Adipokines and insulin resistance, predictors of response to therapy in Egyptian patients with chronic hepatitis C virus genotype 4

Saad, Yasmin; Ahmed, Amira; Saleh, Doa’a A.; Doss, Wahid

doi:10.1097/meg.0b013e32835f2726

Cited by 21 publications

(17 citation statements)

References 53 publications

(56 reference statements)

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“…On the other hand, the highest percent of relapsers could be seen in patients with severe activity. These findings are the same conclusion of the study done by Saad et al [19] on 100 patients with chronic HCV genotype 4 [19].…”

Section: Discussionsupporting

confidence: 92%

Pathology Predictors of Response to Combined Therapy of Chronic HCV Patients; Is it Applicable in the DAA Era?

El-Sayed

Esmat

Doss

et al. 2016

GHOA

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Introduction & aim: Liver biopsy has been considered the ''gold standard'' of diagnosis, the most direct way of visualizing the necroinflammatory and architectural status of liver in HCV patients planned for therapy. We aimed to study the relation between pathological findings in liver biopsy and their impacts on sustained virological response (SVR) in HCV patients receiving pegylated interferon and ribavirin (Peg/Riba). Methods:A retrospective analysis on data collected from 1486 HCV patients receiving Peg/Riba between May 2012 and May 2013 at the National Hepatology and Tropical Medicine Research Institute (NHTMRI). Initial labs before treatment including percutaneous liver biopsy were analyzed in relation to virological response.Results: 982 (66.1%) of patients were males and 504 (33.9%) were females. The mean age was (43.72 ± 9.527y), with 1008 (67.8%) more than 40 years. Higher SVR achieved in patients with no or mild steatosis than moderate to severe degrees (96% vs 4%, p: 0.001). More than 60% of patients with no or mild fibrosis showed SVR (p: 0.04). Patients with mild activity showed much higher SVR than patients with severe or advanced activity (67.1% vs 32.9%, p: 0.001). Negative viral load at w12 was significantly higher in patients with no or mild fibrosis (96.7% vs 94.9%, p: 0.004), no or mild steatosis (95.7% vs 94%, p: 0.024), but was not related to activity (95.8% vs 95.7%, p: 0.869). Conclusion:Steatosis, fibrosis and activity affected treatment outcome and could directly affect treatment decision. The response rate of peginterferon alpha 2a was comparable to alpha 2b. These findings are important to decide antiviral course in patients with multiple DAA RAVs leading to failure.

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Section: Discussionsupporting

confidence: 92%

Pathology Predictors of Response to Combined Therapy of Chronic HCV Patients; Is it Applicable in the DAA Era?

El-Sayed

Esmat

Doss

et al. 2016

GHOA

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“…There were 51 studies with a total of 11,102 HCV-4 patients included in the primary analysis (Table 1)[10–16, 18, 27, 28, 34, 35, 37–42, 45, 46, 48, 53–56, 59, 62, 63, 65–67, 69, 71–73, 75–81, 83–85, 88, 90, 91, 93, 95, 96]. The majority of studies (40/51, 78%) originated from the Middle East[10–13, 15, 16, 18, 27, 28, 34, 35, 37, 40–42, 45, 46, 53–56, 59, 62, 63, 66, 67, 69, 72, 75, 78, 80, 81, 83–85, 88, 91, 95] and Europe (9/51, 18%)[14, 38, 39, 65, 71, 76, 79, 93, 96].…”

Section: Resultsmentioning

confidence: 99%

“…The majority of studies (40/51, 78%) originated from the Middle East[10–13, 15, 16, 18, 27, 28, 34, 35, 37, 40–42, 45, 46, 53–56, 59, 62, 63, 66, 67, 69, 72, 75, 78, 80, 81, 83–85, 88, 91, 95] and Europe (9/51, 18%)[14, 38, 39, 65, 71, 76, 79, 93, 96]. One originated in Cameroon[77] and one multi-center study was conducted in 19 countries[73].…”

Section: Resultsmentioning

confidence: 99%

Meta-analysis

Yee

Nguyen

Zhang

et al. 2014

European Journal of Gastroenterology &Amp; Hepatology

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Background The burden of hepatitis C virus genotype 4 (HCV-4) is high in Africa and East Mediterranean countries. Previous reports estimate sustained virologic response (SVR) rates in HCV-4 to be ~20–70%. However, many of these studies are limited by different study designs and small sample sizes. Aim Our aim was to evaluate treatment outcome and host/viral factors on SVR in HCV-4 patients treated with pegylated interferon and ribavirin (PEG IFN+RBV) in a systematic and quantitative fashion. Methods A comprehensive literature search in MEDLINE and EMBASE for ‘genotype 4’ was conducted in November 2013. Abstracts from AASLD, APASL, DDW, and EASL in 2012/2013 were reviewed. Inclusion criteria were original studies with ≥25 treatment-naïve HCV-4 patients treated with PEG IFN+RBV. Exclusion criteria were co-infection with HIV, HBV, or other genotypes. Effect sizes were calculated using random-effects models. Heterogeneity was determined by Cochrane Q-test (p-value <0.05) and I-squared statistic (>50%). Results We included 51 studies (11,102 HCV-4 patients) in the primary analysis. Pooled SVR was 53% (95% CI: 50–55%) (Q-statistic = 269.20, p<0.05; I2 = 81.43). On sub-group analyses, SVR was significantly associated with lower viral load, OR 3.05 (CI 1.80–5.17, p<0.001); mild fibrosis, OR 3.17 (CI 2.19–4.59, p<0.001); and favorable IL28B polymorphisms, rs12979860 CC versus CT/TT, OR 4.70 (CI 2.87–7.69, p<0.001), and rs8099917 TT versus GT/GG, OR 5.21 (CI 2.31–11.73, p<0.001). Conclusions HCV-4 patients treated with PEG IFN+RBV may expect SVR rate of ~50%. Lower viral load, mild fibrosis, and favorable IL28B (rs12979860 CC and rs8099917 TT) are positively associated with SVR.

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“…Hypoadiponectinemia was reported to be a positive predictor for SVR in G4 HCV infection, 32 but whether pretherapy HOMA-IR levels determine SVR remains controversial. [33][34] In the current study, neither HOMA-IR nor adiponectin levels independently affected the therapeutic response in patients mainly infected with G1 or G2 HCV.…”

Section: Discussionmentioning

confidence: 99%

The evolving relationship between adiponectin and insulin sensitivity in hepatitis C patients during viral clearance

et al. 2017

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(2017) The evolving relationship between adiponectin and insulin sensitivity in hepatitis C patients during viral clearance, Virulence, 8:7, 1255-1264, DOI: 10.1080/21505594.2017 ABSTRACT Background: The evolution of the relationship between adiponectin and insulin sensitivity in hepatitis C virus (HCV) patients during viral clearance is unclear and warrants investigation. Methods: A prospective study including 747 consecutive chronic hepatitis C (CHC) patients, of whom 546 had completed a course of anti-HCV therapy and underwent pre-, peri-and post-therapy surveys for anthropomorphic, viral, metabolic and hepatic profiles and adiponectin levels, was conducted in a tertiary care center. Results: Multivariate analyses indicated associations of sex, triglyceride levels and hepatic steatosis with adiponectin levels and of triglyceride levels and interferon λ3 (IFNL3) genotype with homeostasis model assessment-estimated insulin resistance (HOMA-IR) levels before anti-HCV therapy. In patients with a sustained virological response (SVR; n D 455), at 24 weeks post-therapy, sex, BMI, aspartate aminotransferase to platelet ratio index (APRI), HOMA-IR and steatosis were associated with adiponectin levels, and IFNL3 genotype was associated with HOMA-IR levels. GEE analysis demonstrated that SVR affected longitudinal trends in adiponectin levels. Compared with pre-therapy levels, adiponectin and APRI levels decreased 24 weeks post-therapy in SVR patients, regardless of baseline insulin resistance (IR). However, HOMA-IR levels decreased in SVR patients with baseline IR but increased in those without baseline IR. Compared with controls, immunohistochemical studies showed that pre-therapy CHC patients had higher hepatic adiponectin expression associated with hepatic fibrosis. Conclusions: During HCV infection, adiponectin may affect insulin sensitivity through triglycerides. After viral clearance, adiponectin levels were directly associated with insulin sensitivity and decreased upon improved hepatic fibrosis; with a link to the IFNL3 genotype, insulin sensitivity improved only in patients with baseline IR.

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Adipokines and insulin resistance, predictors of response to therapy in Egyptian patients with chronic hepatitis C virus genotype 4

Abstract: BMI, pretreatment high leptin levels, and IR are negative predictors for SVR and pretreatment low adiponectin levels are an independent positive predictor for SVR in HCVG4.

Cited by 21 publications

References 53 publications

Pathology Predictors of Response to Combined Therapy of Chronic HCV Patients; Is it Applicable in the DAA Era?

Pathology Predictors of Response to Combined Therapy of Chronic HCV Patients; Is it Applicable in the DAA Era?

Meta-analysis

The evolving relationship between adiponectin and insulin sensitivity in hepatitis C patients during viral clearance

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