Digestive and Liver Disease最新文献

Introduction

The potential benefits of adopting Metabolic dysfunction-associated steatotic liver disease (MASLD) rather than Metabolic dysfunction-associated fatty liver disease (MAFLD) diagnostic criteria in defining the disease progression risk of steatotic (SLD) patients have never been prospectively evaluated.

Aim

To compare MASLD and MAFLD criteria in estimating the 5-year risk of advanced chronic liver disease (ACLD) progression and hepatocellular carcinoma (HCC) occurrence in lean (L) and not-lean (NL) SLD patients.

Materials and Methods

Between January 2014 and June 2019, 931 ultrasonographic-defined-SLD patients were recruited, excluding individuals with ACLD, alcoholism, and other causes of steatosis. Baseline biochemical and clinical data were collected, including Liver Stiffness (LSM) (>9.7 kPa= advanced fibrosis-AF; >15 kPa=ACLD) and Controlled-Attenuation-Parameter (CAP) (>293-db/m=Severe-steatosis-S3). Patients were observed annually or semiannually (AF) over 5 years, reassessing LSM, CAP, and HCC occurrence.

In July 2024, based on baseline features, patients were a posteriori subdivided into “L” (Body-Mass-Index<25 kg/m²) (n.134) and “NL” (n.797) and, subsequently, by separately applying MAFLD and MASLD criteria, in L-MASLD (n.18), L-MASLD/MAFLD (n.82), L-MAFLD (n.34) and NL-MASLD (n.60), NL-MASLD/MAFLD (n.581), NL-MAFLD (n.156).

Results

At baseline, no differences in S3 (L, p:0.163; NL, p:0.103) and AF (L, p:0.718; NL, p:0.277) prevalences emerged. A higher 5-year ACLD progression (RR: 1.83, C.I.95%:1.357-2.431, p:0.0002) and HCC occurrence (RR:1.32, C.I.95%:1.032-1.451, p:0.03) risk was reported in NL-MASLD. Contrariwise, L-MAFLD presented a higher risk of ACLD progression (RR:2.11, C.I.95%: 1.171-2.250, p:0.01) and, even not significant, HCC occurrence (RR:1.588, C.I.95%:0.747-2.781, p:0.371). ACLD progression occurred in 33.34% L-MASLD vs 70.59% L-MAFLD (median: 43 vs 45.50 months; p:0.0091).Logistic regression (adjusted for sex, age, diabetes, steatosis, and fibrosis severity) revealed high-sensitivity-C-reactive protein (aOR: 1.21; C.I. 95%: 1.052-2.183; p:0.02) and Homeostatic-model-assessment-for-insulin-resistance(aOR: 1.38; C.I. 95%: 1.151-2.275; p:0.01) as variables significantly associated with ACLD-progression in L-MAFLD.

Conclusions

MASLD criteria better estimate the liver disease progression risk limitedly to SLD-NL patients.

Hepatic encephalopathy (HE) is a common complication of liver cirrhosis and minimal HE (MHE) increases the risk of falls. Gait alterations in cirrhotic patients are poorly understood, so the aims of this study is to describe the correlation between clinical parameters, such as HE, muscle changes, falls and gait disturbances, and electroneurographic changes.

Twenty-six patients underwent clinical and medical history evaluation to assess the presence of MHE and falls in the past year, and biochemical and instrumental evaluation to determine the presence of gait disturbances or sarcopenia by computed tomography (CT). Gait was assessed with the six-minute walk test (6MWT), the G-Walk device and G-STUDIO software. Ten patients underwent electroneurographic examination (ENG). Data obtained from gait analysis were compared with healthy subjects of the same age and sex.

In the gait analysis, the harmonic ratio (HR) and the recurrence quantification analysis (RQA) were considered. HR provides information on movement fluidity, balance and body coordination during movement, while RQA is based on the identification of parameters that quantify the regularity of time series.

In the subgroup of patients undergoing ENG analysis, lower values of HR in the antero-posterior and vertical directions correlated with the presence of sensory (τbAP= -0.629, p=0.039; τbV= -0.707, p=0.020) and motor (τbAP= -0.707, p=0.020; τbV= -0.629, p=0.039) neuropathy. The highest worsening of RQA index after 6MWT in vertical direction correlated with the presence of motor neuropathy (τbDET= 0.550, p=0.035). The number of falls correlated with sensory and motor electroneurographic parameters, while MELD score was inversely correlated with sensory and motor conduction velocity (ρ=-0.590, p= 0.047; ρ=-0.896, p= 0.003) and directly correlated with motor latency (ρ= 0.783, p= 0.013). Psychometric hepatic encephalopathy score (PHES) values were inversely correlated with distal motor latency signals (ρ=0.854, p= 0.003), while skeletal muscle index (SMI) values were found to be inversely correlated with proximal motor latency (ρ=0.802, p= 0.005).

Gait alterations are common in patients with cirrhosis, especially those with cognitive impairment, and correlate with severity of disease and risk of falls, identifying patients at risk of injuries and hospitalizations.

Background and Aims

Evidence suggests that long-term albumin administration (LTA) prolongs overall survival in patients with cirrhosis and refractory ascites. However, LTA is not yet standard care, and the effects of its combination with TIPS (Transjugular Intrahepatic Portosystemic Shunt) placement remains unclear.

Methods

This observational study compared two groups of patients with cirrhosis and ascites who required at least one large volume paracentesis (LVP). The first group, observed from January 2019 to December 2021, received standard medical treatment (SMT: diuretics and albumin administration after LVP). The second group, observed from January 2022 to February 2024, received SMT plus LTA at a dosage of 40 mg/week. The primary endpoint was mortality and the cause-specific Cox model was used to estimate covariate effects. The Fine and Gray competing risks regression model was used account for death, and LT as competing risk.

Results

A total of 153 patients were analyzed: 63 in the SMT+LTA group and 90 in the SMT group. No differences in liver disease etiology, age, gender, Child-Pugh score, presence of Hepatocellular Carcinoma(HCC), Hepatic Encephalopathy(HE), and eligibility for TIPS and OLT are observed between the two groups.

During the follow-up(median 9 months; range 2-67), 11 patients in the LTA group(17.4%) and 9 in the SMT group(10%) underwent TIPS(p=ns), 7(11.1%) and 8(9%) patients were transplanted in LTA and SMT group respectively(p=ns), and 16 patients in the LTA group(25.4%) versus 71 in the SMT group(79%) died(p<0.001).

Multivariate analysis showed that LTA(HR:0.16; p<0.001), creatinine(HR:1.40; p=0.025), bilirubin (HR:1.16; p=0.014), viral etiology (HR:0.24; p=0.013), and TIPS placement (HR:0.10; p<0.001) were independently associated with mortality. The same results were observed when substituting TIPS placement with TIPS eligibility (Figure 1).

Conclusions

For patients with refractory ascites, LTA in addition to SMT significantly prolongs overall survival and may serve as a disease-modifying treatment, particularly for those contraindicated for TIPS.

Introduction

The spread of SARS-CoV-2 has strained the global health system, necessitating a radical reorganization of health resources. In addition, the escalation in liver disease severity among hospitalized COVID-19 patients is a matter of serious concern, as it may lead to the deterioration of health outcomes for a larger population in the future.

Aim

We aimed at providing a comprehensive overview of COVID-19 impact on monthly hospitalization rates, clinical impairment, Length of Stay (LoS), and mortality of cirrhotic patients admitted to the Local Health Board 1 (LHB1) hospitals in the Abruzzo Region, Italy.

Materials and Methods

Using the International Classification of Diseases, Ninth Revision-Clinical Modification (ICD-9-CM), we identified cases of alcohol-related cirrhosis, nonalcohol-related cirrhosis, and decompensated cirrhosis. We analysed 957 Hospital Discharge Records (HDR) from January 1, 2019, to December 31, 2019 (pre-pandemic), and from January 1, 2022, to December 31, 2022 (post-pandemic) and we evaluated patients' clinical impairment, LoS, and mortality before and after the pandemic.

Results

We identified 494 hospitalizations for nonalcohol-related cirrhosis and 310 for alcohol-related cirrhosis. In the post-pandemic period, hospitalizations for nonalcohol-related cirrhosis significantly decreased (69% vs. 48%; P<.0001), while hospitalizations for alcohol-related cirrhosis significantly increased (31% vs. 52%; P<.0001) compared to pre-pandemic. Additionally, the decompensated patients with alcohol-related cirrhosis significantly increased in the post-pandemic period (77% vs. 65%; P=.0216). Mortality risk significantly increased for both nonalcohol-related (11% vs. 18.5%; P=.0176) and alcohol-related cirrhosis (7.7% vs. 18%; P=.0059) in the post-pandemic era.

Conclusions

Our study pointed out important differences in hospitalization rates and outcomes of cirrhotic patients due to the pandemic, further highlighting the dramatic increase in hospitalizations for alcohol-related cirrhosis. Since this will have a prolonged impact on the natural history of chronic liver disease in Abruzzo Region, continued awareness as well as enhancement of prevention strategies and personalized follow-ups, will be essential.

Introduction

Lifestyle modifications represent the main therapeutic intervention for Metabolic dysfunction-associated Steatotic Liver disease (MASLD). Unfortunately, the dietary-behavioral prescription is constantly limited by poor compliance. In this context, the benefits of motivational support remain unexplored.

Aim

To evaluate the effectiveness of a multidisciplinary (hepatologist-nutritionist-psychologist) management in improving clinical outcomes in MASLD, via ameliorating adherence to specialistic tailored-indications.

Materials and Methods

MASLD patients (n.286) were consecutively enrolled and randomized in three cohorts: 72 followed generic hepatologist-provided dietary advice (“H”), 71 also received a nutritionists-prescribed individualized intervention (“HN”) (H+N= “standard of care”), and 143 were treated with an approach additionally involving cognitive/behavioral-based psychological support (“HNP”) (“experimental-group”). At baseline, anthropometric, biochemical, clinical, liver stiffness (LSM), controlled attenuation parameter (CAP), lifestyle habits, and body composition values were recorded. Along 18 months, semestral hepatological (for all), nutritional (H and HN), and psychological (HNP) follow-ups reassessed parameters and evaluated compliance.

Results

After 18 months, the prevalence of patients achieving a ≥ 10% decrease in body weight was significantly higher in HNP (HNP:62.09%; HN:44.9%; H:35.8%; HNP vs HN, p:0.01; HNP vs H, p:0.0002). In HNP, a significant improvement in Homeostatic-model-assessment-for-insulin-resistance (p:0.001), HDL (p<0.0001), LSM (p:0.007), CAP (p:0.002), and Fat-Mass (p < 0.0001) was observed. Loss of compliance rate was significantly lower in HNP (HNP:12.08%; HN:34.7%; H:45.8%; HNP vs HN, HNP vs H, p:0.001). Relevantly, HNP patients presented a significantly lower risk of acute cardiovascular events (ACEs) during the observation period [HR: 0.497, IC (0.236-0.751) 95%, p:0.04)] (Figure). Logistic regression analysis (adjusted for sex, age, and cardiovascular risk factors) revealed HNP adherence as significantly associated with lower ACEs occurrence (aOR: 0.81; C.I. 95%: 0.55-0.97; p:0.02). Dynamic work, city life, and large family emerged as social factors influencing compliance (OR: 2.11, 1.78, 1.12) (all p<0.05).

Conclusions

Integrating standard hepatological-nutritional with psychological support significantly improves the outcomes of MASLD patients.

Background

Transjugular intrahepatic portosystemic shunt (TIPS) is a well-established treatment for refractory ascites (RA) in patients with cirrhosis. However, a major drawback is the development of post-procedural hepatic encephalopathy (HE), which results from the diversion of blood from the portal vein. According to the first-pass effect, this diversion reduces the liver's capacity to metabolize substances from the gut, leading to an accumulation of toxic compounds in the brain. Given that liver perfusion relies on arterial compensation (hepatic arterial buffer), it is plausible that effective compensation, which also depends on cardiac function, may reduce the risk of encephalopathy by detoxifying the blood during the second-pass metabolism.

Aims

To evaluate by Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI) the changes in liver perfusion induced by TIPS in patients with RA and their relationship with the risk of HE.

Materials

Twenty-nine consecutive patients underwent DCE-MRI, cardiac and hepatic hemodynamic evaluation before and after TIPS. MRI images were processed by a homemade software using the Dual Input Dual Compartment (DIDC) model, focusing on perfusion parameters.

Results

The DIDC model showed that total hepatic perfusion decreased by 24% after TIPS (248 ml/min/100ml vs 189 ml/min/100ml, p 0.095). As expected, a significant reduction in portal perfusion (decreased by 67%; 128.6 ml/min/100ml vs 42.4 ml/min/100ml, p 0.004) and an increase in hepatic arterial fraction post-TIPS (48% vs 77%, p 0.001) was observed. Post-TIPS residual total hepatic perfusion inversely correlated with one-year HE risk: patients with perfusion ≤ 130 ml/min/100ml had a HE risk of 67.6% vs 36.4% for those > 130 ml/min/100ml (HR: 2.1, p 0.039).

Conclusion

Perfusion MRI is able to elucidate the impact of TIPS on liver perfusion, quantifying the extent of hepatic perfusion and its correlation with the development of post-TIPS HE.

Background

Clinically significant portal hypertension (CSPH) in patients with advanced chronic liver disease (ACLD) is high-risk condition for liver-related events (LRE). According with BAVENO VII, non-invasive tests (NIT) should be preferred to rule in or out for CSPH to avoid endoscopy. The novel score HVPG-3Parameters gave a prediction of HVPG showing good accuracy in CSPH prediction.

Aim

Aim is to evaluate the ability of HVPG-3P in PH and LRE prediction.

Methods

A retrospective study was conducted in two different Italian centers: University of Naples and University of Marche. In 10 years, consecutive compensated-ACLD patients who underwent upper-GI endoscopy for PH assessment were enrolled. NIT (FIB-4,ANTICIPATE,PLT/spleen-diameter ratio and HVPG-3P) were calculated. During the follow-up any LRE were recorded.

Results

Two-hundred and ninety-one ACLD subjects (with no differences between centers) were recruited (62.1% males, mean age 60 years).

Mean LSM was 23.6±11.7kPa; HVPG-3P was 13.3±2.0mmHg, ANTICIPATE was 1.0±1.6, FIB-4 was 5.0±3.2, platelets/spleen-diameter ratio was 906.5±568.2.

One-hundred and forty-two (48,9%) subjects showed PH endoscopic signs. They had higher LSM (26.6±12.4vs20.8±10.3kPa, p=0.00002), HVPG-3P (14.2±1.6vs12.4±2.0mmHg, p<0.001), ANTICIPATE (1.66±1.4vs0.31±1.5, p<0.001), FIB-4 (5.87±3.28vs4.13±2.84, p=0.001) and lower platelets/spleen-diameter ratio (652.4±323.6vs1148.6±641.8, p<0.0001) compared to subjects without PH endoscopic signs.

During a median follow-up of 41.5months (IQR 17.8-74.0) LRE occurred in a median of 18.9months (IQR 7.5-37) in 126/291 (43.2%).

Patients who experienced LRE showed higher LSM (26.0±12.3 vs21.9±11.0kPa, p=0.003), HVPG-3P (14.1±1.7vs12.6±2.0mmHg, p<0.0001), ANTICIPATE (1.54±1.57vs0.55±1.56, p<0.0001), FIB-4 (6.02±3.36vs4.19±2.79, p<0.0001) and lower platelets/spleen-diameter ratio (694.9±385.7vs1068.0±630.0, p<0.0001).

The HVPG-3P seems to have a good performance in PH and LRE prediction (considering the results from Random Forest model: MDA 4.52 and 6.55, higher than the majority of variables).

Conclusions

HVPG-3P is a simple tool for non-invasive prediction of PH and could be used to stratify the risk of LRE in patients with ACLD. However, this score needs to be validated in larger cohorts.

Introduction

Proton pump inhibitors (PPIs) are commonly prescribed for gastroesophageal reflux disease (GERD) or prophylaxis of non-steroidal anti-inflammatory drugs and aspirin-induced gastric damage. However, their prolonged use in cirrhotic patients has been linked to complications like spontaneous bacterial peritonitis (SBP) and hepatic encephalopathy (EE).

Aim

To evaluate the appropriateness of PPI therapy in patients with cirrhosis.

Materials and Methods

We reviewed medical records of 209 cirrhotic patients admitted to our gastrointestinal ward (December 2021-December 2022). Demographics, clinical characteristics, PPI use indications, and incidence of EE and SBP were assessed.

Results

The median age was 69 years, and 74.4% were males. Main reasons for hospitalization were hepatocellular carcinoma (n=63, 28.7%), elective diagnostic-therapeutic procedures (n=63, 28.7%), non-liver-related events (n=54, 24.7%), and acute decompensation (n=39, 17.7%). Etiology of liver disease was alcohol in 91 patients (41.6%), virus-related in 77 (35.1%), and metabolic-associated in 30 (13.7%). The median MELD-Na score was 10 (8-14). At admission, 145 patients (66.2%) were on PPIs: of these, 42 patients (29.0%) had confirmed GERD, 12 (8.3%) had esophagitis ≥grade B, and 27 (18.6%) were on aspirin with bleeding risk-factors. Overall, inappropriate PPI use was observed in 74 patients (44.1%). Patients on PPIs were older, with higher MELD-Na and creatinine, and lower hemoglobin and Na compared to those not on PPIs (p<0.05). Multivariate analysis showed that PPI use was independently associated with older age (OR 1.03, IC95% 1.01-1.07) and lower hemoglobin (OR 0.82, IC95% 0.70-0.97). During a median follow-up of 18 months, the incidence of EE and SBP did not differ between PPI users and non-users.

Conclusions

A significant proportion of patients with cirrhosis is inappropriately prescribed PPIs. Although this did not correlate with major liver-related events in the short term, proper PPI prescription education is crucial to prevent potential long-term consequences.

Background & Aim

The first and further decompensation mark the natural history and the risk of mortality in patients with cirrhosis. We assessed the cumulative incidence of first and further (acute and non-acute) decompensation and evaluated their impact on both liver-related death (LR-D) in patients with compensated advanced chronic liver disease (cACLD) due to metabolic dysfunction-associated steatotic liver disease (MASLD).

Methods

Consecutive patients with clinical (LSM>10 kPa) or biopsy-proven (F3-F4 fibrosis) diagnosis of cACLD due to MASLD were included. First and further decompensation were defined according to Baveno VII criteria. The acute (AD) and non-acute (NAD)[MOU1] [VW(2] presentation of the decompensation was also evaluated. Competing risk analysis and cumulative incidence functions (CIF) [MOU3] were assessed by Fine and Gray. Cause-specific Cox models with baseline and time-dependent variables were applied. Multistate model was built to better assess the clinical course of cACLD due to MASLD.

Results

The cumulative incidence of the first decompensation was 3.5% at 5 years, increasing 20-times the risk of LR-D at cause-specific Cox analysis; the cumulative incidence of further decompensation was 44% at 5 years among patients with first decompensation, additionally increasing 1.6-times the risk of LR-D. Ascites, followed by variceal bleeding, were the most common events in both first and further decompensation. The impact of AD and NAD as both first or further event on LR-D was similar[MOU4] . Hepatocellular carcinoma (HCC) further independently increased the risk of LR-D of 3.2-times and 1.6-times, respectively, in the whole cohort of cACLD due to MASLD and in those who experienced first decompensation.

Conclusions

The first and further decompensations (AD and NAD) represent tipping points in the clinical course of patients with cACLD due to MASLD, increasing 20-times and additionally 1.6-times the risk of LR-D. HCC is an independent predictor of LR-D in patients with cACLD due to MASLD, resulting in an additional risk of LR-D when associated with both first and further decompensation.