Terlipressin therapy is associated with increased risk of colonisation with multidrug-resistant bacteria in patients with decompensated cirrhosis.

BACKGROUND: Patients with cirrhosis are susceptible to develop bacterial infections that trigger acute decompensation (AD) and acute-on-chronic liver failure (ACLF). Infections with multidrug-resistant organisms (MDRO) are associated with deleterious outcome. MDRO colonisation frequently proceeds MDRO infections and antibiotic therapy has been associated with MDRO colonisation. AIM: The aim of the study was to assess the influence of non-antibiotic medication contributing to MDRO colonisation. METHODS: Three hundred twenty-four patients with AD and ACLF admitted to the ICU of Frankfurt University Hospital with MDRO screening were included. Regression models were performed to identify drugs associated with MDRO colonisation. Another cohort (n = 129) from Barcelona was included to validate. A third multi-centre cohort (n = 203) with metagenomic sequencing data of stool was included to detect antibiotic resistance genes. RESULTS: A total of 97 patients (30%) were identified to have MDRO colonisation and 35 of them (11%) developed MDRO infection. Patients with MDRO colonisation had significantly higher risk of MDRO infection than those without (p = 0.0098). Apart from antibiotic therapy (odds ratio (OR) 2.91, 95%-confidence interval (CI) 1.82-4.93, p < 0.0001), terlipressin therapy in the previous 14 days was the only independent covariate associated with MDRO colonisation in both cohorts, the overall (OR 9.47, 95%-CI 2.96-30.23, p < 0.0001) and after propensity score matching (OR 5.30, 95%-CI 1.22-23.03, p = 0.011). In the second cohort, prior terlipressin therapy was a risk factor for MDRO colonisation (OR 2.49, 95% CI 0.911-6.823, p = 0.075) and associated with risk of MDRO infection during follow-up (p = 0.017). The validation cohort demonstrated that antibiotic inactivation genes were significantly associated with terlipressin administration (p = 0.001). CONCLUSIONS: Our study reports an increased risk of MDRO colonisation in patients with AD or ACLF, who recently received terlipressin therapy, while other commonly prescribed non-antibiotic co-medications had negligible influence. Future prospective trials are needed to confirm these results.

Evaluation of Ultrasound-based Surveillance for Hepatocellular Carcinoma in Patients at Risk: Results From a German Multicenter Retrospective Cohort Study.

Background and Aims: Hepatocellular carcinoma (HCC) surveillance in patients at risk is strongly recommended and usually performed by ultrasound (US) semiannually with or without alfa-fetoprotein (AFP) measurements. Quality parameters except for surveillance intervals have not been strictly defined. We aimed to evaluate surveillance success and risk factors for surveillance failure. Methods: Patients with ≥1 US prior to HCC diagnosis performed at four tertiary referral hospitals in Germany between 2008 and 2019 were retrospectively analyzed. Surveillance success was defined as HCC detection within Milan criteria. Results: Only 47% of 156 patients, median age 63 (interquartile range: 57-70) years, 56% male, and 96% with cirrhosis, received recommended surveillance modality and interval. Surveillance failure occurred in 29% and was significantly associated with lower median model for end-stage liver disease (MELD) score odds ratio (OR) 1.154, 95% confidence interval (CI): 1.027-1.297, p=0.025) and HCC localization within right liver lobe (OR: 6.083, 95% CI: 1.303-28.407, p=0.022), but not with AFP ≥200 µg/L. Patients with surveillance failure had significantly more intermediate/advanced tumor stages (93% vs. 6%, p<0.001), fewer curative treatment options (15% vs. 75%, p<0.001) and lower survival at 1 year (54% vs. 75%, p=0.041), 2 years (32% vs. 57%, p=0.019) and 5 years (0% vs. 16%, p=0.009). Alcoholic and non-alcoholic fatty liver disease (OR: 6.1, 95% CI: 1.7-21.3, p=0.005) and ascites (OR: 3.9, 95% CI: 1.2-12.6, p=0.021) were independently associated with severe visual limitations on US. Conclusions: US-based HCC surveillance in patients at risk frequently fails and its failure is associated with unfavorable patient-related outcomes. Lower MELD score and HCC localization within right liver lobe were significantly associated with surveillance failure.

Secondary Sclerosing Cholangitis Following Coronavirus Disease 2019 (COVID-19): A Multicenter Retrospective Study.

BACKGROUND: Secondary sclerosing cholangitis (SSC) is a rare disease with poor prognosis. Cases of SSC have been reported following coronavirus disease 2019 (COVID-SSC). The aim of this study was to compare COVID-SSC to SSC in critically ill patients (SSC-CIP) and to assess factors influencing transplant-free survival. METHODS: In this retrospective, multicenter study involving 127 patients with SSC from 9 tertiary care centers in Germany, COVID-SSC was compared to SSC-CIP and logistic regression analyses were performed investigating factors impacting transplant-free survival. RESULTS: Twenty-four patients had COVID-SSC, 77 patients SSC-CIP, and 26 patients other forms of SSC. COVID-SSC developed after a median of 91 days following COVID-19 diagnosis. All patients had received extensive intensive care treatment (median days of mechanical ventilation, 48). Patients with COVID-SSC and SSC-CIP were comparable in most of the clinical parameters and transplant-free survival was not different from other forms of SSC (P = .443, log-rank test). In the overall cohort, the use of ursodeoxycholic acid (UDCA) (odds ratio [OR], 0.36 [95% confidence interval {CI}, .16-.80], P = .013; log-rank P < .001) and high serum albumin levels (OR, 0.40 [95% CI, .17-.96], P = .040) were independently associated with an increased transplant-free survival, while the presence of liver cirrhosis (OR, 2.52 [95% CI, 1.01-6.25], P = .047) was associated with worse outcome. Multidrug-resistant organism (MDRO) colonization or infection did not impact patients' survival. CONCLUSIONS: COVID-SSC and CIP-SSC share the same clinical phenotype, course of the disease, and risk factors for its development. UDCA may be a promising therapeutic option in SSC, though future prospective trials are needed to confirm our findings.

Diagnostic value of a liver biopsy in patients with an acute liver failure or acute liver injury.

OBJECTIVES: The diagnostic value of liver biopsy in patients with acute liver injury or acute liver failure (ALI/ALF) was investigated. METHODS: Data from the initial event and follow-up visits were retrospectively analyzed in all patients with a liver biopsy during ALI/ALF from January 2010 to May 2020 at the University Hospital Frankfurt, Germany. RESULTS: The cohort comprised 66 patients. Post-biopsy hemorrhage occurred in 2 of 66 but was self-limited. In five patients suspected liver involvement by a systemic extrahepatic disease was confirmed and excluded in eight patients. In 4 of 66 patients, the etiology of ALI/ALF remained unknown. Liver biopsy hinted at the etiology of ALI/ALF in 2 of 6 patients with rare diagnoses (hemophagocytic lymphohistiocytosis: 2 of 66; ischemic liver injury: 1 of 66, ALI/ALF due to a systemic infection: 3 of 66). In 31 of 34 patients with drug-induced liver injury (DILI), histopathology suggested DILI; in further 2 patients, DILI was among the differential diagnoses. However, DILI was also the histopathologically preferred diagnosis in 12 of 15 patients with autoimmune hepatitis (AIH). Only in 3 of 15 patients, histopathology was considered compatible with AIH. Serum immunoglobulin G (IgG) and autoantibodies during ALI/ALF were higher in patients with AIH than with DILI. Patients with AIH did not show a more pronounced biochemical response to corticosteroids in the first 10 days of treatment than patients with DILI. CONCLUSIONS: Liver biopsy is indispensable when liver involvement by an extrahepatic disease is suspected. To distinguish AIH from DILI in ALI/ALF, serum IgG, and autoantibodies seem more helpful than liver biopsy; long-term follow-up is needed in these patients.

Transabdominal ultrasonography to reduce the burden of X-ray imaging in prophylactic pancreatic stent localization after ERCP-A prospective trial.

BACKGROUND: Before performing endoscopy to remove prophylactic pancreatic stents placed in patients with high risk of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP), X-ray imaging is recommended to confirm the stents position in the pancreatic duct. OBJECTIVES: The aim of the present study was to investigate the feasibility of prophylactic pancreatic stent detection by transabdominal ultrasonography, to reduce the burden of X-ray imaging, which is currently the golden standard. METHODS: All patients who received a pancreatic stent for PEP prophylaxis were included in the present prospective trial. First, stent position was determined by transabdominal ultrasonography. Afterwards, it was verified by X-ray imaging. Retained stents were removed by esophagogastroduodenoscopy. Dislocated stents needed no further intervention. RESULTS: Fourty-one patients were enrolled in this study. All prophylactic pancreatic stents were straight 6 cm long 5 Fr stents with external flap. All stents were removed between day 1 and 10 (median: 3 days) in all cases. In 34 of 41 cases (83.0%), the pancreatic stent was still in place on the day of examination. Twenty-nine of 34 (85.3%) stents were detected correctly by transabdominal ultrasonography. Overlying gas prevented visualization of the pancreas in 3/41 (7.3%) cases. Sensitivity of sonographic detection of the stent was 93.5% (29/31). Six of seven stents were determined correctly as dislocated by ultrasonography. Here, specificity was 85.7%. A positive predictive value of 96.7% (29/30) was examined. The negative predictive value was 75.0% (6/8). CONCLUSION: Transabdominal ultrasonography detects the majority of prophylactic pancreatic stents. Thereby, it helps to identify patients with an indication for endoscopy sufficiently. X-ray imaging could subsequently be omitted in about 70% of examinations, reducing the radiation exposure for the patient and the endoscopy staff.

Use of carbapenems and glycopeptides increases risk for Clostridioides difficile infections in acute myeloid leukemia patients undergoing intensive induction chemotherapy.

Patients with acute myeloid leukemia (AML) are often exposed to broad-spectrum antibiotics and thus at high risk of Clostridioides difficile infections (CDI). As bacterial infections are a common cause for treatment-related mortality in these patients, we conducted a retrospective study to analyze the incidence of CDI and to evaluate risk factors for CDI in a large uniformly treated AML cohort. A total of 415 AML patients undergoing intensive induction chemotherapy between 2007 and 2019 were included in this retrospective analysis. Patients presenting with diarrhea and positive stool testing for toxin-producing Clostridioides difficile were defined to have CDI. CDI was diagnosed in 37 (8.9%) of 415 AML patients with decreasing CDI rates between 2013 and 2019 versus 2007 to 2012. Days with fever, exposition to carbapenems, and glycopeptides were significantly associated with CDI in AML patients. Clinical endpoints such as length of hospital stay, admission to ICU, response rates, and survival were not adversely affected. We identified febrile episodes and exposition to carbapenems and glycopeptides as risk factors for CDI in AML patients undergoing induction chemotherapy, thereby highlighting the importance of interdisciplinary antibiotic stewardship programs guiding treatment strategies in AML patients with infectious complications to carefully balance risks and benefits of anti-infective agents.