Sofosbuvir and daclatasvir combination therapy for current hepatitis C virus genotype 4 achieves SVR: a case report of HCV genotype 4 from the Amazon

Abstract Hepatitis C is a worldwide endemic disease. However, hepatitis C virus genotype 4 (HCV GT-4) has rarely been reported in Brazil. HCV GT-4 demonstrates high sustained virological response (SVR). Here, we report the case of a 62-year-old HCV GT-4 positive woman complaining of a headache, nausea, and arthralgia. The patient was treated according to the protocol for genotype 4 (12 weeks administration of 400mg sofosbuvir and 60mg daclatasvir daily) and achieved SVR. Although this is not an Amazonas autochthonous case, the presence of genotype 4 is rarely reported in the region.

Sofosbuvir and daclatasvir combination therapy for current hepatitis C virus genotype 4 achieves SVR: a case report of HCV genotype 4 from the Amazon.

Hepatitis C is a worldwide endemic disease. However, hepatitis C virus genotype 4 (HCV GT-4) has rarely been reported in Brazil. HCV GT-4 demonstrates high sustained virological response (SVR). Here, we report the case of a 62-year-old HCV GT-4 positive woman complaining of a headache, nausea, and arthralgia. The patient was treated according to the protocol for genotype 4 (12 weeks administration of 400mg sofosbuvir and 60mg daclatasvir daily) and achieved SVR. Although this is not an Amazonas autochthonous case, the presence of genotype 4 is rarely reported in the region.

Liver and blood cytokine microenvironment in HCV patients is associated to liver fibrosis score: a proinflammatory cytokine ensemble orchestrated by TNF and tuned by IL-10.

BACKGROUND: In this study, we have evaluated the immunological status of hepatitis C virus (HCV)-infected patients aiming at identifying putative biomarkers associated with distinct degrees of liver fibrosis. Peripheral blood and tissue T-cells as well as cytokine levels were quantified by flow cytometry. RESULTS: Data analysis demonstrated higher frequency of circulating CD8(+) T-cells and Tregs along with a mixed proinflammatory/IL-10-modulated cytokine pattern in HCV patients. Patients with severe liver fibrosis presented lower frequency of circulating CD8(+) T-cells, higher levels of proinflammatory cytokines, but lower levels of IL-10, in addition to the higher viral load. Despite the lower frequency of intrahepatic T-cells and scarce frequency of Tregs, patients with severe liver fibrosis showed higher levels of proinflammatory cytokines (TNF and IFN-γ). The tissue proinflammatory cytokine pattern supported further studies of serum cytokines as relevant biomarkers associated with different liver fibrosis scores. Serum cytokine signature showed that mild liver fibrosis is associated with higher IL-10 serum levels as compared to severe liver disease. There was a clear positive connection of IL-10 with the TNF node in patients with mild liver fibrosis, whereas there is an evident inverse correlation between IL-10 with all other cytokine nodes. CONCLUSIONS: These results suggest the absence of modulatory events in patients with severe liver damage as opposed to mild fibrosis. Machine-learning data mining pointed out TNF and IL-10 as major attributes to differentiate HCV patients from non-infected individuals with highest performance. In conclusion, our findings demonstrated that HCV infection triggers a local and systemic cytokine ensemble orchestrated by TNF and tuned by IL-10 in such a manner that mirrors the liver fibrosis score, which highly suggests the relevance of these set of biomarkers for clinical investigations.

Combined impact of hepatitis C virus genotype 1 and interleukin-6 and tumor necrosis factor-α polymorphisms on serum levels of pro-inflammatory cytokines in Brazilian HCV-infected patients.

We investigated the association between hepatitis C virus (HCV) genotypes and host cytokine gene polymorphisms and serum cytokine levels in patients with chronic hepatitis C. Serum IL-6, TNF-α, IL-2, IFN-γ, IL-4, IL-10, and IL-17A levels were measured in 67 HCV patients (68.2% genotype 1 [G1]) and 47 healthy controls. The HCV patients had higher IL-6, IL-2, IFN-γ, IL-10, and IL-17A levels than the controls. HCV G1 patients had higher IL-2 and IFN-γ levels than G2 patients. The -174IL6G>C, -308TNFαG>A, and -1082IL10A>G variants were similarly distributed in both groups. However, HCV patients with the -174IL6GC variant had higher IL-2 and IFN-γ levels than patients with the GG and CC variants. Additionally, HCV patients with the -308TNFαGG genotype had higher IL-17A levels than patients with the AG genotype, whereas patients with the -1082IL10GG variant had higher IL-6 levels than patients with the AA and AG variants. A significant proportion of HCV patients had high levels of both IL-2 and IFN-γ. The subgroup of HCV patients with the G1/IL6CG/TNFαGG association displayed the highest proportions of high producers of IL-2 and IFN-γ whereas the subgroup with the G1/TNFαGG profile showed high proportions of high producers of IL-6 and IL-17A. HCV patients with other HCV/cytokine genotype associations showed no particular cytokine profile. Our results suggest that HCV genotype G1 and IL-6 and TNF-α polymorphisms have a clinically relevant influence on serum pro-inflammatory cytokine profile (IL-2 and IFN-γ) in HCV patients.

Epidemiology of HIV/HCV coinfection in patients cared for at the Tropical Medicine Foundation of Amazonas.

The association of HIV infection and hepatitis C virus (HCV) infection often occurs because both viruses share the same transmission routes, increasing the possibility of HIV/HCV coinfection. World prevalence greater than 30% of coinfected cases is estimated, and it can reach 90% depending on the transmission route. With the aim of determining the frequency and profile of HIV/HCV coinfected patients, a descriptive analysis was carried out with patients with HIV/AIDS whose serology was positive for hepatitis C virus (HCV), cared for at the Fundação de Medicina Tropical do Amazonas from 2000 to 2007. In the present study, of the 2,653 AIDS cases notified in SINAN, 1,582 patients underwent serology test for hepatitis C, and a frequency of 4.42% (n = 70) of HIV/HCV coinfected patients was identified in the period studied. The most frequent infection route was sexual transmission (84.3%), 68.6% among heterosexual individuals. Most patients were males (72.9%), aged between 25 and 40 years (60.1%), of low income (50% earning up to one minimum wage), and low educational level (80% had completed only middle school). A high percentage of deaths were observed during the study (34.3%). The results indicate a low seroprevalence of HIV/HCV coinfection in this population, in which sexual transmission, characterized by sexual promiscuity among heterosexual individuals, is the major transmission route of the virus rather than the use of injection drugs, as shown in world statistics.

Epidemiology of HIV/HCV coinfection in patients cared for at the Tropical Medicine Foundation of Amazonas

The association of HIV infection and hepatitis C virus (HCV) infection often occurs because both viruses share the same transmission routes, increasing the possibility of HIV/HCV coinfection. World prevalence greater than 30 percent of coinfected cases is estimated, and it can reach 90 percent depending on the transmission route. With the aim of determining the frequency and profile of HIV/HCV coinfected patients, a descriptive analysis was carried out with patients with HIV/AIDS whose serology was positive for hepatitis C virus (HCV), cared for at the Fundação de Medicina Tropical do Amazonas from 2000 to 2007. In the present study, of the 2,653 AIDS cases notified in SINAN, 1,582 patients underwent serology test for hepatitis C, and a frequency of 4.42 percent (n = 70) of HIV/HCV coinfected patients was identified in the period studied. The most frequent infection route was sexual transmission (84.3 percent), 68.6 percent among heterosexual individuals. Most patients were males (72.9 percent), aged between 25 and 40 years (60.1 percent), of low income (50 percent earning up to one minimum wage), and low educational level (80 percent had completed only middle school). A high percentage of deaths were observed during the study (34.3 percent). The results indicate a low seroprevalence of HIV/HCV coinfection in this population, in which sexual transmission, characterized by sexual promiscuity among heterosexual individuals, is the major transmission route of the virus rather than the use of injection drugs, as shown in world statistics.

Characterization of HBeAg-negative chronic hepatitis B in western Brazilian Amazonia.

The present study was conducted with 55 patients native from western Brazilian Amazonia, who were HBV-DNA positive after seroconversion of HBeAg. It is a descriptive case study, with the patients separated into two groups: with hepatitis and without hepatitis on histological examination. The aim of the present study was to describe the clinical and molecular characteristics of patients who are chronic carriers of HBsAg. The prevalence of hepatitis was 63.64%, with a predominance of males (41.82%) and a mean age of 42.5 years, occurring mostly in natives of the southeast sub-region (32.73%). Time was a variable proportional to the course of the disease and the most frequent symptoms were: dyspepsia, asthenia and loss of libido with the majority of the patients having history of prior contact with HBV or positive family history. Splenomegalia was the most frequent sign (40%). Among the tests, platelet count, serum albumin and prothrombin activity were significant in the diagnosis of hepatitis. Alpha-fetoprotein was greater in patients with hepatitis, and hepatocellular carcinoma was detected in 3.63% of the patients with hepatic cirrhosis. Three types of HBV genotypes were diagnosed: A, D and F in the samples amplified for gene S. Genotype A (AA) was observed in 54.54% of the cases with hepatitis, in contrast to other studies showing the predominance of genotype F in this region. We observed mutations in 36.36%, with a predominance of the mutations in the core promoter region (31.81%), due to the greater prevalence of genotype A in this study.

Characterization of HBeAg-negative chronic hepatitis B in western Brazilian Amazonia

The present study was conducted with 55 patients native from western Brazilian Amazonia, who were HBV-DNA positive after seroconversion of HBeAg. It is a descriptive case study, with the patients separated into two groups: with hepatitis and without hepatitis on histological examination. The aim of the present study was to describe the clinical and molecular characteristics of patients who are chronic carriers of HBsAg. The prevalence of hepatitis was 63.64 percent, with a predominance of males (41.82 percent) and a mean age of 42.5 years, occurring mostly in natives of the southeast sub-region (32.73 percent). Time was a variable proportional to the course of the disease and the most frequent symptoms were: dyspepsia, asthenia and loss of libido with the majority of the patients having history of prior contact with HBV or positive family history. Splenomegalia was the most frequent sign (40 percent). Among the tests, platelet count, serum albumin and prothrombin activity were significant in the diagnosis of hepatitis. Alpha-fetoprotein was greater in patients with hepatitis, and hepatocellular carcinoma was detected in 3.63 percent of the patients with hepatic cirrhosis. Three types of HBV genotypes were diagnosed: A, D and F in the samples amplified for gene S. Genotype A (AA) was observed in 54.54 percent of the cases with hepatitis, in contrast to other studies showing the predominance of genotype F in this region. We observed mutations in 36.36 percent, with a predominance of the mutations in the core promoter region (31.81 percent), due to the greater prevalence of genotype A in this study.