Socioeconomic Factors Associated with Poor Prognosis in Patients with Alcoholic Liver Cirrhosis

Background: Alcohol liver cirrhosis is a life-threatening condition, especially if alcohol cessation is not accomplished. Past studies have shown that alcohol abuse is closely linked to low socioeconomic status and social marginalization. Public assistance (PA), or Seikatsu-hogo, a Japanese public assistance ensuring medical care to low-income population, was employed as a proxy for social marginalization. This study aims to investigate the prognostic effect of being a PA recipient on overall mortality in patients with alcoholic cirrhosis.Methods: Patients diagnosed as alcoholic liver cirrhosis in a community hospital between 2006 to 2017 were included in this retrospective cohort study. Baseline demographics and mortality data were extracted from electronic health records. Cirrhosis severity at baseline was measured by mean model for end-stage liver disease (MELD) score and Albumin-Bilirubin (ALBI) score. Primary outcome was survival probability obtained by the Kapan Meier method and Cox proportional hazards regression. Results: 244 participants were included, among which 62 were PA recipients. Baseline cirrhosis severity score was not different between the two groups. Incidence proportion for overall mortality was 48.4% and 31.9% for PA recipients and non-PA recipients, respectively (p=0.002). In cox regression model, adjusted for age, ALBI score and HCV infection, hazard ratio for PA reception was1.57 (95% CI: 0.97-2.5, p=0.06). Conclusions: Being a PA recipient may be a poor prognostic factor of mortality in patients with alcoholic liver cirrhosis.

The role of hepatocellular death and systemic inflammation in the development of acute kidney injury in acute decompensation of alcoholic liver cirrhosis

The aim of the study was to assess the role of hepatocellular death and systemic inflammation in the development of acute kidney injury (AKI) in acute decompensation of alcoholic liver cirrhosis (AD ALC).Materials and methods. 125 patients with ALC were examined: 20 (16.0%) (group I) with signs of hepatorenal syndromeacute kidney injury (HRS-AKI) at the age of 57.13 ± 9,08 years, 13 men (65.0%) and 105 (84.0%) patients (group II) without such a syndrome at the age of 56.30 ± 9.6 years., 62 men (59.0%). Along with liver tests, a markers of hepatocyte apoptosis and cytokines were determined by ELISA: fragments of cytokeratin-18 (FCK-18) ("Biotech" Sweden), cytokines — TNF-α, IL-1β, IL-4, IL-6, IL-8 (“Vector-Best”, Russia). Grade and index of acute on chronic liver failure (ACLF) were determined using an on-line calculator (www.efclif.com/scientific-activity/score-calculators/clif-c-aclf).Results. The hepatocellular death indicators were significantly higher in patients of group I with HRS-AKI compared with patients of group II without HRS-AKI: FCK-18-1609.44 ± 542.79 U / l versus 975.77±607.59 U / l, bilirubin — 242.64 ± 98.14 pmol/l versus 145.09 ± 79.35 pmol/l, inflammation indicators — TNF-α — 9.28 ± 3,11 pg/ml versus 6.59 ± 2.21 pg/ml, IL-6-54.79 ± 17.7 pg/ml versus 36.71 ± 18.05 pg/ml, CRP — 49.68 ± 23.23 mg/l versus 22.07 ± 20.40 mg/l, leukocytes — 12.23 ± 3.28x109/l versus 8,66 ± 2,31x109/l (everywhere p <0.05). ACLF developed in all (100.0%) patients of group I, its grade was 2.73±0.76 and score — 56.33 ± 4.01; ACLF developed only in 37 (35,2%) patients of group II, its grade was1.05±0.24 (p<0,05) and score was 47.45 ± 4,80 (p <0.05).Conclusion. The development of HRS-AKI in patients with acute decompensation of ALC was associated with significantly higher rates of hepatocytic apoptosis, hyperbilirubinemia, systemic inflammation, frequency and severity of ACLF.

Role of tissue molecular pathogens in development of acute chronic liver failure in alcoholic liver cirrhosis

The aim of the study was to assess the pathogenetic, diagnostic and clinical role of tissue molecular pathogens – fragments of cytokeratin-18 in the development of acute chronic liver failure (ACLF) in decompensated alcoholic liver cirrhosis (ALC).Materials and methods. 80 patients with ALC were examined: 30 without signs of ACLF and 50 with signs of ACLF and 36 healthy individuals. Hepatic functional tests were determined, a marker of hepatocyte apoptosis – fragments of cytokeratin-18 (FCK-18) (Biotech, Sweden) by the enzyme immunoassay, ACLF scores were calculated using an on-line calculator at www.efclif.com/scientific-activity/score-calculators/ clif-c-aclf.Results. With ACLF, a high level of FCK-18 was detected – 1505.4 ± 446.9 U/L, more than 20 times higher than that in healthy individuals – 71.5 ± 19.6 U/L (p < 0.05) and three times higher than the level of FCK-18 in patients with ALC without ACLF – 489.4 ± 490.2 U/L. The levels of aminotransferases, bilirubin, creatinine, INR were significantly higher in patients with ACLF compared with patients without ACLF, and the level of albumin was lower. FCK-18 level directly correlated with ALT – r = 0.61 (p < 0.05), AST – r = 0.68 (p < 0.05), with bilirubin level – r = 0.41 (p < 0, 05) and the ACLF score – r = 0.48 (p < 0.05) and inversely correlated with the albumin level r = –0.51 (p < 0.05).Conclusion. Apoptosis of hepatocytes and tissue molecular pathogens released during it – fragments of cytokeratin-18 – play a role in the development of acute chronic liver failure in decompensated alcoholic liver cirrhosis.

EFFICIENCY OF NORFLOXACIN IN THE PROPHYLAXIS OF HEPATORENAL SYNDROME

Purpose - to evaluate norfloxacin efficacy for the prevention of hepatorenal syndrome(HRS) development in patients with alcoholic liver cirrhosis and concomitant chronicpyelonephritis.Material and methods. In all, 157 patients, divided into two groups depending on themethod of HRS prevention, were examined: group 1 (n = 78) - received placebo; group 2(n = 79) - received norfloxacin. The main endpoint of the study was short-term survival.The probability curves were constructed using the Kaplan – Mayer method.Results. The rate of renal failure was much lower in group 2 (7 vs. 16 patients, p = 0.03).HRS was associated with bacterial infection in 4 patients of group 2 and in 6 patients ofgroup 1. HRS developed during the first 3 months of the follow-up period in 9 patientsin group 1 and only 1 patient in group 2 (p = 0.006). The incidence of HRS developmentduring the first 14 days was significantly lower in group 2. In all, 10 patients died ingroup 2 and 13 in group 1. The main cause of death in both groups was HRS (5 and8 patients, respectively). Mortality during the first 3 months was significantly higherin group 1 (10 vs. 2 patients, p = 0.02). Three-month (group 2 - 94%, group 1 - 62%)and annual survival (60% vs. 48%, respectively, p = 0.05) were significantly higher ingroup 2.Conclusions. Peroral antibiotic prophylaxis with norfloxacin almost 5 times reduces therisk of hepatorenal syndrome development type 1 in patients with alcoholic liver cirrhosisand concomitant chronic pyelonephritis, and increases their short-term survival.

Isolated acute hemorrhagic cholecystitis in liver cirrhosis after blunt trauma

Isolated acute hemorrhagic cholecystitis (AHC) after blunt trauma is extremely rare. Thus, alcoholic liver cirrhosis can be a risk factor for this type of injury. The use of point-of-care ultrasound as a monitoring tool for suspicious gallbladder injuries facilitates rapid recognition and decision-making. Therefore, laparoscopic cholecystectomy was recommended for treating traumatic AHC in patients with hemodynamically stable liver cirrhosis.

Serum from Patients with Severe Alcoholic Liver Cirrhosis Inhibits Proliferation and Migration of Human Coronary Artery Smooth Muscle Cells

Liver cirrhosis has been associated with an increased risk of coronary artery disease and clinical complications following percutaneous coronary revascularization. The present study is based on the hypothesis that cirrhosis may influence intimal hyperplasia following PCI. Sera from 10 patients with alcoholic liver cirrhosis and 10 age-matched healthy controls were used to stimulate cultured human coronary artery smooth muscle cells (HCASMC) for 48 h. HCASMC proliferation, migration, gene expression and apoptosis were investigated. Serum concentrations of growth factors and markers of liver function were also determined in patients and healthy controls. Treatment of HCASMC with patient sera reduced cell proliferation and migration (p < 0.05 vs. healthy controls), whereas apoptosis was unaffected (p = 0.160). Expression of genes associated with a synthetic vascular smooth muscle cell phenotype was decreased in cells stimulated with serum from cirrhotic patients (RBP1, p = 0.001; SPP1, p = 0.003; KLF4, p = 0.004). Platelet-derived growth factor-BB serum concentrations were lower in patients (p = 0.001 vs. controls). The results suggest the presence of circulating factors in patients with alcoholic liver cirrhosis affecting coronary smooth muscle cell growth. These findings may have implications for clinical outcomes following percutaneous coronary revascularization in these patients.

CHRONIC PYELONEPHRITIS AS A PRECIPITATING FACTOR OF HEPATORENAL SYNDROME IN PATIENTS WITH ALCOHOLIC LIVER CIRRHOSIS

Introduction. Most attempts to assess renal failure in alcoholic liver cirrhosis have so far focused on acute kidney injury and on the hepatorenal syndrome in particular. However, there are still limited data on the prevalence and clinical impact of chronic kidney disease in cirrhosis. Objectives. This study aimed to assess the influence of chronic pyelonephritis on the incidence of hepatorenal syndrome in patients with alcoholic liver cirrhosis. Material and methods. 165 patients with decompensated alcoholic liver cirrhosis and concomitant chronic pyelonephritis were enrolled in the study. They were divided into two groups according to the presence or absence of chronic pyelonephritis: group 1 had alcoholic liver cirrhosis only (n=82), group 2 had alcoholic liver cirrhosis + chronic pyelonephritis (n=83). Results. The general bacterial infections were more common in group 1 patients. The spectrum of the most frequent bacterial complications in the examined patients typical for alcoholic liver cirrhosis was as follows: the share of urinary tract infection made up 16.0% (95% confidence interval 14.4-27.9), pneumonia constituted 16.7% (95% confidence interval 10.5-22.7, bacteremia made up 4.0% (95% confidence interval 7.7-38.6), the share of skin infections (erysipelas) was 2.7% (95% confidence interval 0.7-6.6). Other infections including pulmonary tuberculosis, lung abscess, right leg abscess, osteomyelitis, bedsores, were less common (6.7%). Spontaneous bacterial peritonitis, taking into account all options, was found in 6 cases (10.5%, 95% confidence interval 4.0-21.5). As expected, the incidence of hepatorenal syndrome within 14 days of inpatient onset was almost twice higher in group 2 – 22 cases (27%), than in group2 – 13 cases (16%). The group 2 demonstrated a more severe course of alcoholic liver cirrhosis on the Child-Pugh scale compared with group I (class B - 29.9%; class C - 70.1% against class B - 46.4%; class C - 53, 6% ); the differences were statistically significant (χ2 = 4.30, p = 0.038). In patients of group 2, the lethal outcome in the hospital occurred in 6 (8.9%) cases. Conclusions: The results of the present study confirm the role of chronic pyelonephritis as one of the major precipitating factors of hepatorenal syndrome incidence in patients with alcoholic liver cirrhosis. This fact should be considered when making the treatment plan for these patients.

NOTCH3 rs1043996 Polymorphism Is Associated with the Occurrence of Alcoholic Liver Cirrhosis Independently of PNPLA3 and TM6SF2 Polymorphisms

Alcoholic liver cirrhosis (ALC) is the most common indication for liver transplantation (LT) in Croatia and presents a risk factor for the development of hepatocellular carcinoma (HCC). However, genetic susceptibility has not yet been systematically studied. We aimed to investigate the contribution of the risk polymorphisms PNPLA3 rs738409, EGF rs4444903, TM6SF2 rs58542926, MTHFR rs1801133, previously identified in other populations and, additionally, the contribution of Notch-related polymorphisms (NOTCH1 rs3124591, NOTCH3 rs1043996 and rs1044116, NOTCH4 rs422951). The study included 401 patients. The ALC group consisted of 260 LT candidates, 128 of whom had histopathologically confirmed HCC, and 132 of whom were without HCC. The control group included 141 patients without liver disease. Genotyping was performed by PCR using Taqman assays. The patients’ susceptibility to ALC was significantly associated with PNPLA3 rs738409, TM6SF2 rs58542926, and NOTCH3 rs1043996 polymorphisms. These polymorphisms remained significantly associated with ALC occurrence in a logistic regression model, even after additional model adjustment for sex and age. Cirrhotic patients with the PNPLA3 GG genotype demonstrated higher activity of ALT aminotransferases than patients with CC or CG genotypes. The susceptibility to the development of HCC in ALC was significantly associated with PNPLA3 rs738409 and EGF rs4444903 polymorphisms, and logistic regression confirmed these polymorphisms as independent predictors.