This document provides information about hepatitis C virus (HCV) including its structure, genome, genotypes, epidemiology, transmission, pathogenesis, diagnosis, and management. It discusses:
- HCV has a single-stranded RNA genome within the Flaviviridae family. It exists as different genotypes that determine treatment response.
- HCV is a major cause of liver disease worldwide, with transmission primarily through blood exposure. Diagnosis involves antibody and RNA testing.
- Treatment aims to eradicate HCV and involves pegylated interferon and ribavirin combinations. Response is monitored via viral load decline. Adverse effects require monitoring and management. New direct-acting antivirals are improving treatment outcomes.
The primary treatment goals for patients with hepatitis B (HBV) infection are to prevent progression of the disease, particularly to cirrhosis, liver failure, and hepatocellular carcinoma (HCC).
Risk factors for progression of chronic HBV include the following :
Persistently elevated levels of HBV DNA and, in some patients, alanine aminotransferase (ALT), as well as the presence of core and precore mutations seen most commonly in HBV genotype C and D infections
Male sex
Older age
Family history of HCC
Alcohol use
Elevated alpha-fetoprotein (AFP)
Coinfection with hepatitis D (delta) virus (HDV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)
A synergistic approach of suppressing viral load and boosting the patient’s immune response with immunotherapeutic interventions is needed for the best prognosis. The prevention of HCC often includes the use of antiviral treatment using pegylated interferon (PEG-IFN) or nucleos(t)ide analogues.
HBV infection can be self-limited or chronic. No specific therapy is available for persons with acute hepatitis B; treatment is supportive.
The primary treatment goals for patients with hepatitis B (HBV) infection are to prevent progression of the disease, particularly to cirrhosis, liver failure, and hepatocellular carcinoma (HCC).
Risk factors for progression of chronic HBV include the following :
Persistently elevated levels of HBV DNA and, in some patients, alanine aminotransferase (ALT), as well as the presence of core and precore mutations seen most commonly in HBV genotype C and D infections
Male sex
Older age
Family history of HCC
Alcohol use
Elevated alpha-fetoprotein (AFP)
Coinfection with hepatitis D (delta) virus (HDV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)
A synergistic approach of suppressing viral load and boosting the patient’s immune response with immunotherapeutic interventions is needed for the best prognosis. The prevention of HCC often includes the use of antiviral treatment using pegylated interferon (PEG-IFN) or nucleos(t)ide analogues.
HBV infection can be self-limited or chronic. No specific therapy is available for persons with acute hepatitis B; treatment is supportive.
Viral hepatitis is the leading cause of liver cancer and the most common reason for liver transplantation
In the United States, an estimated 1.2 million Americans are living with chronic Hepatitis B and 3.2 are living with chronic Hepatitis C
Many do not know they are infected
Each year an estimated 21,000 persons become infected with Hepatitis A; 35,000 with Hepatitis B, and 17,000 with Hepatitis C
Hepatitis A – fecal/oral, contaminated food, vaccine available
Hepatitis B – blood, semen, vertical (mother-child), vaccine available
Hepatitis C – blood (IV drug use, transfusion, organ donation, unsterile injecting equipment, sexual intercourse)
Hepatitis D – survives only in cells co-infected with hepatitis B
Hepatitis E* – contaminated food or water, fecal/oral
*causes short-term disease and is not a chronic carrier state
Hepatitis C
Hepatitis C is a liver disease caused by the hepatitis C virus (HCV): the virus can cause both acute and chronic hepatitis, ranging in severity from a mild illness lasting a few weeks to a serious, lifelong illness.
This lecture is about Spectrum of HCV infection presented by Dr. Muhammad Mostafa Abdel Ghaffar, Head of Tropical Medicine Department, Ahmed Maher Teaching Hospital.
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.
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Viral hepatitis is the leading cause of liver cancer and the most common reason for liver transplantation
In the United States, an estimated 1.2 million Americans are living with chronic Hepatitis B and 3.2 are living with chronic Hepatitis C
Many do not know they are infected
Each year an estimated 21,000 persons become infected with Hepatitis A; 35,000 with Hepatitis B, and 17,000 with Hepatitis C
Hepatitis A – fecal/oral, contaminated food, vaccine available
Hepatitis B – blood, semen, vertical (mother-child), vaccine available
Hepatitis C – blood (IV drug use, transfusion, organ donation, unsterile injecting equipment, sexual intercourse)
Hepatitis D – survives only in cells co-infected with hepatitis B
Hepatitis E* – contaminated food or water, fecal/oral
*causes short-term disease and is not a chronic carrier state
Hepatitis C
Hepatitis C is a liver disease caused by the hepatitis C virus (HCV): the virus can cause both acute and chronic hepatitis, ranging in severity from a mild illness lasting a few weeks to a serious, lifelong illness.
This lecture is about Spectrum of HCV infection presented by Dr. Muhammad Mostafa Abdel Ghaffar, Head of Tropical Medicine Department, Ahmed Maher Teaching Hospital.
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 is a lecture by Katherine A Perry from the Ghana Emergency Medicine Collaborative. To download the editable version (in PPT), to access additional learning modules, or to learn more about the project, see http://openmi.ch/em-gemc. Unless otherwise noted, this material is made available under the terms of the Creative Commons Attribution Share Alike-3.0 License: http://creativecommons.org/licenses/by-sa/3.0/.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
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2. • Hepatitis C virus, which, before its identification was
labeled “non-A, non-B hepatitis,” is a linear, single-
strand, 9600-nucleotide protein molecule.
• RNA virus, the genome of which is similar in
organization to that of flaviviruses and pestiviruses;
HCV is the only member of the genus Hepacivirus in
the family Flaviviridae.
3. • The 5′ end of the genome consists of an
untranslated region (containing an internal
ribosomal entry site, IRES) adjacent to the genes
for three structural proteins, the nucleocapsid core
protein, C, and two structural envelope
glycoproteins, E1 and E2.
STRUCTURE
4. HEP C GENOME
• The 3′ end of the genome also includes an untranslated region
and contains the genes for seven nonstructural (NS) proteins,
p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B. p7 is a
membrane ion channel protein necessary for efficient assembly
and release of HCV
5. • Because HCV does not replicate via a DNA
intermediate, it does not integrate into the host
genome. HCV tends to circulate in relatively low
titer, 103−107 virions/mL, visualization of the 50- to
80-nm virus particles remains difficult. Still, the
replication rate of HCV is very high, 1012 virions per
day; its half-life is 2.7 h.
6. HCV
• 11 genotypes (90 sub-types) , (1a, 1b, 2a, 3b
etc):
• Genotype 1 (subtypes 1a, 1b, and 1c) 70%–75%.
• Genotypes 2 (subtypes 2a, 2b, and 2c) and 3 (3a
and 3b) are less common
• Genotype 4 is common
• Genotype 2, 5 and 6 are least common
• In India Gen 3 is commonest.
Genotype helps determine therapy
duration and likelihood of responding to
therapy
7. EPIDEMIOLOGY
• Worldwide seroprevalence 3% based upon anti- HCV)
up to 180 million people infected chronically.
• Variation in distribution 0.4% to 1.1% in North
America to 9.6% to 13.6% in North Africa.
• A primary cause of death from liver disease
• Responsible for 85% of cases associated with post
transfusional NANB hepatitis.
• HCV carrier rate in India is around 1-2%, around
15million people are infected with this virus. And is
responsible for 20-30% of patients with chronic liver
disease.
8. • Occurs among persons of all ages, highest between
20 to 39 years, with a male predominance.
• The biggest risk factor is among the baby boomer
population, mainly because of their high illicit drug
usage and sexual practices during the 1980s.
10. PATHOGENESIS
• Direct cell injury due to viral replication
• Genotype 1 is associated with higher viral
replication, and infection with the type 1b
genotype is associated with more progressive
liver disease
• Immune mediated cell injury:
• CD8+ and CD4+ lymphocytes in portal, peri-
portal, and lobular areas in patients with HCV
infection
11. COURSE OF DISEASE
• Associated with Acute and Chronic Infections
Feb, 17, 2015Dr. Armaan Singh 11
12. DIAGNOSIS
• Serum anti-HCV antibodies: 99% sensitivity and
specificity
• Serum HCV RNA: “Viral Load”
• Quantitative: used for
• Confirmation of Diagnosis
• Monitoring response to therapy
• Qualitative:
• 50 IU/ml: 100 copies/mL to confirm diagnosis 98%
specificity
13. DIAGNOSIS-CONT
• A specific serologic diagnosis of hepatitis C can be
made by demonstrating the presence in serum of
anti-HCV.
• When contemporary immunoassays are used, anti-
HCV can be detected in acute hepatitis C during
the initial phase of elevated aminotransferase
activity and remains detectable after recovery (rare)
and during chronic infection (common).
14. DIAGNOSIS-CONT
• Assays for HCV RNA are the most sensitive tests
for HCV infection and represent the “gold standard”
in establishing a diagnosis of hepatitis C.
• HCV RNA can be detected even before acute
elevation of aminotransferase activity and before
the appearance of anti-HCV in patients with acute
hepatitis C.
15. • Amplification techniques are required to detect
HCV RNA, and two types are available.
1 Branched-chain complementary DNA (bDNA)
assay.
2 The other involves target amplification (i.e.,
synthesis of multiple copies of the viral genome ) by
PCR or TMA(Transcription mediated amplification).
16. DIAGNOSIS
• Both can be used as quantitative
assays and a measurement of relative
“viral load”; PCR and TMA, with a
sensitivity of 10–102 IU/mL, are more
sensitive than bDNA, with a
sensitivity of 103 IU/mL.
18. GENOTYPE TESTING
• Looking at Nucleotide Patterns
• Test is a simple blood draw test. The test is able to
look at very selected parts of the genetic makeup of
the virus, called nucleotides.
• By looking at that pattern, the ability to see whether
or not that specific nucleotide pattern, almost like a
fingerprint, is for genotype 1, 2, or 3.
• By being able to do that at the molecular basis, the
test will be able to provide details with the type of
genotype that patient has if they are infected with
Hepatitis C.
19. INDICATIONS FOR SCREENING
• Persons who have IV drugs abuse in the recent and
remote past.
• Persons with conditions of a high prevalence of HCV
infection including:
• With HIV infection
• With hemophilia who received clotting factor prior.
• Who have ever been on hemodialysis.
• With unexplained abnormal aminotransferase
levels.
• Immigrants from countries with a high prevalence
of HCV infection.
20. • Children born to HCV-infected mothers
• Health care, emergency medical and public safety
workers after a needle stick injury or mucosal
exposure to HCV-positive blood
• Current sexual partners of HCV-infected persons
21. PREVENTION
• No Vaccine is available
• Risk factor modification
• Intravenous drug abuse: treatment with oral
methadone
• Sexual contact: appropriate barrier contraception
• Avoid blood exposure: Occupational (universal
precautions) or other contact
• Avoid body piercing, sharing razors or receiving a
tattoo.
• HAV and HBV vaccine to prevent further
progression of liver disease
22. TREATMENT KINETICS
Responders Non Responders
Null Responders
Partial Responders
Rapid Virologic Response (RVR)
Early Virologic Response (EVR)
Complete EVR
End Treatment Response (ETR)
23. TREATMENT KINETICS
• Null responders: HCV RNA reduction < 2log10
IU/mL
• Partial Responders: HCV RNA reduction > 2log10
IU/mL but not suppressed to undetectable by week
24.
• Rapid virologic response (RVR): HCV RNA
undetectable within 4 weeks.
• Early virologic response (EVR): HCV RNA reduction
> 2log10 IU/mL with:
1. HCV RNA undetectable at 12 weeks – complete EVR
2. HCV RNA undetectable at 48 weeks – End treatment response
(ETR)
24. GOALS OF THERAPY
• Eradicate HCV infection in acute.
• Decrease HCV associated morbidity and mortality.
• Attain Sustained Virologic Response (SVR).
• Undetectable HVC RNA, 24 weeks after therapy completion
• Normalize biochemical markers.
• Improve clinical symptoms.
• Prevent progression to cirrhosis an HCC.
• Prevent development of end stage liver disease.
• To prevents the development of chronic HCV infection.
These goals
are partly achieved by
Pharmacotherapy
25. INDICATIONS FOR ANTIVIRAL
THERAPY
• Patients with chronic hepatitis C who have detectable
HCV RNA in serum, whether or not aminotransferase
levels are increased, and chronic hepatitis of at least
moderate grade and stage (portal or bridging fibrosis)
are candidates for antiviral therapy.
• Patients who have relapsed after, or failed to respond to
a course of IFN monotherapy are potential candidates
for retreatment with PEG IFN plus ribavirin.
• Compensated liver disease, acceptable hemoglobin (13
g/dL men, 12 g/dL women) and neutrophils (more than
1500/mm3), SCr less than 1.5 mg/dL .
26. ACUTE HCV INFECTION
• In typical cases of acute hepatitis C, recovery is
rare, progression to chronic hepatitis is common.
• Meta-analyses of some small clinical trials suggest
that antiviral therapy with interferon α
monotherapy (3 million units SC three times a
week) is beneficial, reducing the rate of chronicity
considerably by inducing sustained responses in
30–70% of patients.
• Treatment can be delayed for 8-12 weeks for to
assess for spontaneous resolution.
27. • Although treatment of acute hepatitis C is
recommended, the optimum regimen, duration of
therapy, and time to initiate therapy remain to be
determined.
• Many authorities now opt for a 24-week course
(beginning within 2–3 months after onset) of long-
acting pegylated interferon plus the nucleoside
analogue ribavirin.(value of adding ribavirin has not been
demonstrated)
28. TREATMENT OF CHRONIC
HCV INFECTION
• Contraindications to treatment
• Major uncontrolled depressive disorder .
• Solid-organ transplantation (renal, heart, lung)
• Autoimmune hepatitis or other autoimmune
conditions
• Untreated thyroid disease .
• Pregnant or unwilling to adhere to adequate
contraception.
• Severe concurrent medical disease (hypertension,
heart failure, coronary heart disease, poorly controlled
diabetes mellitus, chronic obstructive pulmonary
disease)
• Age younger than 2 years.
• Hypersensitivity to IFN or ribavirin.
29. TREATMENT OF CHRONIC HCV
INFECTION
• Difficult patient population: individualized
consideration
• Advanced liver disease (fibrosis or decompensated
cirrhosis)
• Recurrence after liver transplantation.
• Patients younger than 18 years .
• Co-infection with HIV or HBV.
• Chronic Kidney Disease.
• Non responders or relapses.
30. TREATMENT
• When first approved, IFN-α was administered via
subcutaneous injection three times a week for 6
months but achieved a sustained virologic response
(SVR) (a reduction of HCV RNA to undetectable
levels by PCR when measured ≥6 months after
completion of therapy) below 10%.
• Doubling the duration of therapy—but not
increasing the dose or changing IFN preparations—
increased the SVR rate to ~20%, and addition to the
regimen of daily ribavirin, an oral guanosine
nucleoside, increased the SVR rate to 40%.
31. Treatment
First-line treatment for acute HCV includes pegylated interferon plus
ribavirin.
once-weekly PEG-IFN and a daily oral dose of ribavirin in two divided doses
Genotype Pegylated-IFN
Dose
weight Ribavirin Dose Duration
1 Peginterferon
α2a 180 mcg/wk
Less than 75 Kg 1000 mg 48 weeks
Peginterferon α2b
1.5 mcg/wk
More than 75 kg 1200 mg
2,3 Peginterferon á2a
180 mcg/wk
800 mg 24 weeks
Peginterferon α2b
1.5 mcg/wk
At week 1, 2, 4 and then interval of 4-8 weeks monitor:
• Symptom of Disease
• Side Effects of therapy
• Blood count
• Aminotransferases.
32. FOLLOW UP
• Genotype-1:AT week 12
- Retest HCV RNA level
If Negative or decreased by 2log 10 unit Continue for full 48 wk.
Monitor for :Symptoms, Blood count, ALT at 4-8 week
interval
• If RNA hasn’t fallen by 2log 10 Units: STOP therapy
• Genotype 2, 3
Retest HCV RNA level at 24 weeks.
• After therapy:
Assess ALT 2, & 6 months.
Repeat HCV RNA, 6 months after stopping treatment.
33. RIBAVIRIN ADVERSE EFFECT
MONITORING
• Oral nucleoside analog
• Available as 200-mg tablets (Copegus) or capsules (Rebetol)
• Adverse Effect
• Hemolytic anemia:
• Upto 10% of patients (usually within 1–2 weeks of
initiating therapy).
• decrease dose to 600 mg/day when hemoglobin drops
to 10 g/dL or less, and discontinue when hemoglobin
drops to 8.5 g/dL or less.
(J Clin Gastroenterol 2005;39:S9-S13)
34. • May worsen underlying cardiac disease.
• Monitor complete blood cell count (CBC) at
baseline, 2 weeks, 4 weeks.
• Decrease dose to 600 mg/day if hemoglobin drops
more than 2 g/dL in any 4-week period during
treatment.
• May use erythropoetin or darbepoetin to stimulate
red blood cell production, improve anemia.
(J Clin Gastroenterol 2005;39:S9-S13
35. RIBAVIRIN ADVERSE EFFECT
MONITORING
• Teratogenicity:
• Requires a negative pregnancy test at baseline and every month
up to 6 months after treatment,
• Use of two forms of barrier contraception during treatment
and for 6 months after treatment.
• Contraindicated in patients with a creatinine clearance
(CrCl) less than 50 mL/minute
• pancreatitis, pulmonary dysfunction (dyspnea,
pulmonary infiltrate, and pneumonitis), insomnia,
irritability or depression, and pruritus.
37. • Less common but serious adverse
• severe psychiatric (i.e., suicidal ideation),
• cardiovascular (i.e., myocardial infarction),
• Endocrine (e.g., thyroid dysfunction, diabetes
mellitus),
• immune (e.g., psoriasis, lupus),
• pancreatitis, colitis, and other serious infections.
38. MANAGING THE ADVERSE EFFECTS
OF INTERFERON• Hematological:
• Anemia: common reason for discontinuation and
dose reduction (upto 23% of patients)
• Tx: Erythropoitic growth factor:
• Epoitin Alfa: 40-6000 units weekly
• Darbepoitin alfa 3 mcg every 2 weeks
• IFN induced neutropenia:
• Recombinant granulocyte colony stimulating factor
(filgrastim) is safe and effective.
• Thrombocytopenia:
• Eltrombopag, an orally active thrombopoietin receptor
agonist that received FDA approval for chronic ITP
(hepatotoxic).
39. MANAGING THE ADVERSE EFFECTS
OF INTERFERON
• Neuropsychiatric:
• Prompt recognition and early treatment required
• Depression: 44% during first 3 months.
• Treatment:
• Close monitoring and follow up by a team of
health care providers including psychiatrist
• Prophylactic anti-depressants are debated
• Uncontrolled psychiatric symptoms:
contraindication for treatment.
40. TREATMENT CHALLENGES
• High viral load
• HCV RNA greater than 800,000 IU/mL
• Advanced fibrosis and cirrhosis,
• Continued drug and/or alcohol use,
• Psychiatric conditions,
• Coinfection with HBV or HIV, advanced age,
• Immunosuppression (e.g., liver transplantation recipients),
• African American race,
• Obesity and insulin resistance,
• Previous treatment with suboptimal therapy
41. DEALING WITH THE CHALLENGES:
NEW ANTIVIRALS
• Direct Acting Antiviral Drugs (DAA)
• The NS3 protease inhibitors : Telaprevir and Boceprevir
• In 2011, telaprevir and boceprevir used in combination with
PEG IFN and ribavirin were approved for the treatment of
hepatitis C genotype 1 in adults with stable liver disease, both
in patients who have not been treated before or who have
failed previous treatment.
• Because resistance develops rapidly, both telaprevir and
boceprevir must be used in combination with a PEG IFN and
ribavirin-based regimen and should never be used alone.
An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011
practiceguideline by the American Association for the Study of Liver Diseases
42. • All current telaprevir and boceprevir regimens consist of
periods of triple therapy (protease inhibitor plus PEG
IFN plus ribavirin) and periods of dual therapy (PEG
IFN plus ribavirin).
• Telaprevir regimens begin with 12 weeks of triple
therapy followed by dual therapy of a duration based on
HCV RNA status at weeks 4 and 12 (“response guided
therapy”) and prior treatment status.
• Boceprevir-based regimens consist of a 4-week lead-in
period of dual (PEG IFN–ribavirin) therapy followed by
triple therapy and, in some instances, a further
extension of dual therapy, with duration of response-
guided therapy based on HCV RNA status at weeks 4, 8,
and 24 and prior treatment status
43. HCV GENOTYPE 1
• TREATMENT-NAIVE (telaprevir and boceprevir) and PRIOR
RELAPSERS (telaprevir)
• PEG IFN-α2a 180 μg weekly plus weight-based ribavirin 1000
mg/d (<75 kg) to 1200 mg/d (≥75 kg) or
• PEG IFN-α2b 1.5 μg/kg weekly plus weight-based ribavirin
800 mg/d (≤65 kg), 1000 mg/d (>65–85 kg), 1200 mg/d (>85–
105 kg), or 1400 mg/d (>105 kg)
• Plus response-guided therapy with a protease inhibitor
consisting of either:
• Boceprevir 800 mg three times daily with food started after a
lead-in treatment of 4 weeks with PEG IFN–ribavirin or
• Telaprevir 750 mg three times daily with fatty food started at
the beginning of therapy without a PEG IFN–ribavirin lead-in
46. HCV GENOTYPES 2 AND 3
• 24 weeks of therapy
• PEG IFN-α2a 180 μg weekly plus ribavirin 800
mg/d or
• PEG IFN-α2b 1.5 μg/kg weekly plus ribavirin 800
mg/d (for patients with genotype 3 who have
advanced fibrosis and/or high-level HCV RNA, a
full 48 weeks of therapy may be preferable)
47. HCV GENOTYPE 4
• 48 weeks of PEG IFN–ribavirin therapy
• PEG IFN-α2a 180 μg weekly plus weight-based
ribavirin 1000 mg/d (<75 kg) to 1200 mg/d (≥75 kg) or
• PEG IFN-α2b 1.5 μg/kg weekly plus weight-based
ribavirin 800 mg/d (≤65 kg), 1000 mg/d (>65–85 kg),
1200 mg/d (>85–105 kg), or 1400 mg/d (>105 kg)
• Treatment should be discontinued in patients who do
not achieve an early virologic response at week 12.
• Patients who do achieve an early virologic response
should be retested at week 24, and treatment should be
discontinued if HCV RNA remains detectable.
48. ADVERSE EFECTS
• Both protease inhibitors have potential toxicities.
Telaprevir is associated with a severe, generalized
(trunk and extremities), often confluent,
maculopapular, pruritic rash in ~6% of treated
patients.
• Other common side effects include pruritus, rectal
burning, nausea, diarrhea, fatigue, and anemia, which
may be relatively refractory occasionally requiring
transfusion.
• Complete blood counts should be obtained at baseline
and then at 2, 4, 8, and 12 weeks after starting
telaprevir.
49. • Anemia can occur in half of boceprevir-treated
patients, as can neutropenia in up to 30% and
thrombocytopenia in 3–4%. Complete blood counts
should be obtained at baseline and then at 4, 8, and
12 weeks after starting boceprevir.
• Other side effects of boceprevir include fatigue,
nausea, headache, dysgeusia (altered or unpleasant
taste), dry mouth, vomiting, and diarrhea
50. NEW ANTIVIRALS
SOFOSBUVIR
• Dose -400mg tablet once daily for 12-24 wks
• It’s a prodrug Metabolized to active triposphate . This
triphosphate serves as a defective substrate of
NS5B protein(viral RNA polymerase)
• Thus inhibit viral RNA synthesis.
• Plasma Half life: 0.48 ‐ 0.75 h (sofosbuvir).
51. • The following points should be considered when
initiating treatment with Sofosbuvir:
• Monotherapy of Sofosbuvir is not recommended for
treatment of CHC.
• Treatment regimen and duration are dependent on
both viral genotype and patient population
• Treatment response varies based on baseline host
and viral factors
• The recommended dose of Sofosbuvir is one 400 mg
tablet, taken orally, once daily with or without food
• Sofosbuvir should be used in combination with ribavirin
or in combination with pegylated interferon and
ribavirin for the treatment of CHC in adults
52. • In the FISSION study, among patients receiving
sofosbuvir–ribavirin, response rates were lower among
patients with genotype 3 infection than among those
with genotype 2 infection (56% vs. 97%) and were lower
for patients with cirrhosis than for those without
cirrhosis (47% vs. 72%).
Alessandra Mangia, M.D et al:Sofosbuvir for Previously Untreated Chronic
Hepatitis C Infection. May 16, 2013 DOI: 10.1056/NEJMoa1214
53. • In NEUTRINO trial the efficacy and safety of
sofusbuvir in previously treatment-naïve hepatitis c
patients with or without cirrhosis(gen 1, 4, 5,6) was
studied.
• 99% of patients with gen 1,4,5 or 6 achieved RVR,
and 90% achieved a SVR12.
• Patients with cirrhosis had a slightly lower rate of
SVR(80% compared with that 92% in patients
without cirrhosis.
54. • In ATOMIC trial, the efficacy of sofosbuvir with
peg-interferon and ribavirin in treatment naïve
patients with chronic hepatitis C(Gen 1,4 or 6
without cirrhosis) was studied.
• Results of this study showed very high SVR in all
three genotypes.
55. SIMEPREVIR
• A FDA approved hepatitis C virus protease inhibitor
• A NS3/4A protease inhibitor
• thus preventing viral maturation through inhibition of
protein synthesis.
• Simeprevir is administered as one capsule once daily with
pegylated interferon and ribavirin for the treatment of
genotype 1 or genotype 4 chronic hepatitis C.
56. • The recommended dose 150 mg taken orally OD with food
Should be used in combination with peg interferon alfa
and ribavirin.
• Adverse reactions: Rash, itching, nausea,
• Muscle pain, and indigestion
• Embryo-Fetal toxicity
• Photosensitivity
• contraindications
• In pregnant or may become pregnant women
• Men whose female partners are pregnant because of the
risk for birth defects and fetal death.
57. • Pooled data from the Phase III QUEST- 1 and QUEST-2
trials demonstrated that SMV 150mg QD administered
for 12 weeks in combination with pegIFN alpha-2a/RBV
or PegIFN alpha-2b/RBV resulted in:
• Overall SVR at 12 wk rate of 80% , significantly higher
than placebo.
• 88% of patients able to shorten treatment to 24 weeks,
with 88% among them achieving SVR at 12wk.
Simeprevir (TMC435) with peginterferon/ribavirin for treatment of chronic HCV
genotype 1 infection in treatment-naïve patients: efficacy in difficult-to-treat patient
sub-populations in the QUEST-1 and 2 Phase III trials
58. INTERFERON FREE REGIMENS
• The revolution in therapy came with the
introduction of directly acting drugs(DAA) like
sofusbuvir, simeprevir and ledipasvir in 2012 and in
2014.
• All oral drugs for hepatitis c was approved by the
FDA. In India, all oral medicines was introduced in
april 2015 and the interferon free ribavirin free
regimen in treatment naïve patients involving
sofosbuvir-ledipavir and sofosbuvir-daclatasvir was
approved for use in India in December 2015.
• Combination of DAA in various forms as ‘Drug
cocktails’ is useful.
59. INTERFERON FREE REGIMENS
• European guidelines (EASL)2015 HCV genotype 1
treatment naïve
• If patient is intolerant to RBV, or if there is adverse
outcome the combination has to be extended for
24wks.
Combination drugs No cirrhosis
(SVR12)
Compensated
cirrhosis
Sofosbuvir +
Ledipasvir 12wk
100% 97%
Sofosbuvir +
Ledipasvir
+Ribavarin
12wks
100% 100%
Sofosbuvir +
Ledipasvir 24wks
99% 97%
60. Combination drugs No cirrhosis Compensated
cirrhosis
Sofusbuvir+daclatasvi
r for 12wks
94%
Sofusbuvir+daclatasvi
r+RBV 24wks
100% 88%
Sofusbuvir+daclatasvi
r 24wks
100% 63%
62. HIV/HCV COINFECTION
• In patients with HCV/HIV co-infection, hepatitis C is
more progressive and severe than in HCV-
monoinfected patients.
• Four large national and international trials of
antiviral therapy among patients with HCV/HIV co-
infection have shown that PEG IFN (both α2a and
α2b) plus ribavirin (daily doses ranging from flat-
dosed 600−800 mg to weight-based 1000/1200 mg) is
superior to standard IFN regimens.
63. • However, SVR rates were lower than in HCV-
monoinfected patients, ranging from 14 to 38% for
patients with genotypes 1 and 4 and from 44 to 73%
for patients with genotypes 2 and 3.
• An alternative recommendation for ribavirin doses
was issued by a European Consensus Conference
and consisted of standard, weight-based ribavirin
1000−1200 mg for genotypes 1 and 4, but 800 mg
for genotypes 2 and 3.
64. • A head-to-head trial of combination PEG IFN–ribavirin
therapy in HCV/HIV co-infection demonstrated
statistically indistinguishable efficacy of the two types of
PEG IFN, despite a small advantage for PEG IFN-α2a.
• For PEG IFN-α2b and -α2a, SVRs occurred in 28%
versus 32%, respectively, of patients with genotypes 1
and 4.
and in 62% versus 71%, respectively, of patients with
genotypes 2 and 3.
65. • Although data are limited and recommendations
pending, protease inhibitors may be used for
genotype 1.
• However, because of potential drug-drug
interactions between HCV protease inhibitors and
HIV antiretroviral drugs (especially in ritonavir-
boosted HIV protease inhibitors), HCV protease
inhibitors should be used cautiously in HCV-HIV
co-infected patients.
• If protease inhibitors are used, a full 48-week
course is recommended without response-guided
therapy.
66. • In HCV/HIV-infected patients, ribavirin can
potentiate the toxicity of didanosine (e.g., lactic
acidosis) and the lipoatrophy of stavudine, and
zidovudine can exacerbate ribavirin-associated
hemolytic anemia; therefore, these drug
combinations should be avoided.
67. • Photon study( photon 1 trial)
• This study showed that combination of
sofosbuvir+RBV for 12 or 24 wks achieved high
rates of SVR12 without any deleterious effects.
Genotype Treatment naïve
SVR12
%
Treatment
experienced
SVR12 %
1 76
2 88 92
3 67 94
Sulkowski MS, Naggie et al: sofosbuvir and RBV for HEP C in patients
with HIV coinfection.JAMA 2014;312.
68. DAA IN CKD PATIENTS
• The overall prevalence of HCV infection in CKD
patients on maintenance haemodialysis is 13.5%.
• Positive anti-HCV serologic ststus after kidney
transplantation is implicated in the pathogenesis of
acute glomerulopathy, i.e graft HCV-associated
nephropathy.
69. • A study investigated the safety and efficacy of
sofusbuvir+ RBV in HCV infectetd patients with
severe renal impairement(GFR<30ml/min).
• Ten patients were enrolled and have been treated
for 12-24wks, All patients experienced RVR similar
to those with normal renal function and full dose
sofosbuvir+ RBV. There were no patients with
virologic breakhrough.
Ferenci P. treatment of HEP C in difficult to treat patients.Nat Rev
Gasteroenterol Hepatol.2015;12(5).
70. CONCLUSION
• The era of DAA theray in the treatment of hepatitis
C is evolving rapidly.
• The proof of concept that HCV infection can be
cured without INF to showing that cure can be
attained in an extraordinarily high proportion of
patients has occurred more quickly than most
observers had anticipated.
73. COST OF TREATMENT
• Cost of treatment :
• $84,000 = Rs. 50.4 lacks for 24 weeks
• In September 2014, Gilead announced that it
would permit generic manufacturers to sell
sofosbuvir in 91 developing countries
• New price now is:
• About $1,800 = Rs. 1.1lacks (less than an
IVIG course for GB)