The disease burden of hepatitis C in Belgium: development of a realistic disease control strategy.

BACKGROUND: Novel direct antiviral agents (DAAs) will become available soon with higher sustained viral response (SVR), fewer side-effects and higher compliance. Our aim was to evaluate different realistic strategies to control the projected increase in HCV-related disease burden in Belgium. METHODS: Based on literature review, expert opinions and historical assumptions, HCV-disease progression and mortality in Belgium was modeled to 2030. Strategies exploring the impact of increased treatment, treatment delay, and treatment restrictions were developed. RESULTS: Although the overall HCV prevalence is decreasing in Belgium, the burden of advanced stage HCV, including cirrhosis and hepatocellular carcinoma (HCC), is expected to increase under current treatment and cure rates. By increasing SVR to 90% from 2016 onward and the number of treated cases (from 710 to 2,050), in 2030 the cases with cirrhosis, decompensated cirrhosis and HCC would be significantly lower than in 2013. This strategy was found most efficient when applied to F2-F4 cases. To obtain comparable outcomes with F0-F4 cases, 3,490 patients should be treated. A two year delayed access to the DAAs increased HCV related morbidity and mortality by 15% relative to our strategy. CONCLUSIONS: Considering the evolving burden of HCV disease and the need for efficacious usage of healthcare resources, primary application of new DAAs in Belgium should focus on patients with significant and advanced fibrosis (F2-F4), providing these new drugs without delay upon availability and increasing access to therapy.

Hepatitis C epidemiology in Belgium.

BACKGROUND: The burden of hepatitis C virus (HCV) infection is significant and is increasing with the aging population. The results of a modeling study that included Belgium, along with many other countries, was published in April 2014. An in depth discussion surrounding the epidemiology of HCV in Belgium will be presented here. METHODS: A systematic literature review was conducted to assess the historical and current clinical burden of HCV in Belgium. Two expert panels were convened to discuss the strengths and limitations surrounding the available data and to generate consensus regarding the best estimates for total number of HCV cases, number of cases diagnosed, and the number of patients treated and cured, including potential HCV control strategies. RESULTS: Although no national studies exist, there were an estimated 70,000 (10,000-91,000) viremic HCV infections in 1994. By 2010 there were an estimated 22,900 individuals diagnosed with viremic HCV, and in 2011 approximately 710 patients were treated annually. An estimated 13% of liver transplants were attributable to HCV in 2011. Genotype 1 predominated (59%), followed by genotypes 3 (19%) and 4 (14%). CONCLUSIONS: Estimates of HCV prevalence, diagnosed cases and liver transplants due to HCV were available through published studies. However these publications were subject to bias and were occasionally outdated. Improved estimates of HCV prevalence would be useful for informing treatment, prevention and policy efforts in Belgium.

Current and future health and economic impact of hepatitis C in Belgium.

BACKGROUND AND STUDY AIMS: Chronic hepatitis C virus (HCV) infection is a serious global health problem affecting 150 million individuals worldwide. Although infection rates are decreasing, an aging population with progressing disease is expected to result in increased burden of advanced stage disease with high associated costs. This analysis describes the current and projected future economic impact of HCV sequelae in Belgium. METHODS: A previously described and validated model was populated with Belgian inputs and calibrated to project the current and future health and economic burden of HCV. Monte Carlo and sensitivity analyses were run to quantify uncertainty. All estimates exclude the cost of antiviral therapy. RESULTS: Costs associated with HCV were projected to peak in 2026 at Euro126M (Euro30M-Euro257M), while decompensated cirrhosis and hepatocellular carcinoma costs were projected to increase until 2031 and 2034. The projected 2014-2030 cumulative cost of HCV under current conditions was Euro1,850M. Scenarios to reduce the burden of HCV could result in Euro70M-Euro400M in cumulative cost savings. Starting treatment (1,000 patients) in 2015 could result in Euro150M cost savings. The lifetime cost of HCV increases with life expectancy, with highest future costs projected among young females with early stage disease. CONCLUSIONS: The economic burden of HCV and advanced stage disease were projected to further increase. Cost reductions are possible with timely interventions aimed at minimizing the health burden of advanced stage disease.

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.

Surgical experience with left ventricular free wall rupture.

BACKGROUND: Autopsy studies reveal that left ventricular free wall rupture (LVFWR) accounts for 7% to 24% of deaths after myocardial infarction. The condition occurs up to 10 times more often than papillary muscle or interventricular septal rupture. A high index of suspicion must be maintained to differentiate LVFWR from infarct extension, cardiogenic shock, pulmonary embolus, and even Dressler's syndrome. METHODS: Since 1980, we have operated on 18 patients with LVFWR. Fourteen patients had experienced "blow-out" rupture associated with cardiogenic shock. Four patients had "stuttering" ruptures, a less spectacular occurrence. Echocardiography was the most important diagnostic tool. Repair was performed, usually using infarctectomy and direct suture closure. RESULTS: Eleven patients (61%) died after operation, 4 patients as a result of rerupture 1 to 12 hours after operation. Recently, we have used a "patch/glue" technique to repair ruptures in 2 patients. We believe this technique is superior to direct suture closure in preventing rerupture. There have been 7 long-term survivors (39%) from 6 months to 15 years. CONCLUSIONS: Left ventricular free wall rupture is not always sudden and dramatic. Yet, the operating staff must be willing to race to the operating room even with the patient in full resuscitation. Echocardiography is the most sensitive and efficient diagnostic tool. All rupture sites should be aggressively repaired, possibly combining direct suture and patch/glue techniques.

Multisensory programs in the public schools: A brighter future for LD children.

A longitudinal study followed the progress of a group of elementary SLD students as they were instructed using the Alphabetic Phonics (AP) curriculum. After a three year period, the AP curriculum produced positive results in reading comprehension for most SLD students, particularly those who began the program in first and second grade. Students in resource and self-contained settings made significant gains in reading comprehension, although the two types of students exhibited different patterns of progress. Students of different ability levels responded differently to the AP curriculum. Average and above average students made significant progress in reading comprehension, but below average students did not advance substantially in relation to their ability level. At the end of three years, classroom teachers had a significantly more positive view of students' word attack, oral reading, and silent reading comprehension skills.

Sudden blowout rupture of the myocardium after infarction: urgent management. Report of four cases.

Blowout rupture of the myocardium is intended to describe a syndrome of sudden hemodynamic deterioration after myocardial infarction. Characterized by abrupt hypotension, cardiac tamponade, or electromechanical dissociation, it is an emergency of the first order with no time for cardiac catheterization. Frequently one must make the diagnosis and race for the operating room almost simultaneously. We have managed four such patients, one with a ruptured false aneurysm and three patients with acute rupture of recently infarcted myocardium. All patients were placed on femoro-femoral bypass initially and all survived operation. Two patients died in the hospital of irreversible brain damage and two are long-term survivors. A high index of suspicion, a well-coordinated operating team, and a willingness to take the bold step to the operating room, frequently on the basis of clinical judgment alone, are necessary to salvage patients with this syndrome.

Pyomyositis caused by Yersinia enterocolitica.

Yersinia enterocolitica is known to be associated with gastroenteritis in children and Reiter's syndrome in adults, but it has only rarely been the cause of primary soft tissue infections. A patient with diabetes mellitus developed a calf abscess, from which Y. enterocolitica was isolated in pure culture. Incision, drainage, and intravenous gentamicin therapy resulted in cure.

Biomass energy from crop and forest residues.

Residues remaining after the harvest of crop and forestry products are being proposed as a substantial energy source for the nation. An estimated 22 percent of the residues might be utilized, providing a renewable source of high-grade energy with the potential of supplying 1 percent of the current U.S. gasoline consumption as ethanol or 4 percent of the total electrical energy used. These net energy benefits are limited by high energy costs to collect, transport, and process the residues. Environmental threats include soil erosion, water runoff, and nutrient loss.

Serodiagnosis of viral hepatitis A: detection of acute-phase immunoglobulin M anti-hepatitis A virus by radioimmunoassay.

A modified micro solid-phase radioimmunoassay (RIA) for antibody to hepatitis A virus (anti-HAV) was developed. This double antibody procedure was performed by coating the surface of a polyvinyl microtiter plate "well" with 200 microliter of a 1:1,000 dilution of a patient's test serum. Purified HAV and 125I-labeled immunoglobulin G (IgG) anti-HAV were then sequentially added to form an antibody sandwich. The specificity and sensitivity of the RIA procedure for anti-HAV were verified by examination of coded human and chimpanzee serum specimens. Radioimmunoassay of early-acute-phase serum specimens from human cases of hepatitis A revealed the presence of anti-HAV activity. Differential examination by RIA of IgG and IgM fractions of acute-phase sera from experimentally infected chimpanzees demonstrated that IgM contained the bulk of the anti-HAV activity. A modification of the RIA procedure for anti-HAV (RIA-IgM blocking), incorporating an incubation step with anti-IgM (Mu chain specific), was further shown to differentiate acute- from convalescent-phase hepatitis A sera. This adapted RIA-IgM blocking procedure required less than 1 microliter of a single acute-phase serum specimen for the diagnosis of viral hepatitis A.

Foodborne hepatitis A infection: a report of two urban restaurant-associated outbreaks.

The cities of Portland, Oregon, and Buffalo, New York, each experienced a restaurant-associated foodborne outbreak of viral hepatitis type A during 1975. Although there were several food handlers ill with viral hepatitis A in each of the restaurants involved, each outbreak was the apparent result of food contamination by a single food handler. In the Buffalo outbreak, food contamination was documented to have occurred for a brief period of time six days prior to onset of any symptoms in the index case. These outbreaks point out the uncommon occurrence of food contamination by individuals ill with type A viral hepatitis, the usefulness of two types of food questionnaires in identifying the vehicle(s) of transmission, and the apparent lack of benefit of widespread immune serum globulin administration as a control measure in this setting.

Simultaneous infection with type A and B hepatitis viruses.

The occurrence of a common source hepatitis A epidemic among the residents of a New England state mental institution where hepatitis B is hyperendemic provided an opportunity to observe concurrent infections with both agents. Nine HBsAg-positive individuals developed hepatitis A infections documented by hepatitis A antibody seroconversion in eight. The incidence of hepatitis A infections in susceptible HBsAg-positive persons (67%) did not differ from that in HBsAg-negative individuals (63%). The icteric to anicteric infection ratio in the HBsAG-positives (1:1.7) was similar to that in the negatives (1:2.1), and the clinical course in the antigen positives did not differ significantly from that of the antigen negatives. In addition to confirming previous reports that the viruses of hepatitis A and B are immunologically distinct, these results document that infection with either is independent of the other, and that the morbidity from simultaneous infection is no greater than that caused by either alone.

Nosocomial viral hepatitis B. A cluster among staff with subsequent transmission to patients.

In a 2-month period four cases of hepatitis B occurred in hospital staff. Three months later two patients, hospitalized for open-heart surgery when the staff members had been infected, developed acute hepatitis B. Sera from all six ill individuals were subtype ayw and e-determinant positive. Epidemiologic investigation showed that the four staff had been exposed 3 months earlier to an asymptomatic hepatitis B surface antigen-positive (HBsAg) patient who was also e positive. To determine transmission from staff to patients study of 17 open-heart surgery patients was undertaken. Four of 17 were either HBsAg or anti-HBs positive. No correlation between infection and contact with three of four ill staff members or receipt of blood products was noted; however, 22 (46%) of 48 arterial blood gas specimens had been obtained from infected patients by one staff member, an inhalation therapist; this compared with seven (4%) of 157 specimens she obtained from control subjects (P less than 0.001). Furthermore, she handled indwelling arterial cannulae 25 (76%) of 33 times in infected patients compared with three (3%) of 95 times in control subjects (P less than 0.001). Transmission may have occurred via the arterial cannulae from a severe exudative dermatitis on the therapist's hands.

"e" Antigen, Dane particles, and serum DNA polymerase activity in HBsAg carriers.

Sera of 103 carriers of hepatitis B surface antigen were assayed for e-antigen and anti-e. Twenty-four were e-antigen-positive, 31 anti-e-positive, and 48 had neither detectable (e-negative). Aminotransferases were elevated in 75% of the e-antigen-positive carriers compared with 25% of e-negative carriers (P less than 0.001) and 13% of anti-e-positive carriers (P less than 0.001). Serum DNA polymerase activity was significantly higher in the e-antigen-positive carriers than in carriers without e-antigen. Dane particles were shown in 10 of 12 carriers with e-antigen, compared with one of 12 e-negative carriers (P less than 0.0003) and none of 12 anti-e-positive carriers (P less than 0.00003). These results suggest that ongoing hepatitis B viral replication is more active in e-antigen-positive carriers than in carriers without e-antigen, a finding that may help explain the high prevalence of chronic active hepatitis described in these individuals.

Gram-negative water bacteria in hemodialysis systems.

Gram-negative bacteria can multiply relatively fast in a variety of hospital associated fluids ranging from distilled, deionized, reverse osmosis, and softened water, which are normally considered devoid of nutrients, to intravenous solutions and fluids associated with hemodialysis. Excessive levels of these bacteria in the dialysate of artificial kidney machines can be responsible for pyrogenic reactions or sepsis or both.

Pyrogenic reactions during haemodialysis caused by extramural endotoxin.

Between July 24 and Aug. 19, 1974, an outbreak of pyrogenic reactions occurred in patients at a private haemodialysis centre in a suburb of Washington, D.C. 49 reactions characterised by chills, fever, and hypotension occurred in twenty-three of the seventy patients dialysed during this period. No infections could be documented in any of the affected individuals. Despite the fact that only low levels of gram-negative bacterial contamination of the haemodialysis system were found, high levels of endotoxin contamination of dialysis fluid and endotoxaemia in patients experiencing overt reactions were recorded using the Limulus lysate test. The cause of these reactions was traced to an increase in endotoxin contamination of the tap water used to prepare dialysate, possibly caused by an increase in the algae levels in the local water source. The installation of a reverse osmosis system for water treatment may be a solution to the problem of endotoxin contamination of water used to prepare dialysis fluid.