Hepatitis A

Hepatitis A virus (HAV) infections range from asymptomatic health state to fulminant hepatitis (Jeong & Lee, 2010). Hepatitis A symptomatic infections depend strongly on the age: approximately 30% of infected children develop symptoms (Jeong & Lee, 2010; Ciocca, 2000), whereas, according to literature, this is 70–80% for adults (Jeong & Lee, 2010; Ciocca, 2000; Cuthbert, 2001). The manifestation of HAV infection in young children generally includes mild flu-like, but anicteric symptoms (Gingrich, 1983), whereas in adults frequently reported symptoms are jaundice, dark urine, fatigue, loss of appetite, abdominal pain and light-coloured stool lasting for several weeks (Koff, 1992).

Not only severity, also duration is related to the age of the patient. Symptoms in young children last for one to two weeks (Gingrich, 1983). According to Koff, around 80% of adults are ill for up to eight weeks (Koff, 1992). Haagsma et al. assumed that symptomatic HAV cases not requiring medical help would have symptoms for 14 days, and symptomatic HAV cases requiring any kind of medical help would have symptoms for 30 days (Haagsma, 2009). Havelaar et al. assumed that hospitalised HAV cases would have symptoms for up to 0.3 years(Haavelar, 2012). According to the US Centers for Disease Control and Prevention, clinical illness usually does not last longer than two months, although 10–15% of persons have prolonged or relapsing signs of symptoms for up to six months (CDC, 2012).

The case fatality proportions are reported to be 0.1% (Mead, 1999), 1% of hospitalised HAV cases (Arteaga Rodriguez, 2010) and 0.3% (Bauch, 2007; Fiore, 2004).

Fatal cases occur mainly in elderly people (Bauch, 2007; Jacobs, 2004; Jacobs, 2000). In the following table we have summarised the rates of mortality attributable to HAV as used in various cost-effectiveness analyses (Bauch, 2007; Jacobs, 2004; Jacobs, 2000).

Table 1. Deaths among symptomatic patients per 10 000 stratified for age classes

Age classes
(in years)

Sources

Bauch 2007

Jacobs 2004

Jacobs 2000

 

30

-

 

5-14

18

-

 

15-19

18

-

18 (6-30)

20-29

18

18

18 (6-30)

30-39

21

21

21 (10-32)

40-49

59

36

36 (23-49)

50-59

59

81

81 (70-92)

60-69

272

149

149 (146-152)

70-79

272

283

283 (154-310)

>80

272

283

385 (356-414)

We chose to consider the overall case fatality proportion to be within the range 0.1–0.3% and assumed a different age-group distribution of this risk based on the age-group distribution of fatal cases reported to TESSy between 2009 and 2013 (see Table 4). This table is based on all TESSy notified cases from EU Member States except Bulgaria, Lithuania, Latvia and Poland, because they report only aggregate data, and Liechtenstein which does not report.

Risk of complications

Fulminant hepatitis is a rare complication of hepatitis (Jeong & Lee, 2010). According to Bauch et al. (Bauch, 2007), the probability of fulminant infection in hospitalised HAV cases is 0.011%. Jacobs et al. (Jacobs, 2004) assumed that the probability of liver transplantation would be 0.02% for symptomatic HAV cases in 25 to 29-year olds, increasing slightly with age to 0.08% for symptomatic HAV cases in 70-year olds. According to Jeong and Lee (Jeong & Lee, 2010), a liver transplantation may be necessary, however HAV-related fulminant hepatitis does resolve spontaneously on a more frequent basis than fulminant hepatitis of other aetiologies. Given the low incidence, and the resulting negligible burden, fulminant hepatitis was not considered as a separate health outcome in the current study.

In a current review (Jeong & Lee, 2010), rare atypical clinical manifestations and extra-hepatic manifestations are listed. Atypical clinical manifestations occasionally reported are: relapsing hepatitis, prolonged cholestasis, and complicated cases with acute kidney injury. Rarely reported extra-hepatic manifestations are autoimmune haemolytic anaemia, aplastic anaemia, pure red cell aplasia, pleural or pericardial effusion, acute reactive arthritis, acute pancreatitis, acalculous cholecystitis, mononeuritis, and Guillain-Barré syndrome. None of these manifestations were considered in a recent disease burden study (Havelaar, 2012), nor in cost-effectiveness studies evaluating HAV vaccination programmes (Bauch, 2007; Jacobs, 2000, 2004).

Model input summary

Table 2. Transition probabilities used in the outcome tree

 Health outcome
 (Health state)

Distribution of health states in health outcome

Transition probability

Source/assumption

Fatal cases

 

0.1–0.3%.
Age-dependent (Table 4)

Mead 1999, Bauch 2007, Fiore 2004

Table 3. Disability weights and duration

Health outcome
(Health state)

Disability Weight (DW) (Haagsma, 2015)

Duration

DW

Label

In years

Source/assumption

Symptomatic infection

0.125 (0.104–0.152)

Infectious disease, acute episode, severe

0–9 years: 0.019–0.038 > 10 years: 0.082 (0.038–0.5).
See Table 5.

CDC 2012; Haagsma 2009, age-dependent

Table 4. Age-group redistribution of case fatality proportion (0.1–0.3%)

Age groups

%

0

0.00

1-4

0.00

5-9

0.00

10-14

0.00

15-19

0.00

20-24

10.00

25-29

0.00

30-34

0.00

35-39

0.00

40-44

10.00

45-49

0.00

50-54

10.00

55-59

20.00

60-64

10.00

65-69

0.00

70-74

20.00

75-79

20.00

80-84

0.00

>85

0.00

All ages

100.00

Table 5. Duration of symptomatic disease by age group

Age

%

0-9

0.019–0.038

> 10

0.082 (0.038–0.5)

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