Methodology exploration and reproducibility evaluation of TAI and TSI for quantitative ultrasound assessment of hepatic steatosis.

Background and aim: New quantitative ultrasound techniques can be used to quantify hepatic steatosis, including tissue attenuation imaging (TAI), tissue scatter -distribution imaging (TSI), and the hepatorenal index (HRI). However, the measurement norms and the effects of fasting on these measurements remain unclear. The present study performed a methodological exploration and investigated the reliability of these measurements. Methods: In total, 103 participants were prospectively recruited for ultrasonography and magnetic resonance imaging (MRI) scans. For the TAI and TSI data, the upper (2 cm), middle (4 cm) and lower (6 cm) areas determined according to the depth of the region of interest from the liver capsule, were sampled three times. Correlation analyses were performed to compare the measurements of TAI, TSI, and HRI with the controlled attenuation parameter (CAP) or MRI-proton density fat fraction (MRI-PDFF). Intra- and inter-operator repeatability was assessed using intraclass correlation coefficients. The effects of fasting on these measurements were then compared. Results: The TAI and TSI measurements obtained from the upper and middle depths exhibited stronger correlations with the CAP measurements than those obtained from the lower depth. Specifically, the mean TAI had a significant positive correlation with MRI-PDFF (r = 0.753, P < 0.0001). TAI and TSI measurements exhibited excellent intra- (0.933 and 0.925, respectively) and inter- (0.896 and 0.766, respectively) examiner reliability. However, the correlation between HRI and CAP measurements was only 0.281, with no significant correlation with MRI-PDFF, and intra- and inter-examiner reproducibility of 0.458 and 0.343, respectively. Fasting did not affect these measurements. Conclusions: TAI and TSI measurements demonstrated good intra- and interobserver reliability and correlated well with CAP and MRI-PDFF measurements. However, in practice-based clinical applications, the sampling depth should be controlled within 2-4 cm of the hepatic capsule; no fasting is required before the examination.

Assessment of Liver Transplant Eligibility in Chronic Liver Disease Patients: A Cross-Sectional Study From a Tertiary Care Hospital of Pakistan.

INTRODUCTION: The burden of chronic liver disease (CLD) is increasing globally and the ultimate treatment is a liver transplant. As Pakistan is a developing country, liver transplantation is not easily available due to limited resources. This study aims to assess the patients with CLD for liver transplantation and to find the frequency of eligible candidates for liver transplantation. METHODS: A cross-sectional observational study was conducted on patients with CLD from June 2022 to December 2022. Total bilirubin, serum creatinine complete blood count, serum electrolytes, and international normalised ratio (INR) were done. The Model for End-Stage Liver Disease (MELD) score was calculated and the frequency of eligible patients for liver transplant was determined. Data was entered and analyzed using Statistical Package for Social Sciences (SPSS) version 22 (IBM Corp., Armonk, NY, USA). RESULTS: In our study, 149 patients were enrolled with a mean age of 46.81±15.7 years. There were 58.7% male and 41.6% female patients. The mean duration of liver cirrhosis was 18.22±11.7 months. The mean MELD score was 20.71±5.2. The common liver cirrhosis stages were stage II and stage II was found in 32.2% of each. Hepatocellular carcinoma (HCC) was present in 15.4% of patients. There were 25.5% of patients eligible for liver transplants. CONCLUSION: In our study, we found that significant numbers of patients with CLD were eligible for liver transplantation.

CT-Based Hounsfield Units for Pre-donation Liver Steatosis Assessment: Enhancing Transplant Outcomes and Efficiency.

Steatotic liver grafts are associated with increased post-transplant complications and graft failure. The field of transplantation faces a challenge in the absence of a reliable pre-donation protocol for quantitatively assessing steatosis in cadaveric liver grafts. Current pre-donation evaluation protocols often involve non-contrast computed tomography (CT) scans of the chest and/or abdomen as an initial step in organ donation assessment. These routine scans have the potential to identify and quantify hepatic fat content when more than 20% of the liver parenchyma is affected. By incorporating both abdominal and thoracic CT scans during the donor workup, an assessment of the quality of the liver and spleen can be achieved. Our study is based on the hypothesis that a precise pre-donation evaluation utilizing Hounsfield units (HU) derived from CT images of the liver and spleen can provide transplant programs with crucial data regarding the extent of steatosis. This approach is envisioned as a significant advancement that could potentially eliminate the need for preoperative liver biopsies by offering essential information to streamline the evaluation process.

Quantitative US fat fraction for noninvasive assessment of hepatic steatosis in suspected metabolic-associated fatty liver disease.

OBJECTIVES: To evaluate the agreement between quantitative ultrasound system fat fraction (USFF) and proton magnetic resonance spectroscopy (1H-MRS) and the diagnostic value of USFF in assessing metabolic-associated fatty liver disease (MAFLD). METHODS: The participants with or suspected of MAFLD were prospectively recruited and underwent 1H-MRS, USFF, and controlled attenuation parameter (CAP) measurements. The correlation between USFF and 1H-MRS was assessed using Pearson correlation coefficients. The USFF diagnostic performance for different grades of steatosis was evaluated using receiver operating characteristic curve analysis (ROC) and was compared with CAP, visual hepatic steatosis grade (VHSG). RESULTS: A total of 113 participants (mean age 44.79 years ± 13.56 (SD); 71 males) were enrolled, of whom 98 (86.73%) had hepatic steatosis (1H-MRS ≥ 5.56%). USFF showed a good correlation (Pearson r = 0.76) with 1H-MRS and showed a linear relationship, which was superior to the correlation between CAP and 1H-MRS (Pearson r = 0.61). The USFF provided high diagnostic performance for different grades of hepatic steatosis, with ROC from 0.84 to 0.98, and the diagnostic performance was better than that of the CAP and the VHSG. The cut-off values of the USFF were different for various grades of steatosis, and the cut-off values for S1, S2, and S3 were 12.01%, 19.98%, and 22.22%, respectively. CONCLUSIONS: There was a good correlation between USFF and 1H-MRS. Meanwhile, USFF had good diagnostic performance for hepatic steatosis and was superior to CAP and VHSG. USFF represents a superior method for noninvasive quantitative assessment of MAFLD. CRITICAL RELEVANCE STATEMENT: Quantitative ultrasound system fat fraction (USFF) accurately assesses liver fat content and has a good correlation with magnetic resonance spectroscopy (1H-MRS) for the assessment of metabolic-associated fatty liver disease (MAFLD), as well as for providing an accurate quantitative assessment of hepatic steatosis. KEY POINTS: Current diagnostic and monitoring modalities for metabolic-associated fatty liver disease have limitations. USFF correlated well with 1H-MRS and was superior to the CAP. USFF has good diagnostic performance for steatosis, superior to CAP and VHSG.

The impact of hepatic and splenic volumetric assessment in imaging for chronic liver disease: a narrative review.

Chronic liver disease is responsible for significant morbidity and mortality worldwide. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) can fully visualise the liver and adjacent structures in the upper abdomen providing a reproducible assessment of the liver and biliary system and can detect features of portal hypertension. Subjective interpretation of CT and MRI in the assessment of liver parenchyma for early and advanced stages of fibrosis (pre-cirrhosis), as well as severity of portal hypertension, is limited. Quantitative and reproducible measurements of hepatic and splenic volumes have been shown to correlate with fibrosis staging, clinical outcomes, and mortality. In this review, we will explore the role of volumetric measurements in relation to diagnosis, assessment of severity and prediction of outcomes in chronic liver disease patients. We conclude that volumetric analysis of the liver and spleen can provide important information in such patients, has the potential to stratify patients' stage of hepatic fibrosis and disease severity, and can provide critical prognostic information. CRITICAL RELEVANCE STATEMENT: This review highlights the role of volumetric measurements of the liver and spleen using CT and MRI in relation to diagnosis, assessment of severity, and prediction of outcomes in chronic liver disease patients. KEY POINTS: Volumetry of the liver and spleen using CT and MRI correlates with hepatic fibrosis stages and cirrhosis. Volumetric measurements correlate with chronic liver disease outcomes. Fully automated methods for volumetry are required for implementation into routine clinical practice.

Noninvasive Assessment of Portal Hypertension.

The progressive use of noninvasive tests (NITs) has changed the way hepatologists diagnose and manage patients with chronic liver disease, mainly because of their easiness to use and the ability to be repeated during follow-up. Liver stiffness measurement is the NIT with more scientific evidence. NITs have demonstrated to be useful to detect not only liver fibrosis but also the presence of clinically significant portal hypertension. Moreover, current evidence supports they can also be useful to evaluate the prognosis of patients with chronic liver disease.

Preservation of fat mass at the expense of lean mass in children with end-stage chronic liver disease.

BACKGROUND: Sarcopenia predicts morbidity and mortality in end-stage chronic liver disease (ESCLD). Here, we describe changes in body composition in children with ESCLD before and after liver transplantation (LT). METHODS: Retrospective analysis of whole body DXA scans performed before and after LT over 4 years. Appendicular and whole-body fat mass and lean mass were expressed as fat mass (FMI) and lean mass (LMI) index z-scores. Sarcopenia was defined as leg LMI z-score <-1.96. RESULTS: Eighty-three DXA scans of children before or after LT were studied. Sarcopenia had a positive correlation with weight (0.8, p < .01), height (0.48, p < .05), and BMI z-score (0.77, p < .01), as well as arm, trunk, and total mean mass indices. It correlated negatively with indices of hypersplenism: PLTs (-0.57, p < .01), Neu (-0.50, p < .05), WCC (-0.44, p < .05), and days to discharge (-0.46, p < .05). At baseline: 13/25 (52%) children were sarcopenic and stayed in the hospital after LT for longer. Eight were stunted with a higher WCC and Ne/Ly ratio. All had normal FM indices. One year after LT, 12/26 children remained sarcopenic. Seven were stunted. Two years after LT, 5/15 were sarcopenic, and 5 were stunted. Three years after LT, 1/10 was sarcopenic, and 2 were stunted. By 4 years after LT, 1/7 was sarcopenic, and the same one was stunted. FM indices remained normal. CONCLUSIONS: Sarcopenic patients stayed longer in the hospital after LT. Lean mass indices were mostly within the normal range by 4 years after LT. 32% of children were stunted, and markers of inflammation were correlated with stunting. Fat mass was preserved at the cost of lean mass.

Head-to-head comparison of three different US-based quantitative parameters for hepatic steatosis assessment: a prospective study.

PURPOSE: To evaluate the diagnostic performance of attenuation coefficient (AC), hepato-renal index (HRI) and controlled attenuation parameter (CAP) in quantitative assessment of hepatic steatosis by employing histopathology as reference standard. METHODS: Participants with suspected metabolic-associated fatty liver disease (MAFLD) who underwent US-based parameter examinations and liver biopsy were prospectively recruited. The distributions of US parameters across different grades of steatosis were calculated, and diagnostic performance was determined based on the areas under the receiver operating characteristic curve (AUC). RESULTS: A total of 73 participants were included, with hepatic steatosis grades S0, S1, S2, and S3 distributed as follows: 13, 20, 27, and 13 respectively. The correlation coefficients for CAP, AC, and HRI ranged from 0.67 to 0.74. AC and HRI showed a strong correlation with steatosis grade. The AUC for CAP and AC in diagnosing steatosis ≥ S1 were significantly higher at 0.99 and 0.98 compared to HRI's value. For diagnosing steatosis ≥ S2, the AUC of CAP (AUC: 0.85) was lower than that of AC (AUC: 0.94), and HRI (AUC: 0.94). Similarly for diagnosing steatosis S3, the AUC of CAP (AUC: 0.68) was lower than that of AC (AUC: 0.88), and HRI (AUC: 0.88). CONCLUSION: The AC and HRI values increased with the progression of hepatic steatosis grade, while CAP increased from S0 to S2 but not from S2 to S3. For mild steatosis diagnosis, CAP and AC showed superior diagnostic performance compared to HRI, while AC and HRI were more advantageous in differentiating moderate and severe steatosis.

Modelling and assessment of glucose-lactate kinetics in youth with overweight, obesity and metabolic dysfunction-associated steatotic liver disease: A pilot study.

AIM: In this study, we investigated glucose and lactate kinetics during a 75 g oral glucose tolerance test (OGTT) in 23 overweight and obese adolescents and assessed putative differences among participants with and without metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: We enrolled 23 young people (six girls) with obesity [body mass index 33 (29-37)]. Glucose-lactate kinetics parameters (disposal glucose insulin sensitivity, SID; fraction of glucose converted into lactate, fr; fractional lactate clearance rate, kL) and lactate production rate (LPR) were estimated using the oral glucose-lactate minimal model. MASLD presence was assessed using the proton density fat fraction. We analysed glucose, lactate and LPR time to peak, peak values and area under the curve and evaluated differences using the Wilcoxon test. MASLD and no-MASLD participants were compared using the Mann-Whitney test. Correlations between parameters were assessed using the Spearman correlation coefficient (ρ). We also tested the performance of two (4 or 3 h OGTT) protocols in estimating oral glucose-lactate minimal model and LPR parameters. RESULTS: Glucose peaks 30 min earlier than lactate (p = .0019). This pattern was present in the no-MASLD group (p < .001). LPR peaks 30 min later in the MASLD group (p = .02). LPR and kL were higher in MASLD, suggesting higher glycolysis and lactate utilization. SID and fr correlate significantly (ρ = -0.55, p = .008). SID and fr were also correlated with the body mass index, (ρ = -0.45, p = .04; and ρ = 0.45; p = .03). The protocol duration did not influence the estimates of the parameters. DISCUSSION: Youth with MASLD showed a delayed glucose metabolism, possibly because of greater utilization of the underlying substrates. A 3-h OGTT may be used to assess lactate metabolism effectively.

Healthcare resource utilization and costs among patients with alpha-1 antitrypsin deficiency with liver and/or lung disease: a longitudinal retrospective study in the USA.

Aim: To evaluate all-cause and liver-associated healthcare resource utilization (HCRU) and costs among patients with alpha-1 antitrypsin deficiency (AATD) with liver disease (LD) and/or lung disease (LgD). Materials & methods: This was a retrospective analysis of linked administrative claims data from the IQVIA PharMetrics® Plus and the IQVIA Ambulatory Electronic Medical Records (AEMR) databases from 1 July 2021 to 31 January 2022. Patients with AATD in the IQVIA PharMetrics Plus database were included with ≥1 inpatient or ≥2 outpatient medical claims ≥90 days apart with a diagnosis of AATD, or with records indicating a protease inhibitor (Pi)*ZZ/Pi*MZ genotype in the IQVIA AEMR database with linkage to IQVIA PharMetrics Plus. For a patient's identified continuous enrollment period, patient time was assigned to health states based on the initial encounter with an LD/LgD diagnosis. A unique index date was defined for each health state, and HCRU and costs were calculated per person-year (PPY). Results: Overall, 5136 adult and pediatric patients from the IQVIA PharMetrics Plus and IQVIA AEMR databases were analyzed. All-cause and liver-associated HCRU and costs were substantially higher following onset of LD/LgD. All-cause cost PPY ranged from US $11,877 in the absence of either LD/LgD to US $74,015 in the presence of both LD and LgD. Among liver transplant recipients in the AATD with LD health state, liver-associated total costs PPY were US $87,329 1-year pre-transplantation and US $461,752 1-year post-transplantation. In the AATD with LgD and AATD with LD and LgD health states, patients who received augmentation therapy were associated with higher all-cause total costs PPY and lower liver-associated total costs PPY than their counterparts who did not receive augmentation therapy. Conclusion: Patients with AATD had increased HCRU and healthcare costs in the presence of LD and/or LgD. HCRU and healthcare costs were highest in the AATD with LD and LgD health state.

Global burden of liver cirrhosis 1990-2019 and 20 years forecast: results from the global burden of disease study 2019.

BACKGROUND: Cirrhosis is a disease that imposes a heavy burden worldwide, but its incidence varies widely by region. Therefore, we analysed data on the incidence and mortality of cirrhosis in 204 countries and territories from 1990-2019 and projected the disease development from 2019-2039. METHODS: Data on the incidence and mortality of liver cirrhosis from 1990 to 2019 were acquired from the public Global Burden of Disease (GBD) study. In addition, the average annual percentage change (AAPC) and estimated annual percentage change (EAPC) of the age-standardized rate (ASR) of cirrhosis in different regions were calculated. The estimates of risk factor exposure were summarized, and the proportion of causes and risk factors of liver cirrhosis and their relationship with the human development index (HDI) and socio-demographic index (SDI) were analysed. Trends in the incidence of cirrhosis in 2019-2039 were predicted using Nordpred and BAPC models. RESULTS: Globally, the ASR of cirrhosis incidence decreased by 0.05% per year from 25.7/100,000 in 1990 to 25.3/100,000 in 2019. The mortality risk associated with cirrhosis is notably lower in females than in males (13 per 100,000 vs 25 per 100,000). The leading cause of cirrhosis shifted from hepatitis B to C. Globally, alcohol use increased by 14%. In line, alcohol use contributed to 49.3% of disability-adjusted life years (DALYs) and 48.4% of global deaths from liver cirrhosis. Countries with a low ASR in 1990 experienced a faster increase in cirrhosis, whereas in 2019, the opposite was observed. In countries with high SDI, the ASR of cirrhosis is generally lower. Finally, projections indicate that the number and incidence of cirrhosis will persistently rise from 2019-2039. CONCLUSIONS: Cirrhosis poses an increasing health burden. Given the changing etiology, there is an imperative to strengthen the prevention of hepatitis C and alcohol consumption, to achieve early reduce the incidence of cirrhosis.

This study is an updated assessment of liver cirrhosis prevalence trends in 204 countries worldwide and the first to project trends over the next 20 years.The disease burden of cirrhosis is still increasing, and despite the decline in ASR, the number and prevalence of cirrhosis will continue to increase over the next two decades after 2019.It is alarming that the global surge in alcohol use is accompanied by an increase in DALYs and deaths due to liver cirrhosis.Liver cirrhosis remains a noteworthy public health event, and our study can further guide the development of national healthcare policies and the implementation of related interventions.

Outcomes and risk factors for mortality in clostridioides difficile infection in patients with NAFLD and NASH.

INTRODUCTION AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and can progress to non-alcoholic steatohepatitis (NASH) and, ultimately, cirrhosis. Clostridioides difficile is the most common nosocomial cause of diarrhea and is associated with worse clinical outcomes in other liver diseases, including cirrhosis, but has not been extensively evaluated in concomitant NAFLD/NASH. MATERIALS AND METHODS: We conducted a retrospective cohort study using the National Inpatient Sample database from 2015 to 2017. Patients with a diagnosis of CDI, NAFLD, and NASH were identified using International Classification of Diseases (Tenth Revision) codes. The outcomes of our study include length of stay, hospitalization cost, mortality, and predictors of mortality. RESULTS: The CDI and NASH cohort had a higher degree of comorbidity burden and prevalence of peptic ulcer disease, congestive heart failure, diabetes mellitus, and cirrhosis. Patients with NASH and CDI had a significantly higher mortality rate compared to the CDI only cohort (mortality, 7.11 % vs. 6.36 %; P = 0.042). Patients with CDI and NASH were at increased risk for liver-related complications, acute kidney injury, and septic shock (P < 0.001) compared to patients with CDI only. Older age, intestinal complications, pneumonia, sepsis and septic shock, and liver failure conferred an increased risk of mortality among the CDI and NASH cohort. CONCLUSIONS: Patients with NASH had a higher rate of liver-related complications, progression to septic shock, and mortality rate following CDI infection compared to the CDI only cohort.

The regional disparities in liver disease comorbidity among elderly Chinese based on a health ecological model: the China Health and Retirement Longitudinal Study.

PURPOSE: This study aimed to investigate the risk factors for liver disease comorbidity among older adults in eastern, central, and western China, and explored binary, ternary and quaternary co-morbid co-causal patterns of liver disease within a health ecological model. METHOD: Basic information from 9,763 older adults was analyzed using data from the China Health and Retirement Longitudinal Study (CHARLS). LASSO regression was employed to identify significant predictors in eastern, central, and western China. Patterns of liver disease comorbidity were studied using association rules, and spatial distribution was analyzed using a geographic information system. Furthermore, binary, ternary, and quaternary network diagrams were constructed to illustrate the relationships between liver disease comorbidity and co-causes. RESULTS: Among the 9,763 elderly adults studied, 536 were found to have liver disease comorbidity, with binary or ternary comorbidity being the most prevalent. Provinces with a high prevalence of liver disease comorbidity were primarily concentrated in Inner Mongolia, Sichuan, and Henan. The most common comorbidity patterns identified were "liver-heart-metabolic", "liver-kidney", "liver-lung", and "liver-stomach-arthritic". In the eastern region, important combination patterns included "liver disease-metabolic disease", "liver disease-stomach disease", and "liver disease-arthritis", with the main influencing factors being sleep duration of less than 6 h, frequent drinking, female, and daily activity capability. In the central region, common combination patterns included "liver disease-heart disease", "liver disease-metabolic disease", and "liver disease-kidney disease", with the main influencing factors being an education level of primary school or below, marriage, having medical insurance, exercise, and no disabilities. In the western region, the main comorbidity patterns were "liver disease-chronic lung disease", "liver disease-stomach disease", "liver disease-heart disease", and "liver disease-arthritis", with the main influencing factors being general or poor health satisfaction, general or poor health condition, severe pain, and no disabilities. CONCLUSION: The comorbidities associated with liver disease exhibit specific clustering patterns at both the overall and local levels. By analyzing the comorbidity patterns of liver diseases in different regions and establishing co-morbid co-causal patterns, this study offers a new perspective and scientific basis for the prevention and treatment of liver diseases.

Prevalence of Sarcopenia and Its Defining Components in Non-alcoholic Fatty Liver Disease Varies According to the Method of Assessment and Adjustment: Findings from the UK Biobank.

Sarcopenia may increase non-alcoholic fatty liver disease (NAFLD) risk, but prevalence likely varies with different diagnostic criteria. This study examined the prevalence of sarcopenia and its defining components in adults with and without NAFLD and whether it varied by the method of muscle mass assessment [bioelectrical impedance (BIA) versus dual-energy X-ray absorptiometry (DXA)] and adjustment (height2 versus BMI). Adults (n = 7266) in the UK Biobank study (45-79 years) with and without NAFLD diagnosed by MRI, were included. Sarcopenia was defined by the 2018 European Working Group on Sarcopenia in Older People definition, with low appendicular skeletal muscle mass (ASM) assessed by BIA and DXA and adjusted for height2 or BMI. Overall, 21% of participants had NAFLD and the sex-specific prevalence of low muscle strength (3.6-7.2%) and sarcopenia (0.1-1.4%) did not differ by NAFLD status. However, NAFLD was associated with 74% (males) and 370% (females) higher prevalence of low ASM when adjusted for BMI but an 82% (males) to 89% (females) lower prevalence when adjusted for height2 (all P < 0.05). The prevalence of impaired physical function was 40% (males, P = 0.08) to 123% (females, P < 0.001) higher in NAFLD. In middle-aged and older adults, NAFLD was not associated with a higher prevalence of low muscle strength or sarcopenia but was associated with an increased risk of impaired physical function and low muscle mass when adjusted for BMI. These findings support the use of adiposity-based adjustments when assessing low muscle mass and the assessment of physical function in NAFLD.

Multiparametric ultrasound as a new concept of assessment of liver tissue damage.

Liver disease accounts for approximately 2 million deaths per year worldwide. All chronic liver diseases (CLDs), whether of toxic, genetic, autoimmune, or infectious origin, undergo typical histological changes in the structure of the tissue. These changes may include the accumulation of extracellular matrix material, fats, triglycerides, or tissue scarring. Noninvasive methods for diagnosing CLD, such as conventional B-mode ultrasound (US), play a significant role in diagnosis. Doppler US, when coupled with B-mode US, can be helpful in evaluating the hemodynamics of hepatic vessels and detecting US findings associated with hepatic decompensation. US elastography can assess liver stiffness, serving as a surrogate marker for liver fibrosis. It is important to note that interpreting these values should not rely solely on a histological classification. Contrast-enhanced US (CEUS) provides valuable information on tissue perfusion and enables excellent differentiation between benign and malignant focal liver lesions. Clinical evaluation, the etiology of liver disease, and the patient current comorbidities all influence the interpretation of liver stiffness measurements. These measurements are most clinically relevant when interpreted as a probability of compensated advanced CLD. B-mode US offers a subjective estimation of fatty infiltration and has limited sensitivity for mild steatosis. The controlled attenuation parameter requires a dedicated device, and cutoff values are not clearly defined. Quan-titative US parameters for liver fat estimation include the attenuation coefficient, backscatter coefficient, and speed of sound. These parameters offer the advantage of providing fat quantification alongside B-mode evaluation and other US parameters. Multiparametric US (MPUS) of the liver introduces a new concept for complete noninvasive diagnosis. It encourages examiners to utilize the latest features of an US machine, including conventional B-mode, liver stiffness evaluation, fat quantification, dispersion imaging, Doppler US, and CEUS for focal liver lesion characterization. This comprehensive approach allows for diagnosis in a single examination, providing clinicians worldwide with a broader perspective and becoming a cornerstone in their diagnostic arsenal. MPUS, in the hands of skilled clinicians, becomes an invaluable predictive tool for diagnosing, staging, and monitoring CLD.

Serum PRO-C3 is useful for risk prediction and fibrosis assessment in MAFLD with chronic kidney disease in an Asian cohort.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is an emerging risk factor for chronic kidney disease (CKD). N-terminal propeptide of collagen type 3 (PRO-C3) is a biomarker of advanced fibrosis in MAFLD and PRO-C3 may be involved in renal fibrosis. We aimed to use PRO-C3 measurements to generate a new algorithmic score to test the prediction of MAFLD with chronic kidney disease (MAFLD-CKD). METHODS: A derivation and independent validation cohort of 750 and 129 Asian patients with biopsy-confirmed MAFLD were included. Serum PRO-C3 concentration was measured and regression analyses were performed to examine associations with MAFLD-CKD. A derivative algorithm for MAFLD-CKD risk prediction was evaluated with receiver operator characteristic (ROC) curve analysis. RESULTS: The study included two Asian cohorts (n = 180 with MAFLD-CKD; mean-eGFR: 94.93 mL/min/1.73 m2; median-urinary albumin-to-creatinine ratio: 6.58 mg/mmol). PRO-C3 was associated with the severity of MAFLD-CKD and independently associated with MAFLD-CKD (adjusted odds ratio = 1.16, 95% confidence interval [CI]: 1.08-1.23, p < .001). A new non-invasive score (termed PERIOD) including PRO-C3 efficiently predicted MAFLD-CKD (AUROC = .842, 95% CI: .805-.875). Accuracy, specificity and negative predictive values were 80.2%, 85.1% and 88.4%, respectively. In the validation cohort, the PERIOD score had good diagnostic performance (AUROC = .807, 95% CI: .691-.893) with similar results in all patient subgroups. In the MAFLD-CKD subgroup, the accuracy for identifying advanced fibrosis was further improved by combining the PRO-C3-based ADAPT with the Agile 3+ scores (AUROC = .90, 95% CI: .836-.964). CONCLUSIONS: The PERIOD score is helpful for accurately predicting the risk of MAFLD-CKD. PRO-C3 can also be used to assess liver fibrosis in people with MAFLD-CKD.

Effect of a Hispanic outreach program on referral and liver transplantation volume at a single center.

BACKGROUND: Although Hispanic patients have high rates of end-stage liver disease and liver cancer, for which liver transplantation (LT) offers the best long-term outcomes, they are less likely to receive LT. Studies of end-stage renal disease patients and kidney transplant candidates have shown that targeted, culturally relevant interventions can increase the likelihood of Hispanic patients receiving kidney transplant. However, similar interventions remain largely unstudied in potential LT candidates. METHODS: Referrals to a single center in Texas with a large Hispanic patient population were compared before (01/2018-12/2019) and after (7/2021-6/2023) the implementation of a targeted outreach program. Patient progress toward LT, reasons for ineligibility, and differences in insurance were examined between the two eras. RESULTS: A greater proportion of Hispanic patients were referred for LT after the implementation of the outreach program (23.2% vs 26.2%, p = 0.004). Comparing the pre-outreach era to the post-outreach era, more Hispanic patients achieved waitlisting status (61 vs 78, respectively) and received a LT (971 vs 82, respectively). However, the proportion of Hispanic patients undergoing LT dropped from 30.2% to 20.3%. In the post-outreach era, half of the Hispanic patients were unable to get LT for financial reasons (112, 50.5%). CONCLUSIONS: A targeted outreach program for Hispanic patients with end-stage liver disease effectively increased the total number of Hispanic LT referrals and recipients. However, many of the patients who were referred were ineligible for LT, most frequently for financial reasons. These results highlight the need for additional research into the most effective ways to ameliorate financial barriers to LT in this high-need community.

Proactive case finding of alcohol-related liver disease in high-risk populations: A systematic review.

BACKGROUND: Alcohol-related liver disease (ARLD) is often diagnosed at a late stage when mortality is unacceptably high. Earlier identification of ARLD may lead to reduced alcohol intake, participation in hepatocellular carcinoma surveillance and reduction in liver-related morbidity and mortality. People with alcohol use disorder (AUD) are at highest risk of ARLD. The aim of this systematic review was to understand the yield of proactive screening for ARLD amongst high-risk groups. METHODS: Embase, Medline, Scopus and grey literature were searched for studies describing proactive assessment for alcohol-related liver disease in people with a history of alcohol excess or diagnosed AUD. Outcomes of interest were fibrosis and cirrhosis detection rates, clinical outcomes, portal hypertension evaluation, attendance at follow-up and cost-effectiveness. RESULTS: Fifteen studies were identified for inclusion from 1115 returned by the search. Four key settings for patient engagement were identified as inpatient addiction services, outpatient addiction services, general acute hospital admissions and community outreach. Of these, acute hospital admissions were the highest yield for cirrhosis at 10.8%-29.6% and community outreach the lowest was 1.2%-2.3%. CONCLUSIONS: Targeted fibrosis assessment of high-risk populations for ARLD is feasible to conduct and identifies a proportion of patients at risk of advanced liver disease. The highest yield is amongst inpatients admitted with AUD. Prospective work is needed to establish which are the most effective and acceptable screening methods and the impact on long-term outcomes.

The Health Care Burden of Hepatic Encephalopathy.

Hepatic encephalopathy-a common and debilitating complication of cirrhosis-results in major health care burden on both patients and caregivers through direct and indirect costs. In addition to risk of falls, inability to work and drive, patients with hepatic encephalopathy often require hospital admission (and often readmission), and many require subacute care following hospitalization. The costs and psychological impact of liver transplantation often ensue. As the prevalence of chronic liver disease increases throughout the United States, the health care burden of hepatic encephalopathy will continue to grow.

Quantitative digital pathology enables automated and quantitative assessment of inflammatory activity in patients with autoimmune hepatitis.

Background: Chronic liver disease diagnoses depend on liver biopsy histopathological assessment. However, due to the limitations associated with biopsy, there is growing interest in the use of quantitative digital pathology to support pathologists. We evaluated the performance of computational algorithms in the assessment of hepatic inflammation in an autoimmune hepatitis in which inflammation is a major component. Methods: Whole-slide digital image analysis was used to quantitatively characterize the area of tissue covered by inflammation [Inflammation Density (ID)] and number of inflammatory foci per unit area [Focal Density (FD)] on tissue obtained from 50 patients with autoimmune hepatitis undergoing routine liver biopsy. Correlations between digital pathology outputs and traditional categorical histology scores, biochemical, and imaging markers were assessed. The ability of ID and FD to stratify between low-moderate (both portal and lobular inflammation ≤1) and moderate-severe disease activity was estimated using the area under the receiver operating characteristic curve (AUC). Results: ID and FD scores increased significantly and linearly with both portal and lobular inflammation grading. Both ID and FD correlated moderately-to-strongly and significantly with histology (portal and lobular inflammation; 0.36≤R≤0.69) and biochemical markers (ALT, AST, GGT, IgG, and gamma globulins; 0.43≤R≤0.57). ID (AUC: 0.85) and FD (AUC: 0.79) had good performance for stratifying between low-moderate and moderate-severe inflammation. Conclusion: Quantitative assessment of liver biopsy using quantitative digital pathology metrics correlates well with traditional pathology scores and key biochemical markers. Whole-slide quantification of disease can support stratification and identification of patients with more advanced inflammatory disease activity.