Dynamics of liver stiffness measurement and clinical course of primary biliary cholangitis.

BACKGROUND & AIMS: In primary biliary cholangitis (PBC), static liver stiffness measurement (LSM) has proven prognostic value. However, the added prognostic value of LSM time course in this disease remains uncertain. METHODS: We conducted an international retrospective cohort study among PBC patients treated with ursodeoxycholic acid (UDCA) and followed by vibration-controlled transient elastography (VCTE) between 2003 and 2022. Using joint modeling, the association of LSM trajectory and the incidence of serious clinical events (SCE), defined as cirrhosis complications, liver transplantation (LT) or death, was quantified using the hazard ratio (HR) and its confidence interval (CI). RESULTS: A total of 6,362 LSMs were performed in 3,078 patients (2,007 on UDCA alone; 13% with cirrhosis), in whom 316 SCE occurred over 14,445 person-years (median follow-up, 4.2 years; incidence rate, 21.9 per 1,000 person-years). LSM progressed in 59% of patients (mean 0.39 kPa/year). After adjusting for prognostic factors at baseline, including LSM, any relative change in LSM was associated with a significant variation in SCE risk (p<0.001). For example, the adjusted HRs (95% CI) associated with a 20% annual variation in LSM were 2.13 (1.89 - 2.45) for the increase and 0.40 (0.33 - 0.46) for the decrease. The association between LSM trajectory and SCE risk persisted regardless of treatment response or duration, when patients with cirrhosis were excluded, and when only death or LT was considered. CONCLUSIONS: Tracking longitudinal changes in LSM using VCTE provides valuable insights into PBC prognosis, offering a robust predictive measure for the risk of SCE. LSM could be used as a clinically relevant surrogate endpoint in PBC clinical trials.

Altered liver function test after Covid-19 vaccines: A retrospective control group study.

BACKGROUND AND PURPOSE: Liver injury after Covid-19 vaccine has been described, although the incidence was not well established. We aimed to compare cumulative incidence of new onset liver test alteration after Covid-19 vaccination, and to compare with an historical control of influenza vaccination. METHODS: We conducted a retrospective cohort study which included adults who received at least one dose of Covid-19 vaccine from January 1 to May 30, 2021 and a control group who received a single dose of influenza vaccine during 2019, in a tertiary medical center from Argentina. RESULTS: We included 29 798 patients in Covid-19 vaccine group and 24 605 in influenza vaccine group. Liver function tests were performed in 7833 (26.9%) in Covid-19 vaccine group and 8459 (34.37%) in influenza vaccine group. Cumulative incidence at 90 days of new onset liver enzyme test alteration was 4.7 per 1000 (95% 4.0-5.5) for Covid-19 group, and 5.1 per 1000 (95% 4.3-6.1) for the influenza vaccine group (p value = 0.489). Two patients in the Covid-19 vaccine group developed immune mediated liver injury. CONCLUSIONS: We found no difference in liver test alteration between groups. These findings support the safety of Covid-19 vaccines. While we have identified two cases that are consistent with immune mediated liver injury following COVID-19 vaccination, we believe that the available data is insufficient to attribute them solely to the vaccination.

Adequate versus deep response to ursodeoxycholic acid in primary biliary cholangitis: To what extent and under what conditions is normal alkaline phosphatase level associated with complication-free survival gain?

BACKGROUND AND AIMS: Normal alkaline phosphatase (ALP) levels in ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC) are associated with better long-term outcome. However, second-line therapies are currently recommended only when ALP levels remain above 1.5 times the upper limit of normal (×ULN) after 12-month UDCA. We assessed whether, in patients considered good responders to UDCA, normal ALP levels were associated with significant survival gains. APPROACH AND RESULTS: We performed a retrospective cohort study of 1047 patients with PBC who attained an adequate response to UDCA according to Paris-2 criteria. Time to liver-related complications, liver transplantation, or death was assessed using adjusted restricted mean survival time (RMST) analysis. The overall incidence rate of events was 17.0 (95% CI: 13.7-21.1) per 1000 out of 4763.2 patient-years. On the whole population, normal serum ALP values (but not normal gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), or aspartate aminotransferase (AST); or total bilirubin < 0.6 ×ULN) were associated with a significant absolute complication-free survival gain at 10 years (mean 7.6 months, 95% CI: 2.7 - 12.6 mo.; p = 0.003). In subgroup analysis, this association was significant in patients with a liver stiffness measurement ≥ 10 kPa and/or age ≤ 62 years, with a 10-year absolute complication-free survival gain of 52.8 months (95% CI: 45.7-59.9, p < 0.001) when these 2 conditions were met. CONCLUSIONS: PBC patients with an adequate response to UDCA and persistent ALP elevation between 1.1 and 1.5 ×ULN, particularly those with advanced fibrosis and/or who are sufficiently young, remain at risk of poor outcome. Further therapeutic efforts should be considered for these patients.

Evaluation of the humoral response to the third dose of SARS-COV-2 vaccines in liver transplant recipients.

Solid organ transplant recipients (SOTR) commonly develop an unsatisfactory humoral response to vaccines compared to immunocompetent individuals (IC). We have previously evaluated the humoral response in liver transplant recipients (LTR) who received two-dose vaccines against SARS-CoV-2 and reported that 38 % of LTR did not produce anti-Spike antibodies. Thus, we set out to evaluate the humoral response after the third dose of SARS-CoV-2 vaccines. For this purpose, samples from a cohort of 81 LTR and 27 IC were extracted between 21 and 90 days after the third dose. Serology for anti-Spike IgG antibodies and neutralizing antibodies against Wuhan, Delta and Omicron variants were evaluated. We found that 73.5 % of LTR were responders for anti-Spike IgG, while all the IC mounted a measurable response. LTR who responded to the third dose showed significantly lower anti-Spike IgG levels and neutralizing antibodies than IC. We found that there is less neutralization in LTR compared to IC across all variants. Specifically, the neutralization titers in both groups decrease when encountering the Delta variant, and this decline is even more pronounced with the Omicron variant, compared to the Wuhan variant. Furthermore, we identified that the use of high doses of mycophenolate and advanced age were factors that negatively affected the development of anti-Spike IgG antibodies. Regarding vaccine regimes, the regime viral vector/mRNA/mRNA elicited significantly higher responses in LTR compared to other vaccine schemes. In addition to the recommended and necessary booster doses in this population, strategies that achieve adequate immunization should be evaluated.

Spontaneous bacteremia and spontaneous bacterial peritonitis share similar prognosis in patients with cirrhosis: a cohort study.

BACKGROUND AND AIMS: Spontaneous bacteremia is a poorly characterized infection in patients with cirrhosis. We compared the incidence of mortality and acute kidney injury in patients with spontaneous bacterial peritonitis and spontaneous bacteremia, and identified risk factors for mortality and acute kidney injury in patients with spontaneous bacteremia. METHODS: We performed a retrospective cohort study of patients with cirrhosis and spontaneous bacteremia or spontaneous bacterial peritonitis from 2008 to 2016 at Hospital Italiano, Buenos Aires. We compared the cumulative incidence of acute kidney injury and death between the two infections, and identified risk factors for these outcomes in patients with spontaneous bacteremia. RESULTS: Seventy-one patients with spontaneous bacteremia and 55 patients with spontaneous bacterial peritonitis were included. Most infections were nosocomial. Overall, 26% of bacteria were resistant and 11% multi-resistant. We found no significant association between acute kidney injury [subhazard ratio (sHR) 1.05 (95% confidence interval, CI 0.67-1.63, p = 0.83)] or death [sHR 1.15 (95% CI 0.60-2.20, p = 0.68)] and type of spontaneous infection in multivariate analyses adjusting for basal Model for End-Stage Liver Disease (MELD) score. In patients with spontaneous bacteremia, baseline MELD score was independently associated with acute kidney injury [sHR 1.07 (95% CI 1.03-1.11, p = 0.001)] and death [sHR 1.07 (95% CI 1.02-1.15, p = 0.03)]. CONCLUSIONS: Short-term acute kidney injury and mortality rates were similar in patients with spontaneous bacteremia and spontaneous bacterial peritonitis. Risk assessment of patients with spontaneous bacteremia can be performed with baseline MELD score.