HBsAg seroclearance reduces the risk of late recurrence in HBV-related HCC

Jin, Bao; Du, Shunda; Yang, Huayu

doi:10.1016/j.jhep.2022.06.030

Cited by 5 publications

(4 citation statements)

References 8 publications

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“…In patients with HCC and CHB, nivolumab treatment decreases HBsAg levels [ 12 , 32 ]. HBsAg seroclearance has been previously suggested to be associated with a lower risk of late recurrence in HBV-related HCC [ 13 ]. Interrupting the PD1 signaling pathway can reverse T cell exhaustion, leading to the inhibition of viral infection and the proliferation of cancer cells [ 33 , 34 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…Anti-PD1 therapy causes a decline in or seroclearance of hepatitis B surface antigen (HBsAg) in patients with CHB [ 12 ]. HBsAg seroclearance is associated with a low risk of hepatitis B virus (HBV)-related HCC [ 13 ]. Anti-PD1 therapies have been approved for the treatment of advanced HCC, melanoma, metastatic non-small-cell lung cancer, and other advanced malignancies [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

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Sequential Therapy with Ropeginterferon Alfa-2b and Anti-Programmed Cell Death 1 Antibody for Inhibiting the Recurrence of Hepatitis B-Related Hepatocellular Carcinoma: From Animal Modeling to Phase I Clinical Results

Qin,

Wu,

et al. 2023

IJMS

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Hepatocellular carcinoma (HCC) usually recurs after curative surgical resection. Currently, no approved adjuvant therapy has been shown to reduce HCC recurrence rates. In this study, the in vivo effect of sequential combination treatment with recombinant mouse interferon-alpha (rmIFN-α) and an anti-mouse-PD1 antibody on hepatitis B virus (HBV) clearance in mice was evaluated. A Phase I clinical trial was then conducted to assess the safety, tolerability, and inhibitory activity of sequential therapy with ropeginterferon alfa-2b and nivolumab in patients with HCC recurrence who underwent curative surgery for HBV-related HCC. The animal modeling study showed that HBV suppression was significantly greater with the rmIFN-α and anti-PD1 sequential combination treatment in comparison with sole treatment with rmIFN-α or anti-PD1. In the Phase I study, eleven patients completed the sequential therapy with ropeginterferon alfa-2b every two weeks for six doses at 450 µg, followed by three doses of nivolumab every two weeks up to 0.75 mg/kg. A notable decrease in or clearance of HBV surface antigen was observed in two patients. The dose-limiting toxicity of grade 3 alanine transaminase and aspartate aminotransferase increases was observed in one patient. The maximum tolerated dose was then determined. To date, no HCC recurrence has been observed. The treatment modality was well tolerated. These data support the further clinical development of sequential combination therapy as a post-surgery prophylactic measure against the recurrence of HBV-related HCC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sequential Therapy with Ropeginterferon Alfa-2b and Anti-Programmed Cell Death 1 Antibody for Inhibiting the Recurrence of Hepatitis B-Related Hepatocellular Carcinoma: From Animal Modeling to Phase I Clinical Results

Qin,

Wu,

et al. 2023

IJMS

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“…Many scholars have studied the risk factors for and recurrence patterns of HCC. Male sex, a high degree of fibrosis, HBV load, tumor diameter, and vascular invasion are positively correlated with HCC recurrence[ 15 - 18 ]. The recurrence pattern of HCC is often divided into early recurrence and late recurrence[ 19 , 20 ].…”

Section: Different Recurrence Patterns and Characteristics Of Recurre...mentioning

confidence: 99%

Combining local regional therapy and systemic therapy: Expected changes in the treatment landscape of recurrent hepatocellular carcinoma

Liang¹,

Bai²,

Ha³

et al. 2023

World J Gastrointest Oncol

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Improvements in early screening, new diagnostic techniques, and surgical treatment have led to continuous downward trends in hepatocellular carcinoma (HCC) morbidity and mortality rates. However, high recurrence and refractory cancer after hepatectomy remain important factors affecting the long-term prognosis of HCC. The clinical characteristics and prognosis of recurrent HCC are heterogeneous, and guidelines on treatment strategies for recurrent HCC are lacking. Therapies such as surgical resection, radiofrequency ablation, and transhepatic arterial chemoembolization are effective for tumors confined to the liver, and targeted therapy is a very important treatment for unresectable recurrent HCC with systemic metastasis. With the deepening of the understanding of the immune microenvironment of HCC, blocking immune checkpoints to enhance the antitumor immune response has become a new direction for the treatment of HCC. In addition, improvements in the tumor immune microenvironment caused by local treatment may provide an opportunity to improve the therapeutic effect of HCC treatment. Ongoing and future clinical trial data of combined therapy may develop the new treatment scheme for recurrent HCC. This paper reviews the pattern of recurrent HCC and the characteristics of the immune microenvironment, demonstrates the basis for combining local treatment and systemic treatment, and reports current evidence to better understand current progress and future approaches in the treatment of recurrent HCC.

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“…Regarding the latter it is clear that we have to define virological end points, but in the mean time we should not forget about clinical end-points (fibrosis, cirrhosis, HCC occurrences); an improved combination therapy (featuring a NA + a CpAM for instance), in terms of virosuppression (even absence of HB-sAg seroclearance), may prove useful to reduce further the incidence of HCC in patients, even if it is not a finite duration regimen; in this respect one could hope that a CpAM or a RNAi will make it to the clinic to increase the number of types of molecule in our arsenal. An increased rate of and durable HBsAg seroclearance (ideally associated with an anti-HBs seroconversion and recovery of T/B cell functions; this latter recovery of immune functions may require an immunological "kick") remain a major objective, as HBsAg loss is clearly associated with a decreased (yet not annihilation) of HCC incidence (Diao et al, 2022b;Jin et al, 2022;Yang et al, 2022;Yip et al, 2022); but do we need to decide that such an HBsAg seroclearance has to be obtained in no more than 48 weeks? Surely not!…”

Section: Conclusion and Final Considerationsmentioning

confidence: 99%

Therapies against chronic hepatitis B infections: The times they are a-changin’, but the changing is slow!

Durantel

2023

Antiviral Research

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HBsAg seroclearance reduces the risk of late recurrence in HBV-related HCC

Cited by 5 publications

References 8 publications

Sequential Therapy with Ropeginterferon Alfa-2b and Anti-Programmed Cell Death 1 Antibody for Inhibiting the Recurrence of Hepatitis B-Related Hepatocellular Carcinoma: From Animal Modeling to Phase I Clinical Results

Sequential Therapy with Ropeginterferon Alfa-2b and Anti-Programmed Cell Death 1 Antibody for Inhibiting the Recurrence of Hepatitis B-Related Hepatocellular Carcinoma: From Animal Modeling to Phase I Clinical Results

Combining local regional therapy and systemic therapy: Expected changes in the treatment landscape of recurrent hepatocellular carcinoma

Therapies against chronic hepatitis B infections: The times they are a-changin’, but the changing is slow!

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