Patients with chronic hepatitis B who have persistently normal alanine aminotransferase or aged < 30 years may exhibit significant histologic damage.

BACKGROUND: The timing of antiviral therapy for chronic hepatitis B (CHB) patients with normal alanine transaminase (ALT) or aged < 30 years is still undetermined. We aimed to elucidate the correlation between liver histology, age, and ALT level in CHB patients and analyze the histological characteristics of the liver among patients with persistently normal ALT or aged < 30 years. METHODS: A retrospective analysis was conducted on 697 treatment-naive CHB patients. Liver biopsies were performed, and significant histological damage was defined as the grade of liver inflammation ≥ G2 and/or fibrosis ≥ S2 based on the Scheuer scoring system. RESULTS: The liver inflammation grades and fibrosis stages correlated positively with age, ALT, AST, GGT levels and negatively with the counts of PLT (all p < 0.050) in HBeAg-positive patients. Higher ALT levels and lower PLT counts were independently associated with significant liver inflammation and fibrosis in both HBeAg-positive and HBeAg-negative patients. Furthermore, among those with persistently normal ALT levels, the incidence of significant liver inflammation and fibrosis were 66.1% and 53.7% in HBeAg-positive groups, and 63.0% and 55.5% in HBeAg-negative groups. Moreover, there was no significant difference in the prevalence of significant liver damage between patients aged < 30 years and those aged ≥ 30 years, in both HBeAg-positive (≥ G2 or ≥ S2: 63.8% vs. 75.8%, p = 0.276) and HBeAg-negative (≥ G2 or ≥ S2: 65.9% vs. 72.5%, p = 0.504) groups, among patients with persistently normal ALT levels. CONCLUSIONS: A considerable proportion of CHB patients with persistently normal ALT, including those below the age of 30 years, exhibited significant histological damage. This highlights the importance of initiating early antiviral therapy for HBV-infected individuals, even in the absence of elevated ALT levels.

Effective Analysis of Antiviral Treatment in Patients with HBeAg-Seropositive Chronic Hepatitis B with ALT < 2 Upper Limits of Normal: A Multi-center Retrospective Cohort Study.

INTRODUCTION: Although the indications for antiviral therapy for patients with chronic hepatitis B have been gradually expanded in different guidelines, antiviral treatment efficacy remains unclear among HBeAg-seropositive patients with alanine aminotransferase (ALT) < 2 upper limits of normal (ULN). This study aimed to evaluate the efficacy of antiviral therapy for these patients. METHODS: In total, 102 treatment-naive patients who were HBeAg seropositive with ALT < 2 ULN and had received nucleotide analogs were included, and their clinical data were retrospectively analyzed. RESULTS: After 96-week treatment, 84.3% (n = 86), 26.5% (n = 27) and 20.6% (n = 21) patients achieved virological response, HBeAg seroclearance and HBeAg seroconversion, respectively. Logistic regression analysis revealed that baseline AST (odds ratio [OR] = 1.069, 95% confidence interval [CI] 1.014-1.127, p = 0.014), serum HBV DNA (OR = 0.540, 95% CI 0.309-0.946, p = 0.031) and quantitative HBsAg levels (OR = 0.147, 95% CI 0.036-0.597, p = 0.007) were independent factors for virological response. At baseline, HBsAg < 4.63 log10 IU/ml was identified as a strong predictor for the 96-week virological response, with a concordance rate of 0.902. Moreover, the levels of liver stiffness values (8.30 ± 3.86 vs. 6.17 ± 1.91, p < 0.001) at week 96 had significantly declined compared to baseline. CONCLUSION: Nucleotide analog treatment effectively suppressed HBV DNA in patients with HBeAg-seropositive chronic hepatitis B with ALT < 2 × ULN and greatly improved liver fibrosis. The study also found that HBsAg < 4.63 log10 IU/ml was a strong predictor of the virological response.

Effectiveness of antiviral treatment in HBeAg-negative chronic hepatitis B patients with normal or mildly elevated alanine aminotransferase: a retrospective study.

BACKGROUND: There are inadequate data and no histological evidence regarding the effects of antiviral treatment for hepatitis B e-antigen (HBeAg)-negative chronic hepatitis B (CHB) patients with normal or mildly elevated alanine aminotransferase (ALT). This study investigated the effects of antiviral treatment on these patients. METHODS: We retrospectively analysed the outcomes of antiviral treatment for HBeAg-negative CHB patients with normal or mildly elevated ALT who were treated with nucleoside/nucleotide analogues (NAs) for up to 96 weeks. RESULTS: A total of 128 patients were enrolled; 74 patients had normal ALT and 54 patients had mildly elevated ALT. The total cumulative rates of viral suppression were 64.06%, 81.97%, and 96.39%, at weeks 24, 48, and 96, respectively. The cumulative rates of viral suppression for the normal and mildly elevated ALT groups were 67.85% and 58.97%, 86.39% and 76.31%, and 93.13% and 97.04% at weeks 24, 48, and 96, respectively. The serum HBV DNA levels at week 12 and hepatitis B surface antigen (HBsAg) levels at week 24 were significant predictors of the 96-week virological response. Of the 128 patients, 54 with normal ALT and 33 with mildly elevated ALT underwent FibroScan at baseline. Significant fibrosis (F ≥ 2) was found in 44.4% (n = 24) and 51.5% (n = 17) of the patients in the normal ALT group and mildly elevated ALT group, respectively. Compared with the values at baseline, liver stiffness values significantly decreased at week 48 (8.12 kPa vs. 6.57 kPa; p < 0.001) and week 96 (8.87 kPa vs. 6.43 kPa; p < 0.001), respectively. CONCLUSIONS: HBeAg-negative CHB patients with normal ALT could benefit from antiviral therapy with NAs, similar to patients with mildly elevated ALT. Antiviral treatment is strongly recommended for HBeAg-negative CHB patients with normal ALT. Additionally, significant liver fibrosis is not rare in HBeAg-negative CHB patients with ALT less than two-times the upper limit of normal, and FibroScan should be performed regularly for these patients.

[A randomized controlled study on the efficacy of inhaled nitric oxide in treatment of neonates with meconium aspiration syndrome].

OBJECTIVE: Meconium aspiration syndrome (MAS) is a disease of the term and near-term infant that is associated with considerable respiratory morbidity. The purpose of this study was to investigate effects of inhaled nitric oxide (iNO) in oxygenation and outcome of newborns with MAS. METHODS: Eligible patients diagnosed as severe MAS admitted consecutively to the neonatal intensive care unit (NICU) of Hebei Children's Hospital from January 2004 to June 2006 were included in the study. The patients with an oxygenation index (OI) > or = 15 were randomized in a nonblinded manner to receive either iNO (NO group, n = 21) or no NO (control group, n = 25). Patients with an OI > or = 15 after enrollment were treated with iNO at 15 ppm initially. The response to iNO was assessed according to the increase in arterial PaO(2) and oxygen saturation (SpO(2)) after exposure to the starting concentration for 60 minutes. A response of 10 mm Hg (1 mm Hg = 0.133 kPa) increase in PaO(2) and a 10% increase in SpO(2) was assessed responsive to iNO. All patients were treated in the same neonatal unit and received the same standard therapy throughout the study period. Arterial blood gas tensions, pulmonary arterial pressure and systemic arterial blood pressures were recorded at baseline, 1 hour, and 24 hours in all patients. Methemoglobin levels were obtained at 12 - 24 hours after inhaled NO treatment. Parameters of fraction of inspired oxygen (FiO(2)), OI, mortality, ventilation time, and incidence of intraventricular hemorrhage (IVH, grade III-IV) were recorded. Informed consent was obtained from parents before enrollment. The protocol and the informed consent forms were approved by the ethic committee of the hospital before patient enrollment. RESULTS: There was no significant difference in gestational age, birth weight, gender ratio, age at admission in hours, c-section delivery between the two groups, and no significant difference was found in respiratory mechanics parameters between the two groups at baseline. The duration of iNO was 34.90 +/- 16.41 hours. At the beginning of the treatment, no significant differences were detected in the OI and PAP between the two groups. One hour later, OI and PAP of NO group decreased significantly (OI, F = 35.27, P < 0.01, PAP, F = 24.30, P < 0.01), while in control group the difference was not found until 24 hours (OI, F = 20.16, P < 0.01, PAP, F = 101.22, P < 0.01). There were significant differences in PAP at 1, 24 hours between the two groups (1 h, t = 2.41, P < 0.05; 24 h, t = 3.11, P < 0.01). The methemoglobin levels were normal. Compared to the controls, hospital stay (t = 2.86, P < 0.05), duration of the need for oxygen supplement (t = 2.53, P < 0.05) and ventilation time were shorter (t = 2.41, P < 0.05), whereas mortality (chi(2) = 0.21, P > 0.05) and incidence of IVH (chi(2) = 0.00, P > 0.05) were not significantly different between the groups. CONCLUSIONS: iNO could effectively improve the oxygenation and shorten the ventilation time and hospital stay without augmentation of risk of IVH and pneumothorax in these neonatal patients.