Hepatic venous pressure gradient predicts risk of hepatic decompensation and liver-related mortality in patients with MASLD.

BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of advanced chronic liver disease (ACLD). Portal hypertension drives hepatic decompensation and is best diagnosed by hepatic venous pressure gradient (HVPG) measurement. Here we investigate the prognostic value of HVPG in compensated (cACLD) MASLD. METHODS: This European multicentre study included MASLD-cACLD patients characterised by HVPG at baseline. Hepatic decompensation (variceal bleeding/ ascites/hepatic encephalopathy) and liver-related mortality were considered the primary events of interest. RESULTS: 340 MASLD-cACLD patients [56.2% men; age: 62 (55-68) years; MELD: 8 (7-9); 71.2% diabetes] were included. Clinically significant portal hypertension (CSPH; i.e., HVPG ≥10 mmHg) was found in 209 patients (61.5%). During a median follow-up of 41.5 (27.5-65.8) months, 65 patients developed hepatic decompensation with a cumulative incidence of 10.0% after 2 years (2Y) and 30.7% after 5 years (5Y) in MASLD-cACLD with CSPH, compared to 2.4% after 2Y and 9.4% after 5Y in patients without CSPH. Variceal bleeding did not occur without CSPH. CSPH (subdistribution hazard ratio, SHR:5.13; p<0.001) was associated with an increased decompensation risk and a higher HVPG remained an independent risk factor in the multivariable model (aSHR per mmHg:1.12; p<0.001). Liver-related mortality occurred in 37 patients with a cumulative incidence of 3.3% after 2Y and 21.4% after 5Y in CSPH. Without CSPH, the incidence after 5Y was 0.8%. Accordingly, a higher HVPG was also independently associated with a higher risk of liver-related death (aSHR per mmHg:1.20; p<0.001). CONCLUSION: HVPG measurement is of high prognostic value in MASLD-cACLD. While MASLD-cACLD patients without CSPH show a very low short-term risk of decompensation and liver-related mortality is rare, the presence of CSPH substantially increases both risks. IMPACT AND IMPLICATIONS: While the incidence of compensated advanced chronic liver disease (cACLD) due to metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing worldwide, insights into the impact of clinically significant portal hypertension (CSPH) on the risk of liver-related events in MASLD-cACLD remain limited. Based on the findings of this European multicentre study including 340 MASLD-cACLD, we could show that increasing HVPG values and the presence of CSPH in particular were associated with a significantly higher risk of first hepatic decompensation and liver-related mortality. In contrast, the short-term incidence of decompensation in MASLD-cACLD patients without CSPH was low and the risk of liver-mortality remained negligible. Thus, HVPG measurements can provide important prognostic information for individualised risk-stratification in MASLD-cACLD and may help facilitate the study of novel and promising treatment possibilities for MASLD.

Decompensation in Advanced Nonalcoholic Fatty Liver Disease May Occur at Lower Hepatic Venous Pressure Gradient Levels Than in Patients With Viral Disease.

BACKGROUND & AIMS: Portal hypertension is the strongest predictor of hepatic decompensation and death in patients with cirrhosis. However, its discriminatory accuracy in patients with nonalcoholic fatty liver disease (NAFLD) has been challenged because hepatic vein catheterization may not reflect the real portal vein pressure as accurately as in patients with other etiologies. We aimed to evaluate the relationship between hepatic venous pressure gradient (HVPG) and presence of portal hypertension-related decompensation in patients with advanced NAFLD (aNAFLD). METHODS: Multicenter cross-sectional study included 548 patients with aNAFLD and 444 with advanced RNA-positive hepatitis C (aHCV) who had detailed portal hypertension evaluation (HVPG measurement, gastroscopy, and abdominal imaging). We examined the relationship between etiology, HVPG, and decompensation by logistic regression models. We also compared the proportions of compensated/decompensated patients at different HVPG levels. RESULTS: Both cohorts, aNAFLD and aHVC, had similar baseline age, gender, Child-Pugh score, and Model for End-Stage Liver Disease score. Median HVPG was lower in the aNAFLD cohort (13 vs 15 mmHg) despite similar liver function and higher rates of decompensation in aNAFLD group (32% vs 25%; P = .019) than in the aHCV group. For any of the HVPG cutoff analyzed (<10, 10-12, or 12 mmHg) the prevalence of decompensation was higher in the aNAFLD group than in the aHCV group. CONCLUSIONS: Patients with aNAFLD have higher prevalence of portal hypertension-related decompensation at any value of HVPG as compared with aHCV patients. Longitudinal studies aiming to identify HVPG thresholds able to predict decompensation and long-term outcomes in aNAFLD population are strongly needed.

Autoimmune hepatitis triggered by SARS-CoV-2 vaccination.

The development of autoimmune diseases has been reported after SARS-CoV-2 infection. Vaccination against SARS-CoV-2 could also trigger auto-immunity, as it has been described with other vaccines. An aberrant immune response induced by molecular mimicry and bystander activation, especially in predisposed individuals, is a potential mechanism. We report the case of a 76-year-old woman with Hashimoto thyroiditis and prior COVID-19 infection who developed severe autoimmune hepatitis (with typical features including strongly positive anti-smooth muscle antibody and markedly elevated immunoglobulins G, as well as typical histological findings) following SARS-CoV-2 vaccination (mRNA-1273 SARS-CoV-2 vaccine, Moderna®). The link between SARS-CoV-2 vaccination and the development of autoimmune diseases needs to be further investigated. Although a causality relationship cannot be proven, caution may be warranted when vaccinating individuals with known autoimmune diseases.

Noninvasive Detection of Clinically Significant Portal Hypertension in Compensated Advanced Chronic Liver Disease.

Patients with compensated advanced chronic liver disease have different prognoses depending on the presence of portal hypertension. Current non-invasive diagnostic methods allow identification of clinically significant portal hypertension. Portosystemic collaterals on imaging or liver stiffness of more than 20 to 25 kPa by using transient elastography identifies patients with clinically significant portal hypertension. Patients with liver stiffness of less than 20 kPa and platelet count of greater than 150 g/L can avoid endoscopy. This rule could be expanded using spleen stiffness. Methods to risk stratify for portal hypertension in compensated advanced chronic liver disease and successfully treated chronic hepatitis C and B are subject of research.

Is topical lidocaine beneficial before catheter insertion in esophageal manometry and ambulatory pH monitoring?

BACKGROUND: Conventionally, topical anesthesia is applied to improve the tolerance of esophageal manometry (EM) and ambulatory pH monitoring (apH) but there is presently no evidence supporting this practice. We aimed to compare the tolerance of EM and apH with vs without topical lidocaine anesthesia. METHODS: A prospective study was conducted at our center between January 2017 and January 2019. All patients who underwent EM or apH and completed a systematically distributed standardized patient survey were included. From January 2017 to June 2018, all patients had a viscous lidocaine solution applied before EM and apH ("lidocaine" group). After June 2018, we ceased applying any topical anesthesia ("no lidocaine" group). Patient-reported adverse effects and satisfaction scores were compared between these two patient groups. KEY RESULTS: Two hundred forty-nine patient surveys were included. "Lidocaine" (n = 124) and "no lidocaine" (n = 125) groups were similar in age (56.9 ± 14.0 vs 56.0 ± 13.7; P = .77) and gender distributions (65.9% vs 63.3% female; P = .68). Patients in the "lidocaine" group were less likely to report pain during catheter insertion (33.6% vs 50.8%; P = .007, OR: 0.49 [95% CI 0.29-0.83]) and reported a lower overall pain score (2.82 ± 1.38 vs 3.20 ± 1.42 on 5; P = .04). There was a tendency toward increased global satisfaction with lidocaine application but that was not statistically significant (4.36 ± 1.05 vs 4.11 ± 1.13; P = .08). In subgroup analyses, female patients, younger patients, and patients who underwent EM were more likely to benefit from lidocaine application. CONCLUSIONS AND INFERENCES: Application of topical lidocaine before esophageal motility tests reduces pain during catheter insertion and overall pain.

Hepatic steatosis progresses faster in HIV mono-infected than HIV/HCV co-infected patients and is associated with liver fibrosis.

BACKGROUND & AIMS: Hepatic steatosis (HS) seems common in patients infected with human immunodeficiency virus (HIV). However, the relative effect of HIV, as well as hepatitis C virus (HCV) in those co-infected, and the influence of HS on liver fibrosis progression are unclear. METHODS: The LIVEr disease in HIV (LIVEHIV) is a Canadian prospective cohort study using transient elastography and associated controlled attenuation parameter (CAP) to screen for HS and liver fibrosis, in unselected HIV-infected adults. HS progression was defined as development of any grade HS (CAP ⩾248dB/m), or transition to severe HS (CAP >292dB/m), for those with any grade HS at baseline. Fibrosis progression was defined as development of significant liver fibrosis (liver stiffness measurement [LSM] >7.1kPa), or transition to cirrhosis (LSM >12.5kPa) for those with significant liver fibrosis at baseline. Cox regression analysis was used to assess predictors of HS and fibrosis progression. RESULTS: A prospective cohort study was conducted, which included 726 HIV-infected patients (22.7% HCV co-infected). Prevalence of any grade HS did not differ between HIV mono-infected and HIV/HCV co-infected patients (36.1% vs. 38.6%, respectively). 313 patients were followed for a median of 15.4 (interquartile range 8.5-23.0) months. The rate of HS progression was 37.8 (95% confidence interval [CI] 29.2-49.0) and 21.9 (95% CI 15.6-30.7) per 100 person-years in HIV mono-infection and HIV/HCV co-infection, respectively. HCV co-infection was an independent negative predictor of HS progression (adjusted hazard ratio [aHR] 0.50, 95% CI 0.28-0.89). HS predicted liver fibrosis progression in HIV mono-infection (aHR 4.18, 95% CI 1.21-14.5), but not in HIV/HCV co-infection. CONCLUSION: HS progresses faster and is associated with liver fibrosis progression in HIV mono-infection but not in HIV/HCV co-infection. Lay summary: Fatty liver is the most frequent liver disease in Western countries. People living with HIV seem at high risk of fatty liver due to frequent metabolic disorders and the long-term effects of antiretroviral therapy. However, due to the invasiveness of liver biopsy, the traditional method of diagnosing fatty liver, there are few data regarding its frequency in people living with HIV. In this study, we used a non-invasive diagnostic tool to analyze the epidemiology of fatty liver in 726 HIV+ patients. We found that fatty liver affects over one-third of people living with HIV. When followed over time, we found that HIV+ patients without HCV co-infection develop fatty liver more frequently than those co-infected with HCV.

Nonalcoholic fatty liver disease diagnosed by transient elastography with controlled attenuation parameter in unselected HIV monoinfected patients.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. HIV-infected persons without viral hepatitis are at increased risk of NAFLD. Nevertheless, data on NAFLD in HIV monoinfection are scarce. DESIGN/METHODS: We prospectively investigated prevalence and predictors of NAFLD and liver fibrosis by transient elastography and associated controlled attenuation parameter (CAP) in unselected HIV-infected adults without significant alcohol intake or viral hepatitis coinfection. NAFLD was defined as CAP at least 238 dB/m. Significant liver fibrosis and cirrhosis were defined as transient elastography measurement at least 7.1 and 13 kPa, respectively. Predictors of NAFLD and significant liver fibrosis were determined using logistic regression analysis. RESULTS: A total of 300 consecutive patients (mean age 50 years, 77% men; mean CD4 cell count 570 cells/µl, 90% on antiretrovirals) were included as a part of a routine screening program. Transient elastography with CAP identified NAFLD and significant liver fibrosis in 48 and 15% of cases, respectively. NAFLD was independently associated with BMI more than 25 kg/m [adjusted odds ratio (aOR) 4.86, 95% confidence interval (CI) 2.55-9.26] and elevated alanine aminotransferase (ALT) (aOR 3.17, 95% CI 1.43-7.03). Independent predictors of significant liver fibrosis were diabetes (aOR 5.84, 95% CI 1.91-17.85), elevated ALT (aOR 3.30, 95% CI 1.27-8.59) and current use of protease inhibitors (aOR 3.96, 95% CI 1.64-9.54). CONCLUSION: NAFLD and significant liver fibrosis diagnosed by transient elastography with CAP are major comorbidities in unselected HIV monoinfected persons on antiretroviral therapy, particularly if metabolic conditions and elevated ALT coexist. Noninvasive screening for NAFLD should be implemented in this population to establish early interventions and prevent complications.

Postoperative anemia does not impede functional outcome and quality of life early after hip and knee arthroplasties.

BACKGROUND: Clinicians have adopted a restrictive transfusion threshold (75-80 g/L) after major orthopedic surgery. Anemia may be associated with a decrease in postoperative vigor. We hypothesize that, in these patients, a threshold hemoglobin (Hb) concentration exists below which functional recovery and quality of life (QoL) become difficult. STUDY DESIGN AND METHODS: A prospective, observational cohort study in 305 patients 60 years or older undergoing a total hip or knee arthroplasty was conducted. Major outcome variables were distance walked in 6 minutes (6MWT), score on the Borg Scale for perception of effort, maximal dominant hand strength, and Short Form 36 (SF-36) QoL assessment in the preoperative and early postoperative periods. Patients were categorized according to their Hb level the day of the postoperative 6MWT (≤ 80, 81-90, 91-100, and >100 g/L). RESULTS: There was no difference between Hb groups in the decrease of the distance walked preoperatively versus postoperatively. For both moments of observation, the 6MWT was not significantly different between Hb groups (p = 0.190). Similar results were found with perception of effort, maximal dominant hand strength, and SF-36 QoL assessment scores. In a regression model, the decrease in Hb concentration could explain only 1.9% of the total variation observed in the 6MWT (p = 0.008). CONCLUSION: Moderate anemia is not associated with an impaired functional recovery or QoL in the immediate postoperative period after major arthroplasties. Further studies will be required to determine the long-term consequences of a restrictive transfusion strategy in these patients.

Red blood cell transfusion practice in elective orthopedic surgery: a multicenter cohort study.

BACKGROUND: The indications for red blood cell (RBC) transfusions remain unclear despite published guidelines. Our hypothesis was that the transfusion practice varies inside the Centre hospitalier de l'Université de Montréal (CHUM). STUDY DESIGN AND METHODS: A total of 701 charts of patients who underwent a knee or hip arthroplasty or prosthesis revision in three hospitals of the CHUM were reviewed. Demography, hemoglobin (Hb) concentrations, details on transfusions, and postoperative adverse events (AEs) were collected up until discharge. The primary outcome was the presence or absence of RBC transfusion. Secondary outcomes were the nadir Hb, number of units transfused, discharge Hb, blood losses, and postoperative AEs. RESULTS: The rate of postoperative transfusion was 29%. We found no significant difference between odds ratios of each site for sex, coronary artery disease, chronic heart failure, type of procedure, American Society of Anesthesiologists physical status, weight, height, body mass index, body surface area, and estimated blood volume. Overall, patients were transfused at a Hb between 75 and 80g/L. Eighty-five percent of postoperative transfusions could be predicted using only nadir Hb and adding patient characteristics did not substantially improve the model (86.1%). Discharge Hb was below 100g/L in 66% of patients. CONCLUSIONS: There was no difference among hospitals regarding the way RBC transfusions are used. Our data suggest that physicians mainly based their decision to transfuse on a single variable, the Hb concentration, with the use of a restrictive strategy. Future trials should focus on the optimal transfusion trigger to adopt in major orthopedic surgery.