Chronic Hepatitis Cirrhosis Research Articles

Validation of FIB-6 score in assessment of liver fibrosis in chronic hepatitis B.

We recently developed a simple novel index called fibrosis 6 (FIB-6) using machine learning data analysis. We aimed to evaluate its performance in the diagnosis of liver fibrosis and cirrhosis in chronic hepatitis B (CHB). A retrospective observational analysis of data was obtained from seven countries (Egypt, Kingdom of Saudi Arabia (KSA), Turkey, Greece, Oman, Qatar, and Jordan) of CHB patients. The inclusion criteria were receiving an adequate liver biopsy and a complete biochemical and hematological data. The diagnostic performance analysis of the FIB-6 index was conducted and compared with other non-invasive scores. A total of 603 patients were included for the analysis; the area under the receiver operating characteristic curve (AUROC) of FIB-6 for the discrimination of patients with cirrhosis (F4), compensated advanced chronic liver disease (cACLD) (F3 and F4), and significant fibrosis (F2-F4) was 0.854, 0.812, and 0.745, respectively. The analysis using the optimal cut-offs of FIB-6 showed a sensitivity of 70.9%, specificity of 84.1%, positive predictive value (PPV) of 40.3%, and negative predictive value (NPV) of 95.0% for the diagnosis of cirrhosis. For the diagnosis of cACLD, the results were 71.5%, 69.3%, 40.8%, and 89.2%, respectively, while for the diagnosis of significant fibrosis, the results were 68.3%, 67.5%, 59.9%, and 75.0%, respectively. When compared to those of fibrosis 4 (FIB-4) index, aspartate aminotransferase (AST)-to-platelet ratio index (APRI), and AST-to-alanine aminotransferase (ALT) ratio (AAR), the AUROC for the performance of FIB-6 was higher than that of FIB-4, APRI, and AAR in all fibrosis stages. FIB-6 gave the highest sensitivity and NPV (89.1% and 92.4%) in ruling out cACLD and cirrhosis, as compared to FIB-4 (63.8% and 83.0%), APRI (53.9% and 86.6%), and AAR (47.5% and 82.3%), respectively. The FIB-6 index could be used in ruling out cACLD, fibrosis, and cirrhosis with good reliability.

Perbedaan Kadar Pentraxin 3 pada Penderita Hepatitis B Kronis dengan Cirrosis dan Tanpa Cirrosis

This study aims to see differences in pentraxin 3 levels in chronic hepatitis B sufferers with cirrosis and without cirrosis. The method uses cross sectional consecutive sampling. The results of this study found a significant difference between the average value of Pentraxin 3 in chronic Hepatitis B patients with liver cirrhosis group compared to the group without liver cirrhosis (p<0.001). There was a significant difference between the Pentraxin 3 levels in the group of Chronic Hepatitis B sufferers with liver cirrhosis compared to the group of Chronic Hepatitis B sufferers without liver cirrhosis (p<0.001) where the Pentraxin 3 levels in the Chronic Hepatitis B group with liver cirrhosis were higher compared to the group without liver cirrhosis. In conclusion, Pentraxin 3 levels can be used as an alternative marker to assess the development of liver cirrhosis in Chronic Hepatitis B patients.
 
 Keywords: Chronic Hepatitis B, Liver cirrhosis, Pentraxin 3

Validity of serum resistin level and Il-6 as prognostic biomarkers of decompensated liver cirrhosis in chronic hepatitis C virus patients

BackgroundDecompensated liver cirrhosis (DLC) is now known as a chronic inflammatory process, evidenced by elevated levels of circulatory pro-inflammatory cytokines and chemokines which in turn lead to the development of more hepatic decompensation and multi-organ failure. Resistin has a pro-inflammatory effect through the production of several cytokines (e.g., IL-1, IL-6, IL-12, and TNF-α) and cell adhesion molecules. Interleukin-6 (IL-6) is a proinflammatory cytokine playing a crucial role in acute phase responses and in regulating immune reactions through activation and differentiation of T and B lymphocytes. The current study aimed to evaluate the value of serum resistin and IL-6 as biomarkers of DLC and their role as prognostic markers of complications in these patients.ResultsThis study was conducted on 90 patients divided into three groups: group I—30 patients with compensated cirrhosis (CLC); group II—40 patients with DLC; and group III consisted of 20 healthy controls. Serum resistin and IL-6 levels were statistically significantly higher in patients with DLC compared to patients with CLC at baseline. A cut-off value of > 302 pg/ml for serum resistin was found to discriminate between CLC and DLC with a specificity of 73.33% and sensitivity of 92.50% and a cut-off level of > 31 pg/mL for IL-6 differentiated between the two groups with a sensitivity of 85.0% and specificity of 76.67%. Patients with DLC were followed up for 3 months, 10 patients (25%) passed away, and 19 patients out of the remaining 30 (63.3%) patients developed complications including acute kidney injury, spontaneous bacterial peritonitis, variceal hemorrhage, encephalopathy, and hepatocellular carcinoma. Serum resistin and IL-6 were found to be significantly higher at baseline in those patients who developed complications or mortality after the follow-up period. In addition, there were positive correlations between IL-6 and resistin and MELD-NA and CRP.ConclusionSerum resistin and IL-6 could be used as sensitive diagnostic and prognostic biomarkers of decompensated cirrhotic patients.

Clinical prediction of HBV-associated cirrhosis using machine learning based on platelet and bile acids

ObjectivesThe present study was conducted to evaluate the performance of serum bile acids in the prediction of cirrhosis in chronic hepatitis B (CHB) population. MethodsDysregulated metabolites were explored using untargeted and targeted metabolomic analyses. A machine learning model based on platelet (PLT) and several bile acids was constructed using light gradient boosting machine (LightGBM), to differentiate HBV-associated cirrhosis (BAC) from CHB patients. ResultsSerum bile acids were dysregulated in BAC compared to CHB patients. The LightGBM model consisted of PLT, TUDCA, UDCA, TLCA, LCA and CA. The model demonstrated a strong discrimination ability in the internal test subset of the training cohort to diagnose BAC from CHB patients (AUC = 0.97). The high diagnostic accuracy of the model was further validated in an independent validation cohort. In addition, the model had high predictive efficacy in discriminating compensated BAC from CHB patients (AUC = 0.89). The performance of the model was better than AST/ALT ratio and the gradient boosting (GB)-based model reported in previous studies. ConclusionsOur study showed that this LightGBM model based on PLT and 5 bile acids has potential in clinical assessments of CHB progression and will be useful for early detection of cirrhosis in CHB patients.

SAT-463 - A diagnostic non-invasive model for liver advanced fibrosis and cirrhosis in chronic hepatitis B (CHB) concurrent with non-alcoholic fatty liver disease (NAFLD) based on machine learning (ML)

SAT-463 - A diagnostic non-invasive model for liver advanced fibrosis and cirrhosis in chronic hepatitis B (CHB) concurrent with non-alcoholic fatty liver disease (NAFLD) based on machine learning (ML)

Construction of a Lasso regression-based prediction model for development of cirrhosis in chronic hepatitis B

Construction of a Lasso regression-based prediction model for development of cirrhosis in chronic hepatitis B

Agreement and reliability of hepatic transient elastography in patients with chronic hepatitis C: Across-sectional test-retest study.

Transient elastography (TE) has largely replaced liver biopsy to evaluate fibrosis stage and cirrhosis in chronic hepatitis C. Previous studies have reported excellent reliability of TE but agreement metrics have not been reported. This study aimed to assess interrater agreement and reliability of repeated TE measurements. Two operators performed TE independently, directly after each other. The primary outcome was disagreement, defined as a difference in TE results between operators of ≥33%, as well as the smallest detectable change, SDC95 (i.e., the difference between measurements needed to state with 95% certainty that there is a difference in underlying stiffness). Secondary outcomes included reliability, measured as intraclass correlation (ICC), and patient and examination characteristics associated with the agreement. In total, 65 patients were included, with a mean liver stiffness of 9.7 kPa. Of these, 21 (32%) had a disagreement in TE results of ≥33% between the two operators. The SDC95 on the log scale was 1.97, indicating that an almost twofold increase or decrease in liver stiffness would be required to confidently represent a change in the underlying fibrosis. Reliability, estimated using the ICC, was acceptable at 0.86. In a post hoc analysis, fasting less than 5 h before TE was associated with a higher degree of disagreement (48% vs. 19%, p = 0.03). In our clinical setting, interrater agreement in directly repeated TE measurements was surprisingly low. It is essential to further investigate the reliability and agreement of TE to determine its validity and usefulness.

Diagnostic performance of Mac-2-binding protein glycosylation isomer (M2BPGi) as a liver fibrosis marker in chronic hepatitis C patients with chronic kidney disease on hemodialysis

Liver fibrosis assessment is essential to determine the initiation, duration, and evaluation of chronic hepatitis C treatment. Therefore, the study aimed to assess the role of Mac-2-binding protein glycosylation isomer (M2BPGi) as a biomarker to measure liver fibrosis in chronic hepatitis C patients with chronic kidney disease on hemodialysis. This study used a cross-sectional design. Serum M2BPGi level and transient elastography results were evaluated in 102 chronic hepatitis C patients with CKD on HD, 36 CKD on HD patients, and 48 healthy controls. ROC analysis was conducted to identify the optimal cutoff values to assess significant fibrosis and cirrhosis among chronic hepatitis C patients with CKD on HD. In chronic hepatitis C patients with CKD on HD, the level of serum M2BPGi had a moderately significant correlation with transient elastography (r = 0.447, p < 0.001). The median serum M2BPGi was higher among CKD on HD patients compared to healthy controls (1.260 COI vs. 0.590 COI, p < 0.001) and was even higher in chronic hepatitis C patients with CKD on HD compared to CKD on HD group (2.190 COI vs. 1.260 COI, p < 0.001). It is also increased according to the severity of liver fibrosis: 1.670 COI, 2.020 COI, and 5.065 COI for F0-F1, significant fibrosis, and cirrhosis, respectively. The optimal cutoff values for diagnosing significant fibrosis and cirrhosis were 2.080 and 2.475 COI, respectively. Serum M2BPGi could be a simple and reliable diagnostic tool for evaluating cirrhosis in chronic hepatitis C patients with CKD on HD.

High-risk population of progressive hepatic fibrosis in chronic hepatitis B patients on antiviral therapy.

Progressive hepatic fibrosis leads to hepatocellular carcinoma (HCC) and decompensated cirrhosis. The aim of this study was to identify the high-risk population for progressive hepatic fibrosis and the incidence of HCC and decompensated cirrhosis in chronic hepatitis B (CHB) patients with antiviral therapy. The data came from a multicenter, center-randomized, double-blind clinical trial that analyzed only patients in the ETV-treated arm. There was 156 hepatitis B e antigen (HBeAg)-positive and 135 HBeAg-negative patients in 14 institutions. The primary endpoint was fibrosis reversal on 72-week Entecavir (ETV) treatment. The 7-year cumulative incidence of HCC and decompensated cirrhosis were analyzed. Multivariate logistic and LASSO regression analyses were used to screen variables associated with fibrosis reversal. 86/156 (55%) HBeAg-positive and 58/135 (43%) HBeAg-negative patients achieved fibrosis reversal on 72-week ETV treatment. Average age was 43years, 203 (69.8%) was male, and 144 (49.5%) patients had cirrhosis. Age ≥ 40years (OR: 0.46, 95% CI 0.23-0.93) and HBcrAg ≥ 8.23 log U/ml (OR: 2.72, 95% CI 1.33-5.54) in HBeAg-positive patients and HBV genotype C (OR: 0.44, 95% CI 0.21-0.97) in HBeAg-negative patients were independent factors of fibrosis reversal. It was confirmed in patients with cirrhosis. After 7-year ETV treatment, seven (4.5%) HBeAg-positive patients occurred HCC or decompensated cirrhosis, including four patients with age ≥ 40 years and six with HBcrAg 8.23log U/ml, while twelve (8.9%) HBeAg-negative patients occurred, including eleven with HBV genotype C. HBeAg-positive patients with a low HBcrAg level or old age, and HBeAg-negative patients with HBV genotype C tended to develop progressive hepatic fibrosis and had a high incidence of HCC and decompensated cirrhosis, even on ETV treatment.

Novel index for the prediction of significant liver fibrosis and cirrhosis in chronic hepatitis B patients in China.

BACKGROUNDNoninvasive, practical, and convenient means of detection for the prediction of liver fibrosis and cirrhosis in China are greatly needed. AIMTo develop a precise noninvasive test to stage liver fibrosis and cirrhosis. METHODSWith liver biopsy as the gold standard, we established a new index, [alkaline phosphatase (U/L) + gamma-glutamyl transpeptidase (U/L)/platelet (109/L) (AGPR)], to predict liver fibrosis and cirrhosis. In addition, we compared the area under the receiver operating characteristic curve (AUROC) of AGPR, gamma-glutamyl transpeptidase to platelet ratio, aspartate transaminase to platelet ratio index, and FIB-4 and evaluated the accuracy of these routine laboratory indices in predicting liver fibrosis and cirrhosis. RESULTSCorrelation analysis revealed a significant positive correlation between AGPR and liver fibrosis stage (P < 0.001). In the training cohort, the AUROC of AGPR was 0.83 (95%CI: 0.78-0.87) for predicting fibrosis (≥ F2), 0.84 (95%CI: 0.79-0.88) for predicting extensive fibrosis (≥ F3), and 0.87 (95%CI: 0.83-0.91) for predicting cirrhosis (F4). In the validation cohort, the AUROCs of AGPR to predict ≥ F2, ≥ F3 and F4 were 0.83 (95%CI: 0.77-0.88), 0.83 (95%CI: 0.77-0.89), and 0.84 (95%CI: 0.78-0.89), respectively.CONCLUSIONThe AGPR index should become a new, simple, accurate, and noninvasive marker to predict liver fibrosis and cirrhosis in chronic hepatitis B patients.

Serum Glial Cell Line-Derived Neurotrophic Factor (sGDNF) Is a Novel Biomarker in Predicting Cirrhosis in Patients with Chronic Hepatitis B.

Objectives We assessed the potential of glial cell line-derived neurotrophic factor (GDNF) as a useful biomarker to predict cirrhosis in chronic hepatitis B (CHB) patients. Methods A total of 735 patients from two medical centers (385 CHB patients and 350 healthy controls) were included to determine the association of serum and tissue GDNF levels with biopsy-proven cirrhosis. The diagnostic accuracy of serum GDNF (sGDNF) was estimated and compared with other indices of cirrhosis. Results We showed significantly higher levels of sGDNF in CHB patients with fibrosis (28.4 pg/ml vs. 11.6 pg/ml in patients without) and patients with cirrhosis (33.8 pg/ml vs. 23.5 pg/ml in patients without). The areas under receiver operating curve (AUROCs) of sGDNF were 0.83 (95% confidence interval (CI): 0.80–0.87) for predicting liver fibrosis and 0.84 (95% CI: 0.79–0.89) for cirrhosis. Findings from the serum protein level and hepatic mRNA expression were consistent. Using the best cutoff to predict cirrhosis, we categorized the patients into sGDNF-high and sGDNF-low groups. The sGDNF-high group had significantly larger Masson's trichrome and reticulin staining-positive area, higher Scheuer score, and METAVIR fibrosis stage (all p < 0.001) but not steatosis. On multivariable regression, sGDNF was independently associated with cirrhosis with an odds ratio of 6.98 (95% CI: 1.10–17.94). Finally, we demonstrated that sGDNF outperformed AST to platelet ratio index, FIB-4, fibroscore, forn index, and fibrometer in differentiating F4 vs. F3. Conclusion Using serum, tissue mRNA, and biopsy data, our study revealed a significant potential of sGDNF as a novel noninvasive biomarker for cirrhosis in CHB patients.

Shear wave elastography-based liver fibrosis assessment in patients with chronic hepatitis E displays elevated liver stiffness regardless of previous antiviral therapy.

Hepatitis E virus (HEV) infection especially in immunocompromised individuals can lead to chronic hepatitis. Aggressive courses of chronic hepatitis E leading to liver cirrhosis in a short period of time have been described, but evidence on the degree of liver involvement in chronic hepatitis E is rare. We therefore aimed to quantify liver fibrosis in patients with chronic active hepatitis E compared to patients with sustained virological response after ribavirin (RBV) treatment using 2D-shear wave elastography (2D-SWE) to measure liver stiffness. Patients with chronic hepatitis E underwent 2D-SWE, B-mode and Doppler ultrasound and laboratory testing in order to assess severity of liver involvement. In this cross-sectional study, we included 14 patients of whom 8 had ongoing chronic hepatitis E and 6 patients had been successfully treated for chronic hepatitis E. The most frequent cause for immunosuppression was prior kidney transplantation (n=12), one patient was a multivisceral transplant recipient, one had been treated for lymphoma. Five patients cleared HEV after RBV therapy, one patient reached viral clearance after reduction of his immunosuppressive medication. Using 2D-SWE measurement, 71.4% displayed increased stiffness indicative of liver fibrosis: 57.1% classified as significant fibrosis and 14.3% as severe fibrosis. Liver stiffness did not differ between patients with active chronic hepatitis E and in patients who had cleared HEV (1.59 and 1.54 m/s respectively). Compared with a control group of kidney transplant recipients without hepatitis E (1.44 m/s), the patients with a history of hepatitis E displayed a significantly higher liver stiffness (P=0.04). In our cohort of chronic hepatitis E patients, elevated liver stiffness indicating liver fibrosis was common and significantly higher than in controls. This is consistent with prior sparse reports of the presence of liver fibrosis or cirrhosis in chronic hepatitis E and emphasizes the need for HEV testing, therapy and research on new therapeutic options. As elevated liver stiffness was also present in patients after HEV treatment, continuous liver surveillance including elastography and ultrasound should be considered.

FRI323 - ATA haplotype of the interleukin-10 gene and low phase angle are associated with liver cirrhosis in chronic hepatitis C

FRI323 - ATA haplotype of the interleukin-10 gene and low phase angle are associated with liver cirrhosis in chronic hepatitis C

Statin use and risk of progression to liver cirrhosis in chronic hepatitis B independent of conventional risk factors: A nationwide study.

Many studies have elucidated the protective associations of statin use with liver cancer or mortality, but studies examining statin's effect on the risk of progression to liver cirrhosis considering medical/metabolic conditions or lifestyle factors are lacking. We aimed to assess statin's benefit independent of conventional risk factors. We identified 25,033 pairs of statin users (using statins for ≥90 days) and nonusers among patients with chronic hepatitis B (CHB) in the Republic of Korea's National Health Insurance Service database from 2010 to 2018. The primary endpoint was progression to cirrhosis from an inactive carrier or simple CHB. The cumulative probability was plotted using the Kaplan‐Meier method. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated using the multivariable Cox proportional hazard model. During a 218,472 person‐year follow‐up, 2210 incident cases of progression to cirrhosis occurred. The 5‐year cumulative risks were 4.0% and 6.3% in statin users and nonusers, respectively (p < 0.001). Statin use was significantly associated with a decreased risk of progression to cirrhosis (aHR, 0.59; 95% CI, 0.55–0.65; p < 0.001), after adjusting for age, sex, hypertension, diabetes, dyslipidemia, antiviral therapy, aspirin use, metformin use, nonstatin medication for dyslipidemia, smoking, drinking, obesity, exercise, and liver dysfunction. This protective association was still significant in a dose–response manner and with different time lags for outcomes. Conclusion: Statin use is associated with a decreased risk of progression to cirrhosis among patients with CHB, independent of metabolic and lifestyle factors. Future studies are required to validate this observation.

Modeling the Combined Effect of Hepatitis B Infection and Heavy Alcohol Consumption on the Progression Dynamics of Liver Cirrhosis

Liver cirrhosis is the liver scarring in human body which causes the liver organ failure to function its regular activities effectively and normally. In this paper, we proposed and analyzed the combined effect of hepatitis B virus (HBV) infection and heavy alcohol consumption on the progression dynamics of liver cirrhosis. In order to study the progression dynamics of cirrhosis and to describe the effect of alcohol intake variation on a chronic hepatitis B patients a deterministic model and a logistic function are considered, respectively. The detailed proof of the positivity, boundedness, and biological feasibility of the proposed model is presented. The disease endemic equilibrium point and the existence of bifurcation were investigated in detail. We established and proved the existence theorems for forward and backward bifurcations, respectively. Finally, we performed large scale numerical simulations to verify the analytic work and the result of the numerical simulations reveal that heavy alcohol consumption significantly accelerates the progression of liver cirrhosis in chronic hepatitis B infected individuals.

Meta-analysis of efficacy and safety of Liuwei Wuling Tablets combined with conventional drugs in treatment of liver fibrosis and cirrhosis in chronic hepatitis B

The present study evaluated the clinical efficacy and safety of Liuwei Wuling Tablets combined with conventional drugs for the treatment of liver fibrosis and cirrhosis in chronic hepatitis B. CNKI, Wanfang, VIP, CBM, PubMed, EMbase and Cochrane Library were searched for the relevant randomized controlled trials(RCTs) published from database inception to February 2021. All the retrieved papers were independently screened, extracted and evaluated by two researchers, followed by Meta-analysis by Review Manager 5.4. Finally, 18 RCTs were included, involving 2 168 patients(1 106 in the treatment group and 1 062 in the control group). The Meta-analysis results showed that compared with conventional drugs alone, Liuwei Wuling Tablets combined with conventional drugs could increase the effective rate of clinical treatment by reducing serum hyaluronic acid(HA), laminin(LN), procollagen type Ⅲ(PCⅢ), and type Ⅳ collagen(Ⅳ-C) to improve liver function, decreasing the levels of total bilirubin(TBiL), alanine amino-transferase(ALT), and aspartate aminotransferase(AST), and improving the negative conversion ratio of hepatitis B virus(HBV) DNA. In terms of safety, there were no serious adverse reactions in the treatment group and the control group. The results showed that Liuwei Wuling Tablets combined with antiviral or other conventional liver-protecting drugs could improve liver function, treat liver cirrhosis, and reduce liver fibrosis with high safety. However, due to the influence of literature quality and quantity, multi-center and high-quality RCTs with large sample size are needed for verification.

Liver Cirrhosis in Chronic Hepatitis B: is it due to Hepatic Vena Cava Syndrome: case report

Chronic hepatitis B (CHB) is a common chronic viral infection of man. Hepatitis B Virus is not a cytopathic virus. Extensive intrahepatic viral replication is compatible with normally functioning hepatocytes. Patients with CHB in the West manifest as a ‘healthy carrier’, whereas in Asia and Africa some develop liver cirrhosis and hepatocellular cancer. Liver cirrhosis in CHB is assumed to evolve through chronic hepatitis but its pathogenesis and the geographic difference in the outcome of CHB is not explained adequately. Nepal is a country with low prevalence of CHB, where patients with CHB have hepatic vena cava syndrome (HVCS) as a comorbid condition. HVCS is a bacterial infection induced chronic obstructive disease of inferior vena cava at the site of hepatic vein opening. It is clinically characterized by long asymptomatic courses and occasional episodes of acute exacerbation precipitated by bacterial infection that result in hepatic venous outflow obstruction. Increased frequencies of acute exacerbations led to development of hypersplenism, liver cirrhosis and hepatocellular carcinoma. Long time follow up of patients with CHB in Nepal showed development of cirrhosis in many but it was not related to the severity of viral replication or to the duration of the viral infection. Cirrhosis developed more frequently in patients with hypersplenism and those with severe and recurrent acute exacerbation of HVCS. These observations suggested that the development of cirrhosis in CHB in Afro-Asian countries may be due to the presence of HVCS as a comorbid condition. Reported here are a few cases of CHB that illustrate this point. Pathogenesis of cirrhosis in these patients is discussed.

Serum free light chain is associated with histological activity and cirrhosis in patients with chronic hepatitis B

BackgroundThe antiviral immune response is the main cause of hepatocyte damage and inflammatory necrosis. The serum free light chain, reflecting the immune function of B-cells, is strongly associated with inflammation and disease activity. We aimed to investigate the association of serum free light chain with the progression of chronic hepatitis B. MethodsA total of 208 eligible chronic hepatitis B patients who had undergone a liver biopsy were studied. Serum free light chains of all patients were measured by turbidimetry using an immunoassay. Liver histology was assessed according to the METAVIR scoring system (which grades the stage of fibrosis on a five-point scale, F0 = no fibrosis to F4 = cirrhosis, and histological activity on a four-point scale, A0 = no activity to A3 = severe activity). The association of serum free light chains with histological activity and fibrosis progression was evaluated. ResultsThe concentration of serum free light chains in CHB patients increased gradually with histological activity and fibrosis progression. The intensity of histological activity was significantly correlated with the serum free kappa chain (r = 0.658, P < 0.001) and the serum free lambda chain (0.675, P < 0.001). The stages of fibrosis were correlated with the serum free kappa chain (r = 0.683, P < 0.001) and serum free lambda chain (0.664, P < 0.001). After adjusting for age, sex and other synergic factors, the serum free kappa chain remained a potential risk factor, but the serum free lambda chain was no longer associated with liver cirrhosis. Similar to FIB-4 and RPR, the serum free kappa chain exhibited excellent performance in the prediction of liver cirrhosis. The AUCs of serum free Kappa chain, FIB-4 and RPR were 0.873, 0.880 and 0.895, respectively, which were significantly higher than those of the AAR and APRI (0.718 and 0.746). ConclusionOur work revealed that serum free light chains were associated with histological activity and cirrhosis in chronic hepatitis B, which could play a crucial role in the immunopathogenesis of HBV-associated cirrhosis. In addition, free kappa light chain could be a useful predictor of liver cirrhosis.

Interferon-λ rs12979860 genotype association with liver fibrosis in chronic hepatitis C (CHC) patients in the Pakistani population

Risk and progression of liver fibrosis and cirrhosis in chronic hepatitis C (CHC) patients is significantly influenced by host genetic factors in a polygenic manner. The rs12979860 genetic polymorphism in the interferon-λ3-interferon-λ4 (IFNL3-IFNL4) region has been found to be a major determinant of hepatic inflammatory and fibrotic progression in CHC patients of mainly Caucasian origin; however, it is not known if this association applies to other ethnicities, including Pakistani CHC patients. Here, we genotyped IFNL3-IFNL4 rs12979860 genetic variants in a sample set of 502 Pakistani patients with CHC and used logistic regression analysis to determine its association with the risk and progression of HCV-related fibrosis and cirrhosis. We demonstrate that the rs12979860 major (CC) genotype, despite not determining the risk of stage-specific hepatic fibrosis independently, is associated with a marginally significant risk of liver cirrhosis (OR: 1.64, p = 0.049) after an adjustment for age, gender, body mass index, HCV viral load, and liver enzymes. In a subgroup of CHC patients with sustained ALT levels of <60 IU/L, a more pronounced impact of the IFNL3-IFNL4 rs12979860 major (CC) genotype on advanced liver fibrosis (OR: 4.99, p = 0.017) and cirrhosis (OR: 3.34, p = 0.005) was seen. The present study suggests that IFNL3-IFNL4 rs12979860 polymorphism may also be a significant predictor of hepatic fibrosis and cirrhosis in Pakistani CHC patients, especially in those with normal or near-normal liver enzyme levels.

A Novel Noninvasive Index for Assessment of Liver Fibrosis and Cirrhosis in Patients with Chronic Hepatitis C Virus Infection

Background: Liver fibrosis and cirrhosis are major causes of morbidity and mortality in chronic hepatitis C (CHC) patients. Objective: To assess a novel non-invasive index in prediction of hepatic fibrosis and cirrhosis in chronic hepatitis c patients by using red cell distribution width to platelet ratio (RPR). Patients and Methods: This cross-sectional study was conducted on 84 patients with hepatitis C virus in El Ahrar Teaching Hospital during the period from May 2019 to October 2019. The patients were classified into 3 groups, group (I) 26 CHC cases without fibrosis, group (II) 48 CHC cases with fibrosis, and group (III) 10 CHC cases with cirrhosis. The patients were subjected to history taking, clinical examination, laboratory investigations (CBC, liver function, kidney function, INR), and imaging modalities. Results: There was a higher sensitivity of RPR (83.3%) in detecting fibrotic liver among CHC cases and ability of 73.4% to negative cases among truly negatives, with higher accuracy of 78.6% than other scores which had high sensitivity of 75%, 77.1% and 68.8% and specificity of 69.4%, 72.2% and 72.2% of APRI score, FIB4 and AAR respectively. While, there was a higher sensitivity of RPR (90%) in detecting cirrhotic liver among CHC cases and ability of 97.4% to detect negative cases among truly negatives, with higher accuracy of 96.4% than other scores, which had high sensitivity of 90%, 80% and 80% and specificity of 95.9%, 85.9% and 95.5% of APRI score, FIB4 and AAR respectively. Conclusion: The progression and prognosis of chronic hepatitis C using a complete blood cell count.