Acquired hemophilia A associated with Epstein-Barr-virus-associated T/natural killer-cell lymphoproliferative disease: A case report.

INTRODUCTION: Acquired hemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies against factor VIII (FVIII). Hematological malignancies, especially lymphoid malignancies, are known to be underlying causes of AHA; however, thus far, there is no report of AHA associated with Epstein-Barr-virus-associated T/natural killer-cell lymphoproliferative disease (EBV-T/NK-LPD). Here, we present a case of AHA that developed during treatment for EBV-T/NK-LPD. HISTORY: A 69-year-old man visited our hospital because of general fatigue. Blood examination showed pancytopenia, and computed tomography revealed whole-body lymphadenopathy, but there were no findings indicating hematological malignancy from bone marrow aspiration and cervical lymph node biopsy. The level of EBV DNA in peripheral blood was extremely high, and he was diagnosed with EBV-T/NK-LPD. EBV-T/NK-LPD improved with prednisolone (PSL) administration. Seventeen months after starting treatment, the patient complained of back and right leg pain. At that time, he had been treated with low-dose PSL, and EBV-T/NK-LPD was well controlled. Imaging revealed hematoma of the right iliopsoas muscle. Prolonged activated partial thromboplastin time (APTT) was the only abnormal finding in a screening coagulation test. FVIII coagulant activity was below detection limit, and FVIII inhibitor level was increased. From these results, he was diagnosed with AHA.A higher dose of PSL was administered, and, after 1 month of treatment, FVIII activity gradually increased, and FVIII inhibitor level became undetectable. APTT also normalized, and complete remission was achieved and maintained for 13 months with low-dose PSL. During treatment, EBV-T/NK-LPD was well controlled. CONCLUSION: It is speculated that proliferating lymphocytes interfere with normal immune functions and that abnormal autoantibodies are produced from those lymphocytes in patients with LPD. Therefore, we speculate that EBV-infected and proliferating monoclonal NK cells might have modulated the immune system and produced autoantibodies against FVIII, thus causing AHA in this patient with EBV-T/NK-LPD.

HIV-associated and idiopathic-acquired haemophilia A: A single-centre case series from Cape Town, South Africa.

Acquired haemophilia A is a rare coagulation disorder, which can lead to life-threatening haemorrhages if not identified and treated promptly. It is characterised by the presence of autoantibodies (inhibitors) to factor VIII. Acquired haemophilia A associated with HIV is a rare but well described phenomenon with limited directions to its management. We comparatively describe four patients - two with HIV and two without - that presented with unusual bleeding episodes with a prolonged activated partial thromboplastin time secondary to factor VIII inhibitors. An empiric observation is that the patients with acquired haemophilia A associated with HIV had higher antibody titres at presentation, that required more prolonged immunosuppressive therapy to induce remission.

Impact of Blood Transfusion on the Prevalence of HHpgV-1, HPgV-1, and B19V Among Iranian HCV-infected Patients With Hemophilia.

OBJECTIVE: Blood-derived products from patient with hemophilia treated by factor VIII concentrates are potential sources of transfusion-transmitted infections, including human immunodeficiency virus, hepatitis, human pegivirus-1 (HPgV-1), B19 virus, and also human hepegivirus-1 (HHpgV-1). In the current study, we investigated the impact of blood transfusion on the prevalence of HHpgV-1, HPgV-1, and B19 virus in plasma of Iranian patient with hemophilia after direct-acting antiviral treatment of hepatitis C virus (HCV) infections for the first time. MATERIALS AND METHODS: A total of 170 patients with hemophilia who received direct-acting antivirals were enrolled in this study. Among them, 92 patients had a history of blood transfusion. The presence of HHpgV-1, HPgV-1, and B19 virus was detected by nested polymerase chain reaction analysis using the conserved primers. The plasmids harboring 5'-UTR and NS3 were used as positive controls for HPgV-1 and HHpgV-1, respectively. RESULTS: Our data identified 3 individuals with HHpgV-1 viremia (1.76%), 11 individuals with HPgV-1 viremia (6.47%), and 33 individuals with B19 viremia (19.4%). All patients were negative for hepatitis B virus, human immunodeficiency virus, and HCV infections. These findings indicated lower transmissibility or higher rates of virus clearance for HHpgV-1, HPgV-1, and B19 virus as compared with other bloodborne human flaviviruses such as HCV. However, the prevalence of B19 virus was significantly higher than the other 2 viruses. CONCLUSION: In general, these findings showed that the history of blood transfusion could increase the risk of viral transmission of bloodborne viruses among patient with hemophilia.

First Report of Prevalence of Blood-Borne Viruses (HBV, HCV, HIV, HTLV-1 and Parvovirus B19) Among Hemophilia Patients in Afghanistan.

Blood-borne viruses including Hepatitis B and C, HIV, HTLV-1 and parvovirus B19 are still a factor of concern, especially for hemophilia patients. Although the safety of the blood supply continues to improve worldwide, the blood supply system in Afghanistan was damaged by many years of conflict and political instability. To date, there are few studies focused on the prevalence of blood-borne viruses in hemophilia patients. This study is first to investigate the prevalence of five blood-borne viruses in Afghanistan hemophilia patients in four cities including Kabul, Herat, Mazar-i-Sharif and Jalal Abad. A total of 80 hemophilia male patients were screening for the presence of five transfusion-transmitted viruses using ELISA and PCR. Data obtained showed 2.5% seropositivity for HBV, 8.75% seropositivity for HCV, and 91.25% seropositivity for parvovirus B19. None of the patients were positive for HIV and HTLV-1 and the prevalence of HCV was higher in older patients rather than younger patients. This finding, the first to report in Afghanistan, shows a high prevalence of parvovirus B19 in Afghanistan hemophilia patients and implementation of highly sensitive screening is necessary.

Selection of TI8-8V mutant associated with long-term control of HIV-1 by cross-reactive HLA-B*51:01-restricted cytotoxic T cells.

Elite controllers of HIV-1-infected HLA-B*51:01(+) hemophiliacs, who remain disease free and have a very low plasma viral load for >30 y, had the 8V mutation at an immunodominant Pol283-8 (TI8) epitope, whereas the 8T mutant was predominantly selected in other HIV-1-infected HLA-B*51:01(+) hemophiliacs, suggesting an important role of the 8V mutant selection in long-term control of HIV-1. However, the mechanism of this selection and the long-term control in these elite controllers remains unknown. In this study, we investigated the mechanism of the 8V mutant selection in these controllers. TI8-specific CTLs from these individuals evenly recognized both TI8 peptide-pulsed and TI8-8V peptide-pulsed cells and effectively suppressed replication of wild-type (WT) and the 8V viruses. However, the results of a competitive viral suppression assay demonstrated that CTLs from the individual who had WT virus could discriminate WT virus from the 8V virus, whereas those from the individuals who had the 8V virus evenly recognized both viruses. The former CTLs carried TCRs with weaker affinity for the HLA-B*51:01-TI8-8V molecule than for the HLA-B*51:01-TI-8 one, whereas the latter ones carried TCRs with similar affinity for both molecules. The reconstruction of the TCRs from these CTLs in TCR-deficient cells confirmed the different recognition of the TCRs for these epitopes. The present study showed that the 8V mutant virus could be selected by cross-reactive CTLs carrying TCR that could discriminate a small difference between the two molecules. The selection of the 8V mutant and elicitation of these two cross-reactive CTLs may contribute to the long-term control of HIV-1.

Potential usefulness of thrombopoietin receptor agonists in haemophiliacs with thrombocytopaenia due to chronic liver disease.

New thrombopoietin receptor agonists (TPO-RA) eltrombopag and romiplostin were initially used for refractory immune thrombocytopaenic purpura, but more recently reported experience shows that they may also be applied to patients with thrombocytopaenia secondary to hepatitis C virus (HCV)-related chronic liver disease (CLD) in certain clinical situations; in haemophilic patients these drugs are always part of a therapeutic approach involving other haemostatic resources required to cover the joint congenital and acquired bleeding diathesis found in these patients. Platelet count elevation before invasive procedures or surgery or prior to and during antiviral therapy involving interferon are the main clinical applications of these drugs; they might also be useful in cases with advanced CLD and severe thrombocytopaenia in order to prevent recurrent bleeding episodes (namely articular and muscular in haemophilic individuals) or reduce bleeding risk in patients with multiple haemorrhagic risk factors. Long-term prophylactic treatment with factor concentrates in such cases is mandatory. There have been some reports of portal or splanchnic thromboses in patients on TPO-RA with CLD, especially in cases undergoing invasive procedures who reach platelet counts at least 200×10/l and often with additional risk factors for thrombosis. For this reason, and although haemophilic patients have an important protection against thrombosis, platelet counts should ideally be maintained between 50 and 100×10/l with dose adjustments carried out as required and initial doses of eltrombopag in patients with moderate or severe CLD, especially in prolonged treatments, should be reduced to 25 g once daily. These new drugs can be a useful adjuvant tool in patients with thrombocytopaenia secondary to CLD.

Sweet's syndrome in a patient with haemophilia, HIV and hepatitis C infection.

Sweet's syndrome is a rare skin condition associated with both drug treatment and a number of different disease processes including haematological malignancies, inflammatory conditions and HIV infection. In this case report, we present a patient with HIV, haemophilia and hepatitis C who presented to our team with significant thrombocytopaenia and Sweet's syndrome. We discuss the difficulties with diagnosis and management in the context of multiple co-morbidities and suggest that both hepatitis C and HIV may have been aetiologically involved by suppressing platelet production and also causing bone marrow-driven neutrophilic disease.

Neutralizing antibodies against adeno-associated virus examined prospectively in pediatric patients with hemophilia.

Recombinant adeno-associated virus (rAAV) is a promising gene delivery vector and has recently been used in patients with hemophilia. One limitation of AAV application is that most humans have experienced wild-type AAV serotype 2 exposure, which frequently generates neutralizing antibodies (NAbs) that may inhibit rAAV2 vector transduction. Employing alternative serotypes of rAAV vectors may circumvent this problem. We investigated the development of NAbs in early childhood by examining sera gathered prospectively from 62 children with hemophilia A, participating in a multi-institutional hemophilia clinical trial (the Joint Outcome Study). Clinical applications in hemophilia therapy have been suggested for serotypes AAV2, AAV5 and AAV8, therefore NAbs against these serotypes were serially assayed over a median follow-up of 4 years. NAbs prevalence increased during early childhood for all serotypes. NAbs against AAV2 (43.5%) were observed more frequently and at higher titers compared with both AAV5 (25.8%) and AAV8 (22.6%). NAbs against AAV5 or AAV8 were rarely observed in the absence of co-prevalent and higher titer AAV2 NAbs, suggesting that NAbs to AAV5 and AAV8 were detected following AAV2 exposure due to partial cross-reactivity of AAV2-directed NAbs. The results may guide rational design of clinical trials using alternative AAV serotypes and suggest that younger patients who are given AAV gene therapy will benefit from the lower prevalence of NAbs.

Correlates of high hepatitis C virus RNA load in a cohort of HIV-negative and HIV-positive individuals with haemophilia.

Hepatitis C virus (HCV) treatment failure and disease progression are more likely with high HCV-RNA load. Correlates of high HCV-RNA load in individuals with haemophilia are largely unknown. Among 1266 interferon naïve HCV-infected individuals with haemophilia, we compared those with high (> 2 x 106 HCV-RNA copies/mL) to lower viral load, overall and stratifying on HIV co-infection status using logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). Overall, high HCV load was independently associated with longer duration of HCV infection (P(trend)=0.0001), body mass index ≥ 25 kg/m² (OR=1.4, 95% CI=1.1-1.9), and HIV co-infection (OR=1.4, 95% CI=1.0-1.8). Among 795 HIV-negative participants, high HCV-RNA load was associated with older age at HCV acquisition (OR=1.9 for > 15 years vs ≤ 2 years, P(trend)=0.008), and lower AST/platelet ratio (P(trend)=0.01), in addition to longer duration of HCV infection (P(trend)=0.0008), and body mass index ≥ 25 kg/m² (OR=1.6, P=0.005). Among 471 HIV-positive individuals, anti-retroviral therapy (ART) was the only variable associated with high HCV-RNA load (OR=1.8, CI=1.1-2.9 for combination ART; OR=1.8, CI=0.9-3.4, for other ART vs no treatment). High HCV-RNA load with haemophilia is more likely with longer duration of infection, older age at infection, higher body mass index, and antiretroviral therapy. These findings may help identify individuals at increased risk of HCV treatment failure and progression to end-stage liver disease.

Acquired haemophilia A and Kaposi's sarcoma in an HIV-negative, HHV-8-positive patient: a discussion of mechanism and aetiology.

BACKGROUND: Acquired haemophilia A (AHA) is a rare bleeding disorder caused by an imbalance in the immune system leading to the production of factor VIII antibodies. In half of the cases, the underlying cause is not known. CLINICAL HISTORY: We report on a patient with AHA and Kaposi's sarcoma (KS), which is caused by the human herpes virus 8 (HHV-8). The patient presented with appendicitis and developed several severe post-operative haemorrhages. He spent 3 months in intensive care due to long and difficult infections. While recuperating on the ward, the patient developed KS in the lower extremities. He had a positive HHV-8 infection. DISCUSSION/CONCLUSION: Due to its latency and replication in the lymphoid system, HHV-8 is an ideal candidate for causing an imbalance in the immune system in susceptible patients. Our conclusion is that AHA was caused or prompted by the HHV-8 infection. Since HHV-8 viral infection is often subclinical, viral testing might be an important tool in acquired haemophilia diagnostics even when viral symptoms are absent.

Long-term control of HIV-1 in hemophiliacs carrying slow-progressing allele HLA-B*5101.

HLA-B*51 alleles are reported to be associated with slow disease progression to AIDS, but the mechanism underlying this association is still unclear. In the present study, we analyzed the effect of HLA-B*5101 on clinical outcome for Japanese hemophiliacs who had been infected with HIV-1 before 1985 and had been recruited in 1998 for this study. HLA-B*5101(+) hemophiliacs exhibited significantly slow progression. The analysis of HLA-B*5101-restricted HIV-1-specific cytotoxic T-lymphocyte (CTL) responses to 4 HLA-B*-restricted epitopes in 10 antiretroviral-therapy (ART)-free HLA-B*5101(+) hemophiliacs showed that the frequency of Pol283-8-specific CD8(+) T cells was inversely correlated with the viral load, whereas the frequencies of CD8(+) T cells specific for 3 other epitopes were positively correlated with the viral load. The HLA-B*5101(+) hemophiliacs whose HIV-1 replication had been controlled for approximately 25 years had HIV-1 possessing the wild-type Pol283-8 sequence or the Pol283-8V mutant, which does not critically affect T-cell recognition, whereas other HLA-B*5101(+) hemophiliacs had HIV-1 with escape mutations in this epitope. The results suggest that the control of HIV-1 over approximately 25 years in HLA-B*5101-positive hemophiliacs is associated with a Pol283-8-specific CD8(+) T-cell response and that lack of control of HIV-1 is associated with the appearance of Pol283-8-specific escape mutants.

Variant CJD infection in the spleen of a neurologically asymptomatic UK adult patient with haemophilia.

SUMMARY: All UK patients with bleeding disorders treated with any UK-sourced pooled factor concentrates between 1980 and 2001 have been informed that they may be at an increased risk of infection with variant Creutzfeldt-Jakob disease (vCJD). We describe a study to detect disease-associated, protease-resistant prion protein (PrP(res)) in 17 neurologically aymptomatic patients with haemophilia considered to be at increased risk of vCJD. Materials from 11 autopsy and seven biopsy cases were analysed for PrP(res). The tissues available from each case were variable, ranging from a single biopsy sample to a wide range of autopsy tissues. A single specimen from the spleen of one autopsy case gave a strong positive result on repeated testing for PrP(res) by Western blot analysis. This tissue came from a 73-year-old male patient with no history of neurological disease, who was heterozygous (methionine/valine) at codon 129 in the prion protein gene. He had received over 9000 units of factor VIII concentrate prepared from plasma pools known to include donations from a vCJD-infected donor, and some 400,000 units not known to include donations from vCJD-infected donors. He had also received 14 units of red blood cells and had undergone several surgical and invasive endoscopic procedures. Estimates of the relative risks of exposure through diet, surgery, endoscopy, blood transfusion and receipt of UK-sourced plasma products suggest that by far the most likely route of infection in this patient was receipt of UK plasma products.

Hepatitis C virus/human immunodeficiency virus coinfection in hemophiliacs: high rates of sustained virologic response to pegylated interferon and ribavirin therapy.

BACKGROUND: Progression of chronic hepatitis C virus (HCV) infection to end-stage liver disease is accelerated in patients coinfected with human immunodeficiency virus (HIV). HCV/HIV-coinfected hemophiliacs are no exception. Although eradication of HCV with pegylated interferon (Peg-IFN) plus ribavirin (Rbv) is the only approach to halt the progression of liver disease, the rates of sustained virologic response (SVR) in coinfected patients are attenuated as compared with those in HCV-monoinfected patients. Nonetheless, in HCV-infected hemophiliacs, who are considered to constitute a difficult-to-treat population, current treatment strategies yielded rates of SVR similar to those obtained in non-hemophiliacs. OBJECTIVES AND PATIENTS: In this open-label, prospective, multicenter study, the efficacy and safety of therapy with Peg-IFNalpha2a plus Rbv was evaluated in 34 HCV/HIV-coinfected adult hemophiliacs naive to previous antiviral therapy. METHODS: Peg-IFNalpha2a was administered at a dose of 180 mug subcutaneously once-weekly plus oral Rbv 1000-1200 mg day(-1) for 48 weeks, irrespective of HCV genotype. RESULTS: All but one patient (3%) completed the study, 15 (44%) achieved an SVR, and 13 (38%) required dose reduction of either drug. A rapid virologic response (HCV-RNA clearance at week 4; P = 0.01), a complete early virologic response (HCV RNA clearance at week 12; P = 0.005) and absence of cirrhosis (P = 0.04) were independent predictors of SVR. During a median post-treatment follow-up of 3 years, a steady increase in CD4+ cell count and CD4+/CD8+ cell ratio was observed in SVR patients. CONCLUSIONS: These results strongly support the use of anti-HCV therapy in HCV/HIV-coinfected hemophiliacs.

[Replication of HCV in bone marrow of patients with haematological disorders]. / Replikacja wirusa zapalenia watroby typu C (HCV) w szpiku kostnym pacjentów z zaburzeniami hematologicznymi.

UNLABELLED: The aim of the study was to evaluate the presence of HCV replication in bone marrow cells derived from patients displaying hematological disorders. We analysed serum, peripheral blood mononuclear cells (PBMC) and bone marrow samples obtained from 27 patients displaying the following dysfunctions: lymphoma, trombocytopenia, haemophilia, pancytopenia and acute myeloid leukemia (AML). The presence of HCV-RNA in samples was detected by RT-PCR. All the serum samples were HCV-RNA positive as well as 9 out of 27 (33%) PBMC and 17 out of 27 (63%) of bone marrow samples. Independently to the disorder type, the co-presence of HCV-RNA in serum and bone marrow with the simultaneous absence of the viral genetic material in PBMC was detected in 5 (18.5%) of patients. This result suggests that bone marrow is a site of active viral replication. To check whether a viral replication generates any mutations, an SSCP analysis of the 5'UTR viral region was performed. The difference in the viral sequence derived from serum, PBMC and bone marrow was detected in one case. This result may indicate the occurrence of mutation process during the viral replication in bone marrow. An immunohistochemical analysis of bone marrow smears showed the presence of HCV antigens. CONCLUSION: bone marrow cells of patients displaying hematological disorders represent a putative site of extrahepatic HCV replication.

Percutaneous liver biopsy in hemophiliac children with chronic hepatitis C virus infection.

OBJECTIVE: To develop a protocol for safe performance of percutaneous liver biopsies in children with deficiency of factor VIII (n = 12) or IX (n = 2) and chronic hepatitis C virus infection. PATIENTS AND METHODS: Liver biopsies were performed after administration of factor VIII or IX, before and 24 weeks after cessation of antiviral therapy. To define the optimal means of providing replacement therapy, 10 children were enrolled in a randomized crossover design study of bolus versus continuous factor VIII for performance of the liver biopsy. For the crossover study, all of the patients were given a loading dose of 50 +/- 5 IU recombinant factor (rF)VIII/kg; a minimum of factor VIII activity of > or = 80% 30 to 60 minutes following factor VIII infusion was required for liver biopsy. For the bolus protocol, rFVIII 25 to 50 IU/kg was given 6, 14, 24, 36, 48, and 60 hours after completion of the loading dose. For the continuous protocol, rFVIII was given 3 to 4 IU/kg per hour for 48 hours, followed by a bolus of 25 IU/kg at 60 hours. In patients with factor IX deficiency, a loading dose of 100 IU/kg was followed by a bolus of 50 IU/kg at 3, 15, 27, and 48 hours after the loading dose. RESULTS: Twenty liver biopsies were performed in children with factor VIII deficiency without major complications. One of the 3 biopsies in the patients with factor IX deficiency was complicated by a hemoperitoneum. Midazolam and fentanyl were used in the first 8 patients. However, postbiopsy pain, presumably secondary to hematoma in 2 patients and hemoperitoneum in 1, prompted us to use ultrasound to locate a suitable biopsy site and to change to propofol; this allowed us to better immobilize the liver, to minimize postbiopsy bleeding. The subsequent 15 biopsies were well tolerated without postbiopsy pain or other complication. CONCLUSIONS: Percutaneous liver biopsy in children with factor VIII deficiency can be safely performed using either bolus or continuous infusion of recombinant factor VIII. A brief general anesthetic and ultrasound guidance are recommended.

Feasibility, safety and cost-effectiveness of transjugular liver biopsy following major surgery in patients with haemophilia.

Prior to the introduction of virally inactivated clotting factor concentrates, the majority of patients with haemophilia became infected with the hepatitis C virus. Although transjugular liver biopsy can be safely performed in these patients, the procedure is associated with a significant financial burden mainly related to replacement therapy with clotting factor. The purpose of this study was to evaluate the feasibility and safety of transjugular liver biopsy in patients with haemophilia substituted with clotting factor concentrates for major surgical procedures. Over the last 5 years, transjugular liver biopsy was performed in nine patients with haemophilia within 1-10 days after orthopaedic (7), thoracic (1) or abdominal surgery (1). All patients had abnormal liver function tests and persistent hepatitis C viraemia. At the time of the biopsy, patients received recombinant factor VIII delivered by dose-adjusted continuous infusion through a central catheter inserted preoperatively in the left internal jugular (n = 8) or in an ante-cubital vein (n = 1). Before the biopsy, basal FVIII levels were raised to 80-100% by a bolus infusion and maintained above 80% for 24 h. The biopsy was informative in all cases. Only one patient developed an episode of supraventricular dysrhythmia. No bleeding or infectious complications were observed. When compared with elective liver biopsy performed outside the postsurgical period, the cost-savings per biopsy were 19 875 +/- 2660 euro. This study shows that intensive replacement therapy required by surgical procedures provides a safe and cost-effective opportunity for transjugular liver biopsy in patients with haemophilia and active hepatitis C.

Prevalence of hepatitis C virus infection and HCV genotypes among hemophiliacs in the State of Bahia, Northeastern Brazil: analysis of serological and virological parameters

O objetivo deste estudo foi analisar parâmetros sorológicos e virológicos em hemofílicos no Estado da Bahia. O anti-VHC foi investigado por ELISA em uma coorte de 268 hemofílicos A/B sob acompanhamento em uma unidade de referência do Estado da Bahia. A viremia do VHC e genótipos foram determinados em um subgrupo de 66 hemofílicos soropositivos para o anti-VHC. A soroprevalência do anti-VHC entre os hemofílicos foi de 42,2% (IC 95% 36,5-48,1) e foi associada significativamente (p<0,05) a idade >10 anos, presenca de anticorpos antifator VIII/IX e outros marcadores sorológicos de infeccão. Nenhum dos hemofílicos com idade inferior a 5 anos foram anti-VHC positivos. A viremia foi detectada em 77,3% (51/66), sendo o genótipo 1 do VHC (74%) o mais prevalente, seguido pelos genótipos 3 (22%) e 2 (4%). Nossos resultados indicam que a prevalência do VHC é ainda alta entre os hemofílicos, muito embora a transmissão não tenha sido observada entre os menores de 5 anos.

Hepatitis C virus infection in adult Chinese hemophilia patients negative for the human immunodeficiency virus: treatment results with interferon and ribavirin.

Hepatitis C virus (HCV) eradication in hemophilia patients depends on viral and patient factors. We report the treatment results with interferon 3 (5 megaunits, 3 times per week) and ribavirin (1 g daily) for 1 year in 17 Chinese patients who were negative for the human immunodeficiency virus. The HCV genotype consisted of a mixture of Western (genotypes 1, 2, and 3) and Chinese (genotypes 1 and 6) patterns. Quasi species were common (29%). Seven patients (41%) stopped treatment because of complications. Sustained HCV eradication was achieved until the end of treatment or for 24 months in 7 of 17 patients, respectively. A sustained response occurred in 50% of the patients completing treatment and occurred only in patients with genotypes 1, 3, and 6 but not with quasi species.