Persistent Low Level of Hepatitis B Virus Promotes Fibrosis Progression During Therapy

Sun, Yameng; Wu, Xiaoning; Zhou, Jialing; Meng, Tongtong; Wang, Bingqiong; Chen, Shuyan; Liu, Hui; Wang, Tailing; Zhao, Xinyan; Wu, Shanshan; Kong, Yuanyuan; Ou, Xiaojuan; Wee, Aileen; Theise, Neil D.; Qiu, Chao; Zhang, Wenhong; Lu, Fengmin; Jia, Jidong; You, Hong

doi:10.1016/j.cgh.2020.03.001

Cited by 61 publications

(65 citation statements)

References 26 publications

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“…However, no specific predictors of response were identified in this study, probably due to the relatively small sample size. Thirdly, since a persistent low level of residual HBV may promote fibrosis progression during therapy, 25 a lower limit of viral load (e.g., 20 IU/mL) may offer an explanation for why three individuals developed worsening of Ishak scores in our study. Last but not least, the presence of a hepatic repair complex 26 among patients couldn't be provided to assess fibrosis regression, although pairing of the 7-stage Ishak fibrosis scoring and quantitative collagen parameter measurement was carried out in the current study.…”

Section: Discussionmentioning

confidence: 80%

Histological Outcome of Fuzheng Huayu plus Entecavir Combination Therapy in Chronic Hepatitis B Patients with Significant Liver Fibrosis

Gui¹,

Zhao²,

Yan³

et al. 2020

Journal of Clinical and Translational Hepatology

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Background and Aims: To evaluate the efficacy of Fuzheng Huayu (FZHY), a Chinese herbal formula, plus entecavir (ETV) in regression of liver fibrosis in chronic hepatitis B (CHB) patients with significant fibrosis/cirrhosis. Methods: The current study was a two-center, randomized, double-blind and placebo-controlled pilot study. Fifty-two currently untreated chronic hepatitis B patients with Ishak fibrosis score $3 points were identified and 1:1 randomized into FZHY plus ETV combination and placebo plus ETV groups. The second liver biopsy was performed after 48-week treatment. Necroinflammatory improvement and regression of fibrosis were assessed. Fine changes in different collagen features in paired liver biopsies were evaluated by dual-photon microscopy for both groups. Results: Forty-nine patients completed the full course of treatment; forty-six of them underwent second liver biopsy (for which twenty-two were in the combination group and twenty-four were in the control group). Compared to those in the control group, patients in the combination group had significantly higher rate of fibrosis regression (82% vs. 54%) (p<0.05). Furthermore, the necroinflammatory improvement was greater in the combination group than in the control group (59% vs. 25%, p<0.05). Among the more than 80 collagen parameters in the dual-photon analysis, 5 decreased significantly in the combination group compared to the control group (p<0.05). However, no significant improvement was detected in either biochemical, virologic or serologic responses between these two groups at week 48. Conclusions: The combination therapy of FZHY plus ETV for 48 weeks resulted in a higher rate of necroinflammatory improvement and fibrosis regression than ETV alone in chronic hepatitis B patients with significant fibrosis/cirrhosis.The clinical trial number is ChiCTR-TRC-11001377.

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Section: Discussionmentioning

confidence: 80%

Histological Outcome of Fuzheng Huayu plus Entecavir Combination Therapy in Chronic Hepatitis B Patients with Significant Liver Fibrosis

Gui¹,

Zhao²,

Yan³

et al. 2020

Journal of Clinical and Translational Hepatology

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“…Although LLV patients may bene t from a low HBV DNA load, LLV is still a risk factor for HCC recurrence [6]. A low level of residual HBV (20-200 IU/mL) may still promote brotic progression in CHB patients during antiviral therapy [16]. For most patients, VR can be achieved after antiviral therapy.…”

Section: Discussionmentioning

confidence: 99%

Correlation between Low-Level Viremia and Hepatitis B-Related Hepatocellular Carcinoma and Recurrence: A Retrospective Study

Sun

Liu²,

Wang³

2021

Preprint

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Background Low-level viremia generally refers to detectable HBV DNA levels lower than 2,000 IU/mL. Studies show that low-level viremia is a risk factor for hepatocellular carcinoma. The aim of this study was to explore the characteristics of low-level viremia patients with hepatitis B-related hepatocellular carcinoma and identify patient prognostic factors following curative hepatectomy. Methods Data from chronic hepatitis B patients with hepatocellular carcinoma receiving curative hepatectomy for the first time in the first hospital of China Medical University were studied. Patients were divided into two groups based on preoperative HBV DNA levels: group 1 (low-level viremia group, HBV DNA < 2,000 IU/mL) and group 2 (HBV DNA ≥ 2,000 IU/mL). Results Of the 212 patients, 104 patients were in group 1 and 108 patients were in group 2. There was a lower proportion of patients with HBsAg levels > 250 IU/mL in group 1 than in group 2 (71.2% vs. 86.1%, P < 0.01). The proportion of patients with a tumor diameter < 5 cm was 67.3% in group 1 and 37.0% in group 2 (P < 0.000). Tumor recurrence was 40.4% (42) in group 1 and 54.6% (59) in group 2 (P < 0.05). Median recurrence-free survival was 30.1 months in group 1 and 17.6 months in group 2 (P < 0.01). Multivariate analysis showed that a tumor diameter > 5 cm (hazard ratio [HR] = 1.819, 95% confidence interval [CI] 1.193–2.775, P = 0.005), intrahepatic metastasis (HR = 1.916, 95% CI 1.077–3.407, P = 0.027), and an HBV DNA level > 100 IU/mL (HR = 2.943, 95% CI 1.916–4.520, P < 0.000) were independent prognostic factors associated with an increased risk of hepatocellular carcinoma recurrence. Conclusion Preoperative low-level viremia was related to a long tumor recurrence interval and post-operative virologic response was associated with a lower risk of hepatocellular carcinoma recurrence.

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“…In an analysis of 239 patients with paired liver biopsy, LLV was more frequently observed for patients with fibrosis progression (50%) than in patients with fibrosis regression (19%) or indeterminate fibrosis (26%) (P =0.015), suggesting that LLV may still promote fibrosis progression. 10 In our previous study, we observed a higher risk of HCC in cirrhotic patients with LLV than with MVR. 5 In a randomized trial conducted in Korea, patients with CHB with detectable HBV DNA (>60 IU/mL) treated with 0.5 mg of entecavir for >12 months showed higher VR (HBV DNA <20 IU/mL) after switched to tenofovir (55%) than in patients that continued with entecavir (20%, P=0.022).…”

mentioning

confidence: 84%

“…In contrast to findings from Lee et al [ 8 ], some studies suggest that changing instead of continuing with the current treatment may be better approach. In an analysis of 239 patients with paired liver biopsy, LLV was more frequently observed for patients with fibrosis progression (50%) than in patients with fibrosis regression (19%) or indeterminate fibrosis (26%) (P=0.015), suggesting that LLV may still promote fibrosis progression [ 10 ]. In our previous study, we observed a higher risk of HCC in cirrhotic patients with LLV than with MVR [ 5 ].…”

mentioning

confidence: 99%

Low-level viremia in patients undergoing antiviral therapy: Does it indicate time for a change?

Kim

Sinn

2020

Clin Mol Hepatol

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Persistent Low Level of Hepatitis B Virus Promotes Fibrosis Progression During Therapy

Cited by 61 publications

References 26 publications

Histological Outcome of Fuzheng Huayu plus Entecavir Combination Therapy in Chronic Hepatitis B Patients with Significant Liver Fibrosis

Histological Outcome of Fuzheng Huayu plus Entecavir Combination Therapy in Chronic Hepatitis B Patients with Significant Liver Fibrosis

Correlation between Low-Level Viremia and Hepatitis B-Related Hepatocellular Carcinoma and Recurrence: A Retrospective Study

Low-level viremia in patients undergoing antiviral therapy: Does it indicate time for a change?

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