Benefits of nucleos(t)ide analog treatments for hepatitis B virus-related cirrhosis

Table 1 Studies characterizing the natural history of hepatitis B-related cirrhosis

Ref.	Publication year	Country	Number of patients with cirrhosis	5-yr survival for patients with compensated cirrhosis (%)	Cause of death
Weissberg et al[4]	1984	United States	130	55	Liver failure (70.3%)
					Unrelated disease (18.9%)
					Unknown causes (10.8%)
Liaw et al[5]	1989	Taiwan	76	80	Hepatic failure or variceal bleeding (100%)
de Jongh et al[6]	1992	The Netherlands	98	71	Hepatocellular carcinoma (38.5%)
					Liver failure or fatal upper gastrointestinal bleeding (38.5%)
					Unrelated disease (23.1%)
Realdi et al[7]	1994	Italy	366	84	Liver failure (53.6%)
					Hepatocellular carcinoma (27.4%)
					Unrelated disease (19.0%)

Table 2 Rates of fibrosis improvement in patients with chronic hepatitis or cirrhosis treated with lamivudine, entecavir, or tenofovir

Ref.	Publication year	Nucleos(t)ide	No. of patients	Treatment duration	Cirrhosis percentage	Improvement ratio of fibrosis
Honkoop et al[8]	1997	LAM (25 mg, 100 mg, 300 mg)	13	6 mo	Not described	No difference in fibrosis was observed
Lai et al[3]	1998	LAM (25 mg, 100 mg, placebo)	358	52 wk	5%	25 mg (n = 72) 5%14
						100 mg (n = 142) 2.5%14
						Placebo (n = 143) 0%14
Suzuki et al[9]	1999	LAM (100 mg)	20	52 wk	0%	All patients (n = 20) 35%1
Dienstag et al[10]	2003	LAM (100 mg, placebo)	63	1 yr + additional 2 yr	17%	Bridging fibrosis (HAI fibrosis score of 3; n = 19)
						63% (1 yr + additional 2 yr)2
						Cirrhosis (HAI fibrosis score of 4; n = 11) 45.5% (1 yr)2; 72.7% (1 yr + additional 2 yr)2
Schiff et al[12]	2008	LAM (100 mg)	245	48 wk	Not described5	ETV (n = 120) HBeAg+ 57%3
		Entecavir (0.5 mg)				HBeAg- 59%3
						LAM (n = 125)
						HBeAg+ 49%3
						HBeAg- 53%3
Chang et al[13]	2010	ETV (0.5 mg)	57	48 wk, long-term (range: 3-7 yr, median: 6 yr)	7%	All patients (n = 57) 32% (48 wk)3
						88% (long-term)3
						Cirrhosis (n = 4)
						100% (long-term)3
Marcellin et al[14]	2012	TDF	348	5 yr	28%	All patients (n = 348)
						51% (5 yr)3
						Cirrhosis (n = 97) 74% (5 yr)3

¹Fibrosis improvement was defined as an HAI fibrosis score decrease of at least 1-point;

²Bridging fibrosis improvement was defined as achieving an HAI fibrosis score of 0 or 1. Cirrhosis improvement was defined as achieving an HAI fibrosis score of 0, 1, or 3;

³Fibrosis improvement was defined as a decrease in the Ishak fibrosis score of at least 1-point;

⁴Approximate value estimated from the published graph;

⁵All patients had advanced fibrosis or cirrhosis (Ishak fibrosis scores of 4-6). LAM: Lamibudine; ETV: Entecavir; TDF: Tenofovir; HBeAg: Hepatitis B e antigen; HAI: Histologic activity index.

Table 3 Effects of treatment with nucleos(t)ide analogs in patients with decompensated cirrhosis

Ref.	Nucleos(t)ide	Patient number	Treatment duration	Improvement ratio of Child-Pugh score	Cumulative survival rate3
Villeneuve et al[18]	LAM (100 mg or 150 mg)	35 (CPB: 10, CPC: 25)	Mean: 19 mo	62.9% (22/35)1	1 yr: 78%4
					2 yr: 63%4
Kapoor et al[19]	LAM (150 mg)	18 (CPB: 14, CPC: 4)	Mean: 17.9 mo (range: 9-31 mo)	CPB to CPA: 50% (4/14)	No deaths attributed to liver disease
				CBC to CPB: 50% (2/4)
Yao et al[20]	LAM (150 mg)	13 (CPB: 0, CPC: 13)	Mean: 17.5 mo (range: 3-39 mo)	69% (9/13)2	Not described
Hann et al[22]	LAM (100 mg)	75 (CPA: 4, CPB: 28, CPB: 43)	Mean: 12.7 mo (range: 0.5-33 mo)	31% (23/75)1	Not described
Tseng et al[23]	LAM (100 mg)	30 (CPB: 16, CPC: 14)	Mean: 39.7 mo (range: 3-128 mo)	CPB to CPA: 62.5% (10/16)	1 yr 70%4
				CBC to CPB: 35.7% (5/14)	2 yr 66%4
					3 yr 55%4
					5 yr 55%4
Bae et al[24]	LAM (100 mg)	17 (CPB: 12, CPC: 5)	Mean: 28 mo (range: 14-42 mo)	CPB to CPA: 83% (10/12)	Not described
				CBC to CPB (1/5) or CPA (3/5): 80% (4/5)
Shim et al[25]	ETV (0.5 mg)	55 (mean CP score 8.1 ± 1.7)	12 mo	49% (27/55)1	12 mo: 87.1%
					24 mo: 83.0%
Hyun et al[26]	LAM (100 mg)	86 (CPB: 45, CPC: 41)	Mean: 2 yr	Mean Child-Pugh score	1 yr
	ETV (0.5 mg)			Baseline	LAM: 92.4%
				LAM: 9.5, ETV: 9.6	ETV: 90.7%
				12 mo	3 yr
				LAM: 6.7, ETV: 6.6	LAM: 86%4
					ETV: 76%4
Liaw et al[27]	TDF (300 mg)/FTC (200 mg) + TDV (300 mg)/ETV (0.5 mg or 1 mg)	112 (median CP score: 7, range: 6-9)	48 wk	TDF: 25.9% (7/27)1	Not described
				FTC/TDF: 48.0% (12/25)1
				ETV: 41.7% (5/12)1
Chan et al[29]	LAM (100 mg), TdT (600 mg)	228 (CPS < 7: 18, CPS 7-9: 155, CPS 9 <: 55)	52-104 wk	52 wk	52 wk
				LAM: 38.6% (44/114), TdT: 31.6% (36/114)1	LAM: 88%, TdT: 94%
				104 wk	104 wk
				LAM: 40.4% (46/114 ), TdT: 38.6% (44/114)1	LAM: 79%, TdT: 87%

¹Improvement of Child-Pugh score was defined as a decrease in the CPS greater than or equal to 2-points;

²Improvement of Child-Pugh score was defined as a decrease in the CPS greater than or equal to 3-points;

³Cumulative survival rates calculated by Kaplan-Meier method;

⁴Approximate value from the published graph. LAM: Lamibudine; ETV: Entecavir; TDF: Tenofovir; FTC: Emtricitabine; TdT: Telbivudine; CPB: Child-Pugh class B; CBC: Child-Pugh class C; CPS: Child Pugh score; CPA: Child-Pugh class A.