Cryptogenic HypertransaminasemiaLIFTNCT07834125
Patients With Cryptogenic Hypertransaminasemia
An observational study of Cryptogenic Hypertransaminasemia, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
Trial summary
Persistent unexplained elevation of serum aminotransferases (ALT and AST) remains undiagnosed in a subset of patients despite a comprehensive diagnostic work-up. Increasing evidence suggests that alterations in the gut-liver axis, including intestinal dysbiosis, increased intestinal permeability, and bacterial… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Cryptogenic Hypertransaminasemia
- How many people
- 30 participants
- Where
- 1 siteItaly
- Study dates
- 1 Oct 2026to 1 Oct 2031
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: The study aims to enroll 30 patients with cryptogenic hypertransaminasemia and a control group of 10 participants with normal aminotransferase levels who are undergoing surgical resection of benign liver lesions in the setting of otherwise healthy liver parenchyma.
Who may be able to join
- Age ≥ 18 years.
- Persistent cryptogenic hypertransaminasemia (elevated ALT and/or AST levels) documented for at least 6 months. For the control group only: normal aminotransferase levels.
- No identifiable etiology after a comprehensive clinical, laboratory, and instrumental evaluation.
- Ability to provide written informed consent.
Who cannot join
- Age < 18 years.
- Histologically documented metabolic dysfunction-associated steatotic liver disease (MASLD).
- Alcohol-related liver disease or active alcohol consumption.
- Active viral hepatitis.
- Hereditary hemochromatosis or other known genetic liver diseases.
- Adverse reactions to potentially hepatotoxic drugs.
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- Celiac disease, thyroid disorders, rhabdomyolysis, or known muscle diseases.
- Ongoing acute infections.
- Systemic antibiotic or probiotic therapy within the 3 months preceding enrollment.
- Ongoing immunosuppressive therapy.
- Active malignancy.
- Pregnancy.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site
Fondazione Policlinico Universitaro A. Gemelli IRCSS,UOC Medicina Interna e Gastroenterologia,Largo A. Gemelli,
Roma, 00168
Francesca Romana Ponziani, 3471227242, francescaromana.ponziani@policlinicogemelli.it
Elisabetta Creta, 3480778584, elisabetta.creta@policlinicogemelli.it
About this study
Official title: From the Gut to the Liver: Unraveling the Role of Bacterial Translocation in Cryptogenic Hypertransaminasemia
Persistent unexplained elevation of serum aminotransferases (ALT and AST) remains undiagnosed in a subset of patients despite a comprehensive diagnostic work-up. Increasing evidence suggests that alterations in the gut-liver axis, including intestinal dysbiosis, increased intestinal permeability, and bacterial translocation, may contribute to liver inflammation and hepatocellular injury. Bacterial components such as lipopolysaccharide (LPS) may reach the portal circulation and activate hepatic immune pathways through receptors including CD14 and Toll-like receptor 4 (TLR4).
This study aims to investigate the potential role of bacterial translocation in patients with unexplained persistent hypertransaminasemia undergoing liver biopsy. Standard histological evaluation will be integrated with immunohistochemical and molecular analyses of liver biopsy specimens to assess markers associated with bacterial translocation, including bacterial DNA, LPS, and soluble CD14 (sCD14). The study may help clarify the underlying mechanisms of otherwise unexplained hypertransaminasemia and identify potential biomarkers for future clinical use.
Read the detailed description
The study will involve the collection of clinical, demographic, anthropometric, laboratory, medication, and imaging data from patients with persistent unexplained hypertransaminasemia. Relevant laboratory parameters will include liver function tests, metabolic parameters, complete blood count, glycated hemoglobin, and hepatitis B and C serological markers.
Additional biological samples will be collected during routine clinical procedures, including a 10 mL blood sample, a liver tissue specimen obtained during clinically indicated liver biopsy, and a stool sample. Liver tissue will undergo standard histological evaluation and additional immunohistochemical analyses. Blood and stool samples will be analyzed to investigate markers of bacterial translocation, intestinal microbiota composition, and inflammatory profiles, with the aim of better characterizing the gut-liver axis and its potential role in unexplained hypertransaminasemia.
All clinical data and biological samples will be collected only after obtaining written informed consent from participants, in accordance with the approval of the competent Ethics Committee. Biological samples and study-related data will be stored and processed at Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome.
- Conditions
- Cryptogenic Hypertransaminasemia
- Keywords
- liver disease, liver cancer, Bacterial translocation, biomarker
- Medical subject headings
- Liver Diseases, Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patients with cryptogenic hypertransaminasemia | Patients with cryptogenic hypertransaminasemia will undergo the collection of additional biological samples during routine clinical procedures. These will include an additional 10 mL blood sample, a liver tissue specimen for histological and immunohistochemical analysis, and a stool sample. The collection of these biological specimens will be performed as part of the routine clinical management and diagnostic work-up of patients undergoing evaluation for persistent hypertransaminasemia. | |
| Healthy Controls | Control participants will be individuals with normal serum aminotransferase levels who are undergoing surgical resection of benign liver lesions in the setting of otherwise healthy liver parenchyma. During routine clinical procedures, an additional 10 mL blood sample will be collected, together with a liver tissue specimen obtained during surgery for histological and immunohistochemical analysis. Participants will also be asked to provide a stool sample. The collection of these biological specimens will be performed in conjunction with routine clinical care and the surgical procedure. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hepatic LPS Expression
Immunohistochemical assessment of lipopolysaccharide (LPS) expression in liver tissue obtained from patients with cryptogenic hypertransaminasemia and control participants.
Measured: 30-45 month
Hepatic LBP Expression
Immunohistochemical assessment of lipopolysaccharide-binding protein (LBP) expression in liver tissue obtained from patients with cryptogenic hypertransaminasemia and control participants.
Measured: 30-45 month
Hepatic CD14 Expression
Immunohistochemical assessment of CD14 expression in liver tissue obtained from participants with cryptogenic hypertransaminasemia and control participants.
Measured: 30-45 month
Hepatic MD-2 Expression
Immunohistochemical assessment of myeloid differentiation factor 2 (MD-2) expression in liver tissue obtained from participants with cryptogenic hypertransaminasemia and control participants.
Measured: 30-45 month
Hepatic TLR2 Expression
Immunohistochemical assessment of Toll-like receptor 2 (TLR2) expression in liver tissue obtained from participants with cryptogenic hypertransaminasemia and control participants.
Measured: 30-45 month
Hepatic TLR4 Expression
Immunohistochemical assessment of Toll-like receptor 4 (TLR4) expression in liver tissue obtained from patients with cryptogenic hypertransaminasemia and control participants.
Measured: 30-45 month
Hepatic TLR5 Expression
Immunohistochemical assessment of Toll-like receptor 5 (TLR5) expression in liver tissue obtained from patients with cryptogenic hypertransaminasemia and control participants.
Measured: 30-45 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2026
- Study start1 Oct 2026 (estimated)
- Primary completion1 Oct 2029 (estimated)
- Study completion1 Oct 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cryptogenic HypertransaminasemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Francesca Romana Ponziani, Principal investigator, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07834125
- Sponsor's protocol ID
- 27818
- Acronym
- LIFT
- Status last verified
- Sep 2026
- First submitted
- 16 Sep 2026
- Last updated
- 22 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- From the Gut to the Liver: Unraveling the Role of Bacterial Translocation in Cryptogenic Hypertransaminasemia
- ClinicalTrials.gov ID
- NCT07834125
- Acronym / sponsor ID
- LIFT / 27818
- Conditions
- Cryptogenic Hypertransaminasemia
- Keywords
- liver disease, liver cancer, Bacterial translocation, biomarker
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Study start
- 1 Oct 2026 (estimated)
- Primary completion
- 1 Oct 2029 (estimated)
- Study completion
- 1 Oct 2031 (estimated)
- First posted
- 22 Sep 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Persistent unexplained elevation of serum aminotransferases (ALT and AST) remains undiagnosed in a subset of patients despite a comprehensive diagnostic work-up. Increasing evidence suggests that alterations in the gut-liver axis, including intestinal dysbiosis, increased intestinal permeability, and bacterial translocation, may contribute to liver inflammation and hepatocellular injury. Bacterial components such as lipopolysaccharide (LPS) may reach the portal circulation and activate hepatic immune pathways through receptors including CD14 and Toll-like receptor 4 (TLR4).
This study aims to investigate the potential role of bacterial translocation in patients with unexplained persistent hypertransaminasemia undergoing liver biopsy. Standard histological evaluation will be integrated with immunohistochemical and molecular analyses of liver biopsy specimens to assess markers associated with bacterial translocation, including bacterial DNA, LPS, and soluble CD14 (sCD14). The study may help clarify the underlying mechanisms of otherwise unexplained hypertransaminasemia and identify potential biomarkers for future clinical use.
Detailed description
The study will involve the collection of clinical, demographic, anthropometric, laboratory, medication, and imaging data from patients with persistent unexplained hypertransaminasemia. Relevant laboratory parameters will include liver function tests, metabolic parameters, complete blood count, glycated hemoglobin, and hepatitis B and C serological markers.
Additional biological samples will be collected during routine clinical procedures, including a 10 mL blood sample, a liver tissue specimen obtained during clinically indicated liver biopsy, and a stool sample. Liver tissue will undergo standard histological evaluation and additional immunohistochemical analyses. Blood and stool samples will be analyzed to investigate markers of bacterial translocation, intestinal microbiota composition, and inflammatory profiles, with the aim of better characterizing the gut-liver axis and its potential role in unexplained hypertransaminasemia.
All clinical data and biological samples will be collected only after obtaining written informed consent from participants, in accordance with the approval of the competent Ethics Committee. Biological samples and study-related data will be stored and processed at Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with cryptogenic hypertransaminasemia | – | –Patients with cryptogenic hypertransaminasemia will undergo the collection of additional biological samples during routine clinical procedures. These will include an additional 10 mL blood sample, a liver tissue specimen for histological and immunohistochemical analysis, and a stool sample. The collection of these biological specimens will be performed as part of the routine clinical management and diagnostic work-up of patients undergoing evaluation for persistent hypertransaminasemia. |
| Healthy Controls | – | –Control participants will be individuals with normal serum aminotransferase levels who are undergoing surgical resection of benign liver lesions in the setting of otherwise healthy liver parenchyma. During routine clinical procedures, an additional 10 mL blood sample will be collected, together with a liver tissue specimen obtained during surgery for histological and immunohistochemical analysis. Participants will also be asked to provide a stool sample. The collection of these biological specimens will be performed in conjunction with routine clinical care and the surgical procedure. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The study aims to enroll 30 patients with cryptogenic hypertransaminasemia and a control group of 10 participants with normal aminotransferase levels who are undergoing surgical resection of benign liver lesions in the setting of otherwise healthy liver parenchyma.
Key inclusion criteria (4 listed)
- Age ≥ 18 years.
- Persistent cryptogenic hypertransaminasemia (elevated ALT and/or AST levels) documented for at least 6 months. For the control group only: normal aminotransferase levels.
- No identifiable etiology after a comprehensive clinical, laboratory, and instrumental evaluation.
- Ability to provide written informed consent.
Key exclusion criteria (12 listed)
- Age < 18 years.
- Histologically documented metabolic dysfunction-associated steatotic liver disease (MASLD).
- Alcohol-related liver disease or active alcohol consumption.
- Active viral hepatitis.
- Hereditary hemochromatosis or other known genetic liver diseases.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Hepatic LPS Expression
Time frame: 30-45 month
Immunohistochemical assessment of lipopolysaccharide (LPS) expression in liver tissue obtained from patients with cryptogenic hypertransaminasemia and control participants.
Hepatic LBP Expression
Time frame: 30-45 month
Immunohistochemical assessment of lipopolysaccharide-binding protein (LBP) expression in liver tissue obtained from patients with cryptogenic hypertransaminasemia and control participants.
Hepatic CD14 Expression
Time frame: 30-45 month
Immunohistochemical assessment of CD14 expression in liver tissue obtained from participants with cryptogenic hypertransaminasemia and control participants.
Hepatic MD-2 Expression
Time frame: 30-45 month
Immunohistochemical assessment of myeloid differentiation factor 2 (MD-2) expression in liver tissue obtained from participants with cryptogenic hypertransaminasemia and control participants.
Hepatic TLR2 Expression
Time frame: 30-45 month
Immunohistochemical assessment of Toll-like receptor 2 (TLR2) expression in liver tissue obtained from participants with cryptogenic hypertransaminasemia and control participants.
Hepatic TLR4 Expression
Time frame: 30-45 month
Immunohistochemical assessment of Toll-like receptor 4 (TLR4) expression in liver tissue obtained from patients with cryptogenic hypertransaminasemia and control participants.
Hepatic TLR5 Expression
Time frame: 30-45 month
Immunohistochemical assessment of Toll-like receptor 5 (TLR5) expression in liver tissue obtained from patients with cryptogenic hypertransaminasemia and control participants.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2026.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Francesca Romana Ponziani principal investigator
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cryptogenic Hypertransaminasemia, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 22 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Francesca Romana Ponziani (3471227242, francescaromana.ponziani@policlinicogemelli.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hepatic LPS Expression (time frame: 30-45 month). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2026; AzTrials last refreshed its copy on 26 Oct 2026.