Hepatitis C virus (genotype 4)-associated mixed cryoglobulinemia vasculitis: effects of antiviral treatment

El-Khayat, Hisham R; Fouad, Yasser; Ahmad, Ezzat Ali; Amin, Hussein El; ismael, faten; Rizk, Amal

doi:10.1007/s12072-011-9303-x

Cited by 11 publications

(8 citation statements)

References 19 publications

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“…When comparing RCTs versus non-RCT studies, we observed a pooled SVR rate of 60% (CI: 53–68%) in the six RCTs[10, 13, 16, 18, 54, 93] compared to 52% (CI: 49–55%) in 45 non-RCTs[11, 12, 14, 15, 27, 28, 34, 35, 37–42, 45, 46, 48, 53, 55, 56, 59, 62, 63, 65–67, 69, 71–73, 75–81, 83–85, 88, 90, 91, 95, 96] (Figure 3). This finding was statistically significant with p =0.043.…”

Section: Resultsmentioning

confidence: 96%

“…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%

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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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Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

Meta-analysis

Yee

Nguyen

Zhang

et al. 2014

European Journal of Gastroenterology &Amp; Hepatology

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“…Available data about the role of SVR in MC CHC treatment were quite heterogeneous because treatment with standard IFN and PEG-IFN with different genotypes and populations were included. Global SVR ranges from 30 to 52 % [10,11], and these lower rates of virological response are likely related to some characteristics of these populations when compared to MC-negative patients. For example, in the examined studies [37], only symptomatic MC patients were included, and consequently, a considerable number of co-morbidities were present with a probable impact on virological response and rate of treatment interruption.…”

Section: Discussionmentioning

confidence: 99%

Role of IL28B genotyping in patients with hepatitis C virus-associated mixed cryoglobulinemia and response to PEG-IFN and ribavirin treatment

et al. 2015

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The role of interleukin (IL) 28B in the treatment of chronic hepatitis C (CHC) has recently been examined in many studies, while a possible relationship between IL28B and the presence of mixed cryoglobulinemia (MC) remains to be clarified. In this study, we analyzed the influence of IL28B rs8099917/rs12979860 on the presence of MC and the role in treatment with PEG-IFN. We retrospectively examined 541 patients affected by CHC who were treated with pegylated interferon (PEG-IFN) and ribavirin from 2003 to 2012. We included all treatment-naïve patients without other viral co-infections or major contraindications to the PEG-IFN and ribavirin standard of care. One hundred seventy-five patients (32.3 %) had MC; 49 of these (33.3 %) had symptomatic MC. The IL28B rs8099917/rs12979860 TT/CC genotype was the most frequent in MC-positive patients with sustained virological response (SVR) (p < 0.001), while the TG/TC genotype was most frequent in non-SVR (p < 0.001). The TT/CC genotype was found to be the main positive predictive factor of MC in HCV patients (OR = 11.914; IQR = 7.092-18.776; p < 0.001); HCV genotype 2/3 was the strongest positive predictive factor of SVR (OR = 10.448; IQR = 8.352-21.561; p < 0.001); IL28B rs8099917/rs12979860 TT/CC was a better predictive factor than rs12979860 CC alone (OR = 9.829 vs. 2.663). Negative predictive factors were Metavir score F3-F4 (OR = 0.625; IQR = 0.416-0.779; p = 0.008), insulin-resistance (OR = 0.315; IQR = 0.224-0.585; p < 0.001) and presence of symptoms (OR = 0.716; IQR = 0.492-0.855; p < 0.001). IL28B rs8099917/rs12979860 is useful in the treatment of MC-positive HCV patients with PEG-IFN and ribavirin; the TT/CC genotype is associated with SVR, the TG/TC with non-SVR; TT/CC is also predictive of MC in HCV patients.

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“…Rituximab monotherapy effectively alleviated MC symptoms in about 71.4%84% HCV patients [111,112] . Rituximab given in combination peg IFNaribavirin was evaluated in patients with severe HCVcryo, resistant to IFNa combination therapy.…”

Section: Antiviral Treatmentmentioning

confidence: 98%

Hepatitis C virus and neurological damage

Mathew

Faheem

Ibrahim

et al. 2016

WJH

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Author contributions: Mathew S and Faheem M contributed equally to this manuscript; Qadri I conceived and designed the topic; Mathew S, Faheem M, Ibrahim SM, Iqbal W and Rauff B contributed to materials and wrote the paper; Faheem M, Ibrahim SM, Iqbal W, Rauff B, Fatima K and Qadri I contributed to proof reading of the manuscript.Supported by KACST large R and D grant to Ishtiaq Qadri (#162-34).Conflict-of-interest statement: Authors declare no conflict of interests for this article. AbstractChronic hepatitis C virus (HCV) infection exhibits a wide range of extrahepatic complications, affecting various organs in the human body. Numerous HCV patients suffer neurological manifestations, ranging from cognitive impairment to peripheral neuropathy. Overexpression of the host immune response leads to the production of immune complexes, cryoglobulins, as well as autoantibodies, which is a major pathogenic mechanism responsible for nervous system dysfunction. Alternatively circulating inflammatory cytokines and chemokines and HCV replication in neurons is another factor that severely affects the nervous system. Furthermore, HCV infection causes both sensory and motor peripheral neuropathy in the mixed cryoglobulinemia as well as known as an important risk aspect for stroke. These extrahepatic manifestations are the reason behind underlying hepatic encephalopathy and chronic liver disease. The brain is an apt location for HCV replication, where the HCV virus may directly wield neurotoxicity. Other mechanisms that takes place by chronic HCV infection due the pathogenesis of neuropsychiatric disorders includes derangement of metabolic pathways of infected cells, autoimmune disorders, systemic or cerebral inflammation and alterations in neurotransmitter circuits. HCV and its pathogenic role is suggested by enhancement of psychiatric and neurological symptoms in patients attaining a sustained virologic response followed by treatment with interferon; however, further studies are required to fully assess the impact of HCV infection and its specific antiviral targets associated with neuropsychiatric disorders. REVIEWSubmit a

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Hepatitis C virus (genotype 4)-associated mixed cryoglobulinemia vasculitis: effects of antiviral treatment

Abstract: The results indicated that treatment with PEG-IFN alfa-2a plus ribavirin can achieve a complete clinical response in patients with HCV-related MC. Complete clinical response correlates with the eradication of HCV.

Cited by 11 publications

References 19 publications

Meta-analysis

Meta-analysis

Role of IL28B genotyping in patients with hepatitis C virus-associated mixed cryoglobulinemia and response to PEG-IFN and ribavirin treatment

Hepatitis C virus and neurological damage

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