Need for hepatitis A prevention in patients with chronic liver disease in the changing epidemiological setting of India

Figures & data

Table 1. Seroprevalence studies showing evidence of previous HAV infection (HAV-IgG or anti-HAV) in patients in India with CLD (or specifically with cirrhosis), listed chronologically

Reference	Study years	Population	HAV seroprevalence (%)	HAV vaccination recommendations for CLD patients	Other observations
Dhotial et al. 2002^Citation46	2000–2001	42 cirrhosis	97.6 (anti-HAV)	May not be needed in their population	Etiologies: alcohol (61.9%), HBV (16.7%), HCV (7.1%), other (14.3%)
Acharya et al. 2002^Citation30	1997–2001	254 CLD	97.6 (anti-HAV)	Not required	Etiologies: chronic hepatitis due to HCV (33.1%) or HBV (29.8%), cirrhosis due to HBV (18.5%) or HCV (18.5%)
Xavier and Anish 2003^Citation31	≤2002^a	52 cirrhosis vs. 50 controls	98.1 vs. 100 (anti-HAV)	Routine vaccination not required; nor routine anti-HAV screening	Main etiologies: alcoholic cirrhosis (25.0%), HBV (13.5%); high/low socioeconomic class (51.9%/48.1%)
Ramachandran et al. 2004^Citation27	2001–2002	100 CLD vs. 79 controls^b	99.0 vs. 100 (HAV-IgG)	Not needed	Main etiologies: cryptogenic (32.0%), alcohol (25.0%), HBV (25.0%)
Anand et al. 2004^Citation28	2002	187 CLD vs. 89 controls	95.7 vs. 94.6 (HAV-IgG)	Not routinely required	Main etiologies: HBV (48.7%), HCV (33.2%), cryptogenic (12.8%)
Duseja et al. 2004^Citation47	1999–2000	55 cirrhosis	98.2 (anti-HAV)	Routine vaccination cannot be recommended	Etiologies: alcohol (45.5%), HBV (23.6%), HCV (9.1%), Budd–Chiari Syndrome (3.6%), cryptogenic (20.0%)
Hussain et al. 2006^Citation26	1999–2003	300 CLD^c vs. 500 controls	98.0 vs. 71.2 (HAV-IgG)	Selective vaccination of high-risk population would be a rational and cost-effective approach	Etiologies: HBV (56.3%), HCV (24.3%), alcohol (16.0%), HBV+HCV (3.3%)
Khanna et al. 2006^Citation50	1999–2004	127 cirrhosis	60.6% (HAV-IgG)	All seronegative cirrhotic patients were vaccinated	All patients were upper/upper middle socioeconomic class
Joshi et al. 2007^Citation25	2004–2005	133 cirrhosis vs. 75 controls^b	93.2 vs. 94.6 (anti-HAV)	Not routinely required screening for HAV antibodies may be more cost effective than vaccination	Main etiologies: HBV (29.3%), cryptogenic (23.3%), alcohol (21.8%), HCV (14.3%)
John et al. 2009^Citation48	≤2007^a	300 CLD	93.3 (HAV-IgG)	Routine vaccination without testing for HAV antibodies not recommended	Etiologies: alcohol (62%), HBV/HCV (12%), cryptogenic (24%), Wilson’s (2%)

^aThese studies did not report study dates, so these dates are based on “received” and “accepted” publication dates.

^bAge- and sex-matched.

^cAnd HBV and/or HCV infection or alcoholism; CLD patients with unclassified etiology were excluded.

CLD, chronic liver disease; HAV, hepatitis A virus; HBV, hepatitis B virus; HCV, hepatitis C virus; IgG, immunoglobulin G; NR, not reported.

Figure 1. Opposing, but converging, trends in HAV susceptibility among (A) higher and lower middle socioeconomic status populations (created based on data from Arankalle et al.⁵⁹) and (B) urban general and lower socioeconomic status populations (created based on data from Deoshatwar et al.⁶¹)

HAV, hepatitis A virus; HSS, high socioeconomic status; LMSS, lower middle socioeconomic status; LSS, lower socioeconomic status; NS, not significant; p, p value.

Figure 2. Increasing acute HAV infection among adults with acute viral hepatitis, created based on data from Acharya et al. 2003,⁶² Khanna et al. 2006 (middle adult age group used),⁵⁰ Hussain et al. 2006,²⁶ Kumar et al. 2007 (mainly adults),⁶³ Irshad et al. 2010,⁶⁴ Jain et al. 2013,⁶⁵ Tewari et al. 2016,⁶⁶ and Sharma et al. 2016 (suspected viral hepatitis).⁶⁷ Further information on these studies can be found in Table 2

HAV, hepatitis A virus; IgM, immunoglobulin M.

Table 2. Seroprevalence studies showing evidence of current HAV infection in patients in India with (suspected) acute viral hepatitis, listed chronologically

Reference	Study years	Population	Age	Seroprevalence (HAV-IgM) (%)	Other observations
Poddar et al. 2002^Citation68	1997–2000	172 AVH	Children	72.7 (64.5 HAV alone; 8.1 with HCV and/or HEV)	Other etiologies: HEV 16.3%, HBV 7.6%
Acharya et al. 2003^Citation62	1992–2001	998 AVH vs. 492 FHF	Adults	7.7 vs 5.9	No significant change in the proportion of AVH or FHF due to HAV from 1992 to 2001
Hussain et al. 2006^Citation26	1999–2003	1932 AVH	751 children, 1181 adults	16.2 (children), 8.4 (adults)	See line in Figure 2 for evolution over time
Khanna et al. 2006^Citation50	1999–2004	500 AVH	90 children, 410 adults	72.2 (children), 28.0 (adults)	All middle/upper socioeconomic status; see line in Figure 2 for evolution over time
Kumar et al. 2007^Citation63	2002–2006	685 AVH vs. 70 FHF vs. 53 CLD vs. 11 ATT-induced jaundice vs. 24 pregnant	10–70 years	17.5 vs. 4.3 vs. 0 vs. 0 vs. 0	–
Irshad et al. 2010^Citation64	2006–2009	76 AVH vs. 54 FHF vs. 102 CVH vs. 96 cirrhosis vs 42 HCC	Adults	8.1 vs. 0 vs. 0 vs. 0 vs. 0	–
Jain et al. 2013^Citation65	2011–2012	205 AVH vs. 62 FHF	AVH: 97 children, 108 adults; FHF: 46 children, 16 adults	AVH: 34.0 (children), 28.7 (adults); FHF: 13.0 (children), 12.5 (adults)	Other etiologies (AVH and FHF combined): HEV 18.0%, HBV 16.1%, HCV 12.0%
Sharma et al. 2016^Citation67	2012–2015	285 suspected viral hepatitis	Adults	36.8 (31.2 HAV alone; 5.6 with HBV, HCV, or HEV) ^a	Other etiologies: HBV 1.8%, HCV 1.4%, HEV 1.4%
Tewari et al. 2016^Citation66	2014	89 AVH	36 children, 53 adults	72.2 (children), 7.5 (adults)	–
Mittal et al. 2016^Citation69	2015	1654 AVH	Children and adults	7.7	Most seropositive cases were aged 11–20 years (45.6%), 0–10 years (29.1%), 21–30 years (18.1%)

AVH, acute viral hepatitis; ATT, antituberculosis treatment; CVH, chronic viral hepatitis; CLD, chronic liver disease; FHF, fulminant hepatic failure; HAV, hepatitis A virus; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HEV, hepatitis E virus; IgM, immunoglobulin M.

Table 3. Adult HAV vaccination guidelines from various associations and scientific societies in India

	API 2009^Citation72	ISN 2016^Citation73	IMA 2018^Citation74
All adults	No	No	Yes
CLD and not immune to HAV	Unclear^a	Unclear^a	NM
Other hepatitis viruses	Unclear^a	Unclear^a	NM
Liver transplantation	Unclear^a	Unclear^a	Yes
Transplant candidates with CLD	NM	Yes	NM
ESRD and chronic HBV or HCV	NM	Yes	NM
Other at-risk people^b	Unclear^a	Unclear^a	Yes

^aGuideline specifies that these people are at high risk for acquiring HAV, and are most likely to benefit from HAV vaccination, but it is not clear whether vaccination is recommended.

^bDefinitions vary by guideline.

API, Association of Physicians of India; CLD, chronic liver disease; ESRD, end-stage renal disease; HAV, hepatitis A virus; HBV, hepatitis B virus; HCV, hepatitis C virus; IMA, Indian Medical Association; ISN, Indian Society of Nephrology; NM, not mentioned.

Figure 3. Plain language summary

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