Immunogenetic studies of the hepatitis C virus infection in an era of pan-genotype antiviral therapies - Effective treatment is coming.

What are the factors that influence human hepatitis C virus (HCV) infection, hepatitis status establishment, and disease progression? Firstly, one has to consider the genetic background of the host and HCV genotypes. The immunogenetic host profile will reflect how each infected individual deals with infection. Secondly, there are environmental factors that drive susceptibility or resistance to certain viral strains. These will dictate (I) the susceptibility to infection; (II) whether or not an infected person will promote viral clearance; (III) the immune response and the response profile to therapy; and (IV) whether and how long it would take to the development of HCV-associated diseases, as well as their severity. Looking at this scenario, this review addresses clinical aspects of HCV infection, following by an update of molecular and cellular features of the immune response against the virus. The evasion mechanisms used by HCV are presented, considering the potential role of exosomes in infection. Genetic factors influencing HCV infection and pathogenesis are the main topics of the article. Shortly, HLAs, MBLs, TLRs, ILs, and IFNLs genes have relevant roles in the susceptibility to HCV infection. In addition, ILs, IFNLs, as well as TLRs genes are important modulators of HCV-associated diseases. The viral aspects that influence HCV infection are presented, followed by a discussion about evolutionary aspects of host and HCV interaction. HCV and HIV infections are close related. Thus, we also present a discussion about HIV/HCV co-infection, focusing on cellular and molecular aspects of this interaction. Pharmacogenetics and treatment of HCV infection are the last topics of this review. The understanding of how the host genetics interacts with viral and environmental factors is crucial for the development of new strategies to prevent HCV infection, even in an era of potential development of pan-genotypic antivirals.

Use of HCV+ Donors Does Not Affect HCV Clearance With Directly Acting Antiviral Therapy But Shortens the Wait Time to Kidney Transplantation.

BACKGROUND: Hepatitis C virus (HCV) infection is prevalent in the renal transplant population but direct acting antiviral agents (DAA) provide an effective cure of HCV infection without risk of allograft rejection. METHODS: We report our experience treating 43 renal transplant recipients with 4 different DAA regimens. RESULTS: One hundred percent achieved a sustained viral response by 12 weeks after therapy, and DAA regimens were well tolerated. Recipients transplanted with a HCV+ donor responded equally well to DAA therapy those transplanted with a kidney from an HCV- donor, but recipients of HCV+ organs experienced significantly shorter wait times to transplantation, 485 days (interquartile range, 228-783) versus 969 days (interquartile range, 452-2008; P = 0.02). CONCLUSIONS: On this basis, we advocate for a strategy of early posttransplant HCV eradication to facilitate use of HCV+ organs whenever possible. Additional studies are needed to identify the optimal DAA regimen for kidney transplant recipients, accounting for efficacy, timing relative to transplant, posttransplant clinical outcomes, and cost.

Chronic Hepatitis C Treatment with Direct-Acting Antiviral Agents in a Real-Life Setting.

BACKGROUND: In clinical trials, new oral direct-acting antiviral agent therapies have demonstrated a high sustained virological response rate in patients with hepatitis C virus infection. We aimed to analyze the efficacy and safety data from direct-acting antiviral agent interferon-free therapy in hepatitis C virus infection in a study performed in five different clinical settings in Mexico City; four private practice sites and one academic medical center in a real-world scenario. METHODS: Eighty-one patients were treated with seven different direct-acting antiviral agent regimens, in which the end of treatment, sustained virological response at 12 weeks post-treatment, and adverse effects were evaluated. At their discretion, attending physicians selected the treatment regimens and durations. RESULTS: In total, 70.4% of the patients were female and the mean age was 60.7 years; 74.1% had blood transfusion as a risk factor. The most common genotype was 1b (70.4%). The fibrosis stage was F3 or F4 in 55.5% of patients; liver cirrhosis was present in 44%. The overall end of treatment response was 98.8%, and the rate of sustained virological response was 96%, independent of the regimen. Three patients did not achieve sustained virological response; they had cirrhosis and were treatment-experienced, and two had hepatocarcinoma. Non-significant adverse effects during treatment were documented. CONCLUSIONS: In this real-life setting in Mexico, a rate of 96% of sustained virological response to direct-acting antiviral agents was achieved in an older population of patients with advanced fibrosis. This study provides data that may be useful in guiding health professionals and authorities in the development of health policies.

Chronic hepatitis C virus infection: it is not only about the liver.

BACKGROUND AND AIMS: Although hepatitis B virus (HBV) and hepatitis C virus (HCV) are both hepatotropic and quite similar in terms of clinical manifestations and histopathology, their respective infections are distinct in terms of epidemiology and prognosis. Recognizing the differences between patients with HBV and HCV infection with respect to demographic characteristics, prevalence of comorbidities, and presence of lifestyle factors aids the proper treatment of these patients. We aimed to compare two populations with chronic viral liver disease (chronic HCV and chronic HBV), each of them with resolved hepatitis C. PATIENTS AND METHODS: We included patients referred to a municipal reference clinic from March 2009 through May 2012. Patient data were collected using standardized questionnaires at the patients' first visit to clinic. Questionnaires included epidemiological information, presence of comorbidities, and lifestyle. RESULTS: A total of 756 patients were included in the study, 348 (46.0%) with chronic HCV infection, 176 (23.3%) with chronic HBV infection, and 232 (30.7%) with resolved HCV infection. Multivariate analysis including patients with chronic HCV infection and chronic HBV infection indicated that age [adjusted odds ratio (AOR)=1.06; 95% confidence interval (CI): 1.03-1.08], alcohol abuse (AOR=1.58; 95% CI: 1.01-2.49), smoking (AOR=1.64; 95% CI: 1.00-2.17), and illicit drug (AOR=2.92; 95% CI: 1.69-5.02) use were associated independently with chronic HCV infection. Multivariate analyses including patients with chronic HCV infection and those patients with resolved HCV infection, presence of at least one comorbidity (AOR=1.94; 95% CI: 1.12-3.3), illicit drug use (AOR=3.24; 95% CI: 1.90-5.54), and age (AOR=1.03; 95% CI: 1.01-1.05) were independently associated with chronic HCV infection. Age (AOR=0.98; 95% CI: 0.96-0.99) and male sex (AOR=1.93; 95% CI: 1.26-2.95) were the only variables associated significantly with chronic HBV infection in the multivariate analysis between patients with chronic HBV infection and resolved HCV infection. CONCLUSION: Our results highlight that patients with chronic HCV infection are complex and require a multidisciplinary approach during patient follow-up and clinical management.

Enhanced chronic hepatitis C surveillance in New York City, April 2009-January 2011.

OBJECTIVE: We analyzed and evaluated enhanced chronic hepatitis C virus (HCV) surveillance in New York City (NYC), which involved detailed investigations on a sample of newly reported HCV patients. METHODS: Beginning in July 2009, we generated a simple random sample bimonthly from all patients newly reported with a positive HCV test. We administered questionnaires to clinicians and patients to collect clinical and epidemiological information on patients diagnosed from April 2009 to January 2011 and evaluated the staff resources required to conduct enhanced surveillance. RESULTS: Of 205 patients meeting inclusion criteria, 40 (19.5%) tested HCV ribonucleic acid (RNA) negative. For the remaining 165 patients, questionnaires were completed by 164 clinicians (99.4%) and 77 patients (46.7%). Many patients (54.0%) were born between 1945 and 1964, and most patients were Hispanic (32.7%) or non-Hispanic black (32.7%). Common risk factors were injection (43.0%) and intranasal (33.9%) drug use. One-third of patients were diagnosed in nontraditional medical settings including substance abuse/detoxification centers (25.0%), jail/prison (6.7%), and psychiatric facilities (1.8%). Of 98 patients with positive HCV RNA tests, 38.8% were immune to hepatitis A and 39.8% were immune to hepatitis B. Investigators required approximately 3.5 hours to complete each investigation and averaged 50 days from assignment to completion. CONCLUSIONS: Although conducting enhanced HCV surveillance requires significant resources, investigating a representative sample provides detailed information about NYC's HCV population. Surveillance data have been used to plan educational initiatives for clinicians and patients, which may have led to increased awareness of HCV status, improved patient support, and better overall care.

Histological evolution of hepatitis C virus infection after renal transplantation.

BACKGROUND: information regarding histological progression of hepatitis C after renal transplant (RTx) is scarce. AIMS: To analyze clinical and laboratory evolution and histological progression of hepatitis C in patients evaluated before and after RTx. METHODS: Twenty-two HCV-infected patients submitted to liver biopsy pre- and post-RTx were included. A semiquantitative analysis of necroinflammatory activity and fibrosis staging was performed and the two biopsies were compared. RESULTS: Patients were mostly men (73%) with mean age of 36±9 yr. Time post-transplant was 4±2 yr and time between biopsies was 5±2 yr. An elevation of alanine aminotransferase (p=0.041) and aspartate aminotransferase (p=0.004) levels was observed in the post-transplant period. Fibrosis progression after renal transplantation was observed in 11 (50%) of the patients, and necroinflammatory activity worsening was observed in 7 (32%) of the patients. The histological progression occurred even among those without significant histological lesions in pre-transplant biopsy. CONCLUSION: The findings of this study suggest that the practice of indicating treatment in the pre-transplant phase based mainly on histological disease should be revised, because a high proportion of patients present disease progression. Because interferon cannot be used safely after RTx, treatment should be indicated for all ESRD patients with hepatitis C.

[Hepatitis C recurrence after living donor and cadaveric liver transplantation]. / Recurrência da Hepatite C após transplante hepático de doador vivo e falecido.

OBJECTIVE: To determine the recurrence of hepatitis C in patients subjected to living donor liver transplantation compared to those subjected to cadaveric liver transplantation. METHODS: Of a total of 333 liver transplantations, 279 (83.8%) were cadaveric liver transplantation and 54 (16.2%) living donor liver transplantation. Hepatic cirrhosis due to hepatitis C virus was the most common indication of both cadaveric liver transplantation (82 patients) and living donor liver transplantation (19 patients). The electronic study protocols of all patients with hepatic cirrhosis due to hepatitis C virus were reviewed. All data, including patients' age and sex, laboratory tests, hepatitis C virus recurrence and acute rejection were evaluated statistically. RESULTS: A total of 55 cadaveric liver transplantation and 10 living donor liver transplantation performed in patients with liver cirrhosis due to hepatitis C virus was included in the study. Clinical and laboratory characteristics of the two groups before the transplantation were similar, except for the prothrombin time that was higher for the cadaveric liver transplantation than the living donor liver transplantation (P = 0.04). Hepatitis C virus recurrence was similar in the cadaveric liver transplantation (n = 37; 69.3%) and living donor liver transplantation (n = 7; 70%) groups (P = 0.8). The incidence of acute rejection was similar in cadaveric liver transplantation (n = 27; 49%) and living donor liver transplantation (n = 2; 20%) groups (P = 0.08). Hepatitis C virus recurrence in patients of the cadaveric liver transplantation group who received bolus doses of corticosteroids (9 of 11 patients) was similar to the remained patients (28 of 44 patients) (P = 0.25). Recurrence was also similar in patients of the living donor liver transplantation group who received bolus doses of corticosteroids (one of one patient) in relation to those who did not receive them (six of nine patients) (P = 0.7). CONCLUSION: Hepatitis C recurrence is similar in patients who underwent living donor liver transplantation or cadaveric liver transplantation.

Recurrência da hepatite C após transplante hepático de doador vivo e falecido / Hepatitis C recurrence after living donor and cadaveric liver transplantation

OBJETIVO: Determinar a recurrência da hepatite C em pacientes submetidos a transplante hepático de doador vivo comparados com os submetidos a transplante hepático de doador falecido. MÉTODOS: Do total de 333 transplantes hepáticos, 279 (83,8 por cento) eram de doador falecido e 54 (16,2 por cento) de doador vivo. Hepatopatia crônica pelo vírus da hepatite C foi a indicação mais comum tanto de transplante hepático de doador falecido (82 pacientes) como de doador vivo (19 pacientes). O protocolo de estudo eletrônico de todos pacientes com hepatopatia crônica pelo vírus da hepatite C foi avaliado. Os dados coletados foram analisados estatisticamente conforme a idade, sexo, resultado dos exames laboratoriais, recidiva do vírus da hepatite C e rejeição aguda. RESULTADOS: O total de 55 transplantes hepáticos de doador falecido e 10 de doador vivo realizados em pacientes com cirrose hepática pelo vírus da hepatite C, foi incluído no estudo. As características clínicas e laboratoriais pré-transplante dos dois grupos foram similares, exceto o tempo de atividade de protrombina que foi maior no grupo de transplante hepático de doador falecido do que no de doador vivo (P = 0,04). A recidiva da hepatite C foi similar nos grupos de transplante hepático de doador falecido (n = 37; 69,3 por cento) e de doador vivo (n = 7; 70 por cento) (P = 0,8). A incidência de rejeição aguda foi igual no grupo de transplante hepático de doador falecido (n = 27; 49 por cento) e no grupo de doador vivo (n = 2; 20 por cento) (P = 0,08). A recurrência do vírus da hepatite C nos pacientes do grupo de transplante hepático de doador falecido que receberam pulsoterapia (9 de 11 pacientes) foi similar aos demais pacientes (28 de 44 pacientes) (P = 0,25). A recurrência também foi similar nos pacientes do grupo de transplante hepático de doador vivo que receberam pulsoterapia (1 de 1 paciente) em relação aos que não receberam (6 de 9 pacientes) (P = 0,7). CONCLUSÕES: A recurrência...

OBJECTIVE: To determine the recurrence of hepatitis C in patients subjected to living donor liver transplantation compared to those subjected to cadaveric liver transplantation. METHODS: Of a total of 333 liver transplantations, 279 (83.8 percent) were cadaveric liver transplantation and 54 (16.2 percent) living donor liver transplantation. Hepatic cirrhosis due to hepatitis C virus was the most common indication of both cadaveric liver transplantation (82 patients) and living donor liver transplantation (19 patients). The electronic study protocols of all patients with hepatic cirrhosis due to hepatitis C virus were reviewed. All data, including patients' age and sex, laboratory tests, hepatitis C virus recurrence and acute rejection were evaluated statistically. RESULTS: A total of 55 cadaveric liver transplantation and 10 living donor liver transplantation performed in patients with liver cirrhosis due to hepatitis C virus was included in the study. Clinical and laboratory characteristics of the two groups before the transplantation were similar, except for the prothrombin time that was higher for the cadaveric liver transplantation than the living donor liver transplantation (P = 0.04). Hepatitis C virus recurrence was similar in the cadaveric liver transplantation (n = 37; 69.3 percent) and living donor liver transplantation (n = 7; 70 percent) groups (P = 0.8). The incidence of acute rejection was similar in cadaveric liver transplantation (n = 27; 49 percent) and living donor liver transplantation (n = 2; 20 percent) groups (P = 0.08). Hepatitis C virus recurrence in patients of the cadaveric liver transplantation group who received bolus doses of corticosteroids (9 of 11 patients) was similar to the remained patients (28 of 44 patients) (P = 0.25). Recurrence was also similar in patients of the living donor liver transplantation group who received bolus doses of corticosteroids (one of one patient) in relation to those who did...

Prognostic factors for progression of liver structural lesions in chronic hepatitis C patients.

AIM: To evaluate the epidemiological, clinical, laboratory and histological variables capable of predicting the progression of hepatic structural disturbances in chronic hepatitis C patients during the time interval between two liver biopsies. METHODS: Clinical charts of 112 chronic hepatitis C patients were retrospectively analyzed, whereas liver biopsies were revised. Immunohistochemical detection of interferon receptor was based on the Envision-Peroxidase System. RESULTS: In the multivariate analysis, the variables in the age at first biopsy, ALT levels, presence of lymphoid aggregates and siderosis were the determinants of the best model for predicting the severity of the disease. The direct progression rate of hepatic structural lesions was significantly higher in untreated patients, intermediate in treated non-responders and lower in treated responders to antiviral therapy (non-treated vs responders, 0.22 +/- 0.50 vs -0.15 +/- 0.46, P = 0.0053). Immuno-expression of interferon receptor is not a relevant factor. CONCLUSION: The best predictors of the progression of fibrosis are age at the first liver biopsy, extent of ALT elevation, inflammation at liver histology and hepatic siderosis. Antiviral treatment is effective in preventing the progression of liver structural lesions in chronic hepatitis C patients.

Oral lichen planus and chronic hepatitis C: a controversial association.

Our aim was to study the possible association between oral lichen planus and chronic hepatitis C in patients from the state of Minas Gerais, Brazil. Two groups of patients were studied: group 1, 50 patients with oral lichen planus evaluated for the presence of chronic hepatitis C; and group 2, 215 patients with chronic hepatitis C examined for evidence of oral lichen planus. Diagnosis of oral lichen planus in both groups was based on clinical and histologic findings. One case of chronic hepatitis C was diagnosed in group 1 (2.0%), which was not considered statistically significant (P = .464). In group 2, the prevalence of oral lichen planus was 2.3% (5 cases), which showed statistical significance (P = .002). Although our results suggest oral lichen planus as an extrahepatic manifestation of chronic hepatitis C in the studied population, the association between these two entities should be further investigated.

Tratamento assistido e compartilhado da hepatite C com interferon preguilado alfa-2b: a perspectiva do paciente / Hepatitis C treatment with pegylated interferon alpha-2b

Introdução: Para o tratamento de pacientes com o vírus da hepatite C, a terapêutica preconizada é baseada no interteron (IFN) combinado com a ríbavirína. Modificações introduzidas no IFN convencional por peguilação (PEG-INF) resultaram em resposta mais eficaz, proporcionando comodidade, adesão e melhora na qualidade de vida. O PEG-INF está disponível nos pólos de aplicação e por razões de farmacoeconomia, racionalização de dose e aplicação, a administração semanal deve ser praticada em serviços identifica- dos pelos órgãos de Saúde. Assim, as ampolas ficam em poder dos serviços já mencionados e não dos pacientes em tratamento. Objetivos. Em virtude disso, buscamos avaliar o nível de satisfação dos pacientes e profissionais paramédicos, com os serviços oferecidos nos pólos de aplicação do tratamento para hepatite C. Material e método: A pesquisa foi conduzida por um instituto de pesquisa independente, e foi implementada com base no método descritivo de pesquisa, com foco quantitativo. Foram realizadas coletas prospectivas de dados por meio de entrevistas pessoais com 253 pacientes em oito pólos de aplicação das regiões metropolitana, capital e cidades do interior. Resultados: Compartilhar experiências com pessoas portadoras da mesma doença estimula a grande maioria dos pacientes a continuar o tratamento e quase 90por cento destes pacientes se sentem satisfeitos em participar da possibilidade de compartilhar a aplicação do alfa PEG- INF 2b Na visão dos pacientes, o bom atendimento, a economia e a presença de enfermagem treinada e especializada foram os três pontos positivos mais mencionados. A vasta maioria tomou todas as doses de alfa PEG-INF 2b e, aqueles que deixaram de tomar, omitiram somente cerca de 10 por cento do total das doses prescritas. Conclusão: Pelos resultados da pesquisa pode concluir-se que é elevado o nível de satisfação com o trata- mento assistido e compartilhado do alfa PEG-INF2b,- fica mais evidenciado quando mais de 30por cento dos pacientes não encontram nenhum ponto que possa ser melhorado no tratamento assistido e compartilhado do alfa PEG-INF 2b

Chronic liver disease in kidney recipients with hepatitis C virus infection.

BACKGROUND: The prevalence of anti-hepatitis C virus (HCV) positive test is higher among patients in dialysis and in kidney recipients than in general population. Hepatitis C virus infection is the main cause of chronic liver disease in renal transplant patients. Liver biopsy and virological analysis were performed to clarify the grade of liver damage in kidney recipients. METHODS: Renal recipients patients with at least 5 yr under immunosuppression were submitted to clinical and laboratory analysis. Patients who tested anti-HCV positive were candidates to liver biopsy with no regard to transaminase levels. RESULTS: Forty-five patients tested anti-HCV positive and 42 anti-HCV negative. Twenty-six anti-HCV and RNA-HCV positive patients were submitted to liver biopsy. Seventy-three percentage of these patients presented chronic active hepatitis, from these only one patient presented cirrhosis. Only 29% of the anti-HCV positive group presented elevated alanine aminotransferase levels. Anti-HCV positive patients presented longer previous time on dialysis and less rejection episodes than the group anti-HCV negative (p < 0.05). All anti-HCV positive patients but one tested RNA-HCV positive by polymerase chain reaction (PCR). CONCLUSIONS: In this series the prevalence of anti-HCV positive is 51.7%. Most of the patients presented liver damage in histology caused by HCV. However, we found only mild or minimal fibrosis and inflammatory activity grade, despite 10 yr of HCV infection and 5 yr of immunosuppressive treatment. Only one patient presented cirrhosis (4%). Performing serial liver biopsies in a long-term follow-up is needed to clarify the impact of HCV infection in renal transplant patients.

Hepatite colestática associada ao vírus da hepatite C pós-transplante hepático: estudo virológico, histopatológico e imuno-histoquímico / Severe recurrent cholestatic hepatitis after liver transplantation: virological, histological and immuno-histochemical evaluation

A evolução da recorrência da hepatie C pós-transplante hepático pode ter um curso bastante variável. Raramente a doença pode progredir para uma forma conhecida como hepatite recorrente colestática grave, cuja patogenia ainda não é bem conhecida. Nós estudamos nesse trabalho alguns aspectos virológicos, histológicos e imunohistoquímicos de seis pacientes com essa forma rara de recorrência da doença, tendo como comparação um grupo pareado de seis pacientes transplantados com a forma leve de hepatite C recorrente, e como controle imunocompetente, cinco pacientes não transplantados com hepatite crônica pelo vírus C. Foram avaliados como possíveis fatores preditivos de gravidade da progressão da recorrência: viremia do VHC, evolução de quasispécies, parâmetros histopatológicos, e imunoreatividade para o antígeno core do VHC.Following liver transplantation (OLT) HCV-related disease severity is highly variable, with a minority of cases progressing to an extremely severe form of cholestatic hepatitis, in which the pathogenesis is not yet understood. We aim to compare virological, histological and immunohistological changes in patients developing mild and severe post-OLT HCV recurrence. Twelve patients with recurrent HCV infection were studied (6 with severe and 6 with mild disease). Five HCV-infected immunocompetent patients were used as controls. We looked at viral load, quasispecies evolution of HCV, several histological parameters and immuno-reactivity of core antigens at three time-points (pre-OLT, early post-OLT and late post-OLT) as predictors of severity of recurrence post-OLT...

[Pathogenesis of hepatitis C virus infection]. / Patogénesis de la infección por virus de hepatitis C.

The hepatitis C virus (HCV) is the leading cause of chronic liver disease worldwide. Chronic hepatitis C is a mayor cause of cirrhosis and hepatocellular carcinoma and HCV-related end-stage liver disease is, in many countries, the first cause of liver transplantation. HCV infection is characterized by its propensity to chronicity. Because of its high genetic variability, HCV has the capability to escape the immune response of the host. HCV is not directly cytopathic and liver lesions are mainly related to immune-mediated mechanisms that are characterized by a predominant type 1 helper cell response. Co-factor influencing the outcome of the disease including age, gender and alcohol consumption are poorly understood and other factors such as immunologic and genetic factors may play and important role. Recent studies have shown that the combination therapy with alpha interferon and ribavirin induces a sustained virological response in about 40% of patients with chronic hepatitis C. The lack of animal models and of in vitro cultures systems hampers the understanding of the pathogenesis of chronic hepatitis C and the development of new antivirals. The conjugation of polyethyleneglycol improved the pharmacodynamics and the efficacy of alpha interferon. The development of an effective vaccine remains the most difficult challenge. Because of the high protein variability of HCV, protective vaccines could be extremely difficult to produce and therapeutic vaccines seem more realistic. Considerable progress has been made in the field of HCV since its discovery 10 years ago but a major effort needs to be made in the next decade to control HCV-related disease.

The impact of azathioprine on chronic viral hepatitis in renal transplantation: a long-term, single-center, prospective study on azathioprine withdrawal.

BACKGROUND: In transplanted patients, viral hepatitis progresses to chronic liver disease and patient's death after many years of transplantation. Also, it is well known that azathioprine (AZA) is harmful to the liver of these patients. However, it is unclear whether a low dose of AZA still represents a threat to the viral liver disease. METHODS: A total of 79 patients with hepatitis C, B, or both, transplanted between 1973 and 1990, were grouped according to whether they had AZA either withdrawn from the immunosuppressive regimen [group (G) I, n=45] or a dosage reduction only (group II, n=34). The decision to remove or to keep AZA was restricted to the patient's doctor. Patients records were reviewed by April 1997. RESULTS: After an equal time of follow-up, after the AZA changing (64+/-26 vs. 58+/-29 months), patients in GI showed a significant decrease in the serum liver parameters when compared to baseline [alanine aminotransferase (ALT): P=0.001; gamma-glutamyl transferase (gamma-GT): P=0.001 and total bilirubin: P=0.002], whereas in GII only ALT decreased (P=0.04) although gamma-GT and total bilirubin did not. Compared to baseline, serum creatinine (SCr) increased only in GI (P=0.001) but, at last follow-up, did not differ from GII. The intention-to-perform liver biopsies was equal in GI and GII (16 vs. 14) but the hystological findings of severe chronic liver disease (either chronic active hepatitis or cirrhosis) were more frequent in GII (P=0.004). Death with a functioning graft was much more frequent in GII than in GI (P=0.001). Infection and cirrhosis were more common as a cause of death in GII than in GI. CONCLUSIONS: The use AZA is harmful to renal transplantation patients with both chronic hepatitis C and B and, therefore, should be avoided. AZA withdrawal, but not dose adjustments, diminishes the serum liver enzymes and the progression rate of the chronic viral liver disease as well as the rate of death secondary to infection and cirrhosis.

Antibody-negative chronic hepatitis C virus infection in immunocompetent children.

Antibody-negative hepatitis C virus (HCV) infection, defined by the presence of HCV viremia in the absence of a serologic response to HCV, was detected in two immunocompetent and symptom-free children; each had a history of exposure to blood products. HCV infection may occasionally explain cryptogenic elevation of aminotransferases, even in the absence of serum anti-HCV. HCV-RNA should be investigated in these cases, particularly in the presence of previous exposure to blood products.