV, 0.5 mg daily), and LAM/ADV combination were compared among three groups according to treatment outcomes: synchronous HBeAg loss and HBeAg seroconversion, anti-HBe development after treatment, and no anti-HBe. Adherence was also evaluated. Results: In real clinical setting, cumulative HBeAg seroconversion rates were 14.3%, 32.7%, 43.0%, 46.9%, and 50.5% after 1, 2, 3, 5, and 8 years, respectively. 45 patients (17.9%) were non-adherent. Adherence (p < 0.001, Hazard Ratio (HR) = 2.203), elevated alanine aminotransferase (ALT) levels (p < 0.001, HR = 2.049), and non-vertical transmission (p = 0.006, HR = 1.656) were predictors of HBeAg seroconversion. Conclusion: Adherence, elevated ALT, and non-vertical transmission are predictors of HBeAg seroconversion in CHB patients treated with NAs.

Association of PRKAA1 gene polymorphisms with chronic hepatitis B virus infection in Chinese Han population

ABSTRACT Objective: Studies have indicated that AMPK play critical roles in the regulation of innate immunity and inflammatory responses. However, the role of the polymorphisms of PRKAA1 gene in immune-response to infectious organisms remains unknown. To evaluate the potential role of PRKAA1/AMPKα1 in the immune-response to HBV, we conducted this case-control study. Methods: We recruited 276 patients (145 men and 131 women; average age, 51.6 years) with chronic HBV infection (CHB) and 303 healthy controls (166 men and 137 women; average age, 54.2 years). All the subjects were unrelated individuals of Chinese Han Population. Three SNPs of PRKAA1gene were tested. Results: Rs1002424 polymorphism showed significant difference in the allele frequencies, but no difference in the genotype frequencies (allele: p = 0.039411, OR95%CI = 0.783479 [0.621067-0.988362]; genotype: p = 0.104758); rs13361707 polymorphism showed significance in allele analysis, but not in genotype analysis (allele: p = 0.034749, OR95%CI = 1.284303 [1.017958-1.620335]; genotype: p = 0.098027); rs3792822 polymorphism was demonstrated to have significant differences in both genotype and allele frequencies between cases and controls (allele: p = 0.029286, OR95%CI= 0.741519 [0.566439-0.970716]; genotype: p = 0.034560). The haplotype results showed that CTG and TCA in the rs13361707-rs1002424-rs3792822 block were significantly associated with the happening of HBV (CTG: p = 0.036854, OR95%CI = 1.281 [1.015-1.617]; p = 0.030841, OR95%CI = 0.743 [0.568-0.973]). Conclusion: These findings suggest that PRKAA1 polymorphisms may contribute to the susceptibility of chronic HBV infection in Chinese Han origin.

Plasma myeloperoxidase activity and apolipoprotein A-1 expression in chronic hepatitis B patients

Hepatitis B virus initiates a complicated cascade process leading to chronic hepatitis B, cirrhosis, and hepatocellular carcinoma. In inflammatory situations, myeloperoxidase is released in plasma and binds to apolipoprotein A-1 in high-density lipoproteins. This study aims to evaluate the level of plasma myeloperoxidase as well as the pattern of plasma proteins in patients with chronic hepatitis B. Included in this study were 30 male subjects: 19 chronic hepatitis B patients, 6 HBV-related cirrhotic patients, and 5 healthy controls. Plasma myeloperoxidase was measured using enzyme-linked immunosorbent assay. Proteomic analysis of plasma proteins was performed by two-dimensional gel electrophoresis [2-DE] and mass spectrometry. One way ANOVAwas used for data analysis. Mean plasma myeloperoxidase levels were higher in patients with liver cirrhosis [65.5 +/- 12.5; P=0.007] and chronic hepatitis B [53.7 +/- 10.6; P=0.18] when compared with healthy subjects [45 +/- 7.6]. Moreover, a positive correlation was found between plasma myeloperoxidase levels and hepatic fibrosis stage [r=0.53, P=0.002; r=0.63, P=0.000]. Proteomic analysis showed an altered plasma protein pattern in progressive hepatitis B and down-regulation of the major apolipoprotein A-1 along with the appearance of a variety of spots noted to be apolipoprotein A-1isoforms with different molecular masses. In this study, progressive liver injury due to HBV infection correlated with higher plasma myeloperoxidase and an altered plasma apolipoprotein A-1 pattern

Lamivudina por tempo prolongado no tratamento da hepatite B crônica no estado de Mato Grosso / Long-term use of lamivudine for treating chronic hepatitis B in the State of Mato Grosso

Para avaliar resultados do tratamento da hepatite B crônica com lamivudina, 100mg ou 150mg diários, foram acompanhados 34 pacientes em um serviço em Cuiabá, Mato Grosso. Entre os 34, 21 (62 por cento), eram cirróticos e 24 (70 por cento) HBeAg positivos. Genótipo viral foi determinado em 18, sendo predominante o genótipo A (12). O acompanhamento teve mediana de 27 meses (7 a 64). Do total, 23 (67 por cento) apresentaram resposta bioquímica entre dois e 24 meses de tratamento. Dos 24 pacientes com positividade para o HBeAg, 13 (54 por cento) apresentaram negativação do HBeAg durante o acompanhamento. Entre os anti-HBe positivos, 70 por cento tiveram normalização das aminotransferases. Quatorze (41 por cento) não apresentaram resposta bioquímica ou sorológica de início ou apresentaram breakthrough. Em seis dos que não responderam, foram encontradas as mutações L180M e M204V. Quatro pacientes faleceram após pelo menos 21 meses de lamivudina e três cirróticos desenvolveram hepatocarcinoma após 24 meses. A partir do terceiro ano surgiram complicações, como hepatocarcinoma ou hemorragia digestiva. Os presentes achados sugerem que resposta precoce ao tratamento com lamivudina pode estar associada a um melhor controle da hepatite B crônica.

To assess the results from lamivudine treatment (100 mg or 150 mg) for chronic hepatitis B, 34 patients were followed at a clinic in Cuiabá, Mato Grosso, Central Brazil. Among them, 21 (62 percent) had liver cirrhosis and 24 (70 percent) were HBeAg-positive. The viral genotype was determined for 18 patients, among whom genotype A was the most prevalent (12). The median follow-up was 27 months (range from 7 to 64 months). Among the total, 23 (67 percent) presented a biochemical response after 2 to 24 months of treatment. Among the 24 HBeAg-positive subjects, 13 (54 percent) became HBeAg-negative during the follow-up. Among the anti-HBe-positive patients, 70 percent obtained normalization of aminotransferase levels. Fourteen (41 percent) did not present any initial biochemical or serological response or presented breakthrough. The L180M and M204V mutations were found in six of the non-responders. Four patients died after at least 21 months of lamivudine and three patients with liver cirrhosis developed liver cancer after 24 months. From the third year onwards, complications such as digestive system hemorrhage or liver cancer started to emerge. The present findings suggest that an early response to lamivudine treatment may be associated with better control over chronic hepatitis B.