Gastroenterology · Medical Literature
[Clinical study on the efficacy of Wuling capsules combined with nucleos(t)ide analogues in the treatment of low-level viremia patients with chronic hepatitis B].
Abstract
Objective: To comprehensively evaluate the efficacy and safety profile of Wuling capsules combined with nucleos(t)ide analogues in the treatment of low-level viremia in chronic hepatitis B. Methods: A randomized, controlled, multicenter clinical trial was conducted. One hundred patients with low-level viremia in chronic hepatitis B admitted between December 2021 and March 2024 were randomly divided into an experimental group and a control group, with 50 cases in each group. The experimental group received nucleos(t)ide analogues combined with Wuling capsules, while the control group received nucleos(t)ide analogues alone. Of the 100 subjects, 96 in the full analysis set (FAS) (experimental group: 47; control group: 49) were included for statistical analysis. Changes in hepatitis B virus (HBV) DNA levels, serological markers of hepatitis B, liver function parameters, and clinical symptom scores were compared following 180 days of treatment between the two groups. Categorical data were analyzed using the χ2 test, with results expressed as percentages (%). Quantitative data were expressed as mean ± standard deviation (x¯±s) for normally distributed datasets and analyzed using the t-test. The Wilcoxon rank-sum test was used for non-normally distributed data. Results: The HBV DNA seroconversion rate was significantly higher in the experimental group compared to the control group [67.39% (31/46) vs. 48.98% (24/49), χ2=6.65, P<0.05], while HBsAg, HBeAg, and anti-HBc were all lower in the experimental group than the control group (P<0.05) following 180 days of treatment. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin were all significantly higher in the experimental group than in the control group [(24.17±10.07) U/L vs. (30.77±19.00) U/L, (23.70±6.58) U/L vs. (27.66±10.46) U/L, and (12.69±5.72) μmol/L vs. (15.36±5.90) μmol/L, P<0.05]. The normalization rates of ALT, AST, and γ-glutamyl transferase were significantly higher in the treatment group than those in the control group (85.71% vs. 66.67%, 83.33% vs. 60.00%, and 100% vs. 66.67%, P<0.05). The visual analogue scale (VAS) scores and clinical symptom scores were also superior in the treatment group to those in the control group (P<0.01 or P<0.05). The main symptoms of patients, including hypochondriac pain, belching, and anorexia, were significantly improved in the treatment group compared to the control group (P<0.05 or P<0.01). No adverse reactions related to Wuling Capsules were found. Conclusion: Wuling capsules combined with nucleos(t)ide analogues achieved significant efficacy in treating low-level viremia patients with chronic hepatitis B. This treatment significantly improved HBV DNA seroconversion rate, hepatitis B blood markers, liver function levels, and clinical symptoms, with a favorable safety profile.
Clinical relevance
In patients with chronic hepatitis B who have low-level viremia (LLV) on nucleos(t)ide analogue (NA) therapy, does adding Wuling capsules (a traditional Chinese medicine formulation) to NAs improve HBV DNA seroconversion rates, serological markers, liver function, and clinical symptoms compared to NAs alone over 180 days? __SNAPSHOT__ {"studyDesign":"Randomized, controlled, multicenter clinical trial","setting":"Multiple centers in China (specific institutions not reported); enrollment from December 2021 to March 2024","sampleSize":"n=100 randomized (intervention: 50, control: 50); full analysis set (FAS): n=96 (intervention: 47, control: 49); 4 subjects excluded from FAS without detailed attrition reporting","population":"Adult patients with chronic hepatitis B exhibiting low-level viremia (LLV) while on nucleos(t)ide analogue therapy; specific HBV DNA thresholds defining LLV, HBeAg status distribution, fibrosis stage, and prior NA duration not reported in the abstract","intervention":"Nucleos(t)ide analogue(s) (specific agent(s) not reported) combined with Wuling capsules (traditional Chinese herbal medicine formulation) for 180 days","comparator":"Nucleos(t)ide analogue(s) alone for 180 days","primaryOutcome":"HBV DNA seroconversion rate at 180 days; co-endpoints included hepatitis B serological markers (HBsAg, HBeAg, anti-HBc), liver function parameters (ALT, AST, GGT, total bilirubin), and clinical symptom scores including VAS — the single pre-specified primary outcome is not explicitly distinguished from secondary outcomes in the abstract","followUp":"180 days (approximately 6 months); no post-treatment follow-up period reported","fundingSource":"Not reported"}
Key findings
At 180 days, the HBV DNA seroconversion rate was statistically significantly higher in the Wuling capsule combination group compared to the NA-alone group [67.39% (31/46) vs. 48.98% (24/49); χ²=6.65, p<0.05]. The absolute risk difference was approximately 18.4 percentage points (calculated), yielding a number needed to treat (NNT) of approximately 6 (calculated). HBsAg, HBeAg, and anti-HBc levels were all reported to be lower in the experimental group (p<0.05), though specific values and confidence intervals were not reported in the abstract. ALT, AST, and total bilirubin were reported as statistically higher in the experimental group, with total bilirubin values of (12.69±5.72) μmol/L vs. (15.36±5.90) μmol/L (direction of difference as stated in abstract; clinical interpretation unclear given phrasing). Normalization rates for ALT, AST, and γ-glutamyl transferase were significantly higher in the treatment group (85.71% vs. 66.67%, 83.33% vs. 60.00%, and 100% vs. 66.67%, respectively; all p<0.05). VAS scores and composite clinical symptom scores (including hypochondriac pain, belching, and anorexia) were superior in the treatment group (p<0.01 or p<0.05). No adverse reactions attributable to Wuling capsules were identified. Confidence intervals for any outcome were not reported in the abstract.
Practice implications
This study reports statistically significant improvements in HBV DNA seroconversion, hepatitis B serological markers, liver enzyme normalization rates, and patient-reported symptoms with the addition of Wuling capsules to NAs in LLV patients with chronic hepatitis B over 6 months. However, several critical uncertainties limit direct applicability: (1) the specific NAs used are not identified, preventing assessment of whether LLV was due to suboptimal agent selection, adherence issues, or partial viral resistance; (2) the LLV definition threshold (HBV DNA IU/mL range) is not stated in the abstract, limiting patient matching; (3) HBeAg status distribution and fibrosis staging are not reported; (4) the 180-day follow-up is insufficient to assess long-term virological durability, cirrhosis progression, or HCC risk reduction; (5) no confidence intervals are provided for any endpoint; (6) the mechanism by which Wuling capsules augment viral suppression is not established; and (7) only the abstract is available for this review, which precludes evaluation of randomization concealment, blinding methodology, adherence monitoring, and full adverse event reporting. The apparent discrepancy in the reported direction of transaminase differences (AST/ALT described as 'higher in experimental group' alongside higher normalization rates) requires clarification from the full text. These findings are hypothesis-generating and should not change practice without replication in larger, blinded trials with longer follow-up and clearly defined LLV populations. __LIMITATIONS__ Small sample size (n=96 in FAS) with limited statistical power to detect moderate effect sizes or safety signals,Blinding status not reported in the abstract — if open-label, performance and detection bias are likely, particularly for subjective symptom scores,Specific nucleos(t)ide analogue(s) used in each group not identified, introducing potential confounding if distributions differed,LLV definition threshold not specified, reducing reproducibility and generalizability,No confidence intervals reported for any outcome; statistical significance alone does not establish clinical importance,Follow-up limited to 180 days — inadequate to assess sustained virological response, cirrhosis progression, hepatocellular carcinoma risk, or off-treatment durability,Mechanism of action of Wuling capsules on HBV replication not established,Funding source not disclosed — potential for undisclosed conflicts of interest,Only the abstract was available for review; full methods, randomization concealment, ITT vs. FAS analysis rationale, and complete adverse event data cannot be assessed,Generalizability is limited to Chinese clinical settings; ethnic, genetic, and viral genotype differences may affect applicability to other populations,Apparent internal inconsistency in transaminase data reporting (higher values yet higher normalization rates in the same group) requires full-text verification __BOTTOM_LINE_CATEGORY__ promising_but_preliminary __BOTTOM_LINE__ This small multicenter RCT suggests that adding Wuling capsules to nucleos(t)ide analogues may improve HBV DNA seroconversion rates and liver enzyme normalization in chronic hepatitis B patients with low-level viremia over 6 months, with no identified safety signals. However, the study is significantly limited by small sample size, unclear blinding, absent confidence intervals, short follow-up, and incomplete methodological reporting in the available abstract. This intervention should not be adopted into routine clinical practice without replication in larger, rigorously blinded trials with longer follow-up and clearly defined patient populations.