Validation of Baveno VII criteria and other non-invasive diagnostic algorithms for clinically significant portal hypertension in hepatitis delta.

BACKGROUND & AIMS: Non-invasive tests (NITs) for clinically significant portal hypertension (CSPH) require validation in patients with hepatitis D virus (HDV)-related compensated advanced chronic liver disease (cACLD). Therefore, we aimed to validate existing NIT algorithms for CSPH in this context. METHODS: Patients with HDV-cACLD (LSM ≥10 kPa or histological METAVIR F3/F4 fibrosis) who underwent paired HVPG and NIT assessment at Medical University of Vienna or Hannover Medical School between 2013 and 2023 were retrospectively included. Liver stiffness measurement (LSM), von Willebrand factor to platelet count ratio (VITRO), and spleen stiffness measurement (SSM) were assessed. Individual CSPH risk was calculated according to previously published models (ANTICIPATE, 3P/5P). The diagnostic performance of Baveno VII criteria and refined algorithms (Baveno VII-VITRO, Baveno VII-SSM) was evaluated. The prognostic utility of NITs was investigated in the main cohort and an independent, multicenter, validation cohort. RESULTS: Fifty-one patients (HVPG ≥10 mmHg/CSPH prevalence: 62.7%, varices: 42.2%) were included. Patients with CSPH had significantly higher LSM (25.8 [17.2-31.0] vs. 14.0 [10.5-19.8] kPa; p < 0.001), VITRO (n = 31, 3.5 [2.7-4.5] vs. 1.3 [0.6-2.0] %/[G/L]; p < 0.001), and SSM (n = 20, 53.8 [41.7-75.5] vs. 24.0 [17.0-33.9] kPa; p < 0.001). Composite CSPH risk models yielded excellent AUROCs (ANTICIPATE: 0.885, 3P: 0.903, 5P: 0.912). Baveno VII criteria ruled out CSPH with 100% sensitivity and ruled in CSPH with 84.2% specificity. The Baveno VII 'grey zone' (41.1%) was significantly reduced by Baveno VII-VITRO or Baveno VII-SSM algorithms, which maintained diagnostic accuracy. Hepatic decompensation within 2 years only occurred in patients who had CSPH or met Baveno VII rule-in criteria. The prognostic value of NITs was confirmed in the validation cohort comprising 92 patients. CONCLUSIONS: Standalone and composite NIT/diagnostic algorithms are useful for CSPH diagnosis in patients with HDV-cACLD. Thus, NITs may be applied to identify and prioritize patients with CSPH for novel antiviral treatments against chronic hepatitis D. IMPACT AND IMPLICATIONS: Non-invasive tests (NITs) for clinically significant portal hypertension (CSPH) have been developed to identify patients with compensated advanced chronic liver disease (cACLD) at risk of decompensation, but conflicting data has been published regarding the accuracy of liver stiffness measurement (LSM) for the staging of fibrosis in patients infected with hepatitis D virus (HDV). In our study, including 51 patients with HDV-cACLD, LSM- and lab-based NITs yielded high AUROCs for CSPH. Moreover, only patients with CSPH or high non-invasively assessed CSPH risk were at risk of decompensation within 2 years, with the prognostic value of NITs confirmed in a validation cohort. Thus, NITs should be applied and updated in yearly intervals in clinical routine to identify patients with HDV-cACLD at short-term risk of clinical events; NITs may also guide prioritization for novel antiviral treatment options.

High Prevalence and Clinical Relevance of Intrapulmonary Vascular Dilatations in Patients Undergoing TIPS Implantation.

BACKGROUND & AIMS: Considerate patient selection is vital to ensure the best possible outcomes after transjugular intrahepatic portosystemic shunt (TIPS) insertion. However, data regarding the impact of intrapulmonary vascular dilatations (IPVDs) or hepatopulmonary syndrome (HPS) on the clinical course after TIPS implantation is lacking. Hence, this study aimed to investigate the relevance of IPVD and HPS in patients undergoing TIPS implantation. METHODS: Contrast enhanced echocardiography and blood gas analysis were utilized to determine presence of IPVD and HPS. Multivariable competing risk analyses were performed to evaluate cardiac decompensation (CD), hepatic decompensation (HD), and liver transplant (LTx)-free survival within 1 year of follow-up. RESULTS: Overall, 265 patients were included, of whom 136 had IPVD and 71 fulfilled the HPS criteria. Patients with IPVD had lower Freiburg index of post-TIPS survival (FIPS) scores, lower creatinine, and more often received TIPS because of variceal bleeding. Presence of IPVD was associated with a significantly higher incidence of CD (hazard ratio [HR], 1.756; 95% confidence interval [CI], 1.011-3.048; P = .046) and HD (HR, 1.841; 95% CI, 1.255-2.701; P = .002). However, LTx-free survival was comparable between patients with and without IPVD (HR, 1.081; 95% CI, 0.630-1.855; P = .780). Patients with HPS displayed a trend towards more CD (HR, 1.708; 95% CI, 0.935-3.122; P = .082) and HD (HR, 1.458; 95% CI, 0.934-2.275; P = .097) that failed to reach statistical significance. LTx-free survival did not differ in those with HPS compared with patients without HPS, respectively (HR, 1.052; 95% CI, 0.577-1.921; P = .870). CONCLUSION: Screening for IPVD before TIPS implantation could help to further identify patients at higher risk of CD and HD.

Securing wider EU commitment to the elimination of hepatitis C virus.

In 2016, the Hepatitis B and C Public Policy Association (HepBCPPA), gathered all the main stakeholders in the field of hepatitis C virus (HCV) to launch the now landmark HCV Elimination Manifesto, calling for the elimination of HCV in the EU by 2030. Since then, many European countries have made progress towards HCV elimination. Multiple programmes-from the municipality level to the EU level-were launched, resulting in an overall decrease in viremic HCV infections and liver-related mortality. However, as of 2021, most countries are not on track to reach the 2030 HCV elimination targets set by the WHO. Moreover, the COVID-19 pandemic has resulted in a decrease in HCV diagnoses and fewer direct-acting antiviral treatment initiations in 2020. Diagnostic and therapeutic tools to easily diagnose and treat chronic HCV infection are now well established. Treating all patients with chronic HCV infection is more cost-saving than treating and caring for patients with liver-related complications, decompensated cirrhosis or hepatocellular carcinoma. It is more important than ever to reinforce and scale-up action towards HCV elimination. Yet, efforts urgently need the dedicated commitment of policymakers at all governmental and policy levels. Therefore, the third EU Policy Summit, held in March 2021, featured EU parliamentarians and other key decision makers to promote dialogue and take strides towards securing wider EU commitment to advance and achieve HCV elimination by 2030. We have summarized the key action points and reported the 'Call-to-Action' statement supported by all the major relevant European associations in the field.

Updated epidemiology of hepatitis C virus infections and implications for hepatitis C virus elimination in Germany.

In 2014, an analysis was conducted to evaluate the hepatitis C virus (HCV) epidemiology and disease burden in Germany. Since then, there have been considerable developments in HCV management such as the implementation of direct acting antivirals. The aim of this analysis was to assess the recent data available for Germany, establish an updated 2020 HCV prevalence and cascade of care and evaluate the impact of what-if scenarios on the future burden of disease using modelling analysis. A dynamic Markov model was used to forecast the HCV disease burden in Germany. Model inputs were retrieved through literature review, unpublished sources and expert input. Next, three "what-if" scenarios were developed to evaluate the status quo, COVID-19 pandemic, and steps needed to achieve the WHO targets for elimination. At the beginning of 2020, there were 189,000 (95% UI: 76,700-295,000) viremic infections in Germany, a decline of more than 85,000 viremic infections since 2012. Annual treatment starts went down since 2015. Compared with 2019, the COVID-19 pandemic resulted in a further 11% decline in 2020. If this continues for two years, it could result in 110 excess HCC cases and 200 excess liver related deaths by 2030. To achieve the WHO targets, 81,200 people need to be diagnosed, with 118,600 initiated on treatment by 2030. This could also avert 1,020 deaths and 720 HCC cases between 2021 and 2030. Germany has made strides towards HCV elimination, but more efforts are needed to achieve the WHO targets by 2030.

[Glecaprevir/Pibrentasvir + Sofosbuvir + Ribavirin as a salvage regimen after Sofosbuvir + Velpatasvir + Voxilaprevir re-treatment failure]. / Glecaprevir/Pibrentasvir + Sofosbuvir + Ribavirin als Reserveregime nach Sofosbuvir + Velpatasvir + Voxilaprevir Re-Therapieversagen.

Antiviral therapy of chronic hepatitis C virus (HCV) achieves sustained virological response (SVR) in the majority of patients. Even after initial virological failure, re-treatment with the combination of sofosbuvir+velpatasvir+voxilaprevir (SOF/VEL/VOX) has been established as an effective second line regimen. However, some patients fail to achieve SVR after a second antiviral course with SOF/VEL/VOX. These patients are considered difficult-to-cure. Currently, the optimal regimen for antiviral re-re-treamtent is a matter of debate and European and American guidelines suggest the combination of SOF+glecaprevir/pibrentasvir (G/P) + Ribavirin as a salvage regimen. However, there is only little evidence to support this. In this study, data of two patients with genotype 3 chronic HCV infection, liver cirrhosis and virological failure after re-treatment with SOF/VEL/VOX that successfully achieved SVR with the combination of SOF+G/P ± RBV. Importantly, one patient had Child B cirrhosis to the time of treatment initiation. No adverse events were reported. Thus, our data support the use of SOF + G/P + RBV as a salvage regimen after re-treatment failure with SOF/VEL/VOX.

Antimicrobial resistance in patients with decompensated liver cirrhosis and bacterial infections in a tertiary center in Northern Germany.

BACKGROUND AND AIMS: Bacterial infections are common in patients with decompensated liver cirrhosis and a leading cause of death. Reliable data on antibiotic resistance are required to initiate effective empiric therapy. We here aim to assess the antimicrobial resistance profile of bacteria among patients with liver cirrhosis and infection. METHODS: Overall, 666 cirrhotic patients admitted to Hannover Medical School between January 2012 and April 2018 with ascites were assessed for bacterial infection. In case of infection, bacteria cultured from microbiological specimens of ascites, blood or urine were identified and analyzed for resistances against common antibiotic agents. Furthermore, analyses compared two periods of time and community-acquired vs. nosocomial infections. RESULTS: In 281 patients with infection, microbiological sampling was performed and culture-positive results were obtained in 56.9%. Multidrug-resistant (MDR)-bacteria were found in 54 patients (19.2%). Gram-positive organisms were more common (n = 141/261, 54.0%) and detected in 116/192 culture-positive infections (60.4%). Comparing infections before and after 2015, a numerical decline for MDR-bacteria (23.8% vs. 15.6%, p = 0.08) was observed with a significant decline in meropenem resistance (34.9% vs. 19.5%, p = 0.03). MDR-bacteria were more frequent in the case of nosocomial infections. Of note, in ascites the majority of the tested bacteria were resistant against ceftriaxone (73.8%) whereas significantly less were resistant against meropenem (27.0%) and vancomycin (25.9%). CONCLUSIONS: In our tertiary center, distinct ratios of gram-positive infection with overall low ratios of MDR-bacteria were found. Adequate gram-positive coverage in the empiric therapy should be considered. Carbapenem treatment may be omitted even in nosocomial infection. In contrast, 3rd generation cephalosporins cannot be recommended even in community-acquired infection in our cirrhotic population.

[Influence of a spontaneous bacterial peritonitis, nosocomial infections and acute-on-chronic liver failure on treatment revenues in patients with decompensated cirrhosis in Germany]. / Einfluss einer spontan bakteriellen Peritonitis, nosokomialer Infektionen und eines akut auf chronischen Leberversagens auf die Behandlungserlöse bei Patienten mit dekompensierter Leberzirrhose in Deutschland.

BACKGROUND: The economic effects of spontaneous bacterial peritonitis (SBP), nosocomial infections (nosInf) and acute-on-chronic liver failure (ACLF) have so far been poorly studied. We analyzed the impact of these complications on treatment revenues in hospitalized patients with decompensated cirrhosis. METHODS: 371 consecutive patients with decompensated liver cirrhosis, who received a paracentesis between 2012 and 2016, were included retrospectively. DRG (diagnosis-related group), "ZE/NUB" (additional charges/new examination/treatment methods), medication costs, length of hospital stay as well as different kinds of specific treatments (e. g., dialysis) were considered. Exclusion criteria included any kind of malignancy, a history of organ transplantation and/or missing accounting data. RESULTS: Total treatment costs (DRG + ZE/NUB) were higher in those with nosInf (€â€Š10,653 vs. €â€Š5,611, p < 0.0001) driven by a longer hospital stay (23 d vs. 12 d, p < 0.0001). Of note, revenues per day were not different (€â€Š473 vs. €â€Š488, p = 0.98) despite a far more complicated treatment with a more frequent need for dialysis (p < 0.0001) and high-complex care (p = 0.0002). Similarly, SBP was associated with higher total revenues (€â€Š10,307 vs. €â€Š6,659, p < 0.0001). However, the far higher effort for the care of SBP patients resulted in lower daily revenues compared to patients without SBP (€â€Š443 vs. €â€Š499, p = 0.18). ACLF increased treatment revenues to €â€Š10,593 vs. €6,369 without ACLF (p < 0.0001). While treatment of ACLF was more complicated, revenue per day was not different to no-ACLF patients (€â€Š483 vs. €â€Š480, p = 0.29). CONCLUSION: SBP, nosInf and/or ACLF lead to a significant increase in the effort, revenue and duration in the treatment of patients with cirrhosis. The lower daily revenue, despite a much more complex therapy, might indicate that these complications are not yet sufficiently considered in the German DRG system.

The impact of proton pump inhibitors on the intestinal microbiota in chronic hepatitis C patients.

Objectives: Proton pump inhibitors (PPI), a class of drugs commonly used, are known to be associated with changes in the intestinal microbiota. Published studies were done in heterogeneous cohorts which could hamper conclusions drawn as effects of diseases were not taken into consideration. We aimed to elucidate differences in the intestinal microbiota being associated to the use of PPI in a cohort study of patients with chronic hepatitis C. Material and Methods: The 16S rDNA gene was analyzed in stool samples of patients with and without PPI use. Patients with concomitant medication influencing the microbiota were excluded. Results were compared with the clinical course of hepatitis C patients with decompensated liver cirrhosis. Results: No differences in alpha diversity could be observed, while the microbial community structure differed significantly, especially in patients with liver cirrhosis. The relative abundance of Streptococcus spp., Enterobacter spp. and Haemophilus spp. was significantly increased in patients with PPI use irrespectively of the stage of liver disease. Finally, in patients with decompensated liver cirrhosis due to chronic HCV infection only in these using PPI bacterial phylotypes were isolated. Conclusions: PPI use was associated with significant alterations in the microbial community in patients with chronic hepatitis C, which were even pronounced in patients with liver cirrhosis. In patients with decompensated liver cirrhosis due to chronic HCV infection, the use of PPI may promote infections either directly or indirectly through changes in the microbial community structure. Future studies should further investigate long-term impact on the microbiota and the clinical outcome.

Dose-dependent impact of proton pump inhibitors on the clinical course of spontaneous bacterial peritonitis.

BACKGROUND & AIMS: Spontaneous bacterial peritonitis is a severe complication in patients with cirrhosis leading to acute kidney injury, hepatic encephalopathy and a high mortality. In this study, we aimed to investigate the impact of proton pump inhibitors and the potential relevance of the taken dosage on the incidence and clinical course of spontaneous bacterial peritonitis. METHODS: Overall, 613 consecutive patients with decompensated cirrhosis were included. All patients were carefully evaluated for proton pump inhibitors intake including the applied dosage and were further followed up for spontaneous bacterial peritonitis development as well as for the incidence of clinical complications like hepatic encephalopathy, acute kidney injury and mortality. RESULTS: Cumulative spontaneous bacterial peritonitis incidence did neither differ between the proton pump inhibitors and the no-proton pump inhibitors group nor between those taking the high (>40 mg/d) and the low (10-40 mg/d) proton pump inhibitors' dose. However, proton pump inhibitors' intake was associated with an impaired clinical course of spontaneous bacterial peritonitis reflected by a higher likelihood for acute kidney injury (71% vs 43%; P = .002), severe hepatic encephalopathy (15% vs 0%; P = .04) and an increased mortality (24% vs 0%; P = .008) within 28 days after spontaneous bacterial peritonitis diagnosis. In particular, patients with proton pump inhibitors dosages >40 mg/d had an increased short-term risk for acute kidney injury (adjusted hazard ratio: 1.86; P = .009) and mortality (adjusted hazard ratio: 2.05; P = .02). In contrast, there was no effect of proton pump inhibitors on acute kidney injury, hepatic encephalopathy and mortality in patients without spontaneous bacterial peritonitis irrespective of the applied proton pump inhibitors dosage. CONCLUSIONS: High dosages of proton pump inhibitors are associated with an adverse outcome in patients with spontaneous bacterial peritonitis. Thus, indication for high-dosage proton pump inhibitors therapy should be evaluated carefully in these patients.

Folic acid supplementation is associated with a decreased mortality and reduced hospital readmission in patients with decompensated alcohol-related liver cirrhosis.

BACKGROUND AND AIMS: Thiamine and folic acid malnutrition is highly frequent in patients with decompensated alcohol-related liver cirrhosis (aLC). Current guidelines therefore recommend vitamin supplementation in these patients. However, implementation and its impact on the clinical outcome remains unknown. Therefore, we aimed to analyze the use of thiamine and folic acid and their effects on mortality and morbidity in patients with decompensated aLC. METHODS: A number of 289 consecutive patients with decompensated aLC who received a paracentesis at Hannover Medical School between 2011 and 2023 were retrospectively investigated. The use of folic acid and thiamine-containing supplements was assessed in the discharge medication. Patients were followed for up to one year regarding liver transplant (LTx)-free survival and the incidence of hepatic encephalopathy, infections and hepatic decompensation requiring rehospitalization. RESULTS: Median baseline MELD was 15, median age 56.6 years. 73.0% (n = 211) were male patients. At hospital discharge, thiamine-containing supplements and folic acid were prescribed to 48.1% (n = 139) and 18.0% (n = 52) patients, respectively. Neither thiamine nor folic acid prescription were linked to improved clinical outcomes within 90 days. However, folic acid intake was associated with a higher one-year LTx-free survival (HR = 0.48; p = 0.04) in the multivariable analysis. Furthermore, folic acid substitution was linked to a decreased risk of rehospitalization within one year (HR = 0.55; p = 0.01) in the multivariable competing risk model. In contrast, thiamine prescription did neither affect LTx-free survival nor the here investigated liver-related complications. CONCLUSION: Folic acid, but not thiamine substitution was linked to an improved outcome in patients with decompensated aLC.

Effects of renin-angiotensin inhibitors on renal function and the clinical course in patients with decompensated cirrhosis.

Patients with decompensated cirrhosis are at risk of developing acute kidney injury (AKI). Studies have suggested that inhibition of the Renin-Angiotensin System (RAS) has certain nephro- and hepatoprotective effects in patients with compensated liver disease. This study aimed to investigate the clinical impact of RAS-Inhibitors in individuals with decompensated liver cirrhosis. Overall, 1181 consecutive hospitalized patients with ascites that underwent paracentesis were considered for this retrospective study. In total, 667 patients with decompensated cirrhosis fulfilled the inclusion criteria and were finally analyzed. RAS-Inhibitor intake was documented in 41 patients (7%). First, 28-day incidences of AKI and grade III AKI of all patients with RAS-Inhibitors were compared to those without intake. Afterwards, propensity score matching was conducted in a 3:1 manner. Here, incidence of further renal endpoints such as need of hemodialysis were analyzed in detail. In the unmatched setting, intake of RAS-Inhibitors was not associated with an increased 28 day-incidence of AKI (P = 0.76) or LTx-free survival (P = 0.60). However, 28 day-incidence of grade III AKI was significantly lower in patients with RAS-Inhibitor intake (P < 0.001). In the matched setting, 28 day-incidence of AKI did not differ (P = 0.81), while grade III AKI was significantly less frequent in the RAS-Inhibitor group (P < 0.001). Need for hemodialysis was also significantly lower in patients with RAS-Inhibitors (P = 0.03) and LTx-free survival was comparable between both groups (P = 0.52). Thus, this study suggests that intake of RAS-Inhibitors is associated with decreased incidences of grade III AKI and need of hemodialysis in patients with decompensated liver disease.

Daily Low-Volume Paracentesis and Clinical Complications in Patients With Refractory Ascites.

Importance: The potential association of low-volume paracentesis of less than 5 L with complications in patients with ascites remains unclear, and individuals with cirrhosis and refractory ascites (RA) treated with devices like Alfapump or tunneled-intraperitoneal catheters perform daily low-volume drainage without albumin substitution. Studies indicate marked differences regarding the daily drainage volume between patients; however, it is currently unknown if this alters the clinical course. Objective: To determine whether the incidence of complications, such as hyponatremia or acute kidney injury (AKI), is associated with the daily drainage volume in patients with devices. Design, Setting, and Participants: This retrospective cohort study of patients with liver cirrhosis, RA, and a contraindication for a transjugular intrahepatic portosystemic shunt who received either device implantation or standard of care (SOC; ie, repeated large-volume paracentesis with albumin infusion), and were hospitalized between 2012 and 2020 were included. Data were analyzed from April to October 2022. Interventions: Daily ascites volume removed. Main outcomes and Measures: The primary end points were 90-day incidence of hyponatremia and AKI. Propensity score matching was performed to match and compare patients with devices and higher or lower drainage volumes to those who received SOC. Results: Overall, 250 patients with RA receiving either device implantation (179 [72%] patients; 125 [70%] male; 54 [30%] female; mean [SD] age, 59 [11] years) or SOC (71 [28%] patients; 41 [67%] male; 20 [33%] female; mean [SD] age, 54 [8]) were included in this study. A cutoff of 1.5 L/d or more was identified to estimate hyponatremia and AKI in the included patients with devices. Drainage of 1.5 L/d or more was associated with hyponatremia and AKI, even after adjusting for various confounders (hazard ratio [HR], 2.17 [95% CI, 1.24-3.78]; P = .006; HR, 1.43 [95% CI, 1.01-2.16]; P = .04, respectively). Moreover, patients with taps of 1.5 L/d or more and less than 1.5 L/d were matched with patients receiving SOC. Those with taps of 1.5 L/d or more had a higher risk of hyponatremia and AKI compared with those receiving SOC (HR, 1.67 [95% CI, 1.06-2.68]; P = .02 and HR, 1.51 [95% CI, 1.04-2.18]; P = .03), while patients with drainage of less than 1.5 L/d did not show an increased rate of complications compared with those receiving SOC. Conclusions and Relevance: In this cohort study, clinical complications in patients with RA performing low-volume drainage without albumin infusion were associated with the daily volume drained. Based on this analysis, physicians should be cautious in patients performing drainage of 1.5 L/d or more without albumin infusion.

Application of CT contrast medium is not associated with an increased risk for acute kidney injury in patients with decompensated cirrhosis.

BACKGROUND: Acute kidney injury (AKI) is a frequent complication in patients with decompensated cirrhosis. Studies reported conflicting results regarding the nephrotoxic potential of iodinated contrast medium (CM) for computer tomography (CT). AIM: To investigate the impact of diagnostic CM application on kidney function in patients with decompensated cirrhosis. METHODS: First, we evaluated the impact of diagnostic CM-CT on AKI incidence in a cross-sectional approach. Second, we analysed 28-day AKI incidence post-CM-CT in patients with impaired kidney function (i.e., creatinine >133 µmoL/L). Third, we excluded all patients with relevant interventions besides CM-CT. All remaining patients were matched via propensity score matching (PPSM) and further analysed. Last, we validated the results in an independent dataset of prospectively collected registry data of 118 patients with decompensated cirrhosis. Here, plasma samples were analysed regarding neutrophil-gelatinase-associated-lipocalin (NGAL). RESULTS: Of the 611 included patients, 98 (16%) received CM-CT. CM-CT was not associated with AKI in the cross-sectional approach (CM-CT:8% vs. no CM-CT:15%; p = 0.08). Furthermore, CM-CT was not associated with higher 28-day AKI incidence among patients with impaired kidney function (HR:0.79; 95% CI 0.45-1.38; p = 0.40). The PPSM cohort revealed no association between CM-CT and AKI or severe AKI (HR:1.28, p = 0.45 and HR:1.62; p = 0.43). Moreover, CM-CT did not result in worsening of kidney function after CM application. In the validation cohort, CM-CT was also not linked to AKI (p = 0.85) and NGAL levels were not increased in those with CM-CT (CM-CT:309 ng/ml vs. No CM-CT:266 ng/ml, p = 0.35). CONCLUSION: Decompensated cirrhosis per se should not preclude diagnostic CM-CT.

Home-based, tunnelled peritoneal drainage system as an alternative treatment option for patients with refractory ascites.

BACKGROUND: Onset of refractory ascites is the hallmark of end-stage liver disease. If liver transplantation (LTx) is not available and contraindications for a transjugular portosystemic shunt (TIPS) are present, repeated paracentesis remains the standard of care (SOC). Home-based, tunnelled peritoneal catheters (PeCa) have been suggested as an alternative treatment option. However, data on patients with cirrhosis are scarce. AIM: To evaluate the safety of PeCa in these patients compared to SOC. METHODS: Overall, 223 patients with cirrhosis, a contraindication for TIPS and refractory ascites were included in this retrospective study. PeCa implant was performed in 152 patients, whereas 71 were treated with SOC. Analysed end points included device explant-free survival, mortality, acute kidney injury (AKI) and hyponatraemia. In the second approach, propensity score matching (PPSM) was performed to adjust for confounding factors. RESULTS: In patients with PeCa, median device explant-free survival was 74 days and 52 explants were recorded within the first 90 days. Within 90 days, patients with PeCa had lower mortality than SOC (p = 0.11), and spontaneous bacterial peritonitis (SBP) incidence did not differ (p = 0.82). Regarding AKI and hyponatraemia, there was a trend towards a higher incidence in the PeCa group (p = 0.13 and p = 0.08), and the risk for rehospitalisation was higher in those with a PeCa (HR: 2.11, p = 0.04). After PPSM, mortality was lower in the PeCa group (HR:0.40; p = 0.03), whereas the incidence of SBP and hyponatraemia was comparable (p = 0.80 and p = 0.28) and AKI was more frequent in those with a PeCa (p = 0.08). CONCLUSION: The implant of PeCa allows home-based therapy of patients with cirrhosis and refractory ascites and a contraindication for TIPS. However, the risk for complications has to be considered and prospective studies are needed.

Nosocomial infections in female compared with male patients with decompensated liver cirrhosis.

There are considerable differences between males and females regarding the etiology, progression and outcome of liver diseases. Infections are a frequent and severe complication in these patients. This study aimed to examine sex specific differences in the incidence and clinical course of nosocomial infections in patients with decompensated liver cirrhosis. A number of 556 consecutive hospitalized patients with decompensated liver cirrhosis and ascites were analyzed. The patients were followed up for the incidence of nosocomial infections, acute kidney injury (AKI), acute-on-chronic liver failure (ACLF) as well as liver transplantation and death (LTx-free survival). A number of 285 patients (111 women and 174 men) developed a nosocomial infection. Incidence was numerically lower in men (P = 0.076). While the frequency of a nosocomial spontaneous bacterial peritonitis was similar between males and females, the incidence of a nosocomial urinary tract infection was significantly higher in women (P < 0.001). No sex specific differences were documented regarding the outcome of an infection as indicated by a similar incidence of, AKI, ACLF as well as LTx-free survival. There seem to be no major differences in the incidence and outcome of nosocomial infections between male and female patients.

Metamizole-Associated Risks in Decompensated Hepatic Cirrhosis.

BACKGROUND: Because of the increased risk of acute renal failure (ARF), the use of cyclooxygenase (COX) inhibitors is not recommended in patients with decompensated hepatic cirrhosis. Metamizole is not a classic COX inhibitor, but there are insufficient data to support its safe use. In this study, we investigate the effect of metamizole on the risk of ARF in these patients. METHODS: Metamizole use, ARF incidence, and patient mortality were examined in a large, retrospective, exploratory cohort and validated with data from a prospective registry. RESULTS: 523 patients were evaluated in the exploratory cohort. Metamizole use at baseline was documented in 110 cases (21%) and was independently associated with the development of ARF, severe (grade 3) ARF, and lower survival without liver transplantation at follow-up on day 28 (HR: 2.2, p < 0.001; HR: 2.8, p < 0.001; and HR: 2.6, p < 0.001, respectively). Interestingly, the risk of ARF depended on the dose of metamizole administered (HR: 1.038, p < 0.001). Compared to patients who were treated with opioids, the rate of ARF was higher in the metamizole group (49% vs. 79%, p = 0.014). An increased risk of ARF with metamizole use was also demonstrated in the independent validation cohort (p < 0.001). CONCLUSION: Metamizole therapy, especially at high doses, should only be used with a high level of caution in patients with decompensated cirrhosis.