Henrique Sérgio Moraes Coelho

Entecavir treatment for up to 5 years in patients with hepatitis B e antigen-positive chronic hepatitis B.

Sustained virologic suppression is a primary goal of therapy for chronic hepatitis B (CHB). In study entecavir (ETV)‐022, 48 weeks of entecavir 0.5 mg was superior to lamivudine for virologic suppression for hepatitis B e antigen (HBeAg)‐positive CHB. A total of 183 entecavir‐treated patients from ETV‐022 subsequently enrolled in study ETV‐901. We present the results after up to 5 years (240 weeks) of continuous entecavir therapy. The entecavir long‐term cohort consists of patients who received ≥1 year of entecavir 0.5 mg in ETV‐022 and then entered ETV‐901 with a treatment gap ≤35 days. In ETV‐901 the entecavir dose was 1.0 mg daily. For patients with samples available at Year 5, proportions with hepatitis B virus (HBV) DNA <300 copies/mL, normal alanine aminotransferase (ALT) levels, HBeAg loss, and HBeAg seroconversion were determined. In all, 146 patients met criteria for inclusion in the entecavir long‐term cohort. At Year 5, 94% (88/94) had HBV DNA <300 copies/mL and 80% (78/98) had normal ALT levels. In addition to patients who achieved serologic responses during study ETV‐022, 23% (33/141) achieved HBeAg seroconversion and 1.4% (2/145) lost hepatitis B surface antigen (HBsAg) during study ETV‐901. Through 5 years, entecavir resistance emerged in one patient. The safety profile of entecavir was consistent with previous reports. Conclusion: Extended therapy with entecavir through 5 years maintained or increased rates of HBV DNA suppression and ALT normalization. Additional patients also achieved HBeAg loss and seroconversion. Entecavir provides sustained viral suppression with minimal resistance during long‐term treatment of HBeAg‐positive CHB. (HEPATOLOGY 2010.)

Geographic distribution of hepatitis C virus genotypes in Brazil

Brazil is a country of continental dimension with a population of different ethnic backgrounds. Thus, a wide variation in the frequencies of hepatitis C virus (HCV) genotypes is expected to occur. To address this point, 1,688 sequential samples from chronic HCV patients were analyzed. HCV-RNA was amplified by the RT-PCR from blood samples collected from 1995 to 2000 at different laboratories located in different cities from all Brazilian States. Samples were collected in tubes containing a gel separator, centrifuged in the site of collection and sent by express mail in a refrigerated container to Laboratório Bioquímico Jardim Paulista, São Paulo, SP, Brazil. HCV-RNA was extracted from serum and submitted to RT and nested PCR using standard procedures. Nested PCR products were submitted to cycle sequencing reactions without prior purification. Sequences were analyzed for genotype determination and the following frequencies were found: 64.9% (1,095) for genotype 1, 4.6% (78) for genotype 2, 30.2% (510) for genotype 3, 0.2% (3) for genotype 4, and 0.1% (2) for genotype 5. The frequencies of HCV genotypes were statistically different among Brazilian regions (P = 0.00017). In all regions, genotype 1 was the most frequent (51.7 to 74.1%), reaching the highest value in the North; genotype 2 was more prevalent in the Center-West region (11.4%), especially in Mato Grosso State (25.8%), while genotype 3 was more common in the South (43.2%). Genotypes 4 and 5 were rarely found and only in the Southeast, in São Paulo State. The present data indicate the need for careful epidemiological surveys throughout Brazil since knowing the frequency and distribution of the genotypes would provide key information for understanding the spread of HCV.

Historical epidemiology of hepatitis C virus (HCV) in selected countries

Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6 358 000 cases in 2008 and Brazil with 2 106 000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV‐infected populations are critical for addressing HCV‐related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.

Strategies to manage hepatitis C virus (HCV) disease burden

The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV‐related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3–5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.

Trends and projections of hepatitis C virus epidemiology in Latin America

Background and aim: The purpose of the present investigation is to provide an analysis of previous works on the epidemiology of the hepatitis C virus (HCV) infection from six countries throughout Latin America, to forecast the future HCV prevalence trends in Argentina, Brazil, Mexico and Puerto Rico, and to outline deficiencies in available data, highlighting the need for further research.

Hepatitis B virus genotypes circulating in Brazil: molecular characterization of genotype F isolates

BackgroundHepatitis B virus (HBV) isolates have been classified in eight genotypes, A to H, which exhibit distinct geographical distributions. Genotypes A, D and F are predominant in Brazil, a country formed by a miscegenated population, where the proportion of individuals from Caucasian, Amerindian and African origins varies by region. Genotype F, which is the most divergent, is considered indigenous to the Americas. A systematic molecular characterization of HBV isolates from different parts of the world would be invaluable in establishing HBV evolutionary origins and dispersion patterns. A large-scale study is needed to map the region-by-region distribution of the HBV genotypes in Brazil.ResultsGenotyping by PCR-RFLP of 303 HBV isolates from HBsAg-positive blood donors showed that at least two of the three genotypes, A, D, and F, co-circulate in each of the five geographic regions of Brazil. No other genotypes were identified. Overall, genotype A was most prevalent (48.5%), and most of these isolates were classified as subgenotype A1 (138/153; 90.2%). Genotype D was the most common genotype in the South (84.2%) and Central (47.6%) regions. The prevalence of genotype F was low (13%) countrywide. Nucleotide sequencing of the S gene and a phylogenetic analysis of 32 HBV genotype F isolates showed that a great majority (28/32; 87.5%) belonged to subgenotype F2, cluster II. The deduced serotype of 31 of 32 F isolates was adw4. The remaining isolate showed a leucine-to-isoleucine substitution at position 127.ConclusionThe presence of genotypes A, D and F, and the absence of other genotypes in a large cohort of HBV infected individuals may reflect the ethnic origins of the Brazilian population. The high prevalence of isolates from subgenotype A1 (of African origin) indicates that the African influx during the colonial slavery period had a major impact on the circulation of HBV genotype A currently found in Brazil. Although most genotype F isolates belonged to cluster II, the presence of some isolates belonging to clusters I (subgroup Ib) and IV suggests the existence of two or more founder viral populations of genotype F in Brazil.

Calcium-parathyroid hormone-vitamin D axis and metabolic bone disease in chronic viral liver disease

Background: The main process involved in hepatic osteodystrophy seems to be osteoporosis, but decreased 25‐hydroxylation of vitamin D might lead to osteomalacia and secondary hyperparathyroidism.

Acute kidney injury network criteria as a predictor of hospital mortality in cirrhotic patients with ascites.

Background: Acute kidney injury (AKI) is frequent in cirrhotic patients but its best definition is unclear. Recently, the Acute Kidney Injury Network (AKIN) proposed criteria to define AKI. The aims of this study were to apply AKIN criteria to cirrhotic patients with ascites and to evaluate its association to hospital mortality. Study: In this retrospective study, cirrhotic patients with ascites admitted to a university hospital in Brazil between November 2003 and December 2007 were included. AKIN criteria were applied in the first 48 hours of hospitalization, considering 2 values of creatinine in this period. Association of AKI at admission and hospital mortality was analyzed. Results: Of the 198 patients in the study, 91 (46%) presented AKI at hospital admission. Overall hospital mortality was 40.4%. Patients without AKI had a hospital mortality rate of 29.9%, whereas the same rate for patients with this complication was 52.7% (odds ratio=2.6; 95% confidence interval, 1.5-4.7; P=0.001). In a logistic regression analysis, 4 variables were independently associated to hospital mortality: infection, hepatic encephalopathy, Child score, and AKI. A receiver operating characteristic curve analysis revealed that the variation in creatinine proposed by AKIN had the best combination of sensitivity and specificity in relation to hospital mortality. Conclusions: In cirrhotic patients with ascites, prevalence of AKI at hospital admission is high. Patients with renal dysfunction defined by AKIN have significant higher hospital mortality. AKIN criteria are useful in cirrhotic patients with ascites, as it identifies earlier patients with worse prognosis.

Bone marrow mononuclear cell therapy for patients with cirrhosis: a Phase 1 study

Background: Bone marrow‐derived cell therapy has been investigated in patients with severe liver disease.

Gamma-glutamyl transferase (GGT) as an independent predictive factor of sustained virologic response in patients with hepatitis C treated with interferon-alpha and ribavirin.

Background: Recently, gamma-glutamyl transferase (GGT) has been investigated as a predictive factor for therapy response in hepatitis C patients, but so far its value in pretreatment screening has not been established. Therefore, this study aimed at evaluating GGT as an independent predictive factor for the response to treatment with interferon-α and ribavirin in hepatitis C virus (HCV)-infected patients. Methods: Naive chronic hepatitis C patients undergoing a 6-month follow-up after interferon-alpha and ribavirin therapy had their sustained virologic response (SVR) analyzed according to age, sex, body mass index, GGT levels, genotype, and liver histology by use of a multivariate logistic regression model. Results: Of the 211 patients studied with a mean age of 48 ± 10 years, 125 (59%) were males. Overweight was detected in 47% of patients. Genotype 1 was detected in 141 (75%) of the 187 patients tested. Cirrhosis was present in 67 (32%). A high pretreatment GGT level was observed in 134 (63%). SVR was obtained in 84 (40%) patients. In the final logistic regression model, the variables independently associated with SVR were GGT (P < 0.001), genotype (P < 0.001), and liver histology (P < 0.001). Conclusion: A normal GGT level is an independent predictive factor for SVR in HCV-infected patients and should be considered for pretreatment screening.