Risk Factor For Liver Cirrhosis Research Articles

Prevalence of liver cirrhosis in individuals with hepatitis B virus infection in sub-Saharan Africa: Systematic review and meta-analysis.

Background & AimsChronic hepatitis B virus (HBV) infection accounts for 30%‐50% of cirrhosis related deaths in sub‐Saharan Africa (SSA). Since HBV‐related cirrhosis is an indication for immediate antiviral therapy and cancer surveillance, we aimed to estimate the prevalence of cirrhosis among treatment‐naïve patients with chronic HBV infection in SSA.MethodsWe performed a systematic review of published articles which evaluated liver fibrosis stage among treatment‐naïve HBV‐infected individuals who presented to care in SSA. Our primary outcome was the prevalence of cirrhosis in HBsAg‐positive persons, which was estimated using random‐effects meta‐analysis. Risk factors for cirrhosis were explored using subgroup‐analyses and multivariable meta‐regression.ResultsOf 2129 articles identified, 17 met our eligibility criteria. The studies described 22 cohorts from 13 countries, including 13 cohorts (3204 patients) with chronic HBV mono‐infection and nine cohorts (688 patients) with HIV/HBV‐coinfection. Liver fibrosis was assessed using transient elastography (10 cohorts), APRI score (11 cohorts), and Fibrotest (one cohort). The pooled prevalence of cirrhosis was 4.1% (95% confidence interval [CI] 2.6‐6.4) among studies from primary care facilities or general population, compared to 12.7% (95% CI 8.6‐18.3) in studies performed in referral or tertiary care facilities (adjusted odds ratio 0.29, 95% CI 0.15‐0.56). We found no association between cirrhosis and age, gender, fibrosis test used or HIV‐coinfection.ConclusionsDepending on the setting, between 4% and 13% of HBV‐infected individuals in SSA have cirrhosis and need immediate antiviral therapy. These estimates should be considered when planning HBV treatment strategies and resource allocation.

Molecular and Functional Roles of MicroRNAs in the Progression of Hepatocellular Carcinoma-A Review.

Liver cancer is the fourth leading cause of cancer deaths globally, of which hepatocellular carcinoma (HCC) is the major subtype. Viral hepatitis B and C infections, alcohol abuse, and metabolic disorders are multiple risk factors for liver cirrhosis and HCC development. Although great therapeutic advances have been made in recent decades, the prognosis for HCC patients remains poor due to late diagnosis, chemotherapy failure, and frequent recurrence. MicroRNAs (miRNAs) are endogenous, non-coding RNAs that regulate various molecular biological phenomena by suppressing the translation of target messenger RNAs (mRNAs). miRNAs, which often become dysregulated in malignancy, control cell proliferation, migration, invasion, and development in HCC by promoting or suppressing tumors. Exploring the detailed mechanisms underlying miRNA-mediated HCC development and progression can likely improve the outcomes of patients with HCC. This review summarizes the molecular and functional roles of miRNAs in the pathogenesis of HCC. Further, it elucidates the utility of miRNAs as novel biomarkers and therapeutic targets.

S2745 Thinking Outside the Box: Is This Really NASH?

INTRODUCTION: Nonalcoholic steatohepatitis (NASH) is a diagnosis of exclusion and an alternative diagnosis should always be sought. We present a patient with features of portal hypertension and possible sepsis, concerning for decompensated NASH cirrhosis. He was eventually diagnosed with a hemophagocytic syndrome-associated variant of intravascular large B-cell lymphoma on autopsy. CASE DESCRIPTION/METHODS: A 64-year-old Caucasian male with metabolic syndrome presented with a 2-month history of fatigue, fevers, and 20-pound weight loss. Initial work-up was notable for an elevated AST (65 IU/L) and high total bilirubin (2 mg/mL; direct 1.3 mg/mL). Albumin was 3.2 g/dL, INR was 1.0 and platelets were 48,000 cells/mL. CT imaging showed mild hepatosplenomegaly with no ascites. He had no known history of liver disease or alcohol use. He was referred to the liver clinic for possible chronic liver disease and portal hypertension, thought to be from NASH. At the time of presentation, he was febrile (101.8 °F), tachycardic (105 bpm), and hypotensive. Besides hepatosplenomegaly, there were no other stigmata of chronic liver disease on exam. Admission labs were unchanged except an increase in total bilirubin (4 mg/mL) and a high ferritin (2400 ng/ml). Work-up for infectious etiologies, autoimmune liver serologies and drug toxin screen were unrevealing. He met 5 out of 8 criteria to diagnose hemophagocytic lymphohistiocytosis (HLH) including fever, splenomegaly, cytopenia, increased ferritin, and absent NK cell function. A PET scan showed uptake in the bone marrow, liver, spleen and lymph nodes. The patient rapidly declined clinically and died from respiratory failure. Autopsy showed diffuse involvement of the liver, spleen, bone marrow, lymph nodes and several other organs by intravascular large B-cell lymphoma (IVBCL). DISCUSSION: Our case emphasizes the importance of considering a broad differential in patients with thrombocytopenia and hepatosplenomegaly, even if typical risk factors for liver cirrhosis are present. Hematological malignancies should be strongly considered in the differential especially if patients present with B symptoms. Hemophagocytic syndrome-associated variant of IVBCL, the so-called ‘Asian variant’, is a rare and aggressive form of diffuse large B cell lymphoma. A prompt diagnosis is crucial, given its life-threatening potential and possibility of recovery with institution of therapy early in the course of the disease.Figure 1.: The cut sections of the liver looked relatively normal and did not show any gross evidence of cirrhosis.Figure 2.: Histology of the liver, which shows intravascular infiltration of tumor cells.

Decrease in Chitinase 3-Like Protein 1 Levels Reflects Improvement in Liver Fibrosis after HCV Eradication.

Aim The success of direct-acting antivirals (DAAs) against hepatitis C virus is a major breakthrough in hepatology. Previous studies have shown that chitinase 3-like protein 1 (CHI3L1) was a marker for staging of liver fibrosis caused by HCV. In this investigation, we used CHI3L1 as a surrogate marker to compare dynamic hepatic fibrosis variations following the elimination of HCV among cases receiving sofosbuvir (SOF)-based regimens and pegylated interferon/ribavirin (PR) treatments. Methods The study enrolled 105 patients, including 46 SOF-based regimens treated patients, 34 PR-experienced patients, and 25 untreated patients. Serum samples and clinical data were obtained at the baseline, the end of treatment, and at weeks 24 and 48 after treatments. Results First, we found that serum level of CHI3L1 correlated moderately but significantly with LSM (r = 0.615, P < 0.001) at the baseline, and diagnosed liver cirrhosis at baseline with high accuracy (AUC = 0.939) by ROC analysis. So we explored CHI3L1 as a sensitive biomarker to monitor the regression of liver fibrosis after HCV eradication. We found that the serum CHI3L1 level of CHC cases receiving SOF-based regimen treatments was markedly reduced immediately after treatment compared with that at the baseline (123.79 (118.55) vs. 118.20 (103.68), P = 0.001). For cases undergoing PR treatment, the serum CHI3L1 decreased significantly at week 24 posttreatment compared with that at the baseline (69.98 (51.44) vs 89.15 (110.59), P = 0.016). For the untreated cirrhotic patients, CHI3L1 levels increased at week 96 follow-up compared with that at the baseline (194.73 (172.46) vs. 89.50 (242.97), P = 0.048), reflecting continued worsening of liver fibrosis. Conclusion CHI3L1 is suggested to be the sensitive marker to monitor fibrosis variations in weeks during treatments and after achieving SVR. It has the potential to allow the identification of early treatment failure for a timely switch to alternative treatment and to allow monitoring progression of fibrosis as a risk factor for liver cirrhosis.

Aflatoxins as a risk factor for liver cirrhosis: a systematic review and meta-analysis

BackgroundLiver cirrhosis is characterized by fibrosis and nodule formation in the liver, due to a chronic injury, and subsequent alteration of the normal architecture of the liver. Even though there is a huge effort to elucidate the possible etiologic factors of liver cirrhosis, a significant number of cases are cryptogenic, especially in Sub Saharan Africa, where there is a high burden of aflatoxin exposure. Aflatoxins are known to cause hepatocellular carcinoma, which share similar etiologic factors with liver cirrhosis. This study aimed to assess the association between aflatoxin exposure and the risk of liver cirrhosis.MethodsRelevant studies were identified through systematic searches conducted in Ovid MEDLINE, PubMed and Google Scholar. Also, by searching the references of retrieved articles. The abstracts and full text were screened for eligibility and the risk of bias was assessed for each study using Joanna Briggs Institute (JBI) critical appraisal checklist for observational studies. The extracted data from included studies using Microsoft Excel were exported to Stata software version 15.0 for analyses. The overall pooled estimation of outcomes was calculated using a random-effects model of DerSimonian–Laird method at a 95% confidence level. The heterogeneity of studies was determined using I2 statistics. The presence of publication bias between studies was evaluated using the Begg’s and Egger’s tests and funnel plot. The protocol of this systematic review and meta-analysis was registered in the Prospero database with reference number ID: CRD42019148481.ResultsA total of 5 studies published between the years 2005 and 2018 that met the pre-defined inclusion and exclusion criteria were included. The meta-analysis showed that a significant increase in the risk of liver cirrhosis is associated with aflatoxin exposure (unadjusted pooled odds ratio (OR) = 3.35, 95% CI: 2.74–4.10, p = 0.000; I2 = 88.3%, p = 0.000; adjusted OR = 2.5, 95% CI: 1.84–3.39, p = 0.000; I2 = 0%, p = 0.429).ConclusionsThe present meta-analysis suggests that aflatoxin exposure is associated with a higher risk of liver cirrhosis.

Combined alcoholic and non-alcoholic steatohepatitis.

SummaryWhile metabolic syndrome and alcohol consumption are the two main causes of chronic liver disease, one of the two conditions is often predominant, with the other acting as a cofactor of morbimortality. It has been shown that obesity and alcohol act synergistically to increase the risk of fibrosis progression, hepatic carcinogenesis and mortality, while genetic polymorphisms can strongly influence disease progression. Based on common pathogenic pathways, there are several potential targets that could be used to treat both diseases; based on the prevalence and incidence of these diseases, new therapies and clinical trials are needed urgently.

Hepatocellular Carcinoma Mechanisms Associated with Chronic HCV Infection and the Impact of Direct-Acting Antiviral Treatment.

Hepatitis C virus (HCV) infection is the major risk factor for liver cirrhosis and hepatocellular carcinoma (HCC). The mechanisms of HCC initiation, growth, and metastasis appear to be highly complex due to the decade-long interactions between the virus, immune system, and overlapping bystander effects of host metabolic liver disease. The lack of a readily accessible animal model system for HCV is a significant obstacle to understand the mechanisms of viral carcinogenesis. Traditionally, the primary prevention strategy of HCC has been to eliminate infection by antiviral therapy. The success of virus elimination by antiviral treatment is determined by the SVR when the HCV is no longer detectable in serum. Interferon-alpha (IFN-α) and its analogs, pegylated IFN-α (PEG-IFN-α) alone with ribavirin (RBV), have been the primary antiviral treatment of HCV for many years with a low cure rate. The cloning and sequencing of HCV have allowed the development of cell culture models, which accelerated antiviral drug discovery. It resulted in the selection of highly effective direct-acting antiviral (DAA)-based combination therapy that now offers incredible success in curing HCV infection in more than 95% of all patients, including those with cirrhosis. However, several emerging recent publications claim that patients who have liver cirrhosis at the time of DAAs treatment face the risk of HCC occurrence and recurrence after viral cure. This remains a substantial challenge while addressing the long-term benefit of antiviral medicine. The host-related mechanisms that drive the risk of HCC in the absence of the virus are unknown. This review describes the multifaceted mechanisms that create a tumorigenic environment during chronic HCV infection. In addition to the potential oncogenic programming that drives HCC after viral clearance by DAAs, the current status of a biomarker development for early prediction of cirrhosis regression and HCC detection post viral treatment is discussed. Since DAAs treatment does not provide full protection against reinfection or viral transmission to other individuals, the recent studies for a vaccine development are also reviewed.

Relationship between hemodynamics with hepatic reserve function in cirrhotic patients with portal hypertension

Objective To investigate the relationship between hemodynamics with hepatic reserve function in cirrhosis patients complicated with portal hypertension (PHT), and to explore the significances of the two in evaluating the disease. Methods According to the Child score, 80 cirrhosis patients complicated with PHT from January 2016 to January 2018 in our hospital were divided into three grades: A, B and C, 35 healthy persons in the same period were selected as normal control group. The parameters of liver hemodynamics were detected by color Doppler ultrasound, and the items of liver reserve function were detected by automatic biochemical analyzer. The correlation between hemodynamic indexes and liver reserve function was analyzed by Pearson method, and the risk factors of liver cirrhosis with PHT were analyzed by logistic multiple regression. Results The diameter of portal inner vein (DPV), maximum speed of blood flow in the portal vein (PVX), mean speed of blood flow in the portal vein (PVM), quantity of blood flow in the main portal vein (QPV), albumin (ALB), cerealthirdtransaminase (ALT), aspartate transaminase (AST) and prothrombin time (PT) in the observation group were significantly higher than those in the control group (P<0.05), while the total bilirubin (TBIL) was significantly lower than that in the control group (P<0.05). The levels of DPV, PVX, PVM and QPV in patients with grade C were significantly higher than those in grade A and grade B (P<0.05); the levels of DPV, PVX, PVM and QPV in patients with grade B of liver function were significantly higher than those in grade A (P<0.05). The level of TBIL in patients with grade C liver function was significantly lower than that in grade A and grade B patients (P<0.05); ALB, ALT, AST and PT were significantly higher than those of grade A and grade B (P<0.05); the level of TBIL in patients with grade B of liver function was significantly lower than that of grade A (P<0.05), while the ALB, ALT, AST and PT were significantly higher than those in group A (P<0.05). DPV, PVM and QPV were significantly positively correlated with PT in cirrhosis patients with and PHT (P<0.05), PVM and QPV were significantly negatively correlated with TBIL (P<0.05). Regression analysis showed that hemodynamic indexes in DPV, PVX, PVM, QPV and liver reserve function indexes TBIL, ALB, ALT, AST, PT were risk factors for portal hypertension in cirrhosis. Conclusions Hemodynamics and hepatic reserve function indicators have certain regularity in different degrees of cirrhosis complicated with PHT patients, they are closely related and can be used as an important index in the evaluation and monitoring of cirrhosis with PHT. Key words: Liver cirrhosis; Portal hypertension; Hemodynamics; Hepatic reserve functional

Red complex periodontal pathogens are risk factors for liver cirrhosis.

Periodontal disease has been associated with liver disease; however, the identities of the periodontal disease-causing bacteria in patients with viral liver disease remain unknown. The aim of the present study was to determine the counts of the 3 periodontal pathogens that form the red complex in chronic periodontitis (Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola) and 3 other bacteria (Aggregatibacter actinomycetemcomitans, Prevotella intermedia and Fusobacterium necrophorum) in patients with liver disease. A total of 47 patients with liver disease were divided into two groups based on the counts of the red complex bacteria: group A (high counts of red complex bacteria) and group B (low counts of red complex bacteria). The counts of the 6 types of bacteria in saliva and the prevalence of P. gingivalis-specific fimA genotype were determined. In addition, salivary occult blood tests and serological assays were performed. Univariate and multivariate logistic regression analyses were used to analyze the risk factors between the two groups of patients. Hepatitis C virus-related liver disease was the most frequent (41/47; 87.2%) occurrence followed by liver cirrhosis (LC; 12/47; 25.5%) and oral lichen planus (32/47; 68.1%). The significant risk factors between the two groups were LC, albumin (Alb) level, ratios of each bacteria and prevalence of the fimA II genotype. The 3 factors identified in the multivariate analysis to be associated with the red complex bacteria count were low Alb level (<3.7 g/dl), LC and fimA II genotype, with adjusted odds ratios of 6.93, 4.72 and 4.08, respectively (P<0.05). These data indicated that patients with LC were at increased risk of presenting with the red complex bacteria leading to periodontal disease progression. Therefore, these patients may need to take additional care of their oral health compared with patients without LC, which may prove beneficial for the maintenance of their general health.

Association between temperature, sunlight hours and alcohol consumption.

BackgroundAlcohol is a major risk factor for liver cirrhosis. Recently, it was proposed that colder climate might causally lead to increased consumption of alcohol.MethodsWe performed an ecologic study, using monthly updated data on mean temperature, sunlight hours and alcohol consumption from ten regions in Sweden, using publicly available data. A generalised additive model, adjusted for region, was applied to examine the association between mean temperature and mean sunlight hours with mean alcohol consumption.ResultsWe found a non-linear inverse association between mean monthly temperature and mean alcohol consumption, suggesting that warmer temperature was associated with increased alcohol consumption and colder temperature with a decreased consumption. We found no association between mean sunlight hours and alcohol consumption. Consumption was highest during public holidays.ConclusionsWe found no association between a colder climate and increased alcohol consumption. Socio-economic factors are likely to explain the suggested association.

Alcohol Consumption and Risk of Liver Cirrhosis: A Systematic Review and Meta-Analysis.

To systematically summarize the risk relationship between different levels of alcohol consumption and incidence of liver cirrhosis. MEDLINE and Embase were searched up to March 6, 2019, to identify case-control and cohort studies with sex-specific results and more than 2 categories of drinking in relation to the incidence of liver cirrhosis. Study characteristics were extracted and random-effects meta-analyses and meta-regressions were conducted. A total of 7 cohort studies and 2 case-control studies met the inclusion criteria, providing data from 2,629,272 participants with 5,505 cases of liver cirrhosis. There was no increased risk for occasional drinkers. Consumption of one drink per day in comparison to long-term abstainers showed an increased risk for liver cirrhosis in women, but not in men. The risk for women was consistently higher compared to men. Drinking ≥5 drinks per day was associated with a substantially increased risk in both women (relative risk [RR] = 12.44, 95% confidence interval [CI]: 6.65-23.27 for 5-6 drinks, and RR = 24.58, 95% CI: 14.77-40.90 for ≥7 drinks) and men (RR = 3.80, 95% CI: 0.85-17.02, and RR = 6.93, 95% CI: 1.07-44.99, respectively). Heterogeneity across studies indicated an additional impact of other risk factors. Alcohol is a major risk factor for liver cirrhosis with risk increasing exponentially. Women may be at higher risk compared to men even with little alcohol consumption. More high-quality research is necessary to elucidate the role of other risk factors, such as genetic vulnerability, body weight, metabolic risk factors, and drinking patterns over the life course. High alcohol consumption should be avoided, and people drinking at high levels should receive interventions to reduce their intake.

Relative factors of liver cirrhosis complicated with liver palms and spider nevus

Objective To analyze the risk factors of liver cirrhosis complicated with liver palms and spider nevus and to summarize treatment measures. Methods Totally 160 patients with liver cirrhosis admitted in the Department of Gastroenterology of Xuanhan County People's Hospital from August 2016 to February 2019 were selected by convenient sampling and divided into observation (n=70) and control (n=90) group based on the presence of liver palms and spider nevus. Patients' demographic and disease information was collected and used to analyze the relative factors of liver palms and spider nevus. Results There were statistically significant differences in sex and etiology between the two groups (P 0.05) . There were statistically significant differences in the estradiol level, morbidity of stomachache, fever, upper gastrointestinal hemorrhage and esophageal variceal bleeding between the two groups (P<0.05) . Conclusions The risk factors of liver cirrhosis complicated with liver palms and spider nevus are diverse, and the medical staff shall provide diagnosis and treatment based on an overall analysis of the illness and the patient's condition. Key words: Liver cirrhosis; Liver palms; Spider nevus; Relative factors

MyD88-dependent signaling in non-parenchymal cells promotes liver carcinogenesis.

In Western countries, a rising incidence of obesity and type 2 diabetes correlates with an increase of non-alcoholic steatohepatitis (NASH)-a major risk factor for liver cirrhosis and hepatocellular carcinoma (HCC). NASH is associated with chronic liver injury, triggering hepatocyte death and enhanced translocation of intestinal bacteria, leading to persistent liver inflammation through activation of Toll-like receptors and their adapter protein myeloid differentiation factor 88 (MyD88). Therefore, we investigated the role of MyD88 during progression from NASH to HCC using a mouse model of chronic liver injury (hepatocyte-specific deletion of nuclear factor κB essential modulator, Nemo; NemoΔhepa). NemoΔhepa; NemoΔhepa/MyD88-/- and NemoΔhepa/MyD88Δhepa were generated and the impact on liver disease progression was investigated. Ubiquitous MyD88 ablation (NemoΔhepa/MyD88-/-) aggravated the degree of liver damage, accompanied by an overall decrease in inflammation, whereas infiltrating macrophages and natural killer cells were elevated. At a later stage, MyD88 deficiency impaired HCC formation. In contrast, hepatocyte-specific MyD88 deletion (NemoΔhepa/MyD88Δhepa) did not affect disease progression. These results suggest that signaling of Toll-like receptors through MyD88 in non-parenchymal liver cells is required for carcinogenesis during chronic liver injury. Hence, blocking MyD88 signaling may offer a therapeutic option to prevent HCC formation in patients with NASH.

Laparoscopic Sleeve Gastrectomy After Orthotopic Liver Transplantation, Video Reported.

The immunosuppressive therapy for life after liver transplantation (LT) is considered as a risk factor for obesity. Seven percent of the transplanted patients develop severe or morbid obesity. The obesity induces non-alcoholic steatohepatitis (NASH), which is a major risk factor for liver cirrhosis and hepatocellular carcinoma, without forgetting the cardiovascular risk and the devastating impact of obesity on quality of life of the transplanted patients. Consequently, obesity exposes these patients to future transplant loss. Bariatric surgery has been proposed for transplant patients to reduce the obesity-related comorbidities and to improve survival. We report in this video the surgical technique of laparoscopic sleeve gastrectomy (LSG) after LT. We have performed between 2008 and 2017 the sleeve gastrectomy (SG) after LT in nine patients. Six procedures (66%) were performed totally by laparoscopy and three by upfront laparotomy. All the patients had a standard preoperative evaluation for obesity. All the procedures were assisted by a hepatic surgeon. Postoperatively patients were transferred to the liver ICU for 24h then to the liver unit ward. The median BMI was 41.9kg/m2 (range 38-46.1kg/m2). Median operative time was 120min (range, 90-240min). No intra-operative complications occurred. The median length of hospital stay was 7days (range, 4-81days). The postoperative course of the majority of the patients was uneventful except for one patient who develops a staple line leak. LSG after LT is technically feasible. Larger series are needed to improve the safety of the procedure in this high-risk population.

Development and surveillance of hepatocellular carcinoma in patients with sustained virologic response after antiviral therapy for chronic hepatitis C.

Hepatitis C virus (HCV) infection is a major risk factor for liver cirrhosis and hepatocellular carcinoma (HCC), and is a leading cause of liver-related deaths worldwide. Recently available direct-acting antiviral agent is very safe and highly effective (>95% sustained virologic response, SVR) against all genotypes of HCV. Achievement of SVR has been associated with a significant reduction of hepatic decompensation, development of HCC, and liver-related mortality. However, HCC risk is not eliminated even after SVR. The annual incidences of HCC in advanced fibrosis or cirrhosis have been estimated to be up to 2.5–4.5% even in patients with SVR. Therefore, surveillance for HCC is recommended in this high-risk patients. In this review, we will describe the clinical outcomes and the risk of HCC in patients with SVR and suggest who should receive surveillance for HCC.

Association of SNPs in the Promoter Regions of VEGF (rs699947 и rs2010963), ICAM1 (rs281437) and ET-1 (rs1800541) with Serum Levels of Related Proteins and Alcoholic Liver Cirrhosis Risk

Background: Uncontrolled use of alcohol can lead to the development of cirrhosis of the liver, which is manifested by fibrosis with the formation of regenerative nodes, an increase in pressure in the portal vein system and impaired liver function. Hepatic endothelium dysfunction during the formation of portal hypertension is accompanied by an increase in the level of protein molecules involved in the functioning of the endothelium: vascular endothelial growth factor A (VEGF-A), a soluble form of the intercellular adhesion molecule (s-ICAM-1) and endothelin-1 (ET -one). It is assumed that elevated levels of VEGF-A, s-ICAM-1 and ET-1 in alcoholic liver cirrhosis (AHC) may be interconnected with the structure of polymorphic loci, the promoter regions of the respective genes, which in turn may be a genetic risk factor for developing cirrhosis.Aims: Investigate the relationship of carriage of variant forms of polymorphic loci located in the promoter regions of VEGF-A, ICAM-1 and ET-1 with the level of the corresponding proteins in the blood serum and the risk of AHC.Materials and methods: The main group consisted of patients with pathological dependence on alcohol, aggravated by cirrhosis of the liver (AHC, n=60). The control group consisted of persons suffering from alcohol abuse, without liver pathology (AA, n=24). The observation period was the period of hospitalization. The serum levels of VEGF-A, s-ICAM-1 and ET-1 were evaluated by enzyme immunoassay. The distribution of variant forms of polymorphic loci located in the promoter regions of the VEGF-A genes (rs699947 and rs2010963), ICAM1 (rs281437) and ET-1 (rs1800541) in the studied sample was performed by real-time PCR.Results: The development of alcoholic cirrhosis was accompanied by a significant increase in the concentration of VEGF-A, s-ICAM-1 and ET-1 in serum. At the same time, direct correlations between the concentrations of VEGF-A, s-ICAM-1 and ET-1 in serum and the diameter of the portal vein in persons with liver cirrhosis were revealed. Patients with AHC are often carriers of the G allele of rs1800541 locus, located in the promoter of the ET-1 gene, compared with individuals suffering from control without liver pathology, which is associated with an increased risk of developing cirrhosis in alcohol dependence. The carriage of the C allele rs699947, as well as the C allele rs2010963 located in the promoter of the VEGF gene was associated with an increased level of VEGF-A in the AHC compared to carriers of this allele in the AA group. In addition, in the group of patients with AHC, carriers of allele C, homozygous CC genotype and heterozygous GC genotype of rs2010963 locus compared with carriers of G allele or homozygous GG genotype, respectively, were characterized by elevated serum VEGF-A levels.Conclusion: Carrier allele G of the rs1800541 locus (ET-1) is a risk factor for liver cirrhosis with alcohol abuse. The carriage of the C allele rs699947, as well as the C allele rs2010963 located in the promoter of the VEGF gene, can determine the elevated serum VEGF-A level in the AHC.

The roles of HLA-DQB1 gene polymorphisms in hepatitis B virus infection

BackgroundInfection with the hepatitis B virus (HBV) is an independent risk factor for liver cirrhosis and hepatocellular carcinoma, polymorphisms in HLA-DQB1 play an important role in HBV infections.MethodsThis study examined the relationships between HLA-DQB1 alleles and HBV infection susceptibility among 256 HBV carriers and 433 healthy controls. Venous blood samples were subjected to DQB1 high-resolution typing and testing for interferon-gamma, interleukin-4 (IL-4), interleukin-10, and DQB1 mRNA expression. A meta-analysis was also performed using relevant case–control studies that evaluated the associations of HLA-DQB1 alleles with HBV infection and clearance.ResultsWe found that HLA-DQB1*06:03 protected against HBV infection. Levels of IFN-γ and IL-4 were significantly elevated in HBV cases with HLA-DQB1*06:05 (vs. HLA-DQB1*05:03), and the HBV group had higher DQB1 mRNA expression than the healthy control group with HLA-DQB1*05:03 and HLA-DQB1*06:02. The meta-analysis revealed that HLA-DQB1*04:01, HLA-DQB1*05:02, HLA-DQB1*05:03, and HLA-DQB1*06:01 were risk factors for HBV infection susceptibility, while HLA-DQB1*05:01, HLA-DQB1*06:03, and HLA-DQB1*06:04 protected against HBV infection. Spontaneous HBV clearance was associated withHLA-DQB1*06:04, while chronic HBV infection was associated with HLA-DQB1*02:01 and HLA-DQB1*05:02.ConclusionDBQ1 typing can be used to identify patients who have elevated risks of HBV infection (i.e., patients with HLA-DQB1*04:01, HLA-DQB1*05:02, HLA-DQB1*05:03, and HLA-DQB1*06:01) or elevated risks of chronic HBV infection (i.e., patients with HLA-DQB1*02:01 and HLA-DQB1*05:02).

Control of progression towards liver fibrosis and hepatocellular carcinoma by SOCS3 polymorphisms in chronic HCV-infected patients

Background & aimsChronic Hepatitis C is one of the most important risk factors of liver cirrhosis and hepatocellular carcinoma. Before reaching these ultimate steps, insulin resistance triggered by hepatitis C virus infection is known to participate in the progression of liver disease. The present study aims to investigate the influence of two functional polymorphisms on SOCS3 mRNA expression and on the outcomes of CHC progression in a North African context. Patients & methodsIn this case-control study, 601 Moroccan subjects composed of 200 healthy controls, 101 resolvers and 300 patients with persistent HCV infection including 95 mild chronic hepatitis, 131 Advanced Liver Diseases and 74 HCC were enrolled. They were genotyped for the 4874 A/G (rs4969170) and A + 930– > G (rs4969168) SOCS3 variants using TaqMan SNPs assays. SOCS3 mRNA expression was assessed using Real Time PCR technique. ResultsLogistic regression analysis showed that variation at rs4969168 was associated with spontaneous clearance of HCV (P < 0.05). In addition, minor allele frequencies were significantly higher in AdLD patients when compared to the mCHC group both for rs4969168 (P = 7.0 E-04) and rs4969170 (P = 4.0 E-05). A significant association between haplotype and liver disease progression was also found. Moreover, SOCS3 mRNA was significantly more expressed in peripheral leukocytes from patients with HCC than in those from mCHC. Finally, rs4969170 was significantly associated with LDL-lipoprotein (P = 0.04), total cholesterol (P = 5.0 E-04), and higher fasting glucose levels (P = 0.005) in patients with persistent HCV infection. ConclusionsOur results underline the importance of the functional SOCS3 polymorphisms in the modulation of CHC progression and suggest their contribution to HCC development by affecting its mRNA expression and perturbing key metabolic parameters.

Noninvasive indices for monitoring disease course in Chinese patients with autoimmune hepatitis

Objective: Noninvasive and simple tests to forecast cirrhosis is in great need clinically. This study aimed to assess the clinical significance of several noninvasive indices in predicting cirrhosis in Chinese patients with autoimmune hepatitis (AIH). Materials and Methods: Liver function test and blood cell analysis were conducted in 76 AIH patients and 75 paired healthy subjects to calculate aspartate aminotransferase to alanine aminotransferase ratio(AAR), aspartate aminotransferase to platelet ratio index (APRI), fibrosis index based on the four factors (FIB-4), gamma-glutamyl transferase to platelet ratio (GPR), red blood cell distribution width (RDW), neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), and platelet to lymphocyte ratio (PLR). Binary logistic regression was performed to analysis the risk factors of liver cirrhosis and receiver operating characteristic (ROC) curve was conducted to evaluate the diagnostic value of each index and compare their diagnostic performance with serum biomarkers commonly used in the clinical setting for liver fibrosis assessing including hyaluronic acid (HA), laminin(LN), procollagen III N terminal peptide (PIIINP) and type IV collagen (ColIV). Results: AAR, APRI, FIB-4, GPR, NLR and RDW were elevated remarkably in AIH patients with cirrhosis; AAR, FIB-4 and RDW were identified to be independent risk factors of cirrhosis with OR (95%CI) of 3.517 (1.300–9.514), 1.247(1.032–1.506) and 1.414 (1.086–1.842) respectively; ROC analysis showed that the area under the ROC curve (AUC) of AAR, FIB-4 and RDW were 0.801,0.82 and 0.739, with moderate diagnostic value and better than HA, LN, PIIINP and ColIV in identifying those with cirrhosis from AIH patients. Conclusion: AAR, FIB-4 and RDW were independent risk factors of AIH cirrhosis and can be served as reference indices to monitor disease course in AIH.

Diabetes mellitus is a significant risk factor for the development of liver cirrhosis in chronic hepatitis C patients

We explored the association between diabetes mellitus (DM) and the risk of hepatitis C virus (HCV)-related liver cirrhosis in Chinese patients with chronic hepatitis C (CHC). To examine the link between DM and liver cirrhosis, we conducted a case-control study of 210 Chinese CHC patients diagnosed with liver cirrhosis, comparing them to an age- and sex-matched control group of 431 CHC patients without liver cirrhosis. We conducted logistic regression analyses adjusting for demographic features and liver cirrhosis risk factors, and found that DM increased the risk of developing liver cirrhosis 2-fold [adjusted odds ratio (AOR), 2.132; 95% confidence interval (CI), 1.344–3.382]. Furthermore, the proportion of liver cirrhosis patients and CHC-only patients with elevated serum triglycerides (>1.8 mmol/L) were 5.2% and 17.4%, respectively, yielding an AOR of 0.264 (95% CI, 0.135–0.517). Multivariate analyses that stratified the risk of developing HCV-related liver cirrhosis in DM patients by gender revealed that the estimated AOR (95% CI) for males was 0.415 (0.178–0.969). In conclusion, DM was associated with an increased risk of developing liver cirrhosis in CHC patients in China. Furthermore, among patients diagnosed with both CHC and DM, females had an increased risk of liver cirrhosis development.