Clinical Profile and HLA Typing of Autoimmune Hepatitis From Pakistan

Abstract

BackgroundHuman leukocyte antigen (HLA) typing in autoimmune hepatitis (AIH) has been investigated in different populations and ethnic groups, but no such data is available from Pakistan.ObjectivesThe aim of this study was to evaluate the clinical profile of autoimmune hepatitis (AIH), and determine the associated antigens and alleles by performing HLA typing.Patients and MethodsA total of 58 patients, diagnosed and treated as AIH in the last 10 years were reviewed. Diagnosis was based on International AIH Group criteria. Forty one patients underwent liver biopsy. HLA typing was performed in 44 patients and 912 controls by serological method for HLA A and B, and by PCR technique using sequence specific primers for DR alleles.ResultsOf 58 cases, 35 were females (60.3%). The median age was 14.5 (range 4-70 years), and AIH score was 14 (10-22). Thirty-six (62.0%) patients had type 1 AIH, 10 (17.2%) type 2, and the remaining 12 were seronegative with biopsy proven AIH. Forty-nine patients (84.4%) had cirrhosis. Twenty-four (41.4%) patients had ascites at the time of presentation. Among 41 patients who underwent liver biopsy, thirty-two had advance stages III and IV disease, and twenty had severe grade of inflammation. Fifteen patients had other associated autoimmune diseases and one developed hepatocellular carcinoma. HLA A2 (P = 0.036), HLA A9 (23) (P = 0.018), HLA A10 (25) (P = 0.000), HLA A19 (33) (P = 0.000), HLA B15 (63) (P = 0.007), HLA B40 (61) ( P = 0.002), HLA DR6 (P = 0.001) with its subtypes HLA-DRB1*13 (P = 0.032) and HLA-DRB1*14 (p = 0.017) were more prevalent in AIH with statistical significance than controls.ConclusionsAIH in our region presents with advanced disease affecting predominantly children and adolescents. There is a genetic association of HLA DR6 along with other alleles and antigens in our patients with AIH.

Precision medicine for autoimmune hepatitis

“…HLA DRB1*0405 was a major susceptible locus for AIH‐1 in China and Japan, and the HLA DRB1*0405‐DQB1*0401 haplotype indicates a high risk of AIH in Japan . However, it was HLA B27 and cw4 that had significant associations with AIH‐1 in West India, and HLA DR6 in Pakistan . The HLA DQB1*0201 allele had a close association with susceptibility to AIH‐2 in Caucasians .…”

Serum Positivity of Ana and Asma Among Khat and Nonkhat Chewers as Markers for Autoimmune Hepatitis Type 1

“…The etiology of AIH remains unknown but is postulated to be related to an autoimmune process triggered by either genetic predisposition or environmental agents. AIH is strongly associated with human leukocyte antigens (HLA-DR3 and HLA-DR4, HLA-DR6) [11][12][13][14] . Environmental factors are thought to be the triggering factors for the development of AIH in genetically susceptible individuals.…”

Similarities and Differences in Autoimmune Hepatitis Epidemiology between East and West: Autoimmune Hepatitis in East Asia, Southeast Asia, and South Asia

“…In South Asian countries, type 2 AIH is relatively prevalent (11.2% in India [26] and 17.2% in Pakistan [27] ), resulting in a lower frequency of type 1 AIH than in East Asian countries ( Table 1 ). However, pediatric patients were only surveyed in Japan, India, and Pakistan.…”

“…In one study from Pakistan [27] , HLA-A2, HLA-A9, HLA-A10, HLA-A19, HLA-B15, HLA-B40, and HLA-DR6 were reported as potential disease-related genetic characteristics. These authors reported that HLA-DR6 was the most strongly related factor; however, its clinical significance remains unclear and needs to be further evaluated.…”

“…Additionally, liver cirrhosis was frequently observed at diagnosis in South Asia (71.2% in India [26] and 84.1% in Pakistan [27] ). On comparison with AIH patients in non-Asian countries [17,[29][30][31] , the frequencies of cirrhotic patients at diagnosis were markedly high in South Asia ( Fig.…”