A Human Gut-Associated Picobirnavirus Establishes the Picobirnaviridae as the Third Clade of RNA Bacteriophages
A virus frequently detected in human stool may not infect human cells at all. New research identifies a human gut-associated picobirnavirus as an RNA bacteriophage, revealing a previously unrecognized bacterial host and establishing Picobirnaviridae as the third major clade of RNA phages.
KEY FINDINGS: The study changes the interpretation of picobirnaviruses detected in human and animal specimens. Their presence in stool does not necessarily indicate direct infection of the host or zoonotic transmission; the same virus may instead be detected in different animals because they carry the same bacterial species. The findings also have implications for research into the gut microbiome and human disease. Although PBVs have previously been associated with several clinical conditions, this study does not establish a causal role in those diseases. If PBVs are predominantly bacterial viruses, their potential effects on health may involve changes in bacterial populations and microbiome function.
The authors acknowledge that the host range of PBVs remains uncertain and that the findings from PBV-18941 cannot automatically be generalized to every member of the Picobirnaviridae family. Further work is needed to characterize additional PBVs, establish their bacterial hosts and determine whether they influence disease-associated microbial communities.
BACKGROUND: This study challenges the traditional understanding of picobirnaviruses as viruses associated with eukaryotic hosts. It presents evidence that a human gut-associated picobirnavirus belongs to a distinct lineage of RNA bacteriophages—viruses that infect bacteria—positioning the family Picobirnaviridae as a third major clade of RNA bacteriophages.
Picobirnaviruses (PBVs) are double-stranded RNA viruses frequently detected in faecal samples from humans and animals. They have been associated with several conditions, including diarrhoea, enteric graft-versus-host disease, irritable bowel syndrome and type 1 diabetes in pregnant women. However, these associations have not established that PBVs directly infect vertebrate cells or cause disease. Despite their widespread detection, PBVs had remained difficult to characterize because no reliable culture system or animal model was available. Their true biological hosts were therefore uncertain. The possibility that they infect microorganisms living in the gut, rather than human or animal cells, had been proposed but not experimentally established.
DETAILS: Researchers investigated two previously unreported PBVs identified in human stool samples collected in the United Kingdom. The viruses, designated PBV-18941 and PBV-19022, were first propagated in germ-free mice following faecal microbiota transplantation. Viral RNA increased substantially in at least one mouse for each virus: PBV-18941 increased 10⁷-fold and PBV-19022 increased 10⁶-fold. Both persisted through day 23. Further experiments demonstrated that PBV-19022 could be serially propagated in mice. Neomycin treatment eventually eliminated the virus, suggesting a possible relationship with an antibiotic-sensitive bacterial host. The investigators subsequently established an anaerobic in vitro culture system using the gut microbial community from PBV-positive mouse stool. PBV-18941, but not PBV-19022, persisted through 20 passages. Its growth was eliminated by neomycin, vancomycin and metronidazole, providing further evidence that bacterial growth was necessary for its propagation.
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RNA fluorescence in situ hybridization demonstrated that both genomic segments of PBV-18941 were present inside bacterial cells. Fluorescence-activated cell sorting and sequencing identified a previously undescribed Anaerotignum species, proposed as ‘Candidatus Anaerotignum faecalis', as the bacterial host. PBV RNA was detected in this organism but not in the other prominent bacterial species identified in the sorted community. The identified bacterium represented approximately 0.3% of the total bacterial community, and approximately 10% of its cells were infected by PBV-18941. The researchers were unable to isolate ‘Ca. A. faecalis' as a pure culture, which remains an important limitation.
The findings provide direct experimental evidence that PBV-18941 infects bacteria rather than vertebrate cells, establishing it as an RNA bacteriophage. The study therefore identifies Picobirnaviridae as the third recognized clade of RNA bacteriophages, alongside leviviruses and cystoviruses. Importantly, PBV-18941 infects a Gram-positive bacterium, expanding the known host range of characterized RNA phages, which had previously been associated primarily with Gram-negative bacteria.
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Source: Gan, T., Rosen, A. L., Wang, L., et al. A human gut-associated picobirnavirus establishes the Picobirnaviridae as the third clade of RNA bacteriophages. Nature Microbiology. Published: October 29, 2026. DOI: 10.1038/s41564-026-02523-z.
Avatrombopag Improves Persistent Chemotherapy-Induced Thrombocytopenia in Gastrointestinal Cancers: Results From the Phase II ACT-GI Trial
Persistent chemotherapy-induced thrombocytopenia can disrupt cancer treatment by forcing dose reductions and delays. In the phase II ACT-GI trial, oral avatrombopag improved platelet recovery and helped more patients with gastrointestinal cancers complete chemotherapy without CIT-related treatment modifications.
KEY FINDINGS: Avatrombopag significantly improved platelet recovery and reduced the likelihood of recurrent CIT that would interfere with chemotherapy delivery in patients with GI cancers. The oral administration and once-daily dosing may offer a practical approach to managing persistent CIT. However, the trial enrolled only 47 patients and was stopped early for efficacy, which may affect the precision of the estimated treatment benefit. The findings establish efficacy for the study's platelet and chemotherapy-delivery endpoints, but do not demonstrate improved cancer survival or other long-term oncologic outcomes. Larger studies are needed to establish the durability of benefit, broader safety profile, and impact on cancer treatment outcomes. ASCO Publications
BACKGROUND: Chemotherapy-induced thrombocytopenia (CIT) is a clinically important complication of cytotoxic cancer treatment. Persistent thrombocytopenia can lead to repeated chemotherapy delays, dose reductions, and compromised treatment intensity, potentially affecting cancer outcomes. Management remains challenging because widely available approved therapies are limited. Avatrombopag, an oral thrombopoietin receptor agonist, stimulates platelet production and may offer an alternative to injectable therapies for patients with persistent CIT. The ACT-GI trial evaluated its efficacy and safety in patients with gastrointestinal (GI) cancers receiving cytotoxic chemotherapy.
DETAILS: ACT-GI was a multicenter, randomized, double-blind, placebo-controlled, investigator-initiated phase II trial conducted in the United States. Adults with GI cancers and persistent CIT were randomly assigned in a 1:1 ratio to receive avatrombopag or placebo. Persistent CIT was defined as a platelet count of ≤85 x 109/L on the first day of a chemotherapy cycle, despite sufficient time for recovery from the preceding cycle. The primary endpoint was successful platelet recovery to ≥100 x 109/L, completion of the on-study chemotherapy cycle without dose modification or delay due to thrombocytopenia, and prevention of CIT recurrence at the subsequent cycle. Treatment began with avatrombopag 40 mg once daily, with protocol-directed dose adjustments. The trial enrolled 47 patients, including 23 assigned to avatrombopag and 24 to placebo. Enrollment was stopped at a planned interim analysis after prespecified efficacy criteria were met. The primary endpoint was achieved by 16 of 23 patients receiving avatrombopag (70%; 95% CI, 47 to 87) compared with 4 of 24 patients receiving placebo (17%; 95% CI, 5 to 37; Z = 3.67, P .001). Platelet recovery to ≥100 x 109/L during the initial treatment period occurred in 19 of 23 patients (83%) in the avatrombopag group and 11 of 24 patients (46%) in the placebo group. At the end of the chemotherapy treatment period, median platelet counts were 157 (IQR, 136-202) x 109/L with avatrombopag and 72 (IQR, 68-134) x 109/L with placebo. Adverse events occurred in 78% of patients receiving avatrombopag and 46% receiving placebo. Serious adverse events were reported in 17% and 0%, respectively. No serious adverse events were attributed to the study drug, and no treatment-related adverse events resulted in death or discontinuation of study medication.
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Source: Al-Samkari, H., Shatzel, J. J., Panch, S.R., et al. Avatrombopag Versus Placebo for Persistent Chemotherapy-Induced Thrombocytopenia in GI Cancers: The Phase II ACT-GI Trial. Journal of Clinical Oncology. 2026; 44(31): 3006-3014. Published: November 1, 2026. DOI: 10.1200/JCO-26-00568.
Lean MASLD Associated With Higher In-Hospital Mortality and Hepatic Complications
Lean body weight does not necessarily mean lower risk in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). In a US hospitalization-based analysis, lean MASLD was associated with higher odds of mortality, hepatic complications, and several gastrointestinal malignancies compared with nonlean MASLD. Although the observational findings cannot establish causality, they highlight the importance of assessing disease severity rather than relying on BMI alone.
KEY FINDINGS: Lean MASLD may carry substantial hepatic and oncological risks despite the absence of obesity. Clinicians should avoid relying on BMI alone when assessing disease severity and should consider liver complications and associated comorbidities in patients with steatotic liver disease across body-weight categories.
The study's retrospective design and reliance on hospitalization data are important limitations. The findings do not establish causality and may not be generalizable to all individuals with MASLD, particularly those managed in outpatient settings. Further research is needed to clarify the mechanisms underlying these associations and determine how risk assessment and management should be tailored to lean patients.
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an important cause of chronic liver disease and related complications. Although it is commonly associated with overweight and obesity, the condition also occurs in individuals with a lean body mass index (BMI). The clinical risks in this population remain an important area of investigation, particularly because normal body weight may not reliably indicate the absence of advanced liver disease or metabolic dysfunction.
DETAILS: Researchers conducted a retrospective comparative study using the US National Inpatient Sample (NIS) database from 2016 through 2020. Adult hospitalizations involving MASLD were identified, with exclusions for other specified liver conditions, including viral hepatitis, alcoholic hepatitis, primary biliary cholangitis, hereditary hemochromatosis, autoimmune hepatitis, and Wilson disease. Outcomes were compared between patients classified as lean and those with nonlean BMI. The analysis assessed mortality, hepatic complications, and gastrointestinal malignancies among hospitalized patients with MASLD.
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Hospitalized patients with lean MASLD had significantly higher odds of mortality than those with nonlean MASLD (odds ratio, 2.10; P .001). The lean group also had higher odds of cirrhosis, portal hypertension, spontaneous bacterial peritonitis (SBP), and ascites.
In addition, lean MASLD was associated with higher odds of several gastrointestinal malignancies, including esophageal, gastric, pancreatic, and colorectal cancers. These findings suggest that lean body weight should not be interpreted as a reliable indicator of lower clinical risk in patients hospitalized with MASLD.
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Source: Desai, C., Lohani, S., Sharma, A. R., et al. Lean Metabolic Dysfunction-Associated Steatotic Liver Disease: A Comparative Analysis of Hepatic and Oncological Outcomes. Journal of Clinical Gastroenterology. 2026; 60(10): 922-926. Published: November/December 2026. DOI: 10.1097/MCG.0000000000002153.s
AI-Assisted Colonoscopy for Colorectal Lesion Detection in Lynch Syndrome
A multicentre randomized trial of 733 patients with Lynch syndrome found that AI-assisted colonoscopy did not significantly increase adenoma detection compared with high-definition white-light colonoscopy alone (33.8% vs 30.9%; P=0.41). AI-based lesion characterization showed good sensitivity and specificity but did not clearly improve on expert optical diagnosis in specialized surveillance settings.
KEY FINDINGS: In this international randomized trial conducted at specialized Lynch syndrome surveillance centres, adding AI-assisted detection to high-definition white-light colonoscopy did not significantly increase adenoma detection. Although the CADx system demonstrated good sensitivity and specificity for lesion differentiation, it did not clearly provide an advantage over expert optical diagnosis in this specialist setting. The findings indicate that the benefit of AI-assisted colonoscopy may depend on the expertise and clinical setting in which it is deployed.
BACKGROUND: Individuals with Lynch syndrome undergo regular colonoscopic surveillance because of their increased risk of colorectal cancer. Artificial intelligence (AI)-based computer-aided detection (CADe) has improved adenoma detection in average-risk colorectal cancer screening, but evidence in Lynch syndrome surveillance has been limited. The CADLY2 trial evaluated whether AI-assisted colonoscopy could improve adenoma detection and whether computer-aided optical diagnosis (CADx) could accurately differentiate neoplastic from non-neoplastic colorectal lesions.
DETAILS: This international, multicentre, open-label, randomized controlled trial was conducted at nine specialized hereditary cancer surveillance centres in Belgium, Germany, the Netherlands, and Spain. Adults aged 18 years or older with genetically confirmed Lynch syndrome undergoing surveillance colonoscopy were randomly assigned to high-definition white-light (HD-WL) colonoscopy alone or HD-WL colonoscopy assisted by the CAD EYE AI system. CADe was used during withdrawal to identify lesions, while CADx was used after lesion detection to assist with optical differentiation. The primary outcome was adenoma detection rate, defined as the proportion of patients with at least one histopathologically confirmed adenoma.
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Between May 9, 2023, and October 30, 2025, 757 patients were randomly assigned to HD-WL colonoscopy (377) or AI-assisted colonoscopy (380). The primary analysis included 733 patients: 369 in the HD-WL group and 364 in the AI-assisted group. Adenoma detection occurred in 30.9% of patients undergoing HD-WL colonoscopy compared with 33.8% receiving AI-assisted colonoscopy. The odds ratio was 1.14 (95% CI, 0.83-1.57; P=0.41), indicating no statistically significant improvement in adenoma detection with CADe. In the lesion-level analysis, CADx differentiated neoplastic from non-neoplastic lesions with a sensitivity of 85.9% (95% CI, 82.0-89.1) and specificity of 91.4% (95% CI, 89.4-93.0). Three adverse events occurred in the AI-assisted group, including two mild post-polypectomy bleeding events and one serious pulmonary embolism or deep venous thrombosis considered unrelated to the procedure. No adverse events were reported in the HD-WL group.
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Source: Hüneburg, R., van Bokhorst, Q. N. E., Pellisé, M., et al. Artificial intelligence-assisted detection and optical differentiation of colorectal lesions in Lynch syndrome surveillance (CADLY2): a multicentre, open-label, randomised controlled superiority trial. The Lancet Gastroenterology & Hepatology. 2026; 11(10): 875-886. Published: October, 2026. DOI: 10.1016/S2468-1253(26)00163-9.
IL-17 Inhibitors Not Associated With Increased IBD Risk in Hidradenitis Suppurativa
A systematic review and meta-analysis of 24 studies found that inflammatory bowel disease events were rare among patients with hidradenitis suppurativa receiving IL-17 inhibitors. In randomized trials, new-onset IBD occurred in 0.23% of patients receiving IL-17 inhibitors versus 0% with placebo, with no significant difference between groups. The findings are reassuring but support continued monitoring because event numbers were low and reporting was inconsistent.
KEY FINDINGS: IBD events were uncommon among patients with HS receiving IL-17 inhibitors, and randomized trial data did not demonstrate a significant increase in IBD risk compared with placebo. The higher incidence observed in nonrandomized studies may reflect differences in patient populations, follow-up, or other sources of bias and should not be interpreted as evidence of causation. Because event numbers were low and reporting of IBD outcomes was inconsistent, continued monitoring remains important, particularly in patients with existing or suspected IBD. The findings support the use of IL-17 inhibitors in HS while emphasizing the need for further prospective data on gastrointestinal outcomes.
BACKGROUND: Interleukin-17 (IL-17) inhibitors are increasingly used to treat moderate to severe hidradenitis suppurativa (HS), but concern remains about their potential relationship with inflammatory bowel disease (IBD), particularly Crohn disease and ulcerative colitis. Because patients with HS already have an elevated background risk of IBD, it can be difficult to determine whether IBD events occurring during IL-17 inhibitor therapy are treatment-related or reflect the underlying disease. This systematic review and meta-analysis evaluated the incidence of IBD among patients with HS receiving IL-17 inhibitors and compared event rates with placebo in randomized clinical trials.
DETAILS: The investigators searched PubMed, Embase, and the Cochrane CENTRAL database from inception through November 2025. Twenty-four studies met the inclusion criteria, comprising 10 randomized clinical trials, 11 nonrandomized studies, and 3 case reports. Overall, the analysis included 3,015 patients with HS treated with an IL-17 inhibitor. Outcomes included new-onset IBD, worsening of preexisting IBD, IBD subtype, clinical features, and time to IBD onset.
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Across the 10 randomized clinical trials, new-onset IBD occurred in 6 of 2,572 patients receiving IL-17 inhibitors (0.23%) compared with 0 of 1,066 patients receiving placebo through week 16. The pooled risk difference was 0.002 (95% CI, -0.003 to 0.007), indicating no statistically significant difference between treatment and placebo groups.
In the nonrandomized studies, 7 new-onset IBD events were reported among 469 patients, corresponding to a crude incidence of 1.49%. The pooled incidence was 3.90% (95% CI, 2.30%-6.50%). Across randomized trials, long-term extension studies, and nonrandomized studies, 17 new-onset IBD cases and 4 IBD flares were reported.
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Source: Cutrona, M., Jolkovsky, E. L., Romanelli, S., et al. Inflammatory Bowel Disease and Interleukin-17 Inhibitors in Hidradenitis Suppurativa: A Systematic Review and Meta-Analysis. JAMA Dermatology. 2026; Published: September 9, 2026. DOI: 10.1001/jamadermatol.2026.3373.
Multi-Analyte Blood Test Improves Early Detection of Hepatocellular Carcinoma in Patients With Cirrhosis
In adults with cirrhosis, HelioLiver Dx demonstrated superior sensitivity to ultrasound for HCC detection, including small lesions, while maintaining non-inferior specificity. The blood-based test detected 47.8% of all HCC versus 28.3% with ultrasound and 28.6% versus 0% for lesions less than or equal to 2 cm, meeting both prespecified co-primary endpoints.
KEY FINDINGS: In a prospective multicenter validation study of 1,268 adults with cirrhosis, HelioLiver Dx demonstrated greater sensitivity than ultrasound for HCC detection, including small lesions. Sensitivity was 47.8% versus 28.3% for all HCC and 28.6% versus 0% for lesions ≤2 cm. Although specificity was lower with HelioLiver Dx, the test met prespecified criteria for superior sensitivity and non-inferior specificity.
BACKGROUND: Patients with cirrhosis who are at high risk for hepatocellular carcinoma (HCC) are recommended to undergo biannual abdominal ultrasound surveillance. However, ultrasound has limited sensitivity for small HCC lesions, and adherence to surveillance can be poor. A multianalyte cell-free DNA (cfDNA)-based blood test, HelioLiver Dx, was developed to facilitate HCC detection in this high-risk population.
DETAILS: This cross-sectional, prospective, blinded, multicenter validation study evaluated HelioLiver Dx and abdominal ultrasound in adults with cirrhosis. Participants underwent both tests, while multiphasic magnetic resonance imaging (MRI) served as the reference standard for determining HCC status. The study included 1,268 evaluable participants from 42 clinical sites in the United States.
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HelioLiver Dx combines cfDNA methylation features with patient age and sex and serum concentrations of alpha-fetoprotein (AFP), AFP-L3, and des-gamma-carboxy prothrombin (DCP). The test provides a qualitative positive or negative result, with its algorithm and cutoffs established before testing of the validation cohort.
The co-primary endpoints compared HelioLiver Dx with ultrasound for sensitivity and specificity in detecting HCC. Superiority required the lower bound of the 95% confidence interval for the sensitivity difference to exceed a prespecified 5% margin, while noninferiority for specificity required the lower bound to remain above −10%.
Of the 1,268 evaluable participants, 46 (3.6%) had HCC identified by MRI. Among these, 46% had small HCC lesions ≤2 cm in diameter. HelioLiver Dx detected HCC with a sensitivity of 47.8% (95% CI 32.9-63.1), compared with 28.3% (95% CI 16.0-43.5) for ultrasound.
For HCC lesions ≤2 cm, HelioLiver Dx had a sensitivity of 28.6% (95% CI 11.3-52.2), whereas ultrasound detected 0% (95% CI 0.0-16.1). Specificity was 87.6% (95% CI 85.6-89.4) for HelioLiver Dx and 93.9% (95% CI 92.5-95.2) for ultrasound.
The HelioLiver Dx test met the prespecified co-primary endpoints for superior sensitivity and non-inferior specificity compared with ultrasound. The study also found that the blood test identified more HCC lesions overall and more early lesions than ultrasound.
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Source: Taggart, D. J., Mahajan, S., Gallant, M. A., et al. A Multi-Analyte cfDNA-Based Blood Test for Early Detection of Hepatocellular Carcinoma. Journal of Hepatology. 2026; 85(3): 528-536. Published: September, 2026. DOI: 10.1016/j.jhep.2026.04.012.
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