Patrick J. Carey, MD1, Nimish Thakral, MD2, Venkata Rajesh Konjeti, MD2, Alla Y. Grigorian, MD, PhD2 1University of Kentucky College of Medcine, Lexington, KY; 2University of Kentucky, Lexington, KY
Introduction: Although chemotherapy has been shown to improve survival rates in metastatic colorectal cancer (mCRC), it can be associated with severe side effects. Regorafenib, an oral multikinase inhibitor, is used in treatment-refractory mCRC but carries a risk of developing pseudocirrhosis. We present a rare case of pseudocirrhosis resulting from regorafenib use.
Case Description/Methods: A 39-year-old male with Stage IV adenocarcinoma of the colon with metastatic liver lesions presented with a few days of diffuse abdominal pain and mild jaundice. CT abdomen showed cirrhotic liver morphology, ascites, splenomegaly, and non-obstructed biliary tract. He recently started regorafenib 4 months prior, after failing three prior chemo/immunotherapy regimens. Initial labs were – T Bili 5.5 mg/dl (direct 3.8 mg/dl), alkaline phosphatase 594 IU/L, GGT 272 IU/L, AST 55 IU/L, ALT 39 IU/L, and INR 1.4.
MRCP demonstrated an interval increase in hepatic metastases burden with non-obstructed biliary tract. MRI abdomen is shown in Figure 1. Serology showed positive ANA 1:640 and elevated IgG. Infectious workup was negative. Ascitic fluid studies showed a SAAG of 2 without evidence of SBP or malignancy. Liver biopsy demonstrated normal lobular architecture, severe cholestasis, and focally prominent sinusoidal dilatation but was negative for cirrhosis, bridging fibrosis, sinusoidal obstruction, fatty change, or centrilobular necrosis. Portosystemic gradient ranged from 1-8 mmHg. He was started on spironolactone, furosemide, and ursodiol and underwent pre-emptive biliary stenting. Ultimately, the patient was diagnosed with regorafenib-induced pseudocirrhosis. Due to persistently increasing bilirubin, no further treatment options were available. He was offered hospice care.
Discussion: Pseudocirrhosis refers to the radiological appearance of cirrhotic liver morphology sans histological evidence of fibrosis. Regorafenib-induced pseudocirrhosis falls under the realm of idiosyncratic drug-induced liver injury. Although studies postulate nodular regenerative hyperplasia (NRH) as the causative pathology, no evidence of NRH was found in our case. The presence of concomitant cholestasis and sinusoidal dilation was indicative of a post-sinusoidal pathology. Given the increasing incidence of CRC, high suspicion and awareness about this condition are warranted.
Patrick Carey indicated no relevant financial relationships.
Nimish Thakral indicated no relevant financial relationships.
Venkata Rajesh Konjeti indicated no relevant financial relationships.
Alla Grigorian indicated no relevant financial relationships.
Patrick J. Carey, MD1, Nimish Thakral, MD2, Venkata Rajesh Konjeti, MD2, Alla Y. Grigorian, MD, PhD2. B0570 - Not All Cirrhosis Is Created Equal: A Rare Case of Regorafenib-Induced Pseudocirrhosis, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.