Non-alcoholic Cirrhosis Patients Research Articles

An Observational Study showing Dipeptidyl Peptidase-4 (DPP-4) Activity and Gene Expression Variation in Chronic Liver Disease (CLD) Patients from a Tertiary Care Hospital of Eastern India.

Introduction:The studies in animal models of cirrhosis suggest that dipeptidyl peptidase type 4 (DPP-4) enzymes play a crucial role in disease pathogenesis. In this clinical observational study, activity of DPP-4 and related gene expression were analysed in chronic liver disease patients.Objectives:To understand the DPP-4 enzyme activity variation in the common types of chronic liver disease by assessing plasma and peripheral blood mononuclear cell (PBMC) DPP-4 activity and comparing with healthy controls and to explore DPP-4 gene expression in PBMC.Methods:We recruited 130 study subjects in four cohorts—46 nonalcoholic fatty liver disease (NAFLD), 23 non-alcoholic cirrhosis (NAC) excluding viral aetiology, 21 alcoholic liver disease (ALC), and 40 control subjects. Blood samples were analysed for relevant biochemical parameters and plasma DPP-4 activity. PBMC fraction was used for the DPP-4 activity assay and gene expression analysis.Results:We found that lower plasma DPP-4 activity among patient cohorts but this was not statistically significant. The PBMC DPP-4 activity was significantly lower in NAFLD cohort. In the same cohort, DPP-4 gene expression in PBMC fraction was significantly increased (P < 0.05). There was significant correlation between plasma DPP-4 activity and liver injury marker alanine aminotransferase (ALT) among NAFLD (rho = 0.459, P < 0.01), NAC (rho = 0.475, P < 0.05), and ALC (rho = –0.572, P < 0.01) patients. Plasma DPP-4 activity modestly predicted ALT plasma level (beta coefficient = 0.489, P < 0.01).Conclusions:The PBMC DPP-4 activity and DPP-4 gene expression gets significantly altered in NAFLD patients. Plasma DPP-4 activity also shows correlation with ALT levels in CLD patients. The role of DPP-4 in disease pathology in NAFLD and other forms of CLD needs to be explored.

Impact of the COVID-19 Pandemic on Hospitalizations for Alcoholic Hepatitis or Cirrhosis in Alberta, Canada

Background & AimsCoronavirus disease 2019 (COVID-19) pandemic lockdown and restrictions had significant disruption to patient care. We aimed to evaluate the impact of COVID-19 restrictions on hospitalizations of patients with alcoholic and nonalcoholic cirrhosis as well as alcoholic hepatitis (AH) in Alberta, Canada.MethodsWe used validated International Classification of Diseases (ICD-9 and ICD-10) coding algorithms to identify liver-related hospitalizations for nonalcoholic cirrhosis, alcoholic cirrhosis, and AH in the province of Alberta between March 2018 and September 2020. We used the provincial inpatient discharge and laboratory databases to identify our cohorts. We used elevated alanine aminotransferase or aspartate aminotransferase, elevated international normalized ratio, or bilirubin to identify AH patients. We compared COVID-19 restrictions (April–September 2020) with prior study periods. Joinpoint regression was used to evaluate the temporal trends among the 3 cohorts.ResultsWe identified 2916 hospitalizations for nonalcoholic cirrhosis, 2318 hospitalizations for alcoholic cirrhosis, and 1408 AH hospitalizations during our study time. The in-hospital mortality rate was stable in relation to the pandemic for alcoholic cirrhosis and AH. However, nonalcoholic cirrhosis patients had lower in-hospital mortality rate after March 2020 (8.5% vs 11.5%; P = .033). There was a significant increase in average monthly admissions in the AH cohort (22.1/10,000 admissions during the pandemic vs 11.6/10,000 admissions before March 2020; P < .001).ConclusionsBefore and during COVID-19 monthly admission rates were stable for nonalcoholic and alcoholic cirrhosis; however, there was a significant increase in AH admissions. Because alcohol sales surged during the pandemic, future impact on alcoholic liver disease could be detrimental.

Minimal Hepatic Encephalopathy and Biejia-Ruangan Are Associated with First Hospital Readmission in Nonalcoholic Cirrhosis Patients.

Introductionand Aim. Patients with cirrhosis are often hospitalized repeatedly for a variety of complications. This retrospective study aimed to assess the effects of minimal hepatic encephalopathy (MHE) and Biejia-Ruangan (BR) on first hospital readmission in nonalcoholic cirrhosis patients without previous overt hepatic encephalopathy (OHE) or hepatocellular carcinoma (HCC). Materials and Methods. A total of 176 hospitalized patients with nonalcoholic cirrhosis were included in this retrospective study. Patients who were first admitted to Beijing Ditan Hospital of Capital Medical University from January 2017 to September 2019 were enrolled. The primary endpoint was their first liver-related hospital readmission. The risk factors for readmission were analyzed by Cox proportional hazard regression analysis. Results. A total of 176 nonalcoholic cirrhosis patients without previous OHE or HCC were included; 57 patients (32.4%) were diagnosed with MHE, and 63 patients (35.8%) were administered BR (2 g, three times a day). Multivariate analysis revealed that nonalcoholic cirrhosis patients with MHE (HR, 5.805; 95% CI, 3.007–11.206; x, P < 0.001) and a higher Model for End-Stage Liver Disease (MELD) score (HR, 1.145; 95% CI, 1.068–1.227; P < 0.001) had an increased risk of first hospital readmission, and patients treated with BR (HR, 0.318; 95% CI, 0.151–0.670; P=0.003) had a decreased risk of first hospital readmission. Conclusion. MHE increased the risk of hospital readmission in nonalcoholic cirrhosis patients without previous OHE or HCC, and this risk was decreased by BR administration.

The burden of cirrhosis on the Canadian healthcare system: a comparison between alcoholic and non-alcoholic cirrhosis patients

The burden of cirrhosis on the Canadian healthcare system: a comparison between alcoholic and non-alcoholic cirrhosis patients

45. Evaluation and comparison of cardiac dysfunction among alcohol and non alcohol related cirrhosis patients and controls

Background and Aims: Patients with advanced liver cirrhosis may develop cirrhotic cardiomyopathy, which is defined as a chronic cardiac dysfunction in patients with cirrhosis, characterized by blunted contractile responsiveness to stress, and/or altered diastolic relaxation with electrophysiological abnormalities, in the absence of known cardiac disease. This study was done to assess and compare the cardiac functional status of alcoholic and non-alcoholic cirrhosis patients and controls. Methods: This was a cross-sectional descriptive study evaluating the cardiac functional status of 100 liver cirrhosis patients (40 patients of alcoholic cirrhosis and 60 patients of non-alcoholic cirrhosis), admitted in gastroenterology Department of SMS Medical College, from Jan 2017 to Jan 2018. Age and sex matched forty healthy subjects without any history of cardiac and liver disease was selected as a controls. Selected individuals were subjected to clinical evaluation including history, physical examination, haematological, biochemical, ECG, 2D-ECHO and endoscopic studies. Results: EF of cirrhotic patients was significantly high compared to controls. The mean PASP among the cirrhotics and controls were 28.2 + 9.06 and 20.4 + 4.21 mmHg respectively and the difference was statistically significant. Forty-eight cirrhotic patients (48%) had diastolic dysfunction compared to 10 (25%) in the control group which was significant. QTc interval was significantly higher in cirrhotics (0.44) compared to controls (0.40) and in alcoholic cirrhosis (0.46) compared to non-alcoholic cirrhosis (0.43) patients. Conclusions: Assesing cardiovascular involvement in a cirrhotic patient is important in planning treatment and assessing prognosis. This study has brought out a pattern of cardiac involvement in cirrhosis. The authors have none to declare. Table 1Tabled 1ParameterType of casesRangeMean ± SDP valueLVIDs (cm)Cirrhosis cases2.51–4.353.19 ± 0.48NSControls2.91–3.413.14 ± 0.15LVIDd (cm)Cirrhosis cases3.59–5.74.79 ± 0.5NSControls4.13–5.224.71 ± 0.35EF (%)Cirrhosis cases50–8668.56 ± 6.79<0.001SControls60–7163.13 ± 3.70IVSd (cm)Cirrhosis cases0.45–1.40.86 ± 0.19NSControls0.67–1.040.89 ± 0.09LVPWd (cm)Cirrhosis cases0.5–1.90.88 ± 0.25NSControls0.6–1.150.85 ± 0.15 Open table in a new tab Table 2Tabled 1Pattern of diastolic dysfunctionControls (n = 40)Total Cirrhosis (n = 100)Alcoholic cirrhosis (n = 40)Non-alcoholic cirrhosis (n = 60)Impaired relaxation pattern6 (15%)28 (28%)13 (32.5%)15 (25%)Pseudo normal pattern2 (5%)11 (11%)4 (10%)7 (11.6%)Restrictive pattern2 (5%)9 (9%)2 (5%)7 (11.6%)Total10 (25%)48 (48%)19 (47.5%)29 (48.2%)P Value<0.05 (S)*<0.05 (S)*<0.05 (S)*NS** Open table in a new tab

Non-alcoholic cirrhosis and the risk of stroke: a 5-year follow-up study

As habitual heavy alcohol consumption is one of the major causes of cirrhosis in the western world, the majority of studies on the relationship between cirrhosis and stroke have focused on patients with alcohol-related liver diseases. Using a nationwide population-based dataset, this study therefore aimed to examine the risk of stroke among non-alcoholic cirrhosis patients over a 5-year period following their diagnosis with non-alcoholic cirrhosis, as compared with the general population during the same period. We used the 'Longitudinal Health Insurance Database', derived from the Taiwan National Health Insurance program. The study cohort comprised 2336 patients with cirrhosis and the comparison cohort consisted of 11,680 randomly selected subjects. Stratified Cox's proportional hazard regressions were performed to compare the 5-year stroke survival rate for the two cohorts. In the total sample of 14,016 patients, 1187 patients (8.5%) experienced stroke during the 5-year follow-up period: 176 from the study cohort (7.5% of the patients with cirrhosis) and 1011 from the comparison cohort (8.7% of patients without cirrhosis) (P=0.076). After adjusting for the patients' geographical location, hypertension, diabetes, coronary heart disease, heart failure, atrial fibrillation and hyperlipidaemia, the regression analysis shows that patients with cirrhosis were less likely to experience stroke compared with those without cirrhosis during the 5-year period (hazard ratio=0.59, 95% confidence interval=0.52-0.67, P<0.001). We conclude that patients with non-alcoholic cirrhosis were at a reduced risk for stroke compared with the general population.

Polymorphism in cytochrome P450 2E1 and interaction with other genetic risk factors and susceptibility to alcoholic liver cirrhosis

The association of polymorphism in cytochrome P450 2E1 (CYP2E1), the major microsomal ethanol metabolizing enzyme and its interaction with genes, involved in detoxification of reactive oxygen species, such as glutathione-S-transferases M1 (GSTM1) and alcohol intake, gamma-aminobutyric acid receptor γ2 (GABRG2) was studied with the risk to alcoholic cirrhosis in a case–control study. A total of 160 alcoholic cirrhotic and 125 non-alcoholic cirrhotic cases, visiting the OPD facility of Gastroenterology Department of Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGI), Lucknow, India and 250 non-alcoholic and 100 alcoholic controls having no evidence of liver disease were included in the study. PCR-based RFLP methodology was followed for genotyping studies. Our data revealed that the variant genotypes of CYP2E1*5B exhibited significant association with the alcoholic liver cirrhosis when compared to non-alcoholic controls (OR: 4.3; 95%CI: 1.5–12.4; p: 0.003) or non-alcoholic cirrhosis patients (OR: 5.4; 95%CI: 1.2–24.5; p: 0.01) or alcoholic controls (OR: 4.3; 95%CI: 0.95–19.62; p: 0.04). Haplotype approach revealed that haplotype T–A–T was found to be associated with more than 5-fold increase in risk for alcoholic cirrhosis. Likewise, combination of variant genotype of CYP2E1*5B with null genotype of GSTM1, a phase II detoxification enzyme, resulted in several fold increase in risk in alcoholic cirrhotic patients when compared with non-alcoholic controls or non-alcoholic cirrhotic patients. Further, the combination of variant genotype of CYP2E1*5B with GABRG2, significantly increased the risk upto 6.5-fold in alcoholic cirrhotic patients when compared with non-alcoholic controls thereby suggesting the role of gene–gene interaction in alcoholic cirrhosis.

Probiotic yoghurt can reverse minimal hepatic encephalopathy (MHE) "with high rates of adherence" in nonalcoholic cirrhosis patients,

Probiotic yoghurt can reverse minimal hepatic encephalopathy (MHE) "with high rates of adherence" in nonalcoholic cirrhosis patients,

A Method for Estimating Alcohol-Related Liver Cirrhosis Mortality in Japan

In Japan, per capita alcohol consumption increased sharply during the post World War II period followed by an increase in cirrhosis mortality. The prevalence of alcoholic cirrhosis among hospitalized patients also increased, from 11% in 1969 to 18% in 1985. Despite an increase in the percentage of drinkers among young women, over 80% of women in Japan are still abstainers or light drinkers. Thus, female cirrhosis mortality rates can be used as a proxy measure of non-alcohol-related cirrhosis mortality rates to estimate alcohol-related cirrhosis deaths among Japanese men. Employing this method, we conclude that two-thirds of cirrhosis deaths among men between 24 and 85 years of age and half of all cirrhosis deaths were attributable to alcohol. Two factors are probably responsible for the differences in proportional morbidity and proportional mortality of alcohol-related cirrhosis: differences in survival rates between alcoholic and non-alcoholic cirrhosis patients and detection bias toward post-hepatic cirrhosis. The synergistic effect of alcohol on viral hepatitis may in part explain excess cirrhosis deaths among Japanese men.

Hemodynamic differences between alcoholic and nonalcoholic cirrhotics following distal splenorenal shunt--effect on survival?

The distal splenorenal shunt significantly improves 5-year survival from variceal bleeding in nonalcoholic (70%) compared to alcoholic (45%) cirrhosis patients. This study quantitates hemodynamic differences occurring in the first year after DSRS in 16 alcoholic compared to eight nonalcoholic patients. Portal venous perfusion was retained significantly better (p less than .01) by the nonalcoholic (seven of eight) than by the alcoholic (four of sixteen) patients. Mean liver blood flow (p less than 0.07), flow/unit liver volume (p less than .05), and flow required to perform a specific hepatocyte function (p less than 0.05) all increased significantly in the alcoholic compared to nonalcoholic group. Cardiac output increased significantly in the alcoholic patients (p less than 0.05), but was unchanged in the nonalcoholic patients. The alcoholic patients divided into two subsets, 11 who showed increase in flow (1082 +/- 260 to 1496 +/- 388 ml/min) and five who did not (1246 +/- 269 to 994 +/- 159 ml/min). The former had significantly (p less than 0.05) poorer hepatocyte function and had a significant (p less than 0.05) increase in flow/unit volume and flow/unit function at 1 year, which may have helped to maintain hepatocyte integrity. The latter, in parallel with the nonalcoholic patients, showed no significant change in these parameters and maintained a good functional hepatocyte mass. These data lead us to hypothesize that: 1) alcoholic liver injury has an increased risk of leading to loss of portal perfusion after DSRS, 2) as hepatocyte function falls, there is initial increase in hepatic arterial flow in alcoholic patients, triggered by increase in cardiac output, and 3) progressive injury and/or failure of the compensatory hemodynamic mechanism leads to earlier mortality in alcoholic patients. In contrast, the nonalcoholic cirrhosis patients preserve portal perfusion and maintain liver blood flow, both quantitatively and qualitatively, with retained hepatocyte function and improved survival.