Pilot Study of Peripheral Muscle Function in Primary Biliary Cirrhosis: Potential Implications for Fatigue Pathogenesis  Kieren G. Hollingsworth, Julia L. Newton, Roy Taylor, Claire McDonald, Jeremy M. Palmer, Andrew M. Blamire, David E.J. Jones  Clinical Gastroenterology and Hepatology  Volume 6, Issue 9, Pages 1041-1048 (September 2008) DOI: 10.1016/j.cgh.2008.04.013 Copyright © 2008 AGA Institute Terms and Conditions

Figure 1 Correlation between ADP and PCr recovery half-times in (a) normal controls, (b) non-fatigued PBC patients, (c) fatigued PBC patients, (d) CFS patients, and (e) PSC patients; Pearson test. Clinical Gastroenterology and Hepatology 2008 6, 1041-1048DOI: (10.1016/j.cgh.2008.04.013) Copyright © 2008 AGA Institute Terms and Conditions

Figure 2 Muscle pH at rest, at the end of the exercise period, and at the lowest point seen in the post-exercise recovery period in (a) normal controls, (b) PBC patients (open circles and broken line denote non-fatigued patients and closed circles and solid connecting line denote fatigued PBC patients), (c) CFS patients, (d) PSC patients. Unpaired t test, a and d; Mann-Whitney test, b and c. Clinical Gastroenterology and Hepatology 2008 6, 1041-1048DOI: (10.1016/j.cgh.2008.04.013) Copyright © 2008 AGA Institute Terms and Conditions

Figure 3 Correlation between the ratio of the PCr and ADP recovery half-times (a measure of the response of the mitochondrion to ADP “drive”) and (a) minimum pH value seen in muscle in PBC patients after exercise and (b) the drop in pH seen with exercise from pre-exercise values. Acidosis seen to a variable degree in PBC patients after exercise appears to be associated with degree of mitochondrial dysfunction (Spearman test). (c) Serum IgG anti-PDC levels in PBC patients with normal and significantly elevated PCr/ADP recovery half-time ratios (significant elevation defined as a value greater than the mean value + 2 SDs for the normal control group and is suggestive of mitochondrial dysfunction; nonparametric analysis) (Mann-Whitney test). Clinical Gastroenterology and Hepatology 2008 6, 1041-1048DOI: (10.1016/j.cgh.2008.04.013) Copyright © 2008 AGA Institute Terms and Conditions

Figure 4 (a) Time to pH recovery after exercise in normal controls, PBC patients, and CFS patients. *P < .05 vs PBC. (b) Comparison of severity of fatigue in PBC patients exhibiting normal time to pH recovery after exercise (defined as control mean value + 2 SDs) and in PBC patients exhibiting prolonged pH recovery. Clinically significant fatigue was restricted to the normal pH recovery group. **P < .01. (c) Time to maximum proton efflux in the recovery phase after exercise.*P < .05 vs normal control (Mann-Whitney test). Clinical Gastroenterology and Hepatology 2008 6, 1041-1048DOI: (10.1016/j.cgh.2008.04.013) Copyright © 2008 AGA Institute Terms and Conditions

Figure 5 Kinetics for PCr recovery after exercise. ***P < .005 and *P < .05 vs non-fatigued PBC (unpaired t test). Clinical Gastroenterology and Hepatology 2008 6, 1041-1048DOI: (10.1016/j.cgh.2008.04.013) Copyright © 2008 AGA Institute Terms and Conditions