Development Of Liver Cirrhosis Research Articles

METABOLIC AND CARDIOVASCULAR COMORBIDITIES IN BULGARIAN PATIENTS WITH CHRONIC VIRAL B AND C HEPATITIS

Recent epidemiologic data on chronic viral B and C hepatitis in Bulgaria are limited.The evolution of these infections depends on liver complications and the presence of nonliver comorbidities. The aim of the study was to assess the frequencies of arterial hypertension, ischemic heart disease, myocardial infarction, chronic heart failure, type 2 diabetes mellitus and metabolic syndrome in patients with chronic viral B and C hepatitis, associated liver cirrhosis and to compare with those of uninfected controls. Material/Methods: We conducted a retrospective cross-sectional study in the period 2003-2023. We included 1803 patients, 474 with chronic hepatitis B, 482 with chronic hepatitis C and 847 uninfected controls. The patient's medical records were analyzed for the presence of arterial hypertension, ischemic heart disease, myocardial infarction, chronic heart failure, type 2 diabetes mellitus and metabolic syndrome. Results: The most common comorbidity in the three groups was arterial hypertension, followed by type 2 diabetes mellitus. The frequency increased in chronically infected patients with liver cirrhosis. We observed a higher prevalence of myocardial infarctions in the patients with chronic hepatitis C (p=0.045) and of metabolic syndrome in the hepatitis B group (p=0.028). A higher prevalence of ischemic heart disease was observed in the group with chronic hepatitis B and liver cirrhosis (p=0.01). Conclusions: Chronic hepatitis B and C in our groups were associated with significant morbidity, particularly with arterial hypertension and type 2 diabetes mellitus. The finding was more pronounced in patients with already developed liver cirrhosis.

Retrospective study of the frequency of diagnosing diffuse changes in the liver parenchyma according to the results of radiological studies

Background. The prevalence of chronic liver pathology is high and increasing in most countries of the world. Objective: to evaluate the incidence rate of structural diffuse changes in the liver using radiological methods in different sex-age groups of the adult population. Materials and methods. 65,570 unique protocols of ultrasound examination and 1,212 magnetic resonance imaging (MRI) of the hepatobiliary system were studied in patients aged 18 years and older. During the statistical analysis of quantitative features, the distribution of indicators for normality was checked according to the Shapiro-Wilk test. The chi-square test was used to compare frequencies. To determine the relationship between the risk of diffuse liver changes and factor characteristics, we used the method of building logistic regression models. To assess the relationship between the factor traits and the resulting trait, the odds ratio (OR) and 95% confidence interval (CI) were calculated. To assess the quality of the model’s prediction, the area under the curve (AUC) and 95% CI were calculated. The level of statistical significance was chosen at 5 % (p = 0.05). The study was approved by the local ethics committee. Results. The frequency of diagnosing diffuse changes in the liver parenchyma during B-mode ultrasound examination in the total sample was 12.5 % (in women — 8.7 %, in men — 18.2 %). A statistically significant increase (p < 0.01) in the risk of developing diffuse changes in the liver was found (OR = 1.01 (95% CI 1.01–1.02 %) with increasing age for each year. In the univariate logistic regression model, men had a 2.3 times higher chances of developing diffuse liver changes than wo­men (p < 0.01), AUC = 0.604 (95% CI 0.598–0.61 %). In the gene­ral sample of patients who underwent MRI of the hepatobiliary system, the frequency of diagnosing fatty infiltration of the liver was 37 % (95% CI 34.3–39.8 %). In particular, among 700 women, the frequency of incidents was 34.1 % (95% CI 30.7–37.7 %), among 512 men — 41.0 % (95% CI 36.8–45.3 %). Conclusions. The prevalence of diffuse liver changes is high (12.5 % according to ultrasound and 37 % according to MRI) and increases with age among the adult population of working age. Given the variety of factors contributing to the progression of chronic liver diseases and the importance of identifying patients at high risk of developing liver cirrhosis, there is a need for widespread implementation of non-invasive diagnostic tests and technical upgrading of specialized healthcare facilities. The data obtained can serve as landmarks for calculating the needs for secondary care and improving clinical pathways for patients.

Optimising liver screening in patients with a Fontan circulation: a cost-effective approach to detection of Fontan associated liver disease which enhances patient care

Abstract Introduction Patients with Fontan circulation, require screening for liver cirrhosis and malignancy, to which they are susceptible with time. Surveillance biopsies reveal nearly all adult Fontan patients develop asymptomatic fibrosis, and a majority have abnormal liver function tests (LFTs). This presents significant financial healthcare burden and psychological stress with testing for patients. Objective We aim to present "real-world" liver screening data, from a leading Adult Congenital Heart Disease (ACHD) centre, to propose a cost-reducing testing regimen, which delivers effective screening, while taking account of the challenges of current guidance, patient compliance, and clinical practice. Methods We analysed liver screening data for Fontan patients at a leading ACHD centre, focusing on biochemical tests (bilirubin, ALT, GGT) and imaging. We evaluated the 10-year financial impact of current practices, versus a hypothetical model based on age and risk factors, alongside biannual and annual screening strategies. Tariffs for biochemical test were provided by the local pathology service and we used NHS HRG tariffs for imaging and phlebotomy. Results We included data from 114 patients with a Fontan circulation (median age 32 range 19-56, 42% females). Eighteen patients developed liver cirrhosis diagnosed on imaging (median age 32, range 22-48). None developed hepatocellular carcinoma. A lack of clear and agreed local screening guidelines (over years) resulted in vastly different investigations for FALD, with inconsistent time intervals for testing. Bilirubin was elevated in 59% (55% in age 18-29), ALT was elevated in 41% (31% in age 18-29), GGT was elevated in 83% (80% in age 18-29). We found 3 cases of cirrhosis in the age group 18-29, all with hypoplastic left heart; 4 cases of cirrhosis in age group 30-34 - all had significant comorbidities; 33% had normal bilirubin, LFT and GGT, potentially not requiring further screening until the age of 35. Eleven patients (22%) age 35+ had confirmed cirrhosis (Figure 1). Performing full FALD screening with biochemistry and liver ultrasound every 12-24 months would increase the cost of screening three- to six-fold. We propose rationalising liver screening by age and underlying risk (Figure 2) to minimise the economic burden and equally the psychological impact of frequent testing on patients. Conclusions Our analysis underscores the necessity for an optimised liver screening protocol in Fontan patients, balancing diagnostic accuracy with cost-efficiency. By integrating this data, we have identified a pathway to streamline screening, tailoring it to individual risk profiles and age groups, thereby reducing unnecessary tests, lowering costs and reducing the impact of testing on patients. This approach not only fosters better patient care, but also provides a framework for developing clearer, cost-effective screening guidelines, to monitor liver health, in these complex CHD patients.

Serum Branched-Chain Amino Acids and Long-Term Complications of Liver Cirrhosis: Evidence from a Population-Based Prospective Study.

The role of serum branched-chain amino acids (BCAAs) in long-term liver cirrhosis complication events remains unclear. We aimed to evaluate the associations between serum BCAAs and the risk of liver-related events. We included a total of 64,005 participants without liver cirrhosis complication events at baseline from the UK Biobank. Cox proportional hazards regression models were utilized to estimate multivariable hazard ratios (HRs) and 95% CIs for the incidence of liver cirrhosis complication events, adjusting for potential confounders, including sociodemographic and lifestyle factors. Relationships between serum BCAAs and liver cirrhosis complications were examined using nonparametrically restricted cubic spline regression. During a median follow-up of 12.7 years, 583 participants developed liver cirrhosis complication events. The multivariable Cox regression model suggested that total BCAAs (HR = 0.88, 95% CI 0.82-0.95), serum leucine (HR = 0.88, 95% CI 0.81-0.95), serum isoleucine (HR = 0.88, 95% CI 0.82-0.96), and serum valine (HR = 0.87, 95% CI 0.82-0.96) were all independent protective factors for liver cirrhosis complications after adjustment for sociodemographic and lifestyle factors. Cox models with restricted cubic splines showed U-shaped associations between serum valine and liver cirrhosis complication incidence. Serum total BCAA and isoleucine concentrations might reduce the risk of liver cirrhosis complications by raising the risk of (type 2 diabetes mellitus) T2DM. Lower serum BCAA levels exacerbate the long-term risk of liver cirrhosis complications. Future studies should confirm these findings and identify the biological pathways of these associations.

Do iron homeostasis biomarkers mediate the associations of liability to type 2 diabetes and glycemic traits in liver steatosis and cirrhosis: a two-step Mendelian randomization study

BackgroundPrevious studies, including Mendelian randomization (MR), have demonstrated type 2 diabetes (T2D) and glycemic traits are associated with increased risk of metabolic dysfunction-associated steatotic liver disease (MASLD). However, few studies have explored the underlying pathway, such as the role of iron homeostasis.MethodsWe used a two-step MR approach to investigate the associations of genetic liability to T2D, glycemic traits, iron biomarkers, and liver diseases. We analyzed summary statistics from various genome-wide association studies of T2D (n = 933,970), glycemic traits (n ≤ 209,605), iron biomarkers (n ≤ 246,139), MASLD (n ≤ 972,707), and related biomarkers (alanine aminotransferase (ALT) and proton density fat fraction (PDFF)). Our primary analysis was based on inverse-variance weighting, followed by several sensitivity analyses. We also conducted mediation analyses and explored the role of liver iron in post hoc analysis.ResultsGenetic liability to T2D and elevated fasting insulin (FI) likely increased risk of liver steatosis (ORliability to T2D: 1.14 per doubling in the prevalence, 95% CI: 1.10, 1.19; ORFI: 3.31 per log pmol/l, 95% CI: 1.92, 5.72) and related biomarkers. Liability to T2D also likely increased the risk of developing liver cirrhosis. Genetically elevated ferritin, serum iron, and liver iron were associated with higher risk of liver steatosis (ORferritin: 1.25 per SD, 95% CI 1.07, 1.46; ORliver iron: 1.15 per SD, 95% CI: 1.05, 1.26) and liver cirrhosis (ORserum iron: 1.31, 95% CI: 1.06, 1.63; ORliver iron: 1.34, 95% CI: 1.07, 1.68). Ferritin partially mediated the association between FI and liver steatosis (proportion mediated: 7%, 95% CI: 2–12%).ConclusionsOur study provides credible evidence on the causal role of T2D and elevated insulin in liver steatosis and cirrhosis risk and indicates ferritin may play a mediating role in this association.

Prediction of Liver Cirrhosis Using Classification Algorithms

The liver is known as the largest internal organ of the body and is well known for its unique property of regeneration. One of the most common diseases of the liver is liver cirrhosis. Liver cirrhosis is one of the most widespread chronic diseases. It is characterized by the gradual replacement of the liver tissue with the scarring tissue. Liver cirrhosis, being asymptomatic, makes it difficult to identify the disease and diagnose it. Due to this factor, there is no cure for liver cirrhosis, but rather to prevent the spread of cirrhosis and reverse its effects. The main objective of this case study is to employ machine learning techniques to predict the probability of being affected by this disease. Various machine learning algorithms are employed for classifying whether a patient will develop liver cirrhosis or not [5-7]. By using various classification algorithms, the highest accuracy was achieved through Logistic Regression, XG Boost, and KNN. The accuracy was 81% for all three cases. Logistic regression, with an execution time of 0.094 seconds, outperformed the other two models. This shows that logistic regression provides a significantly more accurate prediction of liver cirrhosis disease.

Plasma Adiponectin Levels in Relation to Chronic Hepatitis B Infection Progression to Liver Cancer Milestones: A Prospective Study

<b><i>Introduction:</i></b> Our previous nested-case-control study demonstrated elevated adiponectin increased liver cirrhosis and HCC risk in HBV carriers. We extended the analysis to the whole REVEAL-HBV cohort to prospectively evaluate whether adiponectin directly affected end-stage liver diseases, or through affecting HBV progression. <b><i>Methods:</i></b> Baseline plasma adiponectin was determined to investigate the association between adiponectin and subsequent HBeAg, HBsAg, and HBV DNA seroclearance, and the development of cirrhosis, HCC and liver-related death. Whether HBV characteristics modify the adiponectin-milestones associations was also examined. <b><i>Results:</i></b> Among 3,931 HBsAg(+)/anti-HCV(−) REVEAL-HBV participants, 3,684 had sufficient biosamples left for adiponectin assay. Elevated adiponectin was associated with a higher chance of HBeAg-seropositive, high HBV viral load (≥2 × 10<sup>5</sup> IU/mL) and high HBsAg titers (≥1,000 IU/mL) in a dose-response manner (OR = 2.25, 95% CI: 1.55–3.28; OR = 2.11, 95% CI: 1.47–3.04; and OR = 1.92, 95% CI: 1.47–2.52 for Q5 vs. Q1, respectively). Those with the highest quintile had a lower chance of achieving HBeAg (HR = 0.48, 95% CI: 0.27–0.85), HBsAg (HR = 0.69, 95% CI: 0.49–0.97), and HBV DNA seroclearance (HR = 0.63, 95% CI: 0.43–0.90) and a higher chance of developing liver cirrhosis (HR = 2.88, 95% CI: 1.98–4.20, HCC (HR = 2.38, 95% CI: 1.52–3.73), and died from liver-related causes (HR = 2.32, 95% CI: 1.51–3.54). HBV genotype significantly modified the adiponectin-HCC (P<sub>interaction</sub> = 0.005) and adiponectin-liver death associations (P<sub>interaction</sub> = 0.0157), with higher risk among genotype C. <b><i>Conclusion:</i></b> Elevated adiponectin is consistently associated with all important chronic HBV infection milestones toward progression to liver cancer. The exact mechanism of how adiponectin mediates HBV infection toward carcinogenesis remains unclear and warrants further investigation. Disentangling this may help us in finding new HBV treatment target, biomarker in HBV surveillance to identify high-risk patients, or even cancer prevention.

Interaction between HOTTIP, H19, and HOTAIR long noncoding RNAs and miRNA-152 in cases of HCC caused by HCV infection

BackgroundLiver cancer (hepatocellular carcinoma “HCC”) remains a significant health issue without prompt detection and appropriate prevention. By interacting with each other, long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) can form gene regulatory networks. Specifically, we aim to determine whether the lncRNAs (HOTTIP, H19, and HOTAIR) and miRNA-152 interact in a significant manner in the progression of Hepatitis C virus (HCV) patients to HCC. This is followed by the question of whether these biomarkers can be used to diagnose and prognose noninvasively. We used online computational techniques to predict which miRNA group is likely to affect the lncRNAs being examined. This study involved 133 participants. 103 patients with HCV were included in the study, which was divided into two groups: Group I, with 65 cases of chronic liver disease without HCC, and Group II, with 38 cases of chronic liver disease with HCC. In addition, 30 healthy volunteers served as controls. In this study, a qRT-PCR was used to test gene expression.ResultsA consistent reverse correlation has been observed between lncRNAs and miRNA-152 as the disease progresses.ConclusionAccording to our findings, the studied biomarkers may be useful as noninvasive biomarkers for prognosis in patients with HCV Genotype 4 who develop liver cirrhosis and HCC. Many miRNAs, including miRNA-19a and miRNA-106a, may interact with lncRNAs that have been investigated in addition to miRNA-152.

Comparison of the clinical effects of dual-modality endoscopy and traditional laparotomy for the treatment of intra- and extrahepatic bile duct stones.

Bile duct stones (BDSs) may cause patients to develop liver cirrhosis or even liver cancer. Currently, the success rate of surgical treatment for intrahepatic and extrahepatic BDSs is not satisfactory, and there is a risk of postoperative complications. To compare the clinical effects of dual-modality endoscopy (duodenoscopy and laparoscopy) with those of traditional laparotomy in the treatment of intra- and extrahepatic BDSs. Ninety-five patients with intra- and extrahepatic BDSs who sought medical services at Wuhan No.1 Hospital between August 2019 and May 2023 were selected; 45 patients in the control group were treated by traditional laparotomy, and 50 patients in the research group were treated by dual-modality endoscopy. The following factors were collected for analysis: curative effects, safety (incision infection, biliary fistula, lung infection, hemobilia), surgical factors [surgery time, intraoperative blood loss (IBL) volume, gastrointestinal function recovery time, and length of hospital stay], serum inflammatory markers [tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8], and oxidative stress [glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), malondialdehyde (MDA), and advanced protein oxidation products (AOPPs)]. The analysis revealed markedly better efficacy (an obviously higher total effective rate) in the research group than in the control group. In addition, an evidently lower postoperative complication rate, shorter surgical duration, gastrointestinal function recovery time and hospital stay, and lower IBL volume were observed in the research group. Furthermore, the posttreatment serum inflammatory marker (TNF-α, IL-6, and IL-8) levels were significantly lower in the research group than in the control group. Compared with those in the control group, the posttreatment GSH-Px, SOD, MDA and AOPPs in the research group were equivalent to the pretreatment levels; for example, the GSH-Px and SOD levels were significantly higher, while the MDA and AOPP levels were lower. Dual-modality endoscopy therapy (duodenoscopy and laparoscopy) is more effective than traditional laparotomy in the treatment of intra- and extrahepatic BDSs and has a lower risk of postoperative complications; significantly shortened surgical time; shorter gastrointestinal function recovery time; shorter hospital stay; and lower intraoperative bleeding volume, while having a significant inhibitory effect on excessive serum inflammation and causing little postoperative oxidative stress.

A280 HEPATOBILIARY DISEASE IN INDIVIDUALS LIVING WITH FRAGILE X SYNDROME: A CASE SERIES

Abstract Background Fragile X syndrome is a genetic disorder known to cause intellectual disability through decreased or absent FMR protein (FMRP). Basic science studies have identified potential associations with hepatobiliary inflammation. Clinical reports of liver disease in Fragile X syndrome are however infrequent. Aims We describe 3 individuals living with Fragile X syndrome and chronic liver disease. Methods A case series and literature review were performed. Results The 1st person is a woman with concurrent Fragile X and autosomal recessive polycystic kidney disease, initially seen by Hepatology at 18 y.o. with evidence of hepatic fibrosis on abdominal ultrasound with normal liver enzymes (Table 1). She subsequently developed liver cirrhosis and portal hypertension, as well as biliary duct dilatation seen on MRI. Her overall presentation was thought to be in keeping with Caroli syndrome and congenital hepatic fibrosis, and she is currently pending genetic screening for hepatorenal ciliopathy. The 2nd person is a woman with Fragile X syndrome and ulcerative colitis, who initially presented to Hepatology at 24 y.o. with mixed liver enzyme abnormalities. Lab tests over time revealed immunology suggestive of autoimmune hepatitis (AIH) (Table 1). Subsequent investigations demonstrated primary sclerosing cholangitis (PSC) with cirrhosis. Her disease is currently managed as AIH/PSC overlap syndrome with ursodeoxycholic acid (UDCA), tacrolimus, mycophenolate, and budesonide. The 3rd person is a man with Fragile X syndrome who initially presented to Hepatology at 17 y.o. with acute hepatitis with AIH immunology (Table 1). Liver biopsy at the time demonstrated findings suggestive of early PSC as well as possible AIH. He continued to have progressive cirrhosis as well as overt PSC on subsequent abdominal imaging and is currently managed as AIH/PSC overlap syndrome with UDCA, azathioprine, and budesonide. A review of literature revealed that asides from known intellectual, behavioral, and physical effects of Fragile X syndrome, there are minimal reports of other associated medical complications including liver problems or autoimmune conditions including IBD. There are however reports of autoimmunity in those with altered FMR1 (Fragile X Mental Retardation 1) gene mutations. Conclusions These 3 cases of liver disease in Fragile X highlight young age of presentation for chronic liver disease with both biliary and immune-mediated characteristics, along with progression to cirrhosis. Additional review for liver manifestations in people living with Fragile X would help understand if this association is incidental or causal. Investigations of individuals with Fragile X syndrome and liver disease Funding Agencies None

COVID-19, Possible Hepatic Pathways and Alcohol Abuse-What Do We Know up to 2023?

The pandemic period due to coronavirus disease 2019 (COVID-19) revolutionized all possible areas of global health. Significant consequences were also related to diverse extrapulmonary manifestations of this pathology. The liver was found to be a relatively common organ, beyond the respiratory tract, affected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Multiple studies revealed the essential role of chronic liver disease (CLD) in the general outcome of coronavirus infection. Present concerns in this field are related to the direct hepatic consequences caused by COVID-19 and pre-existing liver disorders as risk factors for the severe course of the infection. Which mechanism has a key role in this phenomenon-previously existing hepatic disorder or acute liver failure due to SARS-CoV-2-is still not fully clarified. Alcoholic liver disease (ALD) constitutes another not fully elucidated context of coronavirus infection. Should the toxic effects of ethanol or already developed liver cirrhosis and its consequences be perceived as a causative or triggering factor of hepatic impairment in COVID-19 patients? In the face of these discrepancies, we decided to summarize the role of the liver in the whole picture of coronavirus infection, paying special attention to ALD and focusing on the pathological pathways related to COVID-19, ethanol toxicity and liver cirrhosis.

CD81 suppresses NF-κB signaling and is downregulated in hepatitis C virus expressing cells.

The tetraspanin CD81 is one of the main entry receptors for Hepatitis C virus, which is a major causative agent to develop liver cirrhosis and hepatocellular carcinoma (HCC). Here, we identify CD81 as one of few surface proteins that are downregulated in HCV expressing hepatoma cells, discovering a functional role of CD81 beyond mediating HCV entry. CD81 was downregulated at the mRNA level in hepatoma cells that replicate HCV. Kinetics of HCV expression were increased in CD81-knockout cells and accompanied by enhanced cellular growth. Furthermore, loss of CD81 compensated for inhibition of pro-survival TBK1-signaling in HCV expressing cells. Analysis of functional phenotypes that could be associated with pro-survival signaling revealed that CD81 is a negative regulator of NF-κB. Interaction of the NF-κB subunits p50 and p65 was increased in cells lacking CD81. Similarly, we witnessed an overall increase in the total levels of phosphorylated and cellular p65 upon CD81-knockout in hepatoma cells. Finally, translocation of p65 in CD81-negative hepatoma cells was markedly induced upon stimulation with TNFα or PMA. Altogether, CD81 emerges as a regulator of pro-survival NF-κB signaling. Considering the important and established role of NF-κB for HCV replication and tumorigenesis, the downregulation of CD81 by HCV and the associated increase in NF-κB signaling might be relevant for viral persistence and chronic infection.

Dietary rice bran attenuates hepatic stellate cell activation and liver fibrosis in mice through enhancing antioxidant ability

Various endogenous and exogenous stimuli can result in an inflammatory response and collagen deposition in the liver, which affect liver function and increase the risk of developing liver cirrhosis and cancer. Rice bran, the main by-product of rice milling, contains various nutrients which possess hepatoprotective activities. In this study, we investigated the effects of rice bran on carbon tetrachloride (CCl4)-induced liver fibrosis in mice. Mice were fed a rice-bran-containing diet (10% rice bran w/w) or a standard diet with or without an injection of 20% CCl4 to induce liver fibrosis. Our results showed that feeding a rice-bran-containing diet could alleviate CCl4-induced liver damage, collagen deposition, and expressions of fibrosis-related genes, including α-smooth muscle actin (α-SMA), collagen 1a2 (COL1A2), and transforming growth factor-β (TGF-β) in liver tissues. Moreover, consumption of rice bran enhanced phase II detoxification and antioxidant gene expressions, including Gsta3, Gstp1, Catalase, SOD1, SOD2, and SOD3. Treatment with γ-oryzanol, the major bioactive compound in rice bran, decreased the sensitivity of hepatic stellate cells (HSCs) to TGF-β1-induced α-SMA, COL1A2, and phosphorylated smad2 expressions. In conclusion, a rice-bran-containing diet may have beneficial effects on liver fibrogenesis through increased antioxidant and detoxification activities. γ-Oryzanol, the major bioactive compound of rice bran, can inhibit activation of HSCs.

New Treatment Options in Chronic Hepatitis B: How Close Are We to Cure?

Hepatitis B virus (HBV) infection is the leading cause of chronic liver disease worldwide. HBV-infected patients are at a lifetime risk of developing liver cirrhosis and hepatocellular carcinoma (HCC). Today, pegylated interferon (Peg-IFN) and nucleos(t)ide analogs (NAs) are used in the treatment of patients with chronic hepatitis B (CHB). Both treatment options have limitations. Despite effective viral suppression, NAs have little effect on covalently closed circular DNA (cccDNA), the stable episomal form of the HBV genome in hepatocytes. Therefore, the cure rate with NAs is low, and long-term treatment is required. Although the cure rate is better with Peg-IFN, it is difficult to tolerate due to drug side effects. Therefore, new treatment options are needed in the treatment of HBV infection. We can group new treatments under two headings: those that interfere with the viral life cycle and spread and those that modulate the immune response. Clinical studies show that combinations of treatments that directly target the viral life cycle and treatments that regulate the host immune system will be among the important treatment strategies in the future. As new direct-acting antiviral (DAA) and immunomodulatory therapies continue to emerge and evolve, functional cures in HBV treatment may be an achievable goal.

Prevalence and Genotype Distribution of Hepatitis C Virus Infection at Zonal Hospital in Northern India

Abstract Background: Hepatitis C virus (HCV) infection is a major public health concern. Persons living with HCV infection are at risk of developing liver cirrhosis and progressing to end-stage liver disease and liver cancer (hepatocellular carcinoma). The present study was undertaken to assess the prevalence of HCV infection in patients admitted as well as outpatient department services of a Zonal Hospital. Methods: The present study was cross-sectional, observational study, conducted in patients >18 years of age, clinically suspected acute infectious hepatitis or admitted to the intensive care unit, and willing to participate in the study. Results: In the present study, 472 patients were studied for hepatitis C infection. Majority of cases were from 51 to 60 years age group (34.5%), followed by 61–70 years age group (26.7%). Female cases were (51.3%) slightly more than male (48.7%). Rapid method and enzyme-linked immunosorbent assay (ELISA) methods detected HCV prevalence as 5.7% and 12.5%, respectively. After HCV genotype testing, the prevalence was 12.1%. Majority had 3A genotype (69.49%), followed by 1A genotype (16.95%), 1B genotype (8.47%), 3B genotype (3.39%), and 4 genotypes (1.69%). ELISA testing was significantly correlated with HCV genotype testing (P = 0.017) while the rapid method was not correlated with HCV genotype testing (P = 0.937). Conclusion: There is a high prevalence of HCV among the suspected, genotype 3 being the most common.

Copy Number Variation in the GSTM1 and GSTT1 Genes and the Risk of Liver Cirrhosis in Eastern Ethiopia.

Polymorphisms in glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) can cause an entire gene deletion. The current methodology can accurately identify GSTM1 and GSTT1 copy number variants (CNVs), which may shed light on the true contribution of each gene copy to the cellular detoxification process and disease risk. Because liver cirrhosis is becoming a critical worldwide health issue, this study determined the CNVs of GSTM1 and GSTT1 and their relationship to the risk of liver cirrhosis. In this study, we compared 106 patients with liver cirrhosis to 104 healthycontrols. Real-time PCR was used to identify the CNVs of GSTM1 and GSTT1. Logistic and linear regression models were used to estimate the relationship between liver cirrhosis and clinical chemistry variables with the CNVs, respectively. In 3.3% of the study participants, >2 copies of the GSTM1 or GSTT1 genes were detected. GSTT1 carriers had a significantly lower risk of liver cirrhosis (p<0.05) compared with individuals who had homozygous deletion (adjusted odds ratio (AOR) = 0.47; 95% CI: 0.25, 0.86). This risk reduction was significant (p<0.05) in patients with a single copy of the GSTT1 gene (AOR = 0.48; 95% CI: 0.25, 0.91). Those with ≥2 copies of combined GSTM1 and GSTT1 also had a significantly (p<0.05) lower risk of developing liver cirrhosis compared with double null genotypes (AOR = 0.38; 95% CI: 0.16, 0.91, p trend <0.001). Moreover, ≥2 copies of combined GSTM1 and GSTT1 genes were associated with a substantial decrease in alanine amino transferase (ALT) and aspartate aminotransferase (AST) levels, respectively. A single copy number of GSTT1, and ≥2 copies of combined GSTM1 and GSTT1 genes were associated with a reduced risk of liver cirrhosis in Ethiopians. These findings underscore the importance of gene-environment interactions in the multifactorial development of liver cirrhosis.

Sex-differences in the association of interleukin-10 and interleukin-12 variants with the progression of hepatitisB virus infection in Caucasians.

Interleukin (IL)-10 and IL-12 contribute to immune responses against hepatitisB virus (HBV) infection. Polymorphisms in the IL-10 and IL-12A genes might affect the clinical outcome of HBV infection. We evaluated the association of IL-10 rs1800896 and rs3024490, and IL-12A rs568408 and rs2243115 with the progression of HBV infection and development of severe liver disease stages in a white European population. A total of 636 white European patients with chronic HBV infection, 239 individuals with spontaneous HBV surface antigen seroclearance, and 254 healthy controls were enrolled. The chronic HBV infection group included patients with hepatitisB envelope antigen (HBeAg) negative chronic hepatitisB (n=255), with HBeAg positive chronic hepatitisB (n=99) and with HBeAg negative HBV infection (n=228). A total of 104 chronically infected patients were diagnosed with liver cirrhosis. Serum levels of cytokines were measured in patients with HBV infection (n=195) and in healthy controls (n=160). In adjusted multivariate analysis, the IL-10 rs1800896 AG/GG genotypes were significantly associated with an increased probability of HBV surface antigen seroclearance (OR=1.75, 95% CI 1.04-2.94, p=0.034), with an increased likelihood of HBeAg negative chronic infection (OR=1.93, 95% CI 1.05-3.54, p=0.034) and with increased serum cytokines levels in female patients. In contrast, the IL-12A rs568408 AG/AA genotypes were independently associated with an increased risk to develop liver cirrhosis, with an OR of 1.90 (95% CI 1.07-3.39, p=0.029) in male patients. The current study shows a sex-related association of the IL-10 single-nucleotide polymorphism rs1800896 and IL-12A single-nucleotide polymorphism rs568408 with different stages of HBV infection and with HBV-related liver cirrhosis in white European patients.

Exposure to Nickel-Cadmium Contamination of Drinking Water Culminates in Liver Cirrhosis, Renal Azotemia, and Metabolic Stress in Rats.

Drinking water polluted by heavy metals has the potential to expose delicate biological systems to a range of health issues. This study embraced the health risks that may arise from subchronic exposure of thirty-four male Wistar rats to nickel (Ni)-cadmium (Cd)-contaminated water. It was done by using the Box-Behnken design (BBD) with three treatment factors (Ni and Cd doses at 50-150mg/L and exposure at 14-21-28days) at a single alpha level, resulting in seventeen experimental combinations. Responses such as serum creatinine (CREA) level, blood urea nitrogen (BUN) level, BUN/CREA ratio (BCR), aspartate and alanine aminotransferases (AST and ALT) activities, and the De Ritis ratio (DRR), as well as malondialdehyde (MDA) level, catalase (CAT), and superoxide dismutase (SOD) activities, were evaluated. The results revealed that these pollutants jointly caused hepatocellular damage by raising AST and ALT activities and renal dysfunction by increasing CREA and BUN levels in Wistar rats' sera (p < 0.05). These outcomes were further supported by BCR and DRR values beyond 1. In rats' hepatocytes and renal tissues, synergistic interactions of these metals resulted in higher MDA levels and significant impairments of CAT and SOD activities (p < 0.05). In order to accurately forecast the effects on the responses, the study generated seven acceptable regression models (p < 0.05) with r-squared values of > 80% at no discernible lack of fit (p > 0.05). The findings hereby demonstrated that Wistar rats exposed to these pollutants at varied doses had increased risks of developing liver cirrhosis and azotemia marked by metabolic stress.

Association of abnormal glucose tolerance with liver-related disease and cardiovascular diseases in patients with chronic hepatitis C.

Hepatitis C complicated by diabetes mellitus (DM) is considered a risk factor for the progression of fibrosis and development of hepatocellular carcinoma (HCC) and cardiovascular diseases. However, several studies may have lacked appropriate diagnosis of glucose intolerance. We aimed to examine the risk associated with abnormal glucose intolerance in the development of liver-related diseases, including HCC and complications of liver cirrhosis, such as ascites, esophageal and gastric varices, and hepatic encephalopathy, and cardiovascular diseases in patients with hepatitis C accurately diagnosed with impaired glucose tolerance. This longitudinal retrospective study included 365 patients with chronic hepatitis C admitted to Ehime University Hospital for anti-hepatitis C therapy between September 1991 and January 2015. Patients were classified into normal glucose tolerance (NGT), prediabetes, and DM groups based on 75-g oral glucose tolerance test results. Both univariate and multivariate (adjusted for potential confounders) analyses revealed a significantly higher risk of developing HCC and cardiovascular events in the DM group than in the NGT group. However, in multivariate analysis, liver-related events, particularly liver cirrhosis complications, revealed no significant association. In addition, the prediabetes group had no significant risk of any outcome. Patients with hepatitis C complicated by DM, compared with patients with hepatitis C with NGT or complicated with prediabetes, have a higher risk ofHCC and cardiovascular disease events, but not liver-related events, particularlyin not developing liver cirrhosis complications. Therefore, appropriate follow-up is required for patients with hepatitis C based on their glucose tolerance status.

Pathomorphological changes in the organs of laboratory animals with experimental liver cirrhosis

Objective. Develop an experimental model of liver cirrhosis and describe pathomorphological changes in organs and tissues of laboratory animals.Materials and methods. Liver cirrhosis was simulated on 11 sexually mature Wistar male white rats. The control group consisted of 12 healthy laboratory animals. Acute toxic liver injury resulting in cirrhosis was induced by intraperitoneal injection of 50% tetrachloromethane (CCl4) solution on olive oil on the first day of the experiment in the dosage of 0.1 ml CCl4 + 0.4 ml olive oil per 100 g of the animal body weight, on the second day of the experiment 0.3 ml CCl4 + 0.2 ml olive oil per 100 g of the animal body weight. To synergize and potentiate the hepatotoxic effect of CCl4, animals had 10% ethanol solution freely available daily. The duration of the experiment was 65 days. Clinical and laboratory parameters were evaluated, histological evaluation of the preparations was performed. The obtained data were compared with the control group of animals.Results. Reproducibility of the model was 82% (9 animals). The indicator of lymphocyte blabbing index showed the development of liver cirrhosis in animals of the experimental group. Comprehensive morphological confirmation of the developed liver cirrhosis was obtained.Conclusion. The proposed methodology of liver cirrhosis formation correlates with pathomorphological changes in lymphocyte cell wall, changes in liver tissue and internal organs in human liver cirrhosis.