Effects of Metabolic Syndrome on Fibrosis in Chronic Viral Hepatitis

Background/Aims

Metabolic syndrome, comprising diabetes, hypertension, central obesity, and dyslipidemia, is increasingly prevalent worldwide. We aimed to study the relationship between metabolic syndrome and the risk of liver fibrosis in patients with chronic hepatitis B (CHB) and chronic hepatitis C (CHC).

Methods

In total, 954 patients (CHB, 850; CHC, 104 patients) with liver biopsy were included in the retrospective analysis. Extensive clinical and histological data were available. Metabolic syndrome was defined using the International Diabetes Federation definition of metabolic syndrome, 2006 criteria. Histological lesions were evaluated according to the histology activity index system.

Results

Metabolic syndrome was present in 6% of patients and significantly more prevalent in patients with CHC than in patients with CHB (5% vs 13%, p<0.001). Patients with metabolic syndrome were older among patients with CHB and patients with CHC, and, as expected, were mainly overweight or obese. Fibrosis was significantly more severe in patients with metabolic syndrome than in those without, regardless of whether they had CHB and CHC (CHB, 3.3±2.1 vs 2.4±1.3, p=0.025; CHC, 2.6±1.5 vs 1.3±0.7, p=0.006). Liver fibrosis (stages 3 to 4) was independently associated with increased age, higher transaminase level and metabolic syndrome (odds ratio, 2.421; p=0.017).

Conclusions

Metabolic syndrome is associated independently with severe fibrosis in patients with chronic viral hepatitis B and C.     

Dried blood spot sampling as an alternative for the improvement of hepatitis B and C diagnosis in key populations

BACKGROUNDTo achieve the elimination of hepatitis B and C, there is an urgent need to develop alternative strategies to increase the access of diagnosis, particularly among key populations such as people living with human immunodeficiency virus (HIV), individuals with coagulopathies and chronic kidney disease (CKD) patients. AIMTo evaluate the use of dried blood spot (DBS) in the detection of hepatitis B virus (HBV) and hepatitis C virus (HCV) markers. METHODSA total of 430 individuals comprised of people living with HIV, coagulopathies and CKD provided paired serum and DBS samples. HBsAg, anti-HBc and anti-HCV were tested in those samples using a commercial electrochemiluminescence. Demographic and selected behavioral variables were evaluated to assess possible association with HBV and HCV positivity. RESULTSUsing DBS, HBsAg prevalence varied from 3.9% to 22.1%, anti-HBc rates varied from 25.5% to 45.6% and anti-HCV positivity ranged from 15.9% to 41.2% in key populations. Specificities of HBV and HCV tests using DBS varied from 88.9% to 100%. The HBsAg assay demonstrated the best performance in CKD and coagulopathy individuals and the anti-HCV test had a sensitivity and specificity of 100% in people living with HIV. Accuracy of HBV and HCV detection in DBS varied from 90.2% to 100%. In the CKD group, HBsAg positivity was associated with infrequent use of condoms, and anti-HBc positivity was associated with sharing nail cutters/razors/toothbrushes. Anti-HCV reactivity was positively associated with a history of transplantation and length of time using hemodialysis in both specimens. In people living with HIV, only the male gender was associated with anti-HBc positivity in serum and DBS.CONCLUSIONDBS with electrochemiluminescence are useful tools for the diagnosis and prevalence studies of hepatitis B and C among key populations and may increase the opportunity to foster prevention and treatment.     

Sensitivity of individual donor nucleic acid testing (NAT) for the detection of hepatitis B infection by studying diluted NAT yield samples

BackgroundScreening blood donors for the presence of hepatitis B virus surface antigen (HBsAg) has been the backbone of blood safety. However, occult hepatitis B infection (OBI) in donors can be missed when only HBsAg screening is used. Nucleic acid testing (NAT) is capable of detecting OBI among donors. The aim of our study was to analyse the sensitivity of NAT for detecting OBI.ResultsOf the 18 samples studied, nine were NAT-reactive at a dilution of <1:4 and five out of these showed presence of antibody to core antigen (IgG+IgM). Antibody to surface antigen was present in only two of the nine NAT-reactive samples, one with antibody to core antigen and the other without. Six had a viral load in the range from <10 to 38 IU/mL whereas the viral load in the remaining three samples was not determined. Among the other nine samples which were NAT-reactive at dilutions ≥1:4, antibody to core antigen (IgG+IgM) was present in seven.DiscussionOur study showed that ID-NAT testing along with HBsAg screening could detect most potentially HBV infectious donors (including those with OBI). NAT screening for HBV on diluted samples could compromise blood safety because samples with a low viral load will escape detection.     

Noninvasive assessment of liver fibrosis with the aspartate transaminase to platelet ratio index (APRI): Usefulness in patients with chronic liver disease: APRI in chronic liver disease

Background

The aspartate aminotransferases (AST) to platelet ratio index (APRI) may serve as a noninvasive marker to assess liver fibrosis.

Objectives

To assess the diagnostic ability of the APRI for prediction of fibrosis in patients with chronic hepatitis B (CHB), chronic hepatitis C (CHC), and non-alcoholic fatty liver disease (NAFLD).

Patients and Methods

This retrospective study included 207 patients with CHB, 108 with CHC, and 140 patients with NAFLD. The APRI was calculated as (AST level/upper normal limit for AST)/platelet counts (109/L) × 100. The stage of liver fibrosis in patients with chronic viral hepatitis was graded using the METAVIR scale. The Kleiner system for grading fibrosis was used in patients with NAFLD.

Results

Bivariate correlation analyses showed that the APRI was significantly associated with fibrosis scores in patients with CHC (p = 0.2634, p = 0.0059) and NAFLD (p = 0.2273, p = 0.0069), but not in those with CHB (p = 0.1005, p = 0.1495). Receiver operating characteristic (ROC) curves were used for assessing the ability of the APRI as a predictor of the absence or presence of liver fibrosis (fibrosis score of 0 vs fibrosis scores of 1-4). In patients with CHC, the APRI showed a sensitivity of 72.7% and a specificity of 62.4% for detection of fibrosis (p<0.01). In the NAFLD group, the APRI showed a sensitivity of 60.0% and specificity of 73.3% for detection of fibrosis (p<0.01). In patients with CHB, the APRI showed a sensitivity of 55.0% and a specificity of 75.4% for fibrosis (p=NS).

Conclusions

The APRI shows an acceptable accuracy for the assessment of liver fibrosis in patients with CHC and NAFLD, but not in those with CHB.     

Higher risk of hepatocellular carcinoma in chronic hepatitis B vs chronic hepatitis C after achievement of virologic response

It is unclear whether the achievement of virologic response modifies the risk of hepatocellular carcinoma (HCC) differently in chronic hepatitis B (CHB) and chronic hepatitis C (CHC). Our aim was to compare the risk of HCC between patients with CHB and CHC who achieved virological response. We analysed data from patients with CHB treated with entecavir (n=2000) or CHC treated with peg‐interferon and ribavirin (n=733) at a tertiary hospital from 2004 to 2011. Virological response was defined as serum HBV DNA<15 IU/mL at 1 year of treatment for CHB or the achievement of sustained virologic response for CHC. Virological response was achieved in 1520 patients with CHB (76.0%) and 475 patients with CHC (64.8%). During the median follow‐up period of 6 years, 228 patients with CHB (11.4%) and 59 patients with CHC (8.0%) developed HCC. Among patients with virological response, CHB was independently associated with a significantly higher incidence of HCC (hazard ratio, 2.17; 95% CI, 1.30‐3.63; P=.003) than CHC. Among patients without virological response, there were no differences in HCC incidence between the two cohorts (P=.52). In patients with cirrhosis at baseline, the incidence of HCC did not differ between the two cohorts even after achieving virological response (P>.99). In conclusion, patients with CHB treated with entecavir were associated with a higher risk of HCC compared to patients with CHC treated with peg‐interferon and ribavirin after achieving virological response. However, the risk of HCC did not differ between the two cohorts if the patients had cirrhosis at baseline, even if virological response was achieved.     

Serum adipokine levels in chronic liver diseases: Association of resistin levels with fibrosis severity

Objective. Leptin and adiponectin have been implicated in the pathogenesis and progression of non-alcoholic steatohepatitis (NASH) and chronic hepatitis C (CHC), but little is known about the role of resistin in chronic liver diseases. The objective of this study was to investigate serum levels of the above three adipokines in relation to the etiology of liver disease and to determine their associations with histological severity. Material and methods. We prospectively evaluated 146 patients (HBeAg-negative chronic hepatitis B (CHB): 52, CHC: 70, NASH: 24) who consecutively underwent liver biopsy. Detailed epidemiological, anthropometric and laboratory data were recorded. Histological lesions were evaluated blindly according to the Ishak and the Brunt classifications for CHB/CHC and NASH, respectively. Results. Serum adipokine levels were similar between CHB and CHC patients, while CHB/CHC patients had significantly lower leptin levels compared with NASH patients (8.3±7.3 versus 17.6±16.6 ng/ml, p=0.012) and higher adiponectin (10.2±5.1 versus 7.5±4 µg/ml, p=0.018) and resistin levels (7.1±2.5 versus 5.7±2.8 ng/ml, p=0.016). In CHB/CHC, there was no significant association between steatosis or necroinflammation and levels of adipokines, while the presence of moderate/severe fibrosis (stages 4–6) was associated with higher leptin and adiponectin levels in male but not in female patients and with lower resistin levels irrespective of gender or other factors (adjusted odds ratio=0.788, p=0.035). Conclusions. Serum adipokine levels depend on the etiology of liver disease differing between chronic viral hepatitis and NASH, but not between CHB and CHC. In CHB/CHC, resistin levels are independently associated with fibrosis severity, whereas in the association of leptin and adiponectin levels with fibrosis, it seems to be a gender effect.     

Correlation of hepatitis B surface antigen expression with clinicopathological and biochemical parameters in liver biopsies: A comprehensive study

BACKGROUNDChronic viral B hepatitis (CHB) is a potentially life-threatening liver disease that may progress to liver failure and cirrhosis. Currently, although combinations of different laboratory methods are used in the follow-up and treatment of CHB, the failure of these procedures in some cases has led to the necessity of developing new approaches. In CHB, the intrahepatic expression pattern of viral antigens, including hepatitis B surface antigen (HBsAg), is related to different phases of inflammation. However, many studies have focused on the intracytoplasmic properties of HBsAg staining, and HBsAg positivity in liver tissue has not been evaluated by objective quantitative methods.AIMTo investigate the relationship of image analysis-based quantitative HBsAg expression and its staining patterns with clinicopathological factors and treatment in CHB.METHODSA total of 140 liver biopsies from treatment-naïve cases with CHB infection were included in this study. Following diagnosis, all patients were treated with entecavir (0.5 mg) and followed up at three-month intervals. The percentage of immunohistochemical HBsAg (p-HBsAg) expression in the liver was determined in whole tissue sections of biopsies from each case by image analysis. The immunohistochemical staining pattern was also evaluated separately according to 3 different previously defined classifications.RESULTSA positive correlation between p-HBsAg and serum levels of hepatitis B virus (HBV) DNA and HBsAg was observed (P < 0.001). The p-HBsAg value was significantly higher in younger patients than in older patients. When the groups were categorized according to the hepatitis B e antigen (HBeAg) status in HBeAg-positive cases, p-HBsAg was correlated with HBV DNA, hepatitis activity index (HAI) and fibrosis scores (P < 0.001). In this group, p-HBsAg and HBsAg expression patterns were also correlated with the viral response (VR) and the serological response (SR) (P < 0.001). Multivariate analysis revealed that p-HBsAg was an independent predictor of either VR or SR (P < 0.001). In HBeAg-negative patients, although HBsAg expression patterns were correlated with both HAI and fibrosis, no relationship was observed among p-HBsAg, clinicopathological factors and VR.CONCLUSIONIn pretreatment liver biopsies, the immunohistochemical determination of HBsAg expression by quantitative methods, beyond its distribution within the cell, may be a good predictor of the treatment response, especially in HBeAg-positive cases.     

Hepatitis B Surface Antigen Quantification across Different Phases of Chronic Hepatitis B Virus Infection Using an Immunoradiometric Assay

Background/AimsQuantification of hepatitis B surface antigen (HBsAg) is an emerging serologic test and may be useful for identifying treatment strategies for chronic hepatitis B (CHB). This study aimed to evaluate HBsAg titers during the natural course of CHB and identify correlations between HBsAg titers and hepatitis B virus (HBV) DNA concentrations across different CHB phases measured using an immunoradiometric assay (IRMA).MethodsCHB phases were defined on the basis of HBV DNA concentrations, the presence of hepatitis B e antigen/antibody (HBeAg/Ab) and serum alanine aminotransferase levels. Serum HBsAg titers and paired HBV DNA concentrations in the different phases of CHB were compared using 627 serum samples.ResultsMean HBsAg titers were significantly higher in the immunotolerant (IT) phase and immunoreactive (IR) HBeAg-positive phase than in the low-replicative (LR) and HBeAg-negative CHB (ENH) states. The correlation between HBsAg titers and HBV DNA concentrations was modest in the IT (n=36, r=0.804, p<0.001) and IR (n=48, r=0.773, p<0.001) phases, and it was poor in the LR state (n=116, r=0.289, p=0.002); however, no significant correlation was observed in the ENH state (n=67, r=0.146, p=0.237) or in the oral nucleos(t)ide analogue-treated group (n=267).ConclusionsHBsAg quantification using IRMA might be useful for discriminating different CHB phases and different stages of chronic liver disease.     

Hepatitis B Virus Induces Microtubule Stabilization to Promote Productive Infection through Upregulating Microtubule-associated Protein 1S

Background and AimsContinuous release and transmission of hepatitis B virus (HBV) is one of the main factors leading to chronic hepatitis B (CHB) infection. However, the mechanism of HBV-host interaction for optimal viral transport is unclear. Hence, we aimed to explore how HBV manipulates microtubule-associated protein 1S (MAP1S) and microtubule (MT) to facilitate its transport and release.MethodsThe expression of MAP1S or acetylated MT was investigated by immunofluorescence, RT-PCR, immunoblotting, and plasmid transfection. MAP1S overexpression or knockdown was performed by lentiviral infection or sh-RNA transfection, respectively. HBV DNA was quantified using q-PCR.ResultsSignificantly higher level of MAP1S in HepG2215 cells compared with HepG2 cells was detected using RT-PCR (p<0.01) and immunoblotting (p<0.001). Notably, stronger MAP1S expression was observed in the liver tissues of patients with CHB than in healthy controls. MAP1S overexpression or knockdown demonstrated that MAP1S promoted MT acetylation and reduced the ratio of HBV DNA copies inside to outside cells. Further, transfection with the hepatitis B virus X protein (HBx)-expressing plasmids induced significantly higher level of MAP1S than that in controls (p<0.0001), whereas HBVX⁻ mutant-encoding HBV proteins (surface antigen, core protein, and viral DNA polymerase) hardly affected its expression.ConclusionsThese results demonstrate that HBx induces the formation of stable MTs to promote the release of HBV particles through upregulating MAP1S. Thus, our studies delineate a unique molecular pathway through which HBV manipulates the cytoskeleton to facilitate its own transportation, and indicate the possibility of targeting MAP1S pathway for treatment of patients with CHB.     

Smoking is associated with steatosis and severe fibrosis in chronic hepatitis C but not B

Objective. The results of retrospective studies suggest an association between smoking, insulin resistance, steatosis and fibrosis in patients with chronic hepatitis C (CHC); no data are available for chronic hepatitis B (CHB). The purpose of this study was to evaluate the relationship, if any, of such factors on liver fibrosis in a cohort of patients with CHB and CHC. Material and methods. The study prospectively included 271 consecutive patients with CHB (n=95) or CHC (n=176) who had undergone liver biopsies. Each patient completed a questionnaire on smoking habits; anthropometric measurements and laboratory examinations were carried out and histological lesions were recorded. Results. In CHC patients, severe fibrosis was independently associated with a higher body mass index (BMI) (OR: 1.180, 95% CI: 1.028–1.354; p=0.019), heavy smoking (OR: 3.923, 95% CI: 1.356–11.348; p=0.012), higher alanine aminotransferase (ALAT) levels (OR: 1.010, 95% CI: 1.003–1.017; p=0.005) and alkaline phosphatase (ALP) levels (OR: 1.016, 95% CI: 1.001–1.030; p=0.03) and presence of necroinflammation (OR: 11.165, 95% CI: 1.286–96.970; p=0.029). Moreover, steatosis was independently associated with high gamma-glutamyl transpeptidase (GGT) values, heavy smoking and presence of necroinflammation. In CHB patients, no association between smoking habits and fibrosis or steatosis was noted. Conclusions. Heavy smoking is associated with severe fibrosis in CHC but not CHB. Heavy smoking is also significantly associated with steatosis in CHC and this could be the link between smoking and fibrosis progression.     

Diagnostic accuracy of serological diagnosis of hepatitis C and B using dried blood spot samples (DBS): two systematic reviews and meta-analyses

Background

Dried blood spots (DBS) are a convenient tool to enable diagnostic testing for viral diseases due to transport, handling and logistical advantages over conventional venous blood sampling. A better understanding of the performance of serological testing for hepatitis C (HCV) and hepatitis B virus (HBV) from DBS is important to enable more widespread use of this sampling approach in resource limited settings, and to inform the 2017 World Health Organization (WHO) guidance on testing for HBV/HCV.

Methods

We conducted two systematic reviews and meta-analyses on the diagnostic accuracy of HCV antibody (HCV-Ab) and HBV surface antigen (HBsAg) from DBS samples compared to venous blood samples. MEDLINE, EMBASE, Global Health and Cochrane library were searched for studies that assessed diagnostic accuracy with DBS and agreement between DBS and venous sampling. Heterogeneity of results was assessed and where possible a pooled analysis of sensitivity and specificity was performed using a bivariate analysis with maximum likelihood estimate and 95% confidence intervals (95%CI). We conducted a narrative review on the impact of varying storage conditions or limits of detection in subsets of samples. The QUADAS-2 tool was used to assess risk of bias.

Results

For the diagnostic accuracy of HBsAg from DBS compared to venous blood, 19 studies were included in a quantitative meta-analysis, and 23 in a narrative review. Pooled sensitivity and specificity were 98% (95%CI:95%–99%) and 100% (95%CI:99–100%), respectively. For the diagnostic accuracy of HCV-Ab from DBS, 19 studies were included in a pooled quantitative meta-analysis, and 23 studies were included in a narrative review. Pooled estimates of sensitivity and specificity were 98% (CI95%:95–99) and 99% (CI95%:98–100), respectively. Overall quality of studies and heterogeneity were rated as moderate in both systematic reviews.

Conclusion

HCV-Ab and HBsAg testing using DBS compared to venous blood sampling was associated with excellent diagnostic accuracy. However, generalizability is limited as no uniform protocol was applied and most studies did not use fresh samples. Future studies on diagnostic accuracy should include an assessment of impact of environmental conditions common in low resource field settings. Manufacturers also need to formally validate their assays for DBS for use with their commercial assays.

     

Clinical expression of insulin resistance in hepatitis C and B virus-related chronic hepatitis： Differences and similarities

AIM： To investigate the prevalence of the clinical pa- rameters of insulin resistance and diabetes in patients affected by chronic hepatitis C （CHC） or chronic hepa- titis B （CHB）. METHODS： We retrospectively evaluated 852 consec- utive patients （726 CHC and 126 CriB） who had under- gone liver biopsy. We recorded age, sex, ALT, type 2 diabetes and/or metabolic syndrome （MS）, body mass index （BMI）, and apparent disease duration （ADD）. RESULTS： Age, ADD, BMI, prevalence of MS and diabetes in patients with mild/moderate liver fibrosis were significantly higher in CHC. However, the degree of steatosis and liver fibrosis evaluated in liver biop- sies did not differ between CHC and CHB patients. At multivariate analysis, age, sex, BMI, ALT and diabetes were independent risk factors for liver fibrosis in CHC, whereas only age was related to liver fibrosis in CHB. We also evaluated the association between significant steatosis （〉 30%） and age, sex, BMI, diabetes, MS and liver fibrosis. Diabetes, BMI and liver fibrosis were associated with steatosis 〉 30% in CHC, whereas only age and BMI were related to steatosis in CriB. CONCLUSION： These data may indicate that hepatitis C virus infection is a risk factor for insulin resistance.     

Management of hepatitis B and C in special population

Chronic viral hepatitis is one of the leading causes of cirrhosis worldwide. Chronic hepatitis B is more common in the Asia-Pacific region due to the larger population and lower screening availability. Hepatitis C predominates in the west due to injection drug abuse. The discovery of (oral) direct-acting antiviral agents (DAAs) has changed the landscape of chronic hepatitis C (CHC) management. Nucleos(t)ide analogs (NUCs) have also changed the approach to the treatment of chronic hepatitis B (CHB). Oral NUCs and DAAs have excellent efficacy and patient acceptance as well as a lower risk of resistance. However, certain populations have no robust data and safety and efficacy of such oral drugs is still evolving. In this review, we provide an overview of the management of CHB and CHC in special populations, such as those with chronic kidney disease, pregnant women, healthcare workers, and those undergoing chemo- or immunosuppressive therapy.     

Serum aminotransferase levels instead of etiology affects the accuracy of transient elastography in chronic viral hepatitis patients

Background and Aim: It is still uncertain whether the accuracy of transient elastography (TE) in predicting the fibrosis stage is similar in chronic hepatitis B (CHB) and chronic hepatitis C (CHC). The present study was carried out to evaluate whether the underlying cause of chronic viral hepatitis affects the predictive accuracy of TE. Methods: Patients with CHB or CHC who were admitted for a liver biopsy were enrolled. Patients underwent TE and laboratory tests on the same day as the liver biopsy. The predictive accuracy was analyzed by comparing the areas under the receiver‐operating characteristic curves (AUCs). Results: Two‐hundred and seven patients were enrolled, comprising 121 CHB patients and 86 CHC patients). The patients were aged 44 ± 14 years, and 121 (58.5%) of them were men. AUCs for predicting significant fibrosis were significantly lower in CHB patients than in CHC patients (P = 0.043). The serum alanine aminotransferase (ALT) level was associated with overestimation and underestimation of the fibrosis stage, while the cause of chronic hepatitis was not. AUCs for predicting significant fibrosis were significantly lower in patients with ALT levels >70 IU/L (AUC, 0.830; 95% CI, 0.742–0.898) than in patients with ALT levels ≤70 IU/L (0.944; 0.882–0.979; P = 0.015). Conclusions: Although the predictive accuracy of TE in predicting significant fibrosis differed significantly with the cause of chronic hepatitis, this difference was due to the degree of serum ALT levels rather than to the cause of hepatitis itself. Avoiding performing TE in patients with elevated ALT levels is recommended to guarantee the predictive accuracy of TE.     

Serum Iron Markers in Patients With Chronic Hepatitis C Infection

Background

Patients with chronic hepatitis C (CHC) often have elevated serum iron markers, which may worsen liver injury.

Objectives

The aim of this study was to investigate the possible correlations between iron metabolism serum markers, HCV viral load, and liver disease severity in treatment-naive patients with chronic hepatitis C infection.

Patients and Methods

Eighty five patients with untreated hepatitis C chronic infection were investigated.

Results

Twenty one patients (24.7%) had elevated serum iron levels, and 29 subjects (34.1%) had severe liver fibrosis. Significantly elevated levels of serum iron (P < 0.05) and ferritin (P < 0.001), associated with lower levels of TIBC (P < 0.05) were detected in patients with severe fibrosis compared to no/mild fibrosis. Severe necroinflammatory activity was also significantly correlated with serum iron (P < 0.001), TIBC (P < 0.05), and ferritin levels (P < 0.001). Using multiple linear regression analysis, serum levels of ferritin and transferrin were the independent variables selected as being good predictors for advanced fibrosis and severe necroinflammatory activity. No significant correlations were detected between HCV viral load and iron markers.

Conclusions

This study revealed that serum iron markers (especially ferritin and transferrin) might be used as surrogate markers for both liver fibrosis and necroinflammatory activity.Patients with chronic hepatitis C (CHC) often have elevated serum iron markers, which may worsen liver injury.     

Association of Hepcidin mRNA Expression With Hepatocyte Iron Accumulation and Effects of Antiviral Therapy in Chronic Hepatitis C Infection

Background:

Iron overload is frequently observed in patients with chronic hepatitis C (CHC) and is associated with the increased risk of liver fibrosis and carcinogenesis. Hepcidin is a regulator of iron homeostasis and a component of innate immunity. Based on experimental studies, iron overload might be a result of low hepcidin synthesis in CHC.

Objectives:

The aim of this case-control study was to assess hepcidin mRNA expression in liver tissue of patients with CHC in terms of iron metabolism parameters, hemochromatosis (HFE) gene mutations, disease activity, and efficacy of antiviral treatment with pegylated interferon and ribavirin.

Patients and Methods:

A total of 31 patients with CHC, who were qualified for antiviral therapy, were compared with 19 patients with chronic hepatitis B (CHB). In both groups, liver function tests and serum iron parameters were assayed and hepcidin mRNA expression was measured in liver specimens using real time PCR with normalization to reference genes mRNA of stable expression.

Results:

Patients with CHC had lower hepcidin mRNA expression and more frequently iron deposits in hepatocytes than subjects with CHB did. In CHC group, hepcidin mRNA expression was positively correlated with alanine aminotransferase activity and serum iron concentration. Low expression of hepcidin had no correlation with tissue iron overload in those with CHC. In univariate analysis, HCV viral load and efficacy of antiviral treatment were not significantly associated with hepcidin mRNA expression.

Conclusions:

Further studies on the role of hepcidin in pathogenesis of CHC are needed to assess the potency of its use in antiviral treatment.     

Causes of death in patients with Non-alcoholic Fatty Liver Disease (NAFLD), alcoholic liver disease and chronic viral Hepatitis B and C

Introduction and objectivesCause of mortality in patients with chronic liver diseases (CLDs) may differ based on underlying etiology of liver disease. Our aim was to assess different causes of death in patients with the most common types of CLD using a national database from the United States.Materials and methodsDeath data from 2008 and 2018 from the National Vital Statistics System (NVSS) by the National Center for Health Statistics (NCHS) were used. The rank of cause-of-death for each etiology of CLDs was assessed. Causes of death were classified by the ICD-10 codes. Liver-related deaths included liver cancer, cirrhosis and CLDs.ResultsAmong a total of 2,826,531 deaths in 2018, there were 85,807 (3.04%) with underlying CLD (mean age at death 63.0 years, 63.8% male, 70.8% white). Liver-related mortality was the leading cause of death for all types of CLD [45.8% in non-alcoholic fatty liver disease (NAFLD), 53.0% in chronic hepatitis C (CHC), 57.8% in chronic hepatitis B (CHB), 81.8% in alcoholic liver disease (ALD)]. This was followed by death from cardiac causes (NAFLD 10.3%, CHC 9.1%, CHB 4.6%, ALD 4.2%) and extrahepatic cancer (NAFLD 7.0%, CHC 11.9%, CHB 14.9%, ALD 2.1%). Although liver cancer was the leading cause of cancer death, lung, colorectal and pancreatic cancer were also common causes of cancer death.ConclusionsAmong deceased patients with CLD, underlying liver disease was the leading cause of death. Among solid cancers, liver cancer was the leading cause of cancer-related mortality.     

Insulin resistance in chronic hepatitis B and C.

AIM: To determine whether insulin resistance occurs in patients with chronic hepatitis B (CHB) and chronic hepatitis C (CHC) and its relationship with the presence of liver fibrosis and steatosis. METHODS: Untreated patients with CHC (n=60) or CHB (n=40), similar in age, gender, body mass index and waist-hip ratio, were studied. Relationship between anthropometric, biochemical (fasting serum insulin, C-peptide, ferritin, iron, TNF-alpha, cholesterol, triglyceride, bilirubin, hemoglobin and platelet concentrations) and liver biopsy (43 CHC and 20 CHB patients) findings was investigated by insulin resistance determined via the homeostasis model assessment (HOMA-IR). RESULTS: The mean fasting serum insulin was 14.9 (11.9) mU/mL in CHC and 21.4 (17.4) in the CHB group (normal range 0.7-9; p=0.049) and mean HOMA-IR was 3.1 (2.6) in CHC versus 4.7 (4.1) in the CHB group (normal range 0.12-4.61; p=0.036). HOMA-IR was significantly associated with fibrosis stage in the CHC group (p=0.015), but not in the CHB group. CONCLUSION: Hyperinsulinemia occurs in chronic viral hepatitis B and hepatitis C; insulin resistance is associated with stage of fibrosis in hepatitis C.     

Predicting Liver-Related Events Using Transient Elastography in Chronic Hepatitis C Patients with Sustained Virological Response

Background/AimsFew studies have investigated prognostic factors for the development of liver-related events (LREs) in patients with chronic hepatitis C (CHC) who achieve sustained virological response (SVR).MethodsWe analyzed 190 patients with CHC who achieved SVR after treatment with pegylated interferon (peg-IFN) plus ribavirin. LREs were defined as any complications related to cirrhosis, hepatocellular carcinoma (HCC), or liver-related mortality.ResultsThe mean age was 54.1 years, and 84 of the patients (44.2%) were male. The mean liver stiffness (LS) value at SVR was 7.1±5.4 kPa. During the follow-up period (median, 43.0 months), LREs occurred in 10 patients (5.3%; HCC in eight patients, ascites in one patient, and liver-related mortality in one patient). By multivariate Cox regression analysis, age, α-fetoprotein level, and LS value were independent predictors for LRE development (all p<0.05). Patients with LS values ≥7.0 kPa had a greater risk (hazard ratio, 9.472; 95% confidence interval, 1.018 to 88.126; p=0.048) for LRE development compared to those with LS values <7.0 kPa.ConclusionsThe LS value at SVR is useful for predicting LRE development in CHC patients who achieve SVR after treatment with peg-IFN plus ribavirin. Thus, LRE surveillance strategies might be optimized according to the LS values at SVR, even with complete viral eradication.