Hepatitis C virus as possible etiologic factor in idiopathic nephrotic syndrome among Egyptian patients

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1 African Journal of Nehrology (1999) 3:78-83 Original Article Heatitis C virus as ossible etiologic factor in idioathic nehrotic syndrome among Egytian atients Samir M. Sally *, Fawzy M. Khalil** and ShareifNegm** Urology and Nehrology Center", Mansoura Univcrsny. Deartement of Internal Medicine**, Benha Faculty of Medicine. Abstract: Heatitis C virus (HCY) infection is associated with a variety of extraheatic disorders. including cryoglobulinaernia and glomerulonehritis. Heatitis C virus (HCY) glorneruloathy may be resent as a rimary glomerular disease. Our study included 50 adult Egytian atients who were diagnosed as idioathic nehrotic syndrome (NS). We described the clinical, athological and immunological features of these atients. There was a high revalence (509<:) of HCY infection among these atients. The studied risk factors included history of; blood transfusion (16%) oeration (24o/c) or antibilharzial drugs (76%). Heatomegaly was observed in 24% of cases. Mernbranoroliferative glomerulonehritis (MPGN) was the commonest athological tye associated with HCY (48%). Other atterns i ncluded focal segmental glomerulosclerosis (FSGS) in 32o/t-. membranous in 8% and minimal change glomerulonehritis in 12o/t-. Cryoglobulins were detected in 5.6% of 18 atients with HCY and idioathic NS. Pateints having HCY infection and membrarioroliferative glomerulonehritis had hyocomlcmentemia and antinuclear antibodies were detected in 41.6%. Realising that HCY infection may be linked to different glomeruloathies, thus routine screening for HCY should be considered in serologic work-u of atients with glomeruloathy. Nevertheless, scroeiderniological studies including larger number of atients with glorneruloathy are therefore necessary to secify its relation with HCY infection. Corresondence and ojjrinl requevv (0: Dr S, Sail) (IHhldldlll ot Nehrology. Urology & Nehrology Center. Man-oura- Egyt Introd netion Heatitis C virus (HCY) is an RNA virus, identified in 1989 III causing both acute and chronic liver disease 121. Chronic heatitis C virus infection i-, associated with several extraheatic syndromes. including mixed cryoglobulinaemia, olyartcriu-, nodosa, sicca like syndrome and immunologically mediated renal diseases 171. Several studies have been reorted linking HCY and the occurrence of chronic glomerular diseases esecially mernbranorolifcrativc glomerulonehritis (MPGN) Studies in the USA, Italy and Jaan suggest that HCY may be an imortant cause of cryoglobulinaernic and idioathic MPGN It is likely that HCY is also an imortant cause of glomerulonehritis in other areas of the world, but this had been unrecognized. This is due to the fact that these atients often lack clinical evidence or liver disease, and resent clinically as a rimary renal syndrome 18,91 with minimally elevated transarninases and a remote history or exosure to IICY. We have no available data in Egyt regarding this link. Thus the objective or this study was to detect the revalence of' IICY among Egytian atients who were reviously diagnosed as idioathic nehrotic syndrome (NS) and to study il' it has a ossible etiologic role in such atients. Materials and methods This study included fifty atients (unending the outatient clinic or Urology and Nehrology center of Mansoura University) they were diagnosed as idioathic nehrotic syndrome, 32 males and 18 females, their age ranged from 16 to SO years. IICY infection was diagnosed in all atients by testing for the resence of HCY antibodies using (ORTIIO-

2 79 HCY, Ortho Diagnostic system) and HCY-RNA (olymerase chain reaction). According to this result atients were divided into two grous: Grou I (50%) was ositive and grou II (50%) was negative for HCY antigens and antibodies. All atients were investigated for liver function tests, serum creatinine, urinary roteini24h., serum comlement, abdominal ultrasonograhy and renal biosy. Those twenty five atients with HCY infection were investigated rol' antinuclear antibodies and cryoglobulins and then categorised according to the athological findings of renal biosy into 2 grous. one with mernbranorolifcrative glomerulonehritis and the other with other athological tyes. Results The clinicoathological and laboratory features of the studied atients are shown in tables (1-8). Analysis qt the results Table I. shows that males constituted 689(- of atients with HCY infection comared to 60,* of atients without. Females constituted 321'k and 409(- resectively with a statistically insignificant difference (P>0.05). Table 2. shows that the mean age of atients in HCY grou was ± 8.36 years while it was ± 7.31 years in grou Il with a statistically insignificant difference (P> 0.(5). Table 3. shows that history of blood transfusion was resent in 16% of grou I while it was l2(!c in grou II with statistical insignificant difference (P>O.05). IIistory of oeration was resent in 24(!c of grou I atients while il was 12('h in grou Il with statistical insignificant difference (P>0.05). History of antibilharzial drugs was resent in 76('k of HCY osiuvc grou while it was 48(i( alllong IlCY negative grou with statistical significant difference (P< ().()S). Heatomegaly was resent in 241.* of the atients in IlCY ositive grou while it was found in only 4(i(, in the atients of llcy negative grou with statistical significant difference (P<0.05). Table 4. shows that the serum bilirubin was 0.66 ± 0.46 nig/dl in grou Il cases while it was 0.53 ± 0.20 rug/dl among IICY negative grou with statistical insignificant difference (P> 0.(5). The mean level of SGPT was ± lull in grou I while it was lull in grou Il with statistical significant difference (P< 0.05). The mean level of SGOT was ± lull and ± 6.01 lull in groul&liresectivly with statistical significant difference (P< 0.(5). The mean level of serum albumin was 2.48 ± 0.59 gldl and 2.32 ± 0.67 gldl in grou I & II resectivly with statistical insignificant difference CP>0.05). The mean value of cholesterol levels were ±85.8 mg/dl and ± 67.8 mg/dl in grou I & II resectivly with statistical insignificant difference (P>0.05). The mean value of 24 hours urinary rotein was 3.77± 2.26 gm in grou Iwhile it was 3.68 ± 3.11 gm in grou II with statistical insignificant difference (P>0.05). The mean level of serum creatinine was 0.92 ± 0.22 rug/dl and 0.88 ± 0.28 md/dl in grou I & II resectivly with statistical insignificant difference (P>0.05). The athological findings of the renal biosy as shown In table 5 include, focal segmental glomerulosclerosis in 32%, membranoroliferative in 48%, membranous in 8% and minimal change in 12% among atients in grou I while it was focal segmental glomerulosclerosis in 60%, rnernbranoroliferative glomerulonehritis in 8%, membranous glomerulonehritis in 4%, minimal change glomerulonehritis In 12% and rnesangial roliferation in 16% of grou IIcases. A statistical significant difference between both grous was resent in FSGS, MPGN and rnesangial roliferation (P<0.05). Table 6. shows that the mean value of comlement three (C3) was 92.59±40.47 rug/dl among HCY ositive atients with MPGN grou while it was ±33.96 rug/dl among the same grou with other athological tyes with statistical significant difference (P<0.05). The mean value of comlement four (C4) was 22.72± rug/dl in HCY ositive atients with MPGN while it was 45.5l±14.20 mg/dl among atients in the same grou with other athological tyes with statistical significant difference (P<0.05). Table 7. shows that the antinuclear antibodies were strongly ositive in 8.3% but weak ositive in 33.3% or HCY ositive atients with MPGN comared to 23.1 (i( and 7.79(- resectively among atients in the ositive grou with other athological tyes with a statistical significant difference (P>0.05). Table 8. shows that croyoglobulins were detected in 9.1 (k among I I atients with HCY associated MPGN comared to 0% among 7 atients with Hey and with other athological tyes but this comarison is not statistically valid as one grou contains only one subject.

3 80 Table 1. Sex distribution of the studied atients according to HCV infection HCV HCV Total ~v (ositive) (negative) 5 No % No % No % Males Females Total * (P>0.05)= non-significant. Table 2. Means ± S.D. of age among the studied atients according to HCV infection ~A e ( ears) HCV ositive HCV negative T Mean S.D. Range ± ± > 0.05* * = insignificant. Table 3. Risk factor, for HCV infection in <tudied atients HCV o,>itive HCV negative Total (n.=50) I' Character No No "k No History of: BI. transfusion Oeration Anti-B drug, Heatomegaly > > ()40 <0.05 * I <0.05* * Non-vignificaru * Signifïcant Table 4. Liver function test-, and arameter, of nehrotic syndrome among our atient, according to HeV infection HeV o,itivc /lcv»cgativc ~V L x + S.D. x +S.D..5. bilirubin 0.66 ± 0.46 OSl± SGPT ± H ± SGOT ± ± Albumin 2.48 ± ± cholesterol ± ± creatinine 0.92 ± ± u. rotein/24h 3.77 ± ± >O.OS' <O.OS «).()S" >0.05" >O.OS* >O.OS" >O.OS * Non-signi fïcant ** Significant

4 81 Table 5. Renal histoathology in both HCY ositive and negative grous Hey Hey ositive Hey negative To/a! z Pathology No % No % No % FSGS IS 60.0 MPGN Membraous I 4.0 Minimal change Mesangial rolil Total >0.05** >0.05** <0.05** <0.05** * Non-significant ** Significant Table 6. Comlement levels among HCY ositive grou accoding 10 the results or renal histoathology ~osy MPGN a/hers T Comlement X:JS.D. X :JS.D. C3 C :J :J :J :J <0.05** <0.05** * Significant. Table 7. Antinuclear antibodies in both grous ~,y MPGN a/hers To/a! (1/=!2) (11=/3) (11.=25) z P A No '7< No % No % Weak Strong Total >0.05* >0.05* <0.05* Non-significaru Table 8. Cryoglobulins in both grous /Jiosy MPGN (1/=/1) Others (11=7) Tora! (11.=/8) Cryoglobulins No % No % No % Cryoglobulin, 9.1 o Discussion Heatitis C virus (HCY) is an RNA virus, identified in 1989 II]. It causes both acute and chronic liver disease and is a major cause of both transfusion associated and soradic non-a non-b heatitis. Persistent infection occurs in aroximately 50% of atients, it is often clinically silent and may result in chronic active heatitis, cirrhosis and ossibly heatocellular carcinoma [Z]. Chronic heatitis C virus infection, when resist for over ten years and esecially in reseenee of chronic active heatitis or cirrhosis, is associated with several extraheatic syndromes, including mixed cryoglobulinaemia, olyarteritis nodosa and sicca like syndrome [3-6]. HCY infection may be associated with immunologically mediated renal diseases [7]. Several studies reorted the link between HCY and

5 82 chronic glomerular diseases esecially membranoroliferative glomerulonehritis [8-10). However we have no available data in Egyt regarding this link. In this study, we reorted an association of Hey infection with idioathic NS in 50% of the studied atients. Similarly, many reorts confirmed this association [7,9,11). The high ercentage of anti- Hey seroositivity suggests that this virus may lay an imortant role in the athogenesis of this immune-mediated glomerulonehritis. One the other hand, other reorts did not find such association [12,14]. This difference may be related to the endemicity of Hey in Egyt as its revalence ranged from 10-20% among the general oulation [15]. Other factors considered may include secific genotye associated with articular comlication as glomerulonehritis and the duration of infection [16J. Exosure to risk factors was resent in 40% of Hey ositive atients including blood transfusion ( 16%) or oerations (24%) (table 3). Other reorts showed different results (16,9). This may be related to different revalence and endemicity of Hey among di fferent oulation [17], different genotyes [18] and different habits [19]. The majority (76%) of our Hey ositive atients received one or more courses of antibilharzial drugs (table 3). This may be related to the endemicity of schistosomiasis in Egyt [19]. The relationshi between Hey and glomeruloathy in the resence or absence of schistosomiasis should be seciefied as different relations were reorted [16,20]. ft is of interest that the resence of heatomegally among the atients with Hey (24%) was significantly higher than those without Hey (4%) (table 3). The mean values of SGPT and SGOT among atients with Hey were significantly higher than those without Hey (table 4) this is in a greement with other reorts [7,9]. However, the lower values of transaminase may be related to the effect of the administrated corticosteroid [21], different genotyes and the absence of HBY infection [19]. In this study, membranoroliferative glomerulonehritis was the commonest (48%) athological attern among atients with Hey (tables) and this is similar to many reorts [9,11,16). Our atients with Hey and membranoroliferative glomerulonehritis showed lower level of comlement 3 and comlement 4 than those with Hey and other athological tyes (table 6). MPGN is known to be associated with hyocomlementemia and is sometimes called hyocomlementemic glomerulonehritis [22]. The resence of antinuclear antibodies (ANA) was detected in 36% among atients with Hey (table 7) which could be related to the association between chronic Hey infection and develoment of autoantibodies [23]. Cryoglobulins were detected in one out of eighteen ~ atients, with Hey and idioathic NS (table 8). Different reorts showed different results [9,16,24J. This difference may be related to several factors including; the duration and severity of chronic liver disease [25], different geograhical areas [24], the administrated immunosuressive drugs [26,27] and revious HBY infection [7,28]. Follow u of cryoglobulins is recormmended as it may develoe later [9]. We may conclude that there was a high revalence of Hey infection among atients with idioathic NS. Those with MPGN, heaiomegally, elevated transaminases and history of antibilharzial drugs are at increased risk. MPGN was the commonest athological tye associated with Hey. Acceting that Hey infection may be linked to several glomeruloathies, routine screening of these atients for Hey should be considered in their serologic work-u. Nevertheless, seroeidemiological studies including larger number of atients with glomeuloathy are necessary to secify its relation with I:-lCY infection. References Choo, Q.L.. Kuo. G. and Weiner. 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