Francesca Romana Ponziani

LiverLover - 4ever Hepatologist

[Alessandro Vitale @Vaital73]

New letter in Journal of Hepatology (w/ AR & PM)
We respond to Mauro et al.’s framework for non-proportional hazards in pivotal HCC trials — and raise 8 methodological concerns:
→ p-values conflated with clinical relevance
→ GT test misused as a binary trigger
→ Internal numerical inconsistencies (CIs excluding null, yet p>0.05)
→ Retrospective questioning of pre-specified stopping rules
→ Selective inference in secondary analyses
Bottom line: in NPH trials, data maturity, absolute effect size, and clinical applicability must all be evaluated — not just statistical significance.
IMbrave050 says it all: MaxCombo p=0.018 at interim → p=0.326 at final analysis.
GRADE tools already exist to flag this. Let’s use them. 🔬
@LorenzaRimassa @cabibbo78 @casadei_gardini @Gio_Marchegiani

[Alessandro Vitale @Vaital73]

🔄 THE WATERMILL APPROACH 🔄

In the rapidly evolving landscape of hepatocellular carcinoma (HCC) management, the recent article by Edoardo G. Giannini, Jean-François Dufour, and Mario Strazzabosco proposes a compelling conceptual synthesis: the "Watermill Approach" [1].

This elegant metaphor captures the essence of the Multiparametric Therapeutic Hierarchy (MTH) [2] and the Converse Therapeutic Hierarchy (CTH) [3] —two frameworks that challenge the traditional, linear BCLC paradigm.

The direction of the water flow reflects the patient's response to initial oncological treatment, influenced by liver function and frailty. As the mill turns, treatment options ascend or descend along a therapeutic gradient—from best supportive care to transplantation. This visual and conceptual model embodies the shift towards adaptive, personalized, and prognosis-modifying strategies in HCC.

📌 Curative intent is no longer a fixed attribute of early-stage disease, but rather a continuum that can be pursued—even in advanced stages—through intelligent sequencing and reassessment.

A powerful contribution that aligns with the most advanced trends in multidisciplinary, evidence-based hepatology.

🙏 A special thanks to my friend Edoardo G. Giannini for continuing to drive innovation in the way we think about HCC.

[1] https://t.co/VM2dHv48NP

[2] https://t.co/uCC9l15HbC

[3] https://t.co/YmRxrJp2bm

[Francesca Romana Ponziani @FRPonziani]

🔥

[Alessandro Vitale @Vaital73]

FROM RESEARCH TO GUIDELINES 🚀
Proud moment for our team: our study on surgical resection for multinodular BCLC-A #HCC [1] — one of the largest Western matched-cohort analyses — is making waves far beyond its first publication.

🔹 Invited Editorial [2]: praised our methodological rigor, our challenge to restrictive BCLC recommendations, and our role in advancing the Multiparametric Therapeutic Hierarchy.
🔹 Guideline Citations: now included in the latest ESMO 2025 [3] and EASL 2025 [4] HCC guidelines.
🔹 Global Review: featured in CA: A Cancer Journal for Clinicians [5], the world’s top-impact oncology journal, as part of the evolving landscape of surgical management in HCC.
This recognition confirms the growing role of evidence-based expansion of surgical indications for carefully selected multinodular HCC patients — a paradigm shift influencing clinical practice worldwide. 🌍
Grateful to my co-authors, collaborators, and the international HCC community for embracing this debate and moving towards more personalized, curative strategies.

#LiverCancer #HCC #Oncology #Surgery #ESMO #EASL #MedicalResearch #Guidelines #EvidenceBasedMedicine

[1]https://t.co/XhgZlizaMs
[2]https://t.co/WnrxYd0Vl6
[3] https://t.co/IbV3TUC2Zs
[4] https://t.co/xFrQKzyHYP
[5]https://t.co/RKptcnjkBt

[Alessandro Vitale @Vaital73]

Stop saying “p < 0.05 = significant”.

It’s wrong. It’s dangerous. And it’s everywhere.

Our latest commentary explains why this myth still prevails in medicine and what we should do instead.

📄 Why is p-Value Controversial?
🔗 https://t.co/A5cqV85P3w
With @RovettaAless

[Alessandro Vitale @Vaital73]

🚨 New study just out in Cancers:
Laparoscopic microwave ablation (L-MWA) + salvage liver transplantation (SLT) for HCC.
Can we save lives and spare organs?
Turns out, yes. 🧵

👉 https://t.co/FFrjdZh8Jq
#HCC #LiverTransplant

[Francesca Romana Ponziani @FRPonziani]

4ever #young # 😂🫠 AISF2025 ⁦@AisfFegato⁩ ⁦@salvatore_petta⁩ ⁦@AghemoAlessio⁩

[Francesca Romana Ponziani @FRPonziani]

AISF 2025: challenging issues in #liver #transplant drugs #abuse #ageing and social #frailty on the stage ⁦@AisfFegato⁩ ⁦@EASLnews⁩ ⁦@EASLedu⁩

[Francesca Romana Ponziani @FRPonziani]

Liver decompensation is much more than just an adverse event—it should be considered a true outcome!😱
In our paper, we used for the first time Time to Decompensation (TTD) as an outcome in HCC patients receiving Atezolizumab-Bevacizumab. 👍🏻 find it out ➡️ https://t.co/Ojno5Ijf00

[Francesca Romana Ponziani @FRPonziani]

@massimoiava this is the right answer!!

[massimo iavarone @massimoiava]

"The possibility to resume treatment after an episode of decompensation underscores the importance of integrated hepato-oncological management."
The curves are really interesting!
#HCC #liverX #cirrhosis

[Francesca Romana Ponziani @FRPonziani]

@cabibbo78 @fabiomarra_dr

[Francesca Romana Ponziani @FRPonziani]

Can we identify HCC patients at risk of liver decompensation during 💉Atezolizumab-Bevacizumab❓And what should we do if decompensation occurs during treatment🤔❓Is discontinuation always the only option 🙂‍↔️❓
Find the answers in our new paper❗️📄 https://t.co/Ojno5Ijf00

[Francesca Romana Ponziani @FRPonziani]

Can we identify HCC patients at risk of liver decompensation during 💉Atezolizumab-Bevacizumab❓And what should we do if decompensation occurs during treatment🤔❓Is discontinuation always the only option 🙂‍↔️❓
Find the answers in our new paper❗️📄 https://t.co/Ojno5Ijf00

[Alessandro Vitale @Vaital73]

THE END OF THE STAGE HIERARCHY HCC ERA ...

... towards the MTH approach for patients with HCC ...

[272] Vitale A, et al. Personalised management of patients with hepatocellular carcinoma: a multiparametric therapeutic hierarchy concept. Lancet Oncol 2023;24(7):e312–e322.

[Giuseppe Cabibbo @cabibbo78]

👉A post-hoc analysis from the IMbrave150
🔥 ⁠Is it time to redesign the HCC trial design?
💥Clinical Hepatic decompensation is the major driver of death in patients with HCC
https://t.co/AMMMTo9bCa
@DJPinato @ma5RN @docamitgs @ArndtVogel @massimoiava @CiroCelsa
@CCR_AACR

[Francesca Romana Ponziani @FRPonziani]

Our paper selected as Editor’s choice! 📖 a deep insight into 🐛 Akkermansia muciniphila’s role in human diseases 💉 check it out! 🔎 https://t.co/sjL1hz6xdC

[Francesca Romana Ponziani @FRPonziani]

@my_ueg @opnyssen @JulsgaardMette @HannesHagstrom @yourUMG It was an honor to be part of UEGW2024 and to receive this outstanding recognition 🥇

[United European Gastroenterology @my_ueg]

@frponziani @opnyssen @julsgaardmette @hanneshagstrom @yourumg

[United European Gastroenterology @my_ueg]

🌟 Watch Rising Stars shine at UEG Week! 🌟

Don't miss this captivating session by our Rising Star @frponziani at #UEGWeek 2024: 'Gut microbiota and hepatocellular carcinoma: From pathogenesis to modulation of treatment efficacy.'

🔗 https://t.co/I4G2Hmbmbj
#myUEGcommunity

[Nicola Pugliese @nicolapugliese_]

❓Persistent and unexplained elevated #GGT❓

🔎Discover what predicts #PSVD in our 🆕 paper🔥 on @JHEP_Reports 🔥

@AghemoAlessio @FRPonziani @lucavalenti75 @CristianaBianco

[Alessandro Vitale @Vaital73]

What Is the Best Local Therapy for HCC?

"The article in this issue of JAMA Surgery by Vitale et al is a SUPERB multicenter collected series composed of data from 2 large Italian registries collected between 2008 and 2020.”
Yuman Fong; Jonathan Kessler

https://t.co/r2tl3SvPHO

[Alessandro Vitale @Vaital73]

WHO LASTS IT WINS...
We are really proud that our concept of "multiparametric therapeutic hierarchy" is now cited and taken as an example to follow in the new British guidelines on the management of hepatocellular carcinoma published in the prestigious journal Gut…