Hepatology Communications最新文献

Background: Opioid use contributes to significant morbidity, posing specific risks to liver transplant recipients (LTRs). This study aimed to characterize outpatient opioid use before and after liver transplantation (LT) and identify risk factors for high-risk, incident, and chronic use and related complications.

Methods: Adult LTRs were identified from 2006 to 2021 in IQVIA PharMetrics Plus for Academics, a claims database representative of the commercially insured US population. Opioid use was evaluated 30-365 days after LT; high-risk use was defined as >50 morphine milligram equivalents (MMEs) per day or concurrent opioid-benzodiazepine use. Factors associated with use, including high-risk use, were identified using multivariable logistic regression analysis. Landmark analyses assessed the association between outpatient opioid use 30-120 days post-LT and incident adverse events (eg, psychiatric, substance use, chronic pain, fractures/falls, digestive).

Results: Among 1338 LTRs, 899 (67.2%) received outpatient opioid prescriptions >30 days post-LT, of whom 553 (41%) had incident use; 122 (13.6%) had high-risk opioid use. Factors significantly associated with high-risk use were female sex, pre-LT opioid use, and psychiatric disorder. Opioid use was significantly associated with increased adverse events 120-365 days post-LT; 59% of LTRs with opioid use within 1 year of LT developed complications compared to 39% of non-opioid users during this window (p<0.001). In adjusted landmark analyses, low/moderate opioid use within 30-120 days post-LT was associated with 1.87 times the hazard of complications compared to no opioid use at 120 days post-LT (95% CI: 1.14-3.07) and high-risk opioid use was associated with 2.87 (95% CI: 1.05-7.85) times the hazard.

Conclusions: Post-LT opioid use is associated with increased risk of adverse events. Caution is needed in opioid prescribing beyond the perioperative period, particularly for those with preexisting psychiatric conditions.

Background: Terlipressin is the only FDA-approved vasoconstrictor for hepatorenal syndrome (HRS). The CONFIRM study is the largest trial of terlipressin versus placebo. Novel predictors of HRS response are required to enrich patient selection and optimize outcomes.

Methods: Samples at treatment initiation were tested using (a) liquid chromatography-mass spectrometry of 1594 plasma/1420 urine metabolites (Metabolon Inc.), (b) aptamer-based array of 7289 plasma proteins (SomaScan), and (c) 14 plasma/urine pre-specified assays. The CONFIRM trial's original definition of HRS response [2 serum creatinine (SCr) <1.5 mg/dL separated by >2 h] was used as the primary outcome.

Results: In all, 115 patients [79 terlipressin-treated (TT) and 36 placebo-treated (PT)] provided samples. Baseline characteristics, outcomes, and 2:1 TT:PT allocation were preserved from the original 300-patient trial. A total of 36 out of 116 (31.0%) patients achieved HRS reversal. HRS reversal was associated with lower SCr (p=0.001), cystatin C (p=0.005), angiopoietin-2 (p=0.04), and beta-2 microglobulin (p=0.006). In metabolite analysis, PT had the most significant differences in HRS reversal [n=26 plasma, n=50 urine, including lower urine levels of those centered on sulfated secondary bile acids (microbiome-derived), N-acetylated amino acids, catechols (both uremic toxins), and phosphocholines (cell membrane integrity)], with fewer in TT (n=1 plasma, n=2 urine), and in all patients (n=3 plasma, n=7 urine). There were no significant aptamers associated with HRS reversal after false-discovery correction.

Conclusions: SCr, cystatin C, angiopoietin-2, and beta-2 microglobulin were associated with HRS reversal. Protein and metabolite signals centered on microbiome function and uremic toxins appeared more robust in PT patients, likely selecting a subgroup that may recover without terlipressin. Use of novel biomarkers may enrich for terlipressin response.

Background: The Barcelona Clinic Liver Cancer (BCLC) system for HCC was updated in 2022. The aim of the study was to assess the suitability and impact on overall survival (OS) of BCLC_2022, along with "clinical decision-making" (CDM), using BCLC_2018 as a benchmark.

Methods: We retrospectively evaluated 798 patients with de novo HCC followed prospectively from 2006 to 2022: 187 in BCLC 0, 371 in A, 132 in B, 87 in C, and 21 in D, all managed by a multidisciplinary team. Patients were followed until death or at the end of the follow-up period in December 2022.

Results: The suitability of the algorithm increased from 51% for BCLC_2018 to 69% for BCLC_2022 (p<0.001). Among those treated with the newly introduced "lower priority options," 22% were in BCLC 0 and 37% in A, showing lower rates of complete response (CR) and shorter OS compared to first-line treatments. In BCLC 0 and A, CDM was associated with a significant decrease in "downward stage migration" with BCLC_2022 (from 33% to 16%, p<0.001). Conversely, in BCLC B and C, "upward stage migration" correlated with higher CR rates and longer OS [63 (36-72) vs. 28 (18-44) months, p=0.003 in BCLC B; 21 (15-44) vs. 11 (4-25) months, p<0.001 in BCLC C]. Independent predictors of mortality included AFP >200 ng/mL, Child-Pugh score C, advanced BCLC stage, and noncurative treatment.

Conclusions: BCLC_2022 and CDM provide greater flexibility in clinical practice without adversely affecting patient survival. Access to curative treatments improves the outcomes of selected patients in all stages.

Liver fibrosis (LF) refers to the excessive deposition and abnormal distribution of the extracellular matrix (ECM) caused by acute or chronic liver injury, which affects the prognosis of liver diseases. Activated HSCs play a central role in LF through their ability to differentiate into myofibroblasts (MFBs) and secrete ECM. Intercellular communication within the liver is important for HSC activation and LF, whether in the initial or persistent stage. Hepatocytes (HCs), the most abundant cell type in the liver, are closely related to hepatic nutrition metabolism and detoxification. Moreover, HC damage is the initiating factor of LF, and interactions between HCs and HSCs may be the most critical event involved in the process of LF. This article reviews the intercellular communication between HCs and HSCs based on paracrine effects, extracellular vesicles, and inflammasomes, which is expected to lead to the development of effective antifibrotic strategies.

Background: HEV is an important cause of morbidity in solid organ transplant (SOT) recipients. However, the total burden of hepatitis E, including subclinical infections in this group, is not well defined. We compared hepatitis E exposures in SOT recipients to non-transplant controls. We also examined the prevalence of rat HEV (rHEV), an emerging hepatitis agent, in this population.

Methods: This study was conducted in the main SOT center in Hong Kong. Quantitative HEV IgG, RT-PCR, IgM, and IgG avidity assays were used to measure conventional HEV and rHEV exposures in 669 SOT recipients and 667 non-transplant hospitalized controls. Follow-up samples from a subset of SOT recipients were assessed to measure longitudinal HEV exposures.

Results: Age-adjusted HEV IgG seroprevalence in SOT recipients (236/669; 35.3%) was significantly higher than non-transplant controls (185/667; 27.7%; p=0.001). Across baseline and follow-up samples, 25 (3.7%) SOT recipients had viremia (n=3) or serological evidence (n=22) of recent hepatitis E. The latter had IgM positivity (n=5), IgG seroconversion (n=16), or a 5-fold increase in longitudinal HEV IgG concentrations (n=1). Chronic hepatitis occurred in all 3 viremic individuals, while transient hepatitis was observed in 10/22 (45.4%) SOT recipients with serological evidence of recent hepatitis E. rHEV IgG levels were similar between SOT recipients and controls (p=0.424), but 2 viremic infections in the SOT group were due to rHEV and both turned chronic.

Conclusions: SOT recipients have higher hepatitis E seroprevalence than the non-transplant population. Increased exposure is driven by viremic infections and a significant burden of subclinical infections in Hong Kong. rHEV is an important cause of chronic hepatitis E in SOT recipients.