Academic hepatology capacity in Latin America is highly heterogeneous, yet no standardized regional framework exists to quantify structural differences across countries. We aimed to develop and apply the Global Academic Hepatology Capacity Index (IGCAH), a composite metric integrating academic, clinical, and research dimensions, to characterize cross-country inequities in the region. National hepatology societies from 20 Latin American countries completed a 54-item structured survey. Five domain indices: human capacity, academic training, scientific productivity, clinical complexity, and collaboration/networking, were constructed using standardized z-scores and integrated into the IGCAH. Findings were triangulated with bibliometric analysis of PubMed-indexed hepatology publications (2015-2025) and thematic analysis of abstracts submitted to the ALEH 2025 Congress. Complete responses were obtained from all 20 countries. The five highest-performing countries concentrated over 80% of the hepatology workforce, formal training programs, research infrastructure, and access to advanced therapies (IGCAH >0.8). Overall, 55% of countries lacked formal specialty recognition, 45% reported absence of essential laboratory infrastructure, and only 50% met criteria for sufficient diagnostic and therapeutic complexity. Clinical services were centralized in ≤2 major cities in 70% of countries, and ten reported ≤2 national liver disease registries. Scientific productivity was highly concentrated, with four countries accounting for approximately 85% of PubMed-indexed hepatology publications, while more than half produced ≤5 papers annually. ALEH 2025 abstracts mirrored these disparities, with 75% originating from five countries; most were observational and clinical trials were scarce. Profound asymmetries characterize academic hepatology in Latin America. The IGCAH provides a robust framework to identify structural gaps and guide targeted, stage-specific capacity strengthening.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease but remains widely under-recognized in primary care. The 2023 shift from "nonalcoholic fatty liver disease" to MASLD emphasized metabolic dysfunction as a driver of disease but introduced new communication and educational challenges for primary care providers (PCPs). We aimed to assess PCPs' awareness, risk assessment, and management practices related to MASLD in the four most populous U.S. cities. A cross-sectional online survey was conducted from 5 to 13 September 2024 among 800 primary care providers (PCPs; n = 200 per city) in New York City, Los Angeles, Chicago, and Houston. Participants included physicians, physician assistants, nurse practitioners, and other primary care professionals. The survey assessed awareness of "MASLD" and "fatty liver disease", risk assessment practices for high-risk groups, patient discussions, management strategies, and the use of patient-reported outcomes (PROs). Descriptive statistics characterized sample responses, and logistic regression models identified correlates of awareness. Overall, 54.7% of PCPs reported awareness of MASLD and 86.6% were aware of fatty liver disease. Awareness of MASLD was highest among physicians (81.3%) and hospital-based practitioners (odds ratio [OR] = 2.02, 95% confidence interval [CI] 1.02-4.02) and lowest among nurse practitioners (OR = 0.21, 95% CI 0.09-0.49). Awareness of fatty liver disease increased with provider age (OR = 1.04, 95% CI 1.00-1.08). Lifestyle modification was the most recommended management approach (41.3-65.5%), while referral rates to specialists and PRO use varied substantially across cities, and 48.5% were aware of the FIB-4 Index. Only half of PCPs recognized the term MASLD, highlighting gaps in awareness and clinical practice following the mid-2023 terminology change. Targeted educational initiatives and standardized implementation of MASLD guidelines in primary care are needed to improve timely detection and management of this highly prevalent condition.
Patients with end-stage liver disease (ESLD) often experience high symptom burden and frequent hospitalizations. Despite studiedbenefits ofpalliative care consultation services (PCCS), use in patients with ESLD is underutilizedand typically occurs weeks or days before death. Weexamined patterns of PCCS utilization, associated outcomes, and healthcare costs in hospitalized patients with ESLD. We retrospectively reviewed 3,983 patients (13,509 encounters) with ESLD from 2015-2023, excluding188 patients. We compared length of stay (LOS), mortality, disposition, readmissions, emergency department visits, and costs between patients receiving PCCS and those receivingusual care (UC), usingdescriptive analyses (Chi-square, Fisher's exact, and Student's t-tests)and multivariable logistic regression. Analyses were performed using SAS 9.4. Among 12,821 hospitalizations, 6.3% involved PCCS. Because this denominator included all hospitalizations among patients with ESLD, we performed a diagnosis-based secondary analysis using principal problem, primary diagnosis, and diagnosis present on admission fields. Of classified encounters, 70.7% were non-liver primary admissions, 19.8% were supportive of possible ESLD/decompensation admissions, and 9.5% were definite ESLD/decompensation admissions. PCCS occurred in 9.4% of definite ESLD/decompensation admissions. These patients weremore likely to requiremechanical ventilation (OR 2.3, 95% CI [1.79-3.03]), paracentesis (1.9[1.16-3.0]), and ICUadmission (4.2[3.51-5.13]). Theyhad higher in-hospital and 30-day mortality (OR1.48[1.24-1.78] and OR3.1[2.39-3.89], respectively), decreased likelihood of discharge home (OR 0.58 [0.48-0.70]), longer LOS (16.2 versus 7.4 days, p<0.05), and higher total costs($59,684 versus $23,750, p<0.05). Among patients who died during hospitalization after receiving PCCS, the median interval from consultation to death was 7 days (IQR 3-13). In this multihospital retrospective cohort, inpatient palliative care consultation in ESLD was uncommon and often occurred late in the hospitalization course. The overall encounter-level PCCS rate was partly influenced by inclusion of non-liver primary admissions, though PCCS utilization remained low, even among definite ESLD/decompensation admissions. Among in-hospital decedents who received PCCS, the short interval from consultation to death suggests late integration of palliative care near the end of life. Further prospective studies are needed to clarify optimal consultation timing and identify strategies to embed palliative care effectively within ESLD.
Perihilar cholangiocarcinoma (pCCA) is a rare and complex liver malignancy requiring specialized care in academic centers and multidisciplinary teams (MDTs). This study aimed to evaluate the impact of academic centers, academic MDTs, and regional collaboration on treatment outcomes. Patients with pCCA between 2017 and 2021 were identified from the Dutch Cancer Registry. The impact of center of initial diagnosis, including academic and non-academic center, and the involvement of academic MDTs were analyzed. Outcomes included tumor-directed therapy and overall survival (OS). In total, 1365 patients were included; 155 (11.4%) initially presented in an academic centers. Initial biliary drainage in academic centers was associated with lower 90-day mortality (25.0% and 40.5%, P < 0.001) compared with non-academic centers. Initial diagnosis in an academic center was associated with higher rates of tumor-directed therapy (63.5% vs 32.0%, P < 0.001) and surgery (36.1% vs 14.7%, P < 0.001). Expert MDT evaluation, regardless of center of diagnosis, showed higher rates of tumor-directed therapy (45.5% vs 9.9%, P < 0.001) and surgery (23.8% vs 2.5%, P < 0.001). Additionally, academic MDTs were independently associated with improved OS (HR 0.55 95% CI 0.48-0.63, P < 0.001) in multivariable analysis. Patients with pCCA discussed in academic MDTs had higher rates of tumor-directed therapy and improved OS. This association may partly be explained by patient selection and referral patterns. Nevertheless, these findings emphasize the importance of regional collaboration and centralization of care to ensure that all patients benefit from specialized expertise and coordinated treatment planning.
Living donor liver transplantation is a critical treatment for end-stage liver disease, with numerous advantages over deceased donor liver transplant. However, living liver donors face potential long-term physical, psychological, and social challenges. This review summarizes the long-term impact of donation and highlights the ethical need for lifelong follow-up. While major complications occur in 2-8% of donors, evidence on outcomes beyond one year remains limited. Biliary complications remain the most frequent serious morbidity, and are generally managed endoscopically, rarely requiring hepaticojejunostomy. Incisional hernias occur in up to 20% of donors, and diaphragmatic hernias are uncommon but potentially life-threatening. After the first postoperative year, many donors report persistent incisional numbness, and 27% experience chronic pain. Cosmetic concerns affect body image and mental health, though minimally invasive techniques improve these outcomes. Nearly 80% of donors return to work within 3 months, and physical quality of life usually returns to baseline within 6-12 months. However, one-quarter report ongoing activity limitations. Financial burden persists for 22-40% of donors, even two years post-donation. Psychologically, the majority of donors express no donation-related regret, although depression and anxiety affect approximately 8% of donors. Perioperative mortality is extremely low, with further improvements over time, and long-term survival parallels matched controls; however, donors have a higher risk of suicide and certain cancers. Current evidence supports extending donor monitoring beyond one year, with particular emphasis on psychiatric screening and targeted health surveillance. A global registry of long-term donor outcomes would strengthen risk stratification and optimize donor care.
Nonselective β blockers (NSBBs) may be involved in reducing gut-derived inflammation and intrahepatic inflammation to prevent hepatocellular carcinoma (HCC). This study aimed to systematically investigate their association. PubMed, EMBASE, and Cochrane Library databases were searched to identify all relevant studies evaluating the association of NSBBs with HCC in liver cirrhosis patients. Sensitivity analyses were performed to explore potential sources of heterogeneity. Risk ratios (RRs) and hazard ratios (HRs) were pooled. Subgroup meta-analyses were performed according to the study design, regions, type of NSBBs, and indications of NSBBs. Twenty-four studies were finally included. Overall meta-analyses demonstrated that NSBBs were associated with a significantly reduced risk of HCC development in liver cirrhosis patients (RR=0.86; P = 0.048). Sensitivity analysis did not find the source of heterogeneity. Subgroup analyses based on adjusted cohort studies with propensity-score matching (RR=0.85; P = 0.01) and multivariable regression model (HR=0.66; P < 0.00001), studies performed in America (RR=0.83; P = 0.007) and Europe (RR=0.72; P = 0.05), studies included patients receiving carvedilol (RR=0.72; P < 0.00001), nadolol (RR=0.86; P < 0.0001), and propranolol with dosage > 40 mg (RR=0.28; P < 0.00001) or follow-up duration < 20 months (RR=0.38; P = 0.04) demonstrated that NSBBs significantly decrease the risk of developing HCC in liver cirrhosis patients. However, studies included patients receiving primary or secondary prophylaxis of variceal bleeding did not reveal the protective effect of NSBBs on HCC. NSBBs may play a role in preventing the occurrence of HCC in liver cirrhosis patients. Future research should focus on risk stratification and monitoring protocols to advance personalized prevention.
Hepatitis C virus (HCV) infection promotes liver fibrosis through mechanisms involving epithelial-mesenchymal transition (EMT). Plasminogen activator inhibitor-1 (PAI-1), encoded by the SERPINE1 gene, is a known modulator of EMT and is upregulated during HCV infection. This study aimed to explore the contribution of PAI-1 silencing to EMT-related biomarker regulation in the context of HCV protein expression. Huh7 cells were transfected with plasmids encoding HCV Core or NS5A proteins and subjected to SERPINE1 silencing. Some EMT-related biomarkers (TGFβ1, vimentin, E-cadherin) and viral protein levels were assessed by Western blot and nanoluciferase assays. Bioinformatic analysis of RNA-seq public datasets was performed to evaluate SERPINE1 expression in liver fibrosis stages and HCV-infected hepatocytes in vitro. In vitro assays revealed that PAI-1 silencing is associated with the downregulation of E-cadherin and the upregulation of vimentin and TGFβ1 in both Core- and NS5A-expressing Huh7 cells. Temporal analyses confirmed that PAI-1 silencing is related to vimentin and TGFβ1 overexpression over time. Bioinformatic analysis revealed SERPINE1 expression increased with liver fibrosis severity and was elevated in HCV-infected hepatocytes. It showed strong positive correlations with genes involved in EMT. Our data indicate that PAI-1 may contribute to the modulation of certain EMT-related biomarkers during HCV protein expression in Huh7 cells. These findings highlight PAI-1 as a possible target for the modulation of EMT and fibrosis progression in chronic HCV infection.
ASAP is a multivariable risk model for hepatocellular carcinoma (HCC). This prospective pilot study evaluated its performance, based on a previously established cut-off value, in predicting HCC risk in patients with chronic liver disease and compare it to alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) alone. This study followed prospective-specimen collection and retrospective-blinded-evaluation (PRoBE) guidance for a phase III biomarker study. Patients undergoing 6-monthly HCC surveillance with ultrasound and AFP were enrolled between December 2017 and October 2018. Serum samples for AFP and PIVKA-II were obtained at surveillance and ASAP scores were calculated. Kaplan-Meier and Cox regression models were used to evaluate the predictive performance of ASAP algorithm and biomarkers for HCC development. Of 612 patients enrolled, 15 developed HCC (all early stage) during a median follow-up of 52.2 months. Using a two-tier risk approach, ASAP model, AFP and PIVKA-II were able to stratify risk of HCC development over time. ASAP low-risk group had the lowest 12-month HCC cumulative risk at 0.18%, versus PIVKA-II at 0.19%, and AFP at 0.51%. Cox modelling demonstrated that increased ASAP score was associated with higher risk of HCC (HR 1.80 for 10% increase, p < 0.001), with ASAP providing the highest C-index of 0.7706 versus AFP (0.7285) and PIVKA-II (0.6840). In this pilot study, the ASAP model demonstrated high accuracy in stratifying the risk of HCC development in patients. It can potentially identify high-risk patients while sparing low-risk individuals from unnecessary imaging surveillance.
Abernethy malformation, also known as congenital extrahepatic portosystemic shunt (CEPS), is a rare vascular anomaly characterized by diversion of portal venous blood into the systemic circulation. In type I CEPS, intrahepatic portal venous branches are absent, resulting in complete bypass of portal inflow to the liver. Hepatocellular carcinoma (HCC) has been reported as a rare but serious complication of this condition and published data are limited to isolated case reports and small series. We performed a pooled descriptive analysis of published case reports describing histologically confirmed HCC arising in patients with type I Abernethy malformation. Only cases with complete diversion of portal flow and absent intrahepatic portal branches were included. In addition, one case from our institution was incorporated. Demographic characteristics, clinical presentation, laboratory findings, imaging features, management strategies, and reported outcomes were extracted and summarized descriptively. Eighteen patients were identified. The median age at HCC diagnosis was 45.5 years and 13/18 (72%) of patients were male. Clinical presentation varied; 7/18 (39%) of patients were asymptomatic and had tumors that were detected incidentally, while abdominal pain was the most common presenting symptom, with 7/18 (39%) patients presenting with this complaint. Liver biochemistry was normal or mildly abnormal in 13/18 patients (72%), and alpha-fetoprotein was normal or minimally elevated in 13/18 (72%). Cardiac anomalies were present in 7/18 patients (39%), and 9/18 (50%) had multisystem comorbidities. Management strategies included liver transplantation, surgical resection, and locoregional therapies, including transarterial radioembolization and stereotactic body radiation therapy. At last follow-up, 9/18 patients (50%) were alive without recurrence. Hepatocellular carcinoma arising in type I Abernethy malformation occurs across a wide age range and often without serum tumor marker elevation. Imaging-based surveillance and anatomy-driven management strategies are essential to optimize outcomes.
Early allograft dysfunction (EAD) substantially compromises graft and recipient outcomes; the clinical consequences of EAD vary according to severity. Research focusing on EAD in pediatric liver transplantation (pLT) remains notably limited. This study sought to validate the EAD severity grading models in pLT and assess the impact of varying severity grades of EAD on both graft and recipient outcomes. This retrospective study enrolled 360 patients who performed pLT (living-donor liver transplantation (LDLT)=299, deceased-donor liver transplantation (DDLT)=61) between April 2017 and September 2024. The severity of EAD was graded using the Liver Graft Assessment Following Transplantation (L-GrAFT7) risk score. The incidence of binary EAD in pLT was 34.2%. The area under the receiver operating characteristic curve of EAD, Model for Early Allograft Function (MEAF) score, and l-GrAFT7 risk score for predicting graft loss within 90-day post-transplant were 0.84, 0.97, and 0.96 in the LDLT cohort; and 0.79, 0.78, and 0.95 in the DDLT cohort. Significant differences were observed among the low-, moderate-, and high-risk groups in the LDLT cohort regarding ventilator support time, ICU stay time, length of hospitalization, death in hospital, early complications (including hepatic artery thrombosis, portal vein thrombosis, hepatic vein/inferior vena cava stenosis/thrombosis, and biliary complications), and late complications (including hepatic artery thrombosis, portal vein stenosis/thrombosis and hepatic vein/inferior vena cava stenosis). In the DDLT cohort, significant differences were found among the three groups in terms of ICU stay time, death in hospital, early complications (including intra-abdominal bleeding and biliary complications), and late complications (hepatic vein/inferior vena cava stenosis) (p < 0.05). The log-rank test revealed statistically significant differences in graft and recipient survival among the three groups within 90-day, 180-day, and 1-year in both the LDLT and DDLT cohorts (p < 0.05), with this significant difference also observed throughout follow-up period in the DDLT cohort (p < 0.05). The MEAF score and l-GrAFT7 risk score effectively predict early graft loss following pLT, with high-risk EAD markedly compromising both short- and long-term graft and recipient outcomes.
Chronic hepatitis B virus (HBV) infection remains a major cause of cirrhosis and hepatocellular carcinoma worldwide, with substantial public health implications in Latin America. Despite the availability of an effective vaccine, HBV continues to be underdiagnosed and undertreated across the region, where healthcare access is often limited and heterogeneous. In alignment with the World Health Organization's 2024 strategy for HBV elimination, the Latin American Association for the Study of the Liver (ALEH) presents updated regional guidelines to simplify diagnosis, expand treatment eligibility, and improve vaccination coverage. The recommendations emphasize the use of rapid diagnostic tests and reflex HBV DNA testing to overcome barriers to laboratory access, while promoting non-invasive methods to assess liver disease severity. Expanded treatment criteria include patients with significant fibrosis, elevated HBV DNA levels, co-infections, and other risk factors, ensuring broader access to antiviral therapy with tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), or entecavir (ETV). Preventing mother-to-child transmission through universal screening, maternal prophylaxis, and timely neonatal vaccination is prioritized. Additionally, universal HDV testing in HBV-infected patients is recommended. These guidelines highlight the urgent need for decentralization, simplification, and equity in HBV management to achieve elimination goals in Latin America by 2030.
Frailty is highly prevalent in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD). However, the extent to which frailty influences cardiovascular disease (CVD) incidence, cardiovascular mortality, and all-cause mortality in MASLD individuals remains poorly understood. This study aimed to evaluate the impact of frailty on cardiovascular outcomes and mortality in this population. A total of 193,942 participants without prior CVD from the UK Biobank were included. Participants were categorized into three groups based on frailty phenotype: non-frailty, pre-frailty, and frailty. MASLD was defined as hepatic steatosis accompanied by at least one cardiometabolic abnormality. The primary outcome was CVD incidence, with secondary outcomes including cardiovascular and all-cause mortality. After multivariate adjustment, the risk of CVD was higher in MASLD participants with pre-frailty (HR 1.08, 95% CI 1.05-1.12) and frailty (HR 1.41, 95% CI 1.33-1.49) than in those with non-frailty. The association of frailty with CVD was strongest in participants with MASLD and advanced fibrosis (HR 2.60, 95% CI 2.04-3.30), intermediate in MASLD without fibrosis (HR 1.73, 95% CI 1.63-1.84), and weakest in non-MASLD (HR 1.58, 95% CI 1.47-1.70). Similar results were also observed for cardiovascular mortality. Furthermore, among the five components of frailty phenotype, slow gait speed demonstrated the strongest associations with the risks of CVD incidence in MASLD, cardiovascular mortality, and all-cause mortality. Frailty was associated with increased risks of CVD incidence, cardiovascular mortality, and all-cause mortality among individuals with MASLD, particularly those with a higher fibrosis burden as defined by FIB-4.
Treatment response of ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) is assessed after 12 months by Paris II criteria. In the German PBC registry, individuals were stratified into adequate and inadequate Paris II responders. We analyzed the concordance between clinical judgement and formal Paris II classification. Physician-assessed UDCA treatment response was compared to formal Paris II criteria (alkaline phosphatase (ALP) or aspartate-aminotransferase (AST) >1.5 x ULN or bilirubin >1 mg/dL). 10/130 (8%) cases were misclassified as inadequate UDCA responders, 44/253 (17%) as adequate responders despite not meeting Paris II criteria. Incorrectly classified responders occurred in 26% versus 13% of individuals at secondary and tertiary centers (p = 0.0141). At secondary centers, 86% of misclassified responders had ALP >1.5 × ULN and 5% had bilirubin >1 mg/dL, compared with 32% and 27% at tertiary centers. ALP levels >1.5 x ULN occurred significantly more often at secondary centers (p = 0.0005). At secondary centers, ALP levels at diagnosis were higher in misclassified versus correctly classified responders (3.6 ± 3.0 x ULN vs. 1.7 ± 0.9 x ULN, p < 0.001) and remained higher after 12 months of therapy (2.3 ± 1.2 vs. 0.9 ± 0.3 × ULN, p < 0.001). Clinical judgement and Paris II classification differ in 20% of patients. Higher baseline ALP levels and kinetics may lead to misclassification. This may result in withholding of second line treatments in these patients.
The α7 nicotinic acetylcholine receptor (α7nAChR) plays a central role in modulating inflammation and cellular homeostasis. However, its role in liver regeneration remains poorly understood. The role of α7nAChR in liver regeneration was investigated in Chrna7⁻/⁻ mice and wild-type controls subjected to partial hepatectomy (PHx), focusing on autophagy markers. During the priming phase, Chrna7⁻/⁻ mice presented increased levels of adiponectin and IL6 transcripts compared to WT. Female Chrna7⁻/⁻ mice exhibited impaired STAT3 phosphorylation and p62 and LC3-II accumulation, increased protein ubiquitination, and reduced Atg5 gene expression compared to WT. These early defects worsened during the proliferative phase, with increased lipid accumulation, decreased KI67 and PCNA, and sustained modulation of autophagy markers, leading to compromised hepatocyte proliferation and higher mortality. In males, the priming phase was characterized by reduced JAK2 expression but activation of compensatory pathways, such as increased pAMPK and elevated protein ubiquitination in Chrna7⁻/⁻ mice, alongside hints of autophagy changes shown by p62 and LC3-II accumulation, compared to WT. The proliferative phase was marked by increased lipid accumulation and reduced KI67 and PCNA. Alongside a paradoxical autophagic state, characterized by downregulated autophagosome formation genes (Atg5 and Beclin1) with elevated LC3-II and decreased p62 (markers of autophagic flux), suggests a differential modulation of the autophagic machinery. Overall, α7nAChR deficiency led to impaired liver regeneration through distinct sex-specific changes in autophagy markers, resulting in increased mortality. These findings underscore α7nAChR as critical for autophagy homeostasis during liver regeneration and its potential as a therapeutic target.
Autoimmune hepatitis (AIH) is diagnosed based on clinical, biochemical, immunological, and histological parameters, and on the exclusion of other liver diseases. Multiple scoring systems are available for AIH diagnosis, all of which require liver biopsy (LB). With the aim of reducing invasive procedures to minimize patient's risks, this study evaluated whether LB may be spared for AIH diagnosis in some children, similar to primary biliary cholangitis. Children with histologically confirmed autoimmune liver disease (AILD) were evaluated from 5 Pediatric Units. We retrospectively collected clinical, laboratory, imaging and histological data to assess AIH diagnostic scores (International Autoimmune Hepatitis Group [IAIHG] criteria, juvenile AIH score [JAIH], and simplified criteria [s-IAIHG]) in each patient pre- and post-LB. The diagnosis of autoimmune sclerosing cholangitis (ASC) was based on magnetic resonance cholangiopancreatography and liver histology. Ninety-one patients (55 females) were evaluated (36 with AIH type I, 24 with AIH type II, 8 with seronegative AIH, and 23 with ASC). The mean age at diagnosis and duration of follow-up were 8.9 ± 4.8 and 9.6 ± 7.8 years, respectively. Based on IAIHG, JAIH and s-IAIHG scores, pre-LB scores were "definite" for 15.3%, 49.5%, and 0% of patients, respectively. Post-LB, the diagnosis was confirmed in all these patients. We found no associations between liver histological findings or diagnostic scores and relapses or treatment withdrawal. In patients with a "definite" AIH score pre-LB, LB is not necessary for diagnosis. Histological findings and scoring systems do not predict relapses or treatment withdrawal.
Spontaneous bacterial peritonitis (SBP1) is a common complication of cirrhosis. In the United States, inconsistent norfloxacin availability has shifted secondary SBP prophylaxis toward ciprofloxacin or trimethoprim-sulfamethoxazole (TMP-SMX2), but these agents have not been robustly compared head-to-head. We compared clinical outcomes among patients receiving TMP-SMX versus ciprofloxacin for secondary SBP prophylaxis. We conducted a multicenter retrospective cohort study using the TriNetX de-identified electronic health record network. Adults with cirrhosis (ICD-10 K74.6) and SBP (ICD-10 K65.2) from January 2013 to July 2021 were included. Index date was the first prescription for TMP-SMX (RxNorm 10,829/10180) or ciprofloxacin (RxNorm 2551), with follow-up through July 11, 2024. Exclusions included prior exposure to the alternative agent, liver transplant, or end-stage renal disease. We performed 1:1 greedy nearest-neighbor propensity score matching (caliper 0.1) on demographics, comorbidities, and hepatic/renal laboratory variables. Primary outcomes were SBP recurrence and all-cause mortality; secondary outcomes included all-cause hospitalization, variceal bleeding, hepatic encephalopathy, and ascites. Cox proportional hazards models estimated hazard ratios (HRs). Among 31,011 patients (TMP-SMX 11,166; ciprofloxacin 19,845), 11,140 well-balanced matched pairs were analyzed. TMP-SMX was associated with lower SBP recurrence (HR 0.75, 95% CI 0.72-0.79) and all-cause mortality (HR 0.84, 95% CI 0.80-0.87; both p < 0.0001). TMP-SMX also reduced risks of variceal bleeding (HR 0.81), hepatic encephalopathy (HR 0.79), and ascites (HR 0.86), while hospitalization was not significantly different. TMP-SMX was associated with significantly lower SBP recurrence and mortality than ciprofloxacin, supporting TMP-SMX as a potentially more effective secondary prophylaxis option pending randomized confirmation.
Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a rapidly increasing global public health challenge. The objective was to analyze MASLD trends in Mexico by sex and state (1990-2023) and assess the association between the MASLD burden and the Socio-Demographic Index (SDI). Secondary analysis of Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2023 data (NAFLD definition, interpreted under the 2023 MASLD nomenclature) conducted across Mexico's 32 states and nationally. We examined key burden indicators like mortality, years lived with disability (YLD), years of life lost (YLL), and disability-adjusted life years (DALY). We used a Joinpoint regression to identify significant trends and the Pearson correlation coefficient to estimate the relationship between DALY rates and the SDI. Between 1990 and 2023, the national MASLD deaths increased significantly by 229%. Male DALY rates were 2.2 times higher than female rates in 2023, and premature mortality accounted for almost all the burden (around 97%). YLD rates increased significantly, particularly among males, indicating a growing contribution of disability to the total impact of the disease. Sub-nationally, DALY rates rose significantly in 21 states, although declines occurred in Mexico City, Hidalgo, and Jalisco. Nationally, a significant positive correlation (0.71) was found between the DALY rates and the SDI. These results suggest that socioeconomic development in most regions is associated with the adoption of unhealthy lifestyles and dietary patterns. Future policy interventions must include targeted health campaigns, especially for adult men and women aged between 60-84 years, to mitigate the accelerating trend, alongside regulatory actions necessary to control Mexico's obesogenic environment.
Ascites is the most frequent complication in patients with cirrhosis. Although guidelines propose diuretic treatment monitoring through measuring spot urine sodium, data on its application in clinical care as well as its independent prognostic information are surprisingly scarce. We therefore aimed to evaluate the role of spot urine parameters in patients with cirrhosis and ascites. We analysed patients managed at the Medical University of Vienna between 2011 and 2024. Data on urine spot analyses were obtained within 30 days of first ascites development and longitudinally thereafter. The prognostic implication for predicting recurrent ascites within 180 days was evaluated. One-hundred and ten patients (61% male, main aetiology alcohol-related liver disease in 61%) were included. Median spot urine sodium was significantly different according to ascites severity and diuretic therapy (grade II + diuretics: 119.0 vs. grade III + diuretics: 54.5 mmol/L; grade II + no diuretics: 60.0 vs. grade III + no diuretics: 16.0 mmol/L). However, neither baseline nor longitudinal spot urine sodium provided independent prognostic information for the development of recurrent ascites within 180 days after adjustment for liver disease severity. Similarly, the spot urine sodium/potassium ratio, analysed continuously or using established cut-offs, was not independently associated with recurrent ascites. These findings remained consistent in sensitivity analyses considering recurrent ascites within 90 days and after accounting for diuretic therapy. Spot urine analyses around index ascites decompensation were not associated with the development of recurrent ascites in the current study.
Unexplained elevated liver enzymes (ELE) are common and often linked to metabolic dysfunction-associated steatotic liver disease (MASLD). Diagnosis in primary care is difficult due to limited access to advanced imaging, highlighting the need for simple non-invasive tools. This study aimed to develop and validate a pragmatic, laboratory-based score to predict hepatic steatosis in patients with unexplained ELE. A derivation cohort of 206 patients with 40 classified as steatosis-positive with a NAFLD Activity Score (NAS) ≥4 was analyzed. Candidate predictors were tested by univariate analysis and entered into multivariate logistic regression. Regression coefficients were scaled to construct an integer-based score (HABIT). Validation was performed in a retrospective cohort of patients with unexplained ELE attending our hepatology clinic between 2019 and 2021(n = 648), all undergoing standardized diagnostic work-up including ultrasound, elastography, and laboratory testing. Multivariate analysis identified HbA1c, body mass index (BMI), and triglycerides as independent predictors of steatosis. The HABIT score was derived as: (61 × HbA1c [%]) + (3 × BMI [kg/m²]) + Triglycerides [mg/dL]. Diagnostic accuracy was high in the derivation cohort (AUROC: 0.83) and robust in validation (AUROC: 0.81), outperforming the Hepatic Steatosis Index (HSI, AUROC: 0.77). Cut-offs <490 and >630 reliably ruled out (sensitivity 93.6 %) or confirmed (specificity 92.5 %) steatosis. Score values correlated significantly with ultrasound grades and CAP. The HABIT score is a simple, robust tool for identifying hepatic steatosis in unexplained ELE. It outperforms HSI and may facilitate early detection and risk stratification in primary care with limited diagnostic resources.
Stem cell therapies have shown potential in treating liver cirrhosis and acute-on-chronic liver failure by promoting liver regeneration. However, their efficacy and safety remain uncertain due to inconsistent results. This systematic review and meta-analysis aimed to evaluate efficacy and safety of stem cell therapies in patients with liver cirrhosis and acute-on-chronic liver failure, compared to standard of care or placebo. We conducted a systematic review and meta-analysis following PRISMA guidelines. Randomized controlled trials (RCTs) comparing stem cell therapies to standard medical care or placebo for patient important outcomes were included. Risk of bias was assessed using Cochrane RoB 2 tool, and quality of evidence was evaluated with GRADE framework. A total of 19 studies were included. Meta-analysis of 15 RCTs (n = 925) provided very low-certainty evidence regarding effects of stem cell therapy on overall mortality. The pooled risk ratio (RR) for mortality was 0.63 (95% CI 0.43 to 0.91; I² = 60%). Ten RCTs (n = 250) assessed effect of stem cell therapy on Model for End-Stage Liver Disease (MELD) scores. The pooled mean difference (MD) was -1.22 (95% CI -2.25 to -0.19; I² = 51%). The certainty in evidence was rated down for risk of bias and imprecision for most outcomes. This systematic review and meta-analysis provides very low-certainty evidence regarding efficacy of stem cell therapies for liver cirrhosis and acute-on-chronic liver failure. Further high-quality research is necessary to clarify role of stem cells in treating liver diseases and to ensure safety and efficacy.