Journal of Clinical and Experimental Hepatology最新文献

Background: Patients with cirrhosis are susceptible to infections due to abnormalities in humoral and cell-mediated immunity. Fungal infections are associated with delayed diagnosis and high mortality rates, emphasizing the importance of performing fungal cultures and maintaining elevated levels of suspicion in this patient population.

Methods: This retrospective cohort study analyzes cirrhotic patients readmitted with bacterial and fungal infections and investigates outcomes, including in-hospital mortality and hospital resource utilization. Data was acquired from the Nationwide Readmission Database (NRD) from 2016 to 2020. Total hospital costs were calculated using HCUP Cost-to-Charge Ratio files and adjusted for inflation based on the Consumer Price Index (CPI) for medical care services in the U.S., with 2020 as the reference year. The NRD dataset lacks details like ascitic fluid cell counts, antifungal/antibacterial drugs used, and treatment responses, limiting the clinical insights that can be derived.

Results: The study analyzed 393,195 index hospitalizations. Among these, 102,505 account for 30-day and 157,079 account for 90-day readmissions. The 30-day and 90-day readmissions for spontaneous bacterial peritonitis (SBP) are 8478 and 15,690 respectively. The 30-day and 90-day readmissions for spontaneous fungal peritonitis (SFP) are 3106 and 5798 respectively. The mean age of patients was 57.9 years (standard deviation between 57.7 and 58.1). The mean length of stay (LOS) for SBP at 30 days is 9.4 days, while SFP has ranged from 14.9 to 32.3 days for various fungal infections. Aspergilloses have the longest LOS among SFP. There is an increased rate of mortality as well as hospital charges with SFP compared to SBP (P < 0.001). The 30-day index admission total charges for SBP are $42,258 and SFP are $51,739. The 30-day readmission total charges for SBP are 64, 266 and for SFP 89,913.

Conclusions: There is increased mortality, LOS, and hospital costs for SFP compared to SBP. It is important to consider SFP in the diagnostic workup for patients who do not respond to antibiotics. Early recognition and administration of antifungals can be associated with improved outcomes.

Background: Inherited cholestatic liver disorders such as progressive familial intrahepatic cholestasis (PFIC) and Alagille syndrome result in significant pruritus and increased serum bile acids, necessitating liver transplantation. This study aims to evaluate the efficacy and safety of Ileal bile acid transport inhibitors (IBATIs) in children with PFIC and Alagille syndrome.

Methods: We conducted a comprehensive search across the databases to identify relevant randomized controlled trials (RCTs), and Covidence was used to screen eligible articles. All outcomes data were synthesized using risk ratios (RRs) or mean differences (MDs) with 95% confidence intervals (CIs) in RevMan 5.4. PROSPERO: CRD42024564270.

Results: Four multicenter RCTs involving 215 patients were included. IBATIs were associated with a significant reduction in Itch Observer Reported Outcome (Itch (ObsRo)) score (MD: -0.90, 95% CI [-1.17, -0.63], P < 0.01), serum bile acids (MD: -119.06, 95% CI [-152.37, -85.74], P < 0.01), total bilirubin (MD: -0.73, 95% CI [-1.32, -0.15], P = 0.01), and increased proportion of patients achieving ≥1 score reduction in Itch (ObsRo) score (RR: 2.54, 95% CI [3.83, 1.69], P < 0.01) and bile acid responders (RR: 8.76, 95% CI [2.46, 31.23], P < 0.01) compared with placebo. No differences were observed in any treatment-emergent adverse events (TEAs) (RR: 1.02, 95% CI [1.12, 0.93], P = 0.71), TEAs leading to drug discontinuation (1.03, 95% CI [5.56, 0.19], any serious TEAs, or liver-related TEAs.

Conclusion: IBATIs showed significant improvement in various cholestatic parameters with tolerable safety profile; however, future research on optimal dosage and long-term outcomes is needed.

Background: Locoregional therapy (LRT) in patients with hepatocellular carcinoma (HCC) before liver transplantation (LT) has a role in improving the tumor biology and post-LT survival outcome apart from downstaging and bridging. We retrospectively analyzed our database of adult living donor liver transplants (LDLT) for HCC, to compare the survival outcomes in Group-1 (upfront-LT, HCC within Milan/UCSF/AFP<1000 ng/ml) and Group-2 (LT post-LRT, HCC beyond UCSF/irrespective of tumor burden with AFP>1000 ng/ml). We also explored the risk factors for recurrence on follow-up.

Methods: A study group (n = 506, Group-1-348, Group-2 = 158) of patients with HCC who underwent LDLT between July 2006 and December 2022, excluding incidental HCC (n = 42), patients with other histology (n = 13) and in-hospital mortality (n = 43), were analyzed. Study cohort (n = 341), after propensity score matching, was analyzed for survival outcomes (overall survival, OS and disease-free survival, DFS) and risk factors for recurrence between Group-1 (n = 156) and Group-2 (n = 158).

Results: Group-2 exhibited a trend towards better mean OS and DFS compared to Group-1 (OS-133 vs. 107-months, P = NS, DFS-118 vs. 102-months, P = NS). Long-term OS (10-year) for those within Milan and UCSF criteria was superior in Group-2, P = NS. Complete pathological response (cPR) after LRT (46.8%), significantly improved OS and DFS compared to those with partial response and stable disease; 152 vs. 94 vs. 49 months, P = 0.001, and 147 vs. 75 vs. 41 months, P = 0.006, respectively. Recipient age, size of tumor, and pre-LT serum alpha-fetoprotein (AFP) were independent predictors of cPR. Independent risk factors for recurrence included pre-LT AFP, tumors beyond UCSF, perineural invasion, and high-grade tumors.

Conclusion: Locoregional therapy in HCC offers significantly better OS and DFS in those who had a complete pathological response. Risk factors for recurrence post-LT were AFP level, beyond UCSF tumors, and high-grade HCC with PNI on histology.

Background: Due to malnutrition and tumor cachexia, body composition (BC) is frequently altered and known to adversely affect short- and long-term results in patients with cholangiocarcinoma (CCA). Here, we explored immune cell populations in the tumor and liver of CCA patients with respect to BC.

Methods: A cohort of 96 patients who underwent surgery for CCA was investigated by multiplexed immunofluorescence (MIF) techniques with computer-based analysis on whole-tissue slide scans to quantify and characterize immune cells in normal liver and tumor regions. BC was characterized by obesity, sarcopenia, myosteatosis, visceral obesity and sarcopenic obesity. Associations between BC and immune cell populations were determined by univariate and multivariable binary logistic regressions.

Results: BC was frequently altered in intrahepatic CCA (iCCA, n = 48), with 47.9% of the patients showing obesity, 70.8% sarcopenia, 18.8% sarcopenic obesity, 58.3% myosteatosis and 54.2% visceral obesity as well as in perihilar CCA (pCCA, n = 48) with 45.8% of the patients showing obesity, 54.0 sarcopenia, 14.6% sarcopenic obesity, 47.9% myosteatosis and 56.3% visceral obesity. From an immune cell perspective, independent associations within the tumor compartment were observed for iCCA (myosteatosis: TIM-3+CD8+cells; obesity: PD-1+TIM-3+CD4+cells) and for pCCA (myosteatosis: PD-L2+CD68-cells and CD4+cells). Further, independent associations were observed within the normal liver parenchyma for iCCA (visceral obesity: PD-1+PD-L1+PD-L2+CD68+cells) and for pCCA (sarcopenia: CD68+cells and TIM-3+CD8+cells; visceral obesity: ICOS+-TIGIT+CD8+cells and sarcopenic obesity: PD-1+PD-L1+PD-L2+CD8+cells).

Conclusion: This is the first systematic analysis of the association of BC and immune cells in cholangiocarcinoma showing a strong association between BC and distinct immune cell populations within the tumor itself as well as within the normal parenchyma.

The global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is rising due to rapid lifestyle changes. Although females may be less prone to MASLD than males, specific studies on MASLD in females should still be conducted. Previous research has shown that sex hormone levels are strongly linked to MASLD in females. By reviewing a large number of experimental and clinical studies, we summarized the pathophysiological mechanisms of estrogen, androgen, sex hormone-binding globulin, follicle-stimulating hormone, and prolactin involved in the development of MASLD. We also analyzed the role of these hormones in female MASLD patients with polycystic ovarian syndrome or menopause, and explored the potential of targeting sex hormones for the treatment of MASLD. We hope this will provide a reference for further exploration of mechanisms and treatments for female MASLD from the perspective of sex hormones.

Background/aim: Post-hepatectomy liver failure (PHLF) and hepatic steatosis are evident shortly after extensive partial hepatectomy (PH) in rodents. This study aimed to extrapolate the protein expression and biological pathways involved in recovering PHLF (rPHLF) and non-recovering PHLF (nrPHLF).

Methods: Rats were randomly assigned to 90% PH or sham surgery. rPHLF was distinguished from nrPHLF using a quantitative scoring system. The sham (n = 6), rPHLF (n = 8), and nrPHLF (n = 13) groups were compared 24 h post-PH. Proteomics was used to assess protein variations and to investigate differentially regulated biological pathways. Stereological methods were used to quantify hepatic lipid content. The plasma triglyceride levels were measured.

Results: rPHLF demonstrated substantial downregulation of proteins involved in lipid metabolism compared to nrPHLF (P < 0.001). Several proteins associated with lipogenesis, beta-oxidation, lipolysis, membrane trafficking, and inhibition of cell proliferation were markedly downregulated in rPHLF.The hepatic lipid proportion was significantly higher for rPHLF (61% of hepatocyte volume, 95% confidence interval [CI]: 48%-82%) than for nrPHLF (32% of hepatocyte volume, 95% CI: 22%-39%). The median lipid volume per hepatocyte in rPHLF was 2815 μm³ (95% CI: 2208-3774 μm³) and 1759 μm³ in nrPHLF (95% CI: 1188-2134 μm³). Lipid droplets were not detected in the sham-operated rats. No significant differences in plasma triglyceride levels were found between the groups (P > 0.08).

Conclusion: The degree of hepatic steatosis is a promising prognostic indicator for early liver regeneration and nrPHLF onset immediately following extensive PH. Intrahepatic lipid accumulation appears to be linked to the coordinated downregulation of proteins integral to lipid metabolism and cellular transport.

Small-for-size syndrome is a clinical syndrome of early allograft dysfunction usually following living donor liver transplantation due to a mismatch between recipient metabolic and functional requirements and the graft's functional capacity. While graft size relative to the recipient size is the most commonly used parameter to predict risk, small-for-size syndrome is multifactorial and its development depends on a number of inter-dependant factors only some of which are modifiable. Intra-operative monitoring of portal haemodynamics and portal flow modulation is widely recommended though there is wide variation in clinical practice. Management of established small-for-size syndrome centres around meticulous patient care, infection prevention, fluid management and identifying correctable technical complications. However, retransplantation is the only treatment in severe cases. While small-for-size syndrome per se is associated with increased peri-operative mortality, the contribution of non-hepatic organ failure in determining patient outcomes needs further studies.

Background: Renal impairment significantly affects morbidity and mortality rates of cirrhosis patients. Studies on glomerular filtration rate (eGFR) estimation did not include cirrhosis patients. These equations are erroneous and unreliable in cirrhosis due to sarcopenia. Further, the accuracy of eGFR equations varies across different ethnic groups. Measurement of GFR by iohexol clearance is a gold standard method of accurate determination of GFR. There is scarce data on iohexol GFR in cirrhosis and none in Indian population.

Methodology: This was prospective observational study. Consecutive adult patients with cirrhosis with stable renal function for prior 1 month were included. Iohexol weight-based dosage was given and timed blood samples were taken to measure iohexol clearance. Plasma iohexol levels was measured by high performance liquid chromatography (HPLC) and Cystatin-C was measured by ELISA in plasma samples.

Results: Thirty-five patients were enrolled in the study. Hepatitis B (n = 5), hepatitis C (n = 4); alcoholic liver disease (n = 20), metabolic dysfunctional associated steatotic liver disease (n = 2), others/overlap (n = 3). The average eGFR by MDRD4, MDRD6, CKD-EPI Creat, CKD EPI Cys C, CKD EPI Creat-Cys C, RFHand GRAIL formulae were 105.24(24.2),104.75(23.5),102.14(15.9),68.91(16.5),82.91(15.21), 67.27 (14.08) and 112.9 (19.5) ml/min ml/min/1.73m², respectively. The average mGFR measured by iohexol method was 73.44 (16.8)ml/min/1.73 m². 30% agreement with mGFR was found with eGFR by MDRD4 in 38.2% (n = 13), MDRD6 38.2% ((n = 13), CKD-EPI Creat in 35.2% (n = 12), CKD EPI Cys C in 79.41% (n = 27), CKD EPI Creat-Cys C in 76.42% (n = 26), RFH 76.4% (n = 26) and GRAIL 20.5% (n = 7).

Conclusion: The eGFR equations using creatinine are imprecise and less accurate in Indian patients with cirrhosis. All equations overestimate GFR. Equations especially developed for cirrhosis patients like MDRD6 are also not precise. Cystatin C based equations are better than creatinine-based equations. Further studies with large sample size are needed to establish an accurate method of GFR assessment in Indian patients with cirrhosis.