Introduction

Hepatocellular carcinoma (HCC) is a severe outcome during liver disease with limited treatment options when diagnosed lately. It is the leading cause of death in patients with chronic hepatitis, particularly secondary to chronic viral hepatitis. Screening scores are continuously being developed abd assessed to optimize early diagnosis.

Aims & Methods

The aim of this study was to investigate the correlation between FiB-4 score and HCC risk during treated chronic viral hepatitis in Tunisian patients. We conducted a single-center retrospective study analyzing data from patients with chronic viral hepatitis B and C. Patients with co-infection BD, D, VIH or associated nonalcoholic steatohepatitis were excluded. FIB4 score was calculated for each patient at presentation.

Results

In total, 88 consecutive patients were enrolled: 42 with chronic hepatitis B and 46 with chronic hepatitis C. The mean age at diagnosis was 51.5 ±12 years with a sex-ratio M/F of 1.31. At baseline, 37.2% of patients had already developed cirrhosis. Virological response was achieved in 92% of the population. HCC occurred in 16% (N=14) of patients after a mean follow-up period of 79. The stage of HCC was classified as 'A', 'B', 'C' and 'D' according to BCLC clasification in 28.5%, 25%, 43% and 0.7% respectively. Univariate analysis identified: older age (p=0.02), low platelet count (p<0.0001), cirrhosis (p<0.0001), high bilirubin level (p=0.028) and high Fib-4 (p=0.01) as factors associated with the occurrence of HCC. When analyzing the receiver operating characteristic (ROC) curve, AUC of FIB4 score in predicting HCC was 0.845 (95% CI: 0.730–0.960, p<0.0001). The corresponding FIB-4 cut-offs for 90% sensitivities was 1.67, while the cut-offs for 90% specificities was 3.8.

Conclusion

In our study, high FIB-4 score was associated with increased HCC risk in patients with viral hepatitis. FIB-4 index is based on routinely clinical and biological data and showed highly predictive performances in predicting HCC allowing better stratification.

Introduction

The PROFILE trial in patients with newly-diagnosed Crohn’s disease demonstrated that “top-down” therapy, with combination infliximab and immunomodulator from diagnosis, provided superior efficacy and a better safety profile over a one-year follow-up period compared to a conventional “accelerated step-up” management approach.

Aims & Methods

The current study aimed to evaluate cost-effectiveness by assessing the healthcare cost and health outcomes associated with starting anti-TNF medication (intravenous infliximab, subcutaneous infliximab, subcutaneous adalimumab) as soon as possible after diagnosis. A de novo Markov model was developed to model the cost-effectiveness of using a “top-down” compared to “accelerated step-up” strategy in adults newly-diagnosed with active Crohn’s disease (HBI score >7, elevated CRP and/or faecal calprotectin >200ug/g and endoscopic evidence of disease activity with simple endoscopic score of Crohn’s disease activity of >6 [>4 if ileal-only disease]). Parameters were informed by individual patient data from PROFILE and data from the published literature. Use of intravenous infliximab, or subcutaneous infliximab, or subcutaneous adalimumab from diagnosis were modelled with biosimilar costs based on average real-world UK contract drug costs ascertained from 18 PROFILE trial sites in 2024. Key model outcomes included healthcare costs (drug acquisition, drug administration, disease management, hospitalisation, surgery) and health outcomes (quality-adjusted life years gained [QALYs]) measured over a 5-year time horizon.

Results

The base case cost-effectiveness analysis indicated that a “top-down” strategy dominated over an “accelerated step-up” approach. Initiating intravenous infliximab from diagnosis yielded greater clinical benefits, with an incremental gain of 0.17 QALYs per patient over a 5-year period, and was less costly, saving £1,681 per patient over the same time frame. Similar clinical benefits were obtained when modelling use of SC infliximab and adalimumab. The greatest cost savings were with adalimumab, totalling £10,059 per patient over 5 years. Sensitivity analyses further supported the robustness of the results for “top-down” therapy, showing it to be the most cost-effective option in 98.7% of model simulations.

Conclusion

This health economic analysis demonstrates that early effective “top-down” treatment with anti-TNF therapy from diagnosis results in lower healthcare resource use compared to an “accelerated step-up” strategy. The economic benefits align with improved clinical outcomes, as early, effective treatment better controls inflammation. Patients experience longer periods in remission, fewer disease-related flares, and enhanced quality of life. These findings were demonstrated for intravenous infliximab, subcutaneous infliximab and subcutaneous adalimumab. In newly-diagnosed patients with active Crohn’s disease, “top-down” treatment with anti-TNF therapy is more efficacious, safer and cost-effective than “accelerated step-up” based treatment strategies.

References

Noor NM, Lee JC, Bond S et al. A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn's disease (PROFILE): a multicentre, open-label randomised controlled trial. Lancet Gastroenterol Hepatol. 2024 May;9(5):415-427.

Disclosure

NMN declares educational/travel grants and/or speaker fees from AbbVie, Bristol Myers Squibb, Celltrion, Dr Falk Pharma, Ferring, Galapagos, J&J, Lilly, Pfizer, Pharmacosmos, Takeda and Tillotts Pharma AG.

Clinical Case Summary

A 64-year-old woman with a prior diagnosis of type I achalasia underwent Heller myotomy with Dor fundoplication in 2015, which resulted in the resolution of dysphagia and regurgitation. However, she kept experiencing chest pain, which partially improved with nitro-glycerine. In 2018, due to worsening pain, she underwent high-resolution oesophageal manometry (HROM), which demonstrated absent peristalsis without oesophageal pressurization. Also, upper endoscopy was unremarkable, and timed barium swallow (TBS) revealed some tertiary contractions. By 2019, the patient received botulinum toxin injections with partial improvement. Another TBS performed in 2023 showed tertiary contractions in the distal third of the oesophagus, contributing to mild oesophageal emptying delay but without stasis. In 2024, repeat HROM revealed pan-oesophageal pressurization, except in the distal-most centimetres of the oesophagus. During rapid drink challenge, the patient reported pain. Given these findings, she was proposed for peroral endoscopic myotomy (POEM) to extend the myotomy proximally. In August 2024, she underwent a complete distal oesophageal myotomy, including the lower oesophageal sphincter and cardia. Endoscopic assessment in November showed no evidence of stasis, esophagitis, or resistance at the cardia. Latest clinical evaluation in March 2025 confirmed complete resolution of chest pain.
Conclusion: Non-cardiac chest pain is a less common yet challenging symptom to manage in achalasia. Its persistence after disease-directed treatment has been described in the literature, with its primary risk factor being its presence preoperatively¹. However, comparative data on different therapeutic approaches for achalasia-related chest pain remain limited. To our knowledge, only two similar cases have been reported in which pain persisted after Heller myotomy but improved following POEM, probably linked to the inadequate or incomplete myotomy of the oesophageal muscle layer^2,3.

References

1. Olvera-Prado H, et al. Predictive factors associated with the persistence of chest pain in post-laparoscopic myotomy and fundoplication in patients with achalasia. Front Med (Lausanne). 2022 Oct 14;9:941581.
2. Miftahussurur M, Tandan M, Makmun D, Nabi Z. Peroral Endoscopic Myotomy in a Patient with Achalasia Cardia with Prior Heller's Myotomy. Case Rep Gastroenterol. 2020 Jan 22;14(1):48-55.
3. Sato C, et al. Salvage therapy for postoperative residual chest pain due to esophageal achalasia. SAGES 2017 Annual Meeting in Houston [Abstract], https://www.sages.org/meetings/annual-meeting/abstracts-archive/salvage-therapy-for-postoperative-residual-chest-pain-due-to-esophageal-achalasia/

Introduction

Intraductal radiofrequency ablation (RFA) has been proposed as an adjunctive therapeutic method for patients with inoperable perihilar
cholangiocarcinoma(pCCA). Because there is limited data regarding the benefits of RFA, we aimed to evaluate the feasibility, efficacy and safety of a RFA based endoscopic palliation protocol.

Aims & Methods

Consecutive inoperable patients presenting biliary obstruction secondary to pCCA were evaluated according to the ongoing, single center, randomized clinical trial(NCT05563870). Native-papilla patients were randomized 1:1 to biliary drainage of the viable liver territories with plastic stents (control) or drainage plus RFA of the entire length of the tumor (active arm). Following index procedure, patients were scheduled for stent exchange and additional RFA treatment (active arm only) at 8-10 weeks intervals. Primary outcome was clinical efficacy defined as bilirubin levels < 3mg/dL at 4 weeks after index ERCP; secondary outcomes included overall survival and safety outcomes.

Results

Heretofore we included 25 patients (13 active arm) undergoing 72 procedures (37 with RFA) for a median follow-up of 3 months (range 2-15). Most patients received either 2 (10/25) or 3 (3/25) plastic stents at index ERCP and 23/25 of the patients reached effective drainage at 4 weeks, only 7 patients receiving undelayed oncologic treatment. There were 11 deaths during follow-up - 6 unrelated to the cholangiocarcinoma, 3 from therapy-related complications and 2 from cancer progression. 20/25 patients experienced at least 1 adverse event - including 15 severe biliary events with no significant differences between the study groups.

Conclusion

Extensive liver drainage followed by iterative stent exchange with intraductal RFA applications seems feasible and effective in the
palliation of biliary obstruction in pCCA patients, with no additional risk related to RFA applications. However, adverse events related to biliary infection remain a frequent and life-threatening occurrence during follow-up in this patient population. Further data on the optimal timing and RFA application protocol is required.

Disclosure

No conflict of interest

Introduction

Acute-on-chronic liver failure ( ACLF) is a severe form of acute decompensation of chronic liver disease with a high short-term mortality rate. It is characterized by excessive systemic inflammatory response and extrahepatic multiorgan failures (1). Previously published data have shown that therapeutic plasma exchange (TPE) decreases mortality rate in patients with ACLF reducing cytokine levels, serum bilirubin, and coagulopathy (2,3).

Aims & Methods

This retrospective study was conducted at the University Clinical Center of Serbia. All patients diagnosed with ACLF according to the EASL criteria and treated with TPE from January 2021 to January 2024 were included. (1) The main indication for providing TPE was serum bilirubin level >12 mg/dl with no improvement to standard medical treatment (SMT). The following scores were calculated at the hospital admission: Model for end-stage liver disease (MELD), Model for end-stage liver disease-Sodium (MELD-Na), Chronic Liver Failure Consortium- acute-on-chronic liver failure (CLIF-C ACLF). All patients were followed for 90 days. MELD and MELD-Na scores were calculated as well on the day 28.
The aims of this study were: assessment of 28-day and 90-day survival in patients with ACLF, the impact of TPE on MELD, and MELD-Na score.

Results

The study included 40 patients in whom SMT did not lead to improvement, of which 32 (80%) were male and 8 (20%) were female with a median age of 45.5 ( 39.75-58.5) years. The most frequent cause of liver cirrhosis was alcohol ( n=28; 70%), followed by Wilson disease (n=4; 10%), metabolic dysfunction-associated fatty liver disease ( MAFLD) (n=3; 7,5%), autoimmune hepatitis ( n=2; 5%), primary biliary cholangitis ( n=2; %%), AIH/ PSC syndrome overlap (n=1; 2.5%). Eighteen patients (45%) were previously diagnosed with acute decompensation ( Table 1). The average number of performed TPEs was 6±12.73. In alcohol-related liver disease (ALD) cirrhosis, alcoholic hepatitis was the main cause of ACLF in 22 (78.5%) patients. Twenty-two patients (55%) were diagnosed with Community-acquired infections. At admission, the average MELD and MELD-Na scores were 28.5±6.43 and 31±6.21. The mean MELD and MELD-Na scores in surviving patients after 28 days were 24.3 ±7.78 and 25.52±7.58, respectively. The average CLIF C-ACLF score at admission was 47±8.07. ACLF grade 1 was observed in 20 patients (50%), ACLF grade 2 in 18, (45%), and ACLF grade 3 in 2 (5%). The 28-day mortality in this study group was 37.5% (n=15), with 25% (n=5) in ACLF grade 1, 44.4%(n=8) in ACLF grade 2, and 100% (n=2) in ACLF grade 3. Ninety-day mortality was 62.5% (n=25). Regarding the ACLF grade, the following 90-day mortality was observed: grade 1-45%( n=9), grade 2-77.8%( n=14), and grade 3-100 (n=2). With the use of TPE in addition to SMT, a statistically significant decrease in MELD and MELD-Na as well was observed after 28 days (p <0.01).

Conclusion

TPE may be a beneficial treatment option for patients who do not respond to SMT, but in our study, short-term mortality is still high. New prospective randomized studies with a larger number of subjects are needed to examine this therapeutic modality accurately.

References

1. European Association for the Study of the Liver (2023). EASL Clinical Practice Guidelines on acute-on-chronic liver failure. Journal of Hepatology, 79(2), 461–491.
2. Mao WL, Chen Y, Chen YM, Li LJ. Changes of serum cytokine levels in patients with acute on chronic liver failure treated by plasma exchange. J Clin Gastroenterol. 2011;45:551–555.
3. Chris-Olaiya A, Kapoor A, Ricci KS, Lindenmeyer CC. Therapeutic plasma exchange in liver failure. World J Hepatol. 2021;13(8):904-915.

Disclosure

There is no conflict of interest.

Introduction

The decompensation occurrence constitutes the main factor affecting survival for compensated advanced chronic liver disease (cACLD) patients. Based on the type of first decompensation event (DE), two distinct modalities of progression, with relatively different prognostic implications, have been described: “Non-Acute” (NAD) [slow ascites onset, mild hepatic encephalopathy (HE), or progressive jaundice] or “Acute” (AD) [grade 2/3 ascites within 2 weeks, severe HE, or acute bleeding]. Clinically significant portal hypertension (CSPH), defined by Hepatic Venous Pressure Gradient (HVPG) values > 10 mmHg, represents the best predictor for decompensation. However, it’s affected by the invasiveness, the general availability, and the relative strict operator dependence. Alternatively, various noninvasive tools (NITs), usually adopted to estimate liver function and hepatic fibrosis, have been proposed to predict decompensation.
Red cell distribution width (RDW)/Platelet ratio (RPR) has recently been suggested as a routinely assessable NIT predicting fibrosis severity in chronic hepatopathies. However, its predictive role in ACLD patients has never been explored.

Aims & Methods

We aimed to evaluate the accuracy of the RPR in predicting the occurrence and modalities (NAD or AD) of the first DE in cACLD patients.
In this observational study, 140 controls and 680 cACLD patients of various etiologies were prospectively enrolled and followed up (FU) semiannually for 7 years. At baseline, biochemical, clinical, and Liver Stiffness Measurement (LSM) data were collected, as well as the Child-Pugh (CP), MELD, AST/Platelet Ratio Index (APRI), Fibrosis-4 score (FIB-4), Albumin-Bilirubin (ALBI), ALBI-FIB-4, and RPR were calculated. CSPH was defined by the presence of endoscopic esophageal varices and/or assumed for LSM values > 25 kPa. During FU the DEs were recorded.

Results

208 (30.5%) cACLD patients progressed to decompensated ACLD (dACLD): 141 (67.8%) presented NAD and 67 AD (32.2%) as first DE. Baseline RPR resulted significantly higher in dACLD patients compared to cACLD and controls, as well as in AD patients compared to NAD (all p<0.0001). RPR positively correlated with APRI, FIB-4, ALBI, ALBI-FIB-4, MELD, CP, and LSM [R:0.88, R:0.81, R:0.61. R:0.74, R:0.68, R:0.75, R:0.74, R:0.94; all p<0.0001]. ROC analysis revealed RPR > 0.472 and > 0.894 as the best cut-offs [AUC: 0.95; AUC: 0.94] in the prediction respectively of 7-year first DE and relative modality (AD), as well as better predictive performance if compared to APRI [AUC:0.87; AUC:0.90], FIB-4 [AUC: 0.71; AUC:0.80], ALBI [AUC:0.90; AUC:0.77], ALBI-FIB-4 [AUC: 0.93; AUC:0.79], MELD [AUC:0.78; AUC:0.89], CP [AUC:0.77; AUC:0.71], and LSM [AUC:0.87; AUC:0.94] for both first DE and AD occurrence (all p<0.0001). Multivariable analysis revealed the RPR [adjusted hazard ratio (aHR): 2.24[MD1] [MR2] ] and the presence of baseline CSPH (aHR:1.84) as the variables independently and significantly influencing both outcomes (all p <0.0001). The Kaplan-Meier Log-Rank Test analysis on DE occurrence showed HR:4.62 [C.I. 95% 3.110-5.810] for baseline RPR > 0.472 and HR: 5.10 [C.I. 95% 3.481-6.125] for patients presenting simultaneously baseline RPR >0.472 and CSPH.

Conclusion

The availability of a non-invasive tool predicting the decompensation is an unmet need. RPR non-invasively predicts the timing and modalities of decompensation in cACLD patients representing a potential clinically useful biomarker in this context.

References

1. Taefi, Amir, et al. “Red cell distribution width to platelet ratio, a useful indicator of liver fibrosis in chronic hepatitis patients.” Hepatology international vol. 9,3 (2015): 454-60. doi:10.1007/s12072-015-9638-9
2. Abraldes, Juan G, and Guadalupe Garcia-Tsao. “Simple Clinical Tools to Predict Decompensation in Patients With Compensated Cirrhosis: An Unmet Need.” Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association vol. 17,11 (2019): 2179-2181. doi:10.1016/j.cgh.2019.04.026
3. D'Amico, Gennaro et al. “Towards a new definition of decompensated cirrhosis.” Journal of hepatology vol. 76,1 (2022): 202-207. doi:10.1016/j.jhep.2021.06.018