Progression Of Chronic Liver Disease Research Articles

Reply to "Follistatin-like protein 1 and chronic liver disease progression: a novel pro-inflammatory and pro-fibrogenic mediator?".

Reply to "Follistatin-like protein 1 and chronic liver disease progression: a novel pro-inflammatory and pro-fibrogenic mediator?".

Hepatitis B virus X protein induces ALDH2 ubiquitin-dependent degradation to enhance alcoholic steatohepatitis.

Excessive alcohol intake with hepatitis B virus (HBV) infection accelerates chronic liver disease progression and patients with HBV infection are more susceptible to alcohol-induced liver disease. Hepatitis B virus X protein (HBx) plays a crucial role in disease pathogenesis, while its specific role in alcoholic liver disease (ALD) progression has not yet been elucidated. Here, we studied the role of HBx on the development of ALD. HBx-transgenic (HBx-Tg) mice and their wild-type littermates were exposed to chronic plus binge alcohol feeding. Primary hepatocytes, cell lines, and human samples were used to investigate the interaction between HBx and acetaldehyde dehydrogenase 2 (ALDH2). Lipid profiles in mouse livers and cells were assessed by using liquid chromatography-mass spectrometry. We identified that HBx significantly aggravated alcohol-induced steatohepatitis, oxidative stress, and lipid peroxidation in mice. In addition, HBx induced worse lipid profiles with high lysophospholipids generation in alcoholic steatohepatitis, as shown by using lipidomic analysis. Importantly, serum and liver acetaldehyde were markedly higher in alcohol-fed HBx-Tg mice. Acetaldehyde induced lysophospholipids generation through oxidative stress in hepatocytes. Mechanistically, HBx directly bound to mitochondrial ALDH2 to induce its ubiquitin-proteasome degradation, resulting in acetaldehyde accumulation. More importantly, we also identified that patients with HBV infection reduced ALDH2 protein levels in the liver. Our study demonstrated that HBx-induced ubiquitin-dependent degradation of mitochondrial ALDH2 aggravates alcoholic steatohepatitis.

Cellular Senescence in Hepatocellular Carcinoma: The Passenger or the Driver?

With the high morbidity and mortality, hepatocellular carcinoma (HCC) represents a major yet growing burden for our global community. The relapse-prone nature and drug resistance of HCC are regarded as the consequence of varying intracellular processes and extracellular interplay, which actively participate in tumor microenvironment remodeling. Amongst them, cellular senescence is regarded as a fail-safe program, leading to double-sword effects of both cell growth inhibition and tissue repair promotion. Particularly, cellular senescence serves a pivotal role in the progression of chronic inflammatory liver diseases, ultimately leading to carcinogenesis. Given the current challenges in improving the clinical management and outcome of HCC, senescence may exert striking potential in affecting anti-cancer strategies. In recent years, an increasing number of studies have emerged to investigate senescence-associated hepatocarcinogenesis and its derived therapies. In this review, we intend to provide an up-to-date understanding of liver cell senescence and its impacts on treatment modalities of HCC.

Kuhuang alleviates liver fibrosis by modulating gut microbiota-mediated hepatic IFN signaling and bile acid synthesis.

Background: Liver fibrosis is a common outcome of the pathological progression of chronic liver disease; however, no specific and effective therapeutic agent has been approved for its treatment. We investigated the effects of Kuhuang on liver fibrosis and the underlying mechanisms of action. Materials and methods: To induce hepatic fibrosis, either 3,5-diethoxycarbonyl-1,4-dihydro-collidine (DDC) diet was administered, or bile duct ligation (BDL) surgery was performed on C57BL/6 mice. Kuhuang was orally administered to mice for 7days before and after bile duct ligation or 4weeks with a DDC diet. Hematoxylin and eosin, Sirius red staining, and immunohistochemical analyses were performed to evaluate hepatic pathology. Hepatic interferon-β (IFN-β) levels were measured using an enzyme-linked immunosorbent assay. RNA sequencing was performed to examine the gene expression profiles of liver tissues. The mRNA expression of inflammatory, profibrotic, and bile acid (BA)-related genes was further validated by qRT-PCR. A targeted metabolomics assay revealed the alteration of the hepatic bile acid (BA) composition. The composition of the gut microbiota was determined via 16S rRNA sequencing. Results: Treatment with Kuhuang attenuated liver fibrosis and reduced the inflammatory response in bile duct ligation and DDC mouse models. In addition, the hepatic IFN signaling pathway was activated following Kuhuang treatment. Kuhuang treatment also significantly decreased hepatic levels of both primary and secondary BAs. In addition, Kuhuang treatment altered gut microbiota composition, with an increased abundance of interferon-inducing Akkermansia and decreased abundance of bile salt hydrolase-producing Lactobacillus, Clostridium, and Bifidobacterium. Furthermore, the abundance of Akkermansia was positively correlated with the hepatic mRNA expression levels of Ifna4, Ifnb, and Isg15, whereas that of Lactobacillus, Clostridium - sensu - stricto - 1, and Bifidobacterium was positively correlated with levels of bile acid synthesis-related genes. Conclusion: Our results suggest that Kuhuang plays a protective role during the progression of liver fibrosis, potentially by altering the composition of the gut microbiota, which consequently activates interferon signaling and inhibits bile acid synthesis in the liver.

Primary Biliary Cholangitis: A Review

Primary biliary cholangitis (PBC), which is formally known as primary biliary cirrhosis, is a progressive chronic cholestatic liver disease. Previous epidemiologic studies have demonstrated female predominance. Furthermore, the pathophysiology of PBC is multifactorial, and involves loss of immune tolerance to biliary epithelial cells, with interdependent biliary injury, cholestasis, and progressive liver fibrosis. Moreover, its progression to liver fibrosis highly varies among individuals, but most cases are indolent and slowly progressive. Over the past decade, research has provided great insight into personalized care for patients with PBC. Individualized care and early utilization of second- and third-line therapies have improved the outcomes, and decreased the progression of this disease. The present mini-review focused in providing an overview of PBC, including its pathophysiology, clinical presentation, treatment, treatment goals, recommended follow-up, and future research.

Comparison of Shearwave Elastography and Apri Score for Liver Fibrosis in Patients of Chronic Liver Disease

Chronic liver disease of various etiologies is the major causes of mortality and morbidity globally. Liver biopsy is the most accurate and oldest method to determine the chronic liver disease progression and for liver histology. Shear wave elastography (SWE) is a new non-invasive technique that applies localized mechanical compression to the soft tissue with focused ultrasonography and obtains tension images showing the tissue response. Aspartate aminotransferase to platelets ratio (APRI) on the other hand is relatively less expensive test and can be done on outpatient basis. Objective: To find the relation between APRI aspartate and SWE for detection of liver fibrosis in patients with chronic liver disease. Study Design: A Cross Sectional study Setting: Medical Unit-1 Lahore General Hospital Lahore and Department of Gastroenterology & Hepatology, Doctors Hospital and Medical Centre, Lahore. Study Duration: From July 2019 to December 2021. Methods: 180 patients met the criteria of inclusion were included, the blood samples were obtained and sent to the hospital laboratory for valuation of AST and Platelets. Reports were evaluated, APRI was calculated and patients were labeled as negative or positive. Then all patients underwent SWE by a senior radiologist for assessment of liver fibrosis. Patients were labeled as negative or positive. Agreement was noted, all data was entered on a specifically designed proforma, and data were analyzed and entered in SPSS version 20 statistical method. Agreement was calculated by generating 2x2 tables between APRI and SWE findings. Kappa statistics was calculated to measure the strength and significance of agreement. P-value ≤0.05 was taken as significant. Results: In this study, the patients mean age was 46.39 ± 16.02years. There were 119 (66.11%) males and 61 (33.89%) females. The mean BMI of patients was 24.70 ± 5.23kg/m2. The mean duration of CLD was 5.50 ± 2.672 years. The mean AST of patients was 73.98 ± 60.23IU/L while mean platelet count was 200.65 ± 92.47/cm3. The mean APRI was 1.41 ± 1.20. The mean SWE was 18.32 ± 23.85kPa. The APRI and SWE agreed on 73 (54.9%) cases and showed 66.7% agreement between them for diagnosis of liver fibrosis (p<0.05). Conclusion: Thus, APRI and SWE showed strong agreement but further trials are required to confirm the evidence. Keywords: Agreement, APRI, Aspartate aminotransferase to platelets ratio, SWE, Shear-wave elastography, Chronic liver disease and Liver fibrosis.

Identification of a novel interaction site between the large hepatitis delta antigen and clathrin that regulates the assembly of genotype III hepatitis delta virus

BackgroundHepatitis delta virus (HDV), a satellite virus of hepatitis B virus (HBV), is a small, defective RNA virus strongly associated with the most severe form of hepatitis and progressive chronic liver disease and cirrhosis. Chronic hepatitis D, resulting from HBV/HDV coinfection, is considered to be the most severe form of viral hepatitis and affects 12–20 million people worldwide. Involved in the endocytosis and exocytosis of cellular and viral proteins, clathrin contributes to the pathogenesis and morphogenesis of HDV. Previously, we demonstrated that HDV-I and -II large hepatitis delta antigens (HDAg-L) possess a putative clathrin box that interacts with clathrin heavy chain (CHC) and supports HDV assembly.MethodsVirus assembly and vesicular trafficking of HDV virus-like particles (VLPs) were evaluated in Huh7 cells expressing HDV-I, -II and -III HDAg-L and hepatitis B surface antigen (HBsAg). To elucidate the interaction motif between HDAg-L and CHC, site-directed mutagenesis was performed to introduce mutations into HDAg-L and CHC and analyzed using coimmunoprecipitation or pull-down assays.ResultsComparable to HDV-I virus-like particles (VLPs), HDV-III VLPs were produced at a similar level and secreted into the medium via clathrin-mediated post-Golgi vesicular trafficking. Mutation at F27 or E33 of CHC abolished the binding of CHC to the C-terminus of HDV-III HDAg-L. Mutation at W207 of HDV-III HDAg-L inhibited its association with CHC and interfered with HDV-III VLP formation. We elucidated mechanism of the binding of HDV-III HDAg-L to CHC and confirmed the pivotal role of clathrin binding in the assembly of genotype III HDV.ConclusionsA novel W box which was identified at the C terminus of HDV-III HDAg-L is known to differ from the conventional clathrin box but also interacts with CHC. The novel W box of HDAg-L constitutes a new molecular target for anti-HDV-III therapeutics.

Magnitude and genotype of hepatitis delta virus among chronic hepatitis B carriers with a spectrum of liver diseases in Ethiopia

Introduction and ObjectivesChronic hepatitis D infection contributes substantially to the progression of chronic liver disease, especially in most low and middle-income countries, where hepatitis B virus-related chronic liver disease is endemic. Therefore, this study aimed to determine the magnitude and genotype of hepatitis delta virus (HDV) among patients with chronic hepatitis B (CHB)-related liver diseases in Ethiopia. Patients and MethodsIn this cross-sectional study, 323 known HBsAg positive individuals comprising 220 patients with CHB-related liver diseases [121 advanced liver diseases (hepatocellular carcinoma /HCC/ and non-HCC) and 99 chronic hepatitis (CH)], and 103 symptomless blood donors (BD) were enrolled. An ELISA kit was employed to determine HDV infection, and quantitative real-time PCR was used to detect HDV RNA. In addition, a non-coding genomic RNA region was sequenced for genotyping and phylogenetic analysis. ResultsIrrespective of the stage of liver disease, the overall magnitude of HDV was 7.7% (25/323). The frequency of anti-HDV increases with the severity of liver disease, 1.9%, 4%, 10%, and 21.3% among BD, CH, non-HCC, and HCC patients, respectively. HDV RNA has been detected in 1.54 %(5/323) cases with a mean viral load of 4,010,360 IU/ml. All isolates were found to be HDV genotype 1. ConclusionsThe magnitude of HDV infection increased with the severity of liver disease, indicating HDV infection is more common among patients with CHB-related liver diseases in Ethiopia.

Decoding liver fibrogenesis with single-cell technologies

AbstractLiver fibrogenesis is a highly dynamic and complex process that drives the progression of chronic liver disease toward liver failure and end-stage liver diseases. Despite decades of intense studies, the cellular and molecular mechanisms underlying liver fibrogenesis remain elusive, and no approved therapies to treat liver fibrosis are currently available. The rapid development of single-cell RNA sequencing (scRNA-seq) technologies allows the characterization of cellular alterations under healthy and diseased conditions at an unprecedented resolution. In this Review, we discuss how the scRNA-seq studies are transforming our understanding of the regulatory mechanisms of liver fibrosis. We specifically emphasize discoveries on disease-relevant cell subpopulations, molecular events, and cell interactions on cell types including hepatocytes, liver sinusoidal endothelial cells, myofibroblasts, and macrophages. These discoveries have uncovered critical pathophysiological changes during liver fibrogenesis. Further efforts are urged to fully understand the functional contributions of these changes to liver fibrogenesis, and to translate the new knowledge into effective therapeutic approaches.

LOC102553417 silencing facilitates the apoptosis of hepatic stellate cells via the miR‑30e/MTDH axis.

Hepatic fibrosis is an inevitable pathological process in the progression of multiple chronic liver diseases and remains a major challenge in the treatment of liver diseases. The purpose of the present study was to demonstrate whether silencing of the long non-coding RNA LOC102553417 promoted hepatic stellate cell (HSC) apoptosis via the microRNA (miR)-30e/metadherin (MTDH) axis. A LOC102553417 silencing lentivirus was constructed and transduced into HSC-T6 cells. After confirming the silencing efficiency by reverse transcription-quantitative PCR, cell proliferation was assessed using the Cell Counting Kit-8 assay and apoptosis was assessed using flow cytometry. The interaction between LOC102553417 and miR-30e, and that between miR-30e and MTDH, was demonstrated using the dual-luciferase reporter assay and RNA binding protein immunoprecipitation. The apoptosis of HSC-T6 cells was detected after transfection of miR-30e mimics and inhibitors with or without silencing LOC102553417. Silencing of LOC102553417 curbed HSC-T6 cell proliferation and expedited their apoptosis. LOC102553417 was demonstrated to target miR-30e, whereas miR-30e targeted MTDH. In addition, LOC102553417 silencing significantly upregulated miR-30e expression levels, and significantly downregulated MTDH mRNA and protein expression levels, which resulted in a significantly reduced p-Akt/Akt ratio and significantly elevated p53 protein expression levels. Transfection with miR-30e mimic alone significantly enhanced HSC-T6 cell apoptosis and inhibits LOC102553417 and MTDH expressions, In addition, miR-30e mimic expedites the apoptosis of HSCs stimulated by LOC102553417 silencing; consistent results were obtained by reverse validation of miR-30e inhibitor. In conclusion, the present study demonstrated that LOC102553417 silencing stimulated the apoptosis of HSCs via the miR-30e/MTDH axis.

Alcohol intake is associated with a decreased risk of developing primary biliary cholangitis.

BACKGROUNDPrimary biliary cholangitis (PBC) is a chronic progressive liver disease of unknown aetiology characterised by immune-mediated destruction of small and medium-sized intrahepatic bile ducts. There are few well-established risk factors and epidemiological studies are needed to further evaluate the pathogenesis of the disease. AIMTo evaluate the relationship between alcohol intake, smoking and marijuana use with PBC development. METHODSWe conducted a prevalent case control study of 200 cases and 200 age (within a five year age band) and sex-matched controls, identified from the Victorian PBC prevalence study. We assessed lifetime alcohol intake and smoking behaviour (both tobacco and marijuana) prior to PBC onset and used conditional logistic regression for analyses. RESULTSAlcohol intake consistently showed a dose-dependent inverse association with case status, and this was most substantial for 21-30 years and 31-40 years (Ptrend < 0.001). Smoking was associated with PBC, with a stronger association with a longer duration of smoking [e.g., adjusted OR 2.27 (95%CI: 1.12- 4.62) for those who had smoked for 20-35 years]. There was no association between marijuana use and PBC. CONCLUSIONAlcohol appears to have an inverse relationship with PBC. Smoking has been confirmed as an environmental risk factor for PBC. There was no association between marijuana use and PBC.

Rat Hepatic Stellate Cell Line CFSC-2G: Genetic Markers and Short Tandem Repeat Profile Useful for Cell Line Authentication.

Hepatic stellate cells (HSCs) are also known as lipocytes, fat-storing cells, perisinusoidal cells, or Ito cells. These liver-specific mesenchymal cells represent about 5% to 8% of all liver cells, playing a key role in maintaining the microenvironment of the hepatic sinusoid. Upon chronic liver injury or in primary culture, these cells become activated and transdifferentiate into a contractile phenotype, i.e., the myofibroblast, capable of producing and secreting large quantities of extracellular matrix compounds. Based on their central role in the initiation and progression of chronic liver diseases, cultured HSCs are valuable in vitro tools to study molecular and cellular aspects of liver diseases. However, the isolation of these cells requires special equipment, trained personnel, and in some cases needs approval from respective authorities. To overcome these limitations, several immortalized HSC lines were established. One of these cell lines is CFSC, which was originally established from cirrhotic rat livers induced by carbon tetrachloride. First introduced in 1991, this cell line and derivatives thereof (i.e., CFSC-2G, CFSC-3H, CFSC-5H, and CFSC-8B) are now used in many laboratories as an established in vitro HSC model. We here describe molecular features that are suitable for cell authentication. Importantly, chromosome banding and multicolor spectral karyotyping (SKY) analysis demonstrate that the CFSC-2G genome has accumulated extensive chromosome rearrangements and most chromosomes exist in multiple copies producing a pseudo-triploid karyotype. Furthermore, our study documents a defined short tandem repeat (STR) profile including 31 species-specific markers, and a list of genes expressed in CFSC-2G established by bulk mRNA next-generation sequencing (NGS).

MitoQ alleviates carbon tetrachloride-induced liver fibrosis in mice through regulating JNK/YAP pathway.

Liver fibrosis is a pathological wound-healing response caused by chronic liver damage. Mitochondria regulate hepatic energy metabolism and oxidative stress. Accumulating evidence has revealed that increased mitochondrial oxidative stress contributes to the activation of fibrogenesis. However, the roles and underlying mechanisms of mitochondrial oxidative stress in liver fibrosis remain unknown. In this study, C57BL/6 mice were used to establish a model of liver fibrosis via oral gavage with CCl4 treatment for 8weeks. Furthermore, intervention experiments were achieved by CCl4 combined with the intraperitoneal injection of mitoquinone mesylate (mitoQ). We demonstrated that the chronic CCl4 exposure resulted in severe hepatic fibrogenesis and significantly promoted the production of reactive oxygen species (ROS) and mitochondrial abnormalities. Besides, JNK/YAP pathway was also activated. By contrast, the administration of mitoQ markedly inhibited the expression of pro-fibrogenic transforming growth factor-β as well as type I collagen. The antifibrotic effects of mitoQ were also confirmed by hematoxylin and eosin staining and Sirius red staining. Moreover, mitoQ substantially reduced CCl4-induced mitochondrial damage and the release of ROS. Further studies suggested that this protection against liver fibrosis was mechanistically related to the inhibition of phosphorylation of JNK and the nuclear translocation of YAP. In conclusion, these findings revealed that mitoQ attenuated liver fibrosis by inhibiting ROS production and the JNK/YAP signaling pathway. Selective targeting JNK/YAP may serve as a therapeutic strategy for retarding progression of chronic liver disease.

The gut-liver axis: how the gut promotes liver disease

Research over the last two decades has highlighted the major role played by the gut microbiota in health and disease, including chronic liver diseases. The liver and intestine communicate via the portal vein, biliary system, and mediators in the circulation (gut-liver axis). Microbes in the intestine are involved in the maintenance of liver homeostasis. Conversely, alterations in the normal composition or diversity of the gut microbiome-acondition called dysbiosis-can also serve as asource of pathogens and molecules that contribute to the onset or progression of chronic liver diseases, like non-alcoholic fatty liver disease. Through the increased production of bacteria-derived ethanol, altered bile acid metabolism, altered production of short-chain fatty acids, greater abundance of lipopolysaccharide (LPS) containing Gram-negative bacteria and an increased intestinal permeability, dysbiosis impacts metabolic pathways and inflammatory processes. However, the clinical relevance of specific gut microbial alterations associated with chronic liver diseases remains unclear. This review discusses how microbes and their products contribute to liver disease pathogenesis and how targeting the microbiota might be used for therapeutic approaches.

Abstract IA17: Assessing response and time-to-event end-points: RECIST and mRECIST

Abstract In 2010, modified RECIST (mRECIST) criteria were proposed as a way of adapting the RECIST criteria to the particularities of hepatocellular carcinoma (HCC). mRECIST was intended to overcome some limitations of RECIST in measuring tumour shrinkage with local and systemic therapies, and also to refine the assessment of progression that could be misinterpreted with conventional RECIST 1.1, due to clinical events related to the natural progression of chronic liver disease. mRECIST has served its purpose since being adopted or included in clinical practice guidelines (European, American and Asian) for the management of HCC; it has also been instrumental for assessing response and time-to-event endpoints in several phase II and III investigations. Nowadays, mRECIST has become the standard tool for measurement of radiological endpoints at early/intermediate stages of HCC. At advanced stages, guidelines recommend both methods. mRECIST has been proven to capture higher objective response rates in tumours treated with molecular therapies and those responses have shown to be independently associated with better survival. With the advent of novel treatment approaches including immunotherapy combination therapies, there is a need to further refine and clarify some concepts around the performance of mRECIST. Citation Format: Riccardo Lencioni. Assessing response and time-to-event end-points: RECIST and mRECIST [abstract]. In: Proceedings of the AACR Special Conference: Advances in the Pathogenesis and Molecular Therapies of Liver Cancer; 2022 May 5-8; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(17_Suppl):Abstract nr IA17.

LiverMultiScan as an alternative to liver biopsy to monitor autoimmune hepatitis in the National Health Service in England: an economic evaluation

BackgroundAutoimmune hepatitis (AIH) is a rare chronic progressive liver disease, managed with corticosteroids and immunosuppressants and monitored using a combination of liver biochemistry and histology. Liver biopsy (gold standard) is...

Therapeutic Perspectives of IL1 Family Members in Liver Diseases: An Update.

Interleukin (IL) 1 superfamily members are a cornerstone of a variety of inflammatory processes occurring in various organs including the liver. Progression of acute and chronic liver diseases regardless of etiology depends on the stage of hepatocyte damage, the release of inflammatory cytokines and disturbances in gut microbiota. IL1 cytokines and receptors can have pro- or anti-inflammatory roles, even dual functionalities conditioned by the microenvironment. Developing novel therapeutic strategies to block the IL1/IL1R signaling pathways seems like a reasonable option. This mode of action is now exploited by anakinra and canakinumab, which are used to treat different inflammatory illnesses, and studies in liver diseases are on the way. In this mini review, we have focused on the IL1 superfamily members, given their crucial role in liver inflammation diseases, specifically discussing their potential role in developing new treatment strategies.

The role of lifestyle factors on comorbidity of chronic liver disease and cardiometabolic disease in Chinese population: A prospective cohort study

SummaryBackgroundLifestyle factors are associated with chronic liver disease (CLD) and death after CLD diagnosis. However, their associations with pathways of CLD progression have been unclear, particularly transition to cardiometabolic disease (CMD), a major comorbid condition with CLD. We assessed the associations of lifestyle factors with CLD progression.MethodsThe study population involved 486,828 participants of the prospective China Kadoorie Biobank (CKB) aged 30-79 years without a history of cardiovascular disease, diabetes, CLD, or cancer at baseline. Liver-cardiometabolic comorbidity (LCC) was defined as developing CMD subsequently after first CLD (FCLD) in an individual. A multi-state model was used to estimate the associations of high-risk lifestyle factors (smoking, alcohol, physical inactivity, and central adiposity) with CLD progression from healthy to FCLD, subsequently to LCC, and further to death.FindingsDuring a median follow-up of 11 years, 5046 participants developed FCLD, 519 developed LCC, and 157 died afterwards. There were positive associations between the number of high-risk lifestyle factors and risks of all transitions. The hazard ratios (95% CIs) per 1-factor increase were 1.30 (1.25-1.35) for transitions from baseline to FCLD, 1.21 (1.09-1.34) for FCLD to LCC, 1.20 (1.17-1.23) for baseline to death, 1.15 (1.09-1.22) for FCLD to death, and 1.17 (1.06-1.31) for LCC to death. For CLD subtypes, lifestyle factors showed different associations with disease-specific transitions even within the same transition stage.InterpretationHigh-risk lifestyle factors played a key role in all disease transition stages from healthy to FCLD, subsequently to LCC, and then to death, with different magnitude of associations.FundingKadoorie Charitable Foundation, Chinese MoST and NSFC.

TM4SF5-Mediated Regulation of Hepatocyte Transporters during Metabolic Liver Diseases.

Nonalcoholic fatty liver disease (NAFLD) is found in up to 30% of the world’s population and can lead to hepatocellular carcinoma (HCC), which has a poor 5-year relative survival rate of less than 40%. Clinical therapeutic strategies are not very successful. The co-occurrence of metabolic disorders and inflammatory environments during the development of steatohepatitis thus needs to be more specifically diagnosed and treated to prevent fatal HCC development. To improve diagnostic and therapeutic strategies, the identification of molecules and/or pathways responsible for the initiation and progression of chronic liver disease has been explored in many studies, but further study is still required. Transmembrane 4 L six family member 5 (TM4SF5) has been observed to play roles in the regulation of metabolic functions and activities in hepatocytes using in vitro cell and in vivo animal models without or with TM4SF5 expression in addition to clinical liver tissue samples. TM4SF5 is present on the membranes of different organelles or vesicles and cooperates with transporters for fatty acids, amino acids, and monocarbohydrates, thus regulating nutrient uptake into hepatocytes and metabolism and leading to phenotypes of chronic liver diseases. In addition, TM4SF5 can remodel the immune environment by interacting with immune cells during TM4SF5-mediated chronic liver diseases. Because TM4SF5 may act as an NAFLD biomarker, this review summarizes crosstalk between TM4SF5 and nutrient transporters in hepatocytes, which is related to chronic liver diseases.

Association of lipid profile with severity of hepatitis B virus related chronic liver disease in adult

Background: Chronic liver disease (CLD) is a major health problem and contributes to a common cause of hepatocellular carcinoma, disability and death worldwide. Hepatitis B virus (HBV) is the leading cause of CLD in our country. Abnormal lipid profile is expected in those with severe liver dysfunction.&#x0D; Objective: The objective of the study was to determine the alteration of lipid profile (total cholesterol, triglyceride, LDL-C and HDL-C) in HBV positive adult CLD patients and to correlate with severity of liver damage.&#x0D; Methods: This case control study was conducted for one year between January 2018 to December 2018. One hundred and three patients, &gt;18 years old, admitted with HBV positive CLD in Dhaka Medical College Hospital were recorded as case and 103 age and sex matched, healthy population, were recorded as control. A standard case record form including demographics, histories, clinical examinations and different investigations were completed for each group. Then lipid profile values of cases were compared to controls and different Child-Pugh and MELD scores, were used to see severity of liver damage in CLD patients.&#x0D; Results: In patients with HBV positive adult CLD, there were a significant decrease in serum total cholesterol. LDL-C and HDL-C levels compared to the control group (mean 131.4 vs 179.3, 72.5 vs 109.6, and 31.0 vs 40.4 mg/dl, respectively; p&lt;0.001). Comparison of lipid profile with pathologic progression of CLD revealed that these values were diminished gradually with progression of liver damage. Overall triglyceride level was decreased marginally in cases when compared to controls (mean 139.2 vs 146.6 and p=0.047) and this reduction was observed in only advanced stage.&#x0D; Conclusion: Serum total cholesterol, LDL-C and HDL-C level in HBV positive CLD patients were low and diminished gradually with severity of liver damage. Triglyceride level was marginally significant and diminished in advanced CLD.&#x0D; Bang Med J Khulna 2021; 54 : 08-12