Early liver function improvement following successful treatment of chronic hepatitis C in patients with decompensated cirrhosis: a real-life study

OBJECTIVES: Despite higher rates of sustained virologic response (SVR), important concerns remain when patients with decompensated cirrhosis due to hepatitis C virus (HCV) are treated with direct-acting antiviral agents (DAA). Questions include efficacy, safety, and the magnitude of liver function improvement. Here, we aimed to evaluate HCV treatment data in this specific population in Brazil. METHODS: We included 85 patients with decompensated cirrhosis submitted to HCV therapy with DAA followed at two academic tertiary centers in the southeastern region of Brazil. RESULTS: Seventy-nine patients (92.9%) were Child-Pugh (CP) score B, and six (7.1%) were CP score C. The mean MELD score was 12.86. The most common treatment was sofosbuvir plus daclatasvir±ribavirin for 24 weeks. The overall intention-to-treat (ITT) SVR rate was 87.4% (74/85) and modified-ITT 96.1% (74/77). ITT SVR was associated with lower baseline INR values (p=0.029). Adverse events (AE) occurred in 57.9% (44/76) of patients. Serious AE were reported in 12.8% (10/78), and were related to the presence of hepatic encephalopathy (p=0.027). SVR was associated with improvement in CP (p<0.0001) and MELD scores (p=0.021). Among baseline CP score B patients with SVR, 46% (29/63) regressed to CP score A. Ascites was independently associated with no improvement in liver function in patients who achieved SVR (p=0.001; OR:39.285; 95% CI:4.301-258.832). CONCLUSIONS: Patients with decompensated HCV cirrhosis showed a high SVR rate with interferon-free therapy. Early liver function improvement occurred after successful HCV eradication. However, long-term follow-up of these patients after SVR remains strongly advised.

Mutações de resistência aos Inibidores de Protease em pacientes com Hepatite C crônica no Brasil / Resistance-associated variants to Hepatitis C virus Protease Inhibitors in naïve DAA patients in Brazil

A resistência viral aos inibidores de protease aparece rapidamente, pois essas cepas resistentes já existem naturalmente na população de quasispécies do vírus, emergindo como cepas mais prevalentes em relação às cepas selvagens quando o vírus sofre a pressão da droga. Esta seleção de cepas resistentes (RAVs) tem um papel im¬portante na falha terapêutica dessa classe de droga. Análise por sequenciamento direto em pacientes não tratados têm demonstrado diversas RAVs aos inibidores de protease (substituições nas posi¬ções V36, T54, V55, Q80, R155, D168 e V170). As mutações nas posições R155K e A156T da região NS3 estão associadas à alta resistência aos inibidores de protease. Dessa forma, os antivirais de ação direta (DAA) não podem ser utilizados em monoterapia. Aparentemente, existe uma diferença geográfica na distribuição dessas variantes de resistência. Nas populações europeia e america¬na, por exemplo, a variante de resistência na posição Q80K no ge¬nótipo 1a, que confere resistência ao simeprevir, foi encontrada em 25% a 35%. No entanto, na população brasileira uma frequência em torno de 1,8% de RAVs na posição Q80K, em três estudos, dois em VHC monoinfectados e outro em co-infectados VHC-HIV. O conhecimento da distribuição dos subgenótipos e do perfil de mutações nas diversas populações em todo o mundo vai se tornar importante na confecção de guidelines regionais, que seguramente terão suas particularidades de acordo com o perfil de cada região, no intuito de atingirmos máxima eficácia dos diferentes esquemas terapêuticos

Viral resistance to protease inhibitors appear quickly because these resistant strains occur naturally in the virus quasispecies population, emerging as the most prevalent strains compared to wild type strains when the virus is under drug pressure. This selection of resistant strains (RAVs) has an important role in therapeutic failure of this class of drug. Analyses by direct sequencing in untreated patients have shown various RAVs to protease inhibitors (substitutions at positions V36, T54, V55, Q80, R155, A156, D168 and V170). Mutations at positions R155K and A156T on NS3 region are associated with high resistance to protease inhibitors. Thus, the direct action antivirals (DAA) may not be used as monotherapy. Apparently, there is a geographical difference in the distribution of these variants of resistance worldwide. In European and American HCV population for example, resistance variants in the position Q80K genotype 1a, which confers resistance to simeprevir was found in 25% to 35% of patients. However, in the Brazilian population the Q80K mutation was found at a frequency of around 1.8%, in three studies, two in HCV monoinfected and another in coinfected HIV-HCV patients. The distribution of this mutation profile in different populations around the world will become important in the preparation of regional guidelines, which surely will have their particularities according to the HCV subtyping distribution and mutation profile of each region in order to achieve maximum effectiveness of different treatment regimens

Estimativas de custo da hepatite crônica B no sistema único de saúde Brasileiro em 2005 / Cost estimates of chronic hepatitis B virus for the Brazilian unified health system in 2005

OBJETIVO: O objetivo deste estudo foi estimar o padrão de tratamento, a utilização de recursos e os gastos para cada estágio da HCVB, no ambiente do Sistema Único de Saúde (SUS) do Brasil, no ano 2005. MÉTODOS: Foi desenvolvido painel Delphi de especialistas para obter informação sobre o padrão de tratamento da HCVB no Brasil. Os dados foram coletados com dez médicos especialistas em hepatologia e doenças infecciosas. A valoração dos recursos foi obtida predominantemente das tabelas de pagamentos do Sistema Único de Saúde e tabelas de preços de medicamentos. As estimativas de custo tiveram a perspectiva do pagador público. Os dados foram analisados estatisticamente pelo programa SPSS 12.0 para Windows. RESULTADOS: Os gastos estimados dos pacientes foram separados em cada estágio da HCVB. O gasto estimado anual por paciente foi: R$ 980,89 para hepatite B crônica, sem cirrose e sem tratamento antiviral; R$ 1.243,17 para cirrose compensada sem tratamento antiviral; R$ 22.022,61 para cirrose descompensada; R$ 4.764,95 para o carcinoma hepatocelular; e R$ 87.372,60 para o transplante hepático. CONCLUSÃO: Os gastos estimados com procedimentos e medicamentos, excluindo antivirais, representaram os principais componentes do gasto da HCVB. Neste modelo, os gastos aumentam dramaticamente nos estágios mais avançados, sugerindo que retardar a progressão da doença poderá reduzir o gasto no longo prazo.

BACKGROUD: Chronic Hepatitis B Virus (CHBV) is a disease that places a large financial burden on healthcare systems and society. OBJECTIVE: The aim of this study was to estimate patient management patterns, and associated medical resource utilization and expenses, for each of the four stages of chronic HBV infection in the public unified healthcare system settings, in 2005. METHODS. An expert panel comprised of ten physicians, leading specialists in hepathology and infectious diseases, was convened to obtain information regarding management of CHBV patients in Brazil. Expense inputs were mainly obtained from government fee schedules and pharmaceutical price tables. Costs were estimated under the perspective of the public health system. Data were analyzed using Windows SPSS version 12.0. RESULTS: Estimated patient expenses were calculated for the four stages of CHBV infection. The estimated annual expenses per patient were: R$ 980.89 (US$ 392) for chronic hepatitis B with no cirrhosis and without antiviral therapy; R$ 1,243.17 (US$ 496) for compensated cirrhosis without antiviral therapy; R$ 22,022.61 (US$ 8809) for decompensated cirrhosis; R$ 4,764.95 (US$ 1,905) for hepatocellular carcinoma; and R$ 87,372.60 (US$ 34,948) for liver transplant. CONCLUSION: Estimated expenses associated with drugs and procedures represented the main components of the expenses of CHBV infection. In this model, expenses increase dramatically as the disease progresses to more advanced stages, suggesting that over the long term delaying progression may reduce costs.