Prolonged cholestasis after acute viral hepatitis: successfully treated with oral steroid

Abstract

Cholestasis is a rare distinct complication of hepatitis A infection. Usually it runs a long indolent course with significant pruritus and malabsorption lasting for few months. A 9-year-old boy presented with yellowish discolouration of eye for 1 month. Liver function test showed conjugated hyperbilirubinaemia. Serology was positive for hepatitis A IgM antibody. Liver biopsy showed features of hepatitis with cholestasis. Child successfully treated with oral steroids.

Background

Hepatitis A is the most common virus causing viral hepatitis. Infection can be asymptomatic. Usually it is a self-limiting infection. Rarely it may be associated with complications. Most common complication is acute liver failure which is usually seen with concurrent hepatitis E virus (HEV) infection. It can also progress to cholestasis which manifests with intense pruritus and can also cause malabsorption in the long run. We present a case of cholestasis following hepatitis A infection which was treated with oral corticosteroids.

Case presentation

A 9-year-old boy was brought to paediatric outpatient department with symptoms of yellowish discolouration of eyes for 1 month. The condition started 1 month prior to admission with a short fever and vomiting for few days and improved with symptomatic treatment. The parents noticed the child had yellowish discolouration of eyes 1 week post illness. When there was increase in jaundice with associated itching the child was taken to local practitioner who ordered liver function test (LFT). In view of conjugated hyperbilirubinaemia, the child was referred for further workup. There was no significant history. There was no history of blood transfusion and any drug intake. On examination the child was icteric. Liver was palpable and tender on abdominal examination with a span of 12.5 cm. Other systemic examination was unremarkable.

Investigations

Haematological investigation including prothrombin time was normal. LFT showed aspartate aminotransferase (AST) 69 U/L, alanine transaminase (ALT) 31 U/L, alkaline phosphatase 260 U/L, total serum bilirubin 27.22 mg/dL with conjugated fraction of 13.70 mg/dL. Total serum proteins were 6.8 g/dL; serum albumin was 3.94 g/dL. IgM antibodies for hepatitis A virus (HAV) was positive. HbsAg, anti-hepatitis C virus (anti-HCV) and anti-HEV IgM were negative. Serum ceruloplasmin and ultrasonography (USG) of abdomen and Doppler of portal vein were normal. Liver biopsy was done which showed chronic inflammatory infiltrates with lymphocytes with mild portal fibrosis. There was no bridging fibrosis. Mild bile stasis with intracytoplasmic bile pigment with few hepatocytes showing feathery degeneration was also noted.

Differential diagnosis

Other causes of prolonged cholestasis like gall stone was considered but in view of normal ultrasound examination of abdomen, it was ruled out. Other aetiologies for conjugated hyperbilirubinaemia include exposure to environmental toxins and drugs which was also absent in this child.

Treatment

The patient was started on ursodeoxycholic acid (UDCA) at 25 mg/kg/day. One week after starting UDCA, LFT showed persistently high conjugated bilirubin with persistence of pruritus. In view of persistently high conjugated bilirubin child was started on oral prednisolone 2 mg/kg/day. Within 5 days of starting steroid there was reduction in serum bilirubin from 27.22 mg/dL to 23.08 mg/dL with drastic relief in pruritus.

Outcome and follow-up

The patient was discharged on oral steroids. However, he stopped taking steroids in between when repeat serum bilirubin was 15.92 mg/dL. He was restarted on oral steroids. Within 4 weeks of restarting the bilirubin levels normalised (figure 1). Total duration of oral steroids were 6 weeks in this patient. Child remained asymptomatic after 6 months of follow-up.

Figure 1.

Response to steroid on serum bilirubin in index child.

Discussion

Hepatitis A is an acute self-limiting necroinflammatory disease affecting the liver. It is caused by enterally transmitted HAV infection. India is hyperendemic to HAV and studies have shown that by adolescence 90%–100% of population will be seropositive for HAV.¹ HAV infection is common in children of developing nations which commonly causes mild anicteric hepatitis.² However, the icteric infection caused by HAV can be classical, relapsing, fulminant or cholestatic.²

Classical illness is characterised by acute febrile illness with jaundice. Duration can last anywhere between 7 and 14 days. Majority of patients undergo spontaneous remission with normalisation of biochemical parameter and viral load after resolution of infection.³ Relapsing illness is seen in 10%–20% of patients where the patient develops second episode of HAV infection as confirmed by biochemical parameters and detection of virus by PCR after documented resolution of initial infection.³ In about 1% of patients there may be acute liver failure due to HAV infection termed as fulminant hepatitis.

Prolonged cholestasis following HAV is sometimes said to be a complication of HAV infection and sometimes as a variant of HAV infection.⁴ It is defined as a peak serum bilirubin of more than 10 mg/dL (with direct bilirubin higher than 50% of the total bilirubin) and hyperbilirubinaemia or jaundice lasting for more than 12 weeks in the absence of haemolysis and renal failure with the alanine transaminase level below 500 U/L.⁵ The possible mechanisms involve increased response of cellular and humoral immunity and procholestatic polymorphism of hepatocanalicular bile salt transporters. This disease does not affect synthetic functions of the liver and tend to resolve without leaving any sequelae. However, if the child continues to have disabling symptoms of pruritus and fat malabsorption even on therapy with UDCA then a course of steroids can be tried.⁶ Steroids act as anti-inflammatory agents along with stimulation of alternate efflux pathway for bile salts. UDCA acts by stimulating both normal and alternate efflux pathway and even sensitises glucocorticoid receptor. Hence, using both UDCA and steroids have a synergistic effect bringing about maximum response.^3–6

Since prolonged cholestasis following HAV infection itself is a rare entity there has been no consensus regarding the use of steroids in therapy for these patients. This case report may help in clinicians considering the use of oral steroids in prolonged cholestasis following HAV infection.

Learning points.

• Prolonged cholestasis can occur after acute viral hepatitis A infection.

• Increased cellular and humoral immunity response and procholestatic polymorphism of hepatocanalicular bile salt transporters may be responsible for prolonged cholestasis.

• Corticosteroids should be considered in the management of patient with prolonged cholestasis after hepatitis A infection.