Hepatology
Rice-derived recombinant human serum albumin as an alternative to human plasma for patients with decompensated liver cirrhosis: a randomised, double-blind, positive-controlled and non-inferiority trial
Niu J, Gao Y, Wang G, et al. Rice-derived recombinant human serum albumin as an alternative to human plasma for patients with decompensated liver cirrhosis: a randomised, double-blind, positive-controlled and non-inferiority trial. Gut 2025; 74: 1476-1485. doi: 10.1136/gutjnl-2025-335577
Human albumin solution (HAS) is an essential therapy in decompensated cirrhosis. Despite the infectious risk and unacceptability in some cultures of using human products, plasma-derived human serum albumin (pHSA) remains the only source of HAS. Challenges in developing recombinant HSA (rHSA) include high costs and difficult scalability. Niu et al., developed rHSA from rice grains of Oryza sativa (OsrHSA). Its proposed advantages include low immunogenicity, low costs and the relative ease of growing rice.
This phase II clinical trial (HY1001) evaluated the safety and efficacy of OsrHSA compared to pHSA in patients with decompensated cirrhosis, ascites and albumin level ≤30g/L. It was a randomised, double-blinded multicentre trial. Patients received daily infusions of OsrHSA or pHSA for up to 14 days and were followed up for two weeks.
Two hundred twenty-four patients were enrolled. There was no significant difference between the OsrHSA and pHSA groups in: proportion of patients reaching the primary endpoint (albumin ≥35g/L); time to endpoint; change in body weight/ascites. OsrHSA did not generate any anti-drug antibodies in the 20g group, and generated similar levels of anti-host cell protein antibodies as pHSA. Infusion-related adverse events were similar between OsrHSA and pHSA.
OsrHSA holds promise as an alternative to pHSA. Limitations of this trial include HAS being used outside internationally accepted indications (hepatorenal syndrome, spontaneous bacterial peritonitis and paracentesis); a short follow-up period; the exclusion of patients with known rice/cereal allergies; and the uncertain feasibility of producing this protein at the levels required to meet global demand.
Longitudinal paired liver biopsies and transcriptome profiling in alcohol-associated hepatitis reveal dynamic changes in cellular senescence
Rodrigo-Torres D, Kilpatrick A, Ferreira-Gonzalez S, et al. Longitudinal paired liver biopsies and transcriptome profiling in alcohol-associated hepatitis reveal dynamic changes in cellular senescence. Gut 2025; 74:1500-1513. doi: 10.1136/gutjnl-2024-334094
Alcohol associated hepatitis (AH) is an acute manifestation of alcohol-related liver disease which presents with jaundice, elevated liver enzymes and is characterised histologically by steatosis, inflammation and cell death (usually apoptosis). Senescence is a state where cells stop dividing and secrete pro-inflammatory factors, which has been shown to play a role in a range of acute and chronic liver disease. However, the role of senescence in AH is not well understood.
Rodrigo-Torres et al., performed transcriptomic analysis of paired transjugular liver biopsies from day 0 and day 28 post-treatment of patients (n=27) with AH participating in the IL-1 Signal Inhibition In Alcoholic Hepatitis (ISAIAH) clinical trial with either placebo or canakinumab (IL-1 (interleukin-1) inhibitor).
Through bulk ribonucleic acid (RNA) sequencing they found downregulation of senescence markers as well as markers of senescence-associated secretory phenotype (SASP) – a group of proteins associated with senescence that drive inflammation at day 28 compared to day 0 associated with clinical resolution of AH. There was similar downregulation of apoptosis-associated factors. They additionally found upregulation of hepatocyte markers as AH resolved
Re-analysis of other AH datasets confirmed upregulation of senescence markers in AH compared to normal liver along with downregulation of hepatocyte markers. For further validation they used an in vitro model of hepatocytes and found that treating the cells with ethanol led to a transcriptomic increase in senescence markers by RNA sequencing.
Rodrigo-Torres et al., concluded that senescence in AH may play a role in pathogenesis and the dynamic nature highlights it as a potential therapeutic target to modify the progression of disease.
Pancreas
Parecoxib sequential with imrecoxib for occurrence and remission of severe acute pancreatitis: a multicentre, double-blind, randomised, placebo-controlled trial.
Huang L, Feng Z, Yang W, et al. Parecoxib sequential with imrecoxib for occurrence and remission of severe acute pancreatitis: a multicentre, double-blind, randomised, placebo-controlled trial. Gut 2025;74(9): 1467-1475. doi: 10.1136/gutjnl-2024-334038.
This large multicentre randomised controlled trial looked at whether cyclooxygenase-2 inhibitors (COX-2Is) can change the course of acute pancreatitis. Severe acute pancreatitis (SAP) remains a very serious condition, with mortality rates of 20–40%, mainly driven by persistent organ failure and infected necrosis. Presently, management is supportive, with no proven drug that alters outcomes.
In this study, 348 patients with predicted SAP were randomised to receive either sequential COX-2 inhibition (intravenous parecoxib for three days, followed by oral imrecoxib for 30 days) or placebo, on top of standard care. The main outcome was duration of organ failure. Results were striking: patients in the COX-2I group had shorter organ failure (median 4 vs. 7 days) and fewer developed SAP (62% vs. 78%). Respiratory failure was the most common problem, and its duration, as well as need for mechanical ventilation, were both significantly reduced in the treatment arm.
Importantly, COX-2Is were also linked to fewer local complications (pseudocysts, necrotic infection), lower systemic inflammatory markers, shorter hospital stays, and reduced 30-day mortality (3.4% vs. 8.6%). Treatment costs were also lower. The regimen was well tolerated, with only a small number of gastrointestinal bleeds, not clearly drug related. Patients enrolled earlier (within 48 hours of symptom onset) seemed to benefit most, but even later treatment shortened organ failure duration.
In conclusion this trial offers high-quality evidence that COX-2 inhibition could be the first disease-modifying treatment for SAP. If confirmed in further studies, it has the potential to change routine practice by improving survival and reducing complications.
Colon
Colorectal cancer incidence after the first surveillance colonoscopy and the need for ongoing surveillance: a retrospective, cohort analysis
Robbins E, Wooldrage K, Rutter M, et al. Colorectal cancer incidence after the first surveillance colonoscopy and the need for ongoing surveillance: a retrospective, cohort analysis. Gut 2025; 74: 1419-1429. doi: 10.1136/gutjnl-2024-334242
There are established recommendations for the first surveillance colonoscopy (SC1) following polypectomy based on baseline polyp characteristics in patients deemed to remain at increased risk for colorectal cancer (CRC). However, few data exist to inform surveillance beyond SC1. This study sought to identify patient groups who remain at increased risk of CRC after SC1, compared with the general population, to determine the need for ongoing surveillance.
A retrospective cohort of patients who had adenomas removed at colonoscopy at 17 UK hospitals from 1984 to 2010 were identified. Exclusion criteria CRC before or at baseline and conditions that increased CRC risk. 10508 patients were classified into four groups based on combinations of low-risk and/or high-risk findings at baseline and SC1. For example, patients who were defined as ‘high risk, low risk’ (HR-LR) had high risk findings at baseline and low risk findings at SC1. Definition of high-risk findings followed the 2020 UK post polypectomy surveillance guideline.
CRC incidence over a median of 8 years after SC1 were examined and 151 CRCs detected. CRC incidence in the LR-LR group after SC1 was lower when compared to the general population but higher in the HR-HR group. After SC2, this difference did not persist in the HR-HR group. Patients with high-risk findings both at baseline and SC1 required a second surveillance visit. By contrast, those with low-risk findings at SC1 regardless of baseline findings did not. This study suggests classifying patients using both baseline and SC1 findings may add little value and SC1 findings alone may be sufficient.
Combining faecal haemoglobin, iron deficiency anaemia status and age can improve colorectal cancer risk prediction in patients attending primary care with bowel symptoms: a retrospective observational study
Digby J, Nobes J, Strachan J, et al. Combining faecal haemoglobin, iron deficiency anaemia status and age can improve colorectal cancer risk prediction in patients attending primary care with bowel symptoms: a retrospective observational study. Gut 2025; 74: 1430-1436. doi: 10.1136/gutjnl-2024-334248.
The National Institute for Health and Care Excellence suspected colorectal cancer (CRC) guidelines recommend a faecal haemoglobin (f-Hb) with a referral threshold of ≥10 µg Hb/g, but most have a normal colonoscopy.
This retrospective single-centre study identified cumulative 1-year CRC risk in symptomatic patients using age, f-Hb and presence of iron deficiency anaemia (IDA).
Of 34647 valid f-Hb results retrieved; 7889 (22.8%) had f-Hb≥10 µg Hb/g. Of these, 33285 samples (96.1%) had associated FBC results of which 3000 (9.0%) had IDA. Overall, 571 incident CRC were recorded. The risk of CRC breached 3% in patients with f-Hb>99 µg Hb/g aged >40 years and reached 30% (19.4–41.0) with f-Hb>99 µg Hb/g in age >55 years plus IDA. 2029 f-Hb results (25.7%) were in the 10–19 µg Hb/g range of which 27 (1.3%) had CRC. In this subgroup, CRC risk did not exceed 3% in patients <85 years and no IDA.
Digby et al., concluded that the threshold for f-Hb used in practice to trigger referral for colonoscopy in patients presenting with symptoms could be safely raised to ≥20 µg Hb/g faeces, provided safety-netting with FBC (full blood count) analysis (to identify IDA) and repeat FIT (faecal immunochemical test) for persisting bowel symptoms is in place. An important limitation is that data on other significant bowel disease including high-risk adenoma as a potential precursor to CRC, and inflammatory bowel disease, were not available.
Reviewers
Dr Catherine Hsu, Post-ST5 Hepatology Clinical Research fellow, Queen Mary University of London, London, UK
Dr Khurum Hakeem, Gastroenterology Registrar, University Hospital of North Durham, Durham, UK
Dr Abisoye Akintimehin, Gastroenterology Registrar, London North West University Healthcare NHS Trust, London, UK
Dr Kelly Chatten, Bolton NHS Foundation Trust, Bolton, UK
Dr James Sun, Pre-doctoral Clinical Research Excellence Fellow, Francis Crick Institute and King’s College London, London, UK
BSG GUT Highlights is edited by Dr Philip J Smith, Honorary Consultant Luminal Gastroenterologist, Royal Liverpool Hospital, Liverpool University Hospitals NHS Foundation Trust, Mount Vernon, Liverpool, UK. Dr Smith is the Digital and Education Editor of GUT, Editor in chief of Frontline Gastroenterology and Associate Editor of BMJ Open Gastroenterology.
Funding
The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests: None declared.
Provenance and peer review: Not commissioned; internally peer reviewed.