Steatosis In Chronic Hepatitis Research Articles

Does Hepatic Steatosis Influence the Virological Response with Chronic Hepatitis B Patients Treated with Entecavir or Tenofovir Disoproxil Fumarate?

The effect of hepatic steatosis on the response to antiviral therapy administered in chronic hepatitis B patients is yet to be clarified. In this study, our aim was to determine the effect of hepatic steatosis on the virological response in chronic hepatitis B patients who were treated with entecavir or tenofovir disoproxil fumarate. This retrospective cohort study was performed using the data of liver biopsy-proven chronic hepatitis B patients with or without hepatic steatosis, who received entecavir or tenofovir disoproxil fumarate treatment between 2012 and 2017. The undetectable serum hepatitis B virus deoxyribonucleic acid level under treatment was defined as the complete virological response. The predictors of virological response were determined, and it was checked whether the virological response was affected by hepatic steatosis in chronic hepatitis B patients who have undergone entecavir or tenofovir disoproxil fumarate treatment. A total of 324 chronic hepatitis B patients, of which 203 (63%) were males, were included in the study. The median age of the patients was 42 years (range: 35-51 years). Hepatic steatosis was observed in 25% of the patients, and steatohepatitis in 4%. The median time to complete virological response was found to be 6 months (range: 3-9 months). In the full analysis model, the log hepatitis B virus deoxyribonucleic acid was determined as the factor most associated with virological response (P < .001). No statistically signifi- cant relationship was detected between hepatic steatosis and virological response (P = .409). Concomitant hepatic steatosis has no significant impact on the virological response in chronic hepatitis B patients who have undergone entecavir or tenofovir disoproxil fumarate treatment.

Evaluation of hepatosteatosis in patients with chronic hepatitis B virus infection

Background and study aimsThe current study aimed to investigate the frequency of hepatic steatosis in chronic hepatitis B (CHB) patients and determine the possible risk factors associated with its presence. Patients and methodsThis cross-sectional study retrospectively evaluated the medical records of 255 adult CHB patients visiting an infectious disease outpatient clinic. Patients with hepatitis B surface antigen positivity for >6 months and those who did not receive antiviral therapy were included in the study. The presence and stage of hepatic steatosis were determined through hepatobiliary ultrasonography. ResultsThe mean age of the patients was 40.6 ± 12.7 years. Hepatic steatosis was detected in 44.4 % of the patients through ultrasound imaging. Our findings showed that the detected steatosis prevalence in our patients with CHB was significantly higher compared to the highest prevalence of non-alcoholic steatohepatitis found in the general Turkish population (19.9 %) [RR 2.23 (1.75–2.86), p < 0.001]. CHB patients with steatosis had significantly higher age, triglyceride, and gamma-glutamyl transferase levels than those without steatosis (p < 0.05). No significant association was found between the presence of steatosis, sex, liver function test results, and platelet, alkaline phosphatase, cholesterol, alpha fetoprotein, or HBV-DNA levels. No significant relationship was found between aspartate aminotransferase (AST)/platelet ratio index (APRI) and steatosis was examined (p > 0.05). Post-hoc analysis showed a significant relationship between HBV-DNA levels and ALT, AST, and APRI scores. ConclusionOur data showed that hepatic steatosis is more common in CHB patients than in the general population. Older age and high triglyceride levels increased the risk of hepatic steatosis in CHB patients, consequently increasing GGT levels, which are indicative of liver damage, in these patients.

Steatosis in chronic hepatitis B and its impact on the therapeutic response to entecavir

Steatosis in chronic hepatitis B and its impact on the therapeutic response to entecavir

Prevalence and Severity of Steatosis in Chronic Hepatitis C patients

Background: Hepatitis C virus infection is a worldwide health issue. The rise in the prevalence of steatosis may be attributed to alterations in eating patterns, changes in the nutritional content of food, and changes in lifestyle, such as decreased physical activity and high sedentary lifestyle, as well as etio-pathogenic variables that influence individuals from infancy. Objective: To determine prevalence and severity of steatosis in chronic hepatitis C patients Methodology: The current study was cross sectional study piloted at the Gastroenterology Department, Hayatabad Medical Complex, Peshawar. The duration of study was six months after synopsis approval from August 2021 to January 2022. Totally 200 patients fulfilling the inclusion criteria were included in our study. Under aseptic conditions, a liver biopsy was done using an 18G lumbar puncture needle. All the Data analysis was done by using IBM SPSS version 24. Results: The overall frequency of steatosis was 80 (40%). On the basis of degree of steatosis, mild steatosis was observed in 53 (58.89%) subjects, moderate steatosis in 31 (34.44%) patients while severe steatosis was observed in 6 (6.67%) subjects. Conclusion: Our study concludes that steatosis is a common histological characteristic in patients with chronic hepatitis C virus infection. Steatosis is more prevalent in female patients than males. Study based on large sample size is recommended to get better findings. Keywords: Prevalence; Severity; Steatosis; Hepatitis C

Effect of MTTP -493G/T, I128T, Q95H and Q244E polymorphisms on hepatic steatosis in patients with chronic hepatitis

BackgroundChronic hepatitis C is characterized by a progressive deterioration of liver function and is involved in metabolic complications, such as hepatic steatosis. ObjectiveThe aim of this study was to investigate the role of host and viral characteristics associated with -493G/T (rs1800591), I128T (rs3816873), Q95H (rs61733139), and Q244E (rs17599091) Single Nucleotide Polymorphisms (SNPs) in the Microsomal Triglyceride Transfer Protein (MTTP) gene on hepatic steatosis in chronic hepatitis C. MethodsSNPs were genotyped by PCR-RFLP and analyzed in combination with host and viral characteristics by multiple logistic regression in different genetic models of inheritance. ResultsThe authors analyzed 236 patients with chronic hepatitis C, and 53% had hepatic steatosis. The mutated allele frequencies were > 5%, and the genotypes were in Hardy-Weinberg equilibrium (p ≥ 0.05). It was observed that patients with HCV genotype 3 infection (OR = 2.74, 95% CI 1.24‒6.06, p = 0.013), female sex (OR = 2.28, 95% CI 1.21‒4.28, p = 0.011) and moderate- and high-intensity liver inflammatory activity (A2-A3) (OR = 3.61, 95% CI 1.86‒7.01, p < 0.001) alone exhibited a higher risk of steatosis. The results of multiple logistic regression analysis for interaction showed that for the -493G/T SNP, when the GT/TT genotype (dominant model) and the GT genotype (codominant model) were each combined with HCV genotype 3 infection, an 11.51-fold (95% CI 2.08‒63.59, p = 0.005) and a 15.69-fold (95% CI 2.46‒99.85, p = 0.004) increased risk of steatosis, respectively, was observed. For the I128T SNP, when both the IT/TT genotype (dominant model) and the IT genotype (codominant model) were combined with HCV genotype 3 infection, an 8.51-fold (95% CI 1.59‒45.54, p = 0.012) and an 8.40 fold (95% CI 1.51‒46.91, p = 0.015) increased risk of steatosis, respectively, was observed. ConclusionThe present study showed that the viral genotype combined with the -493G/T and I128T SNPs in the MTTP gene influences hepatic steatosis.

Hepatitis C Virus Uses Host Lipids to Its Own Advantage.

Lipids and lipoproteins constitute indispensable components for living not only for humans. In the case of hepatitis C virus (HCV), the option of using the products of our lipid metabolism is “to be, or not to be”. On the other hand, HCV infection, which is the main cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma, exerts a profound influence on lipid and lipoprotein metabolism of the host. The consequences of this alternation are frequently observed as hypolipidemia and hepatic steatosis in chronic hepatitis C (CHC) patients. The clinical relevance of these changes reflects the fact that lipids and lipoprotein play a crucial role in all steps of the life cycle of HCV. The virus circulates in the bloodstream as a highly lipidated lipo-viral particle (LVP) that defines HCV hepatotropism. Thus, strict relationships between lipids/lipoproteins and HCV are indispensable for the mechanism of viral entry into hepatocytes, viral replication, viral particles assembly and secretion. The purpose of this review is to summarize the tricks thanks to which HCV utilizes host lipid metabolism to its own advantage.

Metabolic comorbidities and male sex influence steatosis in chronic hepatitis C after viral eradication by direct-acting antiviral therapy (DAAs): Evaluation by the controlled attenuation parameter (CAP)

BackgroundChronic hepatitis C (CHC) is associated with hepatic steatosis, related to both a direct viral action and metabolic features. Vice-versa data on hepatic steatosis after viral eradication by direct-acting antiviral agents (DAA) are undefined although the presence of metabolic alterations could strongly influence the occurrence of steatosis as in NAFLD. The controlled attenuation parameter (CAP) (FibroscanⓇ) allows the qualitative and quantitative evaluation of fatty liver. Aimto evaluate in patients with CHC whether hepatic steatosis diagnosed by CAP modifies after DAAs-induced sustained virologic response (SVR). MethodsData were collected the day of DAAs therapy starting and six months after SVR. CAP ≥ 248 dB/m defined the presence of steatosis. Results794 CHC SVR patients referring to 2 Italian Units were enrolled. Mean age was 64 ± 16 ys, 50% males, BMI 25.4 ± 4 kg/m2, genotype type-1 in 73%, type-3 in 8%. Prevalence of hepatic steatosis at baseline was 32% by US and 46% by CAP. De novo steatosis developed in 125 (29%), resolution in 122 (30%). At multivariate analysis de novo steatosis was independently associated with male sex (OR 1.7, CI 95% 1.09–2.67; p = 0.02) and baseline BMI (for unit increase OR 1.19, CI 95%1.11–1.29; p < 0.001). Baseline BMI (for unit increase OR 0.47, CI 95% 0.25–0.89; p = 0.02) and triglycerides (for unit increase OR 0.93, CI 95% 0.87–0.99; p = 0.03) prevented steatosis resolution after therapy. Conclusionsafter SVR de novo steatosis and resolution of baseline steatosis are closely related to the presence of metabolic comorbidities.

Impact of Hepatic Steatosis on the Antiviral Effects of PEG-IFNα-2a in Patients with Chronic Hepatitis B and the Associated Mechanism.

Objective To investigate the risk factors for hepatic steatosis in chronic hepatitis B (CHB), to determine its correlation with liver necroinflammation and fibrosis and response to peginterferon alpha-2a (PEG-IFNα-2a) antiviral therapy, and to explore the mechanisms underlying the poor antiviral effect of PEG-IFNα-2a in CHB patients with hepatic steatosis. Methods We analysed the impact of hepatic steatosis on the antiviral effect of PEG-IFNα-2a on CHB patients in a cohort of 226 patients who underwent pretherapeutic liver biopsy. To assess the complete response (CR), virological response (VR), and biochemical response (BR), the 226 patients were treated with PEG-IFNα-2a for 48 weeks and were followed-up for 24 weeks. The expressions of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in the liver tissue were detected in all patients to explore the possible mechanism of hepatic steatosis with regard to antiviral effects. Results The patients were divided into four groups based on the severity of hepatic steatosis: 119 with no steatosis, 76 with mild steatosis, 22 with moderate steatosis, and 9 with severe steatosis. In the hepatic steatosis groups, the proportions of male patients, patients aged >40 years, patients with hyperuricaemia, patients with a BMI > 23 kg/m2, and total cholesterol (TC), triglyceride (TG), glucose (GLU), and uric acid (UA) levels were significantly higher than those in the group without steatosis, whereas the alanine aminotransferase (ALT) and aspartate transaminase (AST) levels were significantly lower than those in the group without steatosis. The multivariate analysis results indicated that a BMI > 23 kg/m2 was independently associated with CHB patients with hepatic steatosis; the levels of baseline AST and UA were independently associated with CHB patients with significant hepatic steatosis, and the baseline AST level was independently associated with significant liver fibrosis. After 48 weeks of treatment and 24 weeks of follow-up, the rates of CR, VR, and BR had gradually decreased, whereas the severity of hepatic steatosis had increased. Conclusion Hepatic steatosis can reduce the efficacy of PEG-IFNα-2a in the treatment of CHB patients, and its mechanism may be related to the different HBcAg expression patterns in liver tissue.

Hepatic Steatosis in Chronic Hepatitis B as Measured by Controlled Attenuation Parameter: Frequency and Distribution.

To determine the frequency of liver steatosis in chronic hepatitis B (CHB) patients measured by controlled attenuation parameter (CAP) and to describe the distribution of fibrosis and inflammation in different steatosis grading. Cross-sectional study. Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University, Jinan, China, from January 2017 to December 2018. CHB patients who were evaluated with transient elastography (TE) for liver fibrosis and steatosis were included. Liver biochemical testing was performed within 3 days of TE measurements. Steatosis grading was assessed as S0 (no steatosis, CAP 0-247 dB/m), S1 (mild steatosis, CAP 248-267 dB/m), S2 (moderate steatosis, CAP 268-279 dB/m) and S3 (severe steatosis, CAP >=280 dB/m). Statistically comparisons of continuous variables or percentages were performed. A total of 1,621 CHB patients were included. The frequencies of liver steatosis in CHB patients were 35.4% (574 patients), of which 314 patients (19.3%) were diagnosed as severe steatosis (grading S3). Comparisons of age, gender and liver fibrosis in different steatosis grading revealed no statistical differences (p=0.109, 0.075 and 0.269, respectively). However, ALT values in patients with severe steatosis (grading S3) were higher than those patients with steatosis grading S0 (p<0.001) and S2 (p=0.047). Steatosis is common in CHB patients. Liver fibrosis seemed not discrepant in different steatosis grading. More obvious hepatic inflammation is seen in CHB patients with severe steatosis.

Prevalence and predictive factors of moderate/severe liver steatosis in chronic hepatitis C (CHC) infected patients evaluated with controlled attenuation parameter (CAP).

A novel controlled attenuation parameter (CAP) using FibroScan® has been developed for assessment of liver steatosis. The aim was to evaluate the frequency and associated factors for moderate/severe steatosis evaluated by CAP in CHC patients submitted to transient elastography (TE) by FibroScan® . CHC patients underwent TE with CAP evaluation. The classification of steatosis was defined as: CAP < 222 dB/m = S0; CAP ≥ 222 dB/m and <233dB/m = S1; ≥233 dB/m<290dB/m = S2 and >= 290 dB/m = S3. The prevalence of moderate/severe steatosis (CAP ≥ S2) and the related independent factors were identified by a logistic regression analysis. A significance level of 5% was adopted. 1104 CHC patients, 85% genotype-1 were included (mean age 55±11years; 46% male, mean BMI 25±4 Kg/m2 ). Systemic arterial hypertension and type 2 diabetes mellitus prevalences were 39% and 17%, respectively. Liver stiffness measurement ≥ 9.5 kPa was observed in 39% of patients and steatosis was identified in 50% (S1=7%, S2=28% and S3=15%). The variables independently associated with moderate/severe steatosis were: male gender (OR=1.35; P=.037; 95% CI:1.01-1.81); systemic arterial hypertension (OR=1.57; P=.002; 95% CI:1.17-2.10) and BMI (OR=1.17; P<.01;95% CI:1.12-1.22). In conclusion, when CAP was adopted as a tool to detect steatosis, genotype 1 CHC patients presented a high prevalence of moderate/advanced steatosis. In these patients, liver steatosis was associated mostly to metabolic factors (arterial hypertension and high BMI).

Effect of hepatitis B virus on steatosis in hepatitis C virus co-infected subjects: A multi-centre study and systematic review.

It remains unclear whether hepatitis B virus (HBV) infection may modify the severity of viral steatosis in patients coinfected with chronic hepatitis C virus (HCV). We examined the influence of coinfection with HBV on prevalence of steatosis in chronic hepatitis C in a multi-centre cohort of HBV-HCV subjects, and by performing a systematic review and meta-analysis of the literature. We centrally and blindly assessed steatosis prevalence and severity in a cohort of HBV-HCV coinfected subjects compared to HCV and HBV monoinfected controls and we performed a systematic review of studies addressing the prevalence of steatosis in HBV-HCV subjects compared to HCV controls. In the clinical cohort, we included 85 HBV-HCV, 69 HBV and 112 HCV subjects from 16 international centres. There was no significant difference in steatosis prevalence between the HBV-HCV and the HCV groups (33% vs 45%, P=.11). In subgroup analysis, lean HBV-HCV subjects with detectable HBV DNA had less steatosis than lean HCV subjects matched for HCV viremia (15% vs 45%, P=.02). Our literature search identified 5 additional studies included in a systematic review. Overall, prevalence of steatosis > 5% was similar in HBV-HCV infection compared to HCV (pooled odds ratio [OR] 0.91, 95% CI 0.53-1.6) although there was significant heterogeneity (I2 69%, P=.007). In conclusion, although the prevalence of steatosis is similar in HBV-HCV compared to HCV subjects, our analysis suggests that there may be an inhibitory effect of HCV-induced steatogenesis by HBV in certain subgroups of patients.

Effect of treatment with direct acting antivirals on body mass index and hepatic steatosis in chronic hepatitis C.

Direct Acting Agents (DAAs) have high cure rate but still lack the knowledge of their effect on hepatic steatosis in chronic hepatitis C (CHC). Controlled Attenuation Parameter (CAP), evaluated with transient elastography, could help in assessment of steatosis grades. We aim to evaluate the effect of DAAs on BMI and steatosis in CHC using CAP. This cohort study included 155 CHC Egyptian patients divided into three groups according to the DAAs regimens. All patients were subjected to pre-treatment and 3-months post-treatment evaluation including BMI, laboratory workup and liver stiffness measurement with simultaneous CAP determination using the (FibroScan®) M probe. Patients mean age was 45.78 ± 11.6 years, 60.6% were females, mean BMI 26.63 ± 2.75 and 18.1% were cirrhotic. Baseline assessment revealed no steatosis in 43.9%, 32.9% had mild-moderate steatosis and 23.2% had severe steatosis. The overall sustained virological response 12 was 93.6%. Follow-up revealed stationary steatosis in 56.7% of patients and regression in 21.3%. Mean pre-treatment CAP were significantly lower in responders 244.9 ± 62.4 dB/m versus non-responders; 300 ±28.4 dB/m (P = 0.04). ROC curve delineated 273 dB/m as best cutoff for detection of responders with an AUC of 0.801, sensitivity 68.2%, and specificity 100%. BMI significantly increased after treatment (P = 0.004) particularly in patients with worsened steatosis (P = 0.001). Steatosis significantly correlated with BMI (r = 0.3, P value = < 0.001). DAAs causes a significant change in steatosis grade in a subset of treated patients. Pretreatment CAP was significantly lower in responders. BMI significantly increases following treatment particularly in patients with worsened steatosis.

METABOLIC FACTORS ASSOCIATED WITH HEPATIC STEATOSIS AND FIBROSIS IN CHRONIC HEPATITIS C PATIENTS.

28May 2017 METABOLIC FACTORS ASSOCIATED WITH HEPATIC STEATOSIS AND FIBROSIS IN CHRONIC HEPATITIS C PATIENTS. Ramy M ElSharkawy , GhadaMostafa K1 , Mahmoud Saif-Al-Islam Abd Elfatah , Eman Mohamed Salah-Eldein , Tamer Elmokadem , Ahmed Hassan and Hydi Ahmed. Departments of Tropical Medicine and Gastroenterology, Faculty of Medicine, SohagUniversity. Pathology, Faculty of Medicine, Sohag University. Microbiology and Immunology, Faculty of Medicine, Sohag University. Clinical Pathology,Faculty of Medicine, Sohag University and Ibn Sina National College, Jeddah,Saudi Arabia.

PNPLA3 rs1010023 Predisposes Chronic Hepatitis B to Hepatic Steatosis but Improves Insulin Resistance and Glucose Metabolism.

PNPLA3 polymorphisms serve as the genetic basis of hepatic steatosis in normal population and lead to dysregulated glucose metabolism. Whether it underlies the hepatic steatosis and glucose homeostasis in chronic hepatitis B patients remains uncertain. Here, we investigated the PNPLA3 polymorphisms in biopsy-proven chronic hepatitis B patients with (CHB+HS group, n = 52) or without hepatic steatosis (CHB group, n = 47) and non-CHB subjects with (HS group, n = 37) or without hepatic steatosis (normal group, n = 45). When compared to the TT genotype, C-allele at PNPLA3 rs1010023 (CC and TC genotypes) conferred higher risk to hepatic steatosis in chronic hepatitis B patients (odds ratio (OR) = 1.768, 95% confidence interval (CI): 1.027–3.105; P = 0.045) independent of age, gender, and body mass index. In contrast to their role in hepatic steatosis, CC and TC genotypes of PNPLA3 rs1010023 were correlated to significant improvement of homeostasis model assessment index (HOMA-IR) as compared to TT genotype in the CHB+HS group. Downregulated fasting blood glucose also characterized the CHB+HS patients with C-allele at PNPLA3 rs1010023 (CC/TC versus TT: 4.81 ± 0.92 mmol/L versus 5.86 ± 2.11 mmol/L, P = 0.02). These findings suggest that PNPLA3 rs1010023 may predispose chronic hepatitis B patients to hepatic steatosis but protects them from glucose dysregulation by attenuating insulin resistance.

Association of IFNL3 Genotype with Hepatic Steatosis in Chronic Hepatitis C Patients Treated with Peginterferon and Ribavirin Combination Therapy.

Background: Genetic variation near the interferon lambda 3 (IFNL3) is known to be associated with response to pegylated interferon (pegIFN) and ribavirin combination therapy in patients with chronic hepatitis C virus (HCV) infection which is often accompanied by hepatic steatosis.Aims: We examined whether this genetic variation is associated with host lipids and treatment response.Methods: A total of 101 Japanese patients who had underwent liver biopsy before treatment with pegIFN and ribavirin for HCV genotype 1b infection were retrospectively analyzed for association between IFNL3 genotypes (rs8099917) and clinical factors including histopathological features of the liver. The presence of >5% steatosis in the liver specimen was defined as hepatic steatosis.Results: Forty patients (40%) had liver steatosis before therapy. Patients with IFNL3 minor genotype (non-TT) showed lower low-density lipoprotein cholesterol level (p=0.0045), higher γ-glutamyl transpeptidase level (p=0.0003) and higher prevalence of hepatic steatosis (p=0.0002). Advanced fibrosis [odds ratio (OR) 4.63, p=0.03] and IFNL3 major genotype (OR 0.13, p=0.001) were 2 independent factors for determining the presence of hepatic steatosis. Among the factors associated with sustained virological response, IFNL3 genotype was the most significant predictor, as per multivariate analysis.Conclusions: Our results confirmed that IFNL3 genotype is associated with hepatic steatosis as well as IFN response.

Correlation between non-alcoholic fatty liver disease (NAFLD) and dyslipidemia in type 2 diabetes

Non-alcoholic fatty liver means the presence of hepatosteatosis without significant alcohol consumption; it is strongly associated with obesity and metabolic disorder like type 2 diabetes and dyslipideamia. NASH may progress to advanced stages of hepatic fibrosis and cirrhosis. Increased body mass index and viral genotype contribute to steatosis in chronic hepatitis. The sonographic features of NAFLD include the presence of bright hepatic echotexture deep attenuation, and vascular blurring either singly or in combination. Dyslipidemia in patients with NAFLD is atherogenic in nature and it is characterized by increased levels of serum triglycerides and decreased levels of HDL cholesterol. Statins are potent lipid-lowering agents which decrease LDL cholesterol by 20-60%, decrease triglycerides by 10-33% and increase HDL cholesterol by 5-10% for the patients with NAFLD.

TM6SF2 E167K variant is associated with severe steatosis in chronic hepatitis C, regardless of PNPLA3 polymorphism.

A common non-synonymous polymorphism, E167K, in transmembrane six superfamily member 2 (TM6SF2) gene has been recently associated with an increased hepatic triglyceride content, dyslipidemia and liver fibrosis in NAFLD patients. We investigated possible associations between the TM6SF2 variants and liver lesions in chronic hepatitis C. 148 consecutive patients with biopsy proven anti-HCV/HCV-RNA-positive chronic hepatitis, naive for antiviral therapy, were genotyped for TM6SF2 E167K and PNPLA3 I148M variants. The score of liver steatosis was higher in the 18 patients with TM6SF2 E167K variant (mean 1.9 ± 1.3) than in the 130 homozygotes for TM6SF2 167E allele (1.1 ± 1.1, P = 0.02), and the prevalence of a steatosis score ≥ 3 was 33.3% vs. 12.3% respectively (P = 0.02). No difference in necroinflammatory or fibrosis scores was found between the two groups. A general linear model identified as independent predictors of steatosis TM6SF2 E167K and PNPLA3 M148M variants and waist circumference (P = 0.0376, P = 0.0069 and P = 0.0273 respectively). This is the first demonstration that TM6SF2 E167K variant is an independent predictor of liver steatosis in chronic hepatitis C.

Sa1053 High Hepatic Iron and Low Serum Betaine Levels Are Associated With Hepatic Steatosis Among Males With Chronic Hepatitis B

Nonalcoholic fatty liver disease (NAFLD) is an important cause of liver disease. The prevalence of hepatic steatosis in chronic hepatitis B (CHB) is not well understood. There are reports that low betaine level contributes to hepatic steatosis by increasing oxidative stress. Our aims are to determine the prevalence and impact of hepatic steatosis on CHB and the role of betaine in this disease state. In a single center, CHB patients with pretreatment liver biopsy between 1998 and 2013 were reviewed. The analysis excluded patients with alcoholism (>50g/day), HCV, HDV or HIV coinfection, other liver diseases and liver transplantation. To date, 231 patients (75% Asians) met the inclusion criteria. Serum betaine levels were measured in 40 randomly selected serum samples from patients with and without steatosis in both genders. Results: Total 127 (55%) pts had hepatic steatosis in biopsied tissue. Steatosis was more common in males (91/136, 67%) than females (36/95, 38%) [p=0.0001]. Among those with steatosis, males (mean 41.5 yrs) were younger than females (mean 48.5 yrs) [p=0.02]. For both genders, those with steatosis had higher rate of severe hepatic inflammation (M 63%, F 30%) compared to those without (M 5%, F 3%) [p=0.0001]. Advanced fibrosis (Stage 3+4) was more frequent in males (14%) than females (8%). Hepatic iron was present in 47 of 91 (52%) males with steatosis but in only 7 of 36 (19%) females with steatosis [p=0.0001]. Females with steatosis had higher rates of elevated LDL cholesterol (64% vs. 41%) [p=0.04], triglyceride (31% vs.13%) [p=0.02] and increased body weight (150lbs vs. 126lbs) [p=0.001] compared to those without. The lipid profiles and weight, however, were similar in males with and without steatosis. Interestingly, males with steatosis (N=10) had lower serum level of betaine compared those without steatosis (N=10) [28.3 vs. 43.3 umol/L; p=0.056]. In contrast, females with (N=10) or without steatosis (N=10) had similar betaine levels [42.9 vs. 39.3umol/L; p=0.3]. Viral factors such as serum HBV DNA levels, HBeAg status were not different between those with and without steatosis. Conclusions: High prevalence of hepatic steatosis is identified in this predominantly Asian cohort of patients with chronic hepatitis B. Steatosis is more common in males. For both genders, steatosis is associated with more severe hepatic inflammation. There appears to be a gender difference in predisposition to steatosis. In females, metabolic syndrome is a major contributing factor. In males, presence of hepatic iron and lower betaine levels correlate with steatosis and inflammation. It is possible that betaine attenuates iron-iduced oxidative stress in the liver. The gender differences in steatosis predisposition in CHB warrant further evaluation. Its understanding likely will contribute to better preventive and therapeutic strategies.

Accuracy of Ultrasonography and Different CT Techniques in Diagnosis and Grading of Hepatic Steatosis in Chronic Hepatitis C Virus Patients

Objective: This study aims to assess the diagnostic utility of ultrasonography and which methods of measuring attenuation on computed tomography scans is best for detection and grading of hepatic fat content in patients with chronic hepatitis C virus (HCV) infection. Materials and Methods: This study included 65 patients, withchronic hepatitis C virus infection, who had liver biopsies as a part of pre-requirement for interferon therapy. All patients submitted to ultrasound; non enhanced and enhanced CT. Attenuation measurements were obtained from 3 regions of interest in the liver and three in the spleen on both unenhanced and portal phase contrast-enhanced CT images. Hepatic attenuation measurements were analyzed both with and without normalization with the spleen. Normalization included both differences and ratios between hepatic and splenic attenuation values. Average attenuation values of the liver were compared with pathologic fat content, as were the differences and ratios between hepatic and splenic attenuation values. Results: Ultrasound had a sensitivity of 76% and specificity 73.3% in the diagnosis of hepatic steatosis. Also ultrasound accurately graded 41 out of the 65 (63.1%) patients included in the study. The simple measurement of hepatic attenuation on non enhanced CT (CTL) had the best parameters for diagnosis of hepatic steatosis with sensitivity 83%, specificity 93.3% and positive predictive value (PPV) 97.6%. All series of R2 values for the unenhanced CT scans were higher than those for the contrast-enhanced images. The R2 values for simple liver attenuation measurement without comparison with splenic attenuation were higher than the values in which splenic measurements were considered. Conclusion: Ultrasound and non enhanced CT can be used as screening tools for detection of hepatic steatosis in patients with chronic hepatitis C virus patients. Simple measurement of hepatic attenuation on unenhanced CT is more accurate than differential liver spleen values. Also, unenhanced CT can differentiate between mild-moderate and severe steatosis.

Insulin resistance and liver steatosis in chronic hepatitis C infection genotype 3.

Hepatitis C virus (HCV) infection is a common chronic liver disease worldwide. Non-alcoholic fatty liver disease and insulin resistance (IR) are the major determinants of fibrosis progression and response to antiviral therapy. The pathogenetic link between IR and chronic HCV infection is complex, and is associated with HCV genotype. Liver steatosis is the most common in the patients infected with genotype 3 virus, possibly due to direct effects of genotype 3 viral proteins. To the contrary, hepatic steatosis in the patients infected with other genotypes is thought to be mostly due to the changes in host metabolism, involving IR. In HCV genotype 3, liver steatosis correlates with viral load, reverts after reaching the sustained virologic response and reoccurs in the relapsers. A therapeutic strategy to improve IR and liver steatosis and subsequently the response to antiviral treatment in these patients is warranted.