The early onset of type 1 autoimmune hepatitis has a strong genetic influence: role of HLA and KIR genes.

We have previously reported a strong association between HLA-DRB1*1301 and type 1 pediatric autoimmune hepatitis (PAH) and between HLA-DR*0405 and adult autoimmune hepatitis (AAH). Because human killer cell immunoglobulin-like receptors are known to be associated with susceptibility to autoimmune diseases, we investigated the frequencies of HLA-A, B, C, DRB1 and KIR genes in 144 type 1 PAH and 86 AAH patients, which were compared with 273 healthy controls. We demonstrated in PAH the increased frequency of the functional form of KIR2DS4-Full Length (KIR2DS4-FL), which in combination with HLA-DRB1*1301 revealed a strong synergistic effect (odds ratio=36.5). PAH-KIR2DS4-FL+ subjects have shown an increased frequency of their putative HLA-C*02, 04 and 06 ligands. KIR analysis of PAH also revealed a decreased frequency of KIR2DL2 gene and its ligand. In contrast, AAH cases have shown a weaker increased frequency of KIR2DS4-FL, a lack of synergistic effect with HLA class II antigens and a moderate association with HLA-DRB1*0405. Of note, we demonstrated that liver T cells have a unique pattern of KIR expression. These results show a KIR gene involved in autoimmune hepatitis and suggest a stronger genetic influence for the early onset type I autoimmune hepatitis.

Relapse rates in chronic hepatitis B naïve patients after discontinuation of antiviral therapy with entecavir.

Registration studies show entecavir (ETV) to be effective and safe in NUC-naïve patients with chronic hepatitis B, but relapse rates after treatment discontinuation have not been well established. Relapse rates and predictors of relapse were evaluated in naïve HBeAg-positive and HBeAg-negative patients treated with ETV. Treatment duration was defined according to international guidelines. Virological relapse was defined as reappearance in serum of hepatitis B virus (HBV) DNA to >2000 IU/mL after discontinuation of treatment. A hundred and sixty-nine consecutive patients were treated for a median 181 weeks. 61% were HBeAg positive, 23% had cirrhosis, and mean HBV DNA level was 6.88 ± 1.74 log10 IU/mL. Ninety-two per cent became HBV DNA negative; 71% of HBeAg+ve patients became HBeAg negative and 68% anti-HBe positive; 14% became HBsAg negative and 13% anti-HBs positive. At the end of the study, 36 patients discontinued treatment: one due to breakthrough associated with resistant variants and 35 (20%) due to sustained virological response; 33 of these patients developed HBeAg seroconversion and 18 HBsAg seroconversion. Median off-treatment time was 69 weeks. Nine patients (26%), all HBeAg positive at baseline, developed virological relapse after a median 48 weeks off-treatment, 3 of them showed HBeAg reversion and 4 lost anti-HBe. No patient with HBsAg seroconversion relapsed. HBeAg clearance after week 48 of treatment was associated with an increase risk of relapse. After ETV discontinuation, HBsAg seroconversion was maintained in 100% of the patients, HBeAg seroconversion maintained in 90%, and virological relapse rate was 24%.

Effectiveness of entecavir in chronic hepatitis B NUC-naive patients in routine clinical practice.

INTRODUCTION: Registration studies showed entecavir (ETV) to be effective and safe in NUC-naïve patients with chronic hepatitis B virus (HBV), but its effectiveness in routine clinical practice is unknown. MATERIALS AND METHODS: Sixty-nine HBeAg positive and negative NUC naïve chronic HBV patients were treated with ETV for 110 weeks. 63% were HBeAg positive, 16% were cirrhotics, mean HBV-DNA was 7.09 log IU/ml and mean ALT was 157 IU/ml. RESULTS: Sixty-one (88%) patients achieved undetectable DNA, with 46%, 77% and 100% virological response rates at week 24, 48 and 96 of treatment, respectively. Thirty-seven (84%) patients in the HBeAg-positive population achieved undetectable DNA, with 67% and 100% virological response rates at week 48 and 96 of treatment, respectively. Twenty-four (96%) patients in the HBeAg-negative population achieved undetectable DNA, with 91% and 100% virological response rates at week 48 and 96 of treatment, respectively. Twenty-three (53%) patients cleared HBeAg and 19 (44%) patients seroconverted to antiHBe positive status; seven (10%) patients cleared hepatitis B surface antigen and five (7%) patients developed antiHBs. At the end of the study, 10 patients successfully stopped therapy: nine HBeAg positive (four developed antiHBs positive) and one HBeAg negative. None of the patients had primary non-response. ETV resistance was not tested. None of the patients developed hepatocellular carcinoma, underwent liver transplantation or died because of liver-related events. No serious adverse events were reported. CONCLUSION: The ETV monotherapy showed high virological response rates, a favourable safety profile for NUC-naive HBeAg-positive and negative patients treated in routine clinical practice.

Liver infiltrating mononuclear cells in children with type 1 autoimmune hepatitis.

OBJECTIVE: To investigate infiltrating cells in the liver of children with type 1 autoimmune hepatitis (AH-1). METHODS: liver biopsies from 24 untreated AH-1 patients (14 children, 10 adults), five patients with hepatitis C virus related chronic hepatitis (HCV), and 10 control liver specimens (CL) were processed for immunohistochemical cell characterisation. RESULTS: Two different cell distribution patterns were detected in the liver of patients with AH-1: (1) CD4(+) and CD20(+) cells were found in the central areas of the portal tracts (portal distribution); (2) CD8(+) cells were observed at the periphery of the portal space (periportal distribution). Some cell subsets, like CD56, CD57, Fas-L, and Bak, showed a non-defined distribution pattern. The presence of two well defined patterns of cell distribution was not observed in HCV and CL (CD4(+), CD20(+), and CD8(+) cells were uniformly distributed in the portal space). In AH-1 and CL, the NK markers CD56 and CD57 were found scattered throughout the liver parenchyma. However, in HCV biopsies, CD56(+) cells were also clearly increased in both the portal and the periportal areas. Biopsies of AH-1 and HCV patients showed a uniform distribution of Fas-L and Bak in the portal and periportal areas, with Bak staining also detected in the hepatic parenchyma. CONCLUSIONS: Despite clinical and genetic differences, there was a similar distribution of liver infiltrating mononuclear cells in children and adults with AH-1. These results raise the possibility of reclassifying cryptogenic chronic hepatitis by immunohistochemical analysis of infiltrating liver cells.

Expression of CD1 antigens by peripheral blood mononuclear cells from hepatitis B patients.

We have studied the expression of CD1 antigens on peripheral blood mononuclear cells (PBMC) from acute hepatitis B patients in order to analyse a possible role for CD1 antigens in hepatitis B virus (HBV) infection. Using immunofluorescence and the monoclonal antibodies which recognized CD1a, CD1b and CD1c molecules, we have shown that CD1 antigens were expressed on PBMC from acute hepatitis B patients but not from other acute and chronic liver disease. Dot blot analysis on nitrocellulose sheets of the lysates of the cells confirmed these observations. Cell fractionation and double-labelling experiments clearly demonstrated the CD1 antigens were expressed only on non-T cells. Furthermore, CD1 antigens were coexpressed with hepatitis B surface antigen (HBsAg) on the surface of Ig-positive cells. These results could indicate that CD1 expression may be associated with the lymphotropic effect of HBV.

Analysis of hepatitis B surface antigen expression on leucocyte subpopulations by two-color fluorescence with flow cytometry.

We have analyzed the expression of HBsAg on different subpopulations of peripheral blood cells from hepatitis B virus (HBV) infected patients using two-color immunofluorescence and flow cytometry. An average of 7.4 +/- 0.8% and 9.8 +/- 1.2% HBsAg + cells were found among cells from acute and chronic hepatitis B patients, respectively. When studied by two-color immunofluorescence, HBsAg was limited to cells expressing the B-cell restricted antigen CD19 (16.7 +/- 2.4%), whereas for the other subsets studied (CD3+, CD4+, CD8+, CD67+, CD68+) the percentage of positivity was lower than 4%. The expression of viral antigen on B cells might be relevant for a number of functional interactions between HBsAg+ B and T lymphocytes.

[Low prevalence of autoimmune antiphospholipid antibodies in hepatic diseases]. / Baja prevalencia de anticuerpos antifosfolípidos autoinmunes en enfermedades hepáticas.

Antiphospholipid antibodies (aPL) have been associated with different diseases. They are defined as a large family of immunoglobulins (Ig) of either alloantibodies or autoantibodies. The autoimmune antibodies are associated with venous and/or arterial thrombosis, thrombocytopenia and recurrent fetal loss in the so-called antiphospholipid syndrome or in systemic lupus erythematosus. These antibodies are directed against proteins or phospholipid-protein complexes. On the contrary, antiphospholipid antibodies (alloantibodies) which are found in infectious diseases sera (syphilis, HIV, and other viral diseases), disappear with illness remission and are directed to phospholipids alone (particularly cardiolipin) and are not associated with thrombosis or recurrent fetal loss. However, the role and type of aPL found during hepatic diseases is still unclear. To investigate the prevalence of autoimmune aPL (IgG and IgM) during different hepatic diseases, we have studied 128 patients with hepatitis C virus, hepatitis B virus and hepatic autoimmune diseases without treatment as well as 40 healthy control subjects. We have used a specific ELISA kit, that uses a mixture of phospholipid instead of cardiolipin alone, and allows a better detection of aPL of the autoimmune type. Our results show that autoimmune aPL are not significantly increased in viral hepatic diseases (2%) or autoimmune diseases of the liver (3%) when compared to the control group (0%).

[Identification of Enterocytozoon bieneusi in a patient with sclerosing cholangitis and AIDS]. / Identificación de enterocytozoon bieneusi en un paciente con colangitis esclerosante y SIDA.

Enterocytozoon bieneusi is the most common microsporidian parasite found in patients with AIDS. We report the clinical features of a patient with chronic diarrhea, pancreatitis, and AIDS-related sclerosing cholangitis. Ultrasonography and endoscopic retrograde cholangiopancreatography disclosed intrahepatic and extrahepatic bile duct changes identical to those seen in sclerosing cholangitis. Enterocytozoon bieneusi was found in duodenum and peripapillary duodenum by means of light microscopy, and confirmed by PCR amplification of paraffin-embedded tissues with species-specific primers. Microsporidian infection should be suspected in patients with advanced immunodeficiency and AIDS-related sclerosing cholangitis in our country.

[Idiophatic inflammatory myophaties: its asociation with liver disorders]. / Miopatías inflamatorias idiopática: su asociación a hepatopatías.

UNLABELLED: The aspartate aminotransferase (SGOT) and alanine aminotransferase (SGPT) are sensitive indicators of liver damage. While the TSGOT is also found in other organs, the SGPT is considered an enzyme specific liver. However, some authors state that the TGP can rise also in cases of muscle injury. Furthermore, there are reports in the literature suggesting the association of idiopathic inflammatory myopathies (IIM) with viral hepatitis. OBJECTIVE: To determine the frequency of abnormal liver function tests in patients with idiopathic inflammatory myopathies, evaluate possible associationsto liver diseases, determine its relationship with elevation of muscle enzymes and whether these patients have particular clinical and / or serological characteristics. MATERIAL AND METHODS: Consecutive patients older than 16 years diagnosed with DM / PM according to Bohan and Peter criteria during 1999-2000 were included. Patients with other connective tissue disease (CTD) were excluded. Demographic data were recorded, characteristics of the disease, laboratory data and elevated liver enzymes and muscle during the course of the disease. Serologic tests were performed for viral hepatitis B and C and confirmatory tests (HBV-DNA and HCV-RNA by PCR). Autoantibodies were determined: ANA (antinuclear antibody) by Hep II, ASMA (anti smooth muscle antibody), AMA (anti-mitochondrial antibodies) and LKM (Liver Kidney Microsomal) by mouse wound, MSA (myositis-specific antibodies) by ELISA. Patients who had abnormal liver tests underwent hepatic ultrasonography. For statistical analysis, descriptive statistics, categorical variables were compared by Fisher's exact test. RESULTS: We included 27 patients, of whom 22 had sufficient data for analysis. Mean age 47.95 years ± 16, 18 female (81.8%) and mean disease duration 8.09 ± 5.6 years. With regard to liver enzymes, 14/22 patients (63.3%) had elevated SGPT and 11/22 (50%) elevated SGOT, 10 of these patients also had elevated SGPT concomitantly. In the 10/15 (66.7%) abdominal ultrasonography showed abnormalities, 8 patients had liver hyperechogenicity, 4 cholelithiasis and 1 patient hepatomegaly. No patient bearing of HBV or HCV. The 8 patients with liver hyperechogenicity matched the 8 patients with isolated elevation of SGPT/SGOT. As for the 10 patients who had both elevated liver enzymes (SGPT and SGOT), only one case could be explained by liver disease (patient ASMA +). However in the 15 cases studied, elevations of SGPT and / or SGOT coincided with outbreaks of myositis,findingconcomitant apparent liver disease in only 9 of them. CONCLUSIONS: In this study, elevated transaminases, including the TGP, was observed concomitantly with the activity of myositis. Approximately half of these cases could not be associated with coexisting liver disease, which could be attributed to injury to muscle secondary to inflammatory myopathy.

Hepatitis B virus in Buenos Aires, Argentina: genotypes, virological characteristics and clinical outcomes.

Hepatitis B virus (HBV) is classified into eight major genotypes, A-H, which are geographically distributed worldwide. The aim of this work was to describe the clinical characteristics associated with the HBV genotypes circulating in Buenos Aires city. The study included 139 patients infected with HBV, whose clinical courses were classified as acute symptomatic self-limiting hepatitis, inactive carrier state and chronic active hepatitis (HBV e-antigen (HBeAg)-positive and HBeAg-negative). The HBV genotypes were determined in 128 patients by PCR-restriction fragment length polymorphism and phylogenetic analysis. Biochemical, virological, clinical and histological features were analysed. A differential distribution of genotypes between acute symptomatic and chronic infections was found. Among the acute cases, genotype F was predominant (65.2%, 30/46) and genotype D was rare (4.3%, 2/46), whereas among the chronic infections, a homogeneous distribution of genotypes A (26.8%, 22/82), D (31.7%, 26/82) and F (36.6%, 30/82), with an unusual presence of genotypes B (1.2%, 1/82) and C (3.7%, 3/82), was observed. Regarding the liver histology of chronically infected patients, genotype F tended to display higher histological activity indexes. Mutations related to HBV surface antigen immunoreactivity, antiviral resistance and HBeAg-negative status were studied. This work constitutes, to our knowledge, the first description of the clinical characteristics related to HBV genotypes in Argentina, where the distribution of genotypes in patients with acute infection has not been reported previously. Finally, it was established that genotype F is the prevalent genotype among the acute symptomatic infections in Buenos Aires city, and that it shows a tendency to cause an adverse disease outcome among the chronic cases.

Increased frequencies of activating natural killer receptors are associated with liver injury in individuals who do not eliminate hepatitis C virus.

This study was designed to investigate the role of killer immunoglobulin-like receptor (KIR) genes in the outcome of hepatitis C virus (HCV) infection. In patients who cleared the virus (HCV RNA-) we found a decrease of 2DL2 (P= 0.04), and 2DS2 (P= 0.014) accompanied by an increase of 2DS5 (P= 0.04). Those RNA+ patients with elevated levels of hepatic transaminases (HCV RNA+ elevated alanine aminotransferase) showed an increased frequency of 2DS3 (P= 0.018). Additionally, in cirrhotic patients we found an increased frequency of individuals having two copies of 3DS1 and HLA-Bw4 (P= 0.016). We conclude that higher natural killer cytotoxicity might be associated with a worse progression of the HCV infection.

Association of chronic active hepatitis and HLA B35 in patients with hepatitis B virus.

Fifty-one patients with chronic active hepatitis were typed for their HLA-A, B, C, and DR antigens. We observed a significant increase in the antigen frequency of HLA B35 in patients compared with controls.

Hepatitis B virus antigens in peripheral blood mononuclear cells during the course of viral infection.

We studied the expression of surface (HBsAg) and core (HBcAg) proteins of hepatitis B virus (HBV) on the surface of peripheral blood mononuclear cells (PBMC) from HBV-infected patients. A total of 122 patients with different liver viral diseases was analyzed by indirect immunofluorescence with monoclonal antibodies. The 35 patients with HBV chronic active hepatitis (CAH) and 38 of 60 patients with acute hepatitis B (63%) expressed HBsAg on the PBMC. No expression was detected on the cells from both normal and HBV-unrelated viral hepatitis control groups. Serial follow-up of patients with acute hepatitis B showed that HBsAg expression by PBMC tended to be undetectable 4 months after the onset of the disease and at the same time the clinical improvement was evident. Cell cultures of EBV-transformed B lymphocytes were established from PBMC of HBV-infected patients; immunoelectron microscopy demonstrated the HBsAg on the cellular membrane. One-third of HBV-infected patients who were studied showed the expression of HBcAg by PBMC. HBcAg was detected in patients with acute hepatitis B at the early stage of infection. The cells of these patients also expressed HBsAg in PBMC. In CAH patients, a positive association was observed between the expression of HBcAg and the presence of serum HBeAg.

HIV-1 infection in intravenous drug abusers with clinical manifestations of hepatitis in the city of Buenos Aires.

A serologic study of hepatitis and HIV infections among 99 I.V. drug abusers with hepatitis was conducted between December 1986 and September 1987. The average age of the study subjects was 21 years. Eighty-nine (90%) of the subjects were male, including four whose sexual orientation was homosexual/bisexual. Serologic tests indicated that 87 of the 99 subjects had hepatitis B virus infections, 62 acute and 25 chronic. Nine (10%) of these 87 patients were coinfected with the delta agent. Two subjects had acute cases of hepatitis A, and the 10 remaining subjects had non-A non-B hepatitis. Forty-seven of the study subjects were also found to be infected with HIV-1. The prevalence of the delta marker was surprisingly high, because Argentina has been regarded as nonendemic for the delta virus. Given the trend of increasing I.V. drug abuse in Argentina, these results presage a significant increase in the delta agent's prevalence in the immediate future.

[Prevalence of antibody against the hepatitis B core antigen (anti-HBc)among hospital personnel in Buenos Aires]. / Prevalencia del anticuerpo contra el antígeno central del virus de la hepatitis B (anti-HBc) en personal hospitalario de Buenos Aires.

A group of 1,479 employees in 19 Buenos Aires hospitals were tested for antibody to hepatitis B core antigen (anti-HBc) to identify those who should be vaccinated against this infection. The average age of the subjects was 38.22 years; 70.86% of them were women and 85.5% were working in services where the risk of infection was high. The enzyme-linked immunosorbent assay (ELISA) was used, and the data were analyzed by the chi-square test. The results showed that 1,257 subjects (85.0%) did not have anti-HBc and thus were considered candidates for vaccination. The antibody was present in 222 individuals (15.0%). The prevalence of anti-HBc increased with age and with length of service, and it was greater in laboratory technicians, nurses, and those in high-risk services. These differences were statistically significant (P less than 0.01). A total of 23 carriers of hepatitis B surface antigen (AgHBs) were identified. In high-risk groups, vaccination against hepatitis B should be preceded by serological screening of susceptible individuals; the use of anti-HBc for this purpose allows carriers of AgHBs to be identified. The high prevalence of anti-HBc in laboratory technicians, nurses, and nurses' aides might justify their systematic vaccination.

Two-locus involvement in the association of human leukocyte antigen with the extrahepatic manifestations of autoimmune chronic active hepatitis.

We investigated the association of human leukocyte antigen antigens and type 1 chronic active "autoimmune" hepatitis in a population of 65 white Argentinian patients, taking into account the different manifestations of the disease. Standard microlymphocytotoxicity was used for human leukocyte antigen A, B, C, DR and DQ typing. Human leukocyte antigen class 2 alleles were also typed on genomic DNA by means of polymerase chain reaction amplification and hybridization to sequence specific oligonucleotides. A primary association with human leukocyte antigen DR4 was present (human leukocyte antigen DR4: 44% in patients vs. 29% in controls; chi 2, 5.6; p = 0.02, relative risk, 2.1). However, a novel association was observed with human leukocyte antigen A11 (31% in patients vs. 6% in the controls; chi 2, 25.3; corrected p = 0.001; relative risk, 6.8). Moreover, of the 20 human leukocyte antigen A11 patients, 18 had extrahepatic manifestations associated with autoimmune chronic active hepatitis. This represented 60% of the patients bearing this form of the disease (n = 30), conferring a relative risk of 22.2 (chi 2, 46.3; corrected p = 0.00008). In this group, human leukocyte antigen DR3 and DR4 had a weak association. When present together, human leukocyte antigen DR4 and human leukocyte antigen A11 had a synergistic effect, yielding an odds ratio of 357. Statistical analysis and family segregation studies suggest that the two loci products may represent independent risk factors for this form of autoimmune chronic active hepatitis. This synergistic effect was not evident with A11 plus DR3. In autoimmune chronic active hepatitis patients without extrahepatic manifestations, a weak association with human leukocyte antigen DR6 was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence of hepatitis viruses in an anti-human immunodeficiency virus-positive population from Argentina. A multicentre study.

The objectives of this study were to investigate the prevalence of infections with hepatotrophic viruses in an anti-human immunodeficiency virus (HIV)-positive population from Buenos Aires and to compare it among the main risk groups for HIV infection. Four hundred and eighty-four consecutive patients attending the HIV outpatients clinic were studied: 359 men and 125 women, median age 29 years (range 16-67 years); 35.5% had presented acquired immune deficiency syndrome (AIDS)-defining conditions. Two hundred and thirty-four patients were intravenous drug users (IVDU), 99 had homosexual and 142 heterosexual preference, seven had received blood transfusions and two had no risk factors. Hepatitis B surface antigen (HBsAg), and antibodies to hepatitis B core antigen (HBcAb) and to hepatitis C virus (anti-HCV) were investigated in all patients; antibodies to HBsAg (HBsAb) and IgG antibodies to hepatitis D virus (anti-HDV) in all HBcAb-positive patients; hepatitis B e antigen and antibodies to HBeAg (HBeAg) in all HBsAg-positive patients; IgG antibodies to hepatitis A virus (anti-HAV) in the first 307 patients; and IgG antibodies to hepatitis E virus (anti-HEV) in the first 91 patients. As control groups, contemporary voluntary blood donors were studied for prevalence of HAV, HBV, HCV and HEV. The percentages of HBcAb, HBsAg, anti-HCV and anti-HEV (58.5, 14.5, 58.5 and 6.6%, respectively) were significantly higher in anti-HIV-positive patients than in control groups (3.2, 0.5, 1.0 and 1.8%, respectively) (P = 0.000). The prevalence of HBcAb was significantly higher in IVDU (72.6%) than in heterosexuals (33.8%) (P = 0.0001) and in homosexuals (59.6%) (P = 0.0189). The percentage of HBsAg was significantly higher in IVDU (19.2%) than in heterosexuals (6.3%) (P = 0.0004). Anti-HCV was significantly higher in IVDU (92.3%) than in homosexuals (14.1%) and in heterosexuals (33.1%) (P = 0.000 in both cases). The prevalence of anti-HDV was relatively low (1.9%). There was no difference in the percentage of anti-HAV between HIV-positive and negative subjects. In conclusion, there is a high prevalence of HBV and HCV infections in HIV-positive patients from our area. Drug use is the main route of transmission, but prevalence of HCV in patients with, probably, sexually acquired HIV infection is also higher than in the control group. The increased prevalence of HEV infection in HIV-positive individuals is another provocative finding that warrants further study.

Pediatric and adult forms of type I autoimmune hepatitis in Argentina: evidence for differential genetic predisposition.

The aim of this study was to compare major histocompatibility complex (MHC) class II susceptibility to type 1 autoimmune hepatitis (AH) between children and adults of the same ethnic group. HLA-DRB1, HLA-DRB3, HLA-DQA1, and HLA-DQB1 gene subtypes were examined by high resolution oligonucleotide typing in 122 pediatric (PAH) and 84 adult (AAH) patients and in 208 controls. In children, HLA-DRB1*1301 was the primary susceptibility allele (66.4% patients vs. 10.6% controls, relative risk [RR] = 16.3, Pc < 10(-24)) whereas HLA-DRB1*1302, which differs from HLA-DRB1*1301 by only 1 amino acid, appeared to be protective. The exclusion of individuals with HLA-DRB1*1301 from control and pediatric patients allowed us to find a secondary association of PAH with HLA-DRB1*0301. Possession of HLA-DRB1*1301, however, was associated with a lower therapeutic response rate. Analysis of peptide binding pocket residues indicated that Tyr 10, Ser 11, Ser 13, and Val 86 in the class II beta chain were present in 85% of patients compared with 37% of controls, suggesting that a high proportion of AH susceptibility is attributable to these residues (etiologic fraction [EF] = 76%). In contrast to the class II associations in children, AAH was associated with HLA-DRB1*0405 (RR = 10.4, Pc <.005) but not with HLA-DRB1*1301 or HLA-DRB1*0301. In addition, HLA-DR4 with the class I gene, HLA-A11, appeared synergistic in predisposing AAH patients to develop extra-hepatic autoimmune (AI) manifestations (odds ratio [OR] = 104.9, Pc < 10(-4)). Concomitant differences in autoantibody profiles were also observed in PAH versus AAH: smooth muscle antibodies (SMA) were most prevalent in PAH but antinuclear antibodies were most prevalent in AAH (P =.003). This study therefore reveals that different HLA-DRB1 allotypes confer susceptibility to AH in children and adults and raises the possibility that PAH and AAH may be triggered by different factors.

Hepatitis C virus and GBV-C/hepatitis G virus in Argentine patients with porphyria cutanea tarda.

To investigate hepatitis C virus (HCV) and GBV-C/hepatitis G virus (HGV) genotype prevalence among HCV-infected porphyria cutanea tarda (PCT) patients, 19 HCV-infected patients with associated PCT were studied. A control group of 53 age-matched HCV-infected patients without associated PCT was selected. Eighteen of the 19 serologically positive HCV-PCT patients showed HCV RNA in serum. Genotype 1b was the most prevalent among both HCV-PCT patients (72.2%; 13/18) and age-matched HCV controls (50.9%; 27/53). Such different genotypic prevalence failed to reach statistical significance (chi(2) with Yates' correction, p = 0.19). The single HCV-PCT patient without detectable HCV RNA was also infected with genogroup 3 GBV-C/HGV. This GBV-C/HGV RNA prevalence (5.3%) among HCV-PCT patients is not statistically different from that observed among Argentine blood donors (5.5%; 11/200). To our knowledge, these results show for the first time the molecular epidemiology of both HCV and GBV-C/HGV associated to PCT in America.