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Prevention and Risk-Based Surveillance Key to Curbing HCC
BERLIN — according to a joint statement from United European Gastroenterology (UEG) and the German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS).
The statement calls on EU and national policymakers to embed a twofold approach into healthcare systems that combines surveillance and prevention, rather than relying on voluntary participation. It also encourages stronger prevention measures, such as improved food labeling and restrictions on marketing unhealthy foods to children. The statement — which was also endorsed by the European Association for the Study of the Liver (EASL) — was presented at UEG Week 2025 .
“Curing HCC in early stages rather than treating the disease in a palliative setting should be the goal for all liver doctors and carers, and this is certainly the goal for patients,” said Thomas Seufferlein, MD, professor of gastroenterology at Ulm University, Germany, and one of the members of the DGVS who initiated the statement.
“We have to take HCC screening seriously which means setting up a structured, nationwide, well-documented, and evaluated program for HCC screening in Germany,” he said in an interview.
HCC is mainly curable in the early stages by local ablation, resection, or liver transplantation, “so early diagnosis is of the utmost importance for improving survival,” added Patrick Michl, MD, gastroenterologist, University of Heidelberg, Germany, DGVS member and co-initiator of the statement.
Risk-Stratified HCC Surveillance
In the face of rising rates worldwide, the UEG/DGVS call on policymakers to recognize liver cancer as a preventable and growing public health priority and to implement structured surveillance programs guided by risk thresholds. In particular, they support the recent policy statement from EASL recommending risk-based screening.
EASL’s key recommendations include:
- Targeted surveillance for individuals with an annual HCC risk exceeding 1.5%, where it is both clinically beneficial and cost-effective
- Risk scoring tools such as the age-male-albumin-bilirubin-platelets score that incorporates age, sex, platelet count, albumin, and bilirubin, to stratify patients by HCC risk, including those without established cirrhosis
- Enhanced surveillance for very high-risk groups, where MRI-based surveillance may be warranted despite higher costs, given its superior sensitivity for early-stage disease
- A de-escalation in low-risk individuals
- Patients with an annual HCC risk < 0.5% may be safely spared surveillance, avoiding unnecessary interventions
Evidence from France, Italy, and the UK showed that structured surveillance in high-risk groups is both clinically beneficial and cost-effective. National models in France have demonstrated higher curative treatment rates and fewer costly late-stage cases with structured surveillance. In the UK, health technology assessments indicate targeted surveillance is an efficient use of National Health Services resources, particularly when uptake is optimized. Italian models show that earlier diagnosis in well-defined high-risk groups can offset downstream treatment costs.
Seufferlein noted that Germany needs a “structured program to be implemented and there is currently little public awareness regarding this surveillance strategy.” However, he added there is a structured hepatitis B vaccination program in Germany, which has been successful. “Studies show that the inclusion of hep B vaccination in infancy and childhood has led to good uptake among young age groups.”
Germany, however, has yet to conduct national studies. “Prospective data on HCC surveillance benefits in Germany are lacking,” said Michl, “but multi-country models incorporating Germany’s cost structures suggest similar benefits would accrue if there were greater adherence to guideline-based recommendations and if publicly funded screening programs were implemented.”
Current recommendations in Germany for surveillance are based on evidence-based guidelines of the DGVS with stronger (‘should’) or weaker (‘may’) evidence-based recommendations. For example, patients with chronic hepatitis B virus infection should be offered regular surveillance once their platelet age gender–hepatitis B risk score is ≥ 10. In patients with advanced fibrosis because of chronic hepatitis C virus infection, regular surveillance should also be offered.
Barriers to Screening Uptake
HCC remains one of the most lethal cancers in Europe, largely because it is often diagnosed too late. Underdiagnosis of chronic liver disease, limited access to imaging, and reimbursement gaps prevent timely intervention.
Maria Buti, MD, consultant hepatologist, Hospital Vall d’Hebron, Barcelona, Spain, who was not involved in drafting the statement, remarked that “Patients with liver cirrhosis, or with advanced fibrosis, and also some high-risk noncirrhotic patients such as those with hepatitis B, clearly benefit from surveillance. Surveillance can change life expectancy and also reduce morbidity.”
However, structural barriers continue to impede uptake. “It is not always easy to identify patients with liver cirrhosis because the majority are completely asymptomatic in the early stages,” she said.
Even when risk factors are identified, adherence to 6-monthly surveillance remains patchy. “Sometimes physicians forget to request ultrasounds, or patients don’t understand the importance of it because they feel well,” Buti told GI & Hepatology News.
Expanded Training and Public Health Measures
The joint statement also advocates for expanded physician training in nutrition and hepatology, equitable access to diagnostic tools including MRI, and EU-wide nutrition labeling systems such as Nutri-Score.
The authors also called for strengthened public health measures to tackle obesity, alcohol misuse, and hepatitis transmission, and fiscal and regulatory measures such as taxation of obesogenic foods, and reducing the cost burden of healthier foods.
“If we decrease the percentage of people with liver cirrhosis through prevention, fewer people will need surveillance,” Buti stated.
Seufferlein, Michl, and Buti all declared no relevant disclosures. All three experts are members of the UEG Public Affairs Group.
A version of this article appeared on Medscape.com.
BERLIN — according to a joint statement from United European Gastroenterology (UEG) and the German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS).
The statement calls on EU and national policymakers to embed a twofold approach into healthcare systems that combines surveillance and prevention, rather than relying on voluntary participation. It also encourages stronger prevention measures, such as improved food labeling and restrictions on marketing unhealthy foods to children. The statement — which was also endorsed by the European Association for the Study of the Liver (EASL) — was presented at UEG Week 2025 .
“Curing HCC in early stages rather than treating the disease in a palliative setting should be the goal for all liver doctors and carers, and this is certainly the goal for patients,” said Thomas Seufferlein, MD, professor of gastroenterology at Ulm University, Germany, and one of the members of the DGVS who initiated the statement.
“We have to take HCC screening seriously which means setting up a structured, nationwide, well-documented, and evaluated program for HCC screening in Germany,” he said in an interview.
HCC is mainly curable in the early stages by local ablation, resection, or liver transplantation, “so early diagnosis is of the utmost importance for improving survival,” added Patrick Michl, MD, gastroenterologist, University of Heidelberg, Germany, DGVS member and co-initiator of the statement.
Risk-Stratified HCC Surveillance
In the face of rising rates worldwide, the UEG/DGVS call on policymakers to recognize liver cancer as a preventable and growing public health priority and to implement structured surveillance programs guided by risk thresholds. In particular, they support the recent policy statement from EASL recommending risk-based screening.
EASL’s key recommendations include:
- Targeted surveillance for individuals with an annual HCC risk exceeding 1.5%, where it is both clinically beneficial and cost-effective
- Risk scoring tools such as the age-male-albumin-bilirubin-platelets score that incorporates age, sex, platelet count, albumin, and bilirubin, to stratify patients by HCC risk, including those without established cirrhosis
- Enhanced surveillance for very high-risk groups, where MRI-based surveillance may be warranted despite higher costs, given its superior sensitivity for early-stage disease
- A de-escalation in low-risk individuals
- Patients with an annual HCC risk < 0.5% may be safely spared surveillance, avoiding unnecessary interventions
Evidence from France, Italy, and the UK showed that structured surveillance in high-risk groups is both clinically beneficial and cost-effective. National models in France have demonstrated higher curative treatment rates and fewer costly late-stage cases with structured surveillance. In the UK, health technology assessments indicate targeted surveillance is an efficient use of National Health Services resources, particularly when uptake is optimized. Italian models show that earlier diagnosis in well-defined high-risk groups can offset downstream treatment costs.
Seufferlein noted that Germany needs a “structured program to be implemented and there is currently little public awareness regarding this surveillance strategy.” However, he added there is a structured hepatitis B vaccination program in Germany, which has been successful. “Studies show that the inclusion of hep B vaccination in infancy and childhood has led to good uptake among young age groups.”
Germany, however, has yet to conduct national studies. “Prospective data on HCC surveillance benefits in Germany are lacking,” said Michl, “but multi-country models incorporating Germany’s cost structures suggest similar benefits would accrue if there were greater adherence to guideline-based recommendations and if publicly funded screening programs were implemented.”
Current recommendations in Germany for surveillance are based on evidence-based guidelines of the DGVS with stronger (‘should’) or weaker (‘may’) evidence-based recommendations. For example, patients with chronic hepatitis B virus infection should be offered regular surveillance once their platelet age gender–hepatitis B risk score is ≥ 10. In patients with advanced fibrosis because of chronic hepatitis C virus infection, regular surveillance should also be offered.
Barriers to Screening Uptake
HCC remains one of the most lethal cancers in Europe, largely because it is often diagnosed too late. Underdiagnosis of chronic liver disease, limited access to imaging, and reimbursement gaps prevent timely intervention.
Maria Buti, MD, consultant hepatologist, Hospital Vall d’Hebron, Barcelona, Spain, who was not involved in drafting the statement, remarked that “Patients with liver cirrhosis, or with advanced fibrosis, and also some high-risk noncirrhotic patients such as those with hepatitis B, clearly benefit from surveillance. Surveillance can change life expectancy and also reduce morbidity.”
However, structural barriers continue to impede uptake. “It is not always easy to identify patients with liver cirrhosis because the majority are completely asymptomatic in the early stages,” she said.
Even when risk factors are identified, adherence to 6-monthly surveillance remains patchy. “Sometimes physicians forget to request ultrasounds, or patients don’t understand the importance of it because they feel well,” Buti told GI & Hepatology News.
Expanded Training and Public Health Measures
The joint statement also advocates for expanded physician training in nutrition and hepatology, equitable access to diagnostic tools including MRI, and EU-wide nutrition labeling systems such as Nutri-Score.
The authors also called for strengthened public health measures to tackle obesity, alcohol misuse, and hepatitis transmission, and fiscal and regulatory measures such as taxation of obesogenic foods, and reducing the cost burden of healthier foods.
“If we decrease the percentage of people with liver cirrhosis through prevention, fewer people will need surveillance,” Buti stated.
Seufferlein, Michl, and Buti all declared no relevant disclosures. All three experts are members of the UEG Public Affairs Group.
A version of this article appeared on Medscape.com.
BERLIN — according to a joint statement from United European Gastroenterology (UEG) and the German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS).
The statement calls on EU and national policymakers to embed a twofold approach into healthcare systems that combines surveillance and prevention, rather than relying on voluntary participation. It also encourages stronger prevention measures, such as improved food labeling and restrictions on marketing unhealthy foods to children. The statement — which was also endorsed by the European Association for the Study of the Liver (EASL) — was presented at UEG Week 2025 .
“Curing HCC in early stages rather than treating the disease in a palliative setting should be the goal for all liver doctors and carers, and this is certainly the goal for patients,” said Thomas Seufferlein, MD, professor of gastroenterology at Ulm University, Germany, and one of the members of the DGVS who initiated the statement.
“We have to take HCC screening seriously which means setting up a structured, nationwide, well-documented, and evaluated program for HCC screening in Germany,” he said in an interview.
HCC is mainly curable in the early stages by local ablation, resection, or liver transplantation, “so early diagnosis is of the utmost importance for improving survival,” added Patrick Michl, MD, gastroenterologist, University of Heidelberg, Germany, DGVS member and co-initiator of the statement.
Risk-Stratified HCC Surveillance
In the face of rising rates worldwide, the UEG/DGVS call on policymakers to recognize liver cancer as a preventable and growing public health priority and to implement structured surveillance programs guided by risk thresholds. In particular, they support the recent policy statement from EASL recommending risk-based screening.
EASL’s key recommendations include:
- Targeted surveillance for individuals with an annual HCC risk exceeding 1.5%, where it is both clinically beneficial and cost-effective
- Risk scoring tools such as the age-male-albumin-bilirubin-platelets score that incorporates age, sex, platelet count, albumin, and bilirubin, to stratify patients by HCC risk, including those without established cirrhosis
- Enhanced surveillance for very high-risk groups, where MRI-based surveillance may be warranted despite higher costs, given its superior sensitivity for early-stage disease
- A de-escalation in low-risk individuals
- Patients with an annual HCC risk < 0.5% may be safely spared surveillance, avoiding unnecessary interventions
Evidence from France, Italy, and the UK showed that structured surveillance in high-risk groups is both clinically beneficial and cost-effective. National models in France have demonstrated higher curative treatment rates and fewer costly late-stage cases with structured surveillance. In the UK, health technology assessments indicate targeted surveillance is an efficient use of National Health Services resources, particularly when uptake is optimized. Italian models show that earlier diagnosis in well-defined high-risk groups can offset downstream treatment costs.
Seufferlein noted that Germany needs a “structured program to be implemented and there is currently little public awareness regarding this surveillance strategy.” However, he added there is a structured hepatitis B vaccination program in Germany, which has been successful. “Studies show that the inclusion of hep B vaccination in infancy and childhood has led to good uptake among young age groups.”
Germany, however, has yet to conduct national studies. “Prospective data on HCC surveillance benefits in Germany are lacking,” said Michl, “but multi-country models incorporating Germany’s cost structures suggest similar benefits would accrue if there were greater adherence to guideline-based recommendations and if publicly funded screening programs were implemented.”
Current recommendations in Germany for surveillance are based on evidence-based guidelines of the DGVS with stronger (‘should’) or weaker (‘may’) evidence-based recommendations. For example, patients with chronic hepatitis B virus infection should be offered regular surveillance once their platelet age gender–hepatitis B risk score is ≥ 10. In patients with advanced fibrosis because of chronic hepatitis C virus infection, regular surveillance should also be offered.
Barriers to Screening Uptake
HCC remains one of the most lethal cancers in Europe, largely because it is often diagnosed too late. Underdiagnosis of chronic liver disease, limited access to imaging, and reimbursement gaps prevent timely intervention.
Maria Buti, MD, consultant hepatologist, Hospital Vall d’Hebron, Barcelona, Spain, who was not involved in drafting the statement, remarked that “Patients with liver cirrhosis, or with advanced fibrosis, and also some high-risk noncirrhotic patients such as those with hepatitis B, clearly benefit from surveillance. Surveillance can change life expectancy and also reduce morbidity.”
However, structural barriers continue to impede uptake. “It is not always easy to identify patients with liver cirrhosis because the majority are completely asymptomatic in the early stages,” she said.
Even when risk factors are identified, adherence to 6-monthly surveillance remains patchy. “Sometimes physicians forget to request ultrasounds, or patients don’t understand the importance of it because they feel well,” Buti told GI & Hepatology News.
Expanded Training and Public Health Measures
The joint statement also advocates for expanded physician training in nutrition and hepatology, equitable access to diagnostic tools including MRI, and EU-wide nutrition labeling systems such as Nutri-Score.
The authors also called for strengthened public health measures to tackle obesity, alcohol misuse, and hepatitis transmission, and fiscal and regulatory measures such as taxation of obesogenic foods, and reducing the cost burden of healthier foods.
“If we decrease the percentage of people with liver cirrhosis through prevention, fewer people will need surveillance,” Buti stated.
Seufferlein, Michl, and Buti all declared no relevant disclosures. All three experts are members of the UEG Public Affairs Group.
A version of this article appeared on Medscape.com.
FROM UEG WEEK 2025
Linerixibat Reduces Itching in PBC
BERLIN — , according to phase 3 results from the GLISTEN trial.
The therapy also improved sleep interference associated with itching and was generally well-tolerated, offering hope for patients who do not respond to existing treatments.
“Linerixibat has the potential to be the first global therapy indicated for pruritus,” asserted Andreas E. Kremer, MD, Department of Gastroenterology and Hepatology, University Hospital Zürich, Switzerland, who presented the findings at United European Gastroenterology (UEG) Week 2025.
Cholestatic pruritus is one of the most distressing and disabling symptoms of PBC, often unrelieved by existing first-line therapies such as ursodeoxycholic acid.
Up to 70% of patients with PBC experience cholestatic pruritus which can seriously impair quality of life, comparable to that seen in severe Parkinson’s disease or heart failure, said Kremer. With the limitations of existing treatments, symptom control remains a major unmet clinical need.
The GLISTEN Trial
Linerixibat is a minimally absorbed oral IBAT inhibitor that inhibits bile acid reuptake and reduces key mediators of pruritus.
Participants in the double-blind, placebo-controlled trial were randomized to oral linerixibat 40 mg twice daily (n = 119) or to placebo (n = 119) for 24 weeks. Patients had PBC and moderate-to-severe pruritus (Worst Itch Numerical Rating Scale [WI-NRS] ≥ 4).
The primary endpoint was change from baseline in monthly worst-itch score over 24 weeks. Key secondary endpoints included change in itch at week 2, change in sleep interference over 24 weeks, responder rates (≥ 2-, ≥ 3-, and ≥ 4-point reduction), and patient-reported global impression of severity and change.
The majority of participants (95%) were women and had a mean WI-NRS of 7.3 at baseline. After 24 weeks of twice daily dosing of linerixibat or placebo, participants entered a blinded crossover period for 8 weeks.
24-Week Data
Linerixibat produced a significant improvement in pruritus vs placebo, with a least-squares mean change in WI-NRS of -2.86 compared with -2.15, respectively, resulting in an adjusted mean difference of -0.72 (P = .001). The benefit appeared rapid, with superiority already evident at 2 weeks (P < .001), noted Kremer, adding this is important for patients.
Pruritus-related sleep interference NRS also improved significantly (-2.77 vs -2.24; difference, -0.53; P = .024). By week 24, 56% of patients with linerixibat achieved a ≥ 3-point reduction compared with 43% of those treated with placebo (nominal P = .043).
“A three-point reduction for a patient with pruritus is a clearly meaningful benefit,” said Kremer.
In addition, a greater proportion of patients with linerixibat rated their itch as “absent” (21% vs 9%) on the patient global impression of severity scales. The ideal goal for these patients is complete relief, “and here we saw that every fifth patient on linerixibat achieved such relief,” he pointed out.
Linerixibat was generally well-tolerated, and the most frequent on-treatment adverse event was diarrhea, which occurred in 61% of patients compared with 18% of those on placebo. There were five (4%) discontinuations on linerixibat vs one (< 1%) on placebo. Abdominal pain was experienced by 18% on linerixibat and 3% on placebo. There was also a slight elevation of alanine aminotransferase in 11 (9%) vs three patients (3%).
“In summary, it is a safe drug from our perspective,” said Kremer.
Focusing on Symptoms, Not Biochemical Response
Commenting for GI & Hepatology News, Frank Tacke, MD, head of the Department of Hepatology and Gastroenterology at Charité Medical University Berlin, Germany, explained that so far drugs for the treatment of PBC focused on the biochemical response. These treatments have shown a reduction in liver enzymes and in disease activity, but less of a reduction in symptoms, he explained. “This is the first drug at phase 3 that focuses on itching, which is one of the major symptoms in people with PBC. As such, this is a major breakthrough.”
Sabine Weber, MD, gastroenterologist at the University Hospital of Munich, Germany, said that the data suggested particular potential for patients whose pruritus doesn’t respond to first-line treatment, even if the treatment is otherwise effective.
“This is so important for patients who — due to their extreme itching — experience serious lifestyle effects such as isolation because they can’t go out socially,” she said. “We desperately need drugs to help these patients, and here we have one drug that seems to do this.”
Weber noted that linerixibat works differently from other PBC treatments. It is licensed in pediatric medicine for a number of diseases, but “this is the first time we’ve seen it for use in adults,” she added.
Kremer disclosed receiving research support from Gilead, Intercept Pharmaceuticals, and Roche; consulting for AbbVie, Advanz, Alentis, Alphasigma, AstraZeneca, Avior, Bayer, CymaBay Therapeutics, Eisai, Escient, Falk, Gilead, GSK, Intercept Pharmaceuticals, Ipsen, Mirum, MSD, Roche, Takeda, and Vifor; and receiving payment or honoraria from AbbVie, Advanz, Alphasigma, Falk, Gilead, GSK, Intercept Pharmaceuticals, Ipsen, Mirum, MSD, Roche, Takeda, and Vifor. Tache declared that he previously gave lectures for GSK. Weber declared no relevant conflicts of interest.
The GLISTEN study was funded by GSK.
A version of this article appeared on Medscape.com.
BERLIN — , according to phase 3 results from the GLISTEN trial.
The therapy also improved sleep interference associated with itching and was generally well-tolerated, offering hope for patients who do not respond to existing treatments.
“Linerixibat has the potential to be the first global therapy indicated for pruritus,” asserted Andreas E. Kremer, MD, Department of Gastroenterology and Hepatology, University Hospital Zürich, Switzerland, who presented the findings at United European Gastroenterology (UEG) Week 2025.
Cholestatic pruritus is one of the most distressing and disabling symptoms of PBC, often unrelieved by existing first-line therapies such as ursodeoxycholic acid.
Up to 70% of patients with PBC experience cholestatic pruritus which can seriously impair quality of life, comparable to that seen in severe Parkinson’s disease or heart failure, said Kremer. With the limitations of existing treatments, symptom control remains a major unmet clinical need.
The GLISTEN Trial
Linerixibat is a minimally absorbed oral IBAT inhibitor that inhibits bile acid reuptake and reduces key mediators of pruritus.
Participants in the double-blind, placebo-controlled trial were randomized to oral linerixibat 40 mg twice daily (n = 119) or to placebo (n = 119) for 24 weeks. Patients had PBC and moderate-to-severe pruritus (Worst Itch Numerical Rating Scale [WI-NRS] ≥ 4).
The primary endpoint was change from baseline in monthly worst-itch score over 24 weeks. Key secondary endpoints included change in itch at week 2, change in sleep interference over 24 weeks, responder rates (≥ 2-, ≥ 3-, and ≥ 4-point reduction), and patient-reported global impression of severity and change.
The majority of participants (95%) were women and had a mean WI-NRS of 7.3 at baseline. After 24 weeks of twice daily dosing of linerixibat or placebo, participants entered a blinded crossover period for 8 weeks.
24-Week Data
Linerixibat produced a significant improvement in pruritus vs placebo, with a least-squares mean change in WI-NRS of -2.86 compared with -2.15, respectively, resulting in an adjusted mean difference of -0.72 (P = .001). The benefit appeared rapid, with superiority already evident at 2 weeks (P < .001), noted Kremer, adding this is important for patients.
Pruritus-related sleep interference NRS also improved significantly (-2.77 vs -2.24; difference, -0.53; P = .024). By week 24, 56% of patients with linerixibat achieved a ≥ 3-point reduction compared with 43% of those treated with placebo (nominal P = .043).
“A three-point reduction for a patient with pruritus is a clearly meaningful benefit,” said Kremer.
In addition, a greater proportion of patients with linerixibat rated their itch as “absent” (21% vs 9%) on the patient global impression of severity scales. The ideal goal for these patients is complete relief, “and here we saw that every fifth patient on linerixibat achieved such relief,” he pointed out.
Linerixibat was generally well-tolerated, and the most frequent on-treatment adverse event was diarrhea, which occurred in 61% of patients compared with 18% of those on placebo. There were five (4%) discontinuations on linerixibat vs one (< 1%) on placebo. Abdominal pain was experienced by 18% on linerixibat and 3% on placebo. There was also a slight elevation of alanine aminotransferase in 11 (9%) vs three patients (3%).
“In summary, it is a safe drug from our perspective,” said Kremer.
Focusing on Symptoms, Not Biochemical Response
Commenting for GI & Hepatology News, Frank Tacke, MD, head of the Department of Hepatology and Gastroenterology at Charité Medical University Berlin, Germany, explained that so far drugs for the treatment of PBC focused on the biochemical response. These treatments have shown a reduction in liver enzymes and in disease activity, but less of a reduction in symptoms, he explained. “This is the first drug at phase 3 that focuses on itching, which is one of the major symptoms in people with PBC. As such, this is a major breakthrough.”
Sabine Weber, MD, gastroenterologist at the University Hospital of Munich, Germany, said that the data suggested particular potential for patients whose pruritus doesn’t respond to first-line treatment, even if the treatment is otherwise effective.
“This is so important for patients who — due to their extreme itching — experience serious lifestyle effects such as isolation because they can’t go out socially,” she said. “We desperately need drugs to help these patients, and here we have one drug that seems to do this.”
Weber noted that linerixibat works differently from other PBC treatments. It is licensed in pediatric medicine for a number of diseases, but “this is the first time we’ve seen it for use in adults,” she added.
Kremer disclosed receiving research support from Gilead, Intercept Pharmaceuticals, and Roche; consulting for AbbVie, Advanz, Alentis, Alphasigma, AstraZeneca, Avior, Bayer, CymaBay Therapeutics, Eisai, Escient, Falk, Gilead, GSK, Intercept Pharmaceuticals, Ipsen, Mirum, MSD, Roche, Takeda, and Vifor; and receiving payment or honoraria from AbbVie, Advanz, Alphasigma, Falk, Gilead, GSK, Intercept Pharmaceuticals, Ipsen, Mirum, MSD, Roche, Takeda, and Vifor. Tache declared that he previously gave lectures for GSK. Weber declared no relevant conflicts of interest.
The GLISTEN study was funded by GSK.
A version of this article appeared on Medscape.com.
BERLIN — , according to phase 3 results from the GLISTEN trial.
The therapy also improved sleep interference associated with itching and was generally well-tolerated, offering hope for patients who do not respond to existing treatments.
“Linerixibat has the potential to be the first global therapy indicated for pruritus,” asserted Andreas E. Kremer, MD, Department of Gastroenterology and Hepatology, University Hospital Zürich, Switzerland, who presented the findings at United European Gastroenterology (UEG) Week 2025.
Cholestatic pruritus is one of the most distressing and disabling symptoms of PBC, often unrelieved by existing first-line therapies such as ursodeoxycholic acid.
Up to 70% of patients with PBC experience cholestatic pruritus which can seriously impair quality of life, comparable to that seen in severe Parkinson’s disease or heart failure, said Kremer. With the limitations of existing treatments, symptom control remains a major unmet clinical need.
The GLISTEN Trial
Linerixibat is a minimally absorbed oral IBAT inhibitor that inhibits bile acid reuptake and reduces key mediators of pruritus.
Participants in the double-blind, placebo-controlled trial were randomized to oral linerixibat 40 mg twice daily (n = 119) or to placebo (n = 119) for 24 weeks. Patients had PBC and moderate-to-severe pruritus (Worst Itch Numerical Rating Scale [WI-NRS] ≥ 4).
The primary endpoint was change from baseline in monthly worst-itch score over 24 weeks. Key secondary endpoints included change in itch at week 2, change in sleep interference over 24 weeks, responder rates (≥ 2-, ≥ 3-, and ≥ 4-point reduction), and patient-reported global impression of severity and change.
The majority of participants (95%) were women and had a mean WI-NRS of 7.3 at baseline. After 24 weeks of twice daily dosing of linerixibat or placebo, participants entered a blinded crossover period for 8 weeks.
24-Week Data
Linerixibat produced a significant improvement in pruritus vs placebo, with a least-squares mean change in WI-NRS of -2.86 compared with -2.15, respectively, resulting in an adjusted mean difference of -0.72 (P = .001). The benefit appeared rapid, with superiority already evident at 2 weeks (P < .001), noted Kremer, adding this is important for patients.
Pruritus-related sleep interference NRS also improved significantly (-2.77 vs -2.24; difference, -0.53; P = .024). By week 24, 56% of patients with linerixibat achieved a ≥ 3-point reduction compared with 43% of those treated with placebo (nominal P = .043).
“A three-point reduction for a patient with pruritus is a clearly meaningful benefit,” said Kremer.
In addition, a greater proportion of patients with linerixibat rated their itch as “absent” (21% vs 9%) on the patient global impression of severity scales. The ideal goal for these patients is complete relief, “and here we saw that every fifth patient on linerixibat achieved such relief,” he pointed out.
Linerixibat was generally well-tolerated, and the most frequent on-treatment adverse event was diarrhea, which occurred in 61% of patients compared with 18% of those on placebo. There were five (4%) discontinuations on linerixibat vs one (< 1%) on placebo. Abdominal pain was experienced by 18% on linerixibat and 3% on placebo. There was also a slight elevation of alanine aminotransferase in 11 (9%) vs three patients (3%).
“In summary, it is a safe drug from our perspective,” said Kremer.
Focusing on Symptoms, Not Biochemical Response
Commenting for GI & Hepatology News, Frank Tacke, MD, head of the Department of Hepatology and Gastroenterology at Charité Medical University Berlin, Germany, explained that so far drugs for the treatment of PBC focused on the biochemical response. These treatments have shown a reduction in liver enzymes and in disease activity, but less of a reduction in symptoms, he explained. “This is the first drug at phase 3 that focuses on itching, which is one of the major symptoms in people with PBC. As such, this is a major breakthrough.”
Sabine Weber, MD, gastroenterologist at the University Hospital of Munich, Germany, said that the data suggested particular potential for patients whose pruritus doesn’t respond to first-line treatment, even if the treatment is otherwise effective.
“This is so important for patients who — due to their extreme itching — experience serious lifestyle effects such as isolation because they can’t go out socially,” she said. “We desperately need drugs to help these patients, and here we have one drug that seems to do this.”
Weber noted that linerixibat works differently from other PBC treatments. It is licensed in pediatric medicine for a number of diseases, but “this is the first time we’ve seen it for use in adults,” she added.
Kremer disclosed receiving research support from Gilead, Intercept Pharmaceuticals, and Roche; consulting for AbbVie, Advanz, Alentis, Alphasigma, AstraZeneca, Avior, Bayer, CymaBay Therapeutics, Eisai, Escient, Falk, Gilead, GSK, Intercept Pharmaceuticals, Ipsen, Mirum, MSD, Roche, Takeda, and Vifor; and receiving payment or honoraria from AbbVie, Advanz, Alphasigma, Falk, Gilead, GSK, Intercept Pharmaceuticals, Ipsen, Mirum, MSD, Roche, Takeda, and Vifor. Tache declared that he previously gave lectures for GSK. Weber declared no relevant conflicts of interest.
The GLISTEN study was funded by GSK.
A version of this article appeared on Medscape.com.