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.

The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm.

The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.

Cognitive assessment of patients with minimal hepatic encephalopathy in Brazil.

Minimal hepatic encephalopathy is a syndrome caused by liver cirrhosis and accompanied by a broad spectrum of cognitive symptoms. The objective of the present study was to describe the prevalence of minimal hepatic encephalopathy in cirrhotic patients and to compare their cognitive performance with controls using standardized tests. Patients receiving medication or experiencing comorbidities associated with cognitive disorders were excluded. The final cohort was compared with a control-matched group using the Mini-Mental State Examination (MMSE), as well as Simple Drawing, Clock Drawing, Rey Auditory-Verbal Learning Test (RAVLT), Random Letter, Stroop, Trail-Making Test (TMT) A and B, Boston Naming, Category Verbal Fluency, Digit Span, Constructional Praxis, Processing Speed, and Similarities Tests. The results indicated no differences in the prevalence of cognitive complaints spontaneously reported by 29 patients with cirrhosis versus 22 healthy controls. The most affected tests included: MMSE (26.3 ± 2 vs. 28.1 ± 1.8 points; p = 0.004), learning (35.4 ± 9 vs. 41 ± 9.1 points; p = 0.041), retroactive interference (0.67 ± 0.22 vs. 0.84 ± 0.16 points; p = 0.004), and recognition (8.7 ± 2.6 vs. 11.2 ± 4.1 points; p = 0.024) in RAVLT, TMT-A (63.2 ± 29.3 vs. 47.6 ± 16.5 s; p = 0.029) and TMT-B (197.9 ± 88.1 vs. 146.8 ± 76.5 s; p = 0.03). No differences were observed with respect to age, gender, and education. In conclusion, MMSE proved to be a useful tool for detecting global cognitive impairment experienced by cirrhosis patients. Moreover, the most impaired cognitive functions were verbal episodic memory and information processing speed. These findings suggest that minimal hepatic encephalopathy represents a disorder that affects the medial temporal system and, possibly, the prefrontal cortex, and this requires further study.

Medical aspects of 137Cs decorporation: the Goiânia radiological accident.

In September 1987, the Goiânia radiological accident involving a source of 137Cs culminated in about 140 victims who presented internal and/or external contamination and/or external exposure to radiation and/or radiation burns. Internal contamination was verified through analysis of urine and fecal samples. Internal contamination was also evaluated by measurements performed at the whole-body counter installed in Goiânia in November 1987. To enhance the decorporation of 137Cs, patients were treated with the following: 1) Prussian Blue, oral administration, in 46 patients; 2) diuretics, oral administration, in 17 patients; 3) induced perspiration, increasing 137Cs elimination. These procedures were done under rigorous clinical evaluation and considering the data from assay of excreta and data obtained from the whole-body counter. The doses of Prussian Blue exceeded about 6.5 times the dose previously indicated in the literature. It was the first time diuretics were used in humans to treat 137Cs internal contamination. The results of these procedures are discussed.

Medical and related aspects of the Goiânia accident: an overview.

On 13 September 1987, a radiation accident occurred in the city of Goiânia in Central Brazil. Approximately 250 people were exposed to a 137Cs source from an abandoned radiotherapy unit. At least 14 patients showed some degree of bone marrow depression, and eight developed the classical signs and symptoms of acute radiation syndrome (ARS). Twenty-eight people presented local radiation injuries ranging from first to third degree, and 104 individuals showed evidence of internal contamination. This paper describes the circumstances of the event, the first-aid measures taken, the criteria adopted for triage of the exposed population, and the radiation protection procedures used during the clinical management of the irradiated individuals.

Localized lesions induced by 137Cs during the Goiânia accident.

A description is given of initial symptoms and clinical observations regarding acute localized radiation lesions in 28 persons exposed to 137Cs during the Goiânia radiological accident. Specialized procedures to estimate the extent and gravity of the lesions and establish a therapeutic strategy, as well as to anticipate the prognosis in each case, are briefly discussed. Measures taken for reduction of pain and inflammation are noted, and an explanation is given for difficulties encountered due to adverse working conditions and the serious clinical manifestations presented by various patients concomitantly with their lesions. Also noted is the difficulty in obtaining credible information regarding exposure, such as source-to-object distance, duration of exposure, and source activity, which precluded dosimetry studies in most cases.

Clinical and hematological aspects of 137Cs: the Goiânia radiation accident.

Fifty persons involved in the 137Cs accident in Goiânia showed symptoms of whole-body and local acute irradiation and also external or internal contamination mainly due to ingestion or absorption of 137Cs. Fourteen of the 50 developed severe bone marrow depression characterized by neutropenia and thrombocytopenia. Eight of these 14 received GM-CSF intravenously. None were submitted to bone marrow transplantation. Four of the 14 died due to hemorrhage and infection. For those with significant internal contamination evaluated by in-vitro and in-vivo assays, Prussian Blue was administered with doses ranging from 1.5 to 10 g d-1. Besides Prussian Blue, other measures were taken to increase decorporation of 137Cs, including administration of diuretics, water overload, and ergometric exercises. From 50 to 100 persons are being followed in a medical protocol.

Novel biodosimetry methods applied to victims of the Goiânia accident.

Two biodosimetric methods under development at the Lawrence Livermore National Laboratory were applied to five persons accidentally exposed to a 137Cs source in Goiânia, Brazil. The methods used were somatic "null" mutations at the glycophorin A locus detected as missing proteins on the surface of blood erythrocytes and chromosome translocations in blood lymphocytes detected using fluorescence in-situ hybridization. Biodosimetric results obtained approximately 1 y after the accident using these new and largely unvalidated methods are in general agreement with results obtained immediately after the accident using dicentric chromosome aberrations. Additional follow-up of Goiânia accident victims will 1) help provide the information needed to validate these new methods for use in biodosimetry and 2) provide independent estimates of dose.

Autoimmune thrombocytopenia related to chronic hepatitis C virus infection.

Since the identification of hepatitis C virus (HCV) in 1989 as a causative agent for a number of the extrahepatic alterations related to HCV infection an underlying immune mediated pathogenetic mechanism has been postulated. HCV-associated thrombocytopenia may be considered complex and multifactorial in origin, since different mechanisms have been implicated in its pathophysiology. With respect to autoimmune thrombocytopenia in chronic HCV infection, the detection of specific antibodies against platelet glycoproteins have been reported only in a few studies, but no systematic study has been carried out. We examined the clinical, laboratory, and virological characteristics of a case series of 10 patients with autoimmune thrombocytopenia (platelet count <150.0 x 10(9)/L) related to chronic HCV infection. Cases, six males and four females, aged 57.1 +/- 12.6 years, presented high titers of antibodies against platelet glycoprotein (GP) IIb/IIIa, GP Ia/IIa, and/or GP Ib/IX, and no other mechanism involved in the pathogenesis of HCV-associated thrombocytopenia was identified. Furthermore, cases were not associated with particular HCV genotype. Complete platelet response was observed in two patients treated with pegylated interferon plus ribavirin, and partial platelet response was seen in two patients treated with anti-D Ig and one patient treated with corticosteroids. These findings indicate that an autoimmune mechanism may play a role in the pathogenesis of HCV-associated thrombocytopenia in a proportion of these patients.