Immunoglobulin A and complement C4 are involved in the progression of liver fibrosis in patients with chronic hepatitis B.

OBJECTIVE: To explore the relationship between immunoglobulin A (IgA), complement C4, and liver fibrosis (L.F.) progression (LFP) in patients with chronic hepatitis B (CHB). METHODS: This is a retrospective cohort study of CHB patients who received liver biopsies. Relevant data, including demographics, clinical serum markers, and immunological results obtained during liver biopsies, were collected and analyzed to assess and verify the relationship between IgA, C4, and LFP. RESULTS: This study included 1,938 CHB patients, of whom 132 received two liver biopsies (group 1). Thirty (22.7%) of these patients were diagnosed with LFP (increase in L.F. stage (Scheuer score F ≥ 1)). IgA (C-IgA) and C4 (C-C4) change values between the first and second biopsies were independent risk factors for LFP. IgA levels increased, and C4 levels decreased during the second liver puncture. The remaining 1,806 patients received one liver puncture (group 2). They were divided into the following subgroups: A (F ≤ 1), B (1 < F ≤ 3), and C (F > 3) to verify whether the same trend was observed by cross-sectional study. IgA levels were highest, and C4 levels were lowest in group C (IgA: C > B > A, p < 0.05; C4: C < B < A, p < 0.05). CONCLUSIONS: The findings of this study suggest that serum IgA and C4 levels are independent risk factors for LFP that could serve as future targets for L.F. management and treatment.

Efficacy and safety of AnluoHuaxian pills on chronic hepatitis B with normal or minimally elevated alanine transaminase and early liver fibrosis: A randomized controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: The AnluoHuaxian pill (AHP) is a widely used patented medicine for chronic hepatitis B (CHB) patients with advanced fibrosis or cirrhosis that has been used in China for more than 15 years. However, data are lacking on whether monotherapy with AHP can be effective in CHB patients with alanine aminotransferase (ALT) levels less than 2 times the upper limit of normal (ALT<2ULN) and early liver fibrosis (F ≤ 2). AIM OF THE STUDY: We aimed to investigate whether monotherapy with AHP improves liver histology in these patients. MATERIALS AND METHODS: In this double-blind, randomized, placebo-controlled trial, 270 CHB patients with ALT<2ULN and F ≤ 2 were treated in 12 hospitals in China. The patients were randomly assigned to an intervention (AHP) group and a placebo group at a ratio of 2:1. Of these 270 enrolled patients, 147 had paired liver biopsies. The primary end point was histological change after 48 weeks of treatment. RESULTS: Per-protocol analysis revealed that the rate of histologic improvement in liver fibrosis patients in the AHP group was significantly higher than that in the placebo group (37.7% vs. 19.5%, P = 0.035) after 48 weeks of treatment, which was consistent with results from intention-to-treat and sensitivity analyses. Moreover, after adjusting for baseline characteristics, AHP was superior to placebo with respect to improving liver fibrosis (odds ratio [OR] = 2.58, 95% confidence interval [CI]: (1.01, 6.63),P = 0.049) and liver histology (OR = 3.62, 95% CI: (1.42, 9.20),P = 0.007). In noninvasive measurement of liver fibrosis (FibroScan®), the level of liver stiffness measurement (LSM) had decreased significantly at 48 weeks (5.1 kPa) compared with that at baseline (5.7 kPa) (P = 0.008) in the AHP group, whereas it did not decrease significantly in the placebo group. Cirrhosis developed in one patient in the placebo group but in no patients in the AHP group. No serious side effects occurred in the AHP-treated patients. CONCLUSIONS: Treatment of CHB patients who had ALT<2ULN and F ≤ 2 with the traditional Chinese medicine AHP for 48 weeks improves liver fibrosis. However, due to the short duration of treatment and the limited sample size of liver pathology, the long-term benefits of AHP in reducing fibrosis and the risk of cirrhosis and hepatocellular carcinoma in these patients need to be further studied in the future.

Differences in MicroRNA Expression in Chronic Hepatitis B Patients with Early Liver Fibrosis Based on Traditional Chinese Medicine Syndromes.

The aim of this study was to determine if microRNA (miRNA) expression is different among chronic hepatitis B (CHB) patients with early liver fibrosis classified according to traditional Chinese medicine (TCM) syndromes. Eighteen CHB-fibrosis patients and 12 CHB patients without fibrosis were enrolled. The CHB-fibrosis group included 9 patients with the TCM syndrome of Ganyu Pixu Xueyu (GYPXXY), characterized by liver stagnation, spleen deficiency, and blood stasis, and 9 patients with the TCM syndrome of Qixu Xueyu (QXXY), characterized by deficiency of qi, blood, and blood stasis. Agilent miRNA microarray was performed first in liver specimens to determine whether miRNA expression is different in patients with these two TCM syndromes of CHB-fibrosis. Gene Ontology (GO) analysis and KEGG analysis were applied to determine the roles of the differentially expressed miRNAs. QRT-PCR was performed to validate the Agilent miRNA microarray results. Compared with GYPXXY patients, 6 differentially expressed miRNAs were upregulated (miR-144-5p, miR-18a-5p, miR-148b-3p, miR-654-3p, miR-139-3p, and miR-24-1-5p) and 1 was downregulated (miR-6834-3p) in QXXY patients. According to qRT-PCR data, miR-144-5p and miR-654-3p were confirmed as upregulated in CHB-liver fibrosis patients compared to CHB patients without fibrosis, whereas the other 4 miRNAs were not significantly different. More importantly, miR-654-3p was confirmed to be significantly upregulated in QXXY patients compared with values in GYPXXY patients, whereas no significant difference was found in miR-144-5p. Moreover, the pathways of central carbon metabolism in cancer and cell cycle related to miR-654-3p and the target genes of PTEN and ATM were found to be different between QXXY patients and GYPXXY patients. These results indicate that there are different miRNAs, pathways, and target genes between QXXY patients and GYPXXY patients. However, due to the limited sample, whether miR-654-3p and the target genes PTEN and ATM could be molecular markers to differentiate TCM syndromes could not be established.

Histological improvement in chronic hepatitis B patients treated with bicyclol: real world experience.

BACKGROUND: Bicyclol, the most commonly-used liver hepatoprotective drug in China, is often selected to control disease progression in CHB patients who refuse anti-viral treatment. However, data on histological changes after bicyclol treatment in these patients are scarce. Therefore, this study has been conducted to find out whether bicyclol has good benefits of histological improvement in CHB patients who refuse anti-viral agents. METHODS: The demographic, clinical and pathological data were collected from CHB patients who received bicyclol from January 2010 to June 2016. Improvement in liver inflammation or fibrosis is defined as at least one-grade or one-stage decrease as measured by the Scheuer scoring system. Thirty patients treated with ETV for 48 weeks were chosen as a control group to compare the histological improvement between bicyclol and entecavir (ETV) after 48-week treatment. RESULTS: A total of 123 patients with CHB treated with bicyclol were included in this study. Paired liver biopsies were performed in 70 patients. Inter-biopsy interval was 17.44 ± 8.90 months (12-60 months). As shown by facts, 41.4% patients achieved liver inflammation improvement, while only 10.0% patients showed liver inflammation progression after bicyclol treatment. In regarding to liver fibrosis, as shown by facts, 28.6% patients achieved fibrosis improvement. More importantly, It was found that the proportions of patients with liver inflammation and fibrosis improvement were both not significantly lower than those in ETV group (53.3% vs 63.3 and 36.7% vs 43.4%). Most of patients (82.4%) with elevated baseline ALT became normal after bicyclol treatment. More importantly, as shown by the multi-variate analysis, the treatment course of bicyclol was an independent factor for liver inflammation improvement. With the HBeAg status adjusted, ALT and HBV-DNA quantity, the odds ratio (95% confidence interval) of patients with ≥48-week treatment was 5.756 (1.893,17.500) when compared with patients via < 48-week treatment. CONCLUSION: Bicyclol can improve liver inflammation and the ALT normalization rate of CHB patients, especially when the treatment course is prolonged. This has confirmed that bicyclol could control hepatitis activity, which might be a good choice for CHB patients who refuse anti-viral treatments.