Introduction
Hepatitis A is a common viral infection in childhood and follows a benign course. However, with improving standards of hygiene and sanitation, there is a shift towards acquiring this infection in adulthood1. The present study was done to determine the clinical outcome and complications encountered in adult patients with acute viral hepatitis A (AVH-A).
Methodology
This is a retrospective analysis of a prospectively maintained database of consecutive patients with AVH- A and or E seen in inpatient and outpatient services by the author. The study period was between 2017 and 2022. Adult patients (>18 years) with clinical symptoms and laboratory investigations suggestive of acute hepatitis illness were included. Patients with associated hepatitis B and C infections, negative serological tests for hepatitis A and E, metabolic liver diseases, Wilson’s disease, pre-existing chronic liver disease, sub-acute hepatic failure, acute on chronic liver failure (ACLF), drug induced liver injury and incomplete reports were excluded (Figure 1). Acute viral hepatitis A and E (AVH-A, AVH-E) was diagnosed based on clinical symptoms, laboratory findings and positive serological tests (Ig M anti HAV and HEV).Ethical clearance was waived off by the Institutional Ethics committee as the study was retrospective and did not involve any patient identifiers.
Hepatic complications included:
1. Acute liver failure- onset of hepatic encephalopathy and/or coagulopathy (INR > 1.5) in a patient without pre-existing liver disease with jaundice to encephalopathy interval of up to 4 weeks2.
2. Prolonged cholestasis- protracted period of jaundice (>3 months) with diagnosed AVH-A and cholestatic features3.
3. Relapsing hepatitis- relapse of symptoms during the six months after AVH-A in the absence of other forms of hepatitis, drug induced liver injury or autoimmune liver disease4.
4. Autoimmune hepatitis - Development of autoimmune hepatitis following AVH-A, diagnosed based on simplified autoimmune hepatitis score and liver histology showing lymphoplasmacytic infiltration, no bile duct injury with or without interface hepatitis5,6.
Extra-hepatic complications were diagnosed based on clinical presentation and appropriate diagnostic tests. Temporal relationship with AVH-A was assessed.Statistical tests used were number, percentages, Mann Whitney test and Chi square test. A p value of <0.05 was considered significant.
Results
The study included 623 patients. Two hundred and seven patients were excluded based on the study criteria. Of the remaining 416 patients, 305 (73.3%) had AVH –E, 104(25%) had AVH-A and 7(1.7%) had combined infection of AVH A+E. Thus, one fourth of AVH in adults was due to AVH-A. (Figure 1)
The study cohort included 104 patients with AVH-A with median age 28 years(range 18-37 years) and male preponderance (70, 67.3%). Eighty five patients (81.7%) had uneventful recovery. Nineteen cases had hepatic and /or extra-hepatic complications. Hepatic complications noted were- acute liver failure (2, 1.9%), prolonged cholestatic jaundice >12 weeks (9, 8.65%), relapsing hepatitis (2, 1.9%) and autoimmune hepatitis (2,1.9%). Both patients with acute liver failure were referred to transplant centres and were lost to follow up thereafter. Patients with prolonged cholestasis were treated with cholestyramine and ursodeoxycholic acid with favourable outcomes. None required plasma exchange and three needed short course of steroids. Both patients with autoimmune hepatitis recovered with steroid therapy and currently are off treatment after >12 months of follow up. Patients with relapsing hepatitis improved with symptomatic treatment. Extra-hepatic complications noted were –Guillian- Barre syndrome (1,0.96%), mild acute pancreatitis (2, 1.9%) and glomerulonephritis(1,0.96%). Both patients with pancreatitis had epigastric pain and elevated amylase/lipase levels with pancreatic edema on imaging. They responded well to conservative treatment and no long term sequelae were noted. A 20 year old student presented with progressive, symmetrical distal and proximal muscle weakness during second week of AVH-A infection.Cerebrospinal fluid analysis showed albumino-cytological dissociation and nerve conduction study revealed acute motor and sensory axonal neuropathy. He was ventilated, given intravenous immunoglobulin and recovered after a period of 14 days. He is currently doing well at 24 months follow up. Another 23 year female presented with anasarca in third week of AVH-A and urine analysis showed nephrotic range proteinuria. Further investigations including renal biopsy showed IgA nephropathy. She is currently under treatment for proteinuria after 8 months of follow up and recovering well. The liver function tests normalised after 2 months of onset of illness.
Patients with extra-hepatic and hepatic complications had a median age of 26 (range: 18-30 years) and majority were males (16/19, 84.2%). Age (p=0.09) and sex distribution (p=0.08) were not significantly different among those with complications and those with uneventful recovery. Seven cases had both hepatitis A and E infection. They had elevated bilirubin levels (median 15, range 8-26 mg/dl), normal INR (median 1.3, range 1.0-1.5) and none developed features of acute liver failure.
Two patients with alcohol related chronic liver disease presented with AVH-A induced ACLF (Figure 1). They were critically sick with multi-organ dysfunction and referred to higher centres for further management. They were lost to follow up. None of the cases developed sub-acute hepatic failure.
Limitations- The study is limited by retrospective design and being a single centre experience. Comparison of patients with AVH A and E could not be done.
To summarize, AVH-A accounts for 25 % of cases of viral hepatitis in adults. It mainly affects young adults and four fifths have uneventful recovery. Prolonged cholestasis is the commonest hepatic complication, followed by relapsing hepatitis, autoimmune hepatitis and acute liver failure. Extra-hepatic complications are rare and have favourable outcome.
References
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- Tandon BN, Bernauau J, O’Grady J, et al. Recommendations of the InternationalAssociation for the Study of the Liver Subcommittee on nomenclature of acute andsubacute liver failure. J Gastroenterol Hepatol 1999;14:403e4
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- Kassas AL, Telegdy L, Méhesfalvi E, et al. Polyphasic and protracted patterns of hepatitis A infection: a retrospective study. Acta Med Hung 1994; 50:93.
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- Hennes EM, Zeniya M, Czaja AJ, et al. Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology. 2008; 48: 169–176.