Primary Biliary Cholangitis (PBC)RELIEFNCT07161245
RELIEF: Multimodal Prehabilitation to Treat Fatigue in Patients With Primary Biliary Cholangitis
A study testing Multimodal prehabilitation in people with Primary Biliary Cholangitis (PBC), run by Hospital Clinic of Barcelona at 1 site in Spain.
Trial summary
The implementation of a non-pharmacological multimodal intervention program-including physical exercise, nutritional counseling, and psychological support-is expected to improve fatigue in patients with primary biliary cholangitis. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Primary Biliary Cholangitis (PBC)
- What is being tested?
- Multimodal prehabilitation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 1 siteSpain
- Study dates
- 6 Feb 2025to 31 Dec 2026
- Phase
- Interventional
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 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age ≥18 years
- PBC diagnosis according to EASL guidelines
- Moderate - severe fatigue defined by ≥ 29 points in PBC-40 questionnaire
Who cannot join
- Age > 80 years
- Severe pruritus
- Decompensated cirrhosis
- Other causes of liver disease than PBC
- Liver transplant (LT) o placement on a waiting-list for LT
- Uncontrolled thyroid disesase
Show all 21Show fewer
- Anemia with haemoglobin <11g/dl
- Uncontrolled cardiovascular risk factors
- BMI > 35,
- Acute myocardial infarct or unstable angina the past 6 months
- Muscle disease or systemic disease with potential muscle involvement
- Dysautonomy
- Untreated osteoporosis
- Untreated celiac disease
- Alcohol consumption > 14 standard drinks (SD) in women and >21 (SD) in men per week
- Chronic kidney disease ≥ 4 KDIGO stage
- Malignancy in the past two years (except for non melanoma skin cancer and in situ cervical carcinoma)
- Not capable of performing or following the prehabilitation program
- Involvement in a clinical trial the previous 2 months
- Refusal of informed consent
- For the study of the pathophysiology of fatigue, additional exclusion criteria will be established: Severe depression or neuropsychiatric disease, 2) Treatment with centrally acting drugs, 3) Muscular or systemic disease with potential muscle involvement, 4) Immunosuppressive treatment, 5) Sleep disorder, 6) Obesity (BMI >30).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Sergio Rodríguez Tajes, MD, PhD contact
Spain1 site, 1 recruiting
- Recruiting
Hospital Clinic de Barcelona
Barcelona, Barcelona, 08036
About this study
Official title: A Randomized Clinical Trial on the Improvement of Fatigue in Patients With Primary Biliary Cholangitis by Implementation of a Multimodal Rehabilitation Program and Study of Its Pathophysiological Mechanisms
The implementation of a non-pharmacological multimodal intervention program-including physical exercise, nutritional counseling, and psychological support-is expected to improve fatigue in patients with primary biliary cholangitis. Consequently, this improvement is anticipated to enhance quality of life and cognitive symptoms, while also positively impacting emotional, social, and occupational aspects.
From a pathophysiological perspective, it is hypothesized that chronic cholestasis and/or immune system activation, with the release of pro-inflammatory cytokines, leads to both central and peripheral alterations causing fatigue.
Read more
At the central level, systemic inflammation may induce neuronal senescence in the basal ganglia, resulting in altered functional connectivity networks dependent on these regions and/or structural and connectivity changes in areas involved in interoception, such as the insula and anterior cingulate cortex.
At the peripheral level, the hypothesis is that chronic inflammation mediated by anti-mitochondrial antibodies causes mitochondrial metabolic dysfunction in muscle cells, which would be reflected in changes observed in the gene expression analysis of these cells.
Improvement in fatigue following the multimodal intervention program is expected to be associated with normalization of the immunological profile, enhanced functional brain connectivity, and improved mitochondrial metabolism in muscle.
Read the detailed description
Primary biliary cholangitis (PBC) is a rare autoimmune disease that damages the small bile ducts and primarily affects women. Although it is a liver disease, its most common symptom is fatigue, affecting up to 60% of patients. Fatigue is a debilitating symptom, described by patients as "a brain fog" that causes concentration problems and memory loss, along with "a lack of energy" that leads to poor exercise tolerance and early exhaustion. This significantly impacts quality of life, negatively affecting family, social, and work-related activities. To the frustration of both patients and healthcare providers, fatigue is not correlated with the severity of liver disease, and there is currently no effective treatment.
Ursodeoxycholic acid (UDCA), the first-line treatment for PBC, has been shown to improve disease survival, but it does not appear to have an effect on fatigue, as demonstrated by a meta-analysis. Other treatments, such as bezafibrate, have also failed to show improvement in fatigue. Several clinical trials have tested treatments targeting different pathophysiological mechanisms, including selective serotonin reuptake inhibitors (SSRIs), stimulants like modafinil, and immunomodulatory therapies such as rituximab, all with negative results.
Currently, new drugs have been approved as second-line treatments for PBC, such as elafibranor and seladelpar. The latter may have some impact on fatigue; however, this was not the primary objective of the study, and the mechanisms associated with this improvement remain unclear.
One of the main reasons why no treatment exists is the lack of understanding of the underlying mechanisms. Fatigue is a complex and likely multifactorial symptom. It has been hypothesized that chronic immune system activation, leading to excessive production of inflammatory substances, could be a trigger. Additionally, it remains unknown whether alterations in bile acid composition, which are molecules with potent biological effects on multiple organs, could worsen fatigue. Furthermore, this chronic inflammation may induce changes in both the brain and muscles, contributing to the development of fatigue.
It has been demonstrated that physical exercise reduces systemic inflammation by lowering inflammatory substances and can also improve abnormalities in muscle energy production. Studies conducted in patients with other diseases associated with fatigue, such as multiple sclerosis, have shown that exercise programs can be beneficial for fatigue management.
At present, experience with physical training programs for PBC patients with fatigue is very limited. The results of a study conducted in the United Kingdom and another in Canada suggest that a home-based exercise program may improve fatigue. However, both studies have certain limitations, as the follow-up was remote, there was no supervision to ensure proper execution of the exercises or that they were performed at the prescribed intensity. Additionally, the effective exercise duration was only about 15 minutes, which, along with its moderate intensity, is unlikely to induce specific adaptations in mitochondrial biogenesis and efficiency. On the other hand, while patients with liver diseases generally express positive attitudes toward the benefits of supervised exercise, they also acknowledge a lack of confidence in initiating it independently.
Based on this evidence, an integrated exercise program is proposed, consisting of two phases: an initial supervised phase lasting eight weeks and a subsequent remote phase, combined with nutritional counseling and psychological support. It is hypothesized that this program will improve fatigue and consequently enhance quality of life, as well as alleviate associated cognitive symptoms (such as depression and sleep disturbances).
To better understand the changes occurring in the organs involved in fatigue, the investigators aim to analyze immune responses and bile acids to determine their potential association with fatigue, as has been observed in other autoimmune diseases. Additionally, potential alterations at both the brain and muscle levels will be explored.
At the neurological level, functional connectivity alterations in brain regions involved in fatigue will be studied using functional magnetic resonance imaging (fMRI). At the muscular level, changes in muscle metabolism will be analyzed by studying gene expression in muscle fibers. Muscle samples will be obtained using a minimally invasive technique called muscle microbiopsy, which involves a fine-needle puncture of a muscle and is not associated with complications. These studies will be conducted before and after the exercise program, aiming to observe the positive changes expected at all levels.
These studies will be conducted before and after the training program.
- Conditions
- Primary Biliary Cholangitis (PBC)
- Being tested
- Multimodal prehabilitation, standard of care
- Keywords
- FATIGUE, PREHABILITATION, PHYSICAL ACTIVITY, MINDFULNESS MEDITATION, NUTRITION, QUALITY OF LIFE
- Medical subject headings
- Liver Cirrhosis, Biliary, Fatigue, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Multimodal prehabilitationOther
The multimodal prehabilitation program will consist of:
- twice-weekly supervised exercise training at the hospital gym for approximately 8 weeks (induction phase), followed by 16 weeks of telematic, supervised, home-based exercise (maintenance phase);
- nutritional consultation, including diet optimization and supplementation if needed;
- individual or group-based psychological support.
standard of careOther
Participants in the control group will follow the standard of care provided by the hospital and will receive general recommendations on physical activity, nutrition, and stress/anxiety management.
| Study group | Role | What they receive |
|---|---|---|
| Multimodal prehabilitation | Experimental | 8 weeks program of tailored physical exercise program with nutritional and psychological counselling to be carried out to a patient on the basis of his/her health condition, social circumstances and adherence profile. Receives: Other: Multimodal prehabilitation |
| Standard of care | Other | Standard Counselling: Patients in the control group will follow standard of care of the hospital and will be given general recommendations on physical activity, nutrition and stress/anxiety management. Receives: Other: standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Fatigue Severity Assessed by PBC-40
To evaluate the effect of a non-pharmacological multimodal intervention program on fatigue severity and its impact in participants with primary biliary cholangitis (PBC). Fatigue will be assessed using the Primary Biliary Cholangitis-40 (PBC-40) fatigue domain, which consists of 11 items scored from 1 to 5. Scoring Range: 11 to 55; higher scores indicate greater fatigue.
Measured: Baseline (week 0), post-intervention (week 8), and end of maintenance phase (6 months).
Change in Fatigue Severity Assessed by Visual Analogue Scale
To evaluate the effect of a non-pharmacological multimodal intervention program on fatigue severity and its impact in participants with primary biliary cholangitis (PBC). Fatigue will be assessed using the Visual Analogue Scale (VAS) for fatigue, which captures the participant's perception of fatigue severity. Scoring Range: 0 (no fatigue) to 10 (worst imaginable fatigue).
Measured: Baseline (week 0), post-intervention (week 8), and end of maintenance phase (6 months).
Change in Fatigue Impact Assessed by Fatigue Impact Scale (FIS)
To evaluate the effect of a non-pharmacological multimodal intervention program on fatigue severity and its impact in participants with primary biliary cholangitis (PBC). Fatigue will be assessed using the Modified Fatigue Impact Scale (MFIS), which assesses the impact of fatigue on physical, cognitive, and psychosocial functioning. Scoring Range: 0 to 84; higher scores indicate greater fatigue-related impairment
Measured: Baseline (week 0), post-intervention (week 8), and end of maintenance phase (6 months).
Secondary outcomes (15)
Change in Cognitive Symptoms Assessed by PBC-40
To evaluate changes in cognitive symptoms using the Primary Biliary Cholangitis-40 (PBC-40) questionnaire. The cognitive domain ranges from 6 to 30 points. Higher scores indicate worse symptoms.
Measured: Baseline, week 8 and/or after the exercise phase, and end of trial.
Change in Extrahepatic Symptoms Assessed by PBC-40
To evaluate changes in extrahepatic symptoms using the Primary Biliary Cholangitis-40 (PBC-40) questionnaire. The symptoms domain ranges from 7 to 35 points. Higher scores indicate worse symptoms.
Measured: Baseline, week 8 and/or after the exercise phase, and end of trial.
Change in Quality of Life Assessed by EQ-5D-5L Index Score
To assess health-related quality of life using only the EQ-5D-5L index score derived from five health dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The index score ranges from -0.594 to 1, where higher scores indicate better health status.
Measured: Baseline, week 8 and/or after the exercise phase, and end of trial.
Change in Self-Perceived Health Status Assessed by EQ Visual Analogue Scale
To evaluate self-perceived overall health using the EQ Visual Analogue Scale (EQ-VAS), part of the EQ-5D-5L instrument, reported separately. The EQ-VAS ranges from 0 to 100, where 0 = worst imaginable health and 100 = best imaginable health.
Measured: Baseline, week 8 and/or after the exercise phase, and end of trial.
Change in Disability Assessed by the WHO Disability Assessment Schedule (WHODAS 2.0)
To measure disability and functional impairment. Scoring Range: 0 to 100; higher scores indicate greater disability.
Measured: Baseline, week 8 and/or after the exercise phase, and end of trial.
Change in Anxiety and Depression Assessed by the Hospital Anxiety and Depression Scale (HADS)
To evaluate levels of anxiety and depression. Scoring Range: 0 to 21 for each subscale (anxiety and depression); higher scores indicate greater symptom severity.
Measured: Baseline, week 8 and/or after the exercise phase, and end of trial.
Change in Sleep Quality Assessed by the Epworth Sleepiness Scale (ESS)
To assess daytime sleepiness as a proxy for sleep quality. Scoring Range: 0 to 24; higher scores indicate greater daytime sleepiness.
Measured: Baseline, week 8 and/or after the exercise phase, and end of trial.
Change in Work Productivity and Activity Impairment Assessed by the WPAI Questionnaire
To measure absenteeism and work productivity impairment. Percentage scores for absenteeism, presenteeism, overall work impairment, and activity impairment; higher percentages indicate greater impairment.
Measured: Baseline, week 8 and/or after the exercise phase, and end of trial.
Change in Systemic Inflammation Assessed by Pro-Inflammatory Cytokines
To evaluate systemic inflammation and bile acid metabolism by analyzing a panel of pro-inflammatory cytokines (measured via ELISA), lysophosphatidic acid, autotaxin, and bile acids. Each biomarker will be quantified by the laboratory using standardized assays.
Units of Measure: Concentrations reported in appropriate laboratory units (e.g., pg/mL, nmol/L) depending on the biomarker.
Measured: Baseline and end of induction phase (2 months) for participants with fatigue; single time point for control groups.
Functional Connectivity Alterations in Brain Regions Assessed by fMRI.
To examine changes in functional connectivity in gray matter regions, including the basal ganglia and insula, using functional magnetic resonance imaging (fMRI).
Measured: Baseline and end of induction phase (2 months) for participants with fatigue; single time point for control groups.
Changes in Muscle Mitochondrial Metabolism Assessed by Gene Expression Analysis
To analyze gene expression profiles related to mitochondrial metabolism in muscle fibers obtained via muscle microbiopsy. Units of measure: Relative gene expression (fold change compared to baseline or control).
Measured: Baseline and end of induction phase (2 months) for participants with fatigue; single time point for control groups.
Change in Aerobic Capacity
Aerobic capacity will be evaluated to measure changes in functional exercise tolerance using the 6-Minute Walk Test (6MWT), which measures distance walked in meters (0-700 m typical; higher distances = better capacity).
Unit of Measure: Meters.
Measured: Baseline (week 0), post-intervention (week 8), and end of maintenance phase (6 months).
Change in Physical Activity Levels
Physical activity levels will be assessed to determine changes in habitual activity, with scores ranging from 0 to 142, where higher scores indicate greater overall physical activity.
Measured: Baseline (week 0), post-intervention (week 8), and end of maintenance phase (6 months).
Change in Frailty Status
Frailty will be evaluated using the Liver Frailty Index (LFI), a continuous scale derived from a combination of grip strength, chair-stand time, and balance testing. In adult liver disease populations, median LFI values range approximately from 2.7 in individuals without liver disease to 3.6 in those with cirrhosis. Established thresholds classify LFI scores of < 3.2 as "robust", 3.2-4.4 as "prefrail", and > 4.4 as "frail"
Measured: Baseline (week 0), post-intervention (week 8), and end of maintenance phase (6 months).
Feasibility and Satisfaction of a Multimodal Rehabilitation Program for the Treatment of Fatigue
Participant experience will be assessed using satisfaction questionnaires. Adherence to the intervention and loss to follow-up will be evaluated by analyzing reasons for non-compliance or withdrawal.
Measured: From enrollment to the end of treatment at 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2025
- Study start6 Feb 2025
- Primary completion30 Sep 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (32)Papers the sponsor has linked to this study.
- Other trials for Primary Biliary Cholangitis (PBC)Studies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Participants with primary biliary cholangitis (PBC) under follow-up in hepatology outpatient clinics who present with moderate to severe fatigue, as defined by a score greater than 29 on the PBC-40 questionnaire, and who agree to participate in the study after providing informed consent, will be eligible for inclusion. Once enrolled, participants with PBC and fatigue will be randomly assigned to either receive the multimodal intervention for 8 weeks or be allocated to the control group. Randomization will be performed using simple randomization via the REDCap platform. For the control group, after the initial 8-week period, the opportunity to participate in the multimodal rehabilitation program will be offered. Subsequently, both groups, after completing the 8-week intervention, will continue with the remote phase of the program for an additional six months of follow-up.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 64 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital Clinic of Barcelona
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sergio Rodríguez Tajes, MD, PhD, Principal investigator, Hospital Clinic of BarcelonaMarta Ubré Lorenzo, MD, PhD, Principal investigator, Hospital Clinic of Barcelona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07161245
- Sponsor's protocol ID
- RELIEF/2025
- Acronym
- RELIEF
- Status last verified
- Mar 2025
- First submitted
- 2 Jun 2025
- Last updated
- 8 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Diaz-Feijoo B, Agusti N, Sebio R, Siso M, Carreras-Dieguez N, Domingo S, Diaz-Cambronero O, Torne A, Martinez-Palli G, Arguis MJ. A multimodal prehabilitation program for the reduction of post-operative complications after surgery in advanced ovarian cancer under an ERAS pathway: a randomized multicenter trial (SOPHIE). Int J Gynecol Cancer. 2022 Nov 7;32(11):1463-1468. doi: 10.1136/ijgc-2022-003652.
PubMed 35793862Gimeno-Santos E, Coca-Martinez M, Arguis MJ, Navarro R, Lopez-Hernandez A, Castel MA, Romano B, Lopez-Baamonde M, Sandoval E, Farrero M, Sanz M, Bofill A, Martinez-Palli G. Multimodal prehabilitation as a promising strategy for preventing physical deconditioning on the heart transplant waiting list. Eur J Prev Cardiol. 2020 Dec;27(19):2367-2370. doi: 10.1177/2047487319889709. Epub 2019 Nov 25. No abstract available.
PubMed 31766879Barberan-Garcia A, Ubre M, Pascual-Argente N, Risco R, Faner J, Balust J, Lacy AM, Puig-Junoy J, Roca J, Martinez-Palli G. Post-discharge impact and cost-consequence analysis of prehabilitation in high-risk patients undergoing major abdominal surgery: secondary results from a randomised controlled trial. Br J Anaesth. 2019 Oct;123(4):450-456. doi: 10.1016/j.bja.2019.05.032. Epub 2019 Jun 25.
PubMed 31248644Williams FR, Vallance A, Faulkner T, Towey J, Kyte D, Durman S, Johnson J, Holt A, Perera MT, Ferguson J, Armstrong MJ. Home-based exercise therapy in patients awaiting liver transplantation: protocol for an observational feasibility trial. BMJ Open. 2018 Jan 21;8(1):e019298. doi: 10.1136/bmjopen-2017-019298.
PubMed 29358444Zenith L, Meena N, Ramadi A, Yavari M, Harvey A, Carbonneau M, Ma M, Abraldes JG, Paterson I, Haykowsky MJ, Tandon P. Eight weeks of exercise training increases aerobic capacity and muscle mass and reduces fatigue in patients with cirrhosis. Clin Gastroenterol Hepatol. 2014 Nov;12(11):1920-6.e2. doi: 10.1016/j.cgh.2014.04.016. Epub 2014 Apr 24.
PubMed 24768811Watt M, Hyde A, Johnson E, Wright GM, Vander Well S, Sadasivan C, Lee-Baggley D, Spence JC, Mason A, Ko HH, Tam E, Tandon P. An online mind-body program improves mental health and quality of life in primary biliary cholangitis: A randomized controlled trial. Hepatol Commun. 2023 Nov 6;7(11):e0316. doi: 10.1097/HC9.0000000000000316. eCollection 2023 Nov 1.
PubMed 38346279Freer A, Williams FR, Durman S, Hayden J, Armstrong MJ, Trivedi PJ. A home-based exercise programme attenuates fatigue in primary biliary cholangitis: Results from the EXCITED clinical trial. JHEP Rep. 2024 Sep 6;6(12):101210. doi: 10.1016/j.jhepr.2024.101210. eCollection 2024 Dec.
PubMed 39640219Kowdley KV, Bowlus CL, Levy C, Akarca US, Alvares-da-Silva MR, Andreone P, Arrese M, Corpechot C, Francque SM, Heneghan MA, Invernizzi P, Jones D, Kruger FC, Lawitz E, Mayo MJ, Shiffman ML, Swain MG, Valera JM, Vargas V, Vierling JM, Villamil A, Addy C, Dietrich J, Germain JM, Mazain S, Rafailovic D, Tadde B, Miller B, Shu J, Zein CO, Schattenberg JM; ELATIVE Study Investigators' Group; ELATIVE Study Investigators' Group. Efficacy and Safety of Elafibranor in Primary Biliary Cholangitis. N Engl J Med. 2024 Feb 29;390(9):795-805. doi: 10.1056/NEJMoa2306185. Epub 2023 Nov 13.
PubMed 37962077Jopson L, Newton JL, Palmer J, Floudas A, Isaacs J, Qian J, Wilkinson J, Trenell M, Blamire A, Howel D, Jones DE. RITPBC: B-cell depleting therapy (rituximab) as a treatment for fatigue in primary biliary cirrhosis: study protocol for a randomised controlled trial. BMJ Open. 2015 Aug 20;5(8):e007985. doi: 10.1136/bmjopen-2015-007985.
PubMed 26297361Talwalkar JA, Donlinger JJ, Gossard AA, Keach JC, Jorgensen RA, Petz JC, Lindor KD. Fluoxetine for the treatment of fatigue in primary biliary cirrhosis: a randomized, double-blind controlled trial. Dig Dis Sci. 2006 Nov;51(11):1985-91. doi: 10.1007/s10620-006-9397-5. Epub 2006 Oct 20.
PubMed 17053955Silveira MG, Gossard AA, Stahler AC, Jorgensen RA, Petz JL, Ali AH, Lindor KD. A Randomized, Placebo-Controlled Clinical Trial of Efficacy and Safety: Modafinil in the Treatment of Fatigue in Patients With Primary Biliary Cirrhosis. Am J Ther. 2017 Mar/Apr;24(2):e167-e176. doi: 10.1097/MJT.0000000000000387.
PubMed 27148676Lee JY, Danford CJ, Trivedi HD, Tapper EB, Patwardhan VR, Bonder A. Treatment of Fatigue in Primary Biliary Cholangitis: A Systematic Review and Meta-Analysis. Dig Dis Sci. 2019 Aug;64(8):2338-2350. doi: 10.1007/s10620-019-5457-5. Epub 2019 Jan 10.
PubMed 30632051Hollingsworth KG, Newton JL, Taylor R, McDonald C, Palmer JM, Blamire AM, Jones DE. Pilot study of peripheral muscle function in primary biliary cirrhosis: potential implications for fatigue pathogenesis. Clin Gastroenterol Hepatol. 2008 Sep;6(9):1041-8. doi: 10.1016/j.cgh.2008.04.013. Epub 2008 Aug 8.
PubMed 18691944Yeaman SJ, Kirby JA, Jones DE. Autoreactive responses to pyruvate dehydrogenase complex in the pathogenesis of primary biliary cirrhosis. Immunol Rev. 2000 Apr;174:238-49. doi: 10.1034/j.1600-0528.2002.00021h.x.
PubMed 10807520Hollingsworth KG, Newton JL, Robinson L, Taylor R, Blamire AM, Jones DE. Loss of capacity to recover from acidosis in repeat exercise is strongly associated with fatigue in primary biliary cirrhosis. J Hepatol. 2010 Jul;53(1):155-61. doi: 10.1016/j.jhep.2010.02.022. Epub 2010 Mar 31.
PubMed 20447719