According to the recent data presented by Central-European HCV experts, the estimated prevalence of HCV is between 0.2% and 1.7% in certain countries in this region. There are no financial limitations to access to treatment in most countries. Patients in these countries have access to at least one pangenotypic regimen. The most common barriers to the elimination of HCV in Central Europe are a lack of established national screening programmes and limited political commitment to the elimination of HCV. Covid-19 has significantly affected the number of patients who have been diagnosed and treated, thus, delaying the potential elimination of HCV. These data suggest that the elimination of HCV elimination projected by WHO before 2030 will not be possible in the Central Europe.Hepatitis D virus may be underestimated because it is a significant problem in HBsAg-positive patients, especially those who inject drugs, have HIV or HCV co-infections and/or live in certain endemic regions. In the past few decades, the prevalence of HDV was expected to have decreased as a result of improvements in public healthcare policies and universal HBV vaccination programs. However, HDV has continued to spread in low-income countries, with local outbreaks and migration to less endemic areas, so that its prevalence has remained stable or even increased in certain regions. As a result, research has been focused on the epidemiology of HDV. Contradicting data from three large recent meta-analyses have reported that the prevalence of HDV may be between 0.16% and 1.00% in the global general population, and 4.5% and 14.6% in HBsAg-positive patients, with an estimated 12 to 70 million HDV patients worldwide. The exact prevalence and estimated number of HDV patients is still a subject of debate for several reasons, including the unreliable assessment of the infection and a lack of real-world screening. HDV infection is associated with an increased risk of progression to cirrhosis and the development of HCC compared to patients with HBV mono-infection, a risk which is even higher in patients with HIV co-infection. Morbidity and mortality from HDV-related cirrhosis should not be overlooked. In conclusion, hepatitis D virus is probably underestimated and certainly underdiagnosed, and screening for HDV should be performed in all HBsAg-positive patients in clinical practice.Non-alcoholic steatohepatitis (NASH) is a result of inflammation and hepatocyte injury in the presence of hepatic steatosis which can progress to cirrhosis. NASH is the most rapidly growing aetiology for liver failure and indication for liver transplantation in the United States. Non-alcoholic fatty liver disease (NAFLD) is associated with obesity, type 2 diabetes, dyslipidaemia and metabolic syndrome. Because of the absence of approved pharmacotherapy, weight loss and lifestyle modifications remain the safest and most effective first-line treatment. However, this may not be effective in patients with advanced fibrosis or cirrhosis and long-term adherence is difficult to achieve. Therefore, effective drugs are urgently needed for the treatment of NASH. Drug development targeting pathological pathways in NASH have exploded in the past decade, with numerous new drugs under investigation. This review summarizes the results of pivotal finalized phase 2 studies and provides an outline of key active studies with trial data of drugs under development.Acute-on-chronic liver failure (ACLF) is defined by the rapid development of organ(s) failure(s) associated with high rates of early (28-day) mortality in patients with cirrhosis. ACLF has been categorized into three grades of increasing severity according to the nature and number of organ failures. In patients with grade 3 ACLF, 28-day mortality is >70%. While the definition of ACLF has been endorsed by European scientific societies, North American and Asian Pacific associations have proposed alternative definitions. A prognostic score called the CLIF-C ACLF score provides a more precise assessment of the prognosis of patients with ACLF. Although bacterial infections and variceal bleeding are common precipitating factors, no precipitating factor can be identified in almost 60% of patients with ACLF. There is increasing evidence that cirrhosis is a condition characterized by a systemic inflammatory state and occult infections or translocation of bacteria or bacterial products from the lumen of the GUT to the systemic circulation which could play a role in the development of ACLF. https://www.selleckchem.com/Androgen-Receptor.html Simple and readily available variables to predict the occurrence of ACLF in patients with cirrhosis have been identified and high-risk patients need careful management. Whether prolonged administration of statins, rifaximin or albumin can prevent ACLF requires further study. Patients with organ(s) failure(s) may needed to be admitted to the ICU and there should be no hesitation in admitting patients with cirrhosis to the ICU. No benefit to survival was observed with albumin dialysis and rescue transplantation is the best option in the most severe patients. One-year post-transplant survival rates exceeding 70%-75% have been reported, including in patients with grade 3 ACLF but these patients were highly selected. Criteria have been proposed to define futile transplantation (too ill to be transplanted), but these criteria need to be refined to include age, comorbidities and frailty in addition to markers of disease severity.Non-alcoholic fatty liver disease (NAFLD) is the fastest growing cause of chronic liver disease worldwide. Although only a small proportion of NAFLD patients will progress to end-stage liver disease and death, the clinical burden of NAFLD is substantial due the sheer number of individuals affected worldwide. In fact, recent estimates suggest that 25% of the world have NAFLD, which is now one of the leading causes of cirrhosis and indications for liver transplantation. Although liver-related mortality is common, the most common cause of death in patients with NAFLD is related to cardiovascular diseases, followed by extra-hepatic cancers. There is a significant interindividual variability in the susceptibility to liver disease. The severity of metabolic alterations is the main risk factor for progressive NAFLD, but the qualitative components of diet, physical activity and genetic factors also play an important role. In particular, common variants in patatin-like phospholipase domain-containing 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), membrane bound O-acyl transferase 7 (MBOAT7) and glucokinase regulator (GCKR) have been shown to contribute to the full spectrum of NAFLD.
According to the recent data presented by Central-European HCV experts, the estimated prevalence of HCV is between 0.2% and 1.7% in certain countries in this region. There are no financial limitations to access to treatment in most countries. Patients in these countries have access to at least one pangenotypic regimen. The most common barriers to the elimination of HCV in Central Europe are a lack of established national screening programmes and limited political commitment to the elimination of HCV. Covid-19 has significantly affected the number of patients who have been diagnosed and treated, thus, delaying the potential elimination of HCV. These data suggest that the elimination of HCV elimination projected by WHO before 2030 will not be possible in the Central Europe.Hepatitis D virus may be underestimated because it is a significant problem in HBsAg-positive patients, especially those who inject drugs, have HIV or HCV co-infections and/or live in certain endemic regions. In the past few decades, the prevalence of HDV was expected to have decreased as a result of improvements in public healthcare policies and universal HBV vaccination programs. However, HDV has continued to spread in low-income countries, with local outbreaks and migration to less endemic areas, so that its prevalence has remained stable or even increased in certain regions. As a result, research has been focused on the epidemiology of HDV. Contradicting data from three large recent meta-analyses have reported that the prevalence of HDV may be between 0.16% and 1.00% in the global general population, and 4.5% and 14.6% in HBsAg-positive patients, with an estimated 12 to 70 million HDV patients worldwide. The exact prevalence and estimated number of HDV patients is still a subject of debate for several reasons, including the unreliable assessment of the infection and a lack of real-world screening. HDV infection is associated with an increased risk of progression to cirrhosis and the development of HCC compared to patients with HBV mono-infection, a risk which is even higher in patients with HIV co-infection. Morbidity and mortality from HDV-related cirrhosis should not be overlooked. In conclusion, hepatitis D virus is probably underestimated and certainly underdiagnosed, and screening for HDV should be performed in all HBsAg-positive patients in clinical practice.Non-alcoholic steatohepatitis (NASH) is a result of inflammation and hepatocyte injury in the presence of hepatic steatosis which can progress to cirrhosis. NASH is the most rapidly growing aetiology for liver failure and indication for liver transplantation in the United States. Non-alcoholic fatty liver disease (NAFLD) is associated with obesity, type 2 diabetes, dyslipidaemia and metabolic syndrome. Because of the absence of approved pharmacotherapy, weight loss and lifestyle modifications remain the safest and most effective first-line treatment. However, this may not be effective in patients with advanced fibrosis or cirrhosis and long-term adherence is difficult to achieve. Therefore, effective drugs are urgently needed for the treatment of NASH. Drug development targeting pathological pathways in NASH have exploded in the past decade, with numerous new drugs under investigation. This review summarizes the results of pivotal finalized phase 2 studies and provides an outline of key active studies with trial data of drugs under development.Acute-on-chronic liver failure (ACLF) is defined by the rapid development of organ(s) failure(s) associated with high rates of early (28-day) mortality in patients with cirrhosis. ACLF has been categorized into three grades of increasing severity according to the nature and number of organ failures. In patients with grade 3 ACLF, 28-day mortality is >70%. While the definition of ACLF has been endorsed by European scientific societies, North American and Asian Pacific associations have proposed alternative definitions. A prognostic score called the CLIF-C ACLF score provides a more precise assessment of the prognosis of patients with ACLF. Although bacterial infections and variceal bleeding are common precipitating factors, no precipitating factor can be identified in almost 60% of patients with ACLF. There is increasing evidence that cirrhosis is a condition characterized by a systemic inflammatory state and occult infections or translocation of bacteria or bacterial products from the lumen of the GUT to the systemic circulation which could play a role in the development of ACLF. https://www.selleckchem.com/Androgen-Receptor.html Simple and readily available variables to predict the occurrence of ACLF in patients with cirrhosis have been identified and high-risk patients need careful management. Whether prolonged administration of statins, rifaximin or albumin can prevent ACLF requires further study. Patients with organ(s) failure(s) may needed to be admitted to the ICU and there should be no hesitation in admitting patients with cirrhosis to the ICU. No benefit to survival was observed with albumin dialysis and rescue transplantation is the best option in the most severe patients. One-year post-transplant survival rates exceeding 70%-75% have been reported, including in patients with grade 3 ACLF but these patients were highly selected. Criteria have been proposed to define futile transplantation (too ill to be transplanted), but these criteria need to be refined to include age, comorbidities and frailty in addition to markers of disease severity.Non-alcoholic fatty liver disease (NAFLD) is the fastest growing cause of chronic liver disease worldwide. Although only a small proportion of NAFLD patients will progress to end-stage liver disease and death, the clinical burden of NAFLD is substantial due the sheer number of individuals affected worldwide. In fact, recent estimates suggest that 25% of the world have NAFLD, which is now one of the leading causes of cirrhosis and indications for liver transplantation. Although liver-related mortality is common, the most common cause of death in patients with NAFLD is related to cardiovascular diseases, followed by extra-hepatic cancers. There is a significant interindividual variability in the susceptibility to liver disease. The severity of metabolic alterations is the main risk factor for progressive NAFLD, but the qualitative components of diet, physical activity and genetic factors also play an important role. In particular, common variants in patatin-like phospholipase domain-containing 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), membrane bound O-acyl transferase 7 (MBOAT7) and glucokinase regulator (GCKR) have been shown to contribute to the full spectrum of NAFLD.
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