TABLE 9.
Examples of validated test protocols for 13C‐liver function breath tests in adults
| Estimated parameter | Marker and test solution | Breath sampling | Endpoints and normal values | Validity | Remarks | |
|---|---|---|---|---|---|---|
| Afolabi et al 2018 161 | Hepatic mitochondrial function | 1 mg/kg body weight of 13 C‐ketoisocaproate plus 20 mg/kg body weight L‐leucine dissolved in 200 ml of water | At baseline and at 10 min intervals for 60 min pp | Cumulative 13C‐recovery, normal >21% of dose | ‐ | Validated in 11 HC and 77 pts with NAFLD, SENS and SPEC to detect significant fibrosis was not determined |
| Portincasa et al 2006 157 | Hepatic mitochondrial function | 1 mg/kg body weight of 13 C‐ketoisocaproate plus 1 g of L‐leucine dissolved in 200 ml of water | At baseline and at 10 min intervals for 60 min pp | Cumulative 13C‐recovery, normal >14% of dose | Diagnostic accuracy at identifying pts with NASH (cut‐off value 9.6%): SENS 68%, SPEC 94%, PPV 90%, NPV 73% | Validated in 28 HC and 39 pts with NAFLD. The test was also able to discriminate fibrosis stages in patients with NASH |
| Banasch et al 2011 156 | Hepatic mitochondrial function | 2 mg/kg body weight [methyl‐ 13 C]‐methionine dissolved in 100 ml of water, prior oral consumption of 200 ml of orange juice | At baseline and at 10 min intervals for 90 min pp | Cumulative 13C‐recovery, normal >6.1% of dose | Cut‐off value <4.20% of dose for separation of pts with NASH from non‐NASH, SENS 81%; SPEC 76% | Validated in 118 pts with NAFLD and 18 HC. Test predicts higher stages of disease activity |
| Korkmaz et al. 2015 160 | Hepatic mitochondrial function | 2 mg/kg body weight [methyl‐ 13 C]‐methionine dissolved in 100 ml water | At baseline and at 10 min intervals for 90 min pp | Cumulative 13C‐recovery, normal >6.2% of dose | Cut off value <3.71%:SENS 95% SPEC 88% for differentiating advanced liver fibrosis (F2–3) from mild (F0–1) fibrosis | Validated in 164 pts with NAFLD and 56 HC |
| Fierbinteanu‐Braticevici et al.2013 163 | Hepatic microsomal function | Fixed dose of 75 mg 13 C‐methacetin dissolved in 200 ml of water | At baseline and at 10 min intervals for 60 min pp | Cumulative 13C‐recovery, normal >22% of dose | Cut off value <15.2%, SENS 91%, SPEC 82% at detecting significant fibrosis (F ≥ 2) | Validated in 90 pts with NAFLD and 20 HC |
| Park et al 2003 167 | Hepatic microsomal function | 2 mg/kg body weight of [3‐methyl‐ 13 C]‐caffeine dissolved in 30 ml of water, followed by 40 ml water wash of the container | At baseline and at 10 min intervals for 60 min pp | Cumulative 13C‐recovery, normal >2.3% of dose | Cut off value <1.85%: 79% SENS 80% SPEC for detecting NASH | Validated in 48 pts with NAFLD, 48 patients with chronic hepatitis B and 24 HC subjects. Results reflect the extent of hepatic fibrosis |
Abbreviations: HC, healthy controls; NAFLD, non‐alcoholic Fatty Liver disease; NASH, nonalcoholic steatohepatitis; NPV, negative predictive value; PPV, positive predictive value; pp, postprandial; SENS, sensitivity; SPEC, specificity.
[Corrections added on June 28, 2021 after first online publication: In Table 9, typos have been corrected. In the 3rd column, 2nd row, “postprandially” has been deleted from “At baseline and at 10 min intervals postprandially for 60 min pp.”]