Risk of further decompensation/mortality in patients with cirrhosis and ascites as the first single decompensation event

Balcar, Lorenz; Tonon, Marta; Semmler, Georg; Calvino, Valeria; Hartl, Lukas; Incicco, Simone; Jachs, Mathias; Bauer, Dávid; Hofer, Benedikt; Gambino, Carmine; Accetta, Antonio; Brocca, Alessandra; Trauner, Michael; Mandorfer, Mattias; Piano, Salvatore; Reiberger, Thomas

doi:10.1016/j.jhepr.2022.100513

Cited by 33 publications

(27 citation statements)

References 31 publications

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“…Additionally, AAT constitutes an acute phase protein and its production likely increases in advanced liver disease with increased bacterial translocation and corresponding chronic inflammation [17,18]. In line with that, there is new evidence that Pi∗MZ carriers with liver cirrhosis decompensate faster than cirrhotic subjects without AAT mutation and that the Pi∗Z allele constitutes an independent risk factor for liver transplantation and death [19 ▪ ,20 ▪ ]. This observation might be responsible for the fact that hepatocellular carcinoma is relatively uncommon in Pi∗MZ subjects [8 ▪ ,21].…”

Section: Mild Alpha-1 Antitrypsin Deficiency (Pi∗mz Genotype) and Its...mentioning

confidence: 84%

Cleaning up alpha-1 antitrypsin deficiency related liver disease

Rademacher

Fromme

Strnad

2023

Current Opinion in Gastroenterology

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Purpose of review Alpha-1 antitrypsin deficiency (AATD) is one of the most common genetic disorders arising due to mutations in alpha-1 antitrypsin (AAT) gene affecting primarily the lung and the liver. This review summarizes the pathophysiology and clinical manifestation of different AATD genotypes and discusses the recent therapeutic developments. The focus is on the severe, rare homozygous Pi∗ZZ and the common heterozygous Pi∗MZ genotype. Recent findings Pi∗ZZ individuals harbor an up to 20 times higher risk of liver fibrosis and cirrhosis than noncarriers and liver transplantation is currently the only available therapeutic option. AATD constitutes a proteotoxic disorder arising from hepatic AAT accumulation and the currently most promising data come from a phase 2, open-label trial of fazirsiran, a hepatocyte-targeted siRNA. Pi∗MZ subjects display an increased risk of advanced liver disease and at the latter stage, a faster deterioration than individuals without AAT mutation. Summary Although the fazirsiran data offer a glimpse of hope to AATD patients, a consensus on appropriate study endpoint, a careful patient selection as well as monitoring of long-term safety will be essential for an approval.

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Section: Mild Alpha-1 Antitrypsin Deficiency (Pi∗mz Genotype) and Its...mentioning

confidence: 84%

Cleaning up alpha-1 antitrypsin deficiency related liver disease

Rademacher

Fromme

Strnad

2023

Current Opinion in Gastroenterology

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“…Finally, we agree that in recently compensated cases with ascites as the first decompensating event, the amount of ascites may be prognostic. [5] However, all patients in our study received TIPS for therapy of recurrent and refractory ascites. Thus, the cited study does not apply to our patients and therefore the concern is unjustified.…”

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confidence: 92%

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et al. 2022

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We agree that baseline liver function correlates with mortality, and we reported in detail no significant differences in baseline characteristics between groups; in particular, Model for End-Stage Liver Disease, Child-Pugh score, and age did not differ significantly, whereas albumin was higher in the groups with higher mortality (table 4).Moreover, Luo et al. stated that bilirubinemia >7 mg/dl is not a contraindication for transjugular intrahepatic portosystemic shunt (TIPS) insertion for ascites. This is a dangerous and misleading statement because studies so far have excluded those patients. [1] There is evidence that bilirubin below 3 mg/dl is a good biomarker to predict outcome in patients with ascites. [2] The strong association of bilirubin levels with post-TIPS outcome reinforces the recommendation of guidelines for extreme caution for TIPS insertion for ascites if bilirubin >3-5 mg/dl. [3,4] Although the quality of stents has improved over time, we included many patients and followed them over a long period of time. Indeed, we have reported the stent types used here (figure S7).Luo et al. raised an important issue of portal hepatic pressure gradient (PPG) variation and changes over time in our patients. It is very unlikely that in the real world outside of clinical trials longitudinal invasive measurements of PPG after TIPS are routinely performed. Ultrasound-based assessment of patency is the routine follow-up of choice. Therefore, we try to elaborate an easy-to-obtain surrogate marker at the time of TIPS insertion that is applicable for most cases in real-life practice. Hereby, percentage decrease in PPG is a good marker for response to treatment in ascites control in our cohort.Finally, we agree that in recently compensated cases with ascites as the first decompensating event, the amount of ascites may be prognostic. [5] However, all patients in our study received TIPS for therapy of recurrent and refractory ascites. Thus, the cited study does not apply to our patients and therefore the concern is unjustified.We thank again Luo et al. and hope that our answers could address their concerns and avoid confusion in further readers. CONFLICT OF INTERESTNothing to report.

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“…A recent study showed that the prognosis of patients with different ascites grades seems completely different. [4] In conclusion, whether PPG reduction after TIPS is associated with ascites control or better survival remains challenging.…”

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confidence: 99%

“…Although the authors adjusted several factors in the multivariable‐adjusted analysis (Child‐Pugh score, white blood cell count, and sodium), some important factors affecting ascites control and survival were not included, such as age, serum ammonia, albumin, bilirubin, creatinine, etiology of liver disease, and International Normalized Ratio 2,3. In particular, a recent study demonstrated that age, albumin, and model for end‐stage liver disease PPG score were associated with mortality in patients with ascites 4. Furthermore, patients with ascites with portal hypertension and hypoproteinemia were reported to have liver dysfunction.…”

mentioning

confidence: 99%

“…[2,3] In particular, a recent study demonstrated that age, albumin, and model for end-stage liver disease PPG score were associated with mortality in patients with ascites. [4] Furthermore, patients with ascites with portal hypertension and hypoproteinemia were reported to have liver dysfunction. Thus, weaker liver function at baseline was an important confounding factor in the study.…”

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confidence: 99%

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