Post-treatment LSM rather than change during treatment predicts decompensation in patients with cACLD after HCV cure.

BACKGROUND & AIMS: Baveno VII has defined a clinically significant (i.e., prognostically meaningful) decrease in liver stiffness measurement (LSM) in cACLD as a decrease of ≥20% associated with a final LSM <20 kPa or any decrease to <10 kPa. However, these rules have not yet been validated against direct clinical endpoints. METHODS: We retrospectively analysed patients with cACLD (LSM ≥10 kPa) with paired liver stiffness measurement (LSM) before (BL) and after (FU) HCV cure by interferon-free therapies from 15 European centres. The cumulative incidence of hepatic decompensation was compared according to these criteria, considering hepatocellular carcinoma and non-liver-related death as competing risks. RESULTS: A total of 2,335 patients followed for a median of 6 years were analysed. Median BL-LSM was 16.6 kPa with 37.1% having ≥20 kPa. After HCV cure, FU-LSM decreased to a median of 10.9 kPa (<10 kPa: 1,002 [42.9%], ≥20 kPa: 465 [19.9%]) translating into a median LSM change of -5.3 (-8.8 to -2.4) kPa corresponding to -33.9 (-48.0 to -15.9) %. Patients achieving a clinically significant decrease (65.4%) had a significantly lower risk of hepatic decompensation (subdistribution hazard ratio: 0.12, 95% CI 0.04-0.35, p <0.001). However, these risk differences were primarily driven by a negligible risk in patients with FU-LSM <10 kPa (5-year cumulative incidence: 0.3%) compared to a high risk in patients with FU-LSM ≥20 kPa (16.6%). Patients with FU-LSM 10-19.9 kPa (37.4%) also had a low risk of hepatic decompensation (5-year cumulative incidence: 1.7%), and importantly, the risk of hepatic decompensation did not differ between those with/without an LSM decrease of ≥20% (p = 0.550). CONCLUSIONS: FU-LSM is key for risk stratification after HCV cure and should guide clinical decision making. LSM dynamics do not hold significant prognostic information in patients with FU-LSM 10-19.9 kPa, and thus, their consideration is not of sufficient incremental value in the specific context of HCV cure. IMPACT AND IMPLICATIONS: Liver stiffness measurement (LSM) is increasingly applied as a prognostic biomarker and commonly decreases in patients with compensated advanced chronic liver disease achieving HCV cure. Although Baveno VII proposed criteria for a clinically significant decrease, little is known about the prognostic utility of LSM dynamics (changes through antiviral therapy). Interestingly, in those with a post-treatment LSM of 10-19.9 kPa, LSM dynamics did not provide incremental information, arguing against the consideration of LSM dynamics as prognostic criteria. Thus, post-treatment LSM should guide the management of patients with compensated advanced chronic liver disease achieving HCV cure.

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.

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.

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.