Liver function as assessed by breath tests in patients with hepatocellular carcinoma.
BACKGROUND
Little is known on hepatic function in patients with hepatocellular carcinoma (HCC). Metabolic changes were explored in HCC patients before/after nonsurgical therapy.


METHODS
HCV-related Child-Pugh A cirrhotic patients with (n = 37) or without HCC (n = 14) and healthy controls (n = 23) were enrolled. Subjects underwent breath testing with (13)C-methacetin or (13)C-ketoisocaproate for exploring microsomal and mitochondrial function, respectively. HCC patients repeated the tests 1-2, 30, and 180 d after radiofrequency ablation (n = 27, RFA) or transarterial chemoembolization (n = 10, TACE).


RESULTS
At baseline, cirrhotic patients showed decreased methacetin demethylation capacity compared with controls (8.1 +/- 2.1 versus 13.7 +/- 1.3% cum. dose exhaled at 60 min, M +/- CI, P < 0.001) and minor changes in ketoisocaproate decarboxylation. HCC patients had methacetin demethylation comparable to cirrhotic subjects, but a significantly lower ketoisocaproate decarboxylation (8.5 +/- 1.0 versus 11.6 +/- 1.9% cum. dose exhaled at 60 min, P < 0.001). Methacetin metabolism was significantly decreased following TACE (-28%, P < 0.05) but not RFA. Ketoisocaproate decarboxylation was unaffected by TACE but decreased after RFA (-27%, P < 0.05). A recovery was noticed with ketoisocaproate as a probe after 1 and 6 mo (P < 0.003). HCC recurrence was associated with early decrease of ketoisocaproate decarboxylation.


CONCLUSIONS
Liver mitochondrial function is decreased in cirrhotic patients with HCC suggesting a possible tumor-induced suppressant effect. RFA but not TACE appears to spare residual (microsomal) liver mass, but induces such a transient stunning effect on mitochondrial function. Improved mitochondrial function after 1 and 6 mo from RFA may represent an additional parameter of treatment efficacy. Breath test assessing liver function may have potential applications in HCC management.
Palmieri
Vincenzo O
VO
Clinica Medica A Murri, Department of Internal Medicine and Public Medicine, University of Bari Medical School, Bari, Italy. v.palmieri@semeiotica.uniba.it
Grattagliano
Ignazio
I
Minerva
Francesco
F
Pollice
Silvana
S
Palasciano
Giuseppe
G
Portincasa
Piero
P
D000081:Acetamides / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001944:Breath Tests / Q000379:methods*; D002247:Carbon Isotopes; D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D017115:Catheter Ablation; D016461:Chemoembolization, Therapeutic; D005260:Female; D006801:Humans; D007651:Keto Acids / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000503:physiopathology*; D008111:Liver Function Tests / Q000379:methods*; D008113:Liver Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D008930:Mitochondria, Liver / Q000502:physiology; D016896:Treatment Outcome
D000081:Acetamides; D002247:Carbon Isotopes; D007651:Keto Acids; C035495:methacetin; C013082:alpha-ketoisocaproic acid