Introduction

Cystic fibrosis (CF) is a chronic, progressive, autosomal recessive disease caused by mutations of a single gene on the long arm of chromosome 7 that codes for the CF transmembrane regulator (CFTR)¹. Gastrointestinal symptoms and pancreatic insufficiency occur in more than 70% of people with CF (pwCF) and 96% of them showed at least one abnormal sign at intestinal ultrasound (IUS)².
Several studies^3,4,6 also documented a significant reduction of pancreatic stiffness in pwCF with pancreatic insufficiency as compared to those without. Elexacaftor-Tezacaftor-Ivacaftor (ETI), a triple combination of CFTR modulators, increases CFTR protein activity and significantly reduces morbidity and improves quality of life in pwCF⁸.

Aims & Methods

The aim of this prospective study, which is still ongoing, was to assess intestinal symptoms, IUS signs and pancreas elastography findings at baseline (T0) and their modification after different predefined lengths (T6 and T 12) of treatment with ETI.
Between October 2021 and March 2023 all consecutive pwCF candidate for starting ETI were enrolled. Clinical, biochemical, IUS signs and pancreas elastography (2D-shear-wave elastography, Philips) were collected at T0, T6 and T12.
The results of pancreatic elastography in CF were compared to those of a group of healthy controls.
Statistical analysis was performed using statistical package (SPSS) trial version 27.0.

Results

At T0, 141 patients (mean age 20±5.8; females 40.4%) were enrolled, 84 (60%) of them were re-assessed at T6 and 34 (24%) at T12. The healthy control group included 22 participants (mean age of 22.5 ±6.6 years, female 50%).
Main gastrointestinal symptoms and IUS signs are summarized in Table 1.
As previously reported, median pancreatic stiffness in pwCF was significantly lower than in controls (4.774 kPa ±0.864 vs 6.178 kPa ± 0.649, p<0.05). In addition, pancreatic stiffness values were similar at T0 and T6 (4.67 kPa ± 0.4 vs 4.774 KPa ±0.864, p=0.7) and significantly increased after one year of ETI treatment (5.442 kPa ±1.275 vs 4.774 kPa ± 0.864, p < 0.05).

Table

	T0 (n 141)	T6 (n 84)	T12 (34)
Abdominal pain	47 (33%)*	5 (6%)	0
Diarrhoea	15 (10.3%)*	1 (1.2%)	1 (3%)
Constipation	8 (5.7%)	3 (3.6%)	0
IUS pathological signs	48 (34.0%)*	13 (15%)^	4 (12%)§
TBW (> 3 mm)	32 (22.7%)*	8 (9.5%)^	2(5.8%)§
BW dilatation	25 (18.0%)*	7 (8.3%)	3 (8%)
Abnormal intestinal content (corpuscular, mixed)	85 (60%)*	32 (38%)	13 (38%)
Mesenteric hypertrophy	13 (9%)	6 (7.1)	0
Thickened appendix	41 (29%)	19 (22.6%)^	2 (6%)§

T0 vs T6 *< 0.05; T0 vs T12 §< 0.05; T6 vs T12 ^< 0.05

Conclusion

In pwCF, ETI significantly reduced gastrointestinal symptoms and pathological IUS signs. Pancreatic stiffness values, significantly lower than in healthy controls at T0, increased to normal values in PwCF treated for one year.

References

1. Shteinberg M, et al. Cystic Fibrosis. Lancet 2021; 397 (10290): 2195-2211.
2. Fraquelli M, et al. Bowel ultrasound imaging in patients with cystic fibrosis: Relationship with clinical symptoms and CFTR genotype. Dig Liver Dis. 2016 Mar;48(3):271-6.
3. Friedrich-Rust M, et al. Non-invasive measurement of liver and pancreas fibrosis in patients with cystic fibrosis. J Cyst Fibros. 2013 Sep;12(5):431-9.
4. Piskin FC, et al. A comparative study of the pancreas in pediatric patients with cystic fibrosis and healthy children using two-dimensional shear wave elastography. J Ultrasound. 2020 Dec;23(4):535-542.
5. Sigrist RMS, et al. Ultrasound Elastography: Review of Techniques and Clinical Applications. Theranostics. 2017 Mar 7;7(5):1303-1329
6. Yılmaz K, et al. Evaluation of children and adolescent with cystic fibrosis by pancreatic elastography. Pediatr Int. 2022 Jan;64(1): e14951.
7. Middleton PG, et al. Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele. N Engl J Med. 2019 Nov 7;381(19):1809-1819.
8. Bacalhau M, et al. Elexacaftor-Tezacaftor-Ivacaftor: A Life-Changing Triple Combination of CFTR Modulator Drugs for Cystic Fibrosis. Pharmaceuticals (Basel). 2023 Mar 8;16(3):410.

Introduction

Ustekinumab has been proven to be effective for treatment of patients with Crohn's disease; however, 30–40% of patients have been reported to lose clinical response within 2 years. We aimed to evaluate the efficacy of ustekinumab and identify predictors of short- and long-term efficacy in Crohn's disease.

Aims & Methods

Patients with Crohn's disease receiving their first ustekinumab infusion in our hospital between June 2017 and September 2020 were prospectively enrolled. Concentrations of serum cytokines and chemokines were measured using a multiplex bead array assay. Trough concentration of ustekinumab in serum samples collected after 8 weeks of intravenous administration were measured by ELISA.

Results

Fifty-nine Crohn's disease patients were enrolled in this study. Among 34 clinically active patients, 38.2% achieved a clinical response at week 8. None of the assayed factors were associated with short-term clinical response. Cumulative persistence rates of ustekinumab were 77.6% at 1 year and 58.9% at 2 years. Univariate Cox regression analysis revealed that Harvey–Bradshaw Index scores at baseline, concomitant immunomodulator treatment, and concentrations of interferon gamma-induced protein-10, monocyte chemoattractant protein-1 (MCP-1), and interleukin (IL)-1RA, IL-4, IL-6, and IL-8, but not other baseline parameters and trough concentrations of ustekinumab (hazard ratio (HR): 0.9846, 95% confidence interval (CI): 0.9561–1.014), were significantly associated with loss of efficacy. Multivariate Cox regression analysis found that biologic naïve status (HR: 0.1264, 95% CI: 0.02595–0.6158) and MCP-1 concentrations (HR: 1.037, 95% CI: 1.014–1.062) were significantly and associated with loss of sustained efficacy for ustekinumab treatment.

	Univariate analysis HR	Lower limit of the 95% CI	Upper limit of the 95% CI	p value	Multivariate analysis HR	Lower limit of the 95% CI	Upper limit of the 95% CI	p value
Biologic naïve, Yes	0.2367	0.05582	1.004	0.05061	0.1264	0.02595	0.6158	0.01047
Concomitant IM, Yes	2.644	1.144	6.113	0.02297
IL-4, pg/mL	1.562	1.028	2.375	0.03685
IL-6, pg/mL	1.07	1.02	1.123	0.00568
IL-8, pg/mL	1.067	1.025	1.111	0.001415
IL-1RA, pg/mL	1.003	1.001	1.005	0.00439
IP-10, pg/mL	1.001	1.001	1.001	0.02067
MCP-1, pg/mL	1.022	1.003	1.04	0.02055	1.037	1.014	1.062	0.001754
Trough level of UST at week 8	0.9846	0.9561	1.014	0.3029

Furthermore, if patients were divided into four groups according to prior biologics use and MCP-1 level which cut-off value was determined from receiver operating characteristics (ROC) at 1 year, MCP-1 low and biologics naïve group had 100% cumulative persistence rate of ustekinumab at week 140. On the other hand, MCP-1 high and biologics exposure group had below 20%.

Conclusion

Our findings suggest that pre-treatment serum MCP-1 analysis, combined with a history of biologic use could be a novel biomarker for predicting the long-term efficacy of ustekinumab in patients with Crohn's disease. However, predicting of long-term efficacy by a trough concentration of ustekinumab at week 8 might be limited.

Disclosure

The authors declare no conflicts of interest associated with this manuscript.

Introduction

Eosinophilic esophagitis (EoE) is a chronic inflammatory and progressive fibrotic condition of the esophagus characterized by the infiltration of eosinophils into the esophageal mucosa and esophageal dysfunction. There remain limited treatment options for EoE and accordingly, a substantial unmet need for effective and safe medical therapies. Drug development in EoE has been hampered by heterogeneous placebo response rates, especially for clinical outcomes, and uncertainty regarding appropriate endpoint configurations. Accurate characterization of placebo response in EoE randomized controlled trials (RCTs) will help inform more future efficient trial designs.

Aims & Methods

To conduct a systematic review and meta-analysis to characterize symptomatic, endoscopic, and histologic placebo response rates in placebo controlled EoE RCTs.
Electronic database (CENTRAL, MEDLINE, EMBASE) searching (inception to 1 JAN 2024) identified placebo controlled RCTs evaluating medical therapies for adults with EoE. Studies were screened independently by 2 reviewers (AR and SA), and full texts were then reviewed for eligibility. The proportion of clinical, endoscopic, and histologic responders (improvement and remission) assigned to placebo were pooled using a random-effect model. The Stuart-Ord inverse double arcsine square root transformation method was used to compute 95% confidence intervals (CI) for point estimates of placebo response. Heterogeneity was evaluated using the I² method. Analyses were conducted in StatsDirect 3.3.6.

Results

A total of 25 placebo-controlled RCTs (placebo sample size range: N = 4–105) were included. The pooled proportion of patients receiving placebo who achieved clinical response was 41.0% (n = 11; 95% CI 29.7%, 52.8%) with substantial heterogeneity (I² = 74.9%%). Definitions of clinical response varied between studies. The pooled proportion for histologic remission (peak eosinophil count [PEC] ≤6 eos per high power field [hpf]) was 4.3% (n = 20; 95% CI 2.6%, 6.2%) with low heterogeneity (I² = 23.6%), while a more stringent definition of histologic remission (PEC ≤1 eos/hpf) yielded a pooled placebo remission rate of 1.3% (n = 18; 95% CI 0.5%, 2.5%) with low heterogeneity (I² = 0%). The pooled histologic improvement rate was 6.2% (n = 15; 95% CI 3.3%, 10.0%) with substantial heterogeneity (I² = 50.6%). Limited studies reported on endoscopic improvement and remission (Table 1).

Conclusion

More than 1 in 3 patients assigned to placebo in EoE RCTs will achieve clinical response (substantial heterogeneity detected), while less than 1 in 10 of these patients will achieve histologic remission (low heterogeneity detected). These findings highlight 1) the need to develop validated and responsive patient-reported outcome measures, which may be difficult due to the episodic nature of symptoms in EoE; and 2) the challenge of using a coprimary clinical and histologic outcome in EoE RCTs, given the discordance between symptoms and objective disease activity measures.

Table 1. Pooled proportion of placebo patients achieving measured outcomes in EoE studies

Outcome Measured in Placebo Patients (n = number of studies)	Sample Size (range)	Pooled Proportion% (95% CI)	Heterogeneity, I2% (95% CI)
Clinical Response/Improvement (n =11)	6 to 105	41.0 (29.7, 52.8)	74.9 (49, 84.8)
Clinical Remission (n = 9)	4 to 33	13.8 (5.9, 24.3)	66.2 (12.2, 81.6)
Endoscopic Response/Improvement (n = 3)	6 to 19	25.1 (12.4, 40.5)	0 (0, 72.9)
Endoscopic Remission (n = 3)	9 to 29	2.8 (0.06, 9.6)	9.1 (0, 75.3)
Histologic Response/Improvement (≤ 15 eos/hpf, n = 15)	6 to 105	6.2 (3.3, 10.0)	50.6 (0, 71.3)
Histologic Remission (n = 24) ≤ 6 eos/hpf (n = 20) ≤ 1 eos/hpf (n = 18)	6 to 105	4.3 (2.6, 6.2) 1.3 (0.5, 2.5)	23.6 (0, 55.2) 0 (0, 43.7)

Disclosure

AR: No conflicts of interest
SA: No conflicts of interest
YY: No conflicts of interest
AQ: Is an employee of Alimentiv Inc.
DBO: Is an employee of Alimentiv Inc.
BGF: consulting fees from AbbVie, Abivax, Adiso, AgomAB Therapeutics, Allianthera, Amgen, AnaptysBio, Arena Pharma, Avoro Capital Advisors, Atomwise,, BioJamp, Biora Therapeutics, Blackbird Laboratories,Boehringer-Ingelheim, Boxer Capital, Celsius Therapeutics, Celgene/BMS, Celltrion, Connect BioPharma, Cytoki, Disc Medicine, Duality, EcoR1, Eli Lilly, Equillium, Ermium, First Wave, Forbion, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, Gossamer Pharma, GSK, Hinge Bio, Index Pharma, Imhotex, Immunic Therapeutics, Intercept, JAKAcademy, Janssen, Japan Tobacco Inc., Kaleido Biosciences, Klick Health, Landos Biopharma, Lenczner Slaght, LifeSci Capital, Lument AB, Mage Biologics, Mestag, Millennium, MiroBio, Monte Rose Tx, Morgan Lewis, Morphic Therapeutics, Mylan, Nexys Therapeutics, Nimbus Therapeutics, OM Pharma, OrbiMed Origo BioPharma, Orphagen, Pandion Therapeutics, Pendopharm, Pfizer, Prometheus Therapeutics and Diagnostics (Merck), Progenity, Protagonist, PTM Therapeutics, Q32 Bio, Rebiotix, REDX, Roche, Roivant/Televant, Sandoz, Sanofi, Seres Therapeutics, Silverback Therapeutics, Sobi, Spyre Therapeutics, Surrozen Inc., Sun Pharma, Synedgen, Takeda, Teva, Thelium, Tigenix, Tillotts, Triastek, TR1X Inc. Ventyx Biosciences, Zagbio, Zealand Pharma. Speaker fees from AbbVie, Janssen, Takeda.
VJ: consulting/advisory board fees from AbbVie, Alimentiv, Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Anaptyis Bio, Astra Zeneca, Avoro Capital, Bristol Myers Squibb, Celltrion, Eli Lilly, Endpoint Health, Enthera, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, Gilde Healthcare, GlaxoSmithKline, Genentech, Gilead, Innomar, JAMP, Janssen, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus Biosciences, Reistone Biopharma, Roche, Roivant, Sandoz, Second Genome, Sorriso, Synedgen, Takeda, TD Securities, Teva, Topivert, Ventyx, Vividion; and speaker’s fees from, Abbvie, Ferring, Bristol Myers Squibb, Galapagos, Janssen Pfizer Shire, Takeda, Fresenius Kabi.
AJB: AJB received research funding from Nutricia, Thelial, Sanofi/Regeneron, SST, and Dr. Falk Pharma and received speaker and/or consulting fees from Laborie, Medtronic, BMS, Dr. Falk Pharma, Calypso Biotech, Eupraxia, Aqilion, Alimentiv, Sanofi/Regeneron, Reckitt and AstraZeneca
ESD: Research funding: Adare/Ellodi, Allakos, Arena/Pfizer, AstraZeneca, Eupraxia, Ferring, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Revolo, Shire/Takeda
Consultant: Abbott, Abbvie, Adare/Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Apollo, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, Eupraxia, Dr. Falk Pharma, Ferring, GSK, Gossamer Bio, Holoclara, Invea, Knightpoint, Landos, LucidDx, Morphic, Nexstone Immunology/Uniquity, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, Upstream Bio
Educational grant: Allakos, Aqilion, Holoclara, Invea
CM: consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Pendopharm, Pfizer, Prometheus Biosciences Inc., Roche, Sanofi, Takeda, Tillotts Pharma; speaker's fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Eli Lilly, Ferring, Fresenius Kabi, Janssen, Organon, Pendopharm, Pfizer, Sanofi, Takeda, Tillotts Pharma; royalties from Springer Publishing; research support from AbbVie, Ferring, Pfizer.

Introduction

Transmural response (TR) and healing (TH) assessed by intestinal ultrasound (IUS) are gaining increasing relevance as treatment targets in Crohn’s disease (CD) [1]. Even though less established in ulcerative colitis [UC], in which the inflammation mainly affects mucosa and submucosa, there is clear evidence that applying IUS in UC is beneficial to monitor short-term response to therapy [2]. However, the long-term IUS outcome, its association to clinical and lab parameters as well as the predictive value of early TR remain elusive.

Aims & Methods

The TRUST BEYOND study is an ongoing, prospective, non-interventional, multi-centre study in patients with active CD or UC who receive a biologic- or Januskinase-inhibitor (JAKi)-therapy at baseline. The study aims to assess the predictive value of TR or TH, evaluated at week 12 for the disease outcome after 52 weeks (TR: reduction of bowel wall thickness (BWT) of at least 25% and/or normalization; TH: normalization of BWT and Colour Doppler signal). For this interim analysis, we report IUS and clinical results as well as fecal calprotectin levels of 77 UC patients on the same therapy after 12 (W12) and 52 weeks (W52) and assessed the predictive value of TR at W12 for clinical remission at W52.

Results

Seventy-seven UC patients (63.6% were male, median age was 38.6 years (30.6 – 55.7) median disease duration of 5.85 years (2.49–12.77)) with clinically active disease (SCCAI 8.5 ± 2.2) with increased BWT at baseline had a documented visit after 52 weeks until February 2023. For the vast majority, the most affected bowel wall segment was the sigmoid colon with a mean BWT of 5.22 ± 1.28 mm at baseline.
At W12 after induction of therapy, the proportion of UC patients with TR and TH was 67.5% (n = 52) and 31.2% (n = 24). At W52, the rates of UC patients increased to 77.9% (n = 60) for TR and 41.6% (n = 32) for TH. Over the study course, patients with TR at W12 and W52 had a numerically lower SCCAI score and reduced fecal calprotectin levels than patients without TR.
Of note, 72.2% (n = 39) of patients with TR at W12 were in clinical remission at W52 compared to 27.8% (n = 15) of patients without early transmural response (p = 0.178).

Conclusion

In this interim analysis of the TRUST BEYOND study, UC patients demonstrated substantial rates of transmural improvements on IUS after 12 and 52 weeks. Patients with early transmural response were more likely to be in remission after one year. This suggests that in UC, IUS has to some degree a predictive value as observed for CD.

References

1. Kucharzik T, Wittig BM, Helwig U, et al. Use of Intestinal Ultrasound to Monitor Crohn's Disease Activity. Clin Gastroenterol Hepatol. 2017; 15:4, 535-42 e2.
2. Maaser C, Petersen F, Helwig U On behalf of the German IBD Study Group and the TRUST&UC study group, et alIntestinal ultrasound for monitoring therapeutic response in patients with ulcerative colitis: results from the TRUST&UC studyGut 2020;69:1629-1636.

Disclosure

T. Kucharzik, U. Helwig, F. Seibold, L. Biedermann, C. Högenauer and C. Maaser have received lecture and consulting fees from AbbVie.
I. Fischer has received consulting fees from AbbVie. L. Hammer and S. Rath are AbbVie employees and may own AbbVie stock or options.
AbbVie sponsored the study; contributed to the design; participated in the collection, analysis, and interpretation of data; in writing, reviewing, and approval of the final version. No honoraria or payments were made for authorship.

Introduction

A successful colonoscopy requires ideal stool preparation, yet the percentage of insufficient bowel preparation is still very high. Frequently, the patients use website information on colonoscopy preparation. Conversely, the daily activity of the hospital staff consists of spending time with patients, communicating with them and giving answers to a high number of questions coming from patients regarding the preparation for the procedure or the exam itself. Hence, the idea to adopt a rapid and intuitive patient-oriented digital service to respond to their needs, the virtual assistant Eric.

Aims & Methods

Endo-Chat is an automated online communication platform, powered by AI (Artificial Intelligence) with the use of the Natural Language Processing and Deep Learning technologies, that answers procedure-related questions in real-time. The engine is named ERIC, stands for "Endoscopy Robot for Intelligent Chat" and is an intelligent chatbot, capable of answering autonomously to most of the doubts of a patient who is supposed to undergo an endoscopic examination.

Results

Since the introduction of the conversational artificial intelligence system at the Policlinico Gemelli starting from 24^th of January 2022 to the 16^th of March 2023, Eric has been able to autonomously manage 94% of the questions sent by patients, thus forwarding only the remaining 6% (of the requests) to specialized human operators.
We calculated that in the pre-pilot phase, a large part of the daily activity of nurses was dedicated to communicating with patients, around 40 hours per week, while in the post-pilot phase, the time spent for communication was significantly reduced to 15 hours per week. According to OECD Health Statistics 2022, the average annual salary of a European nurse is 35,300 euros, with an annual hypothetical saving of 22,062 euros, comparable to a part-time contract.
Also, the number of cancelled procedures for poor patient preparation has fallen from 22 to 7 per week, considering a volume of 200 procedures per week.
Regarding patient's experience, users can leave voluntary feedback on their virtual assistant experience directly on the ERIC website, evaluating the quality of the service. Patient service evaluations were enthusiastic till now, as 63% rated the service as excellent.

Conclusion

In our observational pilot study, the first in Europe to our knowledge, we assessed the benefits measurement for patients and Hospital staff. Starting from these preliminary interesting results, we can speculate that the introduction of Endo-Chat in high-volume endoscopy service is feasible and useful not only for patients but also for hospital staff.

Disclosure

The authors declare no conflict of interest

Introduction

Percutaneous endoscopic gastrostomy (PEG) is a widely recognized procedure for delivering enteral nutrition to head and neck cancer patients who often suffer from dysphagia and malnutrition. Nevertheless, the influence of PEG on survival among ENT cancer patients is yet to be fully understood.

Aims & Methods

This research seeks to determine the overall survival rate of ENT cancer patients with PEG and identify the critical factors affecting survival during the period of 2006-2022. We conducted a retrospective cohort study on ENT cancer patients diagnosed between 2006 and 2022. The Kaplan-Meier method was employed to estimate overall survival, while Cox proportional hazards regression was used to compute hazard ratios (HRs). Forest plots were generated to illustrate the HRs and corresponding 95% confidence intervals (CIs) for factors significantly linked to survival.

Results

Our analysis included 6646 patients, with 1851 undergoing PEG (27.9%) and 4795 without PEG (72.1%). According to the Kaplan-Meier analysis, patients who received PEG had a median survival time of 2.34 years (95% CI: 2.17 to 2.65) compared to 1.09 years (95% CI: 1.03 to 1.16) for non-PEG patients (Figure 1 A). The Forest plot identified several key factors significantly related to improved survival, such as PEG (aHR: 0.66, 95% CI: 0.61 to 0.70), younger age (aHR: 1.02, 95% CI: 1.02 to 1.02), and lower cancer stage (stage 2: aHR: 1.24, 95% CI: 1.08 to 1.43; stage 3: aHR: 1.45, 95% CI: 1.26 to 1.67; stage 4: aHR: 1.87, 95% CI: 1.66 to 2.12) (Figure 1 B). The relationship between PEG and survival suggests a 34% decrease in mortality risk for PEG patients.

Conclusion

This study shows that PEG plays a significant role in enhancing the overall survival of ENT cancer patients. Factors such as age and cancer stage also strongly impact patient outcomes. These results underline the potential advantages of PEG in ENT cancer patient management and stress the necessity for a multidisciplinary strategy to optimize patient care. Further prospective research is needed to establish the causal link between PEG and increased survival and to pinpoint the best timing and selection criteria for PEG in ENT cancer patients.

Introduction

Hepatitis C is a major global health problem caused by the hepatitis C virus, which can result in mild to severe symptoms, including liver cirrhosis and cancer. Unsafe medical practices, lack of awareness, poverty, intravenous drug abuse and limited access to healthcare facilities contribute to the high prevalence of this disease. An estimated 58 million people are effected with hepatitis c worldwide and every year 1.5 million are adding to burden (1).Pakistan is one of the countries with the highest burden of hepatitis C, affecting around 12 million people having 4.2 % prevalence (2). While the Pakistani government and international organizations have taken steps to eliminate hepatitis C, challenges remain, such as the stigma attached to the disease, limited access to screening and treatment in remote areas, and inadequate funding for hepatitis control program (3).

Aims & Methods

To address the issue of hepatitis C elimination in rural Pakistan, a cross-sectional observational study was conducted from January 2021 to December 2022 at the MTI Gajju khan Medical College Swabi. All patients above 18 years of age who visited the gastroenterology OPD were screened for Hepatitis C. Patients who were positive for Anti HCV antibody and had detectable HCV RNA were enrolled in the study. Patients were divided into four groups: Chronic hepatitis C non cirrhotic treatment naïve and treatment experienced, Compensated Cirrhosis naïve and experienced. Sofosbuvir and Daclatasvir for 12 or 24 weeks were given, and Ribavirin was given to treatment-experienced and cirrhotic patients. Prevalence , efficacy of available free DAAs , recommendation to achieve elimination goal were discussed at end of study.

Results

Out of 10,240 patients screened for hepatitis C during their first visit to the gastroenterology OPD, 420 patients with a mean age of 36+16 having positive HCVRNA were enrolled. Almost 90% of the patients were non-affordable. After initial evaluations, the patients were separated into four groups. Chronic hepatitis C without cirrhosis was present in 287 patients, while cirrhotic were 137. Treatment-naïve patients were 307, and 113 patients were treatment-experienced. ETR was achieved in 403 (96%) patients, and SVR was achieved in 413 (91.5%) patients.

Conclusion

To achieve the hepatitis elimination goal 2030 in countries with low human development indexes, chronic hepatitis C screening, diagnosis, and management must be sponsored by national and international organizations. One-time screening should be offered for every patient above 18 years on first contact with healthcare workers. Unsafe medical practices should be strongly discouraged. The freely available drugs Sofosbuvir and Daclatasvir, with or without RBV, are highly effective treatment options for chronic HCV and the most adaptable strategy to eliminate hepatitis C. This regimen has produced excellent results in our country, influenced mainly by the presence or absence of cirrhosis and the easy and free availability of drugs.

References

1. Salari N, Kazeminia M, Hemati N, Ammari-Allahyari M, Mohammadi M, Shohaimi S. Global prevalence of hepatitis C in general population: A systematic review and meta-analysis. Travel Med Infect Dis. 2022 Jan 8;46:102255.
2. Abbas Z, Abbas M. The cost of eliminating hepatitis C in Pakistan. Lancet Glob Health. 2020 Mar;8(3):e323–4.
3. Lim AG, Walker JG, Mafirakureva N, Khalid GG, Qureshi H, Mahmood H, et al. Effects and cost of different strategies to eliminate hepatitis C virus transmission in Pakistan: a modelling analysis. Lancet Glob Health. 2020 Mar;8(3):e440–50.
4. Cox AL, El-Sayed MH, Kao JH, Lazarus JV, Lemoine M, Lok AS, et al. Progress towards elimination goals for viral hepatitis. Nat Rev Gastroenterol Hepatol. 2020;17(9):533.
5. The Lancet. Viral hepatitis elimination: a challenge, but within reach. Lancet. 2022 Jul 23;400(10348):251.
6. Waheed Y, Siddiq M, Jamil Z, Najmi MH. Hepatitis elimination by 2030: Progress and challenges. World J Gastroenterol. 2018 Nov 11;24(44):4959.

Disclosure

Authors have no conflict of interest in study.