Introduction: Drug-induced liver injury (DILI) is a potentially fatal cause of liver disease. Pre-existing liver disease, genetic susceptibility and concomitant hepatitis B or C or HIV may predispose certain individuals to poor outcomes. We describe a case of trimethoprim/sulfamethoxazole (TMP-SMZ) DILI in a patient co-infected with AIDS and hepatitis B. Case Description/Methods: A 53 year-old man with untreated HIV presented to a local hospital with 1 week of dizziness, syncope and right-sided weakness. He was diagnosed with cerebral toxoplasmosis and started on IV TMP-SMZ on hospital day 14 with initial improvement in mental status. His hospitalization was complicated by acute renal failure with worsening mental status and newly elevated liver function tests (LFTs) from normal at baseline. LFTs on hospital day 25 were notable for TBili 0.9, Dbili 0.5, INR 0.96, AlkP 104, AST 121, ALT 407 (Table 1). That day, trimethoprim / sulfamethoxazole was discontinued and IV NAC was initiated on day 27. Liver biopsy revealed “cholestatic hepatitis with pericentral hepatocellular and canalicular cholestasis, mild lobular and portal inflammation consistent with drug induced liver injury”. Subsequent hospital course was complicated by E. coli bacteremia and progressive renal and liver injury (Figure 1). The patient unfortunately passed away from multiorgan failure on hospital day 42. Discussion: TMP-SMZ is a fixed antibiotic combination used for bacterial infections and as prophylaxis against opportunistic infections in HIV patients. Although generally well-tolerated, TMP-SMZ can have a higher rate of adverse reactions in HIV-positive patients: 40%–80% of HIV infected individuals, compared to 3%–5% in the general population. These drug reactions range from hypersensitivity-like reactions to organ failure. AIDS has been suggested to be significantly associated with the development of hepatotoxicity. The pathogenesis is unknown, but may reflect disease-induced alterations in bioactivation or detoxification of reactive metabolites, as well as immune dysregulation. Although typical prognosis for TM P-SMZ-associated DILI is favorable with expected recovery in 2-8 weeks, prognosis is markedly worse in AIDS patients as well as patient’s co-infected with HBV or HCV. There are currently no guidelines for monitoring high risk patients for DILI in the hospital setting. In our case, we incidentally discovered his DILI after 11 days of treatment with TMP-SMZ. Moving forward, we should consider screening parameters in these higher risk populations.Figure 1.: AST, ALT, ALKP Trends During Hospitalization. Table 1. - Workup Hospital Day 25 Total Bilirubin 0.9 Direct Bilirubin 0.5 Alkaline phosphatase 104 AST 121 ALT 407 HbsAG + Hep B Viral Load 193 HBe Ag + HBcIgM, HBsAb - HIV PCR 116k
Introduction: The formation of hepatic abscesses (HA) after locoregional therapy (LT) for hepatocellular carcinoma (HCC) is a rare complication. It is postulated that prior bacterial seeding of peribiliary capillaries acts as a nidus for HA. We report a cohort of 4 patients with decompensated cirrhosis and HCC who developed HA after LT from 2019 to 2022. Case Description/Methods: Patient 1 is an 81-year-old man with NASH cirrhosis (Child-Pugh C) complicated by HCC with microwave ablation (MWA) and transarterial chemoembolization (TACE), ascites, esophageal varices (EV), hepatic encephalopathy (HE) and spontaneous bacterial peritonitis (SBP), who developed biloma and strictures after right hepatectomy, requiring stenting and sphincterotomy. A 9.0 cm segment 2 and 3 HA formed 56 days after MWA growing Morganella and Pseudomonas treated with 6 weeks cefepime and drain placement for 50 days. He had two more recurrences of HA. Patient 2 is a 76-year-old man with HCV cirrhosis (Child B) complicated by HCC with MWA and transarterial radioembolization (TARE), ascites and portal vein thrombus (PVT) who developed ischemic hilar strictures and biloma after yttrium-90 TARE. A 7.3 cm segment 5 and 8 HA formed 12 days after MWA growing Klebsiella treated with 4 weeks ceftriaxone and metronidazole and drain placement for 84 days. Patient 3 is a 72-year-old man with pancreatic adenocarcinoma and HCV cirrhosis (Child A) complicated by HCC and ascites who underwent Whipple procedure and developed biliary strictures after MWA. A 6.9 cm segment 5 HA formed 20 days after MWA growing Enterococcus and Streptococcus treated with 3 weeks moxifloxacin and drain placement for 50 days. Patient 4 is a 70-year-old woman with HIV, cholangiocarcinoma and HCV cirrhosis (Child B) complicated by HCC with MWA and TACE, ascites, EV, HE, SBP and PVT who developed malignant strictures requiring stents and sphincterotomy. A 6.1 cm segment 6 HA formed 1230 days after MWA growing Klebsiella, Streptococcus and Parvinomas complicated by cholangitis and bacteremia treated with 10 weeks of antibiotics narrowed to ceftazidime-avibactam and needle aspiration. All patients received the same perioperative antibiotic prophylaxis. Discussion: This case series demonstrates the role prior biliary manipulation may play in increasing susceptibility to HA formation in HCC patients undergoing LT. Further investigation into rates of HA in patients without biliary manipulation, with other comorbidities, and those receiving alternative prophylaxis is warranted (Table 1). Table 1. - Compiled Patient Cohort Data Demographic Information Patient 1 2 3 4 Age 81 76 72 70 Race White Black White Black Comorbidities Atrial fibrillation, COPD Diabetes mellitus Pancreatic adenocarcinoma, aortic stenosis, COPD Cholangiocarcinoma, HIV, ESRD Cirrhosis Information Patient 1 2 3 4 Cirrhosis Etiology NASH HCV HCV HCV Cirrhosis Complications HCC, ascites, EV, HE, SBP HCC, ascites, PVT HCC, ascites HCC, ascites, EV, HE, SBP, PVT Reason for OLT Rejection Age Patient preference Medical comorbidities, Pancreatic adenocarcinoma Cholangiocarcinoma HCC Information Patient 1 2 3 4 Liver Segments with HCC 2, 3, 4A, 5, 6 2, 3, 4A 4A, 6 6, 7 Child-Pugh Class at Diagnosis C B A B HCC Systemic Therapy Nivolumab, Levatinib SBRT None None Locoregional Treatment Information Patient 1 2 3 4 Number TACE Procedures 2 0 0 2 Number TARE Procedures 0 1 0 0 Number MWA Procedures 4 5 2 2 Hepatic Artery Embolized Right and Left Right Right Right and Left Prophylactic Antibiotics Moxifloxacin Moxifloxacin Moxifloxacin Moxifloxacin Perioperative Antibiotics Piperacillin-tazobactam Piperacillin-tazobactam Piperacillin-tazobactam Piperacillin-tazobactam Procedural Complications None Ischemic hilar stricture Biliary stricture None Abscess and Treatment Information Patient 1 2 3 4 Bilioenteric Risk Factors Right hepatectomy with bilomaLeft hepatic duct stricture with stent, sphincterotomy Hilar stricture with stent, fistulotomyHemobilia, biloma Pancreaticoduodenectomy (Whipple procedure) CholangiocarcinomaMalignant stricture with stent, sphincterotomy Locoregional Treatment Received before Abscess MWA MWA MWA MWA Time from Locoregional Treatment to Abscess Formation 56 days 12 days 20 days 1230 days Labs on Abscess Diagnosis WBC 13.2 B/LCr 1.48 mg/dLTotal bilirubin 0.8 mg/dLAST 83 IU/LALT 69 IU/LINR 1.46 lactate 2.3 mmol/LAFP 10 mg/mL WBC 22.5 B/LCr 1.60 mg/dLTotal bilirubin 3.1 mg/dLAST 18 IU/LALT 11 IU/LINR 1.40 lactate 2.2 mmol/LAFP 2.5 mg/mL No labs collected WBC 13.0 B/LCr 1.50 mg/dLTotal bilirubin 3.3 mg/dLAST 62 IU/LALT 18 IU/LINR 2.20 lactate 3.0 mmol/LAFP 699 mg/mL MELD on Abscess Diagnosis 14 16 7 25 Liver AbscessSegment 2 and 3 5 and 8 5 6 Liver Abscess Size in Largest Dimension 9.0 cm 7.3 cm 6.9 cm 6.1 cm Organisms Isolated Morganella morganiiPseudomonas aeruginosa Klebsiella pneumoniae Enterococcus faeciumStreptococcus viridans Klebsiella pneumoniaeStreptococcus sanguinosisParvinomas micra Antibiotic Treatment Cefepime, 6 weeks Ceftriaxone and metronidazole, 4 weeks Moxifloxacin, 3 weeks Broad coverage 8 weeksCeftazidime-avibactam 2 weeks Abscess Complications Recurrence x2 None None CholangitisStreptococcus sanguinosis bacteremia Drainage Catheter Duration 28 days 84 days 50 days Needle aspiration only Days Hospitalized 4 days 10 days 1 day 72 days COPD: chronic obstructive pulmonary disease, HIV: human immunodeficiency virus, ESRD: end stage renal disease, NASH: nonalcoholic steatohepatitis, HCV: hepatitis C virus, HCC: hepatocellular carcinoma, EV: esophageal varices, HE: hepatic encephalopathy, SBP: spontaneous bacterial peritonitis, PVT: portal vein thrombus, OLT: orthotopic liver transplant, SBRT: sterotactic body radiation therapy, TACE: transarterial chemoembolization, TARE: transarterial radioembolization, MWA: microwave ablation, WBC: white blood cell, Cr: creatinine, AST: aspartate transaminase, ALT: alanine transaminase, INR: interational normalized ratio, AFP: alpha fetoprotein.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease and is associated with significant cardiovascular morbidity and mortality. This study aims to investigate the association of glucagon-like peptide-1 (GLP-1) agonists with major cardiovascular events, clinically significant portal hypertension events, and all-cause mortality in patients with MASLD. A large, population-based retrospective cohort study was conducted using the TriNetX platform, which provided real-time access to electronic health records of 634,265 adult patients with MASLD/MASH. Propensity score matching (PSM) was employed to create two cohorts: A GLP-1 agonists group and a control group without GLP-1 agonists usage. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models along with Kaplan-Meier survival analyses to estimate outcomes at the end of 1, 3, 5, and 7 years. After PSM, 6,243 patients were included in each group. The GLP-1 agonist group had significantly lower risk of heart failure (at 7 years, HR, 0.721; 95% Cl, 0.593–0.876), composite cardiovascular events (at years 7, HR, 0.594; 95% Cl, 0.475–0.745), clinically significant portal hypertension events (at 7 years, HR, 0.463; 95% Cl, 0.348–0.611), and all-cause mortality (at 7 years, HR, 0.303; 95% Cl, 0.239–0.385). These results were consistent at 1-, 3-, 5-, and 7-years post index event. GLP-1 agonists usage in patients with MASLD is associated with reduced risk of major cardiovascular events, clinically significant portal hypertension, and all-cause mortality. These findings highlight the potential of GLP-1 agonists in MASLD/MASH management, warranting further prospective studies.
