An Interesting Case of Autoimmune Liver Disease

Introduction

Autoimmune liver diseases (AILD) are part of a spectrum of autoimmune diseases primarily involving the liver and includes autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC). These diseases usually occur in isolation but sometimes their features may overlap, which is a distinct entity with different therapy known as overlap syndrome. Here, we present an atypical case of PBC with features of AIH, thus presenting a diagnostic and therapeutic dilemma. It was important to differentiate PBC from overlap syndrome, as treatment of former focuses on ursodeoxycholic acid while latter needs steroids along with ursodeoxycholic acid.¹

Case Report

A 60-year-old female who was a known case of type 2 diabetes mellitus (DM) and hypothyroidism presented to the clinic with complaints of easy fatiguability for 2 months, generalized itching for 1 month, and right hypochondriac pain for 15 days. She denied any history of fever, jaundice, or clay-colored stools. Physical examination revealed a nontender, firm liver with sharp regular margins palpable 6 cm below costal margin and a palpable spleen 2 cm below costal margin. There was no evidence of scleral icterus, ascites, or stigmata of chronic liver diseases. Initial laboratories showed hemoglobin 8.2 g%, total leukocyte count 8,400 cells/mL, platelet count 2 lacs/mL, liver function tests (LFT) revealed total bilirubin 0.8 mg/dL, aspartate aminotransferase (AST) levels 186 U/l, alanine aminotransferase (ALT) levels 164 U/L, alkaline phosphatase (ALP) 760 µ/L, total protein 7.5 g/dL, albumin 2.5 g/dL, and prothrombin time (PT) 13 seconds. Ultrasonography showed liver span of 17 cm and heterogenous echotexture without any space-occupying lesion (SOL), portal vein diameter 12 mm with hepatopetal flow, normal common bile duct, gall bladder, and spleen 14 cm with normal echotexture without any SOL. Upper gastrointestinal (GI) endoscopy showed single column of grade 1 esophageal varices. Screening tests for hepatitis virus and human immunodeficiency virus were negative. Further laboratories showed thyroid-stimulating hormone (TSH) 60µIU/mL, antithyroid peroxidase 112.9 IU/mL, positive antimitochondrial antibody (AMA) (4 +) and antiliver kidney microsome (1+), IgM levels 7.58 g/L, IgG levels 26.8 g/L and negative antinuclear antibody, antismooth muscle actin, antisoluble liver antigen, antidouble stranded DNA, antitopoisomerase and anti-U₁ ribonucleoprotein. Magnetic resonance cholangiopancreatography (MRCP) did not show any evidence of intrahepatic biliary radical dilation. Liver biopsy showed lobular architecture disarray with portal-to-portal bridging fibrosis, focal ballooning of hepatocytes, edematous expansion of portal tracts with moderate chronic inflammation and interface hepatitis, bile duct injury and bile ductular proliferation (►Fig. 1). Copper-associated protein was present, indicative of chronic cholangiopathy. The overall picture presented a diagnostic dilemma for us. We initially made a diagnosis of AIH based on modified diagnostic criteria of the International Autoimmune Hepatitis Group, however, on using the extended criterion, that is, Revised Original Scoring System of the International Autoimmune Hepatitis Group, our patient falls in the probable diagnosis (10–15); for definite diagnosis > 15 score is needed.² Also the “Paris Criterion” used in various studies of overlap syndrome was not fulfilled in the case (►Table 1).¹ Hence, a final diagnosis of PBC was made and patient was started on 15 mg/kg UDCA and cholestyramine to which patient responded well both symptomatically and biochemically.

Close

Fig. 1

High power (40x) view of hematoxylin and eosin-stained section of liver biopsy, showing interface hepatitis along with bile duct injury and proliferation.

Export to PPT

Discussion

PBC is an autoimmune disease of the liver involving intrahepatic ducts, leading to cholestatic manifestations, seen mainly in middle aged to elderly females. However, patients may also present late with features of cirrhosis and decompensation.³ Apart from historical pointers like pruritis, presence of easy fatigability is also a common feature (60–80%).³ Biochemically, ALP is raised, although AST/ALT may also be slightly increased. Bilirubin generally rises in advanced disease or after development of cirrhosis.⁴ The serological hallmark is the presence of AMA, which is seen in 95% of cases, although anti-PDCE2 or 2-oxo-glutaric acid dehydrogenase complex may also be seen. Liver biopsy is needed for assessing severity of disease or when there are certain atypical manifestations such as AMA-negative cases or raised AST/ALT. There is no definite treatment for PBC and patients are usually treated with ursodeoxycholic acid, which can slow down the course of the disease.

AIH is a chronic inflammatory disorder of liver usually affecting young females and presents with hepatocellular pattern of jaundice. Laboratory features reveal hypergammaglobinemia, presence of antibodies such as characterized by periportal inflammation, hypergammaglobulinemia, and circulating autoantibodies including antinuclear factor, antisoluble liver antigen and liver kidney microsomal antibody. Interface hepatitis is the hallmark feature of AIH and usually has a better prognosis, being responsive to steroid treatment. Sometimes, the clinical picture does not fit any of these and have overlapping features. Such a case is usually termed as overlap syndrome and can be seen in 3–7% of patients with autoimmune liver disease (AILD).⁵ Recently, a case of overlap syndrome was reported by Bairy et al from south India, who was diagnosed on the basis of Paris criteria and treated with ursodeoxycholic acid.⁶ Rust et al reported another case of overlap syndrome treated with budesonide, ursodeoxycholic acid, and azathioprine.⁷ Differentiating overlap syndrome from AIH and PBC has therapeutic implications, as both ursodeoxycholic acid immunosuppression with steroids would be required in patients with overlap syndrome. There are reports of beneficial effects of azathioprine and cyclosporine in corticosteroid-resistant patients with overlap syndrome.^8,9

In conclusion, overlap syndrome is an important differential to consider in patients with PBC showing features of AIH. However, it is important to differentiate patients with PBC showing AIH features from those of overlap syndrome to prevent unnecessary steroids and other immunosuppressants exposure and side effects.