The Yin and the Yang of Treatment for Chronic Hepatitis B—When to Start, When to Stop Nucleos(t)ide Analogue Therapy
Abstract
:1. Introduction
2. “Treatment for All”—A Public Health Approach to CHB
3. “The Stop Strategy”—A Personalised Approach to NA Therapy for HBeAg-Negative CHB
4. Future Directions
Author Contributions
Funding
Conflicts of Interest
References
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Guidelines | Decision to Treat |
---|---|
APASL 2015 [7] | (i) ALT > 2 × ULN and HBV DNA > 2000 IU/mL or (ii) Moderate to severe hepatic inflammation or significant fibrosis a |
EASL 2017 [5] | (i) ALT > ULN and HBV DNA > 2000 IU/mL or (ii) Moderate liver necroinflammation or fibrosisor or (iii) ≥30 y, HBeAg positive, normal ALT, HBV DNA > 20,000 IU/mL, regardless of severity of liver histology (immune tolerant) |
AASLD 2018 [4] | (i) ALT > 2 × ULN b and HBV DNA > 2000 IU/mL or (ii) Moderate to severe necroinflammation or fibrosis a or (iii) ≥40 y, HBeAg positive, normal ALT, HBV DNA > 1,000,000 IU/mL, liver biopsy specimen showing significant necroinflammation or fibrosis (immune tolerant) |
EASL 2017 [5] | AASLD 2018 [4] | APASL 2015 [7] |
---|---|---|
HBsAg loss | HBsAg loss | HBsAg loss |
“Discontinuation of NAs in selected non-cirrhotic HBeAg-negative patients who have achieved long-term (3 years) virological suppression under NA(s) may be considered if close post-NA monitoring can be guaranteed” | - | “In patients without liver cirrhosis…treatment can be withdrawn after treatment for at least 2 years with undetectable HBV DNA documented on three separate occasions, 6 months apart” |
Reference | n | Median F/U (m) | % Clinical Relapse (EOF) | % HBsAg Loss (EOF) | % NA Restart (EOF) | Notes Prospective/Retrospective % Asian/Caucasian HBeAg + Included Cirrhosis Included Safety If Significant Events |
---|---|---|---|---|---|---|
Berg et al. [43] | 21 | 33 | 58 1,a | 19 | 38; Re-started for CR | RCT 4.8% Asian/95.2% Caucasian |
Cao et al. [55] | 22 | 21 | 53 a | 0 | NR | HBeAg ± cohort |
Chen et al. [48] | 169 | 20 | 52 1,a | 7.7 | 39; Re-start criteria NR | Retrospective Study HBeAg ± and cirrhosis 2% HCC (EOF) 3% Hepatic Decompensation (EOF) 0.4% OLT (EOF) |
Ge et al. [56] | 204 | 24 | NR | 0.5 | NR | Retrospective Study |
Ha et al. [57] | 145 | 16 | NR | 8.3 | 61; Re-start criteria NR | |
Hadziyannis [14] | 33 | 66 | 76 1,b | 39 | 45; Re-started for CR | 100% Caucasian Adefovir only included |
He et al. [58] | 66 | 17 | NR | 0 | NR | Retrospective Study |
Hsu et al. [59] | 133 | 13 | 39 1,a | 0.75 | NR | 3% hepatic decompensation in non-cirrhotic cohort |
Hung et al. [60] | 73 | 67 | NR | 27 | 52; Re-started for VR | Only Cirrhosis included |
Jeng et al. [45] | 95 | 12 | 45 1,a | 0 | 36; Re-start criteria NR | Retrospective-Prospective Study Cirrhosis included |
Jung et al. [61] | 68 | 30 | 28 1,a | 0 | 40; Re-start criteria NR | Cirrhosis included |
Kang et al. [62] | 60 | 67 | 10 2,a | 18.3 | 25; Re-start criteria NR | HBeAg ± and cirrhosis 5% HCC (EOF) |
Kim et al. [63] | 45 | 26 | 53 at 12 m* (EOF NR) 1,a | 0 | NR | Cirrhosis included |
Lee et al. [64] | 37 | 22 | 35 2,b | 5 | NR | HBeAg ± cohort |
Liu et al. [65] | 61 | 15 | NR | 10.2 | 61; Re-start criteria NR | |
Pan et al. [66] | 30 | 115 | 77 b | 9.3 | NR | Retrospective-Prospective Study and HBeAg ± cohort |
Patwardhan et al. [67] | 33 | 36 | 48 1,b | 0 | 48; Re-start criteria NR | Retrospective Study Ethnicity NR |
Peng et al. [68] | 21 | 12 | 33 1,a | 1.5 | 27; Re-started for CR | HBeAg ± cohort |
Seto et al. [46] | 184 | 12 | NR | 0 | 91; Re-started for VR | Cirrhosis included |
Sohn et al. [69] ‡ | 54 | 22 | NR | 0 | 67; Re-started for VR | Retrospective Study HBeAg ± and cirrhosis NA restarted if HBV Detectable |
Wang et al. [70] | 46 | 25 | 59 1,a | 0 | 58; Re-start criteria NR | HBeAg ± cohort |
Yao et al. [16] | 119 | 60 | 27.6 1,a | 54.9 | 24; Re-started for CR | Cirrhosis included |
Chen et al. [54] | 104 | 13 | 49 1,a | 6 | 33; Re-started for CR | Retrospective Study HBeAg ± cohort 2% Hepatic Decompensation (EOF) |
Chen et al. [71] | 263 | 12 | 53 1,a | 13 | 42; Re-start criteria NR | HBeAg ± cohort 0.5% HCC (EOF) |
Jeng et al. [15] | 691 | 36 | 61 1,a | 6 | 41; (Re-start Criteria: ‘discretion of the treating physician’) | Retrospective-Prospective Study; Cirrhosis included 691 HBeAg − patients (0 HBeAg + patients) Hepatic Decompensation Annual Incidence Rates: 0% in non-cirrhosis and 2.95% in cirrhosis; Mortality rates: 1% died in Cirrhosis and 0% in non-cirrhosis; HCC Annual Incidence Rates: 0.083% in non-cirrhotic and 1.52% for cirrhosis |
Kuo et al. [50] | 353 | 25 | 54 1,a | 8 | 44; Re-started for CR | Retrospective-Prospective Study; HBeAg ± cohort 1.16% HCC (EOF) 2.7% Hepatic Decompensation (EOF) |
Liem et al. [72] | 41 | 17 | 73 1,b | 2.2 | 38; Re-start criteria NR | RCT 98% Asian/2% Caucasian HBeAg ± cohort |
Liu et al. [73] | 85 | 60 | NR | 14 | NR | HBeAg ± cohort 1.6% HCC (EOF) |
Ma et al. [74] | 375 | 12 | 55 1,a | 1 | 55; Re-started for CR | HBeAg ± cohort 19% Hepatic Decompensation (EOF) 0.2% Mortality rate (EOF) |
Papatheodoridis et al. [75] | 130 | 15 | 55 3,b | 0 | 33; Re-started for CR | 41.5% Asian/58.5% Caucasian Definition of Virological Relapse (HBV DNA > 60 IU/mL) 0.8% HCC (EOF) |
Papatheodoridis et al. [76] | 57 | 18 | 43 3,b | 21 | 28; Re-started for CR | Ethnicity NR Definition of Virological Relapse (HBV DNA > 60 IU/mL) 1.8% HCC (EOF |
Su et al. [77] | 72 | 34 | 45 1,a | 0 | 40; Re-started for CR | HBeAg ± cohort |
Chi et al. [78] | 59 | 19 | NR | 38 | 38; Re-started for VR | 79.7% Asian/20.3% Caucasian HBeAg ± cohort and cirrhosis included Hepatic Decompensation: 0% in non-cirrhosis and 2% in cirrhosis |
Hsu et al. [79] | 124 | 17 | 25.8 1,a | 6 | NR | HBeAg ± cohort |
Lee et al. [80] | 44 | 21 | 32 1,a | 0 | 42; Re-start criteria NR | HBeAg ± cohort and cirrhosis included |
Lee et al. [81] | 93 | 12 | 41.9 1,a | 0 | NR | Retrospective Study |
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Hall, S.; Howell, J.; Visvanathan, K.; Thompson, A. The Yin and the Yang of Treatment for Chronic Hepatitis B—When to Start, When to Stop Nucleos(t)ide Analogue Therapy. Viruses 2020, 12, 934. https://doi.org/10.3390/v12090934
Hall S, Howell J, Visvanathan K, Thompson A. The Yin and the Yang of Treatment for Chronic Hepatitis B—When to Start, When to Stop Nucleos(t)ide Analogue Therapy. Viruses. 2020; 12(9):934. https://doi.org/10.3390/v12090934
Chicago/Turabian StyleHall, Samuel, Jessica Howell, Kumar Visvanathan, and Alexander Thompson. 2020. "The Yin and the Yang of Treatment for Chronic Hepatitis B—When to Start, When to Stop Nucleos(t)ide Analogue Therapy" Viruses 12, no. 9: 934. https://doi.org/10.3390/v12090934
APA StyleHall, S., Howell, J., Visvanathan, K., & Thompson, A. (2020). The Yin and the Yang of Treatment for Chronic Hepatitis B—When to Start, When to Stop Nucleos(t)ide Analogue Therapy. Viruses, 12(9), 934. https://doi.org/10.3390/v12090934