Long-term outcome and risk stratification in compensated advanced chronic liver disease after HCV-cure.

BACKGROUND AND AIMS: Around 750,000 patients per year will be cured of HCV infection until 2030. Those with compensated advanced chronic liver disease remain at risk for hepatic decompensation and de novo HCC. Algorithms have been developed to stratify risk early after cure; however, data on long-term outcomes and the prognostic utility of these risk stratification algorithms at later time points are lacking. APPROACH AND RESULTS: We retrospectively analyzed a cohort of 2335 patients with compensated advanced chronic liver disease (liver stiffness measurement≥10 kPa) who achieved HCV-cure by interferon-free therapies from 15 European centers (median age 60.2±11.9 y, 21.1% obesity, 21.2% diabetes).During a median follow-up of 6 years, first hepatic decompensation occurred in 84 patients (3.6%, incidence rate: 0.74%/y, cumulative incidence at 6 y: 3.2%); 183 (7.8%) patients developed de novo HCC (incidence rate: 1.60%/y, cumulative incidence at 6 y: 8.3%), with both risks being strictly linear over time.Baveno VII criteria to exclude (FU-liver stiffness measurement <12 kPa and follow-up platelet count >150 g/L) or rule-in (FU-liver stiffness measurement ≥25 kPa) clinically significant portal hypertension (CSPH) stratified the risk of hepatic decompensation with proportional hazards. Estimated probability of CSPH discriminated patients developing versus not developing hepatic decompensation in the gray zone (ie, patients meeting none of the above criteria).Published HCC risk stratification algorithms identified high-incidence and low-incidence groups; however, the size of the latter group varied substantially (9.9%-69.1%). A granular "HCC-sustained virologic response" model was developed to inform an individual patient's HCC risk after HCV-cure. CONCLUSIONS: In patients with compensated advanced chronic liver disease, the risks of hepatic decompensation and HCC remain constant after HCV-cure, even in the long term (>3 y). One-time post-treatment risk stratification based on noninvasive criteria provides important prognostic information that is maintained during long-term follow-up, as the hazards remain proportional over time.

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.

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.