To clarify the impact of adherence, we treated 122 genotype 1 high viral titer chronic hepatitis C patients with pegylated interferon (peg-IFN) and ribavirin for 48 weeks at nine referral hospitals, and evaluated the prognostic factors with a focus on the adherence to the treatment. This study included 68 (55.7%) treatment-naïve patients and 54 (44.3%) patients who did not respond to the previous treatment. Multivariate analysis revealed adherence to peg-IFN and ribavirin as the only significant predictor. Sustained virological response (SVR) rate was 72.2%, 19.0%, and 27.3% in patients given ≥80%, 60%–80%, and &lt;60% dose peg-IFN, respectively, and was 68.6%, 41.2%, and 5.3% in those given ≥80%, 60%–80%, and &lt;60% dose ribavirin, respectively. SVR rate sharply fell when exposure to peg-IFN was below 80% whereas it decreased in a stepwise manner as for ribavirin. Therefore, ≥80% of peg-IFN and as much as possible dose of ribavirin are desired to achieve SVR in the treatment of genotype 1 high viral titer chronic hepatitis C.

Makoto Numata

Tatehiro Kagawa

Sei-ichiro Kojima

Shunji Hirose

Naruhiko Nagata

Koichi Shiraishi

Norihito Watanabe

Hirokazu Shiozawa

Yasuhiro Nishizaki

Shigeyuki Motegi

Shinji Takashimizu

Jun-ichiro Kamochi

Mitsuru Wasada

Takashi Ohno

Yoshihiro Tei

Atsushi Nakano

Takuji Yamada

Kazuhiro Atsukawa

Tetsu Watanabe

Tetsuya Mine

Differential Impact of Adherence to Pegylated Interferon and Ribavirin in the Treatment of Genotype 1 High Viral Titer Chronic Hepatitis C

Multiple extrahepatic manifestations have been associated with chronic hepatitis C, the most important among them being cryoglobulinemia, glomerulonephritis, porphyria cutanea tarda, lichen planus, seronegative arthritis, and lymphoproliferative disorders as in the sudies of Bonkovsky and Mehta (2001) and El-Serag et al. (2002). We will discuss in this paper chronic hepatitis C- related kidney disease and course and management of patients with chronic hepatitis C in special circumstances like hemodialysis and kidney transplantation.

Ashik Hayat

Ahmad Mitwalli

Hepatitis C and Kidney Disease

The present studies assessed the level of tumor necrosis factor receptor (TNFR) expression in peripheral blood mononuclear cells (PBMCs) subsets from patients with chronic HCV undergoing interferon <svg style="vertical-align:-0.1254pt;width:8.9375px;" id="M1" height="7.1750002" version="1.1" viewBox="0 0 8.9375 7.1750002" width="8.9375"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,7.175)">
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			<text transform="matrix(1,0,0,-1,-71.95,66.44)">
				<tspan style="font-size: 12.50px; " x="0" y="0">𝛼</tspan>
			</text>

		</g>
	</g>
</svg>/ribavirin-based therapy (Ifn/R).  <i  >Methods</i>. TNFR family member mRNA expression was determined using quantitative real-time PCR assays (RTPCRs) in PBMC from 39 HCV+ patients and 21 control HCV<svg style="vertical-align:-0.0pt;width:10.825px;" id="M2" height="4.5999999" version="1.1" viewBox="0 0 10.825 4.5999999" width="10.825"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,4.6)">
		<g transform="translate(72,-68.32)">
			<text transform="matrix(1,0,0,-1,-71.95,68.37)">
				<tspan style="font-size: 12.50px; " x="0" y="0">−</tspan>
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		</g>
	</g>
</svg> patients.  Further subset analysis of HCV + patients (untreated (U), sustained virological responders (SVR), and nonresponders (NR)/relapsers (Rel)) PBMC was performed via staining with anti-CD123, anti-CD33, anti-TNFR1 or via RTPCR for TNFR1 mRNA. <i  >Results</i>. A similar level of TNFR1 mRNA in PBMC from untreated HCV+ genotype 1 patients and controls was noted. TNFR1 and TNFR2 mRNA levels in PBMC from HCV+ patients with SVR were statistically different than levels in HCV(<svg style="vertical-align:-0.0pt;width:10.825px;" id="M3" height="4.5999999" version="1.1" viewBox="0 0 10.825 4.5999999" width="10.825"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,4.6)">
		<g transform="translate(72,-68.32)">
			<text transform="matrix(1,0,0,-1,-71.95,68.37)">
				<tspan style="font-size: 12.50px; " x="0" y="0">−</tspan>
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		</g>
	</g>
</svg>) patients. A significant difference was noted between the peak values of TNFR1 of the CD123+ PBMC isolated from SVR and the NR/Rel. <i  >Conclusion</i>. Upregulation of TNFR1 expression, occurring in a specific subset of CD123+ dendritic cells, appeared in HCV+ patients with SVR.

Raul Cubillas

Katherine Kintner

Frances Phillips

Nitin J. Karandikar

Dwain L. Thiele

Geri R. Brown

Tumor Necrosis Factor Receptor 1 Expression Is Upregulated in Dendritic Cells in Patients with Chronic HCV Who Respond to Therapy

<i>Background/aims</i>. This study aims to determine the distribution and clinical features of HBV-genotypes in a population of immigrants affected by HBV-infection. <i>Methods</i>. Between 01/2003 and 03/2009, 1623 immigrants were tested for HBV-infection. Biochemical and virological activities were determined in HBsAg-positive patients; HBV-genotypes were determined, by the INNO-LiPA HBV Genotyping, in the subjects with HBV DNA detectable. In every patient we evaluated the stage and classified the infection as inactive carrier, mild or moderate/severe chronic hepatitis, cirrhosis, and/or HCC. <i>Results</i>. Among the tested subjects, 191 (11.7&#x25;) resulted HBsAg-positive, and in 144/191 (75.4&#x25;) serum HBV-DNA was detectable. The genotype distribution was as follows: 45,13&#x25; genotype E, 18,1&#x25; genotype D, 15,3&#x25; genotype B, 13,2&#x25; genotype C, 4,9&#x25; genotype A, 3,5&#x25; mixed genotypes (A–D). The evaluation of liver disease degree showed that 24.6&#x25; patients were inactive carriers of HBV infection, 19.4&#x25; presented a immunotolerance phase, 34.5&#x25; had mild chronic hepatitis, 13.6&#x25; had a moderate/severe chronic hepatitis, 6.3&#x25; had cirrhosis, and 1.6&#x25; presented HCC. <i>Conclusions</i>. Our study evidences a high prevalence of HBV-infection in immigrants, and the potentiality of migratory flow in the introduction of genotype non-D hepatitis B virus. The Hepatitis B virus genotypes presented significant differences in epidemiological and clinical characteristics.

Gaetano Scotto

Domenico Martinelli

Rocco Di Tullio

Vincenzina Fazio

Epidemiological and Clinical Features of Hepatitis B Virus Genotypes among Immigrants in Southern Italy

HCV-Ag-specific TH17 cells secrete IL17, a cytokine involved in autoimmune diseases and regulated by IL10 and TGF-b. 5&#x2013;12&#x25; of patients with chronic HCV infection have hypothyroidism. We evaluated the role of these cytokines in this patients by determining serum concentration of TsH, T3, free T4, IL2, IL10, IL12, IL17, TGF-b, anti-TG, TPO, CCP, GBM, and cardiolipin antibodies in 87 chronically noninterferon treated HCV-infected patients. 20 patients (group A) had elevated TsH values (&#x3E;5&#x2009;<svg     style="vertical-align:-3.56265pt;width:9.5625px;" id="M1" height="12.175" version="1.1" viewBox="0 0 9.5625 12.175" width="9.5625"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
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</svg>UI/ml) whereas the remaining 67 (group B) had normal values. The percentage of anti-TPO, TG, GBM, and cardiolipin antibodies in group A patients (33&#x25;, 41&#x25;, 5&#x25; and 5&#x25;, resp.) as well as IL17, IL2 and TGF-b concentrations (<svg     style="vertical-align:-0.3003pt;width:50.299999px;" id="M2" height="11.2875" version="1.1" viewBox="0 0 50.299999 11.2875" width="50.299999"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,10.862)"><path id="x32" d="M412 140l28 -9q0 -2 -35 -131h-373v23q112 112 161 170q59 70 92 127t33 115q0 63 -31 98t-86 35q-75 0 -137 -93l-22 20l57 81q55 59 135 59q69 0 118.5 -46.5t49.5 -122.5q0 -62 -29.5 -114t-102.5 -130l-141 -149h186q42 0 58.5 10.5t38.5 56.5z" /></g><g transform="matrix(.017,-0,0,-.017,8.222,10.862)"><path id="x35" d="M153 550l-26 -186q79 31 111 31q90 0 141.5 -51t51.5 -119q0 -93 -89 -166q-85 -69 -173 -71q-32 0 -61.5 11.5t-41.5 23.5q-18 17 -17 34q2 16 22 33q14 9 26 -1q61 -50 124 -50q60 0 93 43.5t33 104.5q0 69 -41.5 110t-121.5 41q-53 0 -102 -20l38 305h286l6 -8&#xA;l-26 -65h-233z" /></g><g transform="matrix(.017,-0,0,-.017,20.155,10.862)"><path id="xB1" d="M535 290h-212v-206h-58v206h-213v50h213v193h58v-193h212v-50zM535 -22h-483v50h483v-50z" /></g><g transform="matrix(.017,-0,0,-.017,33.907,10.862)"><use xlink:href="#x32"/></g><g transform="matrix(.017,-0,0,-.017,42.066,10.862)"><path id="x33" d="M285 378v-2q65 -13 102 -54.5t37 -97.5q0 -57 -30.5 -104.5t-74 -75t-85.5 -42t-72 -14.5q-31 0 -59.5 11t-40.5 23q-19 18 -16 36q1 16 23 33q13 10 24 0q58 -51 124 -51q55 0 88 40t33 112q0 64 -39 96.5t-88 32.5q-29 0 -64 -11l-6 29q77 25 118 57.5t41 84.5&#xA;q0 45 -26.5 69.5t-68.5 24.5q-67 0 -120 -79l-20 20l43 63q51 56 127 56h1q66 0 107 -37t41 -95q0 -42 -31 -71q-22 -23 -68 -54z" /></g>

		
	
</svg> pg/ml, <svg     style="vertical-align:-0.3003pt;width:66.612503px;" id="M3" height="11.4" version="1.1" viewBox="0 0 66.612503 11.4" width="66.612503"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,10.963)"><path id="x36" d="M137 343l67 33q37 17 63 17q79 0 129.5 -53t50.5 -131q0 -92 -58 -156.5t-147 -64.5t-147 68t-58 182q0 63 17 119t43 95.5t61.5 72t69 52t67.5 31.5q62 22 128 33l6 -32q-56 -11 -108 -35q-149 -71 -184 -231zM227 337q-47 0 -95 -27q-6 -23 -6 -70q0 -93 36 -155.5&#xA;t96 -62.5q53 0 78 45.5t25 105.5q0 68 -35 116t-99 48z" /></g><g transform="matrix(.017,-0,0,-.017,8.222,10.963)"><path id="x34" d="M456 178h-96v-72q0 -51 12.5 -62.5t72.5 -16.5v-27h-256v27q65 5 78 17t13 62v72h-260v28q182 271 300 426h40v-407h96v-47zM280 225v295h-2q-107 -148 -196 -295h198z" /></g><g transform="matrix(.017,-0,0,-.017,16.381,10.963)"><use xlink:href="#x33"/></g><g transform="matrix(.017,-0,0,-.017,28.314,10.963)"><use xlink:href="#xB1"/></g><g transform="matrix(.017,-0,0,-.017,42.066,10.963)"><use xlink:href="#x35"/></g><g transform="matrix(.017,-0,0,-.017,50.226,10.963)"><path id="x37" d="M447 623l8 -12l-283 -613l-74 -10l-7 11q174 283 297 551h-216q-48 0 -62.5 -12t-33.5 -63h-29q10 60 18 148h382z" /></g><g transform="matrix(.017,-0,0,-.017,58.385,10.963)"><use xlink:href="#x32"/></g>

		
	
</svg> pg/ml, and <svg     style="vertical-align:-0.3003pt;width:66.612503px;" id="M4" height="11.4" version="1.1" viewBox="0 0 66.612503 11.4" width="66.612503"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,10.963)"><use xlink:href="#x36"/></g><g transform="matrix(.017,-0,0,-.017,8.222,10.963)"><path id="x31" d="M384 0h-275v27q67 5 81.5 18.5t14.5 68.5v385q0 38 -7.5 47.5t-40.5 10.5l-48 2v24q85 15 178 52v-521q0 -55 14.5 -68.5t82.5 -18.5v-27z" /></g><g transform="matrix(.017,-0,0,-.017,16.381,10.963)"><path id="x38" d="M249 635q70 0 116 -43t46 -105q0 -46 -28 -80q-22 -25 -80 -64q62 -35 97 -75t35 -99q0 -81 -63 -131t-135 -50q-83 0 -137.5 45.5t-54.5 123.5q0 52 45 95q29 28 89 64q-109 62 -109 155q0 66 50.5 115t128.5 49zM238 603q-42 0 -67.5 -31t-25.5 -72q0 -50 32.5 -79.5&#xA;t98.5 -62.5q61 48 61 124q0 59 -29.5 90t-69.5 31zM248 20q46 0 76.5 33.5t30.5 89.5q0 50 -39 85.5t-110 71.5q-81 -54 -81 -137q0 -67 35.5 -105t87.5 -38z" /></g><g transform="matrix(.017,-0,0,-.017,28.314,10.963)"><use xlink:href="#xB1"/></g><g transform="matrix(.017,-0,0,-.017,42.066,10.963)"><use xlink:href="#x32"/></g><g transform="matrix(.017,-0,0,-.017,50.226,10.963)"><use xlink:href="#x32"/></g><g transform="matrix(.017,-0,0,-.017,58.385,10.963)"><use xlink:href="#x31"/></g>

		
	
</svg> pg/ml, resp.) were significantly higher than group B. Abnormal Th17 regulation mediated by IL-2 and low TGF-b concentrations is associated with hypothyroidism in chronically-infected HCV patients.

Luis A. Salazar

X&#xf3;chitl Garcia-Samper

Rafael Suarez-Carpio

Mar&#xed;a C. Jimenez-Mart&#xed;nez

Erika P. Rend&#xf3;n-Huerta

Felipe A. Masso

Teresa I. Fortoul

Luis F. Monta&#xf1;o

Hypothyroidism in Noninterferon Treated-HCV Infected Individuals Is Associated with Abnormalities in the Regulation of Th17 Cells

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Hepatitis Research and Treatment