Increased Incidence of Autoimmune Hepatitis Is Associated With Wider Use of Biological Drugs

Kjartan B. Valgeirsson; Jóhann P. Hreinsson; Einar S. Björnsson

Disclosures

Liver International. 2019;39(12):2341-2349. 

In This Article

Abstract and Introduction

Abstract

Background & aims: Population-based studies on the epidemiology of autoimmune hepatitis (AIH) are scarce. Drug-induced AIH (DIAIH) is increasingly recognized in association with immunomodulatory therapy. We aimed to determine the incidence, prevalence and natural history of AIH in a population-based setting.

Methods: We collected data of new diagnosis of AIH in Iceland from 2006 to 2015. Cases were identified through search of diagnostic codes and text search for AIH within electronical medical records of all hospitals in Iceland and through records of smooth muscle antibodies (SMA) test results by the only laboratory in the country analyzing SMA. Patients were included in the final analysis if they received the clinical diagnosis of AIH or were started on immunosuppressive therapy.

Results: The mean annual incidence of AIH in Iceland was 2.2 cases per 100 000 inhabitants. Point prevalence on 31 December 2015 was 27/100 000. The median age at diagnosis was 56 years and 86% of patients were of female gender. DIAIH was suspected in 13 of 71 patients (18%) of which eight cases were related to infliximab. Immunosuppressive treatment was started in all but two patients. At the end of follow-up (median 4.8 years) 66 of 71 (93%) patients were alive.

Conclusion: The incidence and prevalence rates of AIH in Iceland are the highest reported so far in a population-based setting. Higher incidence can partly be explained by the increasing use of biological drugs. Immunosuppressive therapy was very effective in achieving remission and prognosis was favorable.

Introduction

Autoimmune hepatitis (AIH) is a relatively rare chronic progressive liver disease which can if left untreated progress to cirrhosis and liver failure.[1] The diagnosis is based on combination of clinical, serological and histological features and aided by diagnostic scores.[2–4] Epidemiological studies have been scarce but prior studies report annual incidence rates from 0.7 to 3.0 per 100 000 persons with point prevalence from 8.0 to 42.9 per 100 000.[5–18] Many of these studies are single-centered, with some being population-based[8–11,18,19] but only a handful covering entire nations.[5,6,8,10] The previous nationwide studies[8,15] have only relied on diagnostic codes which is an unreliable methodology without validation of diagnoses because of doubtful accuracy of diagnostic codes in daily clinical practice. The data on origin, number of patients, incidence and prevalence of AIH in 14 studies published during the period of 1982–2019 are summarized in Table 1.[5–18]

Drug-induced autoimmune hepatitis (DIAIH) is an increasingly recognized phenomenon which has been reported to make up around 9% of AIH cases.[20,21] These patients have been shown to have similar clinical, serological and histological patterns compared to those with classical AIH, but unlike those with the classical form discontinuation of immunosuppressive therapy is often successful in the drug-induced form.[20] It can be described as drug-induced liver injury with autoimmune features such as presence of antinuclear antibodies (ANA), anti-smooth muscle antibodies (SMA) and/or elevated immunoglobulin G (IgG).[22] The diagnosis is challenging and although patients with DIAIH share similar clinical, laboratory and histological features with classical AIH[20] neither the old or the new criteria for the diagnosis of AIH have been validated in these patients.[3,4] Typical drugs leading to DIAIH are hydralazine, methyldopa, minocycline and nitrofurantoin.[23] More recently immunomodulatory drugs such as infliximab have been established as a cause.[24–29]

The aims of this study were to study the incidence and prevalence of AIH in a nationwide population-based setting.

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