Background Idiosyncratic drug‐induced liver injury (DILI) is an uncommon but potentially severe adverse drug reaction. Although cloxacillin and terbinafine are long‐established, widely prescribed agents, both have been associated with mixed/cholestatic DILI, occasionally resulting in prolonged cholestasis or vanishing bile duct syndrome (VBDS). We report two cases with similar clinical and biochemical presentations but markedly different histological findings and long‐term outcomes, illustrating that the initial biochemical phenotype may not reflect the extent of bile duct injury or predict subsequent clinical evolution. Case Report An 83‐year‐old man presented with jaundice, dark urine, and severe pruritus after receiving cloxacillin for 2 months to treat acute paronychia. A 62‐year‐old man developed similar symptoms following a 2 month course of terbinafine for a fungal infection. Both patients exhibited a mixed biochemical pattern of liver injury. Comprehensive diagnostic evaluation, including detailed medical history, abdominal imaging, viral and autoimmune serology, excluded alternative causes of liver injury. Causality assessment using the updated RUCAM classified both cases as probable DILI. Liver biopsy demonstrated extensive ductopenia with loss of interlobular bile ducts in more than 50% of portal tracts, consistent with VBDS in the cloxacillin case, whereas the terbinafine case showed intracanalicular cholestasis with preserved bile ducts. HLA genotyping identified the HLA‐B∗57:01 and HLA‐A∗33:01 susceptibility alleles, respectively. Both patients received supportive treatment with ursodeoxycholic acid, cholestyramine, and rifampicin. The first patient achieved complete biochemical recovery after 8 months, whereas the second fulfilled criteria for chronic DILI with persistent liver test abnormalities beyond 1 year. Conclusions These cases illustrate marked clinicopathological heterogeneity despite a similar initial presentation and mixed DILI biochemical pattern. The contrast between biopsy‐proven VBDS followed by complete biochemical recovery and preserved bile duct architecture followed by chronic DILI demonstrates that the extent of histological bile duct injury and long‐term outcome cannot necessarily be inferred from the initial biochemical phenotype.
Drug-induced liver injury (DILI) is a leading cause of acute liver failure (ALF) and an increasingly recognised consequence of unregulated performance-enhancing supplements. We report a 17-year-old male who presented with progressive jaundice and rapidly evolving ALF temporally associated with ingestion of the synthetic REV-ERB agonist SR9009. Despite early treatment with N-acetylcysteine, he developed worsening coagulopathy, hyperbilirubinaemia, ascites and Grade 3 hepatic encephalopathy, necessitating emergency liver transplantation. Extensive investigation excluded viral, autoimmune, metabolic and obstructive causes. Liver biopsy demonstrated severe hepatocellular injury with confluent and multiacinar necrosis, consistent with severe DILI. Following transplantation, liver biochemistry and synthetic function improved rapidly. This case highlights the hepatotoxic potential of unregulated supplements, the importance of obtaining a detailed exposure history in young patients with acute liver injury and the need for early recognition of progressive liver failure requiring timely referral to a liver transplant centre.
Background Cholestatic liver injury from 17α‐alkylated anabolic–androgenic steroids is established. We report a longitudinally documented case that emphasises phenotype definition and the limits of agent‐specific attribution. Case Presentation A 26‐year‐old man presented on Day 29 after self‐administering oral oxymetholone 50 mg/day with intramuscular testosterone enanthate 250 mg/week. Peak total bilirubin was 24.6 mg/dL (direct bilirubin 21.3 mg/dL), alanine aminotransferase 5.6 × the upper limit of normal (ULN) and alkaline phosphatase 2.9 × ULN; the R‐ratio was 1.91, indicating cholestatic injury. International normalised ratio (≤ 1.04), albumin (≥ 4.1 g/dL) and creatinine (0.8–0.9 mg/dL) remained preserved. Ultrasonography with hepatic Doppler showed a nondilated biliary tree (common bile duct 1–2 mm), patent visualised vessels and no sonographic evidence of obstruction. The available viral, autoimmune, metabolic and haemolytic evaluation identified no alternative cause. Updated RUCAM assessment was limited by ursodeoxycholic acid use during dechallenge and incomplete molecular virology; concomitant testosterone and absent chemical verification of the products precluded definitive single‐agent attribution. Both agents were withdrawn on Day 30; ursodeoxycholic acid and antipruritic therapies were used as supportive care. Outcome Total bilirubin decreased by 69.1% by Day 57 and by 91.5% by Day 85. Pruritus resolved, daily function returned and renal and hepatic synthetic function remained preserved. Conclusion This report provides granular 8‐week follow‐up of an established phenotype. The course supports oxymetholone as the principal suspect, but recovery cannot be attributed to supportive pharmacotherapy in this uncontrolled case.
Background:Malignant and benign hepatic diseases may both present with systemic symptoms and necrotic liver cavities. Although rare and reported predominantly in East Asia, pyogenic liver abscess (PLA) can represent the initial manifestation of hepatocellular carcinoma (HCC), as necrotic tumors may mimic infectious abscesses. Case Presentation:A 63-year-old Italian man presented with a 2-week history of fever and right upper quadrant pain. Computed tomography revealed a multiloculated lesion with irregular margins and a solid component in the right hepatic lobe, suggestive of a liver abscess, and empirical tigecycline therapy was initiated. Low-titer Entamoeba spp. IgG antibodies were detected, and percutaneous aspiration yielded material initially mischaracterized as "anchovy paste," raising suspicion for amoebic liver abscess. However, the patient failed to improve despite appropriate antiprotozoal therapy. Subsequent percutaneous drainage led to cavity resolution and symptom relief; all microbiological and parasitological tests were negative, and repeat Entamoeba serology became negative. Concurrent biopsy of the solid component revealed well-differentiated pseudoglandular HCC. Magnetic resonance imaging demonstrated a biliary fistula associated with the neoplastic lesion, supporting a diagnosis of PLA secondary to HCC. The patient underwent right hepatectomy, complicated by intraoperative abscess rupture and postoperative intra-abdominal abscesses caused by vancomycin-resistant Enterococcus faecium. Discussion:PLA presenting as the initial manifestation of HCC is associated with poor prognosis, largely due to diagnostic delays. Limited clinical experience outside high-prevalence regions and nonspecific clinical, laboratory, and imaging findings contribute to underrecognition of malignancy. Positive microbiological or serological results and transient clinical improvement during antimicrobial therapy do not exclude an underlying neoplasm. Liver biopsy and close radiologic follow-up are essential in atypical or treatment-refractory cases. Conclusion:PLA as a presenting feature of HCC is unusual, especially in Europe, yet poses substantial diagnostic and therapeutic challenges. Increased clinical awareness and early histopathological evaluation are crucial to avoid delayed oncologic diagnosis.
Isolated polycystic liver disease (PLD) is rare and may cause debilitating mass-effect symptoms despite relatively preserved hepatic synthetic function. Because the Model for End-Stage Liver Disease (MELD) score does not capture nutritional, functional, and mechanical disease burden, affected patients may have low calculated MELD scores despite advanced symptomatic disease. Updated MELD exception guidance broadened consideration for PLD to include malnutrition and sarcopenia. We describe a patient with isolated PLD who was initially considered too well for transplantation but subsequently developed progressive weight loss, sarcopenia, and functional decline, prompting repeat evaluation, wait-list registration, and MELD exception approval. Several weeks after listing, he sustained traumatic hepatic cyst rupture, resulting in fatal hemoperitoneum and abdominal compartment syndrome. This case highlights the evolving clinical course of symptomatic PLD, the importance of longitudinal reassessment, and the potential severity of rare cyst-related complications.
