Inferior survival and frequent hepatic dysfunction in non-Hodgkin’s lymphoma patients with HBV infection: a systematic review and meta-analysis

Figures & data

Figure 1. Literature search and selection.

Table 1. Baseline characteristics of included studies.

Author	Diagnosis	Year	Treatment	Number of patients		Use of rituximab %		HBV reactivation %		HBV reactivation prophylaxis	NOS	Hazard ratio
				HBsAg+	HBsAg−	HBsAg+	HBsAg−	HBsAg+	HBsAg−
Deng L [9]	DLBCL	2015	R ± CHOP	81	506	40.7	53.6	6.2	0	Yes	8	Extrapolated
Guo YF [23]	DLBCL	2018	RCHOP	80	166	100	100	10.2	−	−	7	Extrapolated
Law MF [10]	DLBCL	2015	R ± CHOP ± RT	16	65	50	48	−	−	Yes	9	Reported
Liu WP [11]	DLBCL	2016	R ± CHOP	46	61	63	90.2	21.7	0	Yes	8	Extrapolated
Liu Z [21]	DLBCL	2017	R ± CHOP	30	51	43.3	64.7	10	0	Yes	9	Reported
Ren W [12]	DLBCL	2018	R ± CHOP	56	219	−	−	−	−	−	7	Extrapolated
Wang F [13]	DLBCL	2008	R ± CHOP ± RT	81	181	< 10	< 10	−	−	Yes	7	Extrapolated
Xie W [22]	DLBCL	2013	R ± CHOP	90	361	54.4	68.1	−	−	Yes	8	Extrapolated
Zhao X [14]	DLBCL	2018	R ± CHOP	93	335	53.8	64.8	−	−	−	8	Extrapolated
Huang YH [24]	DLBCL	2012	R ± CHOP ± RT	31	118	26.7	47.3	−	−	No	7	Extrapolated
Li WB [37]	DLBCL	2010	CHOP	41	79	0	0	−	−	−	6	Extrapolated
Shan LZ [25]	DLBCL	2016	R ± CHOP ± RT	76	159	59.2	64.8	−	−	Yes	7	Extrapolated
Wei HM [31]	DLBCL	2015	−	33	117	−	−	−	−	−	7	Extrapolated
Wei Z [32]	DLBCL	2014	R ± CHOP	56	328	35.7	47.9	2.43	−	−	7	−
Zhang Y [34]	DLBCL	2012	R ± CHOP	49	173	40.8	69.4	14.3	2.9	Yes	8	Extrapolated
Wang QX [29]	DLBCL	2016	−	52	200	−	−	−	−	−	6	−
Wang Y [30]	DLBCL	2018	R ± CHOP	120	388	76.1	83.6	−	−	−	7	−
Zhang Y [35]	DLBCL	2017	R ± CHOP	26	68	46.2	45.6	−	−	−	6	−
Feng Y [26]	DLBCL	2016	−	36	124	−	−	−	−	−	7	Extrapolated
Lim ST [27]	NHL	2007	Chemotherapy ± RT	55	443	−	−	20	0	Yes	6	Extrapolated
Wang L [36]	NK/T	2014	EPOCH/GELOX ± RT	14	93	−	−	−	−	Yes	7	Extrapolated
Yi S [33]	SMZL	2017	R−based chemotherapy	25	135	32	45.2	−	−	Yes	8	Extrapolated
Lv R [28]	MZL	2015	Splenectomy, R−based chemotherapy	15	78	−	−	−	−	−	6	Extrapolated

DLBCL: diffuse large B-cell lymphoma; NHL: non-Hodgkin’s lymphoma; NK/T: NK/T-cell lymphoma; SMZL: spleen marginal zone lymphoma; MZL: marginal zone lymphoma; R: rituximab; CHOP: cyclophosphamide, doxorubicin, vincristine and prednisone; EPOCH: etoposide, vincristine adriamycin, cyclophosphamide, and prednisone; GELOX: gemcitabine, oxaliplatin and asparaginase; RT: radiotherapy.

Figure 2. Meta-analysis of the association between status of HBsAg and overall survival of NHL patients.

Table 2. Results of meta-analysis.

Clinical factors	Outcomes	Figure No.	Overall analysis		Subgroup analysis
			Effect size	p-value	Effect size	p-value
Survival	Overall survival	2	1.68 (1.48–1.91)	< 0.00001	1.64 (1.44–1.88)	< 0.00001
	Progression-free survival	3	1.80 (1.20–2.71)	0.004	1.44 (0.91–2.27)	0.12
Treatment response	Complete remission	4	0.59 (0.44–0.80)	0.0005	0.57 (0.41–0.79)	0.0008
Hepatic dysfunction		5	3.46 (2.61–4.57)	< 0.00001	3.46 (2.61–4.57)	< 0.00001
Clinical characteristics	Age of onset	S1	2.57 (2.05–3.24)	< 0.00001	2.61 (2.07–3.29)	< 0.00001
	Advanced disease stage	S2	1.79 (1.55–2.07)	< 0.00001	1.86 (1.60–2.16)	< 0.00001
	Elevated LDH level	S3	1.34 (1.15–1.56)	0.0001	1.35 (1.15–1.57)	0.0002
	Presence of B symptoms	S4	1.72 (1.22–2.43)	0.002	1.69 (1.13–2.52)	0.01
	Spleen involvement	S5	3.09 (2.39–3.99)	< 0.00001	3.09 (2.39–3.99)	< 0.00001
	Liver involvement	S6	2.49 (1.72–3.59)	< 0.00001	2.49 (1.72–3.59)	< 0.00001
	High IPI score	S7	0.96 (0.67–1.39)	0.83	0.94 (0.63–1.39)	0.75
	Bone marrow involvement	S8	1.19 (0.72–1.96)	0.49	1.19 (0.72–1.96)	0.49

Figure 3. Meta-analysis of the association between status of HBsAg and progression-free survival of NHL patients.

Figure 4. Meta-analysis of the association between status of HBsAg and complete remission of NHL patients.

Figure 5. Meta-analysis of the association between status of HBsAg and hepatic dysfunction in NHL patients during chemotherapy.

Table 3. Results of sensitivity analysis.

Outcome	Origin of heterogeneity	Overall effect	p-value
Progression-free survival	Shan [25]	2.07 (1.57–2.72)	< 0.00001
Complete remission	Wang [30]	0.61 (0.50–0.73)	< 0.00001
Presence of B symptoms	Xie [22]	2.06 (1.59–2.66)	< 0.00001

Table 4. Results of Begg’s test and Egger’s test.

Outcome	p Begg’s test	p Egger’s test
Overall survival	1.000	0.806
Progression-free survival	0.675	0.573
Complete remission	0.113	0.019
Age of disease onset	0.631	0.959
Advanced disease stage	0.456	0.615
Elevated LDH level	0.260	0.129
Presence of B symptoms	0.386	0.872
Spleen involvement	0.533	0.353
Liver involvement	0.754	0.506
Bone marrow involvement	0.452	0.337
High IPI score	1.000	0.343
Hepatic dysfunction	0.548	0.788

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