Liver cirrhosis in a patient with alcohol dependence and autoimmune hepatitis.

BACKGROUND: Liver cirrhosis is the end-stage entity for a wide variety of chronic liver pathologies. These include viral hepatitis B and C, alcoholic liver disease, non-alcoholic fatty liver disease, hemochromatosis, Wilson disease, autoimmune hepatitis, primary sclerosing cholangitis, and primary biliary cirrhosis. In the majority of cases, liver cirrhosis remains completely asymptomatic until acute decompensation occurs. Patients may present complications of portal hypertension such as gastro-esophageal varices and upper digestive hemorrhage, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, or hepato-renal syndrome. Establishing the right etiology of cirrhosis is of paramount importance as it helps the treating physician plan the best suitable treatment options and also improves overall outcome. CASE REPORT: We present a case of a chronic alcohol consumer, which, over time, resulted in alcoholic cirrhosis. Initial diagnosis comprised of alcoholic liver disease. However, a further look into the medical history of the patients indicated the presence of underlying autoimmune liver disease, such as autoimmune hepatitis, which might have also contributed to the chronic liver injury. CONCLUSIONS: Multiple factors can lead to liver cirrhosis. Although the most commonly found entity is alcoholism, it cannot be taken as a thumb rule for the only possible etiology. In-depth analysis and proper differential diagnosis should be carefully conducted in order not to miss out on other possible causes. As seen in our case, where an underlying autoimmune hepatitis was found to be the culprit, but due to a long history of alcohol consumption, it was masked at first instance.

Patients with early-stage alcohol-associated liver disease are at increased risk of hospital readmission and death.

BACKGROUND AND AIMS: Patients with alcohol use disorder (AUD) can develop alcohol-associated fatty liver disease (AFLD). However, the impact of AFLD on outcomes remains unclear. We studied the impact of AFLD on readmission, 30-day mortality, and overall mortality in patients admitted with AUD. METHODS: Hospitalized patients with AUD between 2011 and 2019 at a tertiary medical center were retrospectively evaluated. Our population included patients with AUD with AFLD: AST and ALT elevation and serum bilirubin <3 mg/dl. Patients with AUD without evidence of liver disease served as control and were labeled as no ALD. Patients with alcohol-associated cirrhosis (AC) and alcohol-associated hepatitis (AH) were included for comparison. Kaplan-Meier survival analysis and multivariable regression for predictors of mortality and survival were performed. RESULTS: There were 7522 patients of which 32.44% were female with mean age of 51.86 ±â€…14.41 years. Patient distribution included no ALD (n = 3775), AFLD (n = 2192), AC (n = 1017) and AH (n = 538) groups. Compared to no ALD group, AFLD group was associated with significantly higher 30-day mortality [4.43% vs. 1.56%, hazard ratio (HR): 2.84; P  < 0.001], overall mortality [15.97% vs. 12.69%, HR 1.40, P  < 0.001], and 30-day readmission [21.85% vs. 18.49%, odds ratio: 1.21; P  < 0.01]. CONCLUSION: We demonstrated that AFLD is not a benign entity and poses significant mortality risk. Our results suggest that AFLD may be under-recognized and highlight the need for focused management and close follow-up after discharge.

Impact of continued alcohol use on liver-related outcomes of alcohol-associated cirrhosis: a retrospective study of 440 patients.

BACKGROUND AND AIM: The prevalence of alcohol-associated cirrhosis is increasing. In this respect, we investigated the long-term impact of non-abstinence on the clinical course of alcohol-associated cirrhosis. METHODS: We retrospectively evaluated 440 patients with alcohol-associated cirrhosis (compensated cirrhosis: n  = 190; decompensated cirrhosis: n  = 250) diagnosed between January 2000 and July 2017 who consumed alcohol until diagnosis of cirrhosis. We assessed liver-related outcomes including first and further decompensating events (ascites, variceal bleeding, and hepatic encephalopathy), and death in relation to continued alcohol use. RESULTS: Overall, 53.6% of patients remained abstinent (compensated cirrhosis: 57.9%; decompensated cirrhosis: 50.4%). Non-abstinent versus abstinent patients with compensated cirrhosis and decompensated cirrhosis showed significantly higher 5-year probability of first decompensation (80.2% vs. 36.8%; P  < 0.001) and further decompensation (87.9% vs. 20.6%; P  < 0.001), respectively. Five-year survival was substantially lower among non-abstinent patients with compensated cirrhosis (45.9% vs. 90.7%; P  < 0.001) and decompensated cirrhosis (22.9% vs. 73.8%; P  < 0.001) compared to abstinent. Non-abstinent versus abstinent patients of the total cohort showed an exceedingly lower 5-year survival (32.2% vs. 82.4%; P  < 0.001). Prolonged abstinence (≥2 years) was required to influence outcomes. Non-abstinence independently predicted mortality in the total cohort (hazard ratio [HR] 3.371; confidence interval [CI]: 2.388-4.882; P  < 0.001) along with the Child-Pugh class (HR: 4.453; CI: 2.907-6.823; P  < 0.001) and higher age (HR: 1.023; CI: 1.007-1.039; P  = 0.005). CONCLUSION: Liver-related outcomes are worse among non-abstinent patients with alcohol- associated cirrhosis prompting urgent interventions ensuring abstinence.

Difference and clinical value of metabolites in plasma and feces of patients with alcohol-related liver cirrhosis.

BACKGROUND: Alterations in plasma and intestinal metabolites contribute to the pathogenesis and progression of alcohol-related liver cirrhosis (ALC). AIM: To explore the common and different metabolites in the plasma and feces of patients with ALC and evaluate their clinical implications. METHODS: According to the inclusion and exclusion criteria, 27 patients with ALC and 24 healthy controls (HCs) were selected, and plasma and feces samples were collected. Liver function, blood routine, and other indicators were detected with automatic biochemical and blood routine analyzers. Liquid chromatography-mass spectrometry was used to detect the plasma and feces metabolites of the two groups and the metabolomics of plasma and feces. Also, the correlation between metabolites and clinical features was analyzed. RESULTS: More than 300 common metabolites were identified in the plasma and feces of patients with ALC. Pathway analysis showed that these metabolites are enriched in bile acid and amino acid metabolic pathways. Compared to HCs, patients with ALC had a higher level of glycocholic acid (GCA) and taurocholic acid (TCA) in plasma and a lower level of deoxycholic acid (DCA) in the feces, while L-threonine, L-phenylalanine, and L-tyrosine increased simultaneously in plasma and feces. GCA, TCA, L-methionine, L-phenylalanine, and L-tyrosine in plasma were positively correlated with total bilirubin (TBil), prothrombin time (PT), and maddrey discriminant function score (MDF) and negatively correlated with cholinesterase (CHE) and albumin (ALB). The DCA in feces was negatively correlated with TBil, MDF, and PT and positively correlated with CHE and ALB. Moreover, we established a P/S BA ratio of plasma primary bile acid (GCA and TCA) to fecal secondary bile acid (DCA), which was relevant to TBil, PT, and MDF score. CONCLUSION: The enrichment of GCA, TCA, L-phenylalanine, L-tyrosine, and L-methionine in the plasma of patients with ALC and the reduction of DCA in feces were related to the severity of ALC. These metabolites may be used as indicators to evaluate the progression of alcohol-related liver cirrhosis.

Alcoholic cardiomyopathy in patients with alcoholic liver cirrhosis: a study across 10†years.

BACKGROUND AND OBJECTIVES: Available data regarding cardiomyopathy in patients with alcoholic liver cirrhosis (ALC) are very limited because it often requires multidisciplinary assessments. The study aims to evaluate the prevalence of alcoholic cardiomyopathy in ALC and their clinical correlations. METHODS: Adult ALC patients without a previous diagnosis of cardiovascular diseases between January 2010 and December 2019 were included in the study. The prevalence rate of alcoholic cardiomyopathy in patients with ALC was calculated together with a 95% confidence interval (CI) using the Clopper-Pearson exact method. RESULTS: A total of 1022 ALC patients were included. Male patients predominated (90.5%). ECG abnormalities were observed in 353 patients (34.5%). Prolonged QT interval was most common in ALC patients with ECG abnormalities, which occurred in 109. Thirty-five ALC patients underwent the cardiac MRI examination and only one patient was found with cardiomyopathy. The estimated prevalence rate of alcoholic cardiomyopathy in all the ALC patients was 0.0286 (95% CI, 0.0007-0.1492). There was no statistical difference regarding the prevalence rate between the group of patients with ECG abnormalities and the group without ECG abnormalities (0.0400 vs. 0.0000, P  = 1.000). CONCLUSION: Although ECG abnormalities, especially QT prolongation, existed in a proportion of ALC patients, cardiomyopathy in the patient population was not common. Further larger-sample studies based on cardiac MRI are needed to verify our results.

Red blood cell distribution width derivatives in alcohol-related liver cirrhosis and metabolic-associated fatty liver disease.

BACKGROUND: Looking for undiscovered blood markers of liver fibrosis and steatosis still remains an issue worth exploring. There are still plenty of unresolved issues related to the actual role of hematological indices as potential markers of liver function. AIM: To study red blood cell distribution width (RDW), RDW-to-platelet ratio (RPR) and RDW-to-lymphocyte ratio (RLR) in alcohol-related liver cirrhosis (ALC) and metabolic-associated fatty liver disease (MAFLD). METHODS: The study group was composed of 302 people: 142 patients with ALC and 92 with MAFLD; 68 persons were included as controls. RDW, RPR and RLR were measured in each person. Indirect and direct parameters of liver fibrosis were also assessed [aspartate transaminase to alkaline transaminase ratio, aspartate transaminase to platelet ratio index (APRI), fibrosis-4 (FIB-4), gamma-glutamyl transpeptidase to platelet ratio (GPR), procollagen I carboxyterminal propeptide, procollagen III aminoterminal propeptide, transforming growth factor-α, platelet-derived growth factor AB, laminin]. MELD score in ALC patients and non-alcoholic fatty liver disease (NAFLD) fibrosis score together with BARD score were obtained in the MAFLD group. The achieved results were compared to controls. Then a correlation between assessed markers was done. Diagnostic value of each investigated parameter and its suggested cut-off in the research group were evaluated with area under the curve (AUC). RESULTS: RDW, RPR and RLR values turned out to be significantly higher in ALC and MAFLD groups compared to controls (ALC: P < 0.0001; NAFLD: P < 0.05, P < 0.0001 and P < 0.0001, respectively). RPR correlated positively with MELD score (P < 0.01) and indirect indices of liver fibrosis (FIB-4 and GPR; P < 0.0001) in ALC patients; negative correlations were found between PDGF-AB and both: RDW and RPR (P < 0.01 and P < 0.0001, respectively). RPR correlated positively with NAFLD fibrosis score and APRI (P < 0.0001) in the MAFLD group; a positive relationship was observed between RDW and FIB-4, too (P < 0.05). AUC values and suggested cut-offs for RDW, RPR and RLR in ALC patients were: 0.912 (> 14.2%), 0.965 (> 0.075) and 0.914 (> 8.684), respectively. AUC values and suggested cut-offs for RDW, RPR and RLR in MAFLD patients were: 0.606 (> 12.8%), 0.724 (> 0.047) and 0.691 (> 6.25), respectively. CONCLUSION: RDW with its derivatives appear to be valuable diagnostic markers in patients with ALC. They can also be associated with a deterioration of liver function in this group.

Length of Alcohol Abstinence Predicts Posttransplant Delirium in Living Donor Liver Transplant Recipients with Alcoholic Cirrhosis.

OBJECTIVES: History of alcohol abuse is a predictive factor for posttransplant delirium. We aimed to investigate whether preoperative abstinence was associated with posttransplant delirium in liver transplant recipients with alcohol-related cirrhosis. MATERIALS AND METHODS: From January 2014 to December 2019, 84 patients with alcohol-related cirrhosis who received living donor liver transplant were retrospectively reviewed and divided into a delirium group (n = 46, 54.8%) and a nondelirium group (n = 38, 45.2%) using the Richmond Agitation- Sedation Scale and the Confusion Assessment Method for the Intensive Care Unit. RESULTS: In the delirium group versus the nondelirium group, patients were more likely to have preoperative hepatic encephalopathy (58.7% vs 31.6%; P = .013), more likely to have higher Model for End-Stage Liver Disease scores (27.05 ± 10.56 vs 18.85 ± 7.96; P < .001), less likely to have preoperative alcohol abstinence (43.5% vs 68.4%%; P = .022), had longer duration of mechanical ventilation (7.57 ± 7.82 vs 2.50 ± 5.96 days; P = .001), and had longer stays in the intensive care unit (14.85 ± 15.01 vs 8.84 ± 7.84 days; P = .021) and in the hospital (37.89 ± 18.85 vs 27.15 ± 10.43 days; P = .002). Multivariate analysis revealed that preoperative alcohol abstinence (odds ratio 4.953; 95% CI, 1.519-16.152; P = .008) was a significant predictor and that more patients had abstinence durations <3 months (60.9% vs 34.2%; P = .048) in the delirium group. CONCLUSIONS: A high incidence of posttransplant delirium in liver transplant recipients with alcohol- related cirrhosis was associated with preoperative abstinence. Abstinence >6 months before living donor liver transplant is suggested to reduce the risk of posttransplant delirium.

The clinical implication of psychiatric illnesses in patients with alcoholic liver disease: an analysis of US hospitals.

BACKGROUND: In this study, we evaluate the clinical impact of psychiatric illnesses (PI) on the hospital outcomes of patients admitted with alcoholic liver disease (ALD). METHODS: From the National Inpatient Sample from 2012-2017, patients with alcoholic cirrhosis or alcoholic hepatitis were selected and stratified using the presence/absence of PI (which was a composite of psychiatric conditions). The cases were propensity score-matched to PI-absent controls and were compared to the following endpoints: mortality, death due to suicide, length of stay (LOS), hospitalization charges, and hepatic complications. RESULTS: After matching, there were 122,907 PI with and 122,907 without PI. Those with PI were younger (51.8 vs. 51.9 years p = 0.02) and more likely to be female (39.2 vs. 38.7% p = 0.01); however, there was no difference in race. Patients with PI had lower rates of alcoholic cirrhosis but higher rates of alcoholic hepatitis/alcoholic hepatic steatosis. In multivariate, patients with PI had lower rates of all-cause mortality (aOR 0.51 95%CI 0.49-0.54); however, they experienced higher rates of deaths due to suicide (aOR 3.00 95%CI 1.56-5.78) and had longer LOS (aOR 1.02 95%CI 1.01-1.02). CONCLUSION: Presence of PI in ALD patients is associated with prolonged hospital stay and higher rates deaths due to suicide.

Theragnostic Efficacy of K18 Response in Alcohol Use Disorder with Clinically Significant Fibrosis Using Gut-Liver Axis.

(1) Background: Fibrosis in early-stage alcohol-associated liver disease (ALD) is commonly under-diagnosed in routine clinical practice. This study characterized the liver-injury and cell death response in alcohol use disorder (AUD) patients with ALD who also exhibited fibrosis and assessed the efficacy of standard of care (SOC) treatment in the improvement in liver injury. (2) Methods: Forty-eight heavy-drinking AUD patients aged 21−65 yrs. without clinical manifestations of liver injury were grouped by Fibrosis-4 (FIB-4) score, as negative (Gr.1 < 1.45, n = 21) or positive (Gr.2 ≥ 1.45, n = 27). Patients received 2-weeks (2 w) inpatient SOC. Data on demographics, drinking patterns, liver-injury, immune markers, and liver cell death (K18s) markers were analyzed at baseline (BL) and after 2 w SOC. (3) Results: Lifetime drinking (LTDH, yrs.) and acute heavy drinking (Heavy Drinking Days Past 90 Days [HDD90]) markers were significantly higher in Gr.2 vs. Gr.1. BL ALT, AST, AST:ALT and K18M65 were considerably higher in Gr.2. Dysregulated gut dysfunction and elevated immune activity were evident in Gr.2 characterized by TNF-α, IL-8 and LPS levels. After SOC, Gr.2 showed improvement in AST, ALT, AST/ALT ratio; and in the K18M65, K18M30 and K18M65/M30 ratio vs. Gr.1. The true positivity of BL IL-8 response to predict the improvement in K18M65 to normal levels among Gr.2 patients against those who did not have improvement after 2 w SOC was very high (AUROC = 0.830, p = 0.042). (4) Conclusions: Gut dysfunction, elevated cytokine response and necrotic liver cell death were elevated in AUD patients with early-stage ALD. K18 showed promise as a predictive theragnostic factor to differentiate among the AUD patients with early-stage ALD and baseline fibrosis who had improvement in liver injury against those who did not, by the levels of baseline IL-8.

FcGBP and VCAM-1 are ponderable biomarkers for differential diagnosis of alcoholic liver cirrhosis.

BACKGROUND/ AIMS: Early diagnosis of alcoholic liver cirrhosis (ALD) and coexisting ALD and hepatitis B virus-induced cirrhosis (ALD+HBV) is primordial for an optimal management of these conditions. However, the lack of specific noninvasive biomarkers coupled with the inaccuracy of self-reported alcohol consumption make the early diagnosis of these pathologies difficult. This study aimed to identify biomarkers to diagnose ALD and differentiate ALD+HBV from HBV. METHODS: Proteomics mass spectrometry technique was used to identify specific proteins of ALD by contrasting serums of ALD to that of healthy subjects. The accuracy of the selected proteins in diagnosing ALD and discriminating ALD+HBV from HBV was assessed in two independent cohorts using the area under the receiver operator characteristic curve (AUROC). RESULTS: 452 cirrhotic and normal subjects were enrolled in this study. The proteomic results revealed that FcGBP and VCAM-1 were the highest overexpressed proteins while comparing ALD samples to the healthy cohort. The combination of these two biomarkers had an AUROC of 0.986 (P < 0.001, sensitivity: 97.2%, specificity: 100%) in identifying ALD from the healthy cohort, and AUROC of 0.781 (P < 0.001, sensitivity: 81.8%, specificity: 77.0%) in differentiating ALD+HBV from HBV. This combination was more accurate than the combination of AST/ALT, MCV and GGT (ALD vs healthy, AUROC = 0.898; ALD+HBV vs HBV, AUROC = 0.599). The discrimination performance of this combination was further validated in another independent cohort. CONCLUSION: FcGBP and VCAM-1 are two promising biomarkers in the diagnosis of ALD and in the differentiating of ALD+HBV from HBV subjects.

A scoring system for predicting hepatocellular carcinoma risk in alcoholic cirrhosis.

The role of hepatocellular carcinoma (HCC) surveillance is being questioned in alcoholic cirrhosis because of the relative low HCC risk. This study aimed to assess the risk and predictors of HCC in Korean patients with alcoholic cirrhosis by using competing risk analysis. A total of 745 patients with alcoholic cirrhosis were recruited at a university-affiliated hospital in Korea and randomly assigned to either the derivation (n = 507) and validation (n = 238) cohort. Subdistribution hazards model of Fine and Gray was used with deaths and liver transplantation treated as competing risks. Death records were confirmed from Korean government databases. A nomogram was developed to calculate the Alcohol-associated Liver Cancer Estimation (ALICE) score. The cumulative incidence of HCC was 15.3 and 13.3% at 10 years for derivation and validation cohort, respectively. Age, alpha-fetoprotein level, and albumin level were identified as independent predictors of HCC and incorporated in the ALICE score, which discriminated low, intermediate, and high risk for HCC in alcoholic cirrhosis at the cut-off of 60 and 100. The risk of HCC can be stratified by using a combination of readily available clinical parameters (age, AFP level, and albumin level) in patients with alcoholic cirrhosis.

Algorithms to Identify Alcoholic Hepatitis Hospitalizations in Patients with Cirrhosis.

BACKGROUND: Alcoholic hepatitis (AH) is a clinically diagnosed syndrome with high short-term mortality for which liver transplantation may be curative. A lack of validated algorithms to identify AH hospitalizations has hindered clinical epidemiology research. METHODS: This was a retrospective cohort study of patients with cirrhosis using Veterans Health Administration (VHA) data from 2008 to 2015. We randomly sampled hospitalizations based upon abnormal liver tests and administrative codes for acute hepatitis or alcohol-associated liver disease (ALD). Hospitalizations were manually adjudicated for AH per society guidelines. A priori algorithms were evaluated to compute positive predicted value (PPV) and positive likelihood ratio (LR+), and were tested in an external University of Pennsylvania Health System (UPHS) cohort. RESULTS: Of 368 hospitalizations, 142 (38.6%) were adjudicated as AH. AH patients were younger (55 vs. 58 years, p < 0.001), less likely to have prior cirrhosis decompensation (57% vs. 73.9%, p < 0.001), and had higher AST-to-ALT ratios (median 2.9 vs. 1.9 mg/dL, p < 0.001) and higher bilirubin levels (median 2.9 vs. 1.9 mg/dL, p < 0.001). Algorithms combining clinical laboratory criteria (AST > 85 U/L but < 450 U/L, AST-to-ALT ratio > 2, total bilirubin > 5 mg/dL) and administrative coding criteria yielded the highest PPV (96.4%, 95% CI 87.7-99.6) and the highest LR+ (43.0, 95% CI 10.6-173.5). Several algorithms demonstrated 100% PPV for definite AH in the UPHS external cohort. CONCLUSION: We have identified algorithms for AH hospitalizations with excellent PPV and LR+. These high-specificity algorithms may be used in VHA datasets to identify patients with high likelihood of AH, but should not be used to study AH incidence.

A genetic risk score and diabetes predict development of alcohol-related cirrhosis in drinkers.

BACKGROUND & AIMS: Only a minority of excess alcohol drinkers develop cirrhosis. We developed and evaluated risk stratification scores to identify those at highest risk. METHODS: Three cohorts (GenomALC-1: n = 1,690, GenomALC-2: n = 3,037, UK Biobank: relevant n = 6,898) with a history of heavy alcohol consumption (≥80 g/day (men), ≥50 g/day (women), for ≥10 years) were included. Cases were participants with alcohol-related cirrhosis. Controls had a history of similar alcohol consumption but no evidence of liver disease. Risk scores were computed from up to 8 genetic loci identified previously as associated with alcohol-related cirrhosis and 3 clinical risk factors. Score performance for the stratification of alcohol-related cirrhosis risk was assessed and compared across the alcohol-related liver disease spectrum, including hepatocellular carcinoma (HCC). RESULTS: A combination of 3 single nucleotide polymorphisms (SNPs) (PNPLA3:rs738409, SUGP1-TM6SF2:rs10401969, HSD17B13:rs6834314) and diabetes status best discriminated cirrhosis risk. The odds ratios (ORs) and (95% CIs) between the lowest (Q1) and highest (Q5) score quintiles of the 3-SNP score, based on independent allelic effect size estimates, were 5.99 (4.18-8.60) (GenomALC-1), 2.81 (2.03-3.89) (GenomALC-2), and 3.10 (2.32-4.14) (UK Biobank). Patients with diabetes and high risk scores had ORs of 14.7 (7.69-28.1) (GenomALC-1) and 17.1 (11.3-25.7) (UK Biobank) compared to those without diabetes and with low risk scores. Patients with cirrhosis and HCC had significantly higher mean risk scores than patients with cirrhosis alone (0.76 ± 0.06 vs. 0.61 ± 0.02, p = 0.007). Score performance was not significantly enhanced by information on additional genetic risk variants, body mass index or coffee consumption. CONCLUSIONS: A risk score based on 3 genetic risk variants and diabetes status enables the stratification of heavy drinkers based on their risk of cirrhosis, allowing for the provision of earlier preventative interventions. LAY SUMMARY: Excessive chronic drinking leads to cirrhosis in some people, but so far there is no way to identify those at high risk of developing this debilitating disease. We developed a genetic risk score that can identify patients at high risk. The risk of cirrhosis is increased >10-fold with just two risk factors - diabetes and a high genetic risk score. Risk assessment using this test could enable the early and personalised management of this disease in high-risk patients.

Blood-Based Targeted Metabolomics Discriminate Patients with Alcoholic Liver Cirrhosis from Those with Non-Cirrhotic Liver Damage: An Explorative Study.

BACKGROUND: Early detection of liver cirrhosis is crucial for secondary prevention of complications. However, noninvasive blood-based patient monitoring tools are lacking. In this explorative study, we conducted a targeted metabolomic analysis in order to identify possible serum markers indicating alcoholic liver cirrhosis (aLiC) with or without hepatocellular carcinoma (HCC). METHODS: Venous blood of 30 individuals was collected: healthy controls ("Con", n = 12), patients with aLiC without and with HCC ("aLiC": n = 6 and "aLiC + HCC": n = 6), and patients with other liver diseases ("oLiD": n = 6). A targeted metabolomic analysis was conducted using the AbsoluteIDQ® p180 Kit (Biocrates Life Sciences®, Innsbruck, Austria). Statistical analysis was performed by applying a one-way ANOVA on all subgroups followed by a t test for pairwise comparison of subgroups and logistic regression analysis. RESULTS: ANOVA revealed 29 metabolites that significantly discriminate between the different cohorts. Among these analytes, 25 were significantly altered in Con versus aLiC, as indicated by t test, most importantly SM C18:1 (p < 0.001), SM C20:2 (p = 0.001), SM (OH) C22:2 (p < 0.001), lysoPC a C20:4 (p < 0.001), and PC aa C36:5 (p < 0.001). To a similar extent, the metabolites discriminated also between the oLiD and aLiC but less between the Con or oLiD and aLiC + HCC cohorts. Most of these analytes were either lyso- and phosphatidylcholines or sphingomyelins. Results were not significant for comparison of Con versus oLiD and aLiC versus aLiC + HCC. CONCLUSION: Decreased lyso- and phosphatidylcholine as well as sphingomyelin species in venous blood could help to detect liver cirrhosis in patients with non-cirrhotic liver disease.

Hepatic fibrosis of any origin in a large population of type 2 diabetes patients.

BACKGROUND AND AIMS: Excess morbidity and mortality from chronic liver disease in type 2 diabetes (T2DM) is recognized; however, the clinical features associated with liver fibrosis (LF) of any origin are poorly known. Metabolic status and/or coexisting complications over time may play a role. METHODS AND RESULTS: We interrogated the database of the diabetes unit network of Piedmont (Italy) (71,285 T2DM patients) and calculated a fibrosis-4 score (FIB-4) from data recorded between 2006 and 2019. Comorbidities were obtained by linkage with hospital data. The study population was subdivided by aetiology of LF (alcoholic, viral, metabolic). Associations between upper level of FIB-4 and demographic and clinical variables were evaluated separately for each group using robust Poisson models and presented as prevalence ratios. Nearly one-quarter (24%) of T2DM patients had some form of LF: viral (0.44%) and alcoholic (0.53%) forms were far less frequent than metabolic ones (22.7%). Only 1 out of 5 of these patients had a history of known cirrhosis. Age, male sex, duration of diabetes, coronary disease, hyperuricemia, renal failure, and features of liver failure (e.g., lower body-mass index, lipid and HbA1c levels) were positively associated with metabolic LF. More intensive treatments with insulin and segretagogue emerged as a significant predictive indicators of LF of metabolic origin. CONCLUSION: A sizeable proportion of T2DM patients has some degree of LF, mainly of metabolic origin and often undiagnosed. There is a need to clarify whether the link between insulin therapy and advanced LF is causal or not.