Hepatitis C treatment: shorter and better?

Herein, we present a synthesis of two publications that evaluate an abbreviated therapeutic approach to treating chronic hepatitis C virus (HCV) infection. Based on those publications, we discuss the use of the early virologic response (EVR) as a tool for the optimized management of patients under treatment, as well as reviewing concepts of HCV viral kinetics. The fourth-week EVR, characterized by HCV RNA dropping to undetectable levels, allows individuals infected with HCV genotype 1 and presenting low baseline viral loads to be treated with the combination of pegylated interferon and ribavirin for 24 weeks, whereas individuals infected with HCV genotypes 2 or 3 can be treated for only 12 weeks. Therefore, by adopting abbreviated treatment regimens optimized through early prediction of sustained viral response, it is possible to increase the number of patients treated without incurring the excess costs related to high rates of treatment failure and management of adverse outcomes, as well as avoiding the risks of unnecessarily exposing patients to drugs that have the potential to be highly toxic.

Weight-based combination therapy with peginterferon alpha-2b and ribavirin for naïve, relapser and non-responder patients with chronic hepatitis C.

Combination therapy with pegylated interferon and ribavirin is considered the new standard therapy for naïve patients with chronic hepatitis C. We evaluated the efficacy and safety of treatment with weight-based peginterferon alpha-2b (1.5 mg/kg per week) plus ribavirin (800-1,200 mg/day) for 48 weeks in naïve, relapser and non-responder (to previous treatment with interferon plus ribavirin) patients with chronic hepatitis C. Sixty-seven naïve, 26 relapser and 40 non-responder patients were enrolled. The overall sustained virological response (SVR) for the intention-to-treat population was 54% for naïve, 62% for relapser and 38% for non-responder patients. In the naïve subgroup, SVR was significantly higher in patients with the non-1 genotype (67%) compared to those with genotype 1 (45%). In relapsers and non-responders, SVR was, respectively, 69% and 24% in patients with genotype 1 and 43% and 73% in those with genotype non-1. There were no significant differences in SVR rates among the three body weight ranges (<65 kg, 65-85 kg and >85 kg) in any of the subgroups. Early virological response (EVR) was reached by 78%, 81% and 58% of naïve, relapser and non-responder patients, respectively, and among those with EVR, 63%, 67% and 61%, respectively, subsequently achieved SVR. All of the non-responder patients who did not have EVR reached SVR. Treatment was discontinued in 13% of the patients, due to loss to follow-up, hematological abnormalities or depression.

Pharmacodynamics of PEG-IFN-[alpha]-2a and HCV response as a function of IL28B polymorphism in HIV/HCV-coinfected patients.

We examined the association between IL28B single-nucleotide polymorphism rs12979860, hepatitis C virus (HCV) kinetic, and pegylated interferon alpha-2a pharmacodynamic parameters in HIV/HCV-coinfected patients from South America. Twenty-six subjects received pegylated interferon alpha-2a + ribavirin. Serum HCV-RNA and interferon concentrations were measured frequently during the first 12 weeks of therapy and analyzed using mathematical models. African Americans and whites had a similar distribution of IL28B genotypes (P = 0.5). The IL28B CC genotype was overrepresented (P = 0.015) in patients infected with HCV genotype-3 compared with genotype-1. In both genotype-1 and genotype-3, the first-phase viral decline and the average pegylated interferon-alpha-2a effectiveness during the first week of therapy were larger (trend P <= 0.12) in genotype-CC compared with genotypes-TC/TT. In genotype-1 patients, the second slower phase of viral decline (days 2-29) and infected cells loss rate, [delta], were larger (P = 0.02 and 0.11, respectively) in genotype-CC than in genotypes-TC/TT. These associations were not observed in genotype-3 patients.

Hepatitis C virus: molecular and epidemiological evidence of male-to-female transmission.

INTRODUCTION: There is general consensus that hepatitis C virus is efficiently transmitted by the parenteral route, whereas data on viral transmission by sexual or non-sexual intrafamilial contact are conflicting. OBJECTIVE AND METHOD: The aim of this study was to investigate the transmission of hepatitis C virus in nine heterosexual couples. RESULT: The mean age of the couples was 43.7 years. When interviewed, all of the women denied the presence of risk factors for acquisition of the infection, whereas the cause of infection in the nine husbands could be attributed to blood transfusions in two of them (22.2%), use of intravenous and inhaled drugs in six (66.7%), acupuncture in one (11.1%), and tattooing in one (11.1%). All men and none of the women reported sexual relations with sex professionals. The mean homology score (Non Structural 5b-hepatitis C virus) was 98.4%. Among the nine couples with matching subtypes, one (11.1%) was infected with subtype 1a, three (33.3%) with subtype 1b, and five (55.5%) with subtype 3a. Shared personal hygiene items showed a much higher correlation with the possible route of transmission and were better supported by the sequence homology data than the other associated risk factors. Three (33.3%) couples shared toothbrushes, seven (77.8%) shared razor blades, eight (88.8%) shared nail clippers, and six (66.7%) shared manicure cutters. CONCLUSION: Sharing of personal hygiene items was a confounding factor in the discussion of sexual hepatitis C virus transmission and the hypothesis of male-to-female transmission was supported in this study.

Hepatitis C: sexual or intrafamilial transmission? Epidemiological and phylogenetic analysis of hepatitis C virus in 24 infected couples.

The role of sexual or intrafamilial transmission of hepatitis C is controversial. A phylogenetic analysis was performed on the non-structural region 5B of the hepatitis C virus (NS5B-HCV). High percentages of homology (mean of 98.3%) were shown between the couples. Twenty (83.3%) of the 24 men but only two of the women (8.3%) reported having had sexually transmitted diseases during their lives. The risk factors for HCV acquisition were blood transfusion (10 couples), use of illegal injected drugs (17), use of inhalants (15), acupuncture (5) and tattoos (5). The shared use of personal hygiene items included toothbrushes between six couples (25%), razor blades between 16 (66.7%), nail clippers between 21 (87.5%) and manicure pliers between 14 (58.3%). The high degree of similarity of the hepatitis C virus genome supports the hypothesis of hepatitis C virus transmission between these couples. The shared use of personal hygiene items suggests the possibility of intrafamilial transmission of infection.

Hepatitis C virus: molecular and epidemiological evidence of male-to-female transmission

INTRODUCTION: There is general consensus that hepatitis C virus is efficiently transmitted by the parenteral route, whereas data on viral transmission by sexual or non-sexual intrafamilial contact are conflicting. OBJECTIVE AND METHOD: The aim of this study was to investigate the transmission of hepatitis C virus in nine heterosexual couples. RESULT: The mean age of the couples was 43.7 years. When interviewed, all of the women denied the presence of risk factors for acquisition of the infection, whereas the cause of infection in the nine husbands could be attributed to blood transfusions in two of them (22.2 percent), use of intravenous and inhaled drugs in six (66.7 percent), acupuncture in one (11.1 percent), and tattooing in one (11.1 percent). All men and none of the women reported sexual relations with sex professionals. The mean homology score (Non Structural 5b-hepatitis C virus) was 98.4 percent. Among the nine couples with matching subtypes, one (11.1 percent) was infected with subtype 1a, three (33.3 percent) with subtype 1b, and five (55.5 percent) with subtype 3a. Shared personal hygiene items showed a much higher correlation with the possible route of transmission and were better supported by the sequence homology data than the other associated risk factors. Three (33.3 percent) couples shared toothbrushes, seven (77.8 percent) shared razor blades, eight (88.8 percent) shared nail clippers, and six (66.7 percent) shared manicure cutters. CONCLUSION: Sharing of personal hygiene items was a confounding factor in the discussion of sexual hepatitis C virus transmission and the hypothesis of male-to-female transmission was supported in this study.

Hepatitis C: sexual or intrafamilial transmission? Epidemiological and phylogenetic analysis of hepatitis C virus in 24 infected couples / Hepatite C: transmissão sexual ou intrafamiliar? Análise epidemiológica e filogenética do vírus da hepatite C em 24 casais infectados

The role of sexual or intrafamilial transmission of hepatitis C is controversial. A phylogenetic analysis was performed on the non-structural region 5B of the hepatitis C virus (NS5B-HCV). High percentages of homology (mean of 98.3 percent) were shown between the couples. Twenty (83.3 percent) of the 24 men but only two of the women (8.3 percent) reported having had sexually transmitted diseases during their lives. The risk factors for HCV acquisition were blood transfusion (10 couples), use of illegal injected drugs (17), use of inhalants (15), acupuncture (5) and tattoos (5). The shared use of personal hygiene items included toothbrushes between six couples (25 percent), razor blades between 16 (66.7 percent), nail clippers between 21 (87.5 percent) and manicure pliers between 14 (58.3 percent). The high degree of similarity of the hepatitis C virus genome supports the hypothesis of hepatitis C virus transmission between these couples. The shared use of personal hygiene items suggests the possibility of intrafamilial transmission of infection.

O papel da transmissão sexual ou intrafamiliar da hepatite C é controverso. Foi feita análise filogenética, região não estrutural 5B do vírus da hepatite C (NS5B-HCV). Altas percentagens de homologia com média de 98,3 por cento foi revelada entre os casais. Vinte (83,3 por cento) de 24 homens, contra apenas duas (8,3 por cento) mulheres reportaram doença sexualmente transmisível durante suas vidas. Os fatores de risco para aquisição da doença foram: transfusão de sangue para 10 casais, uso de drogas ilícitas injetáveis para 17, inalatórias para 15, acupuntura em 5 e tatuagens para 5. O compartilhamento de utensílios de higiene pessoal incluem: escova de dente para seis (25 por cento) dos casais, lâmina de barbear para 16 (66,7 por cento), cortador de unhas para 21 (87,5 por cento) e alicate de manicure para 14 (58,3 por cento). O alto grau de similaridade genômica entre os vírus da hepatite C suporta a hipótese de transmissão entre os casais. O uso compartilhado de utensílios de higiene pessoal sugere a possibilidade de transmissão intrafamiliar.

Hepatitis C treatment: shorter and better?

Herein, we present a synthesis of two publications that evaluate an abbreviated therapeutic approach to treating chronic hepatitis C virus (HCV) infection. Based on those publications, we discuss the use of the early virologic response (EVR) as a tool for the optimized management of patients under treatment, as well as reviewing concepts of HCV viral kinetics. The fourth-week EVR, characterized by HCV RNA dropping to undetectable levels, allows individuals infected with HCV genotype 1 and presenting low baseline viral loads to be treated with the combination of pegylated interferon and ribavirin for 24 weeks, whereas individuals infected with HCV genotypes 2 or 3 can be treated for only 12 weeks. Therefore, by adopting abbreviated treatment regimens optimized through early prediction of sustained viral response, it is possible to increase the number of patients treated without incurring the excess costs related to high rates of treatment failure and management of adverse outcomes, as well as avoiding the risks of unnecessarily exposing patients to drugs that have the potential to be highly toxic.

Monitoramento de reações adversas da interferona alfa no tratamento ambulatorial da hepatite C crônica / Adverse drug reaction monitoring in chronic hepatitis C outpatients treated with alpha interferon

Pacientes com hepatite C crônica foram monitorados quanto às reaçoes adversas da interferona alfa (tratamento completo de um ano), por meio de entrevistas pós-consulta médica feitas por faramcêutico e apoiadas em aplicação de questionário dirigido e relato espontâneo. Foram observados e analisados o aparecimento, persistência, progressão ou regressão dos efeitos adversos durante e após o tratamento. Os sinais e sintomas mais freqüentes foram: desânimo, irritabilidade, cansaço, dores no corpo (todos os pacientes), cefaléia (96 porcento), boca seca (96 porcento), alterações do sono (91 porcento), queda de cabelos (87 porcento),boca seca (83 porcento) e visão turva (74 porcento). Após o tratamento...