A 57 year old male presented with right upper quadrant abdominal pain, nausea and fatigue for 2 weeks. Medical history was significant for a recent diagnosis of acquired immune deficiency syndrome (AIDS) and chronic hepatitis B virus (HBV). He was hospitalized 2 months prior for ataxia due to neurotoxoplasmosis. Labs previously were notable for CD4 count 36 cells/ml, HIV viral load 5.32 log copies/ml. HBV serologies were consistent with chronic HBV: core Antigen (Ag) +, core IgG Antibody (Ab) +, eAg +, eAb -, surface Ab -, HBV viral load 7.12 log copies/ml, aspartate transferase (AST) level 39, alanine transferase (ALT) level 51. He was treated for Toxoplasmosis and started on highly active anti-retroviral therapy (HAART): emtricitabine, tenofovir and reltegravir. On representation, labs were notable for AST 1955, ALT 2435, bilirubin 1.4 and INR 1.0. CD4 count 214 cells/ml, HIV viral load 1.79 log copies/ml. HBV serologies: eAg -, eAb + and HBV viral load 5.34 log copies/ml. An abdominal ultrasound and CT scan revealed no focal lesions, nodularity or fatty infiltration of the liver. Liver biopsy (Figures) performed revealed active fibrosis on trichrome stain and viral replication with + HBcAg stain. The patient's clinical, laboratory and histological findings suggested HBV-related Immune Reconstitution Syndrome (IRIS) and he was continued on HAART. Subsequently, AST/ALT levels gradually decreased and symptoms subsided with supportive care over 2 months. IRIS is an inflammatory disorder associated with paradoxical worsening of a preexisting infection, either previously recognized or occult. The condition is commonly seen in AIDS patients although transplant patients may be affected. Diagnostic features include: AIDS with low CD4 count; positive virologic/immunological response to HAART; clinical manifestations of an inflammatory condition; temporal association between initiation of HAART and onset; absence of other causes such as drug reactions, noncompliance or ineffective HAART therapy and other infection. The most common associated GI pathogen is HBV with an estimated incidence of 1-5%. Typical onset is 2-8 weeks after initiation of HAART. Symptoms include: B-symptoms, anorexia, nausea, fatigue, tender hepatomegaly and jaundice. IRIS is usually self-limiting and HAART and HBV treatment are usually continued. Providers should have a high index of suspicion for IRIS in recently treated AIDS patients with new onset GI complaints.Figure 1Figure 2