Non-alcohol Related Liver Disease Research Articles

Bisphosphonate effectiveness in patients with cirrhosis: An emulated clinical trial.

Falls and fractures are common and morbid for patients with cirrhosis. Bisphosphonates are recommended for the prevention of fractures for people with osteoporosis cirrhosis; however, data supporting effectiveness in cirrhosis are lacking. We sought to emulate a clinical trial of bisphosphonates in cirrhosis. We used national Medicare data (2008-2020) to examine the 5-year risk of fractures in patients who did or did not receive bisphosphonates with a new-user design among people diagnosed with cirrhosis and osteoporosis. We balanced treated and untreated with inverse probability of treatment weighting, evaluated intention-to-treat and as-treated effects, and examined both control exposures (statin use) and outcomes (decompensation) to test causal relationships. There were 253 and 20,888 new users and non-users of bisphosphonates, respectively. The median age was 74 years. The most common bisphosphonate used was alendronate (73.6%). Bisphosphonates significantly reduced fractures overall (27.5% vs. 33.0%, p = 0.0004) in the intention-to-treat analysis, particularly for people <65 years (sHR 0.56) old, men (sHR 0.64) and those with non-alcohol related liver disease (sHR 0.85). Though there were fewer arm (20.7% vs. 26.4%, p < 0.0001) and femur (28.9% vs. 31.2%, p = 0.005), there were more spinal (25.8% vs. 19.0%), rib (40.0% vs. 32.2%) and skull (10.1% vs. 8.7%) fractures. In the as-treated analysis, cumulative bisphosphonate exposure significantly reduced fractures, sHR 0.95 95% CI (0.91, 0.98). Treatment was inconsistent; bisphosphonate users spent 29.9% person-years of follow-up on the drug. In a nationally representative cohort of elderly patients with cirrhosis, bisphosphonates reduced fractures overall. Efforts to increase uptake and drug continuation are needed.

SAT-433 - Assessing the role of organokines as biomarkers for diagnosing non-alcohol related liver disease

SAT-433 - Assessing the role of organokines as biomarkers for diagnosing non-alcohol related liver disease

Personal comorbidities and their subsequent risks for liver, gallbladder and bile duct cancers.

Many environmental risk factors for hepatobiliary cancers are known but whether they are associated with specific cancer types is unclear. We present here a novel approach of assessing standardized incidence ratios (SIRs) of previously diagnosed comorbidities for hepatocellular carcinoma (HCC), gallbladder cancer (GBC), cholangiocarcinoma (CCA) and ampullary cancer. The 13 comorbidities included alcohol and nonalcohol related liver disease, chronic obstructive pulmonary disease, gallstone disease, viral and other kinds of hepatitis, infection of bile ducts, hepatic and other autoimmune diseases, obesity and diabetes. Patients were identified from the Swedish Inpatient Register from 1987 to 2018, and their cancers were followed from 1997 onwards. SIRs for HCC were 80 to 100 in men and women diagnosed with hepatitis C virus and they were also >10 in patients diagnosed with hepatitis B virus, other kind of hepatitis, hepatic autoimmune disease and nonalcohol related liver disease. Many of these risks, as well as alcohol related liver disease, were either specific to HCC or were shared with intrahepatic CCA. For GBC, CCA and ampullary cancer infection of bile ducts was the main risk factor. Gallstone disease, nonhepatic autoimmune diseases and diabetes were associated with all hepatobiliary cancers. The limitations of the study include inability to cover some rare risk factors and limited follow-up time. Many of the considered comorbidities are characterized by chronic inflammation and/or overt immune disturbance in autoimmune diseases. The results suggest that local chronic inflammation and a related immune disturbance is the carcinogenic trigger for all these cancers.

THU092 - Differential roles of receptor interacting protein 3 and mixed lineage kinase like in murine models and patients with alcohol- and non-alcohol related liver disease

THU092 - Differential roles of receptor interacting protein 3 and mixed lineage kinase like in murine models and patients with alcohol- and non-alcohol related liver disease

PS-173-Differential contribution of RIP3-mediated cell death in alcohol and non-alcohol related liver disease

PS-173-Differential contribution of RIP3-mediated cell death in alcohol and non-alcohol related liver disease

Cirrhosis-associated mortality: Frankly, Scarlet, do we really make a damn?

Cirrhosis-associated mortality: Frankly, Scarlet, do we really make a damn?

Liver disease-related admissions in Portugal: clinical and demographic pattern.

To assess the burden of liver disease in Portugal. Cross-sectional study conducted in 2001 among 773,187 patients, corresponding to 922,611 hospital admissions. Liver disease was defined by International Classification of Diseases (9th edition) codes 570-573. The cost of hospitalization was computed using the groups of homogeneous diagnosis defined by the Portuguese Ministry of Health. In 2001 there were 12,371 patients admitted for liver-related disease, for a total of 16,607 hospital admissions, corresponding to 1.6% and 1.8% of all patients and hospital admissions, respectively. The mean age of the subjects was 57 +/- 16 years, with 8870 (72%) men and 3501 (28%) women. There were 2181 in-hospital deaths, corresponding to 17.6% of the patients admitted. Alcohol-related liver disease (ALD) represented 63% of hospitalizations, and non alcohol-related liver disease (NALD) represented 37%. However, among men there were 69% ALD, while in women this percentage was only 46% (P < 0.001). The median length of stay (interquartile range) for each admission was 8 (11) days in ALD and 8 (13) days in NALD, respectively. Complications were reported in 7446 admissions: upper gastrointestinal bleeding, 3436 (46.1%); ascites, 3425 (46.0%); encephalopathy, 2245 (30.2%); jaundice, 122 (1.6%). The cost of hospital admissions for liver disease was euro 59.4 million, corresponding to 2.4% of all hospital health care expenses. Although there are strong limitations depending mostly on the inadequacy of International Classification of Diseases (9th edition) regarding liver disease, present data indicate that this condition is still mainly associated with alcohol, representing an important burden in what concerns either hospitalization time or economic costs.

EFFECTS OF DIFFERENT HEPATIC PATHOLOGIES ON DISPOSITION OF ALFENTANIL IN ANAESTHETIZED PATIENTS

We have studied the influence of different hepatic pathologies on the disposition of alfentanil in 23 unpremedicated patients (six healthy control subjects, six patients with liver dysfunction of alcoholic aetiology and 11 patients with non-alcohol related liver disease). All patients received a bolus of alfentanil 500 micrograms i.v. as supplement to 67% nitrous oxide and isoflurane in oxygen anaesthesia. Plasma drug concentrations were measured in venous blood samples at intervals up to 24 h by radio-immunoassay and protein binding was determined by equilibrium dialysis. Kinetic estimates were determined using non-compartmental analysis. Patients with non-alcoholic liver disease had lesser plasma clearance (114.8 (range 66.8-213.5) ml min-1) than the alcoholic group (158.8 (100.0-220.7) ml min-1) or controls (187.4 (125.2-269.5) ml min-1). In all three groups, there was considerable intersubject variability, with a bimodal distribution in the non-alcoholic group. This group also had a smaller apparent volume of distribution at steady state. Mean residence time was prolonged in the alcoholic group compared with controls (284.9 (217.8-362.2) min vs 226.8 (201.2-250) min). Protein binding was decreased in the alcoholic group compared with controls (84.9 (SD 4.2)% vs 89.3 (2.1)%); this was attributable to a lesser plasma alpha 1-acid glycoprotein concentration (0.55 (0.18) g litre-1 vs 0.89 (0.21) g litre-1). Free drug clearance was reduced in both liver dysfunction groups compared with controls.

The association between alcohol, hepatic pathology and dupuytren's disease

We have looked at the incidence of Dupuytren's disease in alcoholics, those with non-alcoholic liver disease and a control population. Both alcoholic patients and those with non-alcohol related liver disease had a higher rate (28% and 22% respectively) than the controls (8%), but this did not quite reach statistical significance (p > 0.05). In addition we found no Dupuytren's disease in 50 Egyptian patients with bilharzia and no consistent biochemical abnormalities in 134 patients with significant Dupuytren's disease. We conclude that alcoholics probably do have a higher rate of Dupuytren's disease and that this effect is largely due to the liver disease caused by alcohol abuse, but that the genetic factors are of greater aetiological importance.

Influence of Hepatic Reserve and Cause of Esophageal Varices on Survival and Rebleeding Before and After the Introduction of Sclerotherapy: A Retrospective Analysis

Esophageal variceal sclerotherapy has been enthusiastically accepted as the procedure of choice for patients with variceal hemorrhage. Because the relationships among liver function, different causes of varices, survival, and rebleeding rates have not been well established in sclerotherapy trials, this enthusiasm may be unjustified. We studied these relationships in 80 patients with bleeding esophageal varices who were admitted to hospitals affiliated with our clinic between 1978 and 1980 and who did not receive sclerotherapy and in 162 patients admitted between 1980 and 1982 who received sclerotherapy with ethanolamine oleate. In both groups of patients, survival and bleeding-free intervals were significantly related (P less than 0.005 and P less than 0.01, respectively) to hepatic reserve (Child's class). In addition, patients with nonalcohol-related liver disease and poor hepatic reserve (Child's class C) had reduced survival and bleeding-free intervals compared with patients in class C with alcohol-related liver disease. Similar probabilities of survival and bleeding-free intervals were noted for Child's class subgroups and etiologic subgroups in the sclerotherapy and nonsclerotherapy groups, although a formal comparison was not made because of the retrospective nature of this study. Indications that sclerotherapy increases survival and reduces rebleeding may be due to different distributions of Child's classes and causes of varices within sclerotherapy and nonsclerotherapy groups in published control trials.