Spontaneous Seroclearance of Hepatitis B Surface Antigen and Risk of Hepatocellular Carcinoma

Song, Ci; Zhu, Jian; Ge, Zijun; Yu, Chengxiao; Tian, Ting; Wang, Hui; Han, Jing; Shen, Hongbing; Dai, Juncheng; Lu, Jianguo; Hu, Zhibin

doi:10.1016/j.cgh.2018.08.019

Cited by 16 publications

(13 citation statements)

References 8 publications

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“…A population-based cohort study showed that the cumulative HCC incidence in patients who achieved HBsAg loss is significantly lower than that in CHB patients, yet is still slightly higher than that in HBsAg-negative individuals. 42 43,44 Immunologically, the proportion of patients with HBsAg seroconversion, that is, the detection of anti-HBs together with HBsAg seroclearance, was comparable between patients who had spontaneous and NA-induced HBsAg loss, which is in line with previous studies. 41,45 Anti-HBs positivity appears to protect against HBsAg seroreversion, that is, reappearance of serum HBsAg after HBsAg loss, in patients with spontaneous HBsAg seroclearance.…”

Section: Discussionsupporting

confidence: 89%

“…While most CHB patients have a much improved prognosis after HBsAg seroclearance, a low yet definite risk of HCC persists. A population‐based cohort study showed that the cumulative HCC incidence in patients who achieved HBsAg loss is significantly lower than that in CHB patients, yet is still slightly higher than that in HBsAg‐negative individuals 42 . Clinically, our findings showed that advanced age, male gender, presence of cirrhosis and DM, low serum albumin and high total bilirubin were associated with an increased risk of HCC after HBsAg seroclearance.…”

Section: Discussionmentioning

confidence: 48%

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Similarly low risk of hepatocellular carcinoma after either spontaneous or nucleos(t)ide analogue‐induced hepatitis B surface antigen loss

Yip

Wong

Tse

et al. 2020

Aliment Pharmacol Ther

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SummaryBackgroundIt is unknown whether patients with chronic hepatitis B (CHB) who achieved hepatitis B surface antigen (HBsAg) seroclearance spontaneously or following anti‐viral therapy have similar clinical outcomes.AimTo compare the risk of hepatocellular carcinoma (HCC) in patients with CHB who either cleared HBsAg spontaneously or following anti‐viral therapyMethodsAdult CHB‐monoinfected patients who cleared HBsAg between January 2000 and March 2019 were identified from a territory‐wide database in Hong Kong. Patients with liver transplantation and/or HCC before HBsAg loss were excluded. Patients’ demographics, comorbidities, anti‐viral treatment, laboratory parameters and HCC development were analysed.ResultsOf 7,124 identified patients with CHB who cleared HBsAg, mean age was 58.1 ± 13.8 years; 4,340 (60.9%) were male; 451 (6.3%) had cirrhosis; 5,917 (83.1%) and 1,207 (16.9%) had spontaneous and nucleos(t)ide analogue (NA)‐induced HBsAg seroclearance, respectively. Most patients had normal liver function at HBsAg loss. Patients with NA‐induced HBsAg seroclearance were younger, and more likely to be male and cirrhotic than patients with spontaneous HBsAg loss. At a median (interquartile range) follow‐up of 4.3 (2.2‐7.6) years, 97 (1.6%) and 16 (1.3%) patients with spontaneous and NA‐induced HBsAg loss developed HCC, respectively. Patients who achieved NA‐induced HBsAg loss had comparable HCC risk as those with spontaneous HBsAg loss (adjusted subdistribution hazard ratio 0.75, 95% CI 0.43‐1.32, P = 0.323). The results remained robust in propensity score weighting and matching analyses.ConclusionThe HCC risk was similarly low after either spontaneous or NA‐induced HBsAg seroclearance in a territory‐wide cohort of patients with CHB who had cleared HBsAg.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 48%

Similarly low risk of hepatocellular carcinoma after either spontaneous or nucleos(t)ide analogue‐induced hepatitis B surface antigen loss

Yip

Wong

Tse

et al. 2020

Aliment Pharmacol Ther

View full text Add to dashboard Cite

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“…However, multiple recent studies have definitively demonstrated that HBsAg clearance induced by peg-IFNα was durable during long-term follow-up and the incidence of HCC was extremely low (<1.5%) in HBV clinically cured patients. [27][28][29][30][31] Furthermore, even some patients were not clinically cured, a full course of peg-IFNα treatment also induced favourable outcomes during long-term follow-up, including HBsAg clearance and no disease progression. 32 The long-term effectiveness data collection of this study is ongoing, and the subsequent results will also be reported in the future.…”

Section: Study Limitationsmentioning

confidence: 99%

Efficacy and safety of peginterferon alpha monotherapy in Chinese inactive chronic hepatitis B virus carriers

Liu

et al. 2021

Liver International

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Background & Aims The effectiveness and safety of peginterferon alpha (peg‐IFN‐α) monotherapy in inactive hepatitis B virus (HBV) carriers (IHCs) have not been fully evaluated. Methods This observational study prospectively enrolled 298 IHCs in China from 2015 to 2019. Participants were given the right to choose to either receive peg‐IFN‐α monotherapy (treatment group, n = 142) or be monitored without treatment (control group, n = 156) according to their wishes. The scheduled treatment duration was 48 weeks. All participants were followed up to 72 weeks. The main efficacy endpoint was hepatitis B surface antigen (HBsAg) clearance at 72 weeks. Results Baseline characteristics were similar between both groups. At 72 weeks, intention‐to‐treat analysis showed that the rates of HBsAg clearance and seroconversion of the treatment group were 47.9% (68/142) and 36.6% (52/142), respectively, which were significantly higher than the HBsAg clearance rate of 1.9% (3/156) and the seroconversion rate of 0.6% (1/156) in the control group (both P < .001). Baseline HBV DNA < 20 IU/mL, lower HBsAg levels at baseline, 12 and 24 weeks, alanine aminotransferase elevation at 12 weeks, and greater HBsAg reduction from baseline to 12 and 24 weeks were independent predictors of HBsAg clearance. Generally, the therapy was well tolerated. Only five participants discontinued therapy as a result of peg‐IFNα‐related adverse events. Conclusions Peg‐IFN‐α monotherapy results in high rates of HBsAg clearance and seroconversion and the treatment is safe for IHCs.

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“…The baseline characteristics are provided in Table 1. Among the 57 studies, 2 were prospective population‐based studies, 11,12 22 were prospective 8,9,13‐32 and 33 were retrospective cohort studies 7,33‐64 . Overall, there were a total of 258 744 HBsAg positive patients of whom 63 270 (24.4%) lost HBsAg.…”

Section: Resultsmentioning

confidence: 99%

Systematic review with meta‐analysis: the impact of functional cure on clinical outcomes in patients with chronic hepatitis B

Vittal

Sharma

et al. 2021

Aliment Pharmacol Ther

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Summary Background Although hepatitis B surface antigen (HBsAg) loss is considered the ideal therapeutic endpoint for the treatment of chronic hepatitis B virus (HBV) infection, its impact on clinical outcomes remains uncertain. Aim To assess the impact of HBsAg loss on clinical outcomes following spontaneous and treatment‐related HBsAg loss. Methods We searched PUBMED, Embase, the Cochrane library, and published abstracts through to May 2021 for studies that reported HBsAg loss, had >1 year of follow‐up and reported at least one clinical outcome in adults with chronic HBV infection. Results We identified 57 studies (258 744 HBsAg‐positive patients, 63 270 with HBsAg loss). Based on 24 studies including 160 598 patients with and without HBsAg loss, HBsAg loss was associated with a non‐significant 23% relative risk reduction of developing hepatocellular carcinoma (HCC) compared to those who remained HBsAg‐positive (RR = 0.77; 95% CI: 0.38‐1.57). In subgroup meta‐analysis of 10 studies, treatment‐related HBsAg loss was associated with a non‐significant higher pooled proportion of HCC (0.94%) compared to spontaneous HBsAg loss (0.45%). HCC development after HBsAg loss was significantly higher in males, those with underlying cirrhosis, and those with a family history of HCC. HBsAg loss was associated with lower pooled proportions of incident cirrhosis, hepatic decompensation, overall and liver‐related mortality compared to no HBsAg loss. Substantial heterogeneity was noted across studies for all outcomes. Conclusion HBsAg loss is associated with a reduced risk of clinical outcomes. However, several shortcomings in the published studies prevent a more definitive conclusion on the potential benefits of HBsAg loss.

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Spontaneous Seroclearance of Hepatitis B Surface Antigen and Risk of Hepatocellular Carcinoma

Cited by 16 publications

References 8 publications

Similarly low risk of hepatocellular carcinoma after either spontaneous or nucleos(t)ide analogue‐induced hepatitis B surface antigen loss

Similarly low risk of hepatocellular carcinoma after either spontaneous or nucleos(t)ide analogue‐induced hepatitis B surface antigen loss

Efficacy and safety of peginterferon alpha monotherapy in Chinese inactive chronic hepatitis B virus carriers

Systematic review with meta‐analysis: the impact of functional cure on clinical outcomes in patients with chronic hepatitis B

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