Friday, February 23, 2018

Podcast Series: Diagnosis and Treatment Of Hepatitis C

In case you missed it, interesting podcast. 

Diagnosis and Treatment Of Hepatitis C
February 22, 2018

Hepatitis C (HCV) is the most-deadly infectious disease in America.

  • More than 20,000 die every year because of HCV
  • Half of people infected do not know that they have the virus
  • HCV can remain undetected for decades

HCV is curable, even among past and current drug users. You can help turn the tide. Learn how to screen (hint: it's easy) and how screening can save lives.

Treatment is now simpler, more effective, and shorter than ever. And it should be offered to nearly everyone with HCV, regardless of the level of cirrhosis.

Tune in to START HCV Radio Hour to listen and learn as our expert faculty explore important topics, using patient stories in an engaging moderated DKBmed Talk, modeled after the famous and popular TED Talks.

  • Learn how to detect HCV infection with a simple blood test
  • Become familiar with revolutionary new treatment options that cure 99% of people who use them
  • Prevent the spread of HCV and the morbidity and mortality that can follow

The expert faculty includes Mark Sulkowski, MD, professor of medicine and medical director of the Viral Hepatitis Center at the Johns Hopkins University School of Medicine; Alain Litwin, MD, professor of medicine at Albert Einstein College of Medicine in New York; Kathleen Brady, MD, Distinguished University Professor at the Medical University of South Carolina and Director of the South Carolina Clinical and Translational Research Institute; and Raymond Chung, MD, director of hepatology and the Liver Center at Massachusetts General Hospital in Boston.

Thursday, February 22, 2018

HBV Infection: When to Treat vs When to Monitor?

Latest content at Clinical Care Options 

HBV Infection: When to Treat vs When to Monitor?
Tram T. Tran, MD - 2/21/2018

Would you treat or monitor a patient with low HBV DNA levels and high ALT? Here’s my take.

One of the most complex issues in managing patients infected with HBV is determining when to treat vs when to monitor the infection. For example, what would you recommend for an HBeAg-positive middle-aged woman with HBV DNA < 20,000 IU/mL, ALT ≥ 2 x ULN, but no cirrhosis?

Like many patients with HBV infection, she may be asymptomatic, be reluctant to take long-term medications that do not immediately affect how she feels, have concerns about adverse events, or be at risk for nonadherence.

** Free registration required 

Health News Review: Pulling back the curtain on ‘The Doctors’ and ‘The Dr. Oz Show:’ What our analysis revealed

Pulling back the curtain on ‘The Doctors’ and ‘The Dr. Oz Show:’ What our analysis revealed
Ranit Mishori, MD

Earlier this month, Mehmet Oz, MD celebrated his 1,500th “Dr. Oz” show. Oprah Winfrey, Gayle King and Martha Stewart made appearances, proffering congratulations and discussing everything from mercury in fish to the #metoo movement.

I felt less jubilant: In the decade that The Dr. Oz Show has been on the air, it hasn’t been unusual for me to encounter patients who ask about topics, treatments and suggestions mentioned on the program and another popular medical show, “The Doctors.” The advice my patients tell me they’ve heard on these shows often does not square with what I know about the medical evidence.

While I may know that TV shows should be considered entertainment, my patients may not. After all, in our culture, a white coat and a “Dr.” title is a powerful symbol for a trustworthy person of knowledge.

The characteristics of residents with unawareness of hepatitis C virus infection in community

The characteristics of residents with unawareness of hepatitis C virus infection in community
Pin-Nan Cheng ,Yen-Cheng Chiu,Hung-Chih Chiu, Shih-Chieh Chien

Published: February 22, 2018

Full Text

Control of hepatitis C virus infection (HCV) is an increasingly important issue. Enhancing screening coverage is necessary to discover more HCV infected subjects in community. However, a substantial population is unaware of HCV infection that needs more attention.

The aims of this study were to evaluate the status of HCV infected residents in remote villages, to compare characteristics between already known and unaware HCV infection subjects, and to analyze the disease insights.

Patients and methods
Screening intervention for liver diseases was conducted in remote villages of Tainan City of southern Taiwan from August 2014 to July 2016. Items of screening examinations included questionnaire, blood sampling for liver tests and viral hepatitis markers (hepatitis B surface antigen and anti-HCV antibody), abdominal sonography survey, and liver stiffness measurement by transient elastography. Quantitation of HCV RNA was measured for residents with positive anti-HCV antibody.

A total of 194 (13.5%) out of 1439 participants showed positive for anti-HCV antibody. HCV viremia was detected in 119 (61.3%) residents. Previously unaware HCV infection by questionnaire record was present in 68 (35.1%) of ant-HCV positive residents. By multivariate logistic analysis, unaware HCV infected residents exhibited significantly mild liver fibrosis (OR 0.876, 95% CI 0.782~0.981, p = 0.022), more prevalent of heart diseases (OR 6.082, 95% CI 1.963~18.839, p = 0.002), and less cluster of family history of liver diseases (OR 0.291, 95% CI 0.113~0.750, p = 0.011) when comparing with already known HCV infected residents. Among the 126 already know HCV infected residents, only 59 (46.8%) received antiviral treatment or regular follow-up. No concept or no willing to receive medical care was observed in 44 (34.9%) residents.

In HCV endemic villages of Taiwan, residents with unaware HCV infection comprised about one third of HCV infected residents and exhibited obscure characteristics to identify. Less than half of already known HCV infected residents received adequate medical care. To eliminate HCV infection, vigorous efforts on enhancing screening coverage, educating update knowledge of liver diseases, and linking to medical care are urgently needed.

Young men's drinking tied to later liver disease risk

Young men's drinking tied to later liver disease risk
Last Updated: 2018-02-22
By Lisa Rapaport (Reuters Health)

Men who drink alcohol in late adolescence are more likely to develop severe liver disease decades later than young people who don't drink at all, a Swedish study suggests.

Researchers examined data on alcohol consumption for 43,296 men entering military service in 1969 and 1970 when they were 18 to 20 years old.

After an average follow-up of almost 38 years, a total of 383 men were diagnosed with severe liver disease, including 208 who died.

Each daily gram of alcohol men typically consumed in their youth was associated with a 2% increase in the risk of severe liver disease, even after researchers accounted for other independent risk factors for liver damage like obesity, smoking and cardiovascular disease.

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Hepatitis C: The Bane of Baby Boomers, Though Treatable

Hepatitis C: The Bane of Baby Boomers, Though Treatable
FEBRUARY 21, 2018
Jeannette Y. Wick, RPh, MBA, FASCP

More than 3 million Americans have chronic hepatitis C virus (HCV), and physicians diagnose about 17,000 new cases annually. HCV is a silent disease, and most infected individuals are unaware that they are infected until they develop liver damage, cirrhosis, or liver cancer. Consequently, 12,000 Americans die from HCV complications each year.1,2,3 And people born between 1945 and 1965 are 5 times more likely to have hepatitis C than others.4 Although treatments have been available for many years, the consistent ability to cure HCV is recent.

Choosing the Treatment Regimen
Treatment goals include a persistent absence of HCV ribonucleic acid in serum 6 months or more after completing antiviral treatment, and preventing progression to serious complications.

Since 2013, oral regimens combining direct-acting antivirals from different classes (Table 1) have effectiveness exceeding 90%. These therapies have shorter durations and fewer adverse effects than older options.

Study finds racial differences in cure rates for Hepatitis C

Study finds racial differences in cure rates for Hepatitis C

In a large ethnically diverse group of patients seen at a community-based Veterans Affairs practice, cure rates for chronic hepatitis C were lower for African American individuals relative to White individuals, even when patients were receiving optimal therapies. The findings are published in Pharmacology Research & Perspectives.

The investigators noted that although the results demonstrate the importance of racial/ethnic differences in chronic hepatitis C, the true causes of these differences remain unclear and should be further explored in prospective studies where drug levels and patient genetics are taken into account.

Wednesday, February 21, 2018

New AASLD Guidelines for Hepatocellular Carcinoma: The Big Questions Tackled

New AASLD Guidelines for Hepatocellular Carcinoma: The Big Questions Tackled

David A. Johnson, MD
February 21, 2018

View video and read the complete article at Medscape

Hello. I'm Dr David Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia.

When we see patients with cirrhosis in the clinic, we are concerned about screening for hepatocellular carcinoma (HCC). I'm not a transplant hepatologist, but I deal with these patients all the time, as you do.

HCC is an incredibly common disease. It's the fifth most common tumor in the world and the second leading cause of cancer-related death.[1] In the United States, there are an estimated 39,000 new cases per year and over 27,000 related deaths[2,3]; the incidence is likely to rise at least until 2030.[4] This problem is not going away.

Why is that? It's about cirrhosis. The majority of HCCs, 85%-95%, occur in patients with cirrhosis[5,6]—the exception to the rule being hepatitis B, where patients do not need to be cirrhotic. The incidence of HCC in patients with cirrhosis that I quote to my patients is 2%-4% per year.[7] Thus, it is recommended that we screen these patients because early screening may lead to earlier diagnosis and appropriate interventions.

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Revisiting policy on HCV treatment under the Thai Universal Health Coverage: An economic evaluation and budget impact analysis

Revisiting policy on chronic HCV treatment under the Thai Universal Health Coverage: An economic evaluation and budget impact analysis
Waranya Rattanavipapong ,Thunyarat Anothaisintawee ,Yot Teerawattananon

Published: February 21, 2018

Full Text Article:

Thailand is encountering challenges to introduce the high-cost sofosbuvir for chronic hepatitis C treatment as part of the Universal Health Care’s benefit package. This study was conducted in respond to policy demand from the Thai government to assess the value for money and budget impact of introducing sofosbuvir-based regimens in the tax-based health insurance scheme. The Markov model was constructed to assess costs and benefits of the four treatment options that include: (i) current practice–peginterferon alfa (PEG) and ribavirin (RBV) for 24 weeks in genotype 3 and 48 weeks for other genotypes; (ii) Sofosbuvir plus peginterferon alfa and ribavirin (SOF+PEG-RBV) for 12 weeks; (iii) Sofosbuvir and daclatasvir (SOF+DCV) for 12 weeks; (iv) Sofosbuvir and ledipasvir (SOF+LDV) for 12 weeks for non-3 genotypes and SOF+PEG-RBV for 12 weeks for genotype 3 infection. Given that policy options (ii) and (iii) are for pan-genotypic infection, the cost of genotype testing was applied only for policy options (i) and (iv). Results reveal that all sofosbuvir-based regimens had greater quality adjusted life years (QALY) gains compared with the current treatment, therefore associated with lower lifetime costs and more favourable health outcomes. Additionally, among the three regimens of sofosbuvir, SOF+PEG-RBV for genotype 3 and SOF+LDV for non-3 genotype are the most cost-effective treatment option with the threshold of 160,000 THB per QALY gained. The results of this study had been used in policy discussion which resulted in the recent inclusion of SOF+PEG-RBV for genotype 3 and SOF+LDV for non-3 genotype in the Thailand’s benefit package.

Similarities found in cancer initiation in kidney, liver, stomach, pancreas

Similarities found in cancer initiation in kidney, liver, stomach, pancreas

Potential for therapies that interfere with early cancer growth

by Jim Dryden
February 21, 2018

Recent research at Washington University School of Medicine in St. Louis demonstrated that mature cells in the stomach sometimes revert back to behaving like rapidly dividing stem cells. Now, the researchers have found that this process may be universal; no matter the organ, when tissue responds to certain types of injury, mature cells seem to get younger and begin dividing rapidly, creating scenarios that can lead to cancer.

Older cells may be dangerous because when they revert to stem cell-like behavior, they carry with them all of the potential cancer-causing mutations that have accumulated during their lifespans. However, because mature cells in the stomach, pancreas, liver and kidney all activate the same genes and go through the same process when they begin to divide again, the findings could mean that cancer initiation is much more similar across organs than scientists have thought. That could support using the same strategies to treat or prevent cancer in a variety of different organs.

The findings about how mature cells begin dividing again — a process the researchers have named paligenosis — are reported Feb. 15 in The EMBO Journal.

“When we began the war on cancer in the 1970s, scientists thought all cancers were similar,” said senior investigator Jason C. Mills, MD, PhD, a professor of medicine in the Division of Gastroenterology. “It turned out cancers are very different from one organ to another and from person to person. But if, as this study suggests, the way that cells become proliferative again is similar across many different organs, we can imagine therapies that interfere with cancer initiation in a more global way, regardless of where that cancer may appear in the body.”

Studying cells from the stomach and pancreas in humans and mice, as well as mouse kidney and liver cells, and cells from more than 800 tumor and precancerous lesions in people, the researchers found when tissue is injured by infections or trauma, mature cells can revert back to a stem-cell state in which they divide repeatedly. And along the way, those cells all activate the same genes to break down the mature cells and help them begin to divide again.

“First, we saw a massive increase in the activity of genes associated with cell degradation,” said first author Spencer G. Willet, PhD, a research associate in the Mills lab. “Then, the cell’s growth pathway senses that degradation and releases nutrients that then activate cell growth pathways and allow the mature cells we studied to proliferate.”

Paligenosis, Mills explained, appears similar to apoptosis — the programmed death of cells as a normal part of an organism’s growth and development — in that it seems to happen the same way in every cell, regardless of its location in the body.

“Nature has provided a way for mature cells to begin dividing again,” Mills said, “and that process is the same in every tissue we’ve studied.”

Willet, Mills and their colleagues believe the discovery that cells in different organs go through the same process to become proliferative could lead to new potential targets for cancer treatment because the factors that initiate tumors could be the same in multiple organs.

“If you were to compare this reprogramming of cells to tearing down a building and putting something new in its place, the slow way to go would be to remove and then replace each brick, one at a time,” Mills said. “What we’re seeing is that nature is smarter than just running the building program in reverse. Instead, there is a wrecking ball program: When an old cell begins to divide again, a program runs to clear things out and then rebuild, and the same program runs in every tissue we’ve analyzed.”

Significant Mortality Benefit Seen With Sustained HCV Virologic Response With DAAs

Significant Mortality Benefit Seen With Sustained HCV Virologic Response With DAAs
Hannah Dellabella
For patients infected with hepatitis C virus (HCV) without advanced liver disease, achieving sustained virologic response with direct-acting antivirals (DAAs) is associated with decreased mortality, according to results published in Hepatology.

Gilead’s pan-genotypic treatment for hepatitis C Vosevi has won the National Institute for Health and Care Excellence’s seal of approval for use on the NHS.

NICE nod for Gilead's pan-genotypic hepatitis C therapy
Gilead’s pan-genotypic treatment for hepatitis C Vosevi has won the National Institute for Health and Care Excellence’s seal of approval for use on the NHS.

Vosevi (sofosbuvir/velpatasvir/voxilaprevir; SOF/VEL/VOX) was cleared by European regulators in July last year as the first and only single tablet regimen for patients with any genotype of chronic hepatitis C virus infection.

NICE Guidance
Evidence-based recommendations on sofosbuvir–velpatasvir–voxilaprevir (Vosevi) for treating chronic hepatitis C in adults.

Opinion - It's criminal what Illinois is doing to Medicaid patients with hepatitis C

It's criminal what Illinois is doing to Medicaid patients with hepatitis C

Every day, Illinois Medicaid patients with hepatitis C are denied access to a simple cure to a disease that jeopardizes their life because of outdated and unconscionable restrictions on who can get this proven treatment.

Hepatitis C is a viral infection that causes inflammation and scarring of the liver. People who are infected with hepatitis C usually have no or few symptoms for decades until it reaches the end stages of disease, where patients are at risk of liver failure, liver cancer and death. Hepatitis C is a leading cause of liver-related death and need for liver transplantation in the United States. An estimated 150,000 people are affected by hepatitis C in this state alone, according to the Illinois Department of Public Health.

Hepatitis C Virus Clearance in Older Adults

Hepatitis C Virus Clearance in Older Adults
Does HCV clearance with direct-acting antiviral therapy improve outcomes in individuals aged 80 and older--even in the face of severe liver disease and multiple comorbidities?
February 21, 2018

Journal of the American Geriatrics Society
Hepatitis C Virus Clearance in Older Adults
Antonio Massimo Ippolito, MD; Angelo Iacobellis, MD; Michele Milella, MD; Fabio Conti, MD; Vincenzo Messina, MD; Maria Rosa Valvano, PhD; Grazia Anna Niro, MD; Filomena Morisco, MD; Michele Barone, MD; Antonio Patrizio Termite, MD; Giuseppina Brancaccio, MD; Angelo Andriulli, MD

Full Text

Abstract and Introduction
Objectives To determine whether older adults with the hepatitis C virus (HCV) achieve a sustained viral response (SVR) after treatment with direct-acting antiviral therapy.

Participants Individuals aged 80 and older with chronic HCV infection (N = 253; n = 213 with cirrhosis, n = 40 with advanced fibrosis).

We investigated the efficacy, safety, and global clinical effect of treatment with different combinations of direct antiviral agents (DAAs). Participants with cirrhosis were staged according to Child-Pugh-Turcotte class, Model for End-Stage Liver Disease score, and the D'Amico staging system. The type and number of comorbidities at baseline and hepatic and nonhepatic events during follow-up were registered.

Ninety-five percent of participants with cirrhosis and 95% of those with advanced fibrosis attained SVR. The rate was independent of sex, HCV genotype, and treatment schedule. During a mean follow-up of 14 ± 4 months (range 5–23 months), 34 events occurred in 27 participants: 10 hepatocellular carcinomas, 12 hepatic decompensations, 9 nonhepatic events, 3 deaths. Multivariate analysis of risk factors for experiencing adverse events during follow up showed that participants in D'Amico Stages 4 and 5, with a baseline serum albumin level of 3.5 mg/dL or less, and 3 or more comorbidities were the most at risk.

In a real-world setting, DAAs are safe and effective in older adults with HCV-related advanced fibrosis or cirrhosis. Individuals with preserved albumin synthesis and fewer than 3 comorbidities at baseline have the most to gain from long-term DAA therapy.

Severe fibrosis improves in most patients after hepatitis C cure but persists in a quarter

Severe fibrosis improves in most patients after hepatitis C cure but persists in a quarter
Michael Carter
Published: 20 February 2018

Hepatitis C virus (HCV)-related liver fibrosis improves significantly in the majority of patients with pre-treatment advanced fibrosis or cirrhosis after treatment resulting in a sustained virological response, Swedish investigators report in the Journal of Viral Hepatitis.

However, advanced fibrosis persisted in a quarter of patients and worsened in a small subset of patients, showing the need for regular monitoring after successful HCV therapy. Pre-treatment cirrhosis, older age and high body mass index were risk factors for the persistence of advanced cirrhosis.

“Our study shows that the vast majority of our 269 patients with pre-treatment advanced fibrosis or cirrhosis improved their fibrosis during long-term follow-up after SVR,” comment the researchers. “A minority, however, continued to have advanced fibrosis even after more than 5-10 years follow-up. In this subset of patients, a point of no return for advanced liver fibrosis might have been reached, where improvement is not possible.”

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Tuesday, February 13, 2018

High SVR Rates: Ombitasvir/Paritaprevir-ritonavir plus Ribavirin for 12 wks in HCV Geno 4 patients w-advanced fibrosis

Elisabetta Degasperi, Alessio Aghemo, Stefania Paolucci, Roberta D’Ambrosio, Marta Borghi, Riccardo Perbellini, Federica Novazzi, Stella De Nicola, Giovanna Lunghi, Fausto Baldanti, Pietro Lampertico

Publication stage: In Press Accepted Manuscript
Published online: February 12, 2018

Ombitasvir/Paritaprevir-ritonavir (OBT/PTV-r) plus Ribavirin (RBV) for 12 weeks in hepatitis C virus (HCV) genotype 4 patients with advanced fibrosis has been only investigated in clinical trials.

To assess safety and efficacy of OBT/PTV-r + RBV for 12 weeks in real-life HCV-4 patients with advanced fibrosis.

HCV-4 patients with advanced fibrosis consecutively receiving OBT/PTV-r + RBV for 12 weeks in a single center were enrolled. Fibrosis was staged by transient elastography (TE) (F3: ≥10 kPa; F4 ≥11.9 kPa) or histologically. Sustained virological response (SVR) was defined as undetectable HCV-RNA 12 weeks post-treatment.

Between January 2016 and February 2017, 49 HCV-4 patients were included: median age 54 (39-72) years, 84% males, 59% Egyptians, 35% fibrosis F3 and 65% F4, all Child Pugh class A. Median RBV dose was 1,200 (200-1,200) mg/day. At ITT analysis, 47 (96%) patients achieved an SVR (100% at PP analysis). SVR was not affected by ancestry (Egyptian vs. Italian 97% vs. 95%, p = 1.0), fibrosis stage (F3 vs. F4 100% vs. 94%, p = 0.53), presence of baseline resistance associated substitutions (RASs) or RBV reduction.

We report 100% SVR with 12-weeks of OBT/PTV-r + RBV in HCV-4 patients with advanced liver disease, including compensated cirrhotics.

Understanding Spontaneous Hepatitis C Virus Clearance

MD Magazine

Understanding Spontaneous Hepatitis C Virus Clearance
FEBRUARY 13, 2018
Elizabeth Kukielka, PharmD

Among patients in the acute phase of hepatitis C virus (HCV) infection, a portion will spontaneously clear the infection without treatment, and HCV RNA will completely disappear from the serum. Estimates from various studies project that anywhere from 20% to 30% of patients will spontaneously clear HCV, with the biggest factors being sex, ethnicity, immune status, and genetics.

Capacity of non-invasive hepatic fibrosis algorithms to replace transient elastography to exclude cirrhosis in people with HCV

Capacity of non-invasive hepatic fibrosis algorithms to replace transient elastography to exclude cirrhosis in people with hepatitis C virus infection: A multi-centre observational study
Melissa Louise Kelly ,Stephen M. Riordan,Rohan Bopage,Andrew R. Lloyd,Jeffrey John Post

Published: February 13, 2018

View Full Text Online

Achievement of the 2030 World Health Organisation (WHO) global hepatitis C virus (HCV) elimination targets will be underpinned by scale-up of testing and use of direct-acting antiviral treatments. In Australia, despite publically-funded testing and treatment, less than 15% of patients were treated in the first year of treatment access, highlighting the need for greater efficiency of health service delivery. To this end, non-invasive fibrosis algorithms were examined to reduce reliance on transient elastography (TE) which is currently utilised for the assessment of cirrhosis in most Australian clinical settings.

Materials and methods
This retrospective and prospective study, with derivation and validation cohorts, examined consecutive patients in a tertiary referral centre, a sexual health clinic, and a prison-based hepatitis program. The negative predictive value (NPV) of seven non-invasive algorithms were measured using published and newly derived cut-offs. The number of TEs avoided for each algorithm, or combination of algorithms, was determined.

The 850 patients included 780 (92%) with HCV mono-infection, and 70 (8%) co-infected with HIV or hepatitis B. The mono-infected cohort included 612 men (79%), with an overall prevalence of cirrhosis of 16% (125/780). An ‘APRI’ algorithm cut-off of 1.0 had a 94% NPV (95%CI: 91–96%). Newly derived cut-offs of ‘APRI’ (0.49), ‘FIB-4’ (0.93) and ‘GUCI’ (0.5) algorithms each had NPVs of 99% (95%CI: 97–100%), allowing avoidance of TE in 40% (315/780), 40% (310/780) and 40% (298/749) respectively. When used in combination, NPV was retained and TE avoidance reached 54% (405/749), regardless of gender or co-infection.

Non-invasive algorithms can reliably exclude cirrhosis in many patients, allowing improved efficiency of HCV assessment services in Australia and worldwide.