Seronegative Autoimmune Hepatitis A Clinically Challenging Difficult Diagnosis

Abstract

Autoimmune hepatitis (AIH) is a complex liver disease of unknown cause which results in immune-mediated liver injury with varied clinical presentations. Seronegative AIH follows a similar course to autoantibody-positive disease and diagnosis may be challenging. There are no single serologic tests of sufficient diagnostic specificity, and delay in appropriate treatment may lead to progression of the liver disease and liver failure. The revised conventional diagnostic criteria (RDC) scoring for AIH is complex and not routinely used in the clinical practice. The more recent simplified diagnostic criteria (SDC) scoring proposed by International Autoimmune Hepatitis Group in 2008 has wider application in routine practice facilitating the diagnosis of AIH with a specificity and sensitivity of ~90%. In this report, we describe a case of seronegative autoimmune hepatitis diagnosed using RDC. SDC score calculated in our case was 4 and was not diagnostic for AIH. We subsequently used the complex revised diagnostic criteria for definitive diagnosis. Some of the patients previously diagnosed as cryptogenic active hepatitis of unknown etiology probably had an unrecognized diagnosis of seronegative autoimmune hepatitis. SDC scoring may not be applicable in patients with seronegative autoimmune hepatitis. These patients should be reassessed by using RDC.

Seronegative Autoimmune Hepatitis

“…Autoimmune hepatitis (AIH) is an insidious inflammatory disease of the liver that affects 1 in 200,000 people annually in the USA. [1][2][3] AIH has a bias for women at all ages. The diagnosis of AIH is established through scoring systems developed by The International Autoimmune Hepatitis Group (IAIHG) exclude other diseases and histological features that reflect a chronic inflammatory state.…”

“…The diagnosis of AIH is established through scoring systems developed by The International Autoimmune Hepatitis Group (IAIHG) exclude other diseases and histological features that reflect a chronic inflammatory state. 1 The presentation of AIH can overlap with other autoimmune conditions, complicating efforts to make a diagnosis. 4 In addition to liver biopsy data, serological confirmation of the presence autoantibodies has been helpful in screening and confirming the diagnosis of seropositive autoimmune hepatitis (spAIH).…”

Autoimmune liver disease following acute hepatitis A infection

“…The SDC score for our patient was 5 based on raised IgG, typical features of AIH on histology and the absence of a viral hepatitis. However, there have been case reports of seronegative AIH, where the calculated SDC score has not fulfilled the diagnostic threshold for AIH but when employing the RDC scoring system, the score confirmed the diagnosis of AIH 12. An RDC pretreatment score of >15 and post-treatment score >17 gives a definite diagnosis of AIH 13.…”

“…Antisoluble liver antigen/liver pancreas antigen are specific to AIH but only present in 20% of cases at the time of diagnosis,10 and these were not tested for in our patient. Autoantibodies alone are not required for the diagnosis of AIH but can indicate immune-mediated mechanisms,11 and typically antinuclear and/or antismooth muscle antibodies are positive in up to 80% of patients with AIH 12. Autoantibodies can be negative in up to 10% of patients with AIH and particularly in the acute setting may take several months to develop.…”

A Case of Acute Autoimmune Hepatitis Superimposed on Chronic Hepatitis B Infection

“…These autoantibodies are absent in about 10% of AIH patients [ 10 ]. Seronegative AIH was described both in adults and in children with the same demographic, biochemical, and histologic features of classical AIH but negative autoimmune serology [ 11 , 12 ]. As per the clinical practice guideline for AIH, seronegative patients at diagnosis should be monitored for serologic markers as autoantibody titers may fluctuate and can be expressed later during the course of the disease [ 2 ].…”