Hepatocellular carcinoma after treatment cessation in non‐cirrhotic HBeAg‐negative chronic hepatitis B: A multicentre cohort study

Abstract

Background and Aims: Scarce data exist on the effect of nucleos(t)ide analogue (NA) discontinuation on hepatocellular carcinoma (HCC) risk in HBeAg-negative chronic hepatitis B (CHBe−). Therefore, we assessed whether HCC risk is increased in noncirrhotic CHBe− patients who discontinue compared to those remaining on NAs. Methods: This cohort study included 650 consecutive non-cirrhotic Caucasian or Asian patients with CHBe− without a history of HCC who discontinued NAs after a median of 5 or 3 years (cases, n = 325; Caucasians: 143, Asians: 182) or remained on NA therapy beyond 5 or 3 years respectively (controls, n = 325; Caucasians: 223, Asians: 102). Propensity score (PS) 1:1 matching was applied to adjust for patients' origin, age and sex.Results: During a median follow-up of 44 months, HCC developed in 7/325 cases and 9/325 controls or 7/245 PS-matched cases and 7/245 PS-matched controls with 5year cumulative HCC incidence of 5.1% and 4.9% respectively (log-rank, P = .836). No difference in 5-year HCC risk was observed between cases and controls of Caucasian (3.0% vs 4.8%; log-rank, P = .510) or Asian origin (1.3% vs 2.2%; log-rank, P = .873). In

Incidence of Hepatic Decompensation After Nucleos(t)ide Analog Withdrawal: Results From a Large, International, Multiethnic Cohort of Patients With Chronic Hepatitis B (RETRACT-B Study)

“…There have been several case reports and small studies describing severe hepatic flares or acute exacerbation of hepatitis B after NA cessation, which are sometimes fatal (11)(12)(13)(14)(15). Thus far, there has been 1 large cohort study reporting off-therapy incidence rates of hepatic decompensation and hepatocellular carcinoma among Asian, pretherapy HBeAg-negative patients who discontinued NAs as per the Asian Pacific Association for the Study of the Liver guidelines (16,17). While most studies have reported a higher incidence of liver-related complications among chronic hepatitis B (CHB) patients with cirrhosis, liver failure associated with HBV reactivation after NA withdrawal among patients without documented cirrhosis has also been reported (18).…”

Serious adverse events after cessation of nucleos(t)ide analogues in individuals with chronic hepatitis B: A systematic review and meta-analysis

“…1 ). [12] , [13] , [14] , [17] , [18] , [19] , 27 , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] One of the studies involved two distinct cohorts, of which one consisted exclusively of individuals with prior severe acute exacerbation and the other consisted of patients who had never experienced such an event. 31 Therefore, 50 studies with 51 cohorts were included in the meta-research analysis.…”

“…3 presents the reported proportions of patients who experienced hepatitis flare-related death or liver transplantation according to follow-up duration, inclusion of individuals with cirrhosis, and number of enrolled patients. Most of the studies (30 of 37 studies, 81.08%) with a sample size <500 reported zero events, 13 , 14 , [30] , [31] , [32] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , 46 , [48] , [49] , [50] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , 72 and two of the five studies with a sample size of 500–1,000 also reported zero events ( Fig. S4 ).…”

“…Furthermore, no events were recorded in 30 of 36 (83.33%) studies with a sample size of fewer than 500 individuals. a: references, 13 , 14 , 31 , 32 , 35 , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [45] , [46] , [47] , [48] , 50 , 57 , [59] , [60] , [61] , 64 , 66 , 69 , 70 , 72 b: references, 34 , 65 , 67 , 68 c: references, 12 , 17 , 18 , 27 , 36 , 49 , 56 , 62 , 71 d: references. 30 , 44 , 55 , 58 , 63 …”

Finite nucleos(t)ide analogue therapy in hepatitis B e antigen‐negative chronic hepatitis B: From an “option” to an “active recommendation”

“…This strategy has also been accepted for patients with liver cirrhosis by APASL, 4,17,18,45 but still not by AASLD and EASL guidelines 5,6 . Of note, large studies have demonstrated that the incidence of HCC after cessation of effective finite Nuc therapy in HBeAg‐negative patients with CHB or cirrhosis are not higher than those who continued long‐term Nuc therapy 45–47 . With these favorable results, there seems no contraindication for finite Nuc therapy in patients with cirrhosis if proper off‐Nuc monitoring is guaranteed.…”