Non-alcoholic Liver Cirrhosis Research Articles

Can Periodontitis Affect the Health and Disease of the Digestive System? A Comprehensive Review of Epidemiological Evidence and Biological Mechanisms

Purpose of ReviewThere is increasing evidence on the connections between chronic oral inflammation/infection and the pathophysiological conditions of the gastrointestinal tract and accessory organs of digestion. The aim of this review is to provide a critical synthesis regarding the epidemiological, clinical, and in vivo associations between periodontitis and the most relevant diseases of the digestive system.Recent FindingsAn increasing body of dental and medical literature is supporting the gum-gut axis as a relevant mechanism to explain the associations between periodontitis and systemic diseases. Indeed, shared microbiological and immunological pathways have been identified between periodontitis and gut diseases, and translocation of oral bacteria to the lower parts of the digestive system has been postulated as a driver for peptic ulcers, inflammatory bowel disease, liver disease, and ultimately digestive cancers.SummaryFor the upper digestive tract, epidemiologic association between periodontitis and gastroesophageal reflux disease or squamous cell carcinoma remains conflicting, despite oral keystone pathogens having been consistently found in esophageal and gastric cancer tissue biopsies. The oral cavity represents a reservoir for Helicobacter pylori, with periodontal therapy increasing the eradication and the non-recurrence rate of the infection. Regarding bowel diseases, gut dysbiosis is being progressively ascertained in close relation to periodontal infection, and periodontitis is being investigated among the risk indicators for colorectal cancer. Lastly, non-alcoholic fatty liver disease and cirrhosis were epidemiologically linked to periodontitis, while its association with pancreatic tumors represents one of the most intriguing fields of research in periomedicine.

Does the FT3-to-FT4 ratio easily predict the progression of NAFLD and NASH cirrhosis?

BackgroundFactors causing progression from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH) and liver cirrhosis remain relatively unknown. We aimed to evaluate the power and effectiveness of the free triiodothyronine (FT3)-to-free thyroxine (FT4) ratio to predict non-alcoholic fatty liver disease (NAFLD)/liver fibrosis and NASH cirrhosis severity.MethodsPatients (n = 436) with NASH-associated liver cirrhosis (n = 68), patients with liver biopsy-proven NAFLD (n = 226), or healthy participants (n = 142) were enrolled between January 2010 and January 2020. The aspartate aminotransferase-to-thrombocyte ratio (APRI), NAFLD fibrosis score, albumin–bilirubin score (ALBI), aspartate aminotransferase (AST)-to-alanine aminotransferase (ALT) ratio, FT3-to-FT4 ratio, and Fibrosis-4 (FIB-4) were calculated and evaluated.ResultsAll parameters were significantly higher in NASH cirrhosis than in the healthy group. Body mass index, ALT, fasting insulin, homeostatic model assessment for insulin resistance, and triglyceride levels were significantly higher in liver biopsy-proven NAFLD than in the healthy group. The APRI, NAFLD fibrosis score, ALBI, AST-to-ALT ratio, FT3-to-FT4 ratio, and FIB-4 were significantly higher in the NASH cirrhosis group than in the healthy group. In patients with biopsy-proven NAFLD, the FT3-to-FT4 ratio was significantly lower than in the healthy group.ConclusionThe FT3-to-FT4 ratio is an effective and useful indicator to predict NAFLD/liver fibrosis and NASH cirrhosis severity.

695Gene and environmental factors for liver fibrosis among Japanese general population with NAFLD

Abstract Background A part of nonalcoholic fatty liver disease (NAFLD) develops nonalcoholic steatohepatitis (NASH), liver cirrhosis and hepatocellular carcinoma. Metabolic syndrome is involved in their development, and hepatic fibrosis plays an important role in their pathogenesis. Patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene encode proteins on hepatic lipid metabolism regulation, and PNPLA3 gene polymorphism is associated with the development and progression of NAFLD. To investigate the gene and environmental factors, and their interaction for liver fibrosis, we conducted a prospective study among Japanese general population with NAFLD. Methods The subjects were 295 general residents who participated as a part of the Japan Multi-Institutional Collaborative Cohort (J-MICC) study in Kagoshima, Japan, and were followed for 5 years. NAFLD was defined as fatty liver using abdominal ultrasonography. PNPLA3 C/G polymorphism (rs738409) was analysed using TaqMan PCR. Hepatic fibrosis was defined using FIB 4 index (≥1.3). Logistic regression model was used to estimate the odds ratios (ORs) after adjusted for confounding factors. Results Mean age was 55.1 years and liver fibrosis was observed at 73.2% among NAFLD subjects. No environmental factors were associated with liver fibrosis, and PNPLA3 GG genotype was not associated with liver fibrosis, too. However, the ORs of CC & CG, and GG genotypes for dyslipidemia was respectively 0.45 (0.19-1.04) and 11.9 (1.81-78.4), and their interaction was significant (p = 0.01). Conclusions The interaction between PNPLA3 GG gene polymorphism and dyslipidemia for liver fibrosis was observed. Key messages Genetic susceptibility with dyslipidemia may be involved in liver fibrosis of NAFLD.

COVID‐19 and the Liver: Lessons Learnt from the EAST and the WEST, A Year Later

Globally, the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2 virus) has been a major cause for significant morbidity and mortality. Since the start of the pandemic, several hepato‐biliary manifestations in coronavirus disease 2019 (COVID‐19) have been described and unique considerations raised. The review aims to summarize the pathogenesis and hepato‐biliary manifestations in COVID‐19 and discuss the similarities, contrasting features and disease‐specific management across a range of hepato‐biliary diseases from the EAST and the WEST. Published studies and regional society guidelines from the EAST and the WEST were comprehensively reviewed and summarized. A wide range of hepato‐biliary manifestations, including the infrequent and chronic manifestation of cholangiopathy, has been observed in COVID‐19. The pathogenesis of liver injury is multifactorial and with scant evidence for a direct SARS‐CoV‐2 infection of the liver. Patients with non‐alcoholic fatty liver disease, cirrhosis, and liver cancer are potentially at increased risk for severe COVID‐19, and there are unique considerations in chronic hepatitis B or C, hepatocellular carcinoma, and in those immunosuppressed such as autoimmune hepatitis or liver transplant recipients. With the surges in SARS‐CoV‐2 infection, liver transplant activity has variably been impacted. Preliminarily, SARS‐CoV‐2 vaccines appear to be safe in those with chronic liver disease and in transplant recipients, while emerging data suggest the need for a third dose in immunosuppressed patients. In conclusion, patients with chronic liver disease, particularly cirrhosis, and liver transplant recipients, are vulnerable to severe COVID‐19. Over the past year, several unique considerations have been highlighted across a spectrum of hepato‐biliary diseases. Vaccination is strongly recommended for those with chronic liver disease and liver transplant recipients.

Glutathione-S-transferases genes-promising predictors of hepatic dysfunction.

One of the most commonly known genes involved in chronic diffuse liver diseases pathogenesis are genes that encodes the synthesis of glutathione-S-transferase (GST), known as the second phase enzyme detoxification system that protects against endogenous oxidative stress and exogenous toxins, through catalisation of glutathione sulfuric groups conjugation and decontamination of lipid and deoxyribonucleic acid oxidation products. The group of GST enzymes consists of cytosolic, mitochondrial and microsomal fractions. Recently, eight classes of soluble cytoplasmic isoforms of GST enzymes are widely known: α-, ζ-, θ-, κ-, μ-, π-, σ-, and ω-. The GSTs gene family in the Human Gene Nomenclature Committee, online database recorded over 20 functional genes. The level of GSTs expression is considered to be a crucial factor in determining the sensitivity of cells to a broad spectrum of toxins. Nevertheless, human GSTs genes have multiple and frequent polymorphisms that include the complete absence of the GSTM1 or the GSTT1 gene. Current review supports the position that genetic polymorphism of GST genes is involved in the pathogenesis of various liver diseases, particularly non-alcoholic fatty liver disease, hepatitis and liver cirrhosis of different etiology and hepatocellular carcinoma. Certain GST allelic variants were proven to be associated with susceptibility to hepatological pathology, and correlations with the natural course of the diseases were subsequently postulated.

Frailty in Nonalcoholic Fatty Liver Cirrhosis: A Comparison with Alcoholic Cirrhosis, Risk Patterns, and Impact on Prognosis.

Background Physical frailty increases susceptibility to stressors and predicts adverse outcomes of cirrhosis. Data on disease course in different etiologies are scarce, so we aimed to compare the prevalence and risk factors of frailty and its impact on prognosis in nonalcoholic fatty liver (NAFLD) and alcoholic (ALD) cirrhosis. Patients and Methods. Cirrhosis registry RH7 operates since 2014 and includes hospitalized patients with decompensated cirrhosis, pre-LT evaluation, or curable hepatocellular carcinoma (HCC). From the RH7, we identified 280 ALD and 105 NAFLD patients with at least 6 months of follow-up. Results Patients with NAFLD compared with ALD were older and had a higher proportion of females, higher body mass index (BMI) and mid-arm circumference (MAC), lower MELD score, CRP, and lower proportion of refractory ascites. The liver frailty index did not differ, and the prevalence of HCC was higher (17.1 vs. 6.8%, p=0.002). Age, sex, serum albumin, and C-reactive protein (CRP) were independent predictors of frailty. In NAFLD, frailty was also associated with BMI and MAC and in ALD, with the MELD score. The Cox model adjusted for age, sex, MELD, CRP, HCC, and LFI showed that NAFLD patients had higher all-cause mortality (HR = 1.88 95% CI 1.32–2.67, p < 0.001) and were more sensitive to the increase in LFI (HR = 1.51, 95% CI 1.05–2.2). Conclusion Patients with NAFLD cirrhosis had a comparable prevalence of frailty compared to ALD. Although prognostic indices showed less advanced disease, NAFLD patients were more sensitive to frailty, which reflected their higher overall disease burden and led to higher all-cause mortality.

The European Society for Clinical Nutrition and Metabolism practical guideline: Clinical nutrition in liver disease. Part 2

The Practical guideline is based on the current scientific ESPEN guideline on Clinical Nutrition in Liver Disease (Plauth M., Bernal W., Dasarathy S., Merli M., Plank L. D., Schütz T., Bischoff S. C. ESPEN guideline on clinical nutrition in liver disease // Clin Nutr. — 2019. — 38. — Р. 485—521). It has been shortened and transformed into flow charts for easier use in clinical practice.&#x0D; The guideline is dedicated to all professionals including physicians, dieticians, nutritionists and nurses working with patients with chronic liver disease. A total of 103 statements and recommendations are presented with short commentaries for the nutritional and metabolic management of patients with (i) acute liver failure, (ii) alcoholic steatohepatitis, (iii) non-alcoholic fatty liver disease, (iv) liver cirrhosis, and (v) liver surgery/transplantation. The disease-related recommendations are preceded by general recommendations on the diagnostics of nutritional status in liver patients and on liver complications associated with medical nutrition. This practical guideline gives guidance to health care providers involved in the management of liver disease to offer optimal nutritional care.

The impact of genetic risk on liver fibrosis in non-alcoholic fatty liver disease as assessed by magnetic resonance elastography.

Variants in multiple genetic loci modify the risk of non-alcoholic fatty liver disease (NAFLD) and cirrhosis but there are limited data on the quantitative impact of variant copies on liver fibrosis. To investigate the effect of PNPLA3, TM6SF2, MBOAT7, GCKR and HSD17B13 genotype on liver fibrosis assessed by magnetic resonance elastography (MRE), a reproducible, accurate, continuous biomarker of liver fibrosis. This is a cross-sectional analysis derived from a well-characterised cohort at risk for NAFLD who underwent genotyping and MRE assessment. Liver stiffness (LS) was estimated using MRE and advanced fibrosis was defined as liver stiffness ≥3.63kilopascals (kPa). Univariable and multivariable linear and logistic regression analysis, were used to assess the association between genotype and MRE. Two hundred sixty-four patients (63% women) with a mean age 53 (±17)years, and 31% Hispanic ethnicity with genotyping and MRE were included. The odds of advanced fibrosis were 3.1 (95% CI: 1.1-8.9, P=0.04) for CG and 6.5 (95% CI: 2.2-18.9, P<0.01) for GG compared to CC PNPLA3 genotype. Each PNPLA3 risk variant copy was associated with 0.40kPa (95% CI: 0.19-0.61, P<0.01) increase in LS on MRE in analysis adjusted for age, sex and BMI and there was significant genotype-age interaction (P<0.01). Conversely, the protective TA allele in HSD17B13 was associated with a -0.41kPa (95% CI: -0.76 to -0.05, P=0.03) decrease in liver stiffness on MRE multivariable analysis. Knowledge of PNPLA3 and HSD17B13 genotype may assist in the non-invasive risk stratification of NAFLD with closer monitoring recommended for those with high genetic risk.

Long non-coding RNAs in metabolic disorders: pathogenetic relevance and potential biomarkers and therapeutic targets.

It has been suggested that dysregulation of long non-coding RNAs (lncRNAs) could be associated with the incidence and development of metabolic disorders. Accordingly, this narrative review described the molecular mechanisms of lncRNAs in the development of metabolic diseases including insulin resistance, diabetes, obesity, non-alcoholic fatty liver disease (NAFLD), cirrhosis, and coronary artery diseases (CAD). Furthermore, we investigated the up-to-date findings on the association of deregulated lncRNAs in the metabolic disorders, and potential use of lncRNAs as biomarkers and therapeutic targets. LncRNAs/miRNA/regulatory proteins axis plays a crucial role in progression of metabolic disorders and may be used in development of therapeutic and diagnostic approaches.

Evaluating the Correlation of Hemostatic and Endocrine Parameters with Child-Turcotte-Pugh Scoring in Patients with Non-Alcoholic Liver Cirrhosis

Background: Liver cirrhosis is one of the most significant causes of death in many regions worldwide. This study aimed to assess the correlation of hemostatic and endocrine parameters with Child-Turcotte-Pugh (CTP) scoring in patients with non-alcoholic liver cirrhosis. Materials and Methods: This study included 59 patients monitored for non-alcoholic liver cirrhosis in a gastroenterology clinic from January 2018 to February 2019. The subjects were grouped according to the CTP scores, and their adrenocorticotropic hormone (ACTH), cortisol, dehydroepiandrosterone sulfate (DHEA-SO4), progesterone, growth hormone (GH), insulin-like growth factor-1 (IGF-1), GH/ IGF-1 ratio, fibrinogen, D-dimer, and D-dimer/fibrinogen ratio were measured. Results: According to CTP scoring, 20.3% of patients were CTP-A (n=12), 35.6% were CTP-B (n=21), and 44.1% were CTP-C (n=26). There were statistically significant differences for IGF-1, DHEA-SO4, and GH/IGF-1 ratios between CTP-A and CTP-B groups (P=0.002, P=0.043, P=0.038, respectively). Additionally, there were statistically significant differences between the CTP-B and CTP-C groups for D-dimer and GH values (P=0.024, P=0.006, respectively). There were statistically significant differences for D-dimer, GH, IGF-1, and D-dimer/fibrinogen ratio between the CTP-A and CTP-C groups (P&lt;0.001, P=0.016, P=0.002, P=0.031, respectively). Conclusion: Severe hemostatic and endocrine complications develop in patients with liver cirrhosis due to non-alcoholic causes. Additionally, it seems that using D-dimer and D-dimer/fibrinogen ratio, along with fibrinogen level, can be beneficial in showing liver damage in these patients.

The European Society for Clinical Nutrition and Metabolism practical guideline: Clinical nutrition in liver disease

The Practical guideline is based on the current scientific ESPEN guideline on Clinical Nutrition in Liver Disease (Plauth M., Bernal W., Dasarathy S., Merli M., Plank L. D., Schütz T., Bischoff S. C. ESPEN guideline on clinical nutrition in liver disease // Clin Nutr. — 2019. — 38. — Р. 485—521). It has been shortened and transformed into flow charts for easier use in clinical practice.&#x0D; The guideline is dedicated to all professionals including physicians, dieticians, nutritionists and nurses working with patients with chronic liver disease. A total of 103 statements and recommendations are presented with short commentaries for the nutritional and metabolic management of patients with (i) acute liver failure, (ii) alcoholic steatohepatitis, (iii) non-alcoholic fatty liver disease, (iv) liver cirrhosis, and (v) liver surgery/transplantation. The disease-related recommendations are preceded by general recommendations on the diagnostics of nutritional status in liver patients and on liver complications associated with medical nutrition. This practical guideline gives guidance to health care providers involved in the management of liver disease to offer optimal nutritional care.

Gut Microbiome: A Potential Modifiable Risk Factor in Biliary Atresia.

Biliary atresia (BA) is a fibro-obliterative condition of the biliary tree, presenting in infancy. The bilioenteric conduit formed at Kasai portoenterostomy (KPE), achieves restoration of bile flow in approximately 60% of infants. Even if the operation is successful, cirrhosis and its associated complications are, however, common. BA remains the leading cause for liver transplantation (LT) in children. Antibiotic, choleretic, and steroid therapy post-KPE have not convincingly reduced LT rates. Advances in molecular technology have enabled characterisation of the encoded genes of the gut microbiota (gut microbiome). The gut microbiome plays an important role in host metabolism, nutrition, and immune function, with alterations in its diversity and/or composition, known as dysbiosis, being described in disease states, including liver disease. Liver-gut microbiome exploration in adulthood largely focuses on nonalcoholic liver disease, cirrhosis (mainly alcohol- or viral-based aetiology) and cholestatic liver diseases (eg, primary sclerosing cholangitis), with microbial signatures correlating to disease severity. Investigation of the gut microbiota in BA had been limited to culture-based methodology, but molecular studies are emerging, and although in their infancy, highlight a potential pathogenic role for Enterobacteriaceae and Streptococcus, and a potential beneficial role for Bifidobacteria. Bacterial translocation, and the production of gut microbiome-derived metabolites, are key host-microbiome-mechanistic pathways in liver disease pathogenesis. Microbiome-targeted therapeutics for liver disease are in development, with faecal microbiota transplantation showing promise in cirrhosis. Could the gut microbiome be a novel modifiable risk factor in BA, reducing the need for LT?

National trends and outcomes of genetically inherited non-alcoholic chronic liver disease in the USA: estimates from the National Inpatient Sample (NIS) database.

BackgroundMedical literature on the prevalence of genetic liver disease is lacking. In this study, we investigated the in-hospital healthcare and economic burden from genetic causes of non-alcoholic chronic liver disease (NACLD) and non-alcoholic liver cirrhosis (NALC) in the USA.MethodsData were abstracted from the National Inpatient Sample database between 2002 and 2014 using ICD9 codes for patients discharged with NACLD and NALC secondary to genetic diseases including alpha-1 antitrypsin deficiency (A1ATd), cystic fibrosis (CF), Wilson disease (WD), hereditary hemochromatosis (HHC), glycogen storage disease, and disorders of aromatic amino-acid metabolism (DAAAM).ResultsThroughout the study period, there were 19,332 discharges for NACLD associated with the six genetic diseases including 14,368 for NALC. There were $1.09 billion in hospital charges, 790 in-hospital deaths, and 955 liver transplants performed. Overall, A1ATd was associated with 8,983 (62.52%) hospitalizations for NALC followed by WD, CF, and HHC. The highest in-hospital mortality was seen with HHC. The greatest frequency of liver transplants was seen with DAAAM.ConclusionThe number of hospitalizations for genetic liver diseases continues to increase. With increased funding and directed research efforts, we can aim to improve medical treatments and the quality of life for patients at risk for liver deterioration.

Mortality Risk and Decompensation in Hospitalized Patients with Non-Alcoholic Liver Cirrhosis: Implications for Disease Management.

Here we aimed to assess the mortality risk and distribution of deaths from different complications and etiologies for non-alcoholic liver cirrhosis (NALC) adult inpatients and compare them with that of the general hospitalized adult population. Hospitalized patients with a primary diagnosis of NALC and aged between 30 and 80 years of age from 1999 to 2010 were identified using a population-based administrative claims database in Taiwan. They were matched with a general, non-NALC population of hospitalized patients. Causes of death considered were variceal hemorrhage, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatocellular carcinoma, jaundice, and hepatorenal syndrome. A total of 109,128 NALC inpatients were included and then matched with 109,128 inpatients without NALC. Overall mortality rates were 21.2 (95% CI: 21.0–21.4) and 6.27 (95% CI: 6.17–6.37) per 100 person-years, respectively. Among complications that caused death in NALC patients, variceal hemorrhage was the most common (23.7%, 11.9 per 100 person-years), followed by ascites (20.9%, 10.4 per 100 person-years) and encephalopathy (18.4%, 9.21 per 100 person-years). Among all etiologies, mortality rates were highest for NALC patients with HBV infection (43.7%, 21.8 per 100 person-years), followed by HBV-HCV coinfection (41.8%, 20.9 per 100 person-years), HCV infection (41.2%, 20.6 per 100 person-years), and NAFLD (35.9%, 17.9 per 100 person-years). In this study, we demonstrated that mortality risks in NALC patients may differ with their etiology and their subsequent complications. Patients’ care plans, thus, should be formulated accordingly.

Study of association between chronic liver disease and thyroid function tests at a tertiary hospital

Background: Among the various functions of liver, one function is synthesis of carrier proteins and metabolism of hormones and liver diseases, have been shown to be associated with various endocrinal disturbances. Aim of the study was to evaluate the spectrum of chronic liver disease and association between thyroid profile and severity of liver damage at a tertiary hospital. Material and Methods: Present study was single-center, hospital based, case-control study, conducted in 88 cases of liver cirrhosis/ chronic liver disease and 88 age/sex matched healthy controls (randomly selected from relatives attending OPD with patients) were studied. Thyroid function tests were done and compared among cases and controls. Results: In present study 88 cases of liver cirrhosis/ chronic liver disease and 88 healthy controls were studied. Mean age and gender were comparable in cases and controls and difference was not statistically significant. Most of cases had alcoholic liver cirrhosis (80.7 %), rest had non-alcoholic liver cirrhosis (12.5%) and chronic viral hepatitis (6.8%). As per Child-Pugh Score, most cases were from Child-Pugh B (42%), followed by Child-Pugh C (31.8%) and Child-Pugh A (26.1%). In present study free T3, free T4 and TSH were compared between cases and controls, abnormal values were noted in cases and statistically significant difference was noted. Serum thyroid profile abnormalities were noted as per advancement in Child-Pugh Score Classes and difference was statistically significant for free T3 and free T4. Conclusion: Thyroid function test abnormalities in circulating thyroid hormone concentrations were noted in patients liver cirrhosis as compared to healthy subjects and severe abnormalities were associated with advanced Child Pugh score.

1605. Differences in Clinical Characteristics of Third Generation Cephalosporin Resistance and Treatment Outcomes in Escherichia coli and Klebsiella pneumoniae Bacteremia in Patients with Liver Cirrhosis

BackgroundThis study aimed to identify characteristics of third-generation cephalosporin (3GC) resistance in Escherichia coli bateremia (ECB) and Klebsiella pneumoniae bacteremia (KPB) in patients with liver cirrhosis (LC), and to investigate the effects of appropriateness of empirical antibiotic treatment on outcomes.MethodsWe retrospectively collected demographic, clinical and microbiological information on all ECB and KPB episodes in LC patients ≥ 18 years of age hospitalized to a tertiary-care teaching hospital in South Korea from 2007 to 2018. Clinical characteristics associated with 3GC resistance and treatment failure were analyzed using a multivariate logistic regression model. Treatment failure was defined as persistent bacteremia for ≥ 7 days, or relapsed bacteremia ≤ 30 days, or all-cause mortality ≤ 30 days.Results3GC resistance rates of E. coli were 30.3% overall and increased significantly during the study period (P=0.001), while the rates of K. pneumoniae were not changed (24.3% overall) (P=0.994). Of total 356 ECB and KPB episodes, 112 were caused by 3GC resistant strains. The factor associated with 3GC resistance was isolation of 3GC resistant strain ≤ 1 year in both ECB (OR, 7.754; 95% CI, 2.094~28.716) and KPB (OR, 2.774; 1.318~5.838). In ECB, beta-lactam or fluoroquinolone treatment ≤ 30 days was another factor associated with 3GC resistance (OR, 2.774; 95% CI, 1.318~5.838), but not in KPB. The factor associated with treatment failure was high MELD score in both ECB (OR, 1.193 at 1 increase; 95% CI, 1.118~1.272) and KPB (OR, 1.163; 95% CI 1.083~1.250). Additionally, in ECB, non-alcoholic LC (OR 3.262; 95% CI 1.058~10.063), high Charlson Comorbidity Index (OR, 1.285; 95% CI 1.066~1.548), and inappropriate empirical antibiotic treatment (OR, 3.194; 95% CI 1.207~8.447) were associated with treatment failure.ConclusionDuring the study period, 3GC resistance increased in ECB, but not in KPB. In ECB, the severity of the underlying disease and the appropriateness of empirical antibiotics were associated with treatment failure, but there was no correlation in KPB. In ECB of LC patients, the appropriateness of empirical antibiotics was a factor associated with treatment outcome, and is the only correctable factor in the clinical setting.Disclosures All Authors: No reported disclosures

Medicinal plants and their Anti-inflammatory effects in Hepatic disorders

Herbal medicines are used as an alternative treatment to cure liver diseases and now a days become most commonly used therapy. Herbal medicines are derived from different parts of plants such as bark, roots, leaves, seeds and flowers. Silymarin, Glycyrrhizic acid, Camellia sinensis, Holy Basil and Long pepper are the medicinal plants that are effective and safe for the treatment of liver ailments. Almost 2 million deaths per year occur due to liver diseases while correct Statistics for liver diseases is not available but liver diseases are highly prevalent in Africa and Asia. By using medicinal plants, the prevalence of hepatitis, alcoholic fatty liver disease, non-alcoholic fatty liver disease, liver cirrhosis and hepatocellular carcinoma can be controlled. The increase in use of herbal medicines support the phenomenon of their effectiveness for the prevention of liver disorders. Scientists are now finding the benefits and evaluate the effect of different herbs on human health by using the scientific methods. Further research work should be done on herbal medicines to collect relevant data about effectiveness and safety of herbs that are used in pharmaceuticals as additional components now a days. This article discusses the common liver diseases, categories of herbs, WHO estimated prevalence of liver diseases worldwide and carcinogenic effects of herbal medicines associated with liver injury.

Association of fibroblast growth factor21 with alcohol consumption and alcohol liver cirrhosis.

BackgroundFibroblast growth factor 21 (FGF21) is produced in the liver and binds to different complex receptor/coreceptor systems. Besides many other processes, FGF21 regulates the intake of simple sugars and alcohol. Increased levels of FGF21 decrease harmful alcohol intake in mice. To increase our understanding on the relationship between FGF21 and alcohol intake in humans, we aimed to measure FGF21 levels in patients with alcoholic liver cirrhosis (ALC) in comparison to patients with nonalcoholic liver cirrhosis (NALC) and healthy persons based on their present alcohol consumption.MethodsAlcohol intake was verified by urinary ethyl glucuronide (uETG) levels, eating and drinking behaviour by a Food Frequency Questionnaire and FGF 21 plasma levels were determined by ELISA in 96 persons (ALC n = 41; NALC n = 34; healthy n = 21).ResultsBoth ALC and NALC patients with elevated ETG levels (≥0.5 μg/ml; indicating alcohol consumption in the last 12–72 h) showed significantly higher FGF21 plasma levels in comparison to patients with negative ETG levels. Eating behaviour did not have an impact on FGF21 plasma levels.ConclusionsIncreased FGF21 levels in patients with recent alcohol consumption (verified by ETG) confirmed the first part of the liver–brain endocrine axis: alcohol consumption was associated with increased FGF21 levels. We could not confirm that elevated FGF21 levels were associated with reduced alcohol intake as a result. That points towards a pathology in this pathway, which might be caused by a malfunction of β‑Klotho or FGF receptors according to other studies and chronic alcohol dependency. Further research is required to clarify these pathologies, which may open new pharmacological treatment for patients with alcohol use disorder and alcohol dependence.

The Inter-Relation between Leptin Receptor (Q223R) Gene Polymorphism and the Risk of Egyptian Patients with HCC.

Background:The relationship of leptin (LEP) and polymorphism of leptin receptor (LEPR) were studied in patients with hepatocellular carcinoma (HCC) and compared with those with liver cirrhosis to find out the extent of the risk of LEPR on patients with HCC. Methods:Serum LEP level and LEPR Q223R gene polymorphism were determined in 300 patients with liver disease categorized equally into five groups’ healthy volunteers, patients with hepatitis C (HCV), patients with non-alcoholic steatohepatitis (NASH), liver cirrhosis and HCC. LEPR gene was amplified by polymerase chain reaction (PCR) then digested by the MSP1 restriction enzyme. Results:The isolated 212 bp of LEPR was sequenced. The serum LEP level was reduced in patients with cirrhotic and HCC. Serum LEP level had negatively correlated with both tumor grade and size in HCC patients. The data obtained from restriction fragment length polymorphismPCR and sequencing revealed the existence of a novel synonymous Q223R single nucleotide polymorphism (SNP) in exon 223 of LEPR gene (1137101). LEPR Gln223Arg, GG and GA genotypes were found in all studied groups. LEPR Gln223Arg, AA genotype was found in NASH, HCC, and control. LEPR Gln223Arg GA genotype is associated with some patients with HCC. Conclusion:GA genotype of LEPR Gln223Arg may be regarded as a probable genetic risk factor for Egyptian patients with HCC.

The severity of hepatic disorder is related to vertebral microstructure deterioration in cadaveric donors with liver cirrhosis.

Patients with liver cirrhosis (LC) commonly suffer from osteoporosis and vertebral fracture, but data about their vertebral micro-architectural changes are still limited. This study aimed to evaluate the potential differences in trabecular micro-architecture of lumbar vertebrae between male LC patients and healthy controls, in relation to etiology and pathohistological scoring of the liver disorder. After pathohistological examination of liver tissue, micro-computed tomography was performed on the vertebral samples included into: alcoholic liver cirrhosis group (ALC; n = 16; age: 59 ± 8 years), non-alcoholic liver cirrhosis group (non-ALC; n = 15; age: 69 ± 10 years) and control group (n = 16; age: 58 ± 6 years). Our data showed significant impairment of the trabecular microstructure in the lumbar vertebrae from LC donors, regardless of the alcoholic/non-alcoholic origin of liver disorder, as illustrated by lower BV/TV, Tb.Th, and Tb.N compared with controls (p < .05). Moreover, depredation in trabecular micro-architecture was inversely associated with pathohistological scores (p < .05), indicating that severity of liver disorder could be an important predictor of reduced vertebral strength in LC. We noticed significant micro-architectural deterioration in the trabecular compartment of the lumbar vertebrae of male individuals with alcoholic and non-alcoholic LC, which was associated with the severity of the liver disease. Thus, clinical assessment of fracture risk should be advised for all LC patients, regardless of the alcoholic origin of liver cirrhosis. Additionally, adequate and timely treatment of liver disorder may decelerate the progression of bone impairment in LC patients.