LETTER Chronic HBV-infected subjects older than 35 years with persistently normal ALT and ultrasound, despite high viral load do not have significant fibrosis Akash Shukla 1 & Amit Gupte 1 & Prajakta Gupte 2 & Tejas Modi 1 & Amita Joshi 2 & Rachana Chaturvedi 2 & Hemangini Thakkar 3 & Shobna Bhatia 1 # Indian Society of Gastroenterology 2015 Dear Sir, Liver biopsy is recommended in patients who do not meet clear-cut guidelines for antiviral treatment, especially in pa- tients >40 years of age [1]. At our centre, we perform liver biopsy in all patients with chronic hepatitis B virus (HBV) infection who are >35 years of age and who have normal ALT and ultrasonography (USG), and a significant viral load. Here, we present our data on the stage of fibrosis and grade of inflammation on liver biopsy in these patients, and its com- parison with a group of patients with chronic HBV infection who had mild liver enzyme elevation (1–2× ULN) and/or coarse echotexture of the liver on USG. Institutional review board clearance was obtained. We retrieved records of all the patients with chronic hepatitis B infection (CHB) who underwent liver biopsy between January 2010 and June 2012. ALT levels up to 40 U/L were considered as nor- mal. Normal hepatoportal USG was defined as the presence of normal liver span and contour, and absence of coarse echotexture. Patients with features of portal hypertension on USG (splenomegaly, venous collaterals and ascites) were not included. A team of three dedicated liver pathologists reviewed histopathology at our institute and arrived at a consensus. Stage of fibrosis (using H&E, Masson’ s trichrome and reticulin stains) and grade of activity were analyzed using modified histologic activity index (HAI). Stage ≥2 fibrosis and grade ≥3 inflammation by HAI was considered as signif- icant fibrosis and inflammation, respectively [2]. Patients who had alcohol intake >20 g/day, hepatitis C, HIV, evidence of cirrhosis (clinical, biochemical or imaging), diabetes mellitus or BMI ≥30 kg/m 2 was excluded. Proportions of patients with significant fibrosis and inflammation amongst the groups were analyzed using Fischer exact test. Two hundred and eighty consecutive newly diagnosed pa- tients with chronic HBV infection were seen between January 2010 and June 2012. Sixty-three patients were advised liver biopsy; 9 patients did not give consent. Fifty-four patients underwent liver biopsy. Twenty-nine patients (44.3±6.5 years, 23 men) with normal ALT, normal USG, age >35 years and HBV DNA ≥2000 IU/mL comprised group A and had a medi- an HBV DNA of 4020 IU/mL [2030–1.7×10 8 ]. Twenty-five patients (35.8±11.9 years, 22 men) had either ALT 1–2× ULN or coarse echotexture on USG or both, and comprised group B and had a median HBV DNA of 9000 IU/mL (2000–1.7× 10 8 ). Twelve patients of group A had ALT less than or equal to 20 U/L (subgroup A1), and 17 had an ALT level between 20 and 40 U/L (subgroup A2). The biopsy findings have been shown in Table 1. More patients in group B had fibrosis and inflammation as compared to group A (p =0.001, stage; p =0.001, grade). Within group B, six patients had coarse echotexture on USG and normal ALT; two of them had a significant fibrosis and one had a significant inflammation. In a previous study in patients with chronic hepatitis B infection, 71 % of the subjects with elevated ALT had an HAI >3, and 36 % with normal ALT showed significant his- tological changes [3]. In another study, patients with chronic hepatitis B virus infection with persistently normal ALT (≤40 U/L) had fibrosis stage ≥2 in 39.7 % in hepatitis B e- * Akash Shukla drakashshukla@yahoo.com 1 Department of Gastroenterology, Seth G S Medical College and K E M Hospital, Acharya Dhonde Marg, Parel, Mumbai 400 012, India 2 Department of Pathology, Seth G S Medical College and K E M Hospital, Acharya Dhonde Marg, Parel, Mumbai 400 012, India 3 Department of Radiology, Seth G S Medical College and K E M Hospital, Acharya Dhonde Marg, Parel, Mumbai 400 012, India Indian J Gastroenterol DOI 10.1007/s12664-015-0557-4