Biochemical response to ursodeoxycholic acid (UDCA) therapy is associated with good prognosis in people living with primary biliary cholangitis (PBC). Biochemical response is typically assessed early in disease and it is not known what proportion of patients lose previously attained biochemical response, nor whether this impacts long-term liver transplant (LT)-free survival. We identified all UDCA-treated patients with PBC from the Canadian Network for Autoimmune Liver disease with biochemical measurements at 1 year, and evaluated their liver biochemistry over time. Inadequate biochemical response was defined as serum alkaline phosphatase ≥1.67x the upper limit of normal or abnormal serum total bilirubin at 1 year of UDCA therapy and all time points thereafter. Multistate Markov models were used to estimate transition rates between biochemical response states and from each state to LT or death. Results were validated in an external cohort (GLOBAL PBC registry). A total of 823 patients from eight centers were included. Mean age at diagnosis was 53 years, 91% were female, 33% had inadequate biochemical response to UDCA at 1 year (n = 269). Patients who retained initial adequate response had lower rates of LT or death compared to patients who subsequently lost response (relative rate 0.102, 95% CI 0.047-0.223). Patients who regained adequate response had lower rates than patients who did not (0.016, 95% CI 0.001-0.568), and patients who lost response once more (0.010, 95% CI 0.001-0.340). Patients who regained adequate response for a third time also had lower rates than patients who did not (0.151, 95% CI 0.040-0.566). Analyses in the GLOBAL PBC registry (n = 2,237) validated these results. Loss of biochemical response at any time is associated with heightened risks of LT or death in people living with PBC. Achievement of biochemical response is an important goal throughout follow-up, regardless of biochemical response profile early in therapy. Early biochemical response to ursodeoxycholic acid is associated with good prognosis in patients with primary biliary cholangitis (PBC). Our work demonstrates that patients with PBC transition between biochemical response states over time, and that these transitions correspond with changes in risk of liver transplantation or death. Clinicians should re-evaluate risk and optimize treatment decisions for patients with PBC throughout follow-up, regardless of early biochemical response to therapy.

Living donor liver transplantation (LDLT) offers the opportunity to decrease waitlist time and mortality for patients with autoimmune liver disease (AILD), autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. We compared the survival of patients with a potential living donor (pLDLT) on the waitlist versus no potential living donor (pDDLT) on an intention-to-treat basis. Our retrospective cohort study investigated adults with AILD listed for a liver transplant in our program between 2000 and 2021. The pLDLT group comprised recipients with a potential living donor. Otherwise, they were included in the pDDLT group. Intention-to-treat survival was assessed from the time of listing. Of the 533 patients included, 244 (43.8%) had a potential living donor. Waitlist dropout was higher for the pDDLT groups among all AILDs (pDDLT 85 [29.4%] vs. pLDLT 9 [3.7%], p < 0.001). The 1-, 3-, and 5-year intention-to-treat survival rates were higher for pLDLT versus pDDLT among all AILDs (95.7% vs. 78.1%, 89.0% vs. 70.1%, and 87.1% vs. 65.5%, p < 0.001). After adjusting for covariates, pLDLT was associated with a 38% reduction in the risk of death among the AILD cohort (HR: 0.62, 95% CI: 0.42–0.93 [p<0.05]), and 60% among the primary sclerosing cholangitis cohort (HR: 0.40, 95% CI: 0.22–0.74 [p0.9]). Our study suggests that having a potential living donor could decrease the risk of death in patients with primary sclerosing cholangitis on the waitlist. Importantly, the post-transplant outcomes in this population are similar between the LDLT and DDLT groups.

Solitary hepatocellular carcinoma measuring ≤3 cm represents approximately 30% of hepatocellular carcinoma cases, yet treatment guidelines lack robust evidence. This study compares oncologic outcomes after ablation, liver resection, and liver transplantation for solitary, small hepatocellular carcinoma. We systematically searched databases up to 7 February 2022, for studies including adults with solitary hepatocellular carcinoma ≤3 cm treated by any ablation, liver resection, or liver transplantation. We excluded non-hepatocellular carcinoma cancers, recurrent/metastatic diseases, and alternative therapies. A frequentist network meta-analysis assessed 5-year overall survival and recurrence-free survival using only adjusted effect estimates while accounting for bias risk. We identified 80 studies (4 randomized controlled trials, 72 retrospectives, and 4 prospective cohorts) with 28,211 patients. In the network meta-analysis for 5-year overall survival (26 studies), liver transplantation was associated with the lowest mortality hazard (hazard ratio, 0.47; 95% confidence interval, 0.31-0.73, referenced to liver resection), followed by liver resection (reference), whereas ablation had the greatest mortality hazard (hazard ratio, 1.32; 95% confidence interval, 1.16-1.49, referenced to liver resection). For 5-year recurrence-free survival (19 studies), liver transplantation had the best outcome (hazard ratio, 0.36; 95% confidence interval, 0.20-0.63, referenced to liver transplantation), followed by liver resection (reference), with ablation showing the least favorable outcome (hazard ratio, 1.67; 95% confidence interval, 1.45-1.93, referenced to liver resection). This network meta-analysis provides the evidence for comparing treatment modality outcomes for solitary, small (≤3 cm) hepatocellular carcinoma. LT emerges as the superior choice for achieving a better 5-year OS, followed by liver resection, then ablation. When feasible to preserve liver function, liver resection can be prioritized. Ablation with close surveillance should be reserved for individuals unfit for surgery.

Woo Jin Choi, Fiorella Murillo Perez, Annabel Gravely, Tommy Ivanics, Marco P. A. W. Claasen, Liza Abraham, Phillipe Abreu, Robin Visser, Steven Gallinger, Bettina E. Hansen, Gonzalo Sapisochin. Ann Hepatobiliary Pancreat Surg 2023;27:158-65. https://doi.org/10.14701/ahbps.22-114

Postoperative acute kidney injury is associated with an increase in hospital length of stay and mortality. Intraoperative hemodynamics and fluid management may contribute to acute kidney injury. The aim of this study is to evaluate the association between intraoperative duration of hypotension with adverse events after laparoscopic liver resection. A prospective cohort including adult patients undergoing laparoscopic liver resection between January 2010 and June 2022. Cumulative time below mean arterial blood pressure thresholds and association with major adverse events composing of postoperative acute kidney injury (≤2 days) and complications (Dindo-Clavien ≥3a) ≤30 days were assessed. In 360 patients, the median age was 61 years, 206 (57%) were male, median body mass index was 26.3, and 129 (36%) patients had hepatocellular carcinoma. Acute kidney injury was recorded in 3 (0.8%) patients as stage 1, 6 (1.7%) patients as stage 2, and 7 (1.9%) patients as stage 3. Major adverse events occurred in 31 (8.6%) patients, and the median estimated blood loss was 200 mL. On continuous analysis, a threshold <60 mmHg at ≥15 minutes was found for major adverse events. The mean arterial blood pressure <55 mmHg for ≥20 minutes was associated with an increased risk of major adverse events (odds ratio 7.72; P < .001). In patients with >15 minutes of mean arterial blood pressure <60 mmHg, higher intravenous volume was associated with increase in major adverse events (P = .045), whereas adjusted intravenous volume was not associated with major adverse events (P = .657), acute kidney injury (P = .681), or blood loss (P = .875). Laparoscopic liver resection is a safe procedure with a low risk of acute kidney injury. After ≥15 minutes at mean arterial blood pressure <60 mmHg, the risk of major adverse events increases. Greater intravenous fluid infusion volume was associated with an observed risk for major adverse events, suggesting that mean arterial blood pressure should be managed by vasoactive agents.

Living donor liver transplantation (LDLT) is a curative treatment for various liver diseases, reducing waitlist times and associated mortality. We aimed to assess the overall survival (OS), identify predictors for mortality, and analyze differences in risk factors over time. Adult patients undergoing LDLT were selected from the United Network for Organ Sharing database from inception (1987) to 2023. The Kaplan-Meier method was used for analysis, and multivariable Cox proportional hazard models were conducted. In total, 7257 LDLT recipients with a median age of 54 years (interquartile range [IQR]: 45-61 years), 54% male, 80% non-Hispanic White, body mass index of 26.3 kg/m² (IQR: 23.2-30.0 kg/m²), and model for end-stage liver disease score of 15 (IQR: 11-19) were included. The median cold ischemic time was 1.6 hours (IQR: 1.0-2.3 hours) with 88% right lobe grafts. The follow-up was 4.0 years (IQR: 1.0-9.2 years). The contemporary reached median OS was 17.0 years (95% CI: 16.1, 18.1 years), with the following OS estimates: 1 year 95%; 3 years 89%; 5 years 84%; 10 years 72%; 15 years 56%; and 20 years 43%. Nine independent factors associated with mortality were identified, with an independent improved OS in the recent time era (adjusted hazards ratio: 0.53; 95% CI: 0.39, 0.71). The median center-caseload per year was 5 (IQR: 2-10), with observed center-specific improvement of OS. LDLT is a safe procedure with excellent OS. Its efficacy has improved despite an increase of risk parameters, suggesting its limits are yet to be met.