The document discusses the rapidly evolving landscape of direct-acting antiviral (DAA) treatments for hepatitis C virus (HCV) infection. Three key studies demonstrated that all-oral, interferon-free combinations of DAAs achieved high sustained virologic response rates (SVR) of over 90% for various genotypes and patient populations. These include a combination of sofosbuvir and ledipasvir, a triple therapy of ABT-450/r, ABT-267 and ABT-333, and a combination of daclatasvir and asunaprevir. Several DAAs are now approved or in late-stage trials. These new interferon-free regimens have the potential
The document discusses the evolution of hepatitis C virus (HCV) therapy from interferon-based regimens to all-oral, interferon-free direct-acting antiviral (DAA) combinations. Clinical trials demonstrated that combinations of NS5A inhibitors like ledipasvir or daclatasvir with NS5B inhibitors like sofosbuvir achieved high sustained virologic response rates of over 90%, including in difficult-to-treat groups. New DAA combinations including two or three-drug regimens from AbbVie, Gilead, and BMS were shown to cure HCV in the majority of patients with 8-12 weeks of therapy. While these new therapies represent significant advances, challenges remain
David Wyles, M.D., of the UC San Diego AntiViral Research Center, presents "HCV in 2015: New Medication Approvals and Innovative Studies...Including a One-Shot Cure?" at AIDS Clinical Rounds
Best Practices in the Management of HCV. 2015hivlifeinfo
In this downloadable slideset, Andrew J. Muir, MD, reviews the evidence informing current guidance and best practices on treating patients with hepatitis C.
Format: Microsoft PowerPoint (.ppt)
File size: 1.97 MB
[2015] hcv direct acting antivirals [da as] stumblingAyman Alsebaey
This document summarizes direct-acting antivirals (DAAs) for treating hepatitis C virus (HCV). It describes the HCV lifecycle and targets of DAAs, including NS3/4A protease inhibitors, NS5A inhibitors, and NS5B nucleoside/non-nucleoside inhibitors. Clinical trials show high sustained virologic response rates for DAA combinations compared to pegylated interferon/ribavirin. However, treatment can fail if resistance-associated variants are present or develop. The document discusses factors influencing treatment failure and common resistance mutations for different DAA classes and genotypes. It emphasizes the importance of achieving high barrier to resistance through appropriate drug selection and combination therapy.
This document discusses advances in treatment for hepatitis C virus (HCV) infection. It provides information on:
- The primary goals of HCV treatment as viral eradication and prevention of liver disease progression.
- Definitions of sustained virological response (SVR) and response rates achieved with pegylated interferon and ribavirin treatment.
- New direct-acting antiviral drugs in development that target specific steps in the HCV lifecycle, including protease, polymerase, and NS5A inhibitors.
This document discusses Harvoni and its role in treating Hepatitis C. It provides an overview of Hepatitis C, including epidemiology and clinical presentation. It describes the mechanism of action and pharmacokinetics of the two drugs in Harvoni - Ledipasvir and Sofosbuvir. It summarizes several clinical trials that evaluated Harvoni's efficacy and safety in treating genotype 1 Hepatitis C in treatment-naive and experienced patients, with and without cirrhosis, finding high sustained virologic response rates with 12 weeks of Harvoni treatment.
- An estimated 170 million people worldwide are infected with hepatitis C virus (HCV). New direct-acting antiviral (DAA) drugs such as sofosbuvir have improved sustained virologic response rates and reduced treatment duration and side effects compared to previous interferon-based regimens.
- Phase 2/3 clinical trials showed that 12 weeks of sofosbuvir plus peginterferon and ribavirin achieved high SVR rates of 88-99% in treatment-naive patients with genotypes 1, 4, 5, and 6 HCV. Sofosbuvir is a nucleotide analogue inhibitor of the HCV NS5B polymerase enzyme.
1) Hepatitis C virus genotype 4 is predominant in Egypt, with a prevalence of around 9%.
2) New direct-acting antiviral agents have improved treatment outcomes, but the virus's ability to mutate rapidly can lead to resistance.
3) The document provides treatment recommendations and regimens using direct-acting antivirals like sofosbuvir and daclatasvir to treat hepatitis C genotype 4, including for different patient populations and treatment experiences. It establishes guidelines for Egyptian treatment protocols.
The document discusses the evolution of hepatitis C virus (HCV) therapy from interferon-based regimens to all-oral, interferon-free direct-acting antiviral (DAA) combinations. Clinical trials demonstrated that combinations of NS5A inhibitors like ledipasvir or daclatasvir with NS5B inhibitors like sofosbuvir achieved high sustained virologic response rates of over 90%, including in difficult-to-treat groups. New DAA combinations including two or three-drug regimens from AbbVie, Gilead, and BMS were shown to cure HCV in the majority of patients with 8-12 weeks of therapy. While these new therapies represent significant advances, challenges remain
David Wyles, M.D., of the UC San Diego AntiViral Research Center, presents "HCV in 2015: New Medication Approvals and Innovative Studies...Including a One-Shot Cure?" at AIDS Clinical Rounds
Best Practices in the Management of HCV. 2015hivlifeinfo
In this downloadable slideset, Andrew J. Muir, MD, reviews the evidence informing current guidance and best practices on treating patients with hepatitis C.
Format: Microsoft PowerPoint (.ppt)
File size: 1.97 MB
[2015] hcv direct acting antivirals [da as] stumblingAyman Alsebaey
This document summarizes direct-acting antivirals (DAAs) for treating hepatitis C virus (HCV). It describes the HCV lifecycle and targets of DAAs, including NS3/4A protease inhibitors, NS5A inhibitors, and NS5B nucleoside/non-nucleoside inhibitors. Clinical trials show high sustained virologic response rates for DAA combinations compared to pegylated interferon/ribavirin. However, treatment can fail if resistance-associated variants are present or develop. The document discusses factors influencing treatment failure and common resistance mutations for different DAA classes and genotypes. It emphasizes the importance of achieving high barrier to resistance through appropriate drug selection and combination therapy.
This document discusses advances in treatment for hepatitis C virus (HCV) infection. It provides information on:
- The primary goals of HCV treatment as viral eradication and prevention of liver disease progression.
- Definitions of sustained virological response (SVR) and response rates achieved with pegylated interferon and ribavirin treatment.
- New direct-acting antiviral drugs in development that target specific steps in the HCV lifecycle, including protease, polymerase, and NS5A inhibitors.
This document discusses Harvoni and its role in treating Hepatitis C. It provides an overview of Hepatitis C, including epidemiology and clinical presentation. It describes the mechanism of action and pharmacokinetics of the two drugs in Harvoni - Ledipasvir and Sofosbuvir. It summarizes several clinical trials that evaluated Harvoni's efficacy and safety in treating genotype 1 Hepatitis C in treatment-naive and experienced patients, with and without cirrhosis, finding high sustained virologic response rates with 12 weeks of Harvoni treatment.
- An estimated 170 million people worldwide are infected with hepatitis C virus (HCV). New direct-acting antiviral (DAA) drugs such as sofosbuvir have improved sustained virologic response rates and reduced treatment duration and side effects compared to previous interferon-based regimens.
- Phase 2/3 clinical trials showed that 12 weeks of sofosbuvir plus peginterferon and ribavirin achieved high SVR rates of 88-99% in treatment-naive patients with genotypes 1, 4, 5, and 6 HCV. Sofosbuvir is a nucleotide analogue inhibitor of the HCV NS5B polymerase enzyme.
1) Hepatitis C virus genotype 4 is predominant in Egypt, with a prevalence of around 9%.
2) New direct-acting antiviral agents have improved treatment outcomes, but the virus's ability to mutate rapidly can lead to resistance.
3) The document provides treatment recommendations and regimens using direct-acting antivirals like sofosbuvir and daclatasvir to treat hepatitis C genotype 4, including for different patient populations and treatment experiences. It establishes guidelines for Egyptian treatment protocols.
This document summarizes guidelines from the American Association for the Study of Liver Diseases (AASLD) regarding the management of hepatitis C virus (HCV)-infected patients. It discusses recommendations for treating special populations including nonresponders, patients with normal ALT levels, children, and patients coinfected with HIV. It provides data from clinical studies on treatment outcomes for these groups. The guidelines recommend individualized treatment decisions based on factors like biopsy results, comorbidities, and likelihood of response. Peginterferon and ribavirin are generally recommended treatment options.
Hepatitis (C) Story …. Past & Present & future
Most Recant Updating Guidelines by ASSLD & FDA
RAVS &How to deal with It ----12/7/2016.....
((Residents Lectures))
Hepatitis c treatment in ESRD patients , update Dr Ayman Seddik Ayman Seddik
This document discusses hepatitis C treatment in patients with end-stage renal disease. It outlines that newer direct-acting antiviral drug regimens have achieved over 90% sustained virological response rates in clinical trials, regardless of fibrosis stage, genotype, or viral load. The KDIGO 2008 guidelines recommended liver biopsy for evaluating fibrosis, but non-invasive methods are now sufficient. Recent trials like TARGET and C-SURFER showed high cure rates of over 95% with direct-acting antiviral regimens in dialysis patients. The AASLD recommendations designate specific direct-acting antiviral combinations as recommended or alternative regimens for different genotypes in patients with severe renal impairment or on dialysis.
Patients with acute hepatitis C virus (HCV) infection appear to have an excellent chance of responding to 6 months of standard therapy with interferon (IFN). Because spontaneous resolution is common, no definitive timing of therapy initiation can be recommended; however, waiting 2-4 months after the onset of illness seems reasonable.
Treatment for chronic HCV is based on guidelines from the Infectious Diseases Society of America (IDSA) and the American Associations for the Study of Liver Diseases (AASLD), in collaboration with the International Antiviral Society-USA (IAS-USA). These guidelines are constantly being updated. For more information, see HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C.
The guidelines propose that because all patients cannot receive treatment immediately upon the approval of new agents, priority should be given to those with the most urgent need.
The recommendations include the following :
Patients with advanced fibrosis, those with compensated cirrhosis, liver transplant recipients, and those with severe extraheptic hepatitis are to be given the highest priority for treatment
Based on available resources, patients at high risk for liver-related complications and severe extrahepatic hepatitis C complications should be given high priority for treatment
Treatment decisions should balance the anticipated reduction in transmission versus the likelihood of reinfection in patients whose risk of HCV transmission is high and in whom HCV treatment may result in a reduction in transmission (eg, men who have high-risk sex with men, active injection drug users, incarcerated persons, and those on hemodialysis)
This lecture is about Treatment of HCV Genotype 4 presented by Dr. Tamer Elbaz, Assistant professor of Hepatology & Gastroenterology, Cairo University.
The lecture was presented in the scientific meeting of Internal and Tropical Medicine departments, Ahmed Maher Teaching Hospital titled (Towards Eradication of HCV in Egypt) in celebration of World Hepatitis Day on July 28, 2016.
https://www.facebook.com/AMTH.IM
https://www.facebook.com/events/1072758396145209/
http://www.no4c.com
This document provides an overview and update on treatments for Hepatitis C genotype 4. It discusses direct-acting antiviral (DAA) medications including NS3/4A protease inhibitors, NS5A inhibitors, NS5B polymerase inhibitors, and specific medications from each class. It covers dosing, mechanisms of action, drug interactions and side effects for medications like sofosbuvir, simeprevir, daclatasvir, and paritaprevir/ombitasvir. Guidelines from EASL and AASLD are summarized for genotype 4 treatment and special populations like renal impairment, HIV co-infection, and treatment failure.
A power point presentation on Hepatitis C virus on epidemiology, presentation, diagnosis and current treatment strategies we are practicing in BSMMU at a international standerd.
Pakistan has the second highest prevalence of hepatitis C virus (HCV) infection in the world, with 4.4-9% of the population affected. Testing for HCV involves initial screening with ELISA antibody tests, followed by PCR testing to detect HCV RNA if ELISA is positive. The goal of HCV treatment is sustained virological response (SVR), defined as undetectable HCV RNA 12 or 24 weeks after the end of therapy. Treatment is recommended for all treatment-naive and experienced patients with compensated chronic liver disease due to HCV, prioritizing those with severe fibrosis. Monitoring during and after treatment involves regular clinical and laboratory assessments to check for efficacy and side effects.
Hepatitis c infection, causes, treatment, and preventionNada Sami
1) Hepatitis C virus (HCV) was identified in 1989 and is a leading cause of liver disease. Egypt has the largest HCV epidemic in the world with a prevalence of 14.7% based on antibody testing.
2) HCV is a small enveloped RNA virus that is classified into 6 major genotypes. Genotypes 1 and 4 typically require longer treatment than genotypes 2, 3, 5 and 6.
3) HCV infection may be acute or chronic. About 60-70% of infections become chronic and 20% of chronic carriers may develop cirrhosis or liver cancer over time if left untreated.
The document summarizes results from two phase 3 clinical trials that assessed the efficacy and safety of a fixed-dose combination of sofosbuvir, velpatasvir, and voxilaprevir for 12 weeks in patients with hepatitis C virus (HCV) who had previously received unsuccessful treatment with direct-acting antiviral (DAA)-based regimens. In POLARIS-1, the overall sustained virologic response rate was 96% among those receiving sofosbuvir, velpatasvir, and voxilaprevir, significantly higher than the prespecified goal of 85%. In POLARIS-4, patients receiving sofosbuvir, velpatasvir, and voxilap
This document discusses new drug treatments for hepatitis C virus (HCV) infection. It introduces two new protease inhibitor drugs: simeprevir and sofosbuvir. Simeprevir inhibits the HCV NS3/4A protease to prevent viral maturation. Sofosbuvir is a nucleotide polymerase inhibitor that works by forming a defective substrate of the NS5B viral polymerase. Both drugs have been approved by the FDA for use in combination with pegylated interferon and ribavirin for treating HCV genotypes 1, 2, 3 and 4. The combinations achieve high sustained virologic response rates. The document reviews the pharmacokinetics, mechanisms of action, dosing regimens and adverse effects of these new
Chronic hepatitis C is caused by the hepatitis C virus (HCV). It was previously called "non-A, non-B hepatitis". HCV has 6 major genotypes. Genotype 1 is the most common in the United States and has the lowest response rates to treatment. Standard treatment was pegylated interferon and ribavirin for 48 weeks for genotype 1 and 24 weeks for genotypes 2 and 3. New direct acting antivirals like sofosbuvir have improved treatment outcomes with higher cure rates and fewer side effects while allowing treatment without interferon for most patients. Sofosbuvir inhibits the HCV RNA polymerase and costs around $1,800 for a 24 week course in developing countries, compared to $84,
The patient has abnormal liver enzymes and tested positive for hepatitis C virus antibodies and RNA. She has a history of injection drug use 18 years ago. Her current rash and abnormal liver enzymes suggest she may have cryoglobulinemia associated with her hepatitis C infection. Measuring her serum cryoglobulins would be the most appropriate next step to evaluate for this potential extrahepatic manifestation of hepatitis C.
Reactivation of hepatitis B virus (HBV) can occur when a patient with resolved or inactive HBV undergoes immunosuppression. This document discusses the definition, causes, incidence, risk factors, clinical manifestations, outcomes, prevention and treatment of HBV reactivation. Key points include: screening patients for HBV before immunosuppression, using prophylactic antiviral therapy for high risk patients, and monitoring or using pre-emptive therapy for moderate risk patients. Entecavir is recommended over lamivudine or tenofovir for prevention due to lower resistance risk. Therapy should begin before and continue after immunosuppression.
HBV has been associated with humans for over 1,000 years. Recent evidence from a mummified Korean child who tested positive for HBV DNA establishes that HBV has been present in humans for at least 500 years. Treatment guidelines recommend antiviral therapy for patients with chronic HBV based on HBV DNA levels and ALT levels. Tenofovir and entecavir are preferred first-line treatments due to their superior efficacy, tolerability and low resistance profiles. Long-term antiviral therapy can reduce the risk of liver decompensation, hepatocellular carcinoma, and death in patients with chronic HBV.
Hepatitis C is caused by the hepatitis C virus (HCV). The document discusses HCV including its structure, replication cycle, global prevalence, genotypes found in Pakistan, natural history, extrahepatic manifestations, diagnosis, treatment options, and predictors of response to treatment. Key points are that HCV has a broad global distribution, genotype 3 is most common in Pakistan, most infections become chronic, treatment involves pegylated interferon and ribavirin, and factors like younger age and lower HCV viral load predict better response to therapy.
Treatment of HCV in HIV-infected patients has historically been challenging with low response rates and side effects. However, recent developments in direct-acting antiviral agents now offer highly effective interferon-free regimens. Studies show sofosbuvir-based combinations achieving over 90% cure rates in HIV/HCV coinfected individuals, including those on antiretroviral therapy. Daclatasvir is being studied in phase III trials and may be co-administered with many antiretrovirals. These developments promise to greatly improve outcomes for people living with HIV/HCV coinfection.
Case Studies: HBeAg Negative Chronic Hepatitis B Yeong Yeh Lee
This document presents a clinical case scenario of a 45-year-old man with chronic hepatitis B infection. Key details include that he is HBeAg negative with normal liver enzymes and ultrasound. His HBV DNA level is 55,000 copies/ml. He was started on lamivudine and had an initial good response but later experienced a virologic breakthrough associated with development of lamivudine resistance. Treatment options for lamivudine resistant HBV are discussed.
This document provides guidelines from the WHO on chronic hepatitis C infection from April 2016. It discusses the global burden of HCV, noting over 700,000 deaths per year. New direct-acting antiviral medications have transformed HCV treatment, enabling shorter, oral regimens with over 90% cure rates and fewer side effects. The guidelines recommend screening high-risk populations and using RNA testing to confirm chronic infection before treatment. They provide guidance on clinical assessment, noting the importance of staging liver fibrosis/cirrhosis and assessing severity. Successful treatment results in reduced liver inflammation and fibrosis regression, lowering risks of liver cancer and transplant.
A 45-year-old woman presented with fatigue, weakness, and loss of appetite. Laboratory tests found elevated liver enzymes and HCV RNA. A liver biopsy showed severe inflammation and fibrosis. She was diagnosed with chronic hepatitis C based on her history of blood transfusion, laboratory results, and biopsy findings. The best course of action would be to treat her hepatitis C with pegylated interferon and ribavirin therapy to reduce liver damage and prevent progression to cirrhosis.
This document discusses hepatitis C virus (HCV) and its treatment. It begins by defining hepatitis as inflammation of the liver and describing the various causes, including viral hepatitis from hepatitis viruses A-E. It then focuses on HCV, describing it as an RNA virus that infects liver cells. The document discusses HCV transmission, signs and symptoms, natural progression to chronic infection, and treatment options to cure HCV including various antiviral medications like interferons, ribavirin, boceprevir, and sofosbuvir. It provides details on treatment regimens and success rates depending on HCV genotype.
This document summarizes guidelines from the American Association for the Study of Liver Diseases (AASLD) regarding the management of hepatitis C virus (HCV)-infected patients. It discusses recommendations for treating special populations including nonresponders, patients with normal ALT levels, children, and patients coinfected with HIV. It provides data from clinical studies on treatment outcomes for these groups. The guidelines recommend individualized treatment decisions based on factors like biopsy results, comorbidities, and likelihood of response. Peginterferon and ribavirin are generally recommended treatment options.
Hepatitis (C) Story …. Past & Present & future
Most Recant Updating Guidelines by ASSLD & FDA
RAVS &How to deal with It ----12/7/2016.....
((Residents Lectures))
Hepatitis c treatment in ESRD patients , update Dr Ayman Seddik Ayman Seddik
This document discusses hepatitis C treatment in patients with end-stage renal disease. It outlines that newer direct-acting antiviral drug regimens have achieved over 90% sustained virological response rates in clinical trials, regardless of fibrosis stage, genotype, or viral load. The KDIGO 2008 guidelines recommended liver biopsy for evaluating fibrosis, but non-invasive methods are now sufficient. Recent trials like TARGET and C-SURFER showed high cure rates of over 95% with direct-acting antiviral regimens in dialysis patients. The AASLD recommendations designate specific direct-acting antiviral combinations as recommended or alternative regimens for different genotypes in patients with severe renal impairment or on dialysis.
Patients with acute hepatitis C virus (HCV) infection appear to have an excellent chance of responding to 6 months of standard therapy with interferon (IFN). Because spontaneous resolution is common, no definitive timing of therapy initiation can be recommended; however, waiting 2-4 months after the onset of illness seems reasonable.
Treatment for chronic HCV is based on guidelines from the Infectious Diseases Society of America (IDSA) and the American Associations for the Study of Liver Diseases (AASLD), in collaboration with the International Antiviral Society-USA (IAS-USA). These guidelines are constantly being updated. For more information, see HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C.
The guidelines propose that because all patients cannot receive treatment immediately upon the approval of new agents, priority should be given to those with the most urgent need.
The recommendations include the following :
Patients with advanced fibrosis, those with compensated cirrhosis, liver transplant recipients, and those with severe extraheptic hepatitis are to be given the highest priority for treatment
Based on available resources, patients at high risk for liver-related complications and severe extrahepatic hepatitis C complications should be given high priority for treatment
Treatment decisions should balance the anticipated reduction in transmission versus the likelihood of reinfection in patients whose risk of HCV transmission is high and in whom HCV treatment may result in a reduction in transmission (eg, men who have high-risk sex with men, active injection drug users, incarcerated persons, and those on hemodialysis)
This lecture is about Treatment of HCV Genotype 4 presented by Dr. Tamer Elbaz, Assistant professor of Hepatology & Gastroenterology, Cairo University.
The lecture was presented in the scientific meeting of Internal and Tropical Medicine departments, Ahmed Maher Teaching Hospital titled (Towards Eradication of HCV in Egypt) in celebration of World Hepatitis Day on July 28, 2016.
https://www.facebook.com/AMTH.IM
https://www.facebook.com/events/1072758396145209/
http://www.no4c.com
This document provides an overview and update on treatments for Hepatitis C genotype 4. It discusses direct-acting antiviral (DAA) medications including NS3/4A protease inhibitors, NS5A inhibitors, NS5B polymerase inhibitors, and specific medications from each class. It covers dosing, mechanisms of action, drug interactions and side effects for medications like sofosbuvir, simeprevir, daclatasvir, and paritaprevir/ombitasvir. Guidelines from EASL and AASLD are summarized for genotype 4 treatment and special populations like renal impairment, HIV co-infection, and treatment failure.
A power point presentation on Hepatitis C virus on epidemiology, presentation, diagnosis and current treatment strategies we are practicing in BSMMU at a international standerd.
Pakistan has the second highest prevalence of hepatitis C virus (HCV) infection in the world, with 4.4-9% of the population affected. Testing for HCV involves initial screening with ELISA antibody tests, followed by PCR testing to detect HCV RNA if ELISA is positive. The goal of HCV treatment is sustained virological response (SVR), defined as undetectable HCV RNA 12 or 24 weeks after the end of therapy. Treatment is recommended for all treatment-naive and experienced patients with compensated chronic liver disease due to HCV, prioritizing those with severe fibrosis. Monitoring during and after treatment involves regular clinical and laboratory assessments to check for efficacy and side effects.
Hepatitis c infection, causes, treatment, and preventionNada Sami
1) Hepatitis C virus (HCV) was identified in 1989 and is a leading cause of liver disease. Egypt has the largest HCV epidemic in the world with a prevalence of 14.7% based on antibody testing.
2) HCV is a small enveloped RNA virus that is classified into 6 major genotypes. Genotypes 1 and 4 typically require longer treatment than genotypes 2, 3, 5 and 6.
3) HCV infection may be acute or chronic. About 60-70% of infections become chronic and 20% of chronic carriers may develop cirrhosis or liver cancer over time if left untreated.
The document summarizes results from two phase 3 clinical trials that assessed the efficacy and safety of a fixed-dose combination of sofosbuvir, velpatasvir, and voxilaprevir for 12 weeks in patients with hepatitis C virus (HCV) who had previously received unsuccessful treatment with direct-acting antiviral (DAA)-based regimens. In POLARIS-1, the overall sustained virologic response rate was 96% among those receiving sofosbuvir, velpatasvir, and voxilaprevir, significantly higher than the prespecified goal of 85%. In POLARIS-4, patients receiving sofosbuvir, velpatasvir, and voxilap
This document discusses new drug treatments for hepatitis C virus (HCV) infection. It introduces two new protease inhibitor drugs: simeprevir and sofosbuvir. Simeprevir inhibits the HCV NS3/4A protease to prevent viral maturation. Sofosbuvir is a nucleotide polymerase inhibitor that works by forming a defective substrate of the NS5B viral polymerase. Both drugs have been approved by the FDA for use in combination with pegylated interferon and ribavirin for treating HCV genotypes 1, 2, 3 and 4. The combinations achieve high sustained virologic response rates. The document reviews the pharmacokinetics, mechanisms of action, dosing regimens and adverse effects of these new
Chronic hepatitis C is caused by the hepatitis C virus (HCV). It was previously called "non-A, non-B hepatitis". HCV has 6 major genotypes. Genotype 1 is the most common in the United States and has the lowest response rates to treatment. Standard treatment was pegylated interferon and ribavirin for 48 weeks for genotype 1 and 24 weeks for genotypes 2 and 3. New direct acting antivirals like sofosbuvir have improved treatment outcomes with higher cure rates and fewer side effects while allowing treatment without interferon for most patients. Sofosbuvir inhibits the HCV RNA polymerase and costs around $1,800 for a 24 week course in developing countries, compared to $84,
The patient has abnormal liver enzymes and tested positive for hepatitis C virus antibodies and RNA. She has a history of injection drug use 18 years ago. Her current rash and abnormal liver enzymes suggest she may have cryoglobulinemia associated with her hepatitis C infection. Measuring her serum cryoglobulins would be the most appropriate next step to evaluate for this potential extrahepatic manifestation of hepatitis C.
Reactivation of hepatitis B virus (HBV) can occur when a patient with resolved or inactive HBV undergoes immunosuppression. This document discusses the definition, causes, incidence, risk factors, clinical manifestations, outcomes, prevention and treatment of HBV reactivation. Key points include: screening patients for HBV before immunosuppression, using prophylactic antiviral therapy for high risk patients, and monitoring or using pre-emptive therapy for moderate risk patients. Entecavir is recommended over lamivudine or tenofovir for prevention due to lower resistance risk. Therapy should begin before and continue after immunosuppression.
HBV has been associated with humans for over 1,000 years. Recent evidence from a mummified Korean child who tested positive for HBV DNA establishes that HBV has been present in humans for at least 500 years. Treatment guidelines recommend antiviral therapy for patients with chronic HBV based on HBV DNA levels and ALT levels. Tenofovir and entecavir are preferred first-line treatments due to their superior efficacy, tolerability and low resistance profiles. Long-term antiviral therapy can reduce the risk of liver decompensation, hepatocellular carcinoma, and death in patients with chronic HBV.
Hepatitis C is caused by the hepatitis C virus (HCV). The document discusses HCV including its structure, replication cycle, global prevalence, genotypes found in Pakistan, natural history, extrahepatic manifestations, diagnosis, treatment options, and predictors of response to treatment. Key points are that HCV has a broad global distribution, genotype 3 is most common in Pakistan, most infections become chronic, treatment involves pegylated interferon and ribavirin, and factors like younger age and lower HCV viral load predict better response to therapy.
Treatment of HCV in HIV-infected patients has historically been challenging with low response rates and side effects. However, recent developments in direct-acting antiviral agents now offer highly effective interferon-free regimens. Studies show sofosbuvir-based combinations achieving over 90% cure rates in HIV/HCV coinfected individuals, including those on antiretroviral therapy. Daclatasvir is being studied in phase III trials and may be co-administered with many antiretrovirals. These developments promise to greatly improve outcomes for people living with HIV/HCV coinfection.
Case Studies: HBeAg Negative Chronic Hepatitis B Yeong Yeh Lee
This document presents a clinical case scenario of a 45-year-old man with chronic hepatitis B infection. Key details include that he is HBeAg negative with normal liver enzymes and ultrasound. His HBV DNA level is 55,000 copies/ml. He was started on lamivudine and had an initial good response but later experienced a virologic breakthrough associated with development of lamivudine resistance. Treatment options for lamivudine resistant HBV are discussed.
This document provides guidelines from the WHO on chronic hepatitis C infection from April 2016. It discusses the global burden of HCV, noting over 700,000 deaths per year. New direct-acting antiviral medications have transformed HCV treatment, enabling shorter, oral regimens with over 90% cure rates and fewer side effects. The guidelines recommend screening high-risk populations and using RNA testing to confirm chronic infection before treatment. They provide guidance on clinical assessment, noting the importance of staging liver fibrosis/cirrhosis and assessing severity. Successful treatment results in reduced liver inflammation and fibrosis regression, lowering risks of liver cancer and transplant.
A 45-year-old woman presented with fatigue, weakness, and loss of appetite. Laboratory tests found elevated liver enzymes and HCV RNA. A liver biopsy showed severe inflammation and fibrosis. She was diagnosed with chronic hepatitis C based on her history of blood transfusion, laboratory results, and biopsy findings. The best course of action would be to treat her hepatitis C with pegylated interferon and ribavirin therapy to reduce liver damage and prevent progression to cirrhosis.
This document discusses hepatitis C virus (HCV) and its treatment. It begins by defining hepatitis as inflammation of the liver and describing the various causes, including viral hepatitis from hepatitis viruses A-E. It then focuses on HCV, describing it as an RNA virus that infects liver cells. The document discusses HCV transmission, signs and symptoms, natural progression to chronic infection, and treatment options to cure HCV including various antiviral medications like interferons, ribavirin, boceprevir, and sofosbuvir. It provides details on treatment regimens and success rates depending on HCV genotype.
This document summarizes research on hepatitis C recurrence and treatment after liver transplantation. It discusses patterns of hepatitis C recurrence, the impact of fibrosing cholestatic hepatitis on outcomes, evaluation of recurrence severity, and the effect of antiviral treatment before and after transplantation. Key findings include that hepatitis C recurrence is a major issue after liver transplantation, accounting for most graft losses. Early antiviral treatment with newer direct-acting antivirals has shown promise for preventing or treating recurrence with improved tolerance compared to previous interferon-based regimens.
The document summarizes a presentation about HIV/HCV co-infection given by Dr. Susanna Naggie. It discusses the case of a 34-year-old man with HIV/HCV co-infection and cirrhosis. It reviews the accelerated progression of liver disease seen in HIV/HCV patients and potential mechanisms including the role of hedgehog signaling and immune activation. Treatment options for co-infected patients have advanced significantly in recent years with highly effective all-oral regimens that achieve cure rates over 90% with minimal side effects.
Hepatitis C (HCV) infections are prevalent in the United States, with the most common genotype being genotype 1. New treatments are improving treatment outcomes and reducing side effects. Sofosbuvir combined with ribavirin or pegylated interferon/ribavirin achieves high cure rates of over 90% in 12 weeks of treatment. However, the cost of these new treatments is very high, ranging from $80,000 to $150,000. Upcoming interferon-free regimens using combinations of antiviral drugs may achieve cure rates of over 95% with just 6 weeks of treatment.
Ledipasvir/sofosbuvir for 12 weeks in patients co-infected with HCV and HIV-1Илья Антипин
Naggie S. И др. (докладчик Cooper.) «Ledipasvir/sofosbuvir for 12 weeks in patients co-infected with HCV and HIV-1» 8th IAS Conference on HIV Pathogenesis, Treatment, and Prevention, Vancouver, 2015. TUAB0202.
This document provides an overview of viral hepatitis management in 2012. It discusses hepatitis B virus (HBV) and hepatitis C virus (HCV), including epidemiology, transmission, natural history, testing, and treatment approaches. For HBV, it reviews global prevalence, risk factors for infection, stages of infection, and vaccine indications. It also summarizes HBV treatment options and their pros and cons. For HCV, it discusses the large global disease burden, risk factors for infection, genotypes, and the expectation that cirrhosis cases will peak over the next decade. It also reviews HCV treatment approaches and the curability of chronic HCV infection with interferon-based therapy. The document concludes by summarizing two new protease inhibitors approved to
Christian B. Ramers, M.D., M.P.H., of Family Health Centers of San Diego, presents "The HCV Treatment Revolution: A View from the Community Health Center" for AIDS Clinical Rounds at UC San Diego
March 192015talkforresidents final03232015 (1)katejohnpunag
This document provides an update on viral hepatitis and discusses two case studies. It begins by describing a 71-year-old male presenting with jaundice who is diagnosed with acute hepatitis A infection based on a reactive HAV IgM test. It then reviews hepatitis A virus and the diagnosis and management of acute hepatitis A. The second case discusses a 26-year-old male diagnosed with chronic hepatitis B infection based on positive HBsAg, anti-HBc IgM, and HBV DNA tests. The document concludes by discussing chronic hepatitis B infection and approved treatments.
Epidemiology, prevention and control of viral hepatitis BPreetika Maurya
Hepatitis B is a viral infection that affects the liver and is transmitted through contact with infected blood or bodily fluids. It is endemic worldwide, especially in developing tropical countries, with prevalence depending on behavioral, environmental, and host factors. Countries can be classified as having high, intermediate, or low endemicity based on hepatitis B surface antigen carrier rates. The disease ranges from an acute self-limiting infection to a chronic persistent infection, depending on the age when infected. While there is no specific treatment, prevention through hepatitis B vaccination and immunoglobulin is the main approach for management.
This document provides an overview of bacterial pathogenesis. It discusses Koch's postulates, virulence factors, types of infections, mechanisms of pathogenesis including transmission, adherence, invasion, inflammation and toxin production. Key points covered include the definition of a pathogen and virulence, examples of virulence factors for common bacteria, how bacteria adhere and invade host tissues, and the role of exotoxins and endotoxins in disease.
Hepatitis c new guidelines 2014 by aasld idsa sofosbuvirMuhammad Farooq
The document summarizes new guidelines from the AASLD, IDSA, and IAS-USA for screening, treating, and managing hepatitis C virus (HCV) patients. A panel of 27 specialists and a patient advocate developed evidence-based consensus recommendations that are available online at hcvguidelines.org. The guidelines classify recommendations as "Recommended," "Alternative," or "Not Recommended." They define patients ineligible for interferon and provide information on medications Sofosbuvir and Simeprevir, including trials supporting their use against various HCV genotypes. The document concludes that safer and more effective interferon-free regimens will likely be available by 2015.
1. Antimicrobial resistance arises through genetic mutations and the acquisition of resistance genes from other bacteria.
2. Resistance genes can be acquired horizontally via mobile genetic elements such as plasmids, leading to rapid spread.
3. Common resistance mechanisms include enzymatic inactivation of antibiotics, modification or protection of antibiotic targets, and efflux pumps that pump out antibiotics.
عرض بسيط و ليس علمي و إنما تثقيفي
يتحدث العرض عن التهاب فيروس الكبد الوبائي
في البداية يذكر أهمية الكبد ووظيفته في جسم الإنسان
ثم بعد ذلك يعدد أنواع إلتهابات الكبد و مسبباتها ..
و الفرق بين الكبد الطبيعي و الكبد المصاب
و يتحدث أيضاً عن مسببات الإصابة بالفيروس و تجنبها للوقاية من المرض
كما تم ذكر أعراض المرض التي تظهر على الشخص المصاب
و كيفية الوقاية من الإصابة بالتهاب الكبد الفيروسي
و أخيراً ذكرت الطريقة الصحيحة لغسل اليدين بالماء و الصابون بالصور و التي تعد أحد أهم أسباب الوقاية من الفيروسات .
Hepatitis C is a major global public health problem, infecting around 180 million people worldwide. It is a leading cause of liver disease and liver transplants. The hepatitis C virus is a RNA virus that primarily infects liver cells. Around 70-85% of infections become chronic, and 20-40% of chronic infections can lead to severe liver disease like cirrhosis or liver cancer over time. The most common modes of transmission are through blood exposure, though sexual transmission risk is low. There is no vaccine, but effective antiviral treatment exists.
This document summarizes a seminar on the management of hepatitis C. It discusses the virology of hepatitis C virus and outlines guidelines for patient evaluation, counseling, and antiviral therapy. The summary focuses on the evolution of hepatitis C treatment from interferon-based regimens to highly effective all-oral direct-acting antiviral combination therapies that achieve over 95% cure rates.
Role of antiviral in COVID 19
IDSA GUIDELINE
CDC GUIDELINE
SAUDI MOH GUIDELINE
NEW ORAL ANTIVIRAL FOR COVID 19
INVESTIGTIONAL ANTIVIRAL FOR COVID19
LAST UPDATE OF ANTIVIRAL COVID 19
This study evaluated the efficacy and safety of the combination of daclatasvir and sofosbuvir for 12 weeks or 8 weeks in previously untreated patients with HIV-HCV coinfection, and for 12 weeks in previously treated patients. Among previously untreated patients with HCV genotype 1, the rate of sustained virologic response was 96.4% for those treated for 12 weeks and 75.6% for those treated for 8 weeks. Rates of sustained virologic response across all genotypes were 97.0% for 12 weeks of treatment and 76.0% for 8 weeks. The most common side effects were fatigue, nausea, and headache, and there were no treatment discontinuations due to side effects. HIV viral suppression
A comparison of different treatments for Hepatitis C virus ramoncolon96
This document compares different treatments for hepatitis C virus (HCV), including pegylated interferon plus ribavirin, interferon-beta plus ribavirin, sofosbuvir, simeprevir, and combinations. Studies found sofosbuvir in combination with ribavirin and pegylated interferon-alpha to be the most effective treatment, with an 89% sustained virologic response at 12 weeks and 91% at 24 weeks. The conclusion is that the sofosbuvir combination is the most efficient and safest treatment with the best response rates.
This document summarizes a clinical trial that evaluated the efficacy and safety of a 12-week treatment with sofosbuvir and velpatasvir (a fixed-dose combination tablet) in patients with chronic hepatitis C virus (HCV) genotype 1, 2, 4, 5, or 6 infection, including those with cirrhosis. The trial found that the treatment provided high rates (99%) of sustained virologic response at 12 weeks after treatment in both previously treated and untreated patients with HCV genotypes 1, 2, 4, 5, or 6 infection, including those with cirrhosis. Serious adverse events occurred in 2% of patients receiving sofosbuvir-velpatasvir and none in the placebo group
Hepatitis C is a global health problem that causes 700,000 deaths per year. In Bangladesh, 1% of the population has HCV. New guidelines recommend screening high-risk groups and treating with direct-acting antiviral drugs, which have cure rates over 90% and shorter treatment durations compared to previous interferon-based regimens. Proper treatment can prevent cirrhosis, liver cancer and death from HCV. While challenges remain, scientists hope to eliminate HCV globally by 2030 with new pan-genotypic drugs. Prevention through injection safety, screening blood products, and educating healthcare workers is also important to control the disease.
Diagnosis and management of chronic hepatitis b infection(word)Himanshu Rana
- The document discusses guidelines for screening, assessing, treating, and managing chronic hepatitis B infection. It outlines populations that should be screened, goals and definitions of treatment response, first and second line therapies including tenofovir and entecavir, management of antiviral resistance, and screening for hepatocellular carcinoma.
- Key points covered include screening high-risk populations, treating to suppress HBV DNA and improve liver disease, using pegylated interferon as initial treatment in eligible patients, and treating coinfections like hepatitis C and D.
- Monitoring for treatment response and resistance is important, involving regular HBV DNA testing and considering resistance testing if virologic breakthrough occurs on therapy.
The Role of New HCV Agents in Managing HIV/HCV Coinfection.2014hivlifeinfo
This document summarizes a presentation on new agents for treating hepatitis C virus (HCV) infection in patients coinfected with HIV. It discusses FDA-approved regimens containing simeprevir and sofosbuvir, dosing and administration of these drugs, treatment guidelines from AASLD/IDSA, and clinical trial data on sofosbuvir-containing regimens in HIV/HCV coinfected patients, showing high sustained virologic response rates. The presentation provides an overview of evolving therapeutic options and recommendations for managing HCV/HIV coinfection.
The Role of New HCV Agents in Managing HIV/HCV Coinfection.2014Hivlife Info
This document summarizes a presentation on new agents for treating hepatitis C virus (HCV) infection in patients coinfected with HIV. It discusses FDA-approved regimens containing simeprevir or sofosbuvir, dosing and administration, treatment guidelines from AASLD/IDSA, and clinical trial data on sofosbuvir and simeprevir in HIV/HCV coinfected patients, showing high sustained virologic response rates.
This document discusses hepatitis C virus (HCV) and current treatment options. It provides the following key points:
- HCV is the most common blood-borne pathogen in the US, with around 3.2 million people chronically infected. Chronic infections often progress to cirrhosis over 20-30 years.
- New all-oral treatment regimens that do not require interferon are highly effective. Sofosbuvir-based combinations can achieve over 90% sustained virologic response rates.
- Treatment is now recommended for most patients with chronic HCV to prevent long-term complications like cirrhosis and liver cancer. However, costs remain very high, with prices over $80,000 for a
Jill Blumenthal, M.D., of UC San Diego AntiViral Research Center, presents "International AIDS Conference 2014: A Moderately Rapid Review" at AIDS Clinical Rounds
Dr. Ummed Singh discusses the management of HIV/AIDS, including post-test counseling, stages of untreated HIV infection, types of progression, goals of antiretroviral therapy, commonly used antiretroviral drugs, principles of therapy, selecting regimens, indications for changing therapy, monitoring, adverse effects, prevention, prophylaxis against secondary infections, the UNAIDS 90-90-90 strategy, and the current status of an HIV vaccine. Management involves using combination antiretroviral therapy to suppress viral replication and improve quality of life.
Treatment of HCV in HIV-infected patients has historically been challenging with low response rates and side effects. However, recent developments in direct-acting antiviral agents now offer highly effective interferon-free regimens. Studies show sofosbuvir-based combinations achieving over 90% cure rates in HIV/HCV coinfected individuals, including those on antiretroviral therapy. Daclatasvir is being studied in phase III trials and may be co-administered with many antiretrovirals. These developments promise to greatly improve outcomes for people living with HIV/HCV coinfection.
Treatment of HCV in HIV-infected patients has historically been challenging with low response rates and side effects. However, recent developments in direct-acting antiviral agents now offer highly effective interferon-free regimens. Studies show sofosbuvir-based combinations achieving over 90% cure rates in HIV/HCV coinfected individuals, including those on antiretroviral therapy. Daclatasvir is being studied in phase III trials and may be co-administered with many antiretrovirals. These developments promise to greatly improve outcomes for people living with HIV/HCV coinfection.
This study evaluated the efficacy and safety of a 12-week, all-oral, fixed-dose combination of daclatasvir, asunaprevir, and beclabuvir for the treatment of chronic hepatitis C virus genotype 1 infection in noncirrhotic patients. The study found high rates of sustained virologic response at 12 weeks post-treatment (SVR12) in both treatment-naive (92.0%) and treatment-experienced (89.3%) patients. Adverse events were generally mild and few led to treatment discontinuation. The results demonstrate that this ribavirin-free, direct-acting antiviral regimen achieved high SVR12 rates in noncirrhotic patients with
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
All manuscripts are subject to rapid peer review. Those of high quality (not previously published and not under consideration for publication in another journal) will be published without delay.
This study evaluated a 12-week, all-oral, fixed-dose combination of daclatasvir, asunaprevir, and beclabuvir (DCV-TRIO regimen) in 415 noncirrhotic patients with chronic HCV genotype 1 infection. The primary outcome was sustained virologic response 12 weeks after treatment (SVR12) in treatment-naive patients (n=312). A key secondary outcome was SVR12 in treatment-experienced patients (n=103). Overall SVR12 was observed in 379 patients (91.3%), including 287 treatment-naive patients (92.0%) and 92 treatment-experienced patients (89.3%). The DCV-TRIO
This document summarizes hepatitis C treatments and outreach efforts. It discusses current and upcoming antiviral treatments including simeprevir, sofosbuvir, and direct-acting antivirals. It also describes side effects of pegylated interferon and ribavirin treatments. The document estimates hepatitis C prevalence in Lambeth and the potential impact of untreated infection based on natural disease progression models. It overviews the antiviral therapy outreach service collaboration between Kings College Hospital and South London and Maudsley to engage patients in drug and alcohol centers through peer advocacy.
This document provides an overview of new oral medications for treating hepatitis C virus (HCV) infection, including NS3/4A protease inhibitors telaprevir and boceprevir. It discusses HCV genotypes and lifecycle, focusing on improved understanding of viral targets leading to drug discovery. NS3/4A protease inhibitors and NS5B polymerase inhibitors currently in clinical development are described, targeting polyprotein processing and HCV replication respectively. Nucleoside and non-nucleoside NS5B inhibitors as well as NS5A inhibitors and their mechanisms of action and clinical trial status are summarized.
HAART, or highly active antiretroviral therapy, involves using a combination of antiretroviral drugs to treat HIV. The goals of ART include increased survival, improved quality of life, reduction of viral load, immune reconstitution, and limiting drug toxicity while maintaining treatment options and adherence. Commonly used drug classes include NRTIs, NNRTIs, integrase inhibitors, and protease inhibitors. Treatment involves monitoring viral load, CD4 count, adverse effects, and potential treatment failure or immune reconstitution inflammatory syndrome. Guidelines provide recommendations on treatment initiation and first, second, and third-line regimens for both adults and children.
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotesPsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
Does Over-Masturbation Contribute to Chronic Prostatitis.pptxwalterHu5
In some case, your chronic prostatitis may be related to over-masturbation. Generally, natural medicine Diuretic and Anti-inflammatory Pill can help mee get a cure.
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Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
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Update on Hepatitis C Virus
1. Changing Concepts in HCV Therapy
Lancet 2015; 385: 1124–35
EASL GUIDELINE :2014
WHO GUIDELINE : 2014
Dr.S.M.Amanat Ullah
Department of Medicine
Chittagong Medical College Hospital
17. The Standard of Care Therapy for HCV
Depends upon giving PegIFN / Ribavirin for
24-48 Wks depending upon the Genotype
18. Both drugs depends mainly in their effect upon
Boosting the Host immune response to control
and eradicate the HCV Infection
19. The newly developed Directly Acting Antivirals –
DAAs - acts only at the virus Level with no effect
on the host immune system i.e the host immunity
is passive during these new lines of therapy
.
20. So, we are shifting from the host immune system
manipulation Towards virus body manipulation.
NB : The virus is a living organism and has to
defend its life through
? Resistance? Mutation ? etc
Like Antibiotics with Bacteria .
21. So , do we need to Combine both modalities
in the future Therapy ?
i. e. To have a Whiff of Interferon at the
beginning of therapy with DAAs to boost the host
immune system and this may Decrease the relapse
rate, break-though and resistance
( <<<<< We need more studies >>>>>)
22. The advent of direct-acting antivirals- DAAs
Has revolutionized hepatitis C treatment .
23. The First Protease Inhibitor that was tried in
2004 and was known as PILN 2061 and gave
100% eradication rate after 4 weeks only .
At that time it was considered
a real revolution…..
However at 16 weeks all patients got
cardiac toxicity and the trial was aborted
( Nature 2004 )
24. The Real start of DAAa was Nov. 2011
FDA : PROTEASE INHIBITORS (NS-3 , 4A)
1st
generation
Telaprevir ( Incivek )
Boceprevir ( Vectrelis )
25. ADVANTAGES OF 1ST
GEN. P. I
-INCREASED SVR RATE
( FROM 45 % TO 74% IN G 1A, 1B)
- DECREASED RELAPSE RATE
( FROM 12% TO 4% )
26. DRAWBACKS OF 1ST
GEN. P. I
* HIGHER COST
* FREQUENT SIDE EFFECTS
* HIGH DRUG DOSES ( 12-16 TABLs/D)
* FREQUENT DRUG DISCONTINUTY
( 12% IN SOC # 49% IN TRIPLE TTT)
* INTERFERON DEPENDANT
* GENOTYPE SPECIFIC..G1 ONLY
28. DURING THE 62ND ANNUAL MEETING
OF AASLD, 2011
NEW HCV DRUG ACHIEVES 100% CURE RATE
WITHOUT INTERFERON
29. IN ELECTRON — 1 OF 2 PHASE 2 STUDIES
OF THE INVESTIGATIONAL COMPOUND
PSI-7977 (PHARMASSET) REPORTED HERE
— AN INTERFERON-FREE REGIMEN OF PSI-
7977 PLUS RIBAVIRIN ACHIEVED A 100%
SUSTAINED VIRAL RESPONSE (SVR) AT 12
WEEKS IN ALL STUDY SUBJECTS.
33. BMS : A COMBINATION THERAPY INCLUDING TWO
DIRECT-ACTING ANTIVIRAL AGENTS (DAAS)
ASUNAPREVIR AND DACLATASVIR
SUPPRESSED HEPATITIS C VIRUS (HCV) GENOTYPE 1
INFECTION IN A 93% OF PATIENTS WHO HAD
PREVIOUSLY NOT RESPONDED TO TREATMENT .
34. IN Nov. 22ND
2013 ::: FDA APPROVAL FOR
- POLYMERASE INHIBITOR
* SOFOSBUVIR ( SOFALDI – GILEAD )
- PROTEASE INHIBITOR
* SIMEPREVIR ( OLYSIO- JANSSEN )
35. NEW REVOLUTION :
IN FEB. 8TH
, 2014 … GILEAD COMPANY
APPLIED FOR FDA APPROVAL OF
ONE PREPARATION CONTAINING BOTH
- SOFOSBUVIR + LEDIPASVIR ( COMBO )
TO BE GIVEN IN ONE CAPSULE DAILY
FOR 8 WEEKS WITH RESPONSE RATE 95%
-AND IF ADDED RIBA. , RESPONSE RATE 100 %
36. On the way for FDA Approval, two PIs :
Faldaprivir(Bin) …. Asunaprivir (BMS)
37. IN 2014 … NEW HCV
DAAs COMBINATION –
INTERFERON-FREE THERAPY
38. New hepatitis C therapies -
A medical pick And mix
A plethora of direct-acting anti-virals
41. (DAAs) for the treatment of hepatitis C are now
available and new agents are continually being
added to this list.
To coincide with EASL 2014 in London, UK, the N. E.
J. M. has published a series of new HCV therapy
phase III trial results, demonstrating that
We are now truly in the era of interferon- free,
All-oral combination therapies for HCV infection.
These DAAs could potentially revolutionize
Treatment for HCV , but can we call them
a cure yet?
43. The first set of three open-label trials
( All in one Pill )
Examined the use of the HCV NS5A
inhibitor Ledipasvir in combination with
Sofosbuvir
(an HCV NS5B polymerase inhibitor).
( COMBO )
A number of different patient
populations infected with HCV
genotype 1 were studied:
44. 1. HCV-infected patients who were treatment-
naive (16% had cirrhosis; 12-week versus 24-
week regimen, with or without ribavirin);
2. Patients with chronic HCV infection
without cirrhosis (8-week versus 12-week
treatment regimen, with or without ribavirin);
3. HCV-infected patients who had failed to
achieve a sustained virologic response (SVR)
despite treatment with interferon- based
therapies (20% had cirrhosis; 12-week versus
24-week regimen, with or without ribavirin).
45. Patients typically received 90 mg Ledipasvir
and 400 mg Sofosbuvir in a combination
tablet orally each day; Ribavirin, when
required, was administered at 1,000 mg or
1,200 Mg According to bodyweight.
The studies showed that once-daily
ledipasvir– sofosbuvir (with or without
ribavirin) was highly effective (SVRs >90%,
with some rates as high as 99%) in HCV-
infected patients irrespective of whether
they had received HCV treatment before.
46. Importantly, the studies found that there
was No additional benefit of including
ribavirin within the combination therapy,
Kowdley et al. found no benefit of
extension of the treatment period to
12 weeks
(8 weeks were sufficient).
47. The second set of three trials
( AbbVie )
Examined the use of
a three-in-one pill
50. THE COMBINATION OF THREE DIFFERENT
MECHANISMS OF ACTION OF THIS 3D COMBINATION
INTERRUPTS THE HCV REPLICATION PROCESS
AND OPTIMIZES A SUSTAINED VIROLOGIC
RESPONSE DURING THE 12-WEEK REGIMEN
(SVR12) IN HCV PATIENTS.
51. ABBVIE'S PHASE 2 AVIATOR STUDY COMPARED VARIOUS
INTERFERON-FREE THREE- AND FOUR-DRUG COMBINATIONS
CONTAINING:
* THE HCV PROTEASE INHIBITOR ABT-450 BOOSTED
WITH RITONAVIR,
* THE HCV NS5A INHIBITOR ABT-267 (OMBITASVIR),
* HCV NON-NUCLEOSIDE POLYMERASE INHIBITOR ABT-333
( DASABUVIR )
* AND RIBAVIRIN, FOR DURATIONS OF 8, 12 OR 24 WEEKS.
52. ABBVIE'S PHASE 2 AVIATOR STUDY COMPARED VARIOUS
GROUPS AS REPORTED AT EASL 2013, 96% OF TREATMENT-
NAIVE PATIENTS AND 93% OF PRIOR NULL-RESPONDERS
WHO RECEIVED ALL FOUR DRUGS FOR 12 WEEKS ACHIEVED
SUSTAINED VIROLOGICAL RESPONSE,
OR CONTINUED UNDETECTABLE HCV RNA, AT 24 WEEKS
POST-TREATMENT (SVR24).
THE SUSTAINED RESPONSE RATE WAS LOWER – 87% – FOR
PEOPLE TAKING THE THREE DIRECT-ACTING ANTIVIRALS
WITHOUT RIBAVIRIN FOR 12 WEEKS
53.
54.
55.
56.
57.
58.
59. THIRD STUDY : A COMBINATION OF
TWO DAAA DACLATASVIR & ASUNAPREVIR
DEVELOPED BY BMS CURED 90% OF PREVIOUSLY
UNTREATED PEOPLE WITH G 1B IN 24 WEEKS, WITHOUT
THE NEED FOR PEGYLATED INTERFERON OR RIBAVIRIN.
( MANNS, 49TH ANNUAL MEETING OF EASL IN UK, 2014)
THE INTERFERON- AND RIBAVIRIN-FREE REGIMEN COMBINED THE NS5A
INHIBITOR DACLATASVIR AND THE PROTEASE INHIBITOR
ASUNAPREVIR.
THE TWO DRUGS ARE ALSO BEING TESTED ALONGSIDE A THIRD
AGENT, THE NON-NUCLEOSIDE NS5B POLYMERASE INHIBITOR BMS-
791325, IN TWO PHASE III STUDIES ( TRIPLE THERAPY )
60. IN EUROPE, BMS IS PURSUING AN EARLY
APPROVAL FOR DACLATASVIR AS AN
INDIVIDUAL AGENT, SO THAT IT MAY BE USED
IN COMBINATION WITH SOFOSBUVIR FOR
TREATMENT OF GENOTYPES 1, 3 AND 4 OR IN
COMBINATION WITH PEGYLATED INTERFERON
AND RIBAVIRIN FOR TREATMENT OF
GENOTYPES 1B AND 4, AS RECOMMENDED IN
NEW EASL GUIDELINES, 2014.
61. QUADRUPLE THERAPIES
(THERAPY WITH FOUR DRUGS)
PEOPLE WITH VIRUS WHICH HAS PREVIOUSLY PROVED VERY
DIFFICULT TO TREAT (E.G. NON-RESPONDERS AND NULL-
RESPONDERS), COULD BENEFIT FROM THE COMBINATION OF
:
PEGINTERFERON AND RIBAVIRIN WITH
TWO ANTIVIRAL ACTIVE SUBSTANCES.
IT MAY ALSO BE POSSIBLE TO SHORTEN THE OVERALL
THERAPY PERIOD, ALTHOUGH EVEN MORE SERIOUS SIDE-
EFFECTS MAY HAVE TO BE TAKEN INTO ACCOUNT .
62. Despite their success, a major issue of
concern with these new DAAs has been
their expense, as well as regulatory issues
across different countries.
Hopefully, over the coming years, these
therapies will follow the lead of the HIV
field and substantially reduce in cost ,
63. Several major challenges do remain
before we can truly move towards the
global eradication of HCV infection,
Particularly access to new DAAs in low-
income and middle-income countries and
effective HCV screening programmes .
(Too often diagnosis still comes at a late stage).
64. Moreover, more attention needs to
be focused on special patient
populations.
“We still have yet to explore treatments
in patients with
Decompensated Cirrhosis,
” Manns explains, “which is a major task” .
65. SOFOSBUVIR + RIBAVIRIN IS SAFE AND EFFECTIVE FOR
(LIZ HIGHLEYMAN / 17 APRIL 2014 )
SOFOSBUVIR PLUS RIBAVIRIN IS A SAFE OPTION
THAT CAN LEAD TO SUSTAINED RESPONSE IN
PEOPLE WITH ADVANCED LIVER DISEASE INCLUDING
THOSE WITH DECOMPENSATED CIRRHOSIS AND
PORTAL HYPERTENSION, AND PEOPLE WHO
EXPERIENCE SEVERE HEPATITIS
Q : ( GENOTYPE IV - NON-RESPONDERS, BREAK-
THROUGH- RELAPSERS ? )
66. EASL HCV GUIDELINES 2014: GENOTYPE 1
Genotype Options for Therapy
Genotype 1*
PegIFN/ribavirin + sofosbuvir: 12 wks (A1)
PegIFN/ribavirin + simeprevir†
: 12 wks, followed by 12 wks of pegIFN/ribavirin in
previously untreated pts and prior relapsers (A1), or 36 wks of pegIFN/ribavirin in
previous partial responders and null responders (B1)
PegIFN/ribavirin + daclatasvir (genotype 1b only; B1): 12 wks followed by 12 wks of
pegIFN/ribavirin alone or a further 12 wks of pegIFN/ribavirin + daclatasvir
(response-guided therapy) (B2)
Sofosbuvir + ribavirin: 24 wks for interferon-intolerant pts only, where no other
interferon-free option available (B2)
Sofosbuvir + simeprevir: 12 wks (ribavirin may be added for previous
nonresponders & cirrhotics) (B1)
Sofosbuvir + daclatasvir: 12 wks in previously untreated pts; 24 wks in treatment-
experienced patients (including TVR/BOC-experienced patients) (ribavirin may be
added in previous nonresponders and cirrhotics) (B1)
EASL. J Hepatology. 2014;60:392-420.
*In settings where recommended options are not available, treatment with pegIFN/ribavirin + TVR
or BOC remains acceptable.
†
Not recommended in pts with genotype 1a and detectable Q80K polymorphism.
67. EASL HCV GUIDELINES 2014: GENOTYPE 2-6
Genotype Options for Therapy
Genotype 2*
Sofosbuvir + ribavirin: 12 wks (16-20 weeks in cirrhotic patients, especially treatment
experienced) (A1)
PegIFN/ribavirin + sofosbuvir: 12 wks for cirrhotic and/or treatment-experienced patients (B1)
Genotype 3*
Sofosbuvir + ribavirin: 24 wks (unsuitable for treatment-experienced cirrhotics, no specific
alternative proposed) (A2)
PegIFN/ribavirin + sofosbuvir: 12 wks (A2)
Sofosbuvir + daclatasvir: 12 wks (24 wks for treatment-experienced patients) (B1)
Genotype 4*
PegIFN/ribavirin + sofosbuvir 12 weeks (B1)
PegIFN/ribavirin + simeprevir: 12 wks, followed by 12 wks of pegIFN/ribavirin in previously untreated
patients & prior relapsers (B1), or 36 wks of pegIFN/ribavirin in previous partial responders & null
responders (B1)
PegIFN/ribavirin + daclatasvir: 12 wks followed by 12 wks of pegIFN/ribavirin alone or a further 12 wks of
pegIFN/ribavirin + daclatasvir (response-guided therapy) (B1)
Sofosbuvir + ribavirin: 24 wks for interferon-intolerant patients (C2)
Sofosbuvir + simeprevir: 12 wks (ribavirin may be added in previous nonresponders and cirrhotics) (B2)
Sofosbuvir + daclatasvir: 12 wks in previously untreated patients; 24 wks in treatment-experienced patients
(ribavirin may be added in previous nonresponders and cirrhotics) (B2)
Genotype
5/6*
PegIFN/ribavirin + sofosbuvir 12 wks (B1)
Sofosbuvir + ribavirin: 24 wks for interferon-intolerant patients (C2)
EASL. J Hepatology. 2014;60:392-420.
*In settings where recommended options are not available, treatment with pegIFN/ribavirin remains acceptable.
68. WHO HCV GUIDELINES 2014: RECOMMENDATIONS ON HCV TREATMENT
• All adults and children with chronic HCV infection, including people who inject drugs, should be
assessed for antiviral treatment (strong recommendation; moderate quality of evidence)
• PegIFN + RBV recommended rather than standard nonpegylated IFN with RBV (strong
recommendation; moderate quality of evidence)
• TVR or BOC, in combination with pegIFN/RBV, suggested for GT1 chronic HCV infection rather
than pegIFN/RBV alone (conditional recommendation; moderate quality of evidence)
• Sofosbuvir, in combination with RBV with or without pegIFN (depending on HCV genotype),
recommended for GT1-4 HCV infection rather than pegIFN/RBV alone (and rather than no
treatment for persons who cannot tolerate IFN) (strong recommendation; high quality of
evidence)
• Simeprevir, in combination with pegIFN/RBV, recommended for GT1b HCV infection and
genotype 1a HCV infection without the Q80K polymorphism, rather than pegIFN/RBV alone
(strong recommendation; high quality of evidence)
WHO 2014. Guidelines for the screening, care and treatment of persons with hepatitis C infection.
69. So , do we still need to have a Whiff of Interferon at
the beginning of therapy with DAAs to boost the
host immune system and this may Decrease the
relapse rate, break-though and resistance
( <<<<< We need more studies >>>>>)
71. HCV variants that are resistant to DAAs
emerge in patients who experience
virologic failure.
Multiclass resistance emerges in patients
on interferon alfa- free regimens that
contain DAAs, with the possible exception
of resistance to nucleoside pol. inhibitors.
.
72. The long-term impact of emergence of
resistant variants is not known at this point.
It is known that such variants decay over
time, but it remains unclear whether re-
exposure to the same drug classes will
result in rapid re-emergence of resistance.
.
73. Progress in devising interferon alfa-free
regimens is rapid and can be expected to
continue in this manner for the next
several years.
Hope remains that interferon- free regimens
can be crafted for the vast majority of HCV
patients within the near future….THEN WHAT?
74. We have to keep also in mind that ::
Eradication of HCV infection in one person
Eradicating a source of infection
The best way of HCV Prevention
And approaching the end of HCV Epidemic
BID, twice daily; QD, once daily.
Paul Y. Kwo, MD:
Our discussion covers a number of investigational DAAs representing a variety of drug classes, as outlined in this slide.
BOC, boceprevir; HCV, hepatitis C virus; pegIFN, peginterferon; TVR, telaprevir.
Stefan Zeuzem, MD:
Formal clinical guidelines are challenging to generate and take, on average, 6-12 months to complete. Because of the rapid developments in HCV therapy, currently the field has chosen to switch to reliance on guidelines based on expert opinion. In 2013, EASL established formal guidelines, which proved to be outdated by the time they were published. For the 2014 annual meeting, EASL presented a revised guidance document based on expert opinion,[1] an approach that would not fulfill strict methodological criteria for practice guidelines but functions better in the rapidly evolving field. EASL has summarized treatment options for patients with genotype 1-6 HCV according to the availability of HCV therapies in European countries.
The American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA), in collaboration with the International Antiviral Society-USA, were effective in publishing updated guidelines almost immediately after the US Food and Drug Administration (FDA) approvals of simeprevir and sofosbuvir in late 2013.[2] EASL has gone a step further by including drugs that are not yet available but whose approval is anticipated, such as the NS5A inhibitor daclatasvir, whose approval is anticipated this fall in Europe. The EASL guideline does not include any recommendation on additional combination therapies that are anticipated to be approved in Europe in late 2014 or early 2015, including sofosbuvir/ledipasvir and ABT-450/ritonavir/ombitasvir and dasabuvir.
Jordan J. Feld, MD, MPH:
The EASL guidelines, in contrast to the AASLD/IDSA guidelines, acknowledge that not every country gets approval and access to new drugs at the same time. Specifically, EASL has included the option of using telaprevir and boceprevir, and dual therapy with peginterferon and ribavirin alone, in settings where newer agents are not yet available. I applaud EASL for taking treatment access into account because the AASLD/IDSA guidelines are much stricter in that regard.
Stefan Zeuzem, MD:
The difference, of course, is that the AASLD/IDSA guidelines are written with one country in mind. The European guidelines need to cover approximately 30 countries.
Jordan J. Feld, MD, MPH:
Absolutely. I think EASL was right to include the older regimens because it makes for a more universal guideline. Even though the AASLD/IDSA guidelines are written for the United States, it is certainly the case that many non-Americans read them and rely on them, and so it is useful to have some guidance on other options.
Paul Y. Kwo, MD:
As new HCV therapies continue to be introduced, it will be helpful for the AASLD/IDSA and EASL guidelines to evolve into living documents that will be revised online periodically rather than waiting for the period of time it usually takes for guidelines to be developed. This is an approach that AASLD/IDSA have already adopted and will ensure that practicing clinicians can access expert treatment advice for their patients.
HCV, hepatitis C virus; pegIFN, peginterferon.
Stefan Zeuzem, MD:
In addition to the 6 options recommended for genotype 1 HCV infection, EASL has recommended a range of treatment options for patients with genotypes 2-6 HCV. These include varying durations of sofosbuvir plus ribavirin with or without peginterferon (depending on genotype). Daclatasvir is included as an option for genotypes 3 and 4, and sofosbuvir plus simeprevir is a further option for genotype 4.
BOC, boceprevir; GT, genotype; HCV, hepatitis C virus; pegIFN, peginterferon; RBV, ribavirin; TVR, telaprevir; WHO, World Health Organization.
Paul Y. Kwo, MD:
WHO also took the opportunity to present revised guidelines on HCV management at the EASL annual meeting.[3] Significantly, by publishing recommendations on HCV treatment, WHO has demonstrated that it recognizes the importance of treating those with hepatitis C around the world and that all people who are infected should be assessed for candidacy for antiviral therapy.
Jordan J. Feld, MD, MPH:
The WHO guidelines have put hepatitis C on the radar screen at an international level, which was not previously true. The specific therapy recommendations contained in the EASL and AASLD/IDSA guidelines are more detailed than the WHO guidelines. However, the fact that WHO is taking hepatitis seriously is very important.
Stefan Zeuzem, MD:
I agree, although now that these different guidelines have reinforced the importance of therapy, it also becomes important to find ways to identify patients with HCV. Therefore, EASL and WHO should now consider making further recommendations on how to implement screening strategies across different countries.