Small bites,big impact:The importance of evening snacks in patients with advanced chronic liver disease

People with advanced chronic liver disease(ACLD)have an enhanced risk of malnutrition,which has multifactorial etiology and is mainly linked to a reduced energy and protein intake;malnutrition is critical for patients with cirrhosis since it is often associated with sarcopenia,a skeletal muscle depletion with a loss of muscle mass and function.Late-evening snacks have been extensively studied,and guidelines are recommended to counteract the effects of prolonged fasting at night in patients with ACLD.However,it has not been fully explored whether late evening snacking is clarified as a milestone to address the nutritional needs of people with ACLD or whether it has a potential role in improving body compo-sition.In this randomised control trial,Yu et al demonstrated that long-term nocturnal snacks have the potential to significantly improve body composition by body fat mass,visceral fat area and body cell mass in patients with ACLD.While the improvement in skeletal muscle mass was minor,the promising results in other compositions provide hope for future research and patient care.

Palliative care for end-stage liver disease and acute on chronic liver failure:A systematic review

BACKGROUND End stage liver disease(ESLD)represents a growing health concern characterized by elevated morbidity and mortality,particularly among individual ineligible for liver transplantation.The demand for palliative care(PC)is pronounced in patients grappling with ESLD and acute on chronic liver failure(ACLF).Unfortunately,the historical underutilization of PC in ESLD patients,despite their substantial needs and those of their family caregivers,underscores the imperative of seamlessly integrating PC principles into routine healthcare practices across the entire disease spectrum.AIM To comprehensively investigate the evidence surrounding the benefits of incorporating PC into the comprehensive care plan for individuals confronting ESLD and/or ACLF.METHODS A systematic search in the Medline(PubMed)database was performed using a predetermined search command,encompassing studies published in English without any restrictions on the publication date.Subsequently,the retrieved studies were manually examined.Simple descriptive analyses were employed to summarize the results.RESULTS The search strategies yielded 721 references.Following the final analysis,32 fulllength references met the inclusion criteria and were consequently incorporated into the study.Meticulous data extraction from these 32 studies was undertaken,leading to the execution of a comprehensive narrative systematic review.The review found that PC provides significant benefits,reducing symptom burden,depressive symptoms,readmission rates,and hospital stays.Yet,barriers like the appeal of transplants and misconceptions about PC hinder optimal utilization.Integrating PC early,upon the diagnosis of ESLD and ACLF,regardless of transplant eligibility and availability,improves the quality of life for these patients.CONCLUSION Despite the substantial suffering and poor prognosis associated with ESLD and ACLF,where liver transplantation stands as the only curative treatment,albeit largely inaccessible,PC services have been overtly provided too late in the course of the illness.A comprehensive understanding of PC's pivotal role in treating ESLD and ACLF is crucial for overcoming these barriers,involving healthcare providers,patients,and caregivers.

Influence of nonalcoholic fatty liver disease on response to antiviral treatment in patients with chronic hepatitis B:A meta-analysis

BACKGROUND Although hepatitis B virus infection is the leading cause of chronic liver injury globally,nonalcoholic fatty liver disease(NAFLD)is gradually gaining attention as another major chronic liver disease.The number of patients having chronic hepatitis B(CHB)with concomitant hepatic steatosis has increased.AIM To analyze the effect of NAFLD on the response to antiviral treatment in patients with CHB.METHODS Relevant English studies were systematically searched across PubMed,EMBASE,Web of Science,and Cochrane Library until October 2023.Studies in which the treatment outcomes were compared between patients with CHB only and those with CHB and hepatic steatosis were included.RESULTS Of the 2502 retrieved studies,11 articles were finally included.Biochemical response until 48 wk(OR=0.87,95%CI:0.50–1.53,P=0.000)and 96 wk(OR=0.35,95%CI:0.24–0.53,P=0.24)and virological response until 96 wk(OR=0.80,95%CI:0.43–1.49,P=0.097)were lower in patients with hepatic steatosis than in patients with CHB alone.CONCLUSION Hepatic steatosis lowers the biochemical response to antiviral treatment in patients with CHB.

Progress of mitochondrial and endoplasmic reticulum-associated signaling and its regulation of chronic liver disease by Chinese medicine

The endoplasmic reticulum(ER)is connected to mitochondria through mitochondria-associated ER membranes(MAMs).MAMs provide a framework for crosstalk between the ER and mitochondria,playing a crucial role in regulating cellular calcium balance,lipid metabolism,and cell death.Dysregulation of MAMs is involved in the development of chronic liver disease(CLD).In CLD,changes in MAMs structure and function occur due to factors such as cellular stress,inflammation,and oxidative stress,leading to abnormal interactions between mitochondria and the ER,resulting in liver cell injury,fibrosis,and impaired liver function.Traditional Chinese medicine has shown some research progress in regulating MAMs signaling and treating CLD.This paper reviews the literature on the association between mitochondria and the ER,as well as the intervention of traditional Chinese medicine in regulating CLD.

Effects of SARS-CoV-2 infection on incidence and treatment strategies of hepatocellular carcinoma in people with chronic liver disease

BACKGROUND Chronic liver disease(CLD)was associated with adverse clinical outcomes among people with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.AIM To determine the effects of SARS-CoV-2 infection on the incidence and treatment strategy of hepatocellular carcinoma(HCC)among patients with CLD.METHODS A retrospective,territory-wide cohort of CLD patients was identified from an electronic health database in Hong Kong.Patients with confirmed SARS-CoV-2 infection[coronavirus disease 2019(COVID-19)+CLD]between January 1,2020 and October 25,2022 were identified and matched 1:1 by propensity-score with those without(COVID-19-CLD).Each patient was followed up until death,outcome event,or November 15,2022.Primary outcome was incidence of HCC.Secondary outcomes included all-cause mortality,adverse hepatic outcomes,and different treatment strategies to HCC(curative,non-curative treatment,and palliative care).Analyses were further stratified by acute(within 20 d)and post-acute(21 d or beyond)phases of SARS-CoV-2 infection.Incidence rate ratios(IRRs)were estimated by Poisson regression models.RESULTS Of 193589 CLD patients(>95%non-cirrhotic)in the cohort,55163 patients with COVID-19+CLD and 55163 patients with COVID-19-CLD were included after 1:1 propensity-score matching.Upon 249-d median follow-up,COVID-19+CLD was not associated with increased risk of incident HCC(IRR:1.19,95%CI:0.99-1.42,P=0.06),but higher risks of receiving palliative care for HCC(IRR:1.60,95%CI:1.46-1.75,P<0.001),compared to COVID-19-CLD.In both acute and post-acute phases of infection,COVID-19+CLD were associated with increased risks of allcause mortality(acute:IRR:7.06,95%CI:5.78-8.63,P<0.001;post-acute:IRR:1.24,95%CI:1.14-1.36,P<0.001)and adverse hepatic outcomes(acute:IRR:1.98,95%CI:1.79-2.18,P<0.001;post-acute:IRR:1.24,95%CI:1.13-1.35,P<0.001),compared to COVID-19-CLD.CONCLUSION Although CLD patients with SARS-CoV-2 infection were not associated with increased risk of HCC,they were more likely to receive palliative treatment than those without.The detrimental effects of SARS-CoV-2 infection persisted in post-acute phase.

Quantitative Assessment of Liver Fibrosis by Elastography in Patients with Chronic Liver Disease: A Cross-Sectional Study in Lomé (Togo)

Aim: To describe the two-dimensional elastographic profile according to the Shearwave (2D-SWE) technique in patients with chronic liver disease in Lom. Materials and method: Cross-sectional, descriptive study conducted over seven month at the Autel dElie Clinic in Lom, from January to August 2022, on adult patients with chronic liver disease who underwent abdominal ultrasound coupled with two-dimensional elastography. Results: The sample size was 54 patients. The mean age of the patients was 33 12 years, with extremes of 18 and 66 years. Patients aged 30 years or less accounted for 48.1% (n = 26). All patients (n = 54) had at least one transaminase assay with a mean of 69.3 78.3 IU/l (AST) and 59.3 82.8 IU/l (ALT). There was no statistically significant association between the biological parameters and the presence of fibrosis. Viral liver disease was the main cause, accounting for 81.5% (n = 44) of cases, with no significant association with the degree of fibrosis. Ultrasound revealed a dysmorphic liver (57.4%;n = 31) and portal hypertension (18.5%, n = 10). Fibrosis stages F1, F2 and F4 accounted for (48.1%, n = 26), (24.1%, n = 13) and (13%, n = 7) of cases respectively. Liver dysmorphia was significantly associated with the presence of fibrosis (p = 0.012) and portal hypertension was significantly associated with the degree of fibrosis (p = 0.0063). Conclusion: Assessment of liver fibrosis in patients with chronic liver disease using 2D-SWE elastography is essential for patient follow-up.

Clinical implications,diagnosis,and management of diabetes in patients with chronic liver diseases

Diabetes mellitus(DM)negatively affects the development and progression of chronic liver diseases(CLD)of various etiologies.Concurrent DM and CLD are also associated with worse clinical outcomes with respect to mortality,the occurrence of hepatic decompensation,and the development of hepatocellular carcinoma(HCC).Unfortunately,early diagnosis and optimal treatment of DM can be challenging,due to the lack of established clinical guidelines as well as the medical complexity of this patient population.We conducted an exploratory review of relevant literature to provide an up-to-date review for internists and hepatologists caring for this patient population.We reviewed the epidemiological and pathophysiological associations between DM and CLD,the impact of insulin resistance on the progression and manifestations of CLD,the pathogenesis of hepatogenic diabetes,as well as the practical challenges in diagnosis and monitoring of DM in this patient population.We also reviewed the latest clinical evidence on various pharmacological antihyperglycemic therapies with an emphasis on liver disease-related clinical outcomes.Finally,we proposed an algorithm for managing DM in patients with CLD and discussed the clinical and research questions that remain to be addressed.

Antioxidant and anti-inflammatory agents in chronic liver diseases:Molecular mechanisms and therapy

Chronic liver disease(CLD)is a continuous process that causes a reduction of liver function lasting more than six months.CLD includes alcoholic liver disease(ALD),non-alcoholic fatty liver disease(NAFLD),chronic viral infection,and autoimmune hepatitis,which can lead to liver fibrosis,cirrhosis,and cancer.Liver inflammation and oxidative stress are commonly associated with the development and progression of CLD.Molecular signaling pathways such as AMPactivated protein kinase(AMPK),C-Jun N-terminal kinase,and peroxisome proliferator-activated receptors(PPARs)are implicated in the pathogenesis of CLD.Therefore,antioxidant and anti-inflammatory agents from natural products are new potent therapies for ALD,NAFLD,and hepatocellular carcinoma(HCC).In this review,we summarize some powerful products that can be potential applied in all the stages of CLD,from ALD/NAFLD to HCC.The selected agents such asβ-sitosterol,curcumin,genistein,and silymarin can regulate the activation of several important molecules,including AMPK,Farnesoid X receptor,nuclear factor erythroid 2-related factor-2,PPARs,phosphatidylinositol-3-kinase,and lysyl oxidase-like proteins.In addition,clinical trials are undergoing to evaluate their efficacy and safety.

Inflammation and fibrosis in chronic liver diseases including nonalcoholic fatty liver disease and hepatitis C

At present chronic liver disease(CLD),the third commonest cause of premature death in the United Kingdom is detected late,when interventions are ineffective,resulting in considerable morbidity and mortality.Injury to the liver,the largest solid organ in the body,leads to a cascade of inflammatory events.Chronic inflammation leads to the activation of hepatic stellate cells that undergo transdifferentiation to become myofibroblasts,the main extra-cellular matrix producing cells in the liver;over time increased extra-cellular matrix production results in the formation of liver fibrosis.Although fibrogenesis may be viewed as having evolved as a“wound healing”process that preserves tissue integrity,sustained chronic fibrosis can become pathogenic culminating in CLD,cirrhosis and its associated complications.As the reference standard for detecting liver fibrosis,liver biopsy,is invasive and has an associated morbidity,the diagnostic assessment of CLD by non-invasive testing is attractive.Accordingly,in this review the mechanisms by which liver inflammation and fibrosis develop in chronic liver diseases are explored to identify appropriate and meaningful diagnostic targets for clinical practice.Due to differing disease prevalence and treatment efficacy,disease specific diagnostic targets are required to optimally manage individual CLDs such as non-alcoholic fatty liver disease and chronic hepatitis C infection.To facilitate this,a review of the pathogenesis of both conditions is also conducted.Finally,the evidence for hepatic fibrosis regression and the mechanisms by which this occurs are discussed,including the current use of antifibrotic therapy.

Peripheral blood lymphocytes DNA in patients with chronic liver diseases

BACKGROUND: Viral replication in blood cells with nucleases may lead to the damage of lymphocytes genetic apparatus and the beginning of immunopathological reactions. AIM: Of this investigation is to reveal the damage to peripheral blood lymphocytes (PBL) DNA in the patients with chronic liver diseases. MATERIALS AND METHODS: Sixteen-nine patients with chronic liver diseases (37 patients with chronic viral hepatitis, 2 patients with liver cirrhosis of mixed etiology (alcohol+virus G), 30 women with primary biliary cirrhosis-PBC) were examined. The condition of DNA structure of PBL was measured by the fluorescence analysis of DNA unwinding (FADU) technique with modification. Changes of fluorescence (in %) reflected the DNA distractions degree (the presence of DNA single-stranded breaks and alkalinelabile sights). RESULTS AND CONCLUSION: The quantity of DNA single-stranded breaks and alkalinelabile sights in DNA in all patients with chronic viral hepatitis didn't differ from the control group, excluding the patients with chronic hepatitis (CH) C+G. Patients with HGV and TTV monoinfection had demonstrated the increase of the DNA single-stranded breaks PBL quantity. This fact may be connected with hypothesis about the viruses replication in white blood cells discussed in the literature. Tendency to increase quantity of DNA PBL damages in the patients with primary biliary cirrhosis (PBC) accordingly to the alkaline phosphatase activity increase was revealed. Significant decrease of the DNA single-stranded breaks and alkalinelabile sights in the PBC patients that were treated with prednisone was demonstrated. Probably, the tendency to increase the quantity of DNA single stranded breaks and alkalinelabile sights in lymphocytes of the PBC patients was depended on the surplus of the blood bile acid content.

Vitamin D deficiency in chronic liver disease

Vitamin D is an important secosteroid hormone with known effect on calcium homeostasis,but recently there is increasing recognition that vitamin D also is involved in cell proliferation and differentiation,has immunomodulatory and anti-inflammatory properties.Vitamin D deficiency has been frequently reported in many causes of chronic liver disease and has been associated with the development and evolution of non-alcoholic fatty liver disease(NAFLD)and chronic hepatitis C(CHC)virus infection.The role of vitamin D in the pathogenesis of NAFLD and CHC is not completely known,but it seems that the involvement of vitamin D in the activation and regulation of both innate and adaptive immune systems and its antiproliferative effect may explain its importance in these liver diseases.Published studies provide evidence for routine screening for hypovitaminosis D in patients with liver disease.Further prospectives studies demonstrating the impact of vitamin D replacement in NAFLD and CHC are required.

Aspartate aminotransferase-immunoglobulin complexes in patients with chronic liver disease

AIM: To determine the complex of AST and immunoglobulin and to investigate its clinical significance in patients with liver disease.METHODS: The complex of AST and immunoglobulin was determined by encounter immunoelectrophoresis and its clinical significance was investigated in 128 patients with liver disease.RESULTS: AST was bound to immunoglobulin of antiimmunoglobulin A (IgA) class, but any binding to antiimmunoglobulin G and anti-immunoglobulin M classes was not observed. Although the incidence of ASTimmunoglobulin complex was 41.8% in chronic hepatitis (CH), the incidences in liver cirrhosis and hepatocellular carcinoma were 62.2 and 90.0%, respectively. In alcoholic liver disease with high level of serum IgA, the incidence of the complex was 66.7%, which was higher than that in CH. The ratio of binding to lambda-chain of IgA was higher than that to kappa-chain of IgA. The serum level of IgA and the ratio of AST/alanine aminotransferase (ALT) were significantly higher in patients with AST-IgA complex than in those without complex.CONCLUSION: These results suggest that AST-IgA complex in patients with progressive liver diseases and alcoholic liver injury can lead to elevation of the ratio of AST/ALT.

Clinical utility of viscoelastic testing in chronic liver disease: A systematic review

BACKGROUND Conventional coagulation tests are widely used in chronic liver disease to assess haemostasis and to guide blood product transfusion.This is despite the fact that conventional tests do not reliably separate those with a clinically significant coagulopathy from those who do not.Viscoelastic testing such as thromboelastography(TEG)correlate with bleeding risk and are more accurate in identifying those who will benefit from blood product transfusion.Despite this,viscoelastic tests have not been widely used in patients with chronic liver disease outside the transplant setting.AIM To assess the utility of Viscoelastic Testing guided transfusion in chronic liver disease patients presenting with bleeding or who require an invasive procedure.METHODS PubMed and Google Scholar searches were performed using the key words“thromboelastography”,“TEG”or“viscoelastic”and“liver transplantation”,“cirrhosis”or“liver disease”and“transfusion”,“haemostasis”,“blood management”or“haemorrhage”.A full text review was undertaken and data was extracted from randomised control trials that evaluated the outcomes of viscoelastic test guided transfusion in those with liver disease.The study subjects,inclusion and exclusion criteria,methods,outcomes and length of follow up were examined.Data was extracted by two independent individuals using a standardized collection form.The risk of bias was assessed in the included studies.RESULTS A total of five randomised control trials included in the analysis examined the use of TEG guided blood product transfusion in cirrhosis prior to invasive procedures(n=118),non-variceal haemorrhage(n=96),variceal haemorrhage(n=60)and liver transplantation(n=28).TEG guided transfusion was effective in all five studies with a statistically significant reduction in overall blood product transfusion compared to standard of care.Four of the five studies reported a significant reduction in transfusion of fresh frozen plasma and platelets.Two studies showed a significant reduction in cryoprecipitate transfusion.No increased risk of bleeding was reported in the three trials where TEG was used perioperatively or prior to an invasive procedure.Two trials in the setting of cirrhotic variceal and non-variceal bleeding showed no difference in control of initial bleeding.In those with variceal bleeding,there was a statistically significant reduction in rate of re-bleeding at 42 d in the TEG arm 10%(vs 26.7%in the standard of care arm P=0.012).Mortality data reported at various time points for all five trials from 6 wk up to 3 years was not statistically different between each arm.One trial in the setting of non-variceal bleeding demonstrated a significant reduction in adverse transfusion events in the TEG arm 30.6%(vs 74.5%in the control arm P<0.01).In this study there was no significant difference in total hospital stay although length of stay in intensive care unit was reduced by an average of 2 d in the TEG arm(P=0.012).CONCLUSION Viscoelastic testing has been shown to reduce blood product usage in chronic liver disease without compromising safety and may enable guidelines to be developed to ensure patients with liver disease are optimally managed.

Serum 25-hydroxyvitamin D deficiency and hepatic encephalopathy in chronic liver disease

To investigate the relationship between 25-hydroxyvitamin D (25-OHD) deficiency and hepatic encephalopathy (HE) in patients with chronic liver disease (CLD). METHODSA retrospective analysis of the results of 392 adult patients with chronic liver disease who were assessed for liver transplantation between 2006 and 2010 was undertaken. HE, severity of CLD, nutritional status and 25-OHD were analysed in patients assessed for liver transplantation between 2006 and 2010. Patients who presented with acute, fulminant or subacute disease, with a primary diagnosis of liver cancer, were assessed for re-transplantation or who did not have a 25-OHD measurement were excluded from the analysis. RESULTSOne hundred and sixty-five patients were included in this analysis. The mean age of all patients was 53 ± 8 years. Moderate to severe 25-OHD deficiency was identified in 49 patients of whom 36 had grade 2-3 HE compared with 13 patients who were not encephalopathic (P ≤ 0.0001). Mild 25-OHD deficiency was not associated with HE. There was a significant correlation between the severity of 25-OHD deficiency and the severity of liver disease (r = 0.39, P ≤ 0.0001) and disease severity and the presence of HE (P ≤ 0.0001). Importantly, individuals with 25-OHD deficiency were more likely to have a diagnosis of overt HE (OHE) at a significantly lower model for end stage liver disease (MELD) score than individuals without OHE (P ≤ 0.0001). This significant difference was observed with MELD scores from 10 to 38. CONCLUSION25-OHD deficiency was observed in the majority of patients with CLD and for the first time was found to be significantly worse in patients with OHE.

Hepatitis B virus genotypes in chronic liver disease patients from New Delhi,India

AIM: To study the Hepatitis B virus (HBV) genotypes and their effect on the progression and outcome in patients with chronic liver diseases from New Delhi, India. METHODS: Sera from 100 HBV-related chronic liver disease (CLDB) cases were tested for HBV genotype using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and Type-specific primers-based PCR (TSP-PCR) targeting to the surface (S) gene encoding hepatitis B surface antigen. RESULTS: Only genotypes A and D were present and genotype D was dominant. Genotype D was present in all CLDB patient categories. The genotype distribution for the 100 patients with CLDB was as follows: genotype A, 16/100 (16%) (7/40- 17% chronic hepatitis B (CHB); 8/47, 17%, HBV-related cirrhosis (CRB); 1/13, 7.6%, HBV-related hepatocellular carcinoma (HCCB); genotype D- 84/100 (84%) (32/40- 80% CHB; 38/47- 81%, CRB; 11/13, 85%, HCCB); genotype A + D, 3/100 (3%) (1/40- 3% CHB; 1/47- 2%, CRB; 1/13, 7.6%, HCCB); C, 0; B, 0; E, 0; F, 0; G 0, H 0; (P < 0.01, genotype D vs A). CONCLUSION: Only HBV genotypes A and D were present in patients with CLDB from New Delhi, India. Compared with genotype D, genotype A patients had no significant clinical or biochemical differences (P > 0.05). Mixed infection with genotype A and D were seen in 3% of the cases. Genotype D was the dominant genotype prevalent in all patient categories.

Long-term outcomes of pediatric liver transplantation in acute liver failure vs end-stage chronic liver disease:A retrospective observational study

BACKGROUND Children with acute liver failure(ALF)who meet the criteria are eligible for super-urgent transplantation,whereas children with end-stage chronic liver disease(ESCLD)are usually transplanted electively.Pediatric liver transplantation(PLT)in ALF and ESCLD settings has been well described in the literature,but there are no studies comparing the outcomes in these two groups.AIM To determine if there is a difference in post-operative complications and survival outcomes between ALF and ESCLD in PLT.METHODS This was a retrospective observational study of all primary PLTs performed at a single center between 2000 and 2019.ALF and ESCLD groups were compared for pretransplant recipient,donor and operative parameters,and post-operative outcomes including graft and patient survival.RESULTS Over a 20-year study period,232 primary PLTs were performed at our center;195 were transplanted for ESCLD and 37 were transplanted for ALF.The ALF recipients were significantly older(median 8 years vs 5.4 years;P=0.031)and heavier(31 kg vs 21 kg;P=0.011).Living donor grafts were used more in the ESCLD group(34 vs 0;P=0.006).There was no difference between the two groups concerning vascular complications and rejection,but there were more bile leaks in the ESCLD group.Post-transplant patient survival was significantly higher in the ESCLD group:1-,5-,and 10-year survival rates were 97.9%,93.9%,and 89.4%,respectively,compared to 78.3%,78.3%,and 78.3%in the ALF group(P=0.007).However,there was no difference in 1-,5-,and 10-year graft survival between the ESCLD and ALF groups(90.7%,82.9%,77.3%vs 75.6%,72.4%,and 66.9%;P=0.119).CONCLUSION Patient survival is inferior in ALF compared to ESCLD recipients;the main reason is death in the 1st year post-PLT in ALF group.Once the ALF children overcome the 1st year after transplant,their survival stabilizes,and they have good long-term outcomes.

Impact of chronic liver disease on SARS-CoV-2 infection outcomes:Roles of stage,etiology and vaccination

Since the first identification in December of 2019 and the fast spread of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,it has represented a dramatic global public health concern.Though affecting mainly the respiratory system,SARS-CoV-2 disease,defined as coronavirus disease 2019(COVID-19),may have a systemic involvement leading to multiple organ dysfunction.Experimental evidence about the SARS-CoV-2 tropism for the liver and the increasing of hepatic cytolysis enzymes during infection support the presence of a pathophysiological relationship between liver and SARS-CoV-2.On the other side,patients with chronic liver disease have been demonstrated to have a poor prognosis with COVID-19.In particular,patients with liver cirrhosis appear extremely vulnerable to infection.Moreover,the etiology of liver disease and the vaccination status could affect the COVID-19 outcomes.This review analyzes the impact of the disease stage and the related causes on morbidity and mortality,clinical outcomes during SARS-CoV-2 infection,as well as the efficacy of vaccination in patients with chronic liver disease.

A Review on the Role of Low Glycemic Index Foods for Glycemic Control in Chronic Liver Disease

Liver is an essential organ that maintains fasting and postprandial blood glucose response via various metabolic pathways. The liver function gradually deteriorates in chronic liver disease (CLD) due to inflammation and destruction of liver parenchyma. The development of glucose intolerance and hepatogenous diabetes (HD) in patients with CLD is an inevitable event. Diabetes and CLD can coexist, and function synergistically to cause unfavorable clinical consequences, including poor treatment outcomes and frequent hospitalization. The complications associated with liver disease (malnutrition, hypoglycemia, acute kidney injury, lactic acidosis, etc.) and lack of guidelines limit pharmacological management of HD. Dietary recommendations by The European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines (2019), suggested weight reducing hypocaloric diet along with adequate branched-chain amino acid (BCAA) and micronutrient consumption to improve steatosis and insulin sensitivity in patients with CLD. Dietary glycemic index controls prognosis of obesity, non-alcoholic fatty liver disease (NAFLD) and diabetes. The importance of low GI diet in reducing fasting blood glucose, hepatic glucose influx and fat accumulation, thereby improving weight loss and NAFLD score, is being published in patients with diabetes or liver disease. Several countries have already incorporated GI into their national health policies, for identification of the nutrient value, resulting in establishment of worldwide GI and glycemic load tables for specific food items. However, the apparent complexity of GI and lack of low GI meal choices need to be resolved in order to enhance patient’s quality of life, health and well-being. Low GI nutritional supplements, comprising of balanced proportion of carbohydrate, protein, BCAAs, fibers and micronutrients, may reduce the complexity related to dietary management of HD. The review summarizes the importance of nutritional management in HD with focus on low GI diet in people with CLD.

COVID-19 emergency: Changes in quality of life perception in patients with chronic liver disease-An Italian single-centre study

BACKGROUND In December 2019,the coronavirus disease-2019(COVID-19)emerged and rapidly spread worldwide,becoming a global health threat and having a tremendous impact on the quality of life(QOL)of individuals.AIM To evaluate the awareness of patients with chronic liver disease(CLD)regarding the COVID-19 emergency and how it impacted on their QOL.METHODS Patients with an established diagnosis of CLD(cirrhosis,autoimmune hepatitis,primary biliary cholangitis,and primary sclerosing cholangitis)who had been evaluated at our Outpatient Liver Disease Clinic during the 6-mo period preceding the start of Italian lockdown(March 8,2020)were enrolled.Participants were asked to complete a two-part questionnaire,administered by telephone according to governmental restrictions:The first section assessed patients’basic knowledge regarding COVID-19,and the second evaluated the impact of the COVID-19 emergency on their QOL.We used the Italian version of the CLD questionnaire(CLDQ-I).With the aim of evaluating possible changes in the QOL items addressed,the questionnaire was administered to patients at the time of telephone contact with the specific request to recall their QOL perceptions during two different time points.In detail,patients were asked to recall these perceptions first during time 0(t0),a period comprising the 2 wk preceding the date of ministerial lockdown decree(from February 23 to March 7,2020);then,in the course of the same phone call,they were asked to recall the same items as experienced throughout time 1(t1),the second predetermined time frame encompassing the 2 wk(from April 6 to April 19)preceding our telephone contact and questionnaire administration.All data are expressed as number(%),and continuous variables are reported as the median(interquartile range).The data were compared using the Wilcoxon paired non-parametric test.RESULTS A total of 111 patients were enrolled,of whom 81 completed the questionnaire.Forty-nine had liver cirrhosis,and all of them had compensated disease;32 patients had autoimmune liver disease.The majority(93.8%)of patients were aware of COVID-19 transmission modalities and on how to recognize the most common alarm symptoms(93.8%).Five of 32(15.6%)patients with autoimmune liver disease reported having had the need to receive more information about the way to manage their liver disease therapy during lockdown and nine(28.2%)thought about modifying their therapy without consulting their liver disease specialist.About the impact on QOL,all CLDQ-I total scores were significantly worsened during time t1 as compared to time t0.CONCLUSION The COVID-19 epidemic has had a significant impact on the QOL of our population of patients,despite a good knowledge of preventive measure and means of virus transmission.

Hypoxia,angiogenesis and liver fibrogenesis in the progression of chronic liver diseases

Angiogenesis is a dynamic,hypoxia-stimulated and growth factor-dependent process,and is currently referred to as the formation of new vessels from preexisting blood vessels.Experimental and clinical studies have unequivocally reported that hepatic angiogenesis,irrespective of aetiology,occurs in conditions of chronic liver diseases(CLDs) characterized by perpetuation of cell injury and death,inflammatory response and progressive fibrogenesis.Angiogenesis and related changes in liver vascular architecture,that in turn concur to increase vascular resistance and portal hypertension and to decrease parenchymal perfusion,have been proposed to favour fibrogenic progression of the disease towards the end-point of cirrhosis.Moreover,hepatic angiogenesis has also been proposed to modulate the genesis of portal-systemic shunts and increase splanchnic blood flow,thus potentially affecting complications of cirrhosis.Hepatic angiogenesis is also crucial for the growth and progression of hepatocellular carcinoma.Recent literature has identified a number of cellular and molecular mechanisms governing the cross-talk between angiogenesis and fibrogenesis,with a specifi c emphasis on the crucial role of hypoxic conditions and hepatic stellate cells,particularly when activated to the myofibroblast-like pro-fibrogenic.Experimental anti-angiogenic therapy has been proven to be effective in limiting the progression of CLDs in animal models.From a clinical point of view,anti-angiogenic therapy is currently emerging as a new pharmacologic intervention in patients with advanced fibrosis and cirrhosis.