D. Semela - Academia.edu (original) (raw)
Papers by D. Semela
Swiss medical weekly, 2015
In Switzerland, fewer than 40% of hepatitis C virus (HCV) infected individuals have been diagnose... more In Switzerland, fewer than 40% of hepatitis C virus (HCV) infected individuals have been diagnosed. The aim of this project was to analyse the distribution of HCV cases in order to develop better detection strategies. Historical data on the HCV-infected population in Switzerland were obtained from published literature, unpublished data and government reports. A disease progression model was used to age the infected population to 2015. The HCV distribution was then used to identify 5-year age cohorts with the highest HCV prevalence. The estimated number of cases needed to screen within an age cohort was calculated using the estimated viraemic prevalence, removing the percent previously diagnosed. In 2015, the median age of the viraemic HCV infected population was 49 years, with 75% of the population born between 1951 and 1985. Random screening of the general population could identify one new viraemic HCV case per 159 persons screened, compared with targeted birth cohort screening, wh...
Swiss medical weekly, Jan 4, 2002
starting treatment of reactive macrophage activation syndromes as early as possible (rMAS, haemop... more starting treatment of reactive macrophage activation syndromes as early as possible (rMAS, haemophagocytic lymphohistiocytosis), e.g., with intravenous immunoglobulins (IVIG), seems to be essential for optimal outcome. However, there is no diagnostic gold standard which reliably indicates need for early treatment. We used a simple screening strategy consisting of serum ferritin measurements and/or morphological assessment of haemophagocytosis and compared the studied patient population with published series. Retrospective analysis of clinical and laboratory data of 57 patients experiencing 60 episodes of rMAS. Screening by serum ferritin measurements and/or morphological assessment of haemophagocytosis of patients presenting with a systemic inflammatory response syndrome (SIRS) indicates that rMAS might be considerably more frequent than stated in the literature. Serum ferritin exceeded >10,000 microg/L in 91% rMAS episodes. Although the patient population studied was otherwise s...
Praxis, 2010
We report the case of a 44 year old female gardener who presented to our emergency ward with lumb... more We report the case of a 44 year old female gardener who presented to our emergency ward with lumbago, myalgia and fever of 39 degrees Celsius. She also reported acholic stools, darker looking urine and ikteric skin complexion. The patient was suffering from acute hepatitis A virus induced liver failure and was rapidly announced to a liver transplant centre. In the course of the illness the condition of the patient improved spontaneously and the serious hepatitis resolved and was self limiting. As a source of infection to possibilities were identified. Eating shellfish at the East Sea 4 weeks prior to admission or handling natural animal dung during her work as a gardener. One year after the event the patient once again is healthy and well.
Swiss Medical Weekly, 2012
Hepatocellular carcinoma (HCC) is the most frequent form of primary liver cancer and chronic infe... more Hepatocellular carcinoma (HCC) is the most frequent form of primary liver cancer and chronic infection with hepatitis C virus is one of the main risk factors for HCC. This study analyses the characteristics of the patients with chronic hepatitis C participating in the Swiss Hepatitis C Cohort Study who developed HCC. Analysis of the database of the Swiss Hepatitis C Cohort Study, a multicentre study that is being carried out in eight major Swiss hospitals since the year 2000. Patients with chronic hepatitis C and HCC were regrouped and compared to the patients without HCC. Among the 3,390 patients of the cohort, 130 developed an HCC. Age was one of the determining factors. Cirrhosis and its complications ascites and porto-systemic encephalopathy were associated with HCC. Males presented a higher risk for HCC than females. Alcohol consumption was associated with HCC. Diabetes mellitus was an important risk factor, especially in patients with low fibrosis. Patients with Hepatitis C genotype 2 had significantly less HCC than patients with other genotypes. A low socioeconomic status (income, education, profession) was associated with HCC. Beside the expected characteristics (age, gender, cirrhosis, alcohol), these data stress the role of diabetes mellitus and reveal the importance of low socioeconomic status as a risk factor for HCC in Swiss patients infected with hepatitis C virus. This vulnerable population should be closely monitored.
Journal of Viral Hepatitis, 2014
Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New trea... more 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.
Journal of Viral Hepatitis, 2014
The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ... more 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.
Journal of Viral Hepatitis, 2014
The number of hepatitis C virus (HCV) infections is projected to decline while those with advance... more 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.
Journal of the American Academy of Dermatology, 2014
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](Journal of Hepatology, 2007
Journal of Hepatology, 2014
Journal of Hepatology, 2014
Journal of Hepatology, 2014
Journal of Hepatology, 2014
Journal of Hepatology, 2013
Journal of Hepatology, 2009
Angiogenesis and disruption of liver vascular architecture have been linked to progression to cir... more Angiogenesis and disruption of liver vascular architecture have been linked to progression to cirrhosis and liver cancer (HCC) in chronic liver diseases, which contributes both to increased hepatic vascular resistance and portal hypertension and to decreased hepatocyte perfusion. On the other hand, recent evidence shows that angiogenesis modulates the formation of portal-systemic collaterals and the increased splanchnic blood flow which are involved in the life threatening complications of cirrhosis. Finally, angiogenesis plays a key role in the growth of tumours, suggesting that interference with angiogenesis may prevent or delay the development of HCC. This review summarizes current knowledge on the molecular mechanisms of liver angiogenesis and on the consequences of angiogenesis in chronic liver disease. On the other hand, it presents the different strategies that have been used in experimental models to counteract excessive angiogenesis and its potential role in preventing transition to cirrhosis, development of portal hypertension and its consequences, and its application in the treatment of hepatocellular carcinoma.
Journal of Hepatology, 2012
Journal of Hepatology, 2012
Journal of Hepatology, 2012
Journal of Cell Science, 2007
Endothelial cell-based angiogenesis requires activation of survival signals that generate resista... more Endothelial cell-based angiogenesis requires activation of survival signals that generate resistance to external apoptotic stimuli, such as tumor necrosis factor-alpha (TNF-alpha), during pathobiologic settings. Mechanisms by which this is achieved are not fully defined. Here, we use a model in which the multifunctional cytokine nitric oxide counterbalances TNF-alpha-induced apoptosis, to define a role for membrane trafficking in the process of endothelial cell survival signaling. By perturbing dynamin GTPase function, we identify a key role of dynamin for ensuing downstream endothelial cell survival signals and vascular tube formation. Furthermore, nitric oxide is directly demonstrated to promote dynamin function through specific cysteine residue nitrosylation, which promotes endocytosis and endothelial cell survival signaling. Thus, these studies identify a novel role for dynamin as a survival factor in endothelial cells, through a mechanism by which dynamin S-nitrosylation regulates the counterbalances of TNF-alpha-induced apoptosis and nitric oxide-dependent survival signals, with implications highly relevant to angiogenesis.
Swiss medical weekly, 2015
In Switzerland, fewer than 40% of hepatitis C virus (HCV) infected individuals have been diagnose... more In Switzerland, fewer than 40% of hepatitis C virus (HCV) infected individuals have been diagnosed. The aim of this project was to analyse the distribution of HCV cases in order to develop better detection strategies. Historical data on the HCV-infected population in Switzerland were obtained from published literature, unpublished data and government reports. A disease progression model was used to age the infected population to 2015. The HCV distribution was then used to identify 5-year age cohorts with the highest HCV prevalence. The estimated number of cases needed to screen within an age cohort was calculated using the estimated viraemic prevalence, removing the percent previously diagnosed. In 2015, the median age of the viraemic HCV infected population was 49 years, with 75% of the population born between 1951 and 1985. Random screening of the general population could identify one new viraemic HCV case per 159 persons screened, compared with targeted birth cohort screening, wh...
Swiss medical weekly, Jan 4, 2002
starting treatment of reactive macrophage activation syndromes as early as possible (rMAS, haemop... more starting treatment of reactive macrophage activation syndromes as early as possible (rMAS, haemophagocytic lymphohistiocytosis), e.g., with intravenous immunoglobulins (IVIG), seems to be essential for optimal outcome. However, there is no diagnostic gold standard which reliably indicates need for early treatment. We used a simple screening strategy consisting of serum ferritin measurements and/or morphological assessment of haemophagocytosis and compared the studied patient population with published series. Retrospective analysis of clinical and laboratory data of 57 patients experiencing 60 episodes of rMAS. Screening by serum ferritin measurements and/or morphological assessment of haemophagocytosis of patients presenting with a systemic inflammatory response syndrome (SIRS) indicates that rMAS might be considerably more frequent than stated in the literature. Serum ferritin exceeded >10,000 microg/L in 91% rMAS episodes. Although the patient population studied was otherwise s...
Praxis, 2010
We report the case of a 44 year old female gardener who presented to our emergency ward with lumb... more We report the case of a 44 year old female gardener who presented to our emergency ward with lumbago, myalgia and fever of 39 degrees Celsius. She also reported acholic stools, darker looking urine and ikteric skin complexion. The patient was suffering from acute hepatitis A virus induced liver failure and was rapidly announced to a liver transplant centre. In the course of the illness the condition of the patient improved spontaneously and the serious hepatitis resolved and was self limiting. As a source of infection to possibilities were identified. Eating shellfish at the East Sea 4 weeks prior to admission or handling natural animal dung during her work as a gardener. One year after the event the patient once again is healthy and well.
Swiss Medical Weekly, 2012
Hepatocellular carcinoma (HCC) is the most frequent form of primary liver cancer and chronic infe... more Hepatocellular carcinoma (HCC) is the most frequent form of primary liver cancer and chronic infection with hepatitis C virus is one of the main risk factors for HCC. This study analyses the characteristics of the patients with chronic hepatitis C participating in the Swiss Hepatitis C Cohort Study who developed HCC. Analysis of the database of the Swiss Hepatitis C Cohort Study, a multicentre study that is being carried out in eight major Swiss hospitals since the year 2000. Patients with chronic hepatitis C and HCC were regrouped and compared to the patients without HCC. Among the 3,390 patients of the cohort, 130 developed an HCC. Age was one of the determining factors. Cirrhosis and its complications ascites and porto-systemic encephalopathy were associated with HCC. Males presented a higher risk for HCC than females. Alcohol consumption was associated with HCC. Diabetes mellitus was an important risk factor, especially in patients with low fibrosis. Patients with Hepatitis C genotype 2 had significantly less HCC than patients with other genotypes. A low socioeconomic status (income, education, profession) was associated with HCC. Beside the expected characteristics (age, gender, cirrhosis, alcohol), these data stress the role of diabetes mellitus and reveal the importance of low socioeconomic status as a risk factor for HCC in Swiss patients infected with hepatitis C virus. This vulnerable population should be closely monitored.
Journal of Viral Hepatitis, 2014
Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New trea... more 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.
Journal of Viral Hepatitis, 2014
The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ... more 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.
Journal of Viral Hepatitis, 2014
The number of hepatitis C virus (HCV) infections is projected to decline while those with advance... more 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.
Journal of the American Academy of Dermatology, 2014
Journal of Hepatology, 2007
Journal of Hepatology, 2014
Journal of Hepatology, 2014
Journal of Hepatology, 2014
Journal of Hepatology, 2014
Journal of Hepatology, 2013
Journal of Hepatology, 2009
Angiogenesis and disruption of liver vascular architecture have been linked to progression to cir... more Angiogenesis and disruption of liver vascular architecture have been linked to progression to cirrhosis and liver cancer (HCC) in chronic liver diseases, which contributes both to increased hepatic vascular resistance and portal hypertension and to decreased hepatocyte perfusion. On the other hand, recent evidence shows that angiogenesis modulates the formation of portal-systemic collaterals and the increased splanchnic blood flow which are involved in the life threatening complications of cirrhosis. Finally, angiogenesis plays a key role in the growth of tumours, suggesting that interference with angiogenesis may prevent or delay the development of HCC. This review summarizes current knowledge on the molecular mechanisms of liver angiogenesis and on the consequences of angiogenesis in chronic liver disease. On the other hand, it presents the different strategies that have been used in experimental models to counteract excessive angiogenesis and its potential role in preventing transition to cirrhosis, development of portal hypertension and its consequences, and its application in the treatment of hepatocellular carcinoma.
Journal of Hepatology, 2012
Journal of Hepatology, 2012
Journal of Hepatology, 2012
Journal of Cell Science, 2007
Endothelial cell-based angiogenesis requires activation of survival signals that generate resista... more Endothelial cell-based angiogenesis requires activation of survival signals that generate resistance to external apoptotic stimuli, such as tumor necrosis factor-alpha (TNF-alpha), during pathobiologic settings. Mechanisms by which this is achieved are not fully defined. Here, we use a model in which the multifunctional cytokine nitric oxide counterbalances TNF-alpha-induced apoptosis, to define a role for membrane trafficking in the process of endothelial cell survival signaling. By perturbing dynamin GTPase function, we identify a key role of dynamin for ensuing downstream endothelial cell survival signals and vascular tube formation. Furthermore, nitric oxide is directly demonstrated to promote dynamin function through specific cysteine residue nitrosylation, which promotes endocytosis and endothelial cell survival signaling. Thus, these studies identify a novel role for dynamin as a survival factor in endothelial cells, through a mechanism by which dynamin S-nitrosylation regulates the counterbalances of TNF-alpha-induced apoptosis and nitric oxide-dependent survival signals, with implications highly relevant to angiogenesis.