We quantified the rates of hepatic regeneration and functional recovery for 6 months after right hepatic lobectomy in living donors for liver transplantation. Twelve donors were studied pre-donation (baseline); 8 were retested at a mean +/- SD of 11 +/- 3 days after donation (T1), 10 were retested at a mean of 91 +/- 9 days after donation (T2), and 10 were retested at a mean of 185 +/- 17 days after donation (T3). Liver and spleen volumes were measured with computed tomography (CT) and single-photon emission computed tomography (SPECT). Hepatic metabolism was assessed with caffeine and erythromycin, and hepatic blood flow (HBF) was assessed with cholates, galactose, and the perfused hepatic mass (PHM) by SPECT. The regeneration rates (mL kg1 of body weight day1) by CT were 0.60 +/- 0.22 mL from the baseline to T1, 0.05 +/- 0.02 mL from T1 to T2, and 0.01 +/- 0.01 from T2 to T3; by SPECT they were 0.54 +/- 0.20, 0.04 +/- 0.01, and 0.01 +/- 0.02, respectively. At T3, the liver volumes were 84%+/- 7% of the baseline according to CT and 92%+/- 13% of the baseline according to SPECT. Changes in the hepatic metabolism did not achieve statistical significance. At T1, the unadjusted clearance ratios with respect to the baseline were 0.75 +/- 0.07 for intravenous cholate (P<0.001), 0.88 +/- 0.15 for galactose (P=0.07), 0.84 +/- 0.08 for PHM (P=0.002), and 0.83 +/- 0.19 for the estimated HBF (P=0.06). At T1, these ratios adjusted per liter of liver were up to 50% greater than the baseline values, suggesting recruitment of HBF by the regenerating liver. Increased cholate shunt, increased spleen volume, and decreased platelet count, were consistent with an altered portal circulation. In conclusion, initial hepatic regeneration is rapid, accounts for nearly two-thirds of total regeneration, and is associated with increases in HBF and cholate uptake. Right lobe donation alters the portal circulation of living donors, but the long-term clinical consequences, if there are any, are unknown. Liver Transpl 19:292304, 2013. (c) 2013 AASLD.

obtain a liver stiffness measurement (LSM) in 3.1% of cases and the results are considered unreliable (ratio <60% or interquartile range/stiffness (IQR/LSM) >30%) in 15.8% (Castera et al.Hepatology 2010).Aims: To show the applicability of TE in chronic liver diseases (CLD) patients with inadequate LSM, after a second evaluation by trained operators.Methods: The inadequate LSM evaluated from March 2011 to March 2012 were included.LSM were categorized as inadequate (no values or ratio <60% and/or IQR/LSM >30%) or adequate.A second exploration (M probe) and a third register (XL probe) in patients with body mass index (BMI) >28 were performed by trained operators (>500 LSM) in those with a previous inadequate LSM.Results: 895 LSM were performed in 840 patients with CLD (52.4% with chronic hepatitis C).Inadequate LSM were obtained in 164 (18.3%) patients.The IQR/LSM was>30% in 90 (54.9%), there were no values in 59 (36%) and the ratio was <60% in 15 (9.1%).A second LSM (M probe, n = 119) by trained operators (JAC and MP) achieved valid LSM in 68.9% (n = 82) from those previously considered as inadequate.No values were obtained in 8 (6.7%) patients and 5 (4.2%) had an IQR/LSM >30%.Patients with BMI <24 (n = 17), from 24 to 28 (n = 33) and >28 (n = 69) showed inadequate LSM in 0%, 18.2% and 44.9% of the cases, respectively (p < 0.001).A third LSM was performed with the XL probe in patients with a BMI >28 (n = 31).The XL probe achieved an adequate LSM in 27 (87.1%)patients in whom the M probe performed by trained operators had not obtained adequate values.Conclusions: The operators' experience increases the applicability of TE particularly in patients with a BMI <28.For patients with a BMI >28 the use of XL probe would be recommendable.

Background: Previous cross-sectional studies have shown that serum levels of cytokeratin fragments (CK18) are associated with the presence of steatohepatitis in individuals with nonalcoholic fatty liver disease (NAFLD).However, it is unknown if serial serum CK18 levels can predict longitudinal changes in liver histology in NAFLD.Aim: To determine the degree to which changes in serum CK18 associate with changes in liver histology over a 96-week period in adult patients with nonalcoholic steatohepatitis (NASH).Methods: Serum CK18 levels were measured at baseline and 16, 48, and 96 weeks in 231 of the 247 adults with NASH who participated in the PIVENS trial which investigated the efficacy of pioglitazone vs. vitamin E vs. placebo in non-diabetic individuals with histologically confirmed NASH over a 96-week period.Liver biopsies at baseline and after 96 weeks of treatment were centrally evaluated by the NASH CRN Pathology Committee.Multiple logistic (for categorical outcomes) and linear (for continuous outcome variables) regression models were used to determine the association between changes in histological features, ALT, and % collagen assessed by Sirius red staining, and change in CK18 levels, controlling for baseline CK18 levels and treatment group.Results: At baseline, CK18 levels among the 3 treatment groups were similar (placebo: 440± 350 U/L, vit E: 510± 350 U/L, and pioglitazone: 490± 410 U/L).Compared to placebo, serum CK18 levels among individuals treated with vit E were reduced at week 16 (mean change from baseline -160± 300 vs. -50 ±380 U/L, p= 0.02), week 48 (-220± 390 vs. -10± 370 U/L, p=0.009), and week 96 (-200± 400 vs. 30± 400 U/L, p=0.009).Similarly, compared to placebo, serum CK18 levels among individuals treated with pioglitazone were reduced at week 16 (mean change from baseline -240 ± 390 vs. -50± 380 U/L, p,=0.001),week 48 (-180± 370 vs. -10± 370 U/L, p=0.001, and week 96 (-260 ±400 vs. 30 ± 400 U/L, p=0.001).Strong correlations were seen with change in CK18 levels and the primary histologic endpoint, resolution of NASH, and individual histologic features of NASH (Table 1).In addition, change in CK18 levels strongly correlated with change in ALT levels (b=0.06,95% CI: 0.04, 0.08; P ,0.001).Percent collagen measurements were not related to change in CK18 (b=-0.17%/100*U/L , 95% CI:-0.70,0.37; P= 0.54).Summary: (1) Compared to placebo, treatment with vit E or pioglitazone had significant reduction in serum CK18 levels.(2) Changes in serum CK18 correlated with histologic improvement in non-diabetic adults with NASH treated with vitamin E or pioglitazone.Conclusion: Serum CK18 is a potential useful surrogate marker for detection of improvement in clinical trials.

375 Non-invasive Measurement of the Portal Circulation Using Cholates Quantifies Disease Severity in Primary Sclerosing Cholangitis Ariana Wallack, Steve M. Helmke, Andrea Herman, Halley Isberg, Shannon Lauriski, Gregory T. Everson Section of Hepatology, University of Colorado Denver, Aurora, CO, United States Introduction Primary Sclerosing Cholangitis (PSC) preferentially causes portal fibrosis, altering the portal circulation, and ultimately leading to portal hypertension (PHTN). Liver biopsy is risky and characterized by significant sampling variability, laboratory measurements only detect late stages of disease, and Hepatic Venous Pressure Gradient is invasive and expensive. Accurate assessment of disease severity in PSC represents an unmet medical need. In this study we defined the reproducibility of three tests, Hepatic Filtration Rate (HFR), portal-systemic shunt fraction (SHUNT), and a single point cholate concentration (STAT), and their relationship to clinical features. Methods PSC patients (n=38) were recruited from our Hepatology Clinic and underwent history, physical exam, and standard lab assessment. PSC severity ranged from CTP 4-10, MELD 6-20, and Mayo PSC model scores of -0.67 to 2.37. PHTN features were defined as presence of splenomegaly or varices. Decompensation was defined by history of variceal bleed, hepatic encephalopathy, or ascites. HFR (mL/min/kg) was defined as the clearance of 40 mg orally administered cholate-2,2,4,4d4. SHUNT (%) was calculated from the ratio of HFR to the clearance of 20 mg intravenously administered cholate-24-C. STAT (μM) was the serum level of oral cholate after 60 min. Prior studies established test values in healthy controls. Reproducibility was assessed by duplicate testing (n=37) within 1 month and defined by the intra-class correlation (ICC). The relationships of HFR, SHUNT, and STAT to clinical features were analyzed by t-tests and ROC curves. Results The ICC in PSC patients was 0.90 for HFR, 0.92 for SHUNT, and 0.94 for STAT indicating excellent reproducibility. PSC patients had significantly lower HFR, increased SHUNT, and higher STAT relative to controls (table). Patients with PHTN, especially those with varices, were significantly more functionally impaired than those without PHTN. Within the PHTN group, those with varices had significantly worse function than those without varices. ROC analysis demonstrated the potential of HFR, SHUNT, and STAT to identify PSC patients with PHTN or varices. The small number of decompensated patients with either ascites or variceal bleed (n=4) had extremely poor function (HFR 3.1±0.4, SHUNT 71±5, STAT 3.7±0.5). Conclusions HFR, SHUNT, and STAT reproducibly quantify hepatic function in PSC. These tests differentiate PSC patients from healthy controls, and distinguish those with advanced disease from well compensated patients. HFR, SHUNT, and STAT may be useful in measuring and tracking disease severity in PSC. HFR, SHUNT, and STAT test values are the mean+/-SEM. P-values from t-tests are PSC vs Controls, PSC w PHTN vs PSC w/o PHTN, and PHTN w Varices vs PHTN w/o Varices. C-statistics from ROC curves were calculated for PHTN vs all PSC or for Varices vs all PSC. N P-value c-stat P-value c-stat P-value c-stat Healthy Controls 32 30.1 ± 1.7 19 ± 1 0.4 ± 0.02 PSC Patients 38 14.2 ± 1.1 <0.001 44 ± 3 <0.001 1.1 ± 0.2 <0.001 PSC w/o PHTN 22 16.9 ± 1.1 36 ± 3 0.7 ± 0.1 PSC w PHTN 16 10.5 ± 1.7 0.003 0.76 55 ± 5 <0.001 0.83 1.6 ± 0.4 0.006 0.71 PHTN w/o Varices 5 18.5 ± 2.2 38 ± 5 0.4 ± 0.1 PHTN w Varices 11 6.9 ± 1.1 <0.001 0.94 63 ± 5 0.005 0.93 2.2 ± 0.4 0.015 0.94 HFR (mL/min/kg) SHUNT (%) STAT( uM)