Liver Cirrhosis Secondary to Overlap Autoimmune Liver Disease as the Initial Presentation of Sjögren's Syndrome

The common causes of liver cirrhosis are alcoholic liver disease, nonalcoholic fatty liver disease (NAFLD), and hepatitis B and C viruses [1]. Autoimmune liver diseases (AiLD) account for only approximately 6% of all etiologies causing liver diseases in India and include autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), overlap of these three disorders, and immunoglobulin G4 related disease [2]. AIH is characterized by interface hepatitis and lymphoplasmacytic infiltration on histology, as well as the presence of hypergammaglobulinemia and autoantibodies, such as anti-nuclear antibodies (ANA), anti-smooth muscle antibodies (ASMA), and anti-liver kidney/microsome-1 antibodies (anti-LKM1) [3]. PBC is characterized by progressive intrahepatic duct destruction, leading to cholestasis and the presence of anti-mitochondrial antibodies (AMA) [4]. In India, AIH account for less than 5% of all patients with liver disease. PBC and PSC are much rarer. Some patients present with features of both AIH and PBC; such a condition is called AIH-PBC overlap syndrome. AiLD are more common in females than in males [5]. In two studies from India, the prevalence of AIH-PBC overlap syndrome in patients with AiLD was 11% and 24% respectively [2, 5]. Sjogren's syndrome (SS), characterized by dry eyes, dry mouth, parotid swelling and multisystem involvement, is an autoimmune disease. Anti-Ro and La (SS-A and SS-B) antibodies are usually present in patients with SS. PBC is commonly associated with SS, while hepatitis C, AIH, and nonspecific hepatitis may also occur [6]. Overlap AiLD is rarely observed in SS [7, 8]. A study from China found 4% of liver diseases in SS to be due to AIH-PBC overlap [9]. No case has been reported from India yet. We wish to share an interesting case report of a male patient from India presenting with liver cirrhosis, which was subsequently found to be secondary to AIH-PBC overlap and SS. A 56-year-old man presented with complaints of abdominal distension for 2 weeks. The symptom was insidious in onset and gradually progressive, not associated with vomiting, constipation, abdominal pain, hematemesis, or melena. There was no history of loose stools, fever, or breathlessness. He reported a history of intermittent dry eyes but no history of dryness of mouth, joint pains, chronic fever, or rash. He had never consumed alcohol previously. On examination, he was conscious, oriented, pale, icteric, and had bilateral pitting pedal edema. His pulse rate was 90 beats/min, blood pressure was 110/70 mmHg, oxygen saturation (SpO2) was 98% breathing ambient air, and respiratory rate was 16 cycles/minute. Jugular venous pressure was normal. There were no asterixis. The abdomen was distended with visible dilated veins. The liver was not palpable. The spleen was palpable 3 cm below the left costal margin. Shifting dullness was present. His laboratory findings are summarized in Table 1. His renal function tests and electrolytes were within normal range. He was provisionally diagnosed with ascites secondary to liver cirrhosis with portal hypertension. Negative (< 20) Positive (> 40) Negative (0–0.79); Equivocal (0.80–1.14); Weak positive (1.15–2.49); Positive (2.50–4.00); Strong positive (> 4.00) Abdominal ultrasound (US) revealed a normal-sized liver (right lobe cranio-caudal measurement 13.5 cm) with coarse echotexture and surface nodularity, a dilated portal vein (mean diameter 14.4 mm), an enlarged spleen (17.3 cm from splenic dome to its tip, measured in the coronal view) and gross ascites. A gastroduodenoscopy revealed three columns of large esophageal varices, severe portal hypertensive gastropathy, and duodenopathy, for which endoscopic variceal ligation (EVL) was performed. Based on the presence of portal hypertension signs (varices, splenomegaly, and dilated portal vein) and coarse nodular liver on US, he was diagnosed with liver cirrhosis with portal hypertension. Multiple investigations were performed to identify the cause of liver cirrhosis (Table 1). His ANA, ASMA, AMA, SS-A, and SS-B antibodies were positive on qualitative membrane based enzyme immunoassay. He underwent Schirmer's test and ocular staining with fluorescein dye. Schirmer's test showed a tear distance of 3 mm in both eyes, and the ocular staining score was 5 in both eyes. He did not consent to liver and salivary gland biopsy, so these procedures were not performed. As he met the Paris criteria [10] for AIH-PBC overlap syndrome and the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria [11] for SS, he was diagnosed with liver cirrhosis secondary to AIH-PBC overlap syndrome with SS. He was initiated on ursodeoxycholic acid (UDCA), steroids, propranolol, lactulose, spironolactone, furosemide, and rifaximine. He was also counseled regarding liver transplantation, but he did not consent due to personal reasons. At the 1-month follow-up, the patient's ocular symptoms, liver enzymes, and bilirubin levels showed improvement. To summarize, our patient, who had never consumed alcohol previously, presented with ascites and other symptoms and signs suggestive of chronic liver disease. Further evaluation confirmed liver cirrhosis and portal hypertension. Investigations to assess the etiology of liver cirrhosis showed positive ANA, ASMA, AMA, and SS-A antibodies. The Paris criteria are commonly used to diagnose AIH-PBC overlap syndrome [10]. These criteria require two of the three features associated with AIH, namely: serum alanine aminotransferase levels ≥ 5-fold the upper limit of normal (ULN), immunoglobulin G level ≥ 2-fold ULN or presence of smooth muscle antibodies, and interface hepatitis on histology. They also require two of three features associated with PBC, namely: serum alkaline phosphatase level ≥ 2-fold ULN, positive AMA, and florid duct lesions on histological examination. Our patient satisfied two of the three criteria for both AIH and PBC. The ACR/EULAR criteria [11] are commonly used to classify patients with SS. The criteria are based on the weighted sum of five items: anti-SSA antibody positivity and focal lymphocytic sialadenitis with a focus score ≥ 1 foci/mm2, each scoring 3; an abnormal ocular staining score ≥ 5 (or van Bijsterveld score ≥ 4), a Schirmer test ≤ 5 mm/5 min, and an unstimulated salivary flow rate ≤ 0.1 mL/min, each scoring 1. Individuals with signs or symptoms suggestive of SS who have a total score ≥ 4 based on the above items meet the criteria for primary SS. Our patient's total score was 5. A liver and salivary gland biopsy would have been ideal for this patient. In AIH-PBC overlap, liver biopsy commonly shows features of both AIH (lymphoplasmacytic infiltrates) and PBC (florid duct lesions and granulomas) [12]. For SS, salivary gland biopsy shows focal lymphocytic sialadenitis [11]. As the patient did not consent to these procedures, this was a limiting factor in our study. However, liver and salivary gland biopsies would not have altered our diagnosis as our patient already met the Paris criteria for AIH-PBC overlap syndrome and the ACR/EULAR criteria for SS, respectively. The patient was initiated on a combination of steroids (prednisolone 60 mg tablet once daily for 1 week, followed by a tapering regimen with a dose reduction of 10 mg per week for the next 5 weeks utill reaching 5 mg daily) and UDCA, which is the recommended treatment for AIH-PBC overlap syndrome [13]. Liver transplantation was also considered due to the presence of cirrhosis and portal hypertension, but it could not be done due to lack of patient consent. At the 1-month and 3-month follow-ups, the patient's ocular symptoms, liver enzymes and bilirubin levels showed improvement. To conclude, we reported a case of a male patient who presenting with liver cirrhosis and portal hypertension, who was diagnosed with AIH-PBC overlap syndrome with SS, which is a rare association in the Indian population. He was treated with a combination of UDCA and steroids. Further studies are needed to determine the exact prevalence of overlap syndrome in patients with SS in the Indian population. Saikrishna R. Bana: conceptualization, writing the original draft. Prabhanjan V. Kulkarni: conceptualization, methodology, writing the original draft. Jagannath S. Dhadwad: conceptualization, review and editing of the draft. Roushan Kumar: conceptualization, and review and editing of the draft. All the authors have read and approved the final version of the manuscript. We wish to thank Dr. Sheetal N. K., Dr. Kunal Modi, Dr. Prince Yadav, Dr. Dhairya Sanghani, Dr. Chandan Dash, and Dr. Janvi Panchal for their contribution in this manuscript. The authors received no specific funding for this work. The Ethics Committee of Dr. D.Y. Patil Medical College, Hospital & Research Centre approved this case report. Written informed consent was obtained from the patient. The authors declare no conflicts of interest. Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.