Disease burden of chronic hepatitis C in Brazil

Background: Hepatitis C virus infection is a major cause of cirrhosis; hepatocellular carcinoma; and liver transplantation. The aim of this study was to estimate hepatitis C virus disease progression and the burden of disease from a nationwide perspective.Methods: Using a model developed to forecast hepatitis C virus disease progression and the number of cases at each stage of liver disease; hepatitis C virus-infected population and associated disease progression in Brazil were quantified. The impact of two different strategies was compared: higher sustained virological response and treatment eligibility rates (1) or higher diagnosis and treatment rates associated with increased sustained virological response rates (2).Results: The number of infected individuals is estimated to decline by 35% by 2030 (1,255,000 individuals); while the number of cases of compensated (n= 325,900) and decompen- sated (n= 45,000) cirrhosis; hepatocellular carcinoma (n= 19,100); and liver-related deaths (n= 16,700) is supposed to peak between 2028 and 2032. In strategy 2; treated cases increased over tenfold in 2020 (118,800 treated) as compared to 2013 (11,740 treated); with sustained virological response increased to 90% and treatment eligibility to 95%. Under this strategy; the number of infected individuals decreased by 90% between 2013 and 2030. Compared to the base case; liver-related deaths decreased by 70% by 2030; while hepatitis C virus-related liver cancer and decompensated cirrhosis decreased by 75 and 80%; respectively.Conclusions: While the incidence and prevalence of hepatitis C virus in Brazil are decreasing; cases of advanced liver disease continue to rise. Besides higher sustained virological response rates; new strategies focused on increasing the proportion of diagnosed patients and eligibility to treatment should be adopted in order to reduce the burden of hepatitis C virus infection in Brazil.

Disease burden of chronic hepatitis C in Brazil.

BACKGROUND: Hepatitis C virus infection is a major cause of cirrhosis; hepatocellular carcinoma; and liver transplantation. The aim of this study was to estimate hepatitis C virus disease progression and the burden of disease from a nationwide perspective. METHODS: Using a model developed to forecast hepatitis C virus disease progression and the number of cases at each stage of liver disease; hepatitis C virus-infected population and associated disease progression in Brazil were quantified. The impact of two different strategies was compared: higher sustained virological response and treatment eligibility rates (1) or higher diagnosis and treatment rates associated with increased sustained virological response rates (2). RESULTS: The number of infected individuals is estimated to decline by 35% by 2030 (1,255,000 individuals); while the number of cases of compensated (n=325,900) and decompensated (n=45,000) cirrhosis; hepatocellular carcinoma (n=19,100); and liver-related deaths (n=16,700) is supposed to peak between 2028 and 2032. In strategy 2; treated cases increased over tenfold in 2020 (118,800 treated) as compared to 2013 (11,740 treated); with sustained virological response increased to 90% and treatment eligibility to 95%. Under this strategy; the number of infected individuals decreased by 90% between 2013 and 2030. Compared to the base case; liver-related deaths decreased by 70% by 2030; while hepatitis C virus-related liver cancer and decompensated cirrhosis decreased by 75 and 80%; respectively. CONCLUSIONS: While the incidence and prevalence of hepatitis C virus in Brazil are decreasing; cases of advanced liver disease continue to rise. Besides higher sustained virological response rates; new strategies focused on increasing the proportion of diagnosed patients and eligibility to treatment should be adopted in order to reduce the burden of hepatitis C virus infection in Brazil.

Virus C genotype predisposes to primary hypothyroidism during interferon-α treatment for chronic hepatitis C

OBJECTIVE: The treatment of the chronic hepatitis C (HCV) with α-interferon is associated with thyroid dysfunction (TD). The aim of this study was to evaluate thyroid function outcome among patients with chronic HCV under treatment with conventional interferon (IFN) or peguilated interferon (PEG-IFN) in association with ribavirin. PATIENTS AND METHODS: We studied 293 patients with chronic HCV, submitted to drug therapy for 24 or 48 weeks. Initially, we evaluated FT4, TSH, TPOAb, TgAb, and continued to monitor FT4 and TSH every three months during therapy and six months thereafter. RESULTS: At baseline, TD prevalence was 6.82 percent (n = 20); 6.14 percent hypothyroidism; 0.68 percent hyperthyroidism. TPOAb was present in 5.46 percent of euthyroid patients. Out of 273 euthyroid patients at baseline, 19 percent developed TD: 17.2 percent hypothyroidism; 1.8 percent hyperthyroidism; 5.1 percent destructive thyroiditis (DT). 90 percent of TPOAb-positive patients at baseline developed hypothyroidism vs 14.5 percent of TPOAb-negative patients (p < 0.001). On average, TD occurred after 25.8 ± 15.5 weeks of treatment. 87.2 percent of patients who developed hypothyroidism did so during the first therapeutic cycle (p = 0.004; OR = 3.52; 95 percent CI = 1.36-9.65). Patients infected with genotype 1 virus were 2.13 times more likely to develop hypothyroidism (p = 0.036; 95 percent CI = 1.04-4.38). Hypothyroid and DT patients presented higher TSH levels before-treatment than patients who had remained euthyroid (p < 0.001; p = 0.002, respectively). DT patients presented lower qALT (p = 0.012) than euthyroid patients. CONCLUSION: Hypothyroidism was the most frequent TD, especially during the first cycle of α-interferon. Genotype 1 virus was associated with a risk two times higher for developing the illness. There was no need to interrupt or to change HCV treatment. Therefore, approximately 34 percent of TD was transient.

Occult hepatitis B virus infection in immunocompromised patients.

Occult hepatitis B infection is characterized by hepatitis B virus (HBV) DNA in the serum in the absence of hepatitis B surface antigen (HBsAg). We assessed occult HBV infection prevalence in two groups of immunocompromised patients (maintenance hemodialysis patients and HIV-positive patients) presenting HBsAg-negative and anti-HBc positive serological patterns, co-infected or not by HCV. Thirty-four hemodialysis anti-HIV negative patients, 159 HIV-positive patients and 150 blood donors who were anti-HBc positive (control group) were selected. HBV-DNA was detected by nested-PCR. Occult hepatitis B infection was not observed in the hemodialysis patients group but was found in 5% of the HIV-patients and in 4% of the blood donors. Immunosuppression in HIV positive patients was not a determining factor for occult HBV infection. In addition, no significant relationship between HBV-DNA and HCV co-infection in the HIV-positive patient group was found. A lack of significant associations was also observed between positivity for HBV-DNA and CD4 count, viral load and previous lamivudine treatment in these HIV-positive patients.

Occult hepatitis B virus infection in immunocompromised patients

Occult hepatitis B infection is characterized by hepatitis B virus (HBV) DNA in the serum in the absence of hepatitis B surface antigen (HBsAg). We assessed occult HBV infection prevalence in two groups of immunocompromised patients (maintenance hemodialysis patients and HIV-positive patients) presenting HBsAg-negative and anti-HBc positive serological patterns, co-infected or not by HCV. Thirty-four hemodialysis anti-HIV negative patients, 159 HIV-positive patients and 150 blood donors who were anti-HBc positive (control group) were selected. HBV-DNA was detected by nested-PCR. Occult hepatitis B infection was not observed in the hemodialysis patients group but was found in 5 percent of the HIV-patients and in 4 percent of the blood donors. Immunosuppression in HIV positive patients was not a determining factor for occult HBV infection. In addition, no significant relationship between HBV-DNA and HCV co-infection in the HIV-positive patient group was found. A lack of significant associations was also observed between positivity for HBV-DNA and CD4 count, viral load and previous lamivudine treatment in these HIV-positive patients.

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 percent for naïve, 62 percent for relapser and 38 percent for non-responder patients. In the naïve subgroup, SVR was significantly higher in patients with the non-1 genotype (67 percent) compared to those with genotype 1 (45 percent). In relapsers and non-responders, SVR was, respectively, 69 percent and 24 percent in patients with genotype 1 and 43 percent and 73 percent 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 percent, 81 percent and 58 percent of naïve, relapser and non-responder patients, respectively, and among those with EVR, 63 percent, 67 percent and 61 percent, respectively, subsequently achieved SVR. All of the non-responder patients who did not have EVR reached SVR. Treatment was discontinued in 13 percent of the patients, due to loss to follow-up, hematological abnormalities or depression.

The influence of occult infection with hepatitis B virus on liver histology and response to interferon treatment in chronic hepatitis C patients

Occult hepatitis B virus (HBV) infections have been identified in patients with chronic hepatitis C virus (HCV) infection, although the clinical relevance of occult HBV infection remains controversial. We searched for serum HBV DNA in 106 HBsAg negative/anti-HBc positive patients with chronic HCV infection and in 150 blood donors HBsAg negative/anti-HBc positive/anti-HCV negative (control group) by nested-PCR. HCV genotyping was done in 98 patients and percutaneous needle liver biopsies were performed in 59 patients. Fifty-two patients were treated for HCV infection with interferon alone (n=4) or combined with ribavirin (n=48) during one year. At the end and 24 weeks after stopping therapy, they were tested for HCV-RNA to evaluate the sustained virological response (SVR). Among the 106 HCV-positive patients, 15 (14 percent) were HBV-DNA positive and among the 150 HCV-negative blood donors, 6 (4 percent) were HBV-DNA positive. Liver biopsy gave a diagnosis of liver cirrhosis in 2/10 (20 percent) of the HBV-DNA positive patients and in 6/49 (12 percent) of the HBV-DNA negative patients. The degree of liver fibrosis and portal inflammation was similar in HCV-infected patients HBV-DNA, irrespective of HBV-DNA status. SVR was obtained in 37.5 percent of the HBV-DNA positive patients and in 20.5 percent of the HBV-DNA negative patients; this difference was not significant. In conclusion, these data suggested that occult HBV infection, which occurs at a relatively high frequency among Brazilian HCV-infected patients, was not associated with more severe grades of inflammation, liver fibrosis or cirrhosis development and did not affect the SVR rates when the patients were treated with interferon or with interferon plus ribavirin.

Elevated alanine aminotransferase (ALT) in blood donors: an assessment of the main associated conditions and its relationship to the development of hepatitis C

A determinacao dos niveis de alanina aminotransferase (ALT) tem sido util para o diagnostico de hepatopatias. Ultimamente, a elevacao dos niveis sericos de ALT em doadores de sangue, tem sido associada a um maior risco de hepatites pos-tranfusionais. Este estudo busca identificar os fatores associados com elevados niveis de ALT entre doadores voluntarios de sangue e avaliar as relacoes entre estes aumentos de ALT e o desenvolvimento de infeccao pelo virus da hepatite C. Assim, 116 doadores voluntarios de sangue com niveis de ALT elevados, quando da primeira doacao, foram estudados. Todos foram questionados sobre hepatopatias previas, exposicao a hepatites, exposicao a produtos quimicos, uso de drogas ou medicamentos, comportamento sexual, contacto com sangue ou secrecoes e consumo de alcool...

Hepatites pós-transfusionais na cidade de Campinas, SP, Brasil. II. Presença dos anticorpos anti-HBc e anti-HCV em candidatos a doadores de sangue e ocorrência de hepatites pós-transfusionais pelo vírus C nos receptores de sangue ou derivados / Post-transfusional hepatitis in the city of Campinas, SP, Brazil. II. Presence of anti-HBc and anti-HCV antibodies in blood donor candidates and occurrence of post-transfusional hepatitis C in recipients of blood or derivates

We have analysed anti-HBc and anti-HCV antibodies in serum samples from 799 donors which had their blood or derivates transfused to 111 recipients. Anti-HBc and anti-HCV were reactive in respectively 9 and 2.1 of the donors tested. We have observed that among the 111 recipients, 44 had received at least one positive anti-HBc unit and 67 had been transfused only with negative anti-HBc, units. The risk of developing hepatitis C virus was 4.5 times higher for the recipients who received at least one positive anti-HBc unit. If the test for anti-HBc had been made for the blood donors in the serological screening, about 56 of the HCV cases in the recipients could have been avoided. The population of recipients who received at least one reacting unit of anti-HCV, presented a risk 29 times higher of developing this hepatitis, as compared to the transfused recipients with all anti-HCV negative units. Testing blood from donors for anti-HCV would avoid 79 of the post-transfusional HCV cases. Brazilian candidates to blood donors seem to be carriers either simultaneously or sequentially to hepatitis virus B and C, since 44.4 of the positive anti-HCV were also positive for anti-HBc. Testing for anti-HBc and anti-HCV in blood screening must be indicated in order to prevent post-transfusional hepatitis transmission in our community.