Molecular and clinical aspects of hepatitis D virus infections

Table 1 Molecular interactions between hepatitis B virus and hepatitis D virus

HBV polymerase mutation(s)	Corresponding HBsAg mutation(s)	Clinical relevance	Effect(s) on HDV
rtM204V	sI195M(A)	LMV resistance	Enhanced HDV secretion
rtM204I	sW196L/S/stop	LMV resistance	S, L: no HDV secretion
rtD205H	sW196F	Selected during LMV treatment with reduced binding to anti-HBsAg antibodies	Reduced HDV secretion
rtV173L	sE164D	Selected during LMV treatment with reduced binding to anti-HBsAg antibodies	Reduced HDV secretion
rtV173L/rtM204V	sE164D/sI195M	Selected during LMV treatment with reduced binding to anti-HBsAg antibodies	Support HDV secretion

LMV: Lamivudine; HDV: hepatitis D virus; HBV hepatitis B virus; HBsAg: HBV surface antigen.

Table 2 Selected clinical trials on delta hepatitis therapy

Ref.	Drug used	Dosage	No. of patients included	Main result (s)
Garripoli et al[45], 1994	Ribavirin monotherapy	15 mg/kg for 16 wk	9	Ribavirin did not show significant antiviral effects in chronic hepatitis D
Wolters et al[49], 2000	LAM + IFN add-on	LAM 100 mg at least for 24 wk; afterwards combination therapy with IFN 9 MU/d for 4 wk, followed by 9 MU 3 times/wk for 12 wk	8	Neither LAM alone nor the addition of IFN was capable of reducing HDV
Yurdaydin et al[47], 2002	Famciclovir	500 mg for 6 mo	15	Not effective
Farci et al[40], 2004	High-dose IFN αvs low dose IFN vs no treatment	High dose: 9 million units 3 times/wk, low dose 3 million units 3 times/wk for 48 wk	36	High-dose IFN α significantly improves long term clinical outcome and survival
Kaymakoglu et al[46], 2005	IFN α + ribavirin	IFN 10 MU 3 times/wk, Ribavirin 1000-1200 mg/d for 24 mo	19	Addition of Ribavirin to IFN-α does not increase response rate in patients with CHD
Niro et al[36], 2005	LAM vs placebo	100 mg LAM for 52 wk	31	HDV viraemia was unaffected, even in patients when HBV replication was lowered by LAM therapy
Erhardt et al[43], 2006	PEG-IFN	1.5 μg/kg PEG-IFN per wk for 48 wk	12	PEG-IFN is a promising treatment option in chronic hepatitis D
Castelnau et al[41], 2006	PEG-IFN	1.5 μg/kg PEG-IFN per wk for 12 mo	14	PEG-IFN is safe and efficient for HDV treatment
Niro et al[42], 2006	PEG-IFN mono vs combination therapy with ribavirin	1.5 μg/kg PEG-IFN per wk; 800 mg ribavirin; 48 wk mono or combination therapy, afterwards 24 wk PEG-IFN mono	38	Ribavirin had no effect
Yurdaydin et al[50], 2008	LAM vs LAM + IFN vs IFN mono	IFN 9MU 3 times/wk, LAM 100 mg; totally 12 mo therapy; for combination therapy 2 mo LAM mono, afterwards 10 mo combination	39	Addition of LAM to IFN is of no additional value; both (IFN mono/IFN + LAM) are superior to LAM mono
Mansour et al[52], 2010	PEG-IFN, add-on tenofovir und emtricitabine after 2 mo	PEG-IFN 180 μg/wk; tenofovir 300 mg/d for 10 mo	1	Combination therapy with PEG-IFN and nucleoside/tide analogue seems to be more effective than IFN alone
Wedemeyer et al[44], 2011	PEG-IFN mono vs adefovir vs combination PEG-IFN + adefovir	PEG-IFN 180 μg/wk; adefovir 10 mg/d for 48 wk	90	PEG-IFN α-2a with or without adefovir resulted in sustained HDV clearance in about 25%

LMV: Lamivudine; LAM: Lamivudine; CHD: Coronary heart disease; HDV: hepatitis D virus; HBV hepatitis B virus; PEG-IFN: Pegylated interferon.