Hepatitis E virus infection: Epidemiology and treatment implications

Table 1 Global prevalence of anti-hepatitis E virus IgG in different populations

Regions	Prevalence (%)	Ref.
Low-to-medium income
Kashmir region	49.6	Khuroo et al[35]
India	23.8-28.7	Mathur et al[76]
Myanmar	32.0	Nakai et al[77]
Egypt	67.7	Stoszek et al[71]
Bangladesh	22.5	Labrique et al[78]
China	19.7	Dong et al[79]
Mexico	36.6	Alvarado-Esquivel et al[80]
Thailand	14.0	Gonwong et al[75]
Nigeria	42.7	Junaid et al[81]
Industrialized
Germany	17.0	Wenzel et al[82]
United States	6.0	Teshale et al[83]

Table 2 Recent evidences on the outcome of therapies against acute hepatitis E infection

Ref.	Type of study	Patient profile	HEV genotype	Ribavirin regimen	Results
Gerolami et al[84]	Case report	61-year-old man, 7 d after admission ALT 4565 IU/L	3	1200 mg/d for 21 d	At day 21 of treatment, ALT normalized, RNA almost undetectable
Péron et al[88]	Case report	79-year-old man with chronic liver disease, acute kidney failure	3f	200 mg/d for 3 mo	Serum HEV RNA negative at 1 mo therapy, stopped dialysis at 2 mo
		A patient with chronic liver disease	3f	1000 mg/d for 10 d	Viral load 4.07 log copies/mL declined to 2.54 log copies/mL at day 6, Hgb 12.6 g/dL declined to 11.6 g/dL at day 6 of treatment
Del Bello et al[95]	Case report	65-year-old man, liver transplant recipient Guillain-Barré syndrome with severe necrotizing myositis	3f	400 mg/d adapted to GFR (40 mL/min) for 3 mo	HEV RNA undetectable by day 15, progressive recovery of mobility
Pischke et al[96]	Case from prospective case series	42-year-old woman had traveled to Eritrea and acquired severe acute hepatitis E	1e	For 6 wk (dose: Undefined)	Rapidly improved liver function and cleared HEV
Robbins et al[97]	Case report	39-year-old man HIV (+) CD4 51/mm3 prothrombin index 45%	3c	1200 mg/d (15 mg/kg per day) for 12 wk	Gradual normalization of LFT-HEV RNA decreased to < 100 copies/mL at 1 mo of treatment
Riveiro-Barciela et al[98]	Case report	68-year-old man with Waldenström's macroglobulinemia	3f	800 mg/d for 12 wk	Achieved SVR after 12 wk; no ribavirin-related side effect reported

LFT: Liver function test; ALT: Alanine transaminase; Hgb: Haemoglobin; GFR: Glomerular filtration rate; SVR: Sustained virological response; HIV: Human immunodeficiency virus; HEV: Hepatitis E virus.

Table 3 Treatment of chronic hepatitis E virus with ribavirin regimen

Ref.	Type of study	Patient profile	Ribavirin regimen	Result	Adverse effects
Kamar et al[99]	Prospective case series	6 kidney transplant recipients, HEV RNA (+) for median of 36.5 mo	600-800 mg/d for 3 mo adapted to GFR, Hgb	SVR in 4/6 patients; relapse in 2/6; AST, ALT normalized all	Anemia led to blood transfusion and RBV dose reduction in 2/6 patients
Mallet et al[105]	Case report	A kidney and pancreas transplanted man, a women with idiopathic CD4+ T lymphocytopenia	12 mg/kg daily for 12 wk	Both cleared HEV after 4 wk of treatment and remained undetectable, LFT normalized	Anemia in 1st patient led to Ribavirin dose reduction to 200 mg/d
Pischke et al[96]	Prospective case series	Organ transplant recipients 11 subjects	600-1000 mg/d for 5 mo, dose reduction according to Hgb or anemia	9/11 showed SVR	Anemia, the mean Hgb decline was 3.4 g/dL (range 0-7.9 g/dL)
Neukam et al[106]	Case report	2 HIV (+) male with liver cirrhosis with severe immunosuppression	Oral ribavirin 1200 mg/d (case 1) 1000 mg/d (case 2) for 24 wk	LFT normalized-Liver stiffness improved HEV RNA was detected after the end of treatment in both patients	-
Giordani et al[107]	Case report	60-year-old man with lymphocytic leukemia	1000 mg/d in 2 doses (400 and 600 mg), for 3 mo	HEV cleared and sustained over 6 mo after therapy	Mild anemia (Hgb 10.5 mg/dL)
Kamar et al[100]	Retrospective, multicentre case series	37 kidney, 10 liver, 5 heart, 5 kidneys and pancreas, and 2 lung transplant recipients with chronic HEV	Median dose of 600 mg/d (range 29-1200), for a median of 3 mo (range 1-18 mo)	At the end of the therapy, 95% cleared HEV, 18% recurred after cessation of therapy is stopped, 78% showed SVR	Anemia required dose reduction (29%); use of erythropoietin (54%); required blood transfusion (12%)

LFT: Liver function test; AST: Aspartate aminotransferase; ALT: Alanine transaminase; SVR: Sustained virological response; Hgb: Haemoglobin; GFR: Glomerular filtration rate; HEV: Hepatitis E virus; HIV: Human immunodeficiency virus.

Table 4 Treatment of chronic hepatitis E virus with pegylated interferon-α therapy

Ref.	Patient profile	Peg-IFN-α regimen	Result	Adverse effects
Kamar et al[101]	29-year-old man with liver transplantation	Peg-IFN-α-2a for 12 wk (135 μg/wk)	Liver enzyme levels decreased. HEV RNA levels remained undetectable until week 12	At week 12, signs of acute humoral rejection in liver biopsy
	26-year-old man with liver transplantation	Peg-IFN-α-2a for 12 wk (135 μg/wk)	HEV RNA levels undetectable by week 12; liver enzyme levels normalized by week 12
	58-year-old man with liver transplantation liver cirrhosis from chronic HEV infection	Peg-IFN-α-2a for 12 wk (135 μg/wk)	HEV RNA was redetected 2 wk after completion of treatment; Liver enzyme levels normalized by 3 mo of therapy
Haagsma et al[102]	37-year-old woman with liver transplantation	Peg-IFN-α-2b for 52 wk (80 μg/wk declined to 60 μg/wk)	Serum HEV RNA sustained undetectable during 3 mo follow-up; serum liver enzyme became normalized
	59-year-old man with liver transplantation	Peg-IFN-α-2b 150 μg/wk, dose reduction due to leukopenia	HEV viral load and aminotransferases declined, but Peg-IFN discontinued from lack of further efficacy, HEV RNA level undetectable at 4 wk after the discontinuation of Peg-IFN and aminotransferase normalized	Leukopenia
Alric et al[108]	57-year-old man with hairy cell leukemia	Discontinued at week 16, Peg-IFN-α-2b 1 μg/kg per week for 3 mo	Achieved a complete virologic response by week 4
Kamar et al[109]	24-year-old man with kidney transplantation, kidney failure from chronic HEV infection	3-mo Peg-IFN-α-2a 135 μg/wk	Serum RNA undetectable after 5 mo, SVR for 6 mo after treatment	Acute rejection of the kidney allograft by month 3 of Peg-IFN therapy

Peg-IFN: Pegylated interferon; SVR: Sustained virological response; HEV: Hepatitis E virus.

Table 5 Incidence of detectable hepatitis E virus in blood donors (hepatitis E virus-RNA)

Year of study	Countries	Technique used for detection	No. of tests	Ratio of positive detections	Ref.
2005	China	Real-time fluorescence RT-PCR	10741	1:1094	Ren et al[117]
2011	England	PCR	42000	1:7000	Ijaz et al[118]
2011	German	Real-time RT-PCR	18100	1:4525	Baylis et al[119]
2011	Sweden	Real-time RT-PCR	95835	1:7986	Baylis et al[119]
2011	United States	Real-time RT-PCR	51075	None detected	Baylis et al[119]
2011	German	Real-time RT-PCR	16125	1:1241	Vollmer et al[120]
2011-2012	The Netherlands	Real-time PCR	45415	1:2672	Slot et al[121]
2012-2013	England	RT-PCR	225000	1:2848	Hewitt et al[122]
2012	France	RT-PCR	53234	1:2218	Gallian et al[123]
2013	Spain	Transcription-mediated amplification assay	9998	1:3333	Sauleda et al[124]

RT-PCR: Reverse transcription-polymerase chain reaction.