Etiology Of Liver Cirrhosis Research Articles

Enhancing global hepatocellular carcinoma management: Bridging Eastern and Western perspectives on dexamethasone and N-acetylcysteine before transarterial chemoembolization

This article explores the integration of Eastern and Western perspectives on the use of dexamethasone and N-acetylcysteine as premedications in transarterial chemoembolization for hepatocellular carcinoma (HCC). By examining key concerns raised by Western researchers, particularly regarding the different etiologies of liver cirrhosis, and contrasting them with robust clinical data from Asia, this article highlights the necessity for region-specific research and proposes future directions for global HCC management.

Portal hypertension as an independent risk factor for cirrhotic cardiomyopathy: An investigation on its mechanism based on bioinformatics analysis

AbstractAimsDespite being commonly found in patients with various etiologies of liver cirrhosis, cirrhotic cardiomyopathy (CCM) is often overlooked, and its mechanism remains unknown. This study aimed to illuminate the epidemiological data and risk factors of CCM and to explore its potential mechanisms through a bioinformatics analysis.MethodsClinical data were collected from January 2008 to December 2022 retrospectively, and patients were divided into the CCM and non‐CCM groups based on the criteria proposed by the 2005 World Congress of Gastroenterology. Independent risk factors for CCM were identified through a multivariate logistic regression analysis. CCM‐related genes were explored using the GeneCards database, and enrichment analysis was performed. Protein–protein interaction analysis was conducted using the Search Tool for the Retrieval of Interacting Genes (STRING) database, and hub genes were identified using Cytoscape software. The Transcriptional Regulatory Relationships Unraveled by Sentence‐based Text Mining (TRRUST) database was utilized to explore transcription factors (TFs), and a network regulatory diagram of TF‐gene pathways was constructed. Finally, potential drugs were predicted using the Drug Gene Interaction Database.ResultsA total of 965 patients with liver cirrhosis were included, among whom 563 (58.3%) were diagnosed with CCM. Portal hypertension (PHT) was identified as the only independent risk factor for CCM. The hub genes included IL6, TNF, TGFB1, IL1B, MMP9, and IL10. Enrichment analysis revealed that Forkhead box O (FoxO), mitogen‐activated protein kinase (MAPK), hypoxia‐inducible factor (HIF‐1), phosphoinositide 3‐kinase‐protein kinase B (PI3K‐AKT), interleukin (IL)‐17, tumor necrosis factor (TNF), vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR), Janus kinase/signal transducers and activators of transcription (JAK‐STAT), and transforming growth factor (TGF)‐beta pathways were enriched. TFs such as CEBPB, NFKB1, STAT1, STAT3, and SP1 were also implicated. Potential drugs included pravastatin and atorvastatin.ConclusionsThe morbidity associated with CCM was high, and PHT was the only independent risk factor. The mechanism may be related to inflammation, and statins may hold therapeutic promise.

An Extensive Analysis of Liver Cirrhosis’s Genesis, Pathophysiology, Epidemiology, And Diagnosis

Portal hypertension and liver failure can arise as a result of liver cirrhosis, a chronic illness characterized by the fibrosis and renewal of nodules in the liver. A number of long-term conditions can lead to cirrhosis, a progressive disease. after a few years or perhaps decades. Liver cirrhosis is one public health concern. Metabolic syndrome, autoimmune diseases, storage diseases, drug use, alcohol consumption, viral hepatitis, and toxic chemicals are the usual causes. Cirrhosis is the fourteenth most prevalent cause of death in adults. placing ninth overall and fourth in Europe and the US. Because this condition is symptomatic and often remains undiagnosed in its early stages, its frequency is underestimated. It typically progresses to the decompensated stage at a rate of 5 to 7% annually. Here, we discuss the pathophysiology, epidemiology, diagnosis, and etiology of liver cirrhosis.

Assessment of human Herpes Virus-8 infection in Iranian cirrhotic patients on the waiting list for liver transplantation: A cross-sectional analysis

BackgroundHuman Herpes Virus 8 (HHV-8) is involved in autoimmunity. However, its association with advanced liver disease has not been fully explained. Herein, the prevalence of HHV-8 viremia was assessed in Iranian liver transplant candidates with a confirmed diagnosis of cirrhosis. MethodsThis cross-sectional study was conducted on 230 patients with cryptogenic cirrhosis, virus-related cirrhosis, and autoimmune hepatitis, as well as 140 healthy blood donors from April 2022 to September 2023. The HHV-8 IgG antibody concentration and viral load were evaluated via ELISA and RT‒PCR, respectively. ResultsAnti-HHV-8 IgG antibodies were detected in 25 cirrhotic patients (10.8 %) and four healthy individuals (2.6 %) (p = 0.022). The majority of the seropositive patients had cryptogenic cirrhosis (20.4 %), followed by autoimmune hepatitis (13.1 %) and virus-related cirrhosis (4.7 %). The seropositivity of HHV-8 IgG antibody was significantly different among the etiologies of liver cirrhosis (p = 0.011). However, HHV-8 genomic DNA was not detected in the sera of the patients or healthy blood donors. ConclusionThe role of HHV-8 infection in the development of posttransplant diseases, together with the higher seroprevalence of HHV-8 antibodies in cirrhotic patients than in healthy individuals, highlights the importance of both primary and latent infections in liver transplantation. Therefore, serological and molecular screening of HHV-8 is highly suggested for liver transplant candidates and organ donors. The possibility of antibody-mediated epitope mimicry in cryptogenic and autoimmune groups with moderate HHV-8 antibody positivity and negative viral loads may account for the development of advanced liver diseases.

Study for the Significance of Ascetic Fluid Lactoferrin in Diagnosis of Spontaneous Bacterial Peritonitis in Decompensated Liver Cirrhosis

Abstract Background Cirrhosis represents the inal common histological pathway for a wide variety of chronic liver diseases. Occurrence of ascites is the most common presentation of liver cirrhosis. Spontaneous bacterial peritonitis (SBP) is observed in 15–26% of patients hospitalized with ascites. SBP is deined as the infection of AF in the absence of a contiguous source of infection and/or an intra-abdominal inlammatory focus. An AF-polymorphonuclear (PMN) leukocyte count more than or equal to 250/mm irrespective of the AF culture result is universally accepted nowadays as the best surrogate marker for diagnosing SBP. Frequently, the results of the manual or automated PMN count do not reach the hands of the responsible medical personnel in a timely manner. Aim of the Work to use AF lactoferrin for the diagnosis of SBP and to identify a clinically useful marker that can be used for future development of an important clinical, economic, and time saving rapid bedside test for the diagnosis of SBP in cirrhotic ascites. Patients and Methods This study was conducted on 60 patients with decompensated chronic liver disease and ascites with and without spontaneous bacterial peritonitis admitted to Gastroenterology and Hepatology department inpatient and outpatient clinics at Ain Shams University Hospitals and labs, from April 2023 to September 2023. Results Females were affected more than males by SBP, SBP has higher incidence in elderly compared to control group No significant difference between studied groups regards to risk factors and Child class (p > 0.05). HCV infection was the main etiology of liver cirrhosis in both groups while HBV infection was much less common with no significant difference between studied groups (p > 0.05). Patients in SBP group showed positive reaction to CRP compared to control group with significant difference between them (p < 0.05). No statistical significant differences between studied groups regards to abdominal ultrasonographic indings (p > 0.05). Liver enzymes (ALT and AST) were higher in SBP patients compared to non SBP patients with signiicant difference between them (P < 0.05). SBP patients have higher TLC and lower MCV and platelets count compared to non SBP patients with signiicant difference between them (P < 0.05). No statistical signiicant difference between studied groups regards to INR, Hb and MCH values (p > 0.05). Conclusion Outcomes of our study provide evidence of the clinical usefulness of AF lactoferrin levels in patients with cirrhosis to differentiate those with and without SBP. It is important to note that the correlation of lactoferrin levels and inlammatory markers in blood samples and AF could be inluenced by lysis of PMN cells during transport to the laboratory, which could lead to a false negative result. Moreover, manual measurement of the AF and PMN count is operator dependent, which makes quality control difficult. Commercially available kits for the measurement ascetic luid lactoferrin could be used in a future development of qualitative bedside assay.

Vliv polymorfizmů PNPLA3 rs738409 a TM6SF2 rs58542926 dárce a příjemce na dlouhodobé přežívání pacientů po transplantaci jater

Summary Introduction: The variants rs738409 c.444C>G (p.I148M) in patatin-like phospholipase domain-containing 3 (PNPLA3) and rs58542926 c.499G>A (p.E167K) in TM6SF2 (transmembrane 6 superfamily member 2) are significant genetic risk factors of development and progression of non-alcoholic fatty liver disease (NAFLD). In both variants, increased liver-specific mortality was described, while the impact on all-cause mortality was not proved. The aim of the study was to evaluate the impact of PNPLA3 rs738409 and TM6SF2 rs58542926 genotypes of the donor and recipient respectively on long-term patient survival after LT. Methods: We evaluated long-term patient survival in a cohort of 268 adult LT recipients, in whom PNPLA3 rs738409 and TM6SF2 rs58542926 genotypes of the donor and recipient respectively were available and steatosis was evaluated in liver graft biopsy 6–30 months after LT. The median fol low-up was 17 years. The Kaplan-Meier model was used for the survival estimates and the Cox proportional hazard model was used to assess the predictive value of the chosen variables. Results: Increased recipient age (P < 0.001), male sex (P = 0.014), alcoholic (P = 0.021) or HCV (P = 0.042) etiology of liver cirrhosis, and presence of hepatocellular carcinoma (P = 0.009) negatively influenced long-term patient survival after LT. PNPLA3 rs738409 and TM6SF2 rs58542926 genotypes of the recipient and donor respectively had no effect on patient survival. Conclusion: Although PNPLA3 c.444G and TM6SF2 c.499A variants of the donor increase the risk of steatosis of the liver graft after LT, we did not prove a negative impact of these genotypes of the donor and recipient on long-term patient survival after LT. Keywords PNPLA3, TM6SF2, steatosis, MASLD, NAFLD, liver transplantation, patient survival

Dexamethasone and N-acetylcysteine before transarterial chemoembolization in hepatocellular carcinoma: A Western perspective.

Post-embolization syndrome (PES) is the most common complication in patients with hepatocellular carcinoma treated with transarterial chemoembolization. Many strategies have been evaluated to reduce the incidence of PES, but no standard prevention guidelines currently exist. In a single-center, placebo-controlled trial, Simasingha et al evaluated the prophylactic administration of a combination of dexamethasone and N-acetylcysteine and documented a significant reduction in the incidence of PES (from 80% to 6%), of post-procedural liver decompensation (from 14% to 0%), and a shorter hospital stay (4 days vs 6 days), alongside an acceptable safety profile. The results of this study raise several controversial points regarding their applicability in the Western world. In the West, there is a greater and increasing prevalence of metabolic and alcoholic etiologies of liver cirrhosis, so a not negligible number of patients with type II diabetes or hypertension would be excluded from high-dosage dexamethasone prophylaxis. Furthermore, in the West, there is a preferred use of drug-eluting beads loaded with doxorubicin, which are associated with a lower incidence of PES. A study on prophylaxis with dexamethasone and/or N-acetylcysteine in a Western population is hopefully awaited.

Etiological changes of liver cirrhosis and hepatocellular carcinoma-complicated liver cirrhosis in Japan: Updated nationwide survey from 2018 to 2021.

A nationwide survey in 2018 showed decreasing involvement of viral hepatitis and increasing involvement of nonviral liver diseases in the etiology of livercirrhosis (LC) in Japan. An updated nationwide survey was undertaken in 2023. Cases of LC diagnosed between 2018 and 2021 were collected from 75 institutions, and the etiologies of LC were investigated. In addition, the data obtained were compared with the results of previous studies. Among the 15517 cases, alcohol-related liver disease (ALD)-associated LC was the most frequent cause (n=5,487, 35.4%). Hepatitis C virus-associated LC, nonalcoholic steatohepatitis (NASH)-associated LC, and hepatitis B virus-associated LC were ranked as second, third, and fourth, respectively. In comparison to the previous survey, the ratios of viral hepatitis-associated LC decreased (HBV: from 11.5% to 8.1%; HCV: from 48.2% to 23.4%), while the ratios of ALD-associated LC and NASH-associated LC increased (from 19.9% to 35.4% and from 6.3% to 14.6%, respectively). Regarding cases of LC with hepatocellular carcinoma (n=5906), HCV-associated LC (1986 cases, 33.6%) was the most frequent cause. Alcohol-related liver disease-associated LC, NASH-associated LC, and HBV-associated LC were the second-, third-, and fourth-ranked causes, respectively. In comparison to the previous survey, as the cause of hepatocellular carcinoma-complicated LC, HCV-associated LC decreased from 60.3% to 33.6%, while the ratios of ALD-associated LC and NASH-associated LC increased from 14.2% to 28.6% and from 4.2% to 14.0%, respectively. The major causes of LC in Japan are suggested to have been shifting from viral hepatitis to nonviral chronic liver diseases.

Study of prevalence, risk factors for acute kidney injury, and mortality in liver cirrhosis patients

IntroductionAcute kidney injury (AKI) occurs frequently in patients with end-stage liver disease and cirrhosis and is associated with increased short-term mortality. This study aims to study the prevalence and risk factors associated with AKI development and mortality in cirrhosis of liver patients.MethodologyIn the current prospective study, hospitalized patients with liver cirrhosis from October 2021 to March 2023 were recruited. Demographic, clinical, and laboratory data were collected, which included, the etiology of cirrhosis, comorbidities, severity of liver disease, and relevant biochemical parameters. The patient was followed up for 90 days to record the clinical outcome. The statistical software SPSS was utilized to conduct the analysis.ResultsOf 364 liver cirrhosis patients, 25.2% (n, 92) had AKI and belonged to an average age of 51.54 ± 11.82 years. The majority of individuals in the study were males (90.4%), and alcohol (63.4%) was the most common etiology of liver cirrhosis. The present study showed that higher level of direct bilirubin (p = 0.011) and MELD score (p = 0.0001) were identified as significant risk factors for AKI development in patients with liver cirrhosis. Regarding mortality, the significant risk factors were the presence of AKI (p = 0.045) and MELD score (p = 0.025). Among AKI patients, 90-day mortality rates were higher in patients with acute tubular necrosis (p value = 0.010) and stage 3 AKI (p value = 0.001).ConclusionAKI is common in cirrhosis of liver patients. Elevated levels of direct bilirubin and MELD score emerged as significant factors associated with AKI development. Furthermore, AKI and MELD scores were identified as independent risk factors for mortality at both 30 and 90 days. Survival rates were influenced by both the type and stage of AKI; AKI stage 3 and ATN patients had significantly higher mortality rate. Early AKI detection and management are crucial for reducing mortality risk in liver cirrhosis patients.

Prevalence and risk factors for cirrhotic cardiomyopathy: a prospective cross-sectional study.

This study aimed to assess cardiac structure and function in patients with cirrhosis, to investigate the prevalence of cirrhotic cardiomyopathy (CCM) in patients with cirrhosis of different etiologies and to analyze the risk factors for the development of CCM. This study selected cirrhotic patients aged 18-75 years who were hospitalized in Qilu Hospital of Shandong University. Patients with known heart disease, chronic lung disease, severe renal insufficiency, malignancy, thyroid disease, hypertension, diabetes or pregnancy were excluded. A total of 131 patients with cirrhosis were finally included. Based on the results of echocardiography, patients who met the diagnostic definition of CCM were included in the CCM group, otherwise, they were classified as the non-CCM group. The demographic and clinical data of the two groups were compared, and the clinical characteristics and risk factors of CCM were evaluated. The overall prevalence of CCM was 24.4%, and the occurrence of CCM was not related to the etiology of liver cirrhosis. The prevalence of CCM was significantly higher among cirrhotic patients complicated with ascites (31.4% vs. 16.4%; P = 0.046) or with portal vein thrombosis (PVT) (42.9% vs. 17.1%; P = 0.003). Older age [odds ratio (OR) = 1.058; 95% confidence interval (CI), 1.005-1.113; P = 0.032] and PVT (OR = 2.999; 95% CI, 1.194-7.533; P = 0.019) were independent risk factors for the development of CCM. The prevalence of CCM in cirrhotic patients was 24.4%, and the occurrence of CCM was not related to the etiology of cirrhosis. The prevalence of CCM was higher in cirrhotic patients with ascites or PVT. Older age and PVT are independent risk factors for CCM, but validation in larger sample studies is still needed.

Characteristics of liver cirrhosis patients: A literature review

Introduction: Based on data from the World Health Organization (WHO), there is an increase in the number of deaths due to liver cirrhosis from year to year, with the death rate reaching 905,418 in 2000 and soaring to 1,161,914 in 2015. According to a 2016 government public hospital report in Indonesia, The prevalence of liver cirrhosis is estimated at 3.5% of total internal medicine patients, or an average of around 47.4% of all patients treated for cirrhosis. This research using the literature review method aims to describe the characteristics of liver cirrhosis sufferers (gender, etiology of liver cirrhosis, age, child-turcotte-pugh) in Indonesia. Methods: The type of study in this research is a literature review using secondary data in the form of literature that meets the inclusion and exclusion criteria. The inclusion criteria for this research are literature that has been published in the last 10 years, can be accessed in its entirety, literature set in Indonesia, and meets the search keywords. The exclusion criteria in this study were literature with the type of study in the form of a review. Results: A literature search conducted on Google Scholar and Pubmed found eight pieces of literature that met the inclusion and exclusion criteria. Eight pieces of literature are descriptive observational studies. The total samples obtained from the eight pieces of literature were 1010 samples. The time span of the literature obtained was 2015-2023. Before data extraction, each piece of literature was assessed for risk of bias using JBI (Joanna Briggs Institute) critical appraisal. Conclusions: Based on literature review research, cirrhosis sufferers are more likely to suffer from men (685 samples), the elderly age group (>45 years) with hepatitis B etiology (477 samples), and Child-Turcotte-Pugh score category C (397 samples).

Changing spectrum and mortality disparities of etiology of liver cirrhosis in Beijing, China.

Liver cirrhosis remains a major health concern globally, but its epidemiology and etiology evolve with time. However, the changing pattern in etiology and cause of liver-related mortality for patients with cirrhosis are not fully elucidated. Herein, our aim was to characterize the temporal trend of the etiological spectrum and evaluate the impact of etiology on liver-related death among patients with compensated cirrhosis (CC) in Beijing, China. Clinical profiles of patients with CC discharged between January 2008 and December 2015 were retrieved from the Beijing hospital discharge database. The mortalities of different etiologies of cirrhosis were calculated. The risks of readmission and liver-related death associated with etiologies were evaluated by the Cox regression model. A total of 23 978 cirrhotic patients were included. The predominant cause was hepatitis B virus (HBV) (58.93%), followed by alcohol (21.35%), autoimmune (14.85%), miscellaneous etiologies (3.55%), and hepatitis C virus (HCV) (1.32%). From 2008 to 2015, the proportion of HBV-related cirrhosis decreased to 28.11%. Meanwhile, the proportions of autoimmune- and miscellaneous-related cirrhosis increased to 28.54% and 13.11%. The risk of liver-related death ranked the highest in patients with miscellaneous cirrhosis, followed by HBV-related cirrhosis, alcohol-related cirrhosis, autoimmune-related cirrhosis, and HCV-related cirrhosis. The 5-year rates of liver-related death were 22.56%, 18.99%, 18.77%, 16.01%, and 10.76%, respectively. HBV-related cirrhosis caused the highest risk of hepatocellular carcinoma (HCC)-related death, whereas alcohol- and miscellaneous-related cirrhosis caused higher risks of decompensation (DC)-related death than HBV-related cirrhosis, with hazard ratios of 1.35 (95% confidence interval [CI]: 1.24-1.48) and 1.20 (95% CI: 1.03-1.40), respectively. HBV remained a common cause of liver cirrhosis but gradually decreased. Mortality disparities existed in etiologies, with higher risks of HCC-related death in HBV-related cirrhosis, and DC-related death in alcohol- and miscellaneous-related cirrhosis.

Liver Transplant for Hepatocellular Carcinoma in Post-Milan Criteria Era: A Long-Term Single-Center Experience.

We investigated the outcomes of liver transplant in patients with hepatocellular carcinoma. Prospectively, recipients of deceased donor liver transplants from 2007 to 2021 at Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran, were enrolled into the study. The Milan criteria were applied for selection of liver transplant candidates diagnosed with hepatocellular carcinoma. Patients with diagnosis of acute liver failure and who underwent secondary liver transplant were excluded. All patients diagnosed with hepatocellular carcinoma were given mechanistic target of rapamycin inhibitor with calcineurin inhibitor minimization 4 weeks after liver transplant. Patients were assigned to the experimental group (with hepatocellular carcinoma; n = 82) or the control group (without hepatocellular carcinoma; n = 1076). We recorded the etiologies of liver cirrhosis in the experimental group, demographic data from all patients, and postoperative complications. Of 1158 total patients, mean age was 44.15 ± 14.71 years (range, 1-73 years) and 712 were male patients (61.5%). In the experimental group (n = 82), there were 76 patients (92.68%) who were within the Milan criteria; others were excluded intraoperatively. All patients were followed for a median of 65.3 ± 40.8 months (range 10-197 months). Patient survival rates in the experimental group and control group at 3 months, 1 year, and 3 years were 89%, 80%, and 78% versus 84%, 81%, and 70%, respectively (P = .742). Hepatocellular carcinoma reoccurred in 6 patients (7.31%) at mean of 16.83 months postoperatively. Liver transplant for patients with hepatocellular carcinoma in the post-Milan criteria era is associated with acceptable outcomes.

Liver Cirrhosis: Pathophysiology, Diagnosis, and Management

Liver disease is still a concern in world health and liver cirrhosis is the eleventh leading cause of death in the world. Cirrhosis caused 1.32 million deaths in 2017. Liver cirrhosis is a fibrosis or nodule formation in the liver. The study was conducted on databases, such as PubMed, google scholar and gray literature. With inclusion criteria, that are free full text publications published in 2015-2022 and having relevant discussions. Fibrosis in cirrhosis of liver begins with the activation of Stellate and Kupffer cells, damaged hepatocytes and activated platelets are also invoved. Inflammatory cells will appear as a result of the damage and cause fibrosis due to the secretion of cytokines. In addition, there are pathological features, namely nodule regeneration and loss of normal lobular architecture within the nodule. The patient's diagnosis start from anamnesis to gather information related to risk factors, physical examination, laboratory tests, imaging, liver biopsy if necessary. Management can be carried out according from etiology of the cause of liver cirrhosis. Complications of liver cirrhosis are portal hypertension, ascites, hepatic encephalopathy, hepatocellular carcinoma, hyponatremia, and acute kidney injury. Liver cirrhosis is a liver fibrosis caused by Stellate, Kupffer cells, damaged hepatocytes, and activated platelets. Inflammatory cells cause fibrosis, leading to regenerating nodules and decreased blood flow. Diagnosis involves anamnesis, physical examination, laboratory tests, imaging, and liver biopsy if needed. Treatment is based on the etiology of liver cirrhosis, with complications including portal hypertension, ascites, and hepatic encephalopathy.

“NASH-Worldwide the Commonest Aetiology of Liver Cirrhosis”- a Review Article

NAFLD is defined by the presence of fat in the liver (>5% hepatocytes show macrovesicular steatosis) without evidence of other causes of fat accumulation in the liver such as alcohol use (< 20 g/d for women and <30 g/d for men), hepatitis C or certain medications. The spectrum of disease includes NAFL, NASH, cirrhosis and HCC. Disease progression depends on stages of fibrosis. Patients are usually referred with incidentally noted hepatic steatosis on imaging or elevated liver enzymes. Although liver biopsy is the gold standard for diagnosis but worldwide it’s much under practiced and several non invasive tests are currently recommended to identify at risk NASH (≥ stage 2 fibrosis) or advance fibrosis who are at highest risk of developing to cirrhosis. Screening in high-risk populations - T2DM, obesity with metabolic complications, a family history of cirrhosis or significant alcohol use allows for interventions that may prevent future hepatic complications. Currently, about 38% of the global population has a diagnosis of NAFLD. The incidence of hepatic decompensation, HCC and death related to NASH cirrhosis are expected to increase 2-to 3-fold by 2030. NASH- cirrhosis is already the leading indication of liver transplantation worldwide. Currently no specific treatments is licensed for NASH, lifestyle modification and exercise, primarily weight loss is the key to management. The rising clinical and economic burden of NAFLD has highlighted the need for a streamlined approach to prevention, diagnosis, and treatment of the disease that has been discussed in this narrative review. Bangabandhu Sheikh Mujib Med. Coll. J. 2023;2(2):112-126.

Ambiguous Pathogenic Roles of Macrophages in Alcohol-Associated Liver Diseases.

Alcohol-associated liver disease (ALD) represents a major public health issue worldwide and is a leading etiology of liver cirrhosis. Alcohol-related liver injuries include a range of manifestations including alcoholic hepatitis (AH), simple steatosis, steatohepatitis, hepatic fibrosis, cirrhosis and liver cancer. Liver disease occurs from several pathological disturbances such as the metabolism of ethanol, which generates reactive oxygen species (ROS) in hepatocytes, alterations in the gut microbiota, and the immune response to these changes. A common hallmark of these liver affections is the establishment of an inflammatory environment, and some (broad) anti-inflammatory approaches are used to treat AH (eg, corticosteroids). Macrophages, which represent the main innate immune cells in the liver, respond to a wide variety of (pathogenic) stimuli and adopt a large spectrum of phenotypes. This translates to a diversity of functions including pathogen and debris clearance, recruitment of other immune cells, activation of fibroblasts, or tissue repair. Thus, macrophage populations play a crucial role in the course of ALD, but the underlying mechanisms driving macrophage polarization and their functionality in ALD are complex. In this review, we explore the various populations of hepatic macrophages in alcohol-associated liver disease and the underlying mechanisms driving their polarization. Additionally, we summarize the crosstalk between hepatic macrophages and other hepatic cell types in ALD, in order to support the exploration of targeted therapeutics by modulating macrophage polarization.

Study the Efficacy of Argon Plasma Coagulation or Endoscopic Band Ligation versus Their Companion in Management of Gastric Antral Vascular Ectasia in Cirrhotic Patients

Abstract Background Gastric antral vascular ectasia (GAVE) is a rare and often misdiagnosed cause of upper gastrointestinal bleeding accounts for up to 4% of all non-variceal upper gastrointestinal bleedings. Multiple options are available for the treatment of GAVE including endoscopic, surgical and medical therapies. Aim of the Work The aim of this study to evaluate the effect of APC followed by EBL in comparison to APC or EBL alone for the treatment of bleeding GAVE in cirrhotic patients. Patients and Methods We conducted this study on 45 adult cirrhotic patients with overt or occult bleeding from GAVE. Patients were divided into 3 groups: 15 patients in each group. Group I was treated with APC alone, group II was treated with EBL alone and Group III was treated with APC followed by EBL. Results In the current study, no statistically significant difference was detected between both groups regarding the etiology of liver cirrhosis, clinical presentation, laboratory or ultrasound findings with special emphasis on pre-treatment hemoglobin value, hospitalizations. APC alone was found to was found to be less effective in the treatment of GAVE when compared to both techniques (EBL and the combined therapy) which were effective in the treatment of GAVE and GAVE recurrence. EBL alone was found to require less number of treatment sessions but required more number of rubber bands and. Combined therapy (APC followed by EBL) successfully decreased the number of banding sessions and decreased the number of rubber bands required to treat GAVE. Conclusion Combined therapy (APC followed by EBL) and EBL alone are effective methods in the treatment of bleeding GAVE in Egyptian cirrhotic patients. EBL alone requires less number of treatment sessions but may require a big number of applied rubber bands. Combined therapy (APC followed by EBL) successfully decreased the number of banding sessions and decreased the number of rubber bands required to treat GAVE. So, in mild cases when less number of rubber bands seems to be required, it is advisable to start with EBL alone: while in severe cases where a large number of rubber bands seems to be required, it is advisable to use combination therapy of APC and EBL.

Donor Diabetes and Steatosis Affects Recipient Survival Following Liver Transplantation Based on Etiology of Liver Cirrhosis.

Liver transplantation (LT) offers patients with decompensated cirrhosis the best chance at long-term survival. With the rising prevalence of diabetes, further clarity is needed on the impact of receiving a liver allograft from a donor with diabetes on post-LT outcomes. This study aims to evaluate the impact of donor diabetes on clinical outcomes after LT. This is a retrospective analysis of the United Network for Organ Sharing registry data of LT recipients from January 1, 2000, to December 31, 2021. Outcomes analysis was performed using Cox proportional model for all-cause mortality and graft failure. Confounding was reduced by coarsened exact matching causal inference analysis. Of 66 960 donors identified, 7178 (10.7%) had diabetes. Trend analysis revealed a longitudinal increase in the prevalence of donor diabetes ( P < 0.001). Importantly, donor diabetes was associated with increased all-cause mortality (hazard ratio [HR]: 1.13; 95% confidence interval [CI], 1.07-1.19; P < 0.001) and graft failure (HR: 1.16; 95% CI, 1.11-1.22; P < 0.001). Receiving donor organ with diabetes reduced graft survival in patients who received LT for nonalcoholic steatohepatitis cirrhosis (HR: 1.26; 95% CI, 1.13-1.41; P < 0.001) but not other etiologies of cirrhosis. Donor diabetes was associated with worse outcomes post-LT, particularly in patients receiving LT for nonalcoholic steatohepatitis cirrhosis. Future studies are needed to better understand the mechanism underlying this association to develop better risk stratification and clinical practice to improve the outcomes of the transplanted patients.

Baseline characteristics, grading and mortality in acute on chronic liver failure using CLF-C ACLF CRITERIA.

Objective: To observe baseline characteristics, ACLF (Acute on Chronic Liver Failure) grading and mortality in ACLF patients using EASL CLIF CRITERIA. Study Design: Prospective, Observational study. Setting: Medical unit 111, ward 7, Jinnah Postgraduate Medical Centre, Karachi. Period: January 2022 to June 2022. Material &amp; Methods: We prospectively analysed data of hospitalised liver cirrhosis patients at a tertiary care hospital in Karachi, Pakistan. The data was analysed in SPSS version 25. Results: There were a total of 43 ACLF patients, with the median age of IQR of 56(47-62) years, out of which 20 (46.5%) patients were male and 23 (53.5%) were females. The most common etiology of liver cirrhosis was hepatitis C 26(60.5%) followed by other etiologies nine (20.9%) and hepatitis B eight (18.6%). The most common precipitating factor was infection 19(44.2%) and the most frequent organ failure (OF) was renal failure (60.5%), followed by cerebral failure (46.5%) and other OFs. There were 24 patients in ACLF grade one, 13 in grade two and six in grade three ACLF. All six patients of ACLF grade three belonged to CTP C (Child-turcotte-pugh Cirrhosn) (100%) with 100% mortality. ACLF grade two had nine (69.2%) and ACLF grade one had eight (33.33%) CTP C patients. The in hospital mortality of ACLF was 23%. The median MELD Na of these patients was 28 (23-31), CLIF Consortium Organ Failure score was 9(8-10) and CLIF C ACLF Score was 45 (38-55). Conclusion: Highest mortality was observed in Child Pugh C and ACLF grade three in our patients. Such patients must be closely monitored and referred early for medical management and liver transplantation.

Bone Marrow Assessment in Liver Cirrhosis Patients with Otherwise Unexplained Peripheral Blood Cytopenia

We performed a retrospective single-center analysis to investigate the diagnostic yield of bone marrow puncture in patients with liver cirrhosis and cytopenia. Liver cirrhosis patients receiving bone marrow aspiration or biopsy for the diagnostic work-up of otherwise unexplained peripheral blood cytopenia at our institution between 2004 and 2020 were enrolled in this study. We evaluated findings from cytologic, histologic and immunologic assessment and final diagnostic outcomes. A total of 118 patients with a median age of 55 years and a median Child–Pugh score of B (8 points) were enrolled. The main etiologies of liver cirrhosis were viral hepatitis (B and C) or chronic alcohol consumption. The majority of patients (60%) exhibited concurrent anemia, leukocytopenia and thrombocytopenia. Bone marrow assessment revealed normal, unspecific or reactive alterations in 117 out of 118 patients (99%). One patient was diagnosed with myelodysplastic syndrome. Our findings suggest that peripheral blood cytopenia in patients with liver cirrhosis is rarely associated with a primary bone marrow pathology.