Abstract

INTRODUCTION: The regimen of glecaprevir and pibrentasvir is an effective treatment for hepatitis C (HCV), but FDA data suggests a risk of hepatobiliary toxicity. Here, we discuss the first description of hepatorenal syndrome secondary to hepatobiliary toxicity from glecaprevir/pibrentasvir. CASE DESCRIPTION/METHODS: A 65-year-old man with chronic HCV (genotype 1a), alcohol use disorder, and hepatocellular carcinoma (HCC), presented with abdominal distention and jaundice for one month. He was diagnosed with HCC in 2014 and treated with resection and adjuvant sorafenib without evidence of recurrence, and thus began HCV treatment with glecaprevir/pibrentasvir. At baseline he was Childs-Pugh class A with a total bilirubin of 0.9 mg/dL, INR of 0.95, and albumin of 3.2. Twenty-four days after initiation of glecaprevir/pibrentasvir he presented with fevers, fatigue, and dark urine. On exam he had jaundice, abdominal distension, and right upper quadrant tenderness. His labs showed a total bilirubin of 25.5 mg/dL, direct bilirubin of 16.1 mg/dL, INR of 1.64, and creatinine of 1.6 mg/dL (1.1 mg/dL two weeks prior). He was initially started on a three-day albumin challenge, but his renal function continued to decompensate, raising concern for a type 1 HRS, so he was transitioned to octreotide, midodrine, and albumin. Glecaprevir/pibrentasvir was also discontinued due to his acute liver decompensation after only 29 days of treatment. Eight days later, the patient’s creatinine had decreased from 2.0 to 1.3 mg/dL and his total bilirubin decreased from 25.6 to 16.4 mg/dL. Four months after discharge he has continued to improve with creatinine as low as 1.2mg/dL and a total bilirubin of 3.7 mg/dL. Notably, despite just four weeks of glecaprevir/pibrentasvir, his hepatitis C viral load has remained undetectable. DISCUSSION: In 2019, the FDA distributed a safety communication outlining liver injury in 46 individuals on glecaprevir/pibrentasvir and suggested avoidance in Child-Pugh class B and C patients. While research of the safety profile for glecaprevir/pibrentasvir in Child-Pugh class A is needed, this case reports highlights the importance of early and regular monitoring of liver and renal function in patients on this regimen. Current glecaprevir/pibrentasvir regimens are 12 weeks, yet a shortened four-week regimen still provided virus eradication in this case, raising the possibility of personalized treatment based on viral load. This could reduce potential side effects as well as the cost of antiviral therapy.

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