Friday, July 27, 2018

The thrill of curing hepatitis C and the pain of watching the disease surge with opioid abuse

World Hepatitis Day — July 28th
For World Hepatitis Day, learn more about the different types of viral hepatitis that impact millions worldwide and what CDC is doing to help eliminate hepatitis.

The following article was originally published on The Conversation.
Read the original article.

The thrill of curing hepatitis C and the pain of watching the disease surge with opioid abuse
Anna Suk-Fong Lok, Professor of Internal Medicine, University of Michigan
When I began my medical career in Hong Kong in the early 1980s, I chose to focus on hepatitis B, in part because it was very common and because the hepatitis C virus had not yet been discovered. I witnessed the devastation that this virus caused – cirrhosis, liver failure and liver cancer – and the lack of treatments we could offer to patients. Back then, scientists knew there was another type of hepatitis but no one could identify it, so we called it non-A, non-B hepatitis. I would never have imagined that during the course of my career I would witness the discovery of what came to be known as hep C and the development of a cure for nearly all patients with chronic hepatitis C in 2014.

The development of treatments other researchers and I have seen over the past 30 years reflects the amazing progress the field has made in tackling hepatitis C in a relatively short period of time. Initially, in the late 1980s, before a diagnostic test became available, some physicians started treating well-characterized cases of non-A, non-B hepatitis (hep C) with interferon, a natural protein that the body makes to fight virus, and ribavirin, an antiviral drug. These medications were not specifically developed for hepatitis C, had to be given as injections for 6-12 months, had many side effects and resulted in a cure in only half of the patients who received treatment. It took more than two decades for the first direct-acting antiviral drugs to be approved by the FDA. 

I remember the excitement when I and my colleagues tested one of the new drug combinations in patients and saw the virus count drop from more than 1 million to less than 20 within two weeks. We published the results of our pilot study in the New England Journal of Medicine in 2012. Although the study involved only 21 patients, it was considered a watershed moment because it was the first study to prove that a combination of oral pills without interferon can cure hepatitis C.

World Hepatitis Day is celebrated on July 28, the birthday of Dr. Baruch S. Blumberg, a Philadelphia researcher who shared the 1976 Nobel Prize in physiology or medicine for his discovery of the hepatitis B virus. 

Effective treatment for hepatitis C has become even more relevant today in light of the recent surge in new cases of hepatitis C due to rising opioid use.
A pricey drug and new generics

The first combo pill with two drugs that inhibits different steps in hepatitis C replication was approved by the FDA in 2014. This pill is taken once a day for 8-12 weeks, has little to no side effects and improved the cure rate to 90-95 percent. It was hailed as a magical cure, but it came with a price tag of US$94,500 for a 12-week course of treatment. That led many insurers in the United States and national health departments in other countries to limit access to treatment.

Since then, several other combo pills with similar cure rates that are equally well-tolerated have become available, and the cost has markedly decreased. In addition, low-cost generics and special pricing arrangements are available in many resource-limited countries.

While the current price of hepatitis C virus drugs is still very high, one needs to remember that for 95 percent of patients, this is a cure. It is unlike medicines for many illnesses that need to be taken for a long time, sometimes for the rest of the patients’ lives. Indeed, a cure for hepatitis C virus has allowed some patients who were on the liver transplant waiting list to reverse their liver failure, making transplantation unnecessary. This is good news not only for these patients but also for others on the waiting list.

The remarkable success of hepatitis C treatment has reenergized efforts to find a cure for hepatitis B. Current treatments can suppress hepatitis B virus replication but do not eliminate it. Most patients need to be on long-term treatment to prevent flares of hepatitis when the virus reemerges after treatment is stopped. 

Deaths from hepatitis B and C infections rising worldwide
Learning from the hepatitis C experience and with better understanding of the biology of hepatitis B virus and improved animal models, drugs that target different steps of the hepatitis B virus life cycle are being developed. While cure for hepatitis B will be more challenging because it can integrate into the patient’s DNA, enabling it to evade the patient’s immune response, I am optimistic that we will witness the availability of new combination of drugs that will move us nearer the goal of an hepatitis B virus cure.

Members of Delhi Network of Positive People, a support group for HIV-positive people, shout slogans during a protest in New Delhi, India, Friday, March 21, 2014. The activists urged the Indian government to allow production of generic versions of direct-acting antivirals, that can help thousands get affordable oral doses of medicine to control hepatitis C. Infection progresses more rapidly to damage the liver in HIV-positive patients, and co-infection of HIV and hepatitis C virus is common among HIV-infected injection drug users. 
Saurabh Das/AP Photo 

But the news is not all positive. While we’ve seen mortality rates from HIV, TB and malaria decline in recent years, mortality from hepatitis B and C has risen. Globally, an estimated 257 million people have chronic hepatitis B virus infection, and 71 million have chronic hepatitis C virus. Together hepatitis B and C caused 1.34 million deaths in 2015. This led the World Health Organization to challenge countries around the world to develop national plans to eliminate these two viruses by 2030.

Hepatitis B virus and hepatitis C virus are usually spread through contact with blood or body secretions such as semen from infected persons by sharing needles or sexual exposure. But they can also be spread through contaminated needles used for medical treatment, which continues to happen in many parts of the world. In addition, hepatitis B virus can be spread from infected mothers to newborn babies unless vaccination is given immediately after birth.

For hepatitis C virus, roughly two-third suffer chronic infection. For hepatitis B virus, the chance of chronic liver infection decreases the later the patient encounters the virus: 90 percent if infected during infancy; 20-30 percent if infected during childhood; and 2-5 percent if infected in adult life. Some people infected with hepatitis B virus or hepatitis C virus can recover on their own, but many go on to chronic infection (lasting more than six months and often years or lifelong). Those with chronic infection are at risk of cirrhosis (severe liver damage), liver failure and liver cancer.

Opioid epidemic, homeless lead to rise in hepatitis B and C infections
In this Nov. 8, 2017, photo, Christine Wade sits among her children in front of their donated tent in the city-sanctioned encampment on a parking lot in San Diego. The Wade family is among several hundred people living in the city’s first campground open for the homeless, set up to curb the worst hepatitis A outbreak in the United States in decades. 

In the United States, the number of new hepatitis B virus and hepatitis C virus infections has been decreasing for many years, but this trend has been reversed during recent years due to the opioid epidemic as more people use injection drugs, share needles or other paraphernalia and practice high-risk sexual behavior. This is particularly true for hepatitis C, where the number of new cases in the past 10 years has more than doubled, highlighting the need for a preventive vaccine, which is a vital tool if we want to eliminate hepatitis C. The increase in number of new cases of hepatitis B is smaller and mainly seen in adults in their 30s because most younger persons have benefited from hepatitis B virus vaccination.

When we talk about viral hepatitis, the focus is on hepatitis B and C because they can cause chronic infection, while hepatitis A causes only acute infection and will not lead to cirrhosis or liver cancer. However, starting late 2016, many states in the U.S. have witnessed outbreaks of hepatitis A. The Centers for Disease Control and Prevention (CDC) received more than 2,500 reports of hepatitis A between January 2017 and April 2018 associated with person-to-person transmission, with risk factors in two-thirds of these cases being drug use or homelessness or both. In the state of Michigan, where I live, 859 cases of hepatitis A including 27 deaths were reported between July 2016 and June 2018. We can prevent hepatitis A through vaccination and improved hygienic conditions.

As we celebrate World Hepatitis Day on July 28, a day chosen in honor of the late Dr. Baruch Blumberg, who received a Nobel Prize for discovering the hepatitis B virus, I marvel at how much progress we have made in the last three decades and am delighted to be not just an observer but also a contributor to the progress. Our work is not finished. Much more needs to be done to completely eliminate new cases of viral hepatitis and deaths from chronic hepatitis B and C.

Pain management in patients with cirrhosis

Clinical Liver Disease
Volume 11, Issue 6
Pages: 135-161
Clinical Liver Disease (CLD) is an online learning resource of American Association for the Study of Liver Diseases. CLD blends text, audio, video, webinars, and other interactive content into educational interventions launched every other month.

The latest publication of Clinical Liver Disease is all about cirrhosis, with a summary featuring: Pain management in patients with cirrhosis

Many of the commonly used over-the-counter analgesics such as acetaminophen and prescription pain relievers are metabolized through the liver, posing unique pain management challenges for patients and clinicians. This review will highlight the latter, and discuss the use of opioids, antidepressants, and marijuana, as well.
Patients with cirrhosis often experience pain. Yet pain remains one of the most undertreated symptoms in this patient population. A variety of medications are available to help address pain; however, several factors have to be taken into consideration prior to starting any pain regimen in patients with cirrhosis. Factors to consider include potential for overuse/abuse, severity of hepatic and renal impairment, and presence of hepatic encephalopathy. Chronic pain can be well managed in patients with cirrhosis; however, choice of analgesic and dosing regimen should be highly individualized and side effects carefully monitored.
Mina Rakoski, Preeya Goyal, Michelle Spencer-Safier, Jill Weissman, Gina Mohr and Michael Volk
Version of Record online: 26 JUL 2018 | DOI: 10.1002/cld.711
Watch a video presentation of this article
Full text

Table of Contents

AASLD Debate 2017

Radiology in Liver Disease
Begin here.... 

Updates Elsewhere
Hepatology News Tonight: Managing Complication of Cirrhosis
Naoky Tsai, MD; Ashwani K. Singal, MD
View: Managing Complication Of Cirrhosis, launched April 2018, provided by Chronic Liver Disease Foundation CLDF.

Thursday, July 26, 2018

EBR/GZR safe/effective for people with HCV receiving opioid agonist therapy

Clin Transl Sci. 2018 Jul 24. doi: 10.1111/cts.12564. [Epub ahead of print]

No Pharmacokinetic Interactions Between Elbasvir or Grazoprevir and Methadone in Participants Receiving Maintenance Opioid Agonist Therapy
Feng HP1, Guo Z1, Caro L1, Marshall WL1,2, Liu F1, Panebianco D1, Vaddady P1, Reitmann C1, Jumes P1, Wolford D1, Fraser I1,3, Valesky R1, Martinho M1, Butterton JR1, Iwamoto M1, Webster L4,5, Yeh WW1.

Download Full Text Article
View Online

We conducted two phase I trials to evaluate the pharmacokinetic interactions between elbasvir (EBR), grazoprevir (GZR), and methadone (MK-8742-P010 and MK-5172-P030) in non-hepatitis C virus (HCV)-infected participants on methadone maintenance therapy. Coadministration of EBR or GZR with methadone had no clinically meaningful effect on EBR, GZR, or methadone pharmacokinetics. The geometric mean ratios (GMRs) for R- and S-methadone AUC0-24 were 1.03 (90% confidence interval (CI), 0.92-1.15) and 1.09 (90% CI, 0.94-1.26) in the presence/absence of EBR; and 1.09 (90% CI, 1.02-1.17) and 1.23 (90% CI, 1.12-1.35) in the presence/absence of GZR. The GMRs for EBR and GZR AUC0-24 in participants receiving methadone relative to a healthy historical cohort not receiving methadone were 1.20 (90% CI, 0.94-1.53) and 1.03 (90% CI, 0.76-1.41), respectively. These results indicate that no dose adjustment is required for individuals with HCV infection receiving stable methadone therapy and the EBR/GZR fixed-dose regimen. PMID: 30040872 DOI: 10.1111/cts.12564

Continue to article:

Of Interest
New research: High burden of hepatitis C among people who inject drugs
(University of New South Wales) Globally, more than one in three (39 percent) people who have injected drugs in the last year are living with hepatitis C infection, according to new research from the National Drug and Alcohol Research Centre and the Kirby Institute at UNSW Sydney

HCV antiviral drugs during pregnancy?

Perspective > Medscape Gastroenterology > DDW 2018

Antiviral Therapy for HCV During Pregnancy to Prevent Transmission: 6 Reasons in Favor of a Controversial Concept
July 23, 2018
Nancy Reau 
During this year's Digestive Disease Week in Washington, DC, I was asked to present an argument in favor of the controversial concept of giving antiviral therapy to pregnant patients with HCV to disrupt mother-to-child transmission (MTCT). I must clearly state that this concept is neither evidence-based nor is it recommended by any of the current treatment guidelines. Universally, national and societal guidelines, as well as experts and patient advocates, recommend viral eradication of HCV prior to conception—not during pregnancy. There are, however, several reasons that support the use of HCV antiviral drugs during pregnancy
Read the article:
HCV: 6 Reasons in Favor of Antiviral Therapy During Pregnancy 
Dr Nancy Reau discusses factors that could potentially support the use of antiviral therapy during pregnancy to prevent mother-to-child transmission of hepatitis C virus infection.
Medscape Gastroenterology, July 23, 2018 
Free registration may be required.

Friday, July 20, 2018

Merck To Steeply Cut Price of Hepatitis C Drug Zepatier

Merck To Steeply Cut Price of Hepatitis C Drug Zepatier
July 20, 2018
The company announced that it plans to reduce other drugs in its portfolio as well. Merck will drop the price of its Hepatitis C drug Zepatier by 60%, the company announced yesterday. In addition, it plans to cut the price of “several other” drugs by 10%. In doing so, Merck went further than two competitors—Pfizer and Novartis—who said that they would not increase drug prices for the rest of 2018.
Read more:

Merck Is Lowering Drug Prices. There’s a Catch
July 19, 2018
The drugmaker Merck said Thursday that it would lower prices on several drugs by 10 percent or more, but its rollback affects minor products and would not lower the cost of its top-selling, expensive cancer and diabetes products.
Read more:

Of Interest
Roche Hiked Cancer-Drug Prices Before Pledge to Keep Them Flat
‎July‎ ‎20‎, ‎2018
For example, Fazeli said, Merck's hepatitis C treatment Zepatier was already facing competition from a cheaper, shorter-course treatment from AbbVie Inc. Merck said on Thursday it would cut Zepatier’s price by 60 percent as part of a commitment to responsible pricing. But the company probably would already have had to apply a hefty discount to the list price, Fazeli said.
Louisiana's New Approach To Treating Hepatitis C
Louisiana is working with Gilead Sciences and other companies on a deal that would change how the state pays for expensive hepatitis C drugs, with the goal of eliminating the disease in that state.
Despite highly effective and well-tolerated regimens for treating hepatitis C virus (HCV), patients face barriers in accessing treatment. In addition to suboptimal HCV screening programs and lack of effective linkage-to-care, other barriers include strict requirements from some payers to cover treatment. This study reports insurance status and Hispanic ethnicity as predictors of not receiving treatment. These barriers occur despite the fact that HCV is the most common indication for liver transplantation and cause of hepatocellular carcinoma in the U.S. Therefore, it is critical that policymakers bring all the stakeholders together and develop a national policy to eradicate HCV infection from the U.S.

July 9, 2018
The controversy over expensive new drugs for hepatitis C
Link to research and news articles addressing the high cost of hepatitis C drugs; insurance restrictions - private insurers/Medicaid - and availability of generic versions.

Thursday, July 19, 2018

Systematic overview of hepatitis C infection in the Middle East and North Africa

World J Gastroenterol. Jul 21, 2018; 24(27): 3038-3054
Published online Jul 21, 2018. doi: 10.3748/wjg.v24.i27.3038

Systematic overview of hepatitis C infection in the Middle East and North Africa
Karima Chaabna, Sohaila Cheema, Amit Abraham, Hekmat Alrouh, Albert B Lowenfels, Patrick Maisonneuve, Ravinder Mamtani 


Core Tip: Targeting specific populations at higher risk of acquiring HCV infection and treatment programs require the development of evidence-based health policies. HCV infection epidemiology in the countries of the Middle East and North Africa was characterized in 37 systematic reviews (SR) during the last decade. Our systematic overview critically analyzes and synthesizes the findings of these SRs to map the evidence gaps in the region. Additionally, we assessed the quality of the reported outcomes and documented conflicts of interest of the SR authors who disclosed financial relationships with pharmaceuticals.

To assess the quality of and to critically synthesize the available data on hepatitis C infections in the Middle East and North Africa (MENA) region to map evidence gaps.

We conducted an overview of systematic reviews (SRs) following an a priori developed protocol (CRD42017076736). Our overview followed the preferred reporting items for systematic reviews and meta-analyses guidelines for reporting SRs and abstracts and did not receive any funding. Two independent reviewers systematically searched MEDLINE and conducted a multistage screening of the identified articles. Out of 5758 identified articles, 37 SRs of hepatitis C virus (HCV) infection in populations living in 20 countries in the MENA region published between 2008 and 2016 were included in our overview. The nine primary outcomes of interest were HCV antibody (anti-) prevalences and incidences in different at-risk populations; the HCV viremic (RNA positive) rate in HCV-positive individuals; HCV viremic prevalence in the general population (GP); the prevalence of HCV co-infection with the hepatitis B virus, human immunodeficiency virus, or schistosomiasis; the HCV genotype/subtype distribution; and the risk factors for HCV transmission. The conflicts of interest declared by the authors of the SRs were also extracted. Good quality outcomes reported by the SRs were defined as having the population, outcome, study time and setting defined as recommended by the PICOTS framework and a sample size > 100.

We included SRs reporting HCV outcomes with different levels of quality and precision. A substantial proportion of them synthesized data from mixed populations at differing levels of risk for acquiring HCV or at different HCV infection stages (recent and prior HCV transmissions). They also synthesized the data over long periods of time (e.g., two decades). Anti-HCV prevalence in the GP varied widely in the MENA region from 0.1% (study dates not reported) in the United Arab Emirates to 2.1%-13.5% (2003-2006) in Pakistan and 14.7% (2008) in Egypt. Data were not identified for Bahrain, Jordan, or Palestine. Good quality estimates of anti-HCV prevalence in the GP were reported for Algeria, Djibouti, Egypt, Iraq, Morocco, Pakistan, Syria, Sudan, Tunisia, and Yemen. Anti-HCV incidence estimates in the GP were reported only for Egypt (0.8-6.8 per 1000 person-year, 1997-2003). In Egypt, Morocco, and the United Arab Emirates, viremic rates in anti-HCV-positive individuals from the GP were approximately 70%. In the GP, the viremic prevalence varied from 0.7% (2011) in Saudi Arabia to 5.8% (2007-2008) in Pakistan and 10.0% (2008) in Egypt. Anti-HCV prevalence was lower in blood donors than in the GP, ranging from 0.2% (1992-1993) in Algeria to 1.7% (2005) in Yemen. The reporting quality of the outcomes in blood donors was good in the MENA countries, except in Qatar where no time framework was reported for the outcome. Some countries had anti-HCV prevalence estimates for children, transfused patients, contacts of HCV-infected patients, prisoners, sex workers, and men who have sex with men.

A substantial proportion of the reported outcomes may not help policymakers to develop micro-elimination strategies with precise HCV infection prevention and treatment programs in the region, as nowcasting HCV epidemiology using these data is potentially difficult. In addition to providing accurate information on HCV epidemiology, outcomes should also demonstrate practical and clinical significance and relevance. Based on the available data, most countries in the region have low to moderate anti-HCV prevalence. To achieve HCV elimination by 2030, up-to-date, good quality data on HCV epidemiology are required for the GP and key populations such as people who inject drugs and men who have sex with men.

Tuesday, July 17, 2018

Protective liquid enables oral insulin delivery in rats

July 17, 2018
Protective liquid enables oral insulin delivery in rats
—by Sharon Reynolds

More than 30 million people in the United States live with diabetes, a disease in which the body has trouble managing and using blood glucose, the sugar that serves as the body’s fuel. Tens of millions more live with prediabetes, a condition where blood glucose levels are higher than normal, but not high enough to be considered diabetes. When blood sugar isn’t controlled for long periods of time, it can cause a range of health problems, including nerve damage and heart or kidney disease.

People with diabetes must actively monitor and control their blood sugar levels. Many need injections of insulin, a hormone that helps the body process glucose, several times a day to keep their blood sugar levels under control. But it can be difficult and painful to keep up with insulin injections. An oral form of insulin would drastically ease the difficulty of maintaining healthy blood sugar levels.

Insulin runs into many obstacles when taken by mouth. First, acid in the stomach can degrade it. Second, any insulin that reaches the small intestine from the stomach can be chopped up by the enzymes that help break down food. Finally, insulin needs to be absorbed into the bloodstream through the cells that line the small intestine.

A research team led by Dr. Samir Mitragotri of Harvard University has been exploring the uses of an ionic liquid called CAGE. Ionic liquids contain both positively and negatively charged molecules. CAGE is made from two non-toxic compounds, choline and geranate. In previous work, the team showed that CAGE could be used to deliver antibiotics and insulin through the skin of rats.

In their latest study, the team tested whether CAGE could protect insulin from degradation by the digestive system and help it through the intestinal lining. The research was funded in part by NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Results were published in the Proceedings of the National Academy of Sciences on July 10, 2018.

The researchers first tested whether their insulin-CAGE solution was stable. The structure and function of insulin remained intact in CAGE for 2 months at room temperature and at least 4 months when refrigerated.

When injected directly into the small intestines of non-diabetic rats, the solution quickly lowered blood sugar levels by up to 65%. Insulin-CAGE delivered through the small intestine lasted longer in the bloodstream than insulin injected under the skin.

The researchers next packaged insulin-CAGE into enterically coated capsules. Enteric coatings are resistant to stomach acid but dissolve when they reach the small intestine. When given by mouth to rats, the capsules caused a slow and steady drop in blood sugar, by about half over 10 hours. This drop was smoother and longer lasting than that caused by injection. Samples taken from the intestinal walls after administration showed no damage caused by the insulin-CAGE solution.

“Once ingested, insulin must navigate a challenging obstacle course before it can effectively be absorbed into the bloodstream,” Mitragotri says. “Our approach is like a Swiss Army knife, where one pill has tools for addressing each of the obstacles that are encountered.”

The researchers are now planning studies with diabetic animals to gauge the long-term safety and effectiveness of oral insulin-CAGE. They hope to eventually test the approach in a human clinical trial.

References: Ionic liquids for oral insulin delivery. Banerjee A, Ibsen K, Brown T, Chen R, Agatemor C, Mitragotri S. Proc Natl Acad Sci U S A. 2018 Jul 10;115(28):7296-7301. doi: 10.1073/pnas.1722338115. Epub 2018 Jun 25. PMID: 29941553.

Funding: NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); the National Science Foundation; Harvard University; and the Natural Sciences and Engineering Research Council of Canada.

HCV Next: Physicians Diagnosing,Treating HCV Define New Role in Opioid Crisis

Check out the July/August issue of HCV Next, just released online at Healio

Table of Contents
Cover Story 
Physicians Diagnosing,Treating HCV Define New Role in Opioid Crisis
The opioid epidemic in the United States has affected millions, exposing them to health risks that include a range of infectious diseases.

Point-of-Care HCV Assays: A Turning Point for Decentralized Diagnosis
Compared with traditional hepatitis virological tests, the benefit of point-of-care diagnostics is their use in patient care sites such as outpatient clinics, intensive care units, emergency departments and medical laboratories. Additionally, certain low- and middle-income countries have made use of point-of-care tests in blood banks.

In the Journals Plus
Most iatrogenic HCV cases unidentified until symptom onset
Insurance denials for HCV therapy increase in US

Meeting News
HCV outcomes worse for patients with public insurance, Medicaid
Homeless veterans with HCV diagnosed, treated via PCP outreach

Trend Watch

Begin here.....

On This Blog
The controversy over expensive new drugs for hepatitis C
Link to research and news articles addressing the high cost of hepatitis C drugs; insurance restrictions - private insurers/Medicaid - and availability of generic versions.

Efficacy of Generic Oral DAAs in Patients With HCV Infection
Journal of Viral Hepatitis, July 20, 2018

CDC: Liver cancer death rate up 43% since 2000

In The Media
CDC: Liver cancer death rate up 43% since 2000
By Allen Cone | July 17, 2018 at 9:54 AM
July 17 (UPI) -- Although the mortality rate for all cancers combined has declined over 25 years, death rates from liver cancer increased 43 percent for U.S. adults from 2000 to 2016, according to the Centers for Disease Control and Prevention....

CDC National Center for Health Statistics report
Trends in Liver Cancer Mortality Among Adults Aged 25 and Over in the United States, 2000–2016

NCHS Data Brief No. 314, July 2018
PDF Version
Jiaquan Xu, M.D.

Key findings 
Age-adjusted death rates for liver cancer increased 43%, from 10.5 per 100,000 U.S. standard population to 15.0 for men and 40%, from 4.5 to 6.3 for women, between 2000 and 2016. 

During 2000–2016, liver cancer death rates decreased 22% for non-Hispanic Asian or Pacific Islander (API) adults, but increased 48% for non-Hispanic white, 43% for non-Hispanic black, and 27% for Hispanic adults. 

Trends in liver cancer death rates varied by age group, but increasing trends from 2000 through 2016 were observed for adults aged 65–74 and 75 and over. 

In 2016, among the 50 states and the District of Columbia (D.C.), D.C. had the highest death rate while Vermont had the lowest.

Liver cancer (including intrahepatic bile duct cancer) was the ninth leading cause of cancer death in 2000 and rose to sixth in 2016 (1). Although death rates for all cancer combined have declined since 1990, a recent report documented an increasing trend in liver cancer death rates during 1990–2014 (2,3). In this report, trends in liver cancer death rates are examined by sex, race and Hispanic origin, and age group from 2000 through 2016 for adults aged 25 and over. Death rates in 2016 by state and the District of Columbia (D.C.) are also presented.

Sunday, July 15, 2018

New epidemic of hepatitis C, HIV, and other infections within the opioid abuse epidemic

Within opioid abuse epidemic, infectious disease epidemic emerges
Will Boggs MD

NEW YORK (Reuters Health) - There is a new epidemic of hepatitis C, HIV, and other infections within the opioid abuse epidemic, according to participants in a National Academies of Sciences, Engineering, and Medicine workshop.

There is an urgent need for actions to address this combined threat, they write in Annals of Internal Medicine,

“Opioid use disorder is like any other medical disorder, and through simple screening and starting medication treatment with the FDA-approved medications to prevent relapse to opioid use and decrease opioid craving, people can reduce acquiring infections,” Dr. Sandra A. Springer from Yale School of Medicine, New Haven, Connecticut told Reuters Health by email. “For those who do have associated infections at the time of screening, then starting treatment for their opioid use disorder can help them recover from their infectious diseases as well. Two for the price of one.”
Continue reading:
Sandra A. Springer, MD; P. Todd Korthuis, MD, MPH; Carlos del Rio, MD 
As a result of the opioid use disorder (OUD) epidemic (1), new epidemics of hepatitis C virus (HCV) and HIV infection have arisen and hospitalizations for bacteremia, endocarditis, skin and soft tissue infections, and osteomyelitis have increased (2–4). Optimal treatment of these conditions is often impeded by untreated OUD resulting in long hospital stays, frequent readmissions due to lack of adherence to antibiotic regimens or reinfection, substantial morbidity, and a heavy financial toll on the health care system. Medical settings that manage such infections offer a potential means of engaging people in treatment of OUD; however, few providers and hospitals treating such infections have the needed resources and capabilities (5). There is thus an urgent need to implement and scale up effective OUD treatment in health care settings to address the intersecting epidemics of OUD and its infectious disease (ID) consequences (6). The American College of Physicians (7), the Infectious Diseases Society of America (8), and the National Institutes of Health (9) have issued calls for action. Providers who treat the infectious complications of OUD, including ID physicians, hospitalists, emergency medicine physicians, intensivists, surgeons, obstetrician-gynecologists, pediatricians, nurses, advanced practice registered nurses, and physician assistants are at the forefront of these epidemics and are well-positioned to integrate OUD treatment in the context of ID management.

Thursday, July 12, 2018

Challenges and perspectives of direct antivirals for the treatment of hepatitis C virus infection

Journal of Hepatology
Challenges and perspectives of direct antivirals for the treatment of hepatitis C virus infection
JohannesVermehren, James S. Park, Ira Jacobson, StefanZeuzem


Follow On Twitter 
The following full-text articles downloaded and shared by Henry E. Chang.

Treatment of chronic hepatitis C virus (HCV) infection has been revolutionized with the development of direct-acting antiviral agents (DAAs). Eight to twelve weeks of all-oral, once-daily treatments is now the standard of care and viral eradication can be achieved in >95% across different patient populations. Despite these advances, several unresolved issues remain, including treatment of HCV genotype 3, chronic kidney disease, and in patients in whom DAA therapy has failed. Glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) are the most recently approved DAA regimens. Given the overwhelming success of modern DAA-based therapies, GLE/PIB and SOF/VEL/VOX are also likely to represent the last DAAs to be approved. Both are pangenotypic, once-daily, all-oral DAA combinations that have the potential to close the gaps in the current DAA treatment portfolio. Here, we review the challenges associated with current DAAs and how these two regimens may be implemented in existing treatment algorithms.

Of Special Interest
Hepatitis C Management Simplification From Test to Cure:A Framework for Primary Care Providers
SOF/VEL or GLE/PIB), both highly tolerated and effective for all genotypes.

Sofosbuvir and Ledipasvir is Associated with High Sustained Virologic Response and Improvement of Health-Related Quality of Life in East Asian Patients with Hepatitis C Virus Infection
In summary, our data clearly show the superiority of IFN-free RBV-free LDV/SOF in East Asian patients with chronic HCV genotype 1 infection. The advantages of that regimen are related not only to its high efficacy and excellent tolerability but also to significantly better quality of life during treatment and after achieving SVR. These data provide evidences up porting the comprehensive benefit of LDV/SOF for eligible patients which should inform all stakeholders, including providers, payers, and policy makers in East Asian countries

Absolute denials of DAA regimens by insurers in the U.S. have remained high & increased over time, regardless of type of insurance.

Northwestern Medicine study has newly identified a trigger of some fibrotic diseases

Why internal scars won't stop growing Rogue molecules provoke out-of-control scar tissue, strangle organs 
Northwestern University

-New compound discovered that halts some fibrotic diseases
-Fibrosis accounts for up to 40 percent of all global deaths
-Human fibrotic cells reveal immune abnormality 

CHICAGO --- Normal scar tissue forms to heal an internal wound and quietly retreats when the job is done. But in many common diseases - kidney, liver and lung fibrosis -- the scar tissue goes rogue and strangles vital organs. These diseases are largely untreatable and ultimately fatal.

A new Northwestern Medicine study has newly identified a trigger of some fibrotic diseases and an experimental compound to treat it.

Fibrosis - a progressive scarring and hardening of internal organs - is estimated to cause 35 to 40 percent of deaths in the world. Fibrotic diseases include diabetic kidney fibrosis, alcoholic liver cirrhosis, hepatitis C, pulmonary fibrosis and nonalcoholic fatty liver disease, which may lead to fibrosis of the liver, the leading cause of liver transplant.

In one subset of human fibrosis cells, scientists discovered a delinquent gang of molecules that continually shouted at an immune receptor - the antennae on the cell -- to produce scar tissue instead of quieting down and allowing the scar tissue to go back to sleep.

Scientists collaborated with a University of Colorado researcher who used crystallography and computer modeling to predict a molecule that could block the receptor that leads to the uncontrolled scarring. When they tested the molecule, T53, in three different mouse models of fibrosis, the abnormality was significantly reversed.

"Our study opens a new door into fibrosis by looking at it as an aberrant innate immune response and suggesting a novel approach to treat it," said senior author Dr. John Varga, director of the Northwestern Scleroderma Program and the John and Nancy Hughes Distinguished Professor of Rheumatology at Northwestern University Feinberg School of Medicine.

The paper will be published July 12 in the Journal of Clinical Investigation Insight.

"The leading cause of liver failure in western world is obesity and that's because of liver fibrosis," Varga said. "In the U.S., many of these diseases are lifestyle or age dependent. As we get fatter or older, they get worse."

Most fibrotic disease likely begins as normal repair of an injury, scientists said. "But if the immune system produces too much of an initial scar, it can't go back to normal," Varga said. "You have an unhealed scar that keeps growing and can wipe out the entire organ."

Not everyone's fibrosis is caused by the same abnormality, Varga said. If the compound, T53, is eventually developed into an approved drug, it would be targeted to patients with the specific genetic signature identified in the study.

"There is an emerging direction for treating fibrosis with precision medicine," said first author Swati Bhattacharyya, research associate professor of medicine in rheumatology and scientific director of the Scleroderma Research Laboratory at Feinberg. "Some people live with fibrotic disease for 30 years while others die in two years. We need to identify the rapid progressors from the slow progressors. That's where precision medicine becomes really critical."

"The results of this study are encouraging," Varga said. "We are not saying this compound is ready to be a drug. It's an initial compound that would need to be developed and tweaked. It would need significant funding to go to the next step."

Varga has spent more than a decade researching the cause and treatment of scleroderma, a type of fibrosis that simultaneously affects multiple organs. He directs the Northwestern Scleroderma Program, a clinical and research effort that follows 1,500 patients with scleroderma.

Wednesday, July 11, 2018

Hepatitis B—stopping a silent killer

Hepatitis B—stopping a silent killer

July 11, 2018, University of Michigan

Every year, hepatitis B kills more than 780,000 people around the world, and is the single most serious liver infection, according to the World Health Organization.

David Hutton, associate professor of health management and policy at the University of Michigan’s School of Public Health, says early diagnosis and treatment is key to stopping the spread of the disease in the United States.

He co-authored a study published in Health Affairs that shows testing and treating immigrants from high-risk countries living in the U.S. could help dramatically improve their long-term quality of life, reduce hepatitis B-related diseases such as liver cancer and cirrhosis, and save money in the long term.

What is hepatitis B and who does it affect?

Hutton: Hepatitis B is a blood-borne viral infection that affects the liver. It’s pretty contagious and can be transmitted by blood or bodily fluids, so through things like sharing razors and toothbrushes. It’s been called the silent killer because it is asymptomatic—you might have the virus but not know until it manifests itself until much later.

In the United States, there aren’t that many people who actually acquire hepatitis B because since the early 1980s we’ve been pretty good about vaccinating people and if you’re vaccinated at birth, it’s very good at preventing mother-to-child transmission and also transmission in early childhood. Right now, chronic hepatitis B affects largely nonwhite foreign-born people from Asia and Africa.

How about at a global level?

Hutton: There are a lot of countries where prevalence of hepatitis B is higher because it’s historically been more prevalent there, and because there have been delays and not very good coverage of the hepatitis B vaccine. So, for example, in China it was only made as part of their national immunization plan and made free in the last 10 to 15 years. People who are in their 30s or 40s from China and who immigrated to the United States probably weren’t vaccinated at birth and probably were exposed to hepatitis B from their mothers or friends.

How can you diagnose, treat and cure hepatitis B?

Hutton: There is no cure for hepatitis B. Many people do not know they have it because it usually takes decades for it to manifest itself in terms of cirrhosis or liver cancer, which are very nasty, difficult to treat and have high impacts on quality of life and high mortality.

The good news is there are antiviral treatments. I like to think of it as similar to HIV treatments, so you’re going to be taking pills for the rest of your life. But they’re highly effective and they have very few side effects.

So it’s certainly a disease that can be managed and, if treated, it dramatically reduces the viral load and reduces liver complications like cirrhosis and liver cancer. But because it can be asymptomatic, the key is in testing.

Tell me about your research. Why did you focus on immigrants?

Hutton: We wanted to look at the cost-effectiveness and population health impact of an increase in diagnosis, care and treatment of hepatitis B to meet the World Health Organization’s goals for 2030.

Because the majority of the estimated 1.29 million people living with hepatitis B in the U.S. are adults who, particularly in the Asian and black populations, were born abroad, we developed a model to simulate the prevalence of foreign-born Asian and black adults currently living in the U.S. and projected migration from high-risk areas.

We calculated the costs of screening—either by their personal doctors, through community organizations or health care systems—and examined three diagnosis, care and treatment scenarios to calculate the costs.

What were the results?

Hutton: Based on our analysis, if we met WHO targets for diagnosis and treatment by 2030 (having 90 percent of cases diagnosed and 80 percent treated), we would reduce deaths by 37 percent, reduce liver cancer by 35 percent and decompensated cirrhosis by 51 percent. And, depending on the cost of antiviral drugs, the measures could actually save money.

One of the measurements of health we use is a quality-adjusted life-year. It is a way of aggregating together the loss of quality of life and length of life onto a single measure where one quality-adjusted life-year is equivalent to one year in perfect health. We calculated that meeting these targets would result in 474,000 quality-adjusted life-years gained. At current treatment costs, meeting these goals would mean a net increase in costs of $49 million. But, that means we are only paying $103 per quality-adjusted life-year. We routinely spend more than $50,000 per quality-adjusted life-year gained on other medical interventions. For example, screening all women aged 40-80 annually for breast cancer costs $58,000 per additional quality-adjusted life-year gained. If we achieve the hepatitis B goals earlier or if the treatment cost drop, meeting these WHO goals could be cost-saving.

Why do you think testing is so important?

Hutton: A lot of public health interventions don’t save money. This is one of those rare cases where the intervention actually can save money over the long run and improves people’s quality of life. Over the long run, if you’re going to prevent cirrhosis or liver cancer, and the need for liver transplants—those can get very, very expensive—you’re going to save money and improve people’s lives, especially in these sometimes underrepresented and marginalized groups.

What do you hope people learn from your study?

Hutton: If they are immigrants from Africa and Asia who are in the U.S. but have not been tested, they should get tested as soon as possible. Testing is very simple. And if you find that you have hepatitis B, know that is a manageable treatment that can be very valuable at preventing terrible liver disease.

All-oral direct antiviral treatment for hepatitis C in a real-life cohort: The role of cirrhosis and comorbidities in treatment response

All-oral direct antiviral treatment for hepatitis C chronic infection in a real-life cohort: The role of cirrhosis and comorbidities in treatment response 
Noelle Miotto , Leandro Cesar Mendes, Leticia Pisoni Zanaga,Maria Silvia Kroll Lazarini, Eduardo Sellan Lopes Goncales, Marcelo Nardi Pedro, Fernando Lopes Goncales Jr, Raquel Silveira Bello Stucchi, Aline Gonzalez Vigani

Full Article

Hepatitis C virus (HCV) infection is the major cause of end-stage liver disease (LD) worldwide. The aim of this study was to assess sustained virological response (SVR) rates in a real-world cohort of patients with HCV infection treated with interferon-free direct antiviral agents (DAA).

Patients and methods
All patients with genotypes 1, 2 or 3 HCV infection who started interferon-free treatment at a university hospital from December 2015 through July 2017 were included. The primary outcome was SVR at post-treatment week 12 by intention-to-treat (ITT) and modified ITT (mITT) analysis.

Five hundred twenty seven patients were enrolled, 51.6% with cirrhosis. Most patients received sofosbuvir + daclatasvir + ribavirin (60.7%) and sofosbuvir + simeprevir (25.6%). Overall SVR rates were 90.5% for ITT and 96% for mITT. SVR rates were higher in non-cirrhotic (94.2% in ITT and 96.8% in mITT) versus cirrhotic patients (87.1% in ITT and 95.2% in mITT). In ITT and mITT assessments, SVR rates were higher in patients with Child-Pugh A (n = 222, 88.7% and 95.7%, respectively) versus Child-Pugh B or C (n = 40, 80% and 90%, respectively); SVR rates were higher in patients with genotype 1 (n = 405, 92.1% and 98.2%), followed by genotype 2 (n = 13, 84.6% and 92.7%) and genotype 3 (n = 109, 84.4% and 88.4%). Lower comorbidity index (p = 0.0014) and absence of cirrhosis (p = 0.0071) were associated with SVR. Among cirrhotic patients, lower Model for End-Stage Liver Disease (p = 0.0258), higher albumin (p = 0.0015), and higher glomerular filtration rate (p = 0.0366) were related to SVR. Twenty-two cirrhotic patients (8%) had clinical liver decompensation during treatment. Complications of advanced LD were responsible for discontinuation of treatment and death in 12 and 7 patients, respectively.

Treatment with all-oral DAA achieved high SVR rates, particularly in patients without cirrhosis and few comorbidities. Advanced LD is associated to poor outcome, such as treatment failure and death.

Tuesday, July 10, 2018

July Updates: Hep C Symptoms – How Do Yours Compare?

In The Journals - Catch up with what you may has missed.

Hep C Symptoms – How Do Yours Compare?
Welcome to this months hand-picked hepatitis newsletters, and recommended blogs from around the web. We start over at, where you can read about an array of hepatitis C symptoms, review a poll on the subject, and finally scan all the new blog entries.

Blog Updates Around The Web 
Check out the following articles from your favorite bloggers, along with this months viral hepatitis newsletters.

Lucinda K. Porter
Lucinda Porter is a nurse, speaker, advocate and patient devoted to increasing awareness about hepatitis C.
Latest: Freedom from Worry

Hep is an award-winning print and online brand for people living with and affected by viral hepatitis.
Latest: Remember Your “Bear” Story When Fighting Hepatitis C and Liver Disease
Liver Health: Yet Another Reason to Avoid Alcohol

Life Beyond Hepatitis C
Life Beyond Hep C is where faith, medical resources and patient support meet, helping Hep C patients and their families navigate through the entire journey of Hep C.
Latest: Feeling Depleted with Hepatitis C?

I Help C
Your Best Friend’s Guide to Hepatitis C and Cirrhosis
Latest: All Shook Up with PTSD from Liver Disease

A comprehensive website for HIV and hepatitis C information
Latest: What it will take to eliminate hepatitis C in Canada

Canadian Liver Foundation 
We strive to improve prevention and the quality of life of those living with liver disease by advocating for better screening, access to treatment, and patient care.
Latest: ‘HepBeware’ It begins with a diagnosis.

AGA Journals
Latest: Can Nonlytic T cells be Engineered to Fight HBV Infection?

Hepatitis B Foundation 
The Hepatitis B Foundation is a national nonprofit organization dedicated to finding a cure and improving the quality of life for those affected by hepatitis B worldwide.
Latest: - Finding the Missing Millions in Ghana

An ongoing dialogue on HIV/AIDS, infectious diseases, all matters medical, and some not so medical.
Latest: Surgeon Who Was Denied Disability Insurance for Taking PrEP Tells His Story

The Hepatitis C Mentor and Support Group 
Latest: Needle exchanges have been proved to work against opioid addiction. They’re banned in 15 states.

HCV Advocate
The HCV Advocate newsletter is a valuable resource designed to provide the hepatitis C community with monthly updates on events, clinical research, and education.
July Issue
In this month’s HCV Advocate newsletter we have a plethora of articles for your reading and learning pleasure:
HealthWise: Avoiding Fatty Liver by Lucinda Porter, RN. 
Lucinda shares her personal and professional tips to help you avoid or reduce fatty liver disease.

Hepatitis Headlines:
AASLD and IDSA Announce Updates to HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C
The Canadian Association for the Study of the Liver recommends that Canadians born between 1945 and 1975 should be tested for hepatitis C

Evaluation of Instruments used to Measure Hepatitis C Patient-Reported
Symptoms by Alan Franciscus. 
This is the first in a series of studies from a PCORI funded study. The first one was to evaluate the reliability and validity of several survey instruments.

by Alan Franciscus. 
In this month’s column I write about the following studies:
Prognostic value of viral eradication for major adverse cardiovascular events in hepatitis C cirrhotic patients
Evaluation of the Xpert HCV Viral Load Finger-Stick Point-of-Care Assay
Gut dysbiosis associated with hepatitis C virus infection
Hepatocellular carcinoma incidence and survival among people with hepatitis C an international study
Hepatitis C care in the Department of Veterans Affairs: Building a foundation for success
Impact of sustained virological response on the extrahepatic manifestations of chronic hepatitis C: a meta-analysis
Viral hepatitis screening in transgender patients undergoing gender identity hormonal therapy 

We have updated our entire series of Easy C Facts
View all newsletters here....

Weekly Bull
HepCBC is a Canadian non-profit organization offering awareness with basic information about HCV and a weekly digest of news.
Read the latest issue of the highly successful Weekly Bull.

Hep - Your Guide to Hepatitis
Hep is an award-winning print and online brand for people living with and affected by viral hepatitis. Offering unparalleled editorial excellence since 2010, Hep and are the go-to source for educational and social support for people living with hepatitis.
View - all issues
Read the news
Check out the talented people who blog at Hep.

The National Viral Hepatitis Roundtable
The National Viral Hepatitis Roundtable (NVHR) is national coalition working together to eliminate hepatitis B and C in the United States.
July Newsletter

The New York City Hepatitis C Task Force
The New York City Hepatitis C Task Force is a city-wide network of service providers and advocates concerned with hepatitis C and related issues. The groups come together to learn, share information and resources, network, and identify hepatitis C related needs in the community. Committees form to work on projects in order to meet needs identified by the community.
View: Hep Free NYC Newsletters
Review all news updates.

HCV Action
HCV Action brings together hepatitis C health professionals from across the patient pathway with the pharmaceutical industry and patient representatives to share expertise and good practice.
View recent newsletters

World Hepatitis Alliance
We run global campaigns, convene high-level policy events, build capacity and pioneer global movements, ensuring people living with viral hepatitis guide every aspect of our work.
View Recent Newsletters 
World Hepatitis Alliance (WHA) presents hepVoice, a monthly magazine with updates on the latest projects, news from WHA members and key developments in the field of hepatitis.

GI & Hepatology News
Over 17,000 gastroenterologists and hepatologists rely on GI & Hepatology News every month to cover the world of medicine with breaking news, on-site medical meeting coverage, and expert perspectives both in print and online.
View all updates here....

CATIE strengthens Canada’s response to HIV and hepatitis C by bridging research and practice. We connect healthcare and community-based service providers with the latest science, and promote good practices for prevention and treatment programs.
Updates - News
What's New?
Continuing care needed for HIV-positive people after hospitalization for mental health issues
HepCinfo Update 9.13: Half with HIV/HCV untreated for HCV; HCV cure improves fatty liver; community-based liver screening feasible

Hepatitis Victoria
Hepatitis Victoria is the peak not-for-profit community organisation working across the state for people affected by or at risk of viral hepatitis.
July Newsletter - Download We also produced short podcasts interviewing health experts and practioners on topics related to viral hepatitis - come have a listen!

British Liver Trust
The British Liver Trust is the leading UK liver disease charity for adults – we provide information and support; increase awareness of how liver disease can be prevented and promote early diagnosis; fund and champion research and campaign for better services.
View Recent Newsletters, here.

Hepatitis B Foundation
Hepatitis B Foundation is a national nonprofit dedicated to finding a cure and improving the quality of life for people affected by hepatitis B worldwide.
All newsletters, sign up
Blog & News

National Institutes of Health
A monthly newsletter from the National Institutes of Health, part of the U.S. Department of Health and Human Services
Read: July Newsletter

Thanks for stopping by!

N.J. Expands hepatitis C treatments for all Medicaid enrollees

N.J. Expands Vital Hepatitis C Treatments for Medicaid Enrollees 

TRENTON – The New Jersey Department of Human Services announced expanded hepatitis C treatments for all Medicaid enrollees in the state, a policy facilitated by increased funding in the fiscal year 2019 budget.

The improvement comes amid ongoing concern about increased infections due to the opioid epidemic and a growing focus on identifying and treating hepatitis C infection among Baby Boomers.

New Jersey Human Services Commissioner Carole Johnson said that under the new policy, New Jersey Medicaid will cover hepatitis C curative drug treatment once someone is diagnosed with the virus. Previously, individuals in New Jersey were required to wait until their liver had already been damaged before accessing this treatment.

Hepatitis C management simplification from test to cure: a framework for primary care physicians

Clinical Therapeutics
Available online 5 July 2018
In Press, Corrected Proof

Hepatitis C Management Simplification From Test to Cure: A Framework for Primary Care Providers 
Shashi N. Kapadia, MD, MS; and Kristen M. Marks, MD, MS
Weill Cornell Medicine, Division of Infectious Diseases, New York, New York
Weill Cornell Medicine, Division of Infectious Diseases, New York, New York
Shashi N. Kapadia, MD, MS; and Kristen M. Marks, MD, MS

This article proposes a strategy for primary care providers to begin treating patients with hepatitis C virus (HCV). We are motivated by the need to expand HCV treatment and by developments that have simplified treatment for most patients. This article presents 5 steps to achieving quality HCV treatment in the primary care setting: (1) accurate diagnosis via reflex testing; (2) risk stratification and identifying comorbidities via pretreatment evaluation; (3) simple, once-daily, pan-genotypic HCV treatment regimens; (4) minimized on-treatment monitoring: and (5) posttreatment monitoring and high-quality care for comorbidities such as cirrhosis and injection drug use. We provide indications for referral to specialists: notably children, patients with genotype 3 and cirrhosis, advanced liver or kidney disease, previous treatment failures, drug interactions with recommended regimens, and hepatitis B co-infection. Finally, potential barriers for providers are discussed, as well as further research findings and policy interventions that can promote HCV treatment in the primary care setting. We believe that a substantial portion of patients with HCV can be treated safely and effectively by nonspecialists and that the engagement of primary care providers is critical to efforts to end the HCV epidemic.

Continue to full text article:

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Full-text article shared by Henry E. Chang.

Monday, July 9, 2018

Targeting non-alcoholic fatty liver disease

In Case You Missed It
In the July Issue of the patient-friendly HCV Advocate newsletter, Lucinda Porter, RN., writes a must read article about: Avoiding Fatty Liver.

Targeting non-alcoholic fatty liver disease
One of the lines of research of the UPV/EHU's Lipids & Liver group, which focusses on the mechanisms involved in the development and progression of non-alcoholic fatty liver disease, is achieving significant advances in a range of aspects; these include the identification of proteins that alter the metabolic pathways in the development and progression of liver disease, and even cancer, and the seeking of targets to enable the disease to be reversed.

According to the latest figures, non-alcoholic fatty liver disease affects 30% of the general population, and this percentage rises to between 70% and 80% in certain risk groups, such as obese patients, patients with diabetes, etc., due to the fact that the latter is linked to metabolic diseases. The disease begins with a simple build-up of fat or lipid in the liver which in principle may be benign but which in some patients may progress and lead to hepatitis, steatohepatitis, because of its inflammation, and this is a risk factor for developing hepatic cirrhosis and even liver cancer. Right now, there is no specific treatment for this disease, and owing to the current high prevalence of obesity and diabetes, it is forecast that within a few years liver cancer cases caused by this fat storage could soar, as could the number of transplants caused by non-alcoholic steatohepatitis.

The Lipids & Liver research group in the department of Physiology at the UPV/EHU’s Faculty of Medicine and Nursing is working to find out what mechanisms are involved in the development and progression of liver diseases, and mainly the mechanisms related to alterations linked to lipid (fat) metabolism. Specifically, one of the group’s lines of research, which focusses on the study of non-alcoholic fatty liver disease, is involved in research that aims to “find out why the disease develops in some patients and not others; to find evolution markers that can provide us with a prognosis as to which patients are going to develop the disease; and to find not only hepatic markers (that can be obtained through biopsy) but also serum markers, which by means of simple blood tests can say which phase the patient is in”, explained Dr Patricia Aspichueta, head of the line of research.
The liver is the metabolic centre of the whole body

Basically, the members of the research group are focusing on the study of lipid metabolism in the liver, in other words, on the chemical reactions in which they are formed or consumed. To do this, they work with animal models in which a gene has been silenced and to which different diets and treatments designed to induce the disease are given, and once a target in the animal model has been confirmed or identified, they proceed to validate it in human samples. What is more, they also work with in vitro or cell models, “because there it is easier to find out in which cell the metabolism has been damaged, modified or altered, we can play around with different drugs, different inducers, and it is easier to silence specific metabolic pathways, etc.”, explained Aspichueta.

The members of the group are studying different molecules or targets involved in various liver disease processes. Aspichueta specifies some of the pathways that they have open in the research group: “Firstly, we want to identify the proteins that alter the metabolic pathways and which supply the liver with more lipid. We want to find out why this lipid store forms, and why the store causes the disease to progress to phases such as cancer, even. It is important to know which players are involved in these processes to be able to silence them and see if the disease is reversed.” They are also exploring the involvement of lipids in liver regeneration, “a hugely important perspective with respect to patients who have had a portion of their liver removed, because the liver is the only organ that regains its normal size”. In another of the studies they are exploring “how the liver controls adipose tissue, and how by modulating liver function we can get animals to lose weight”.

Aspichueta confirms that they have found “an important therapeutic target that modulates the metabolism and the progression of the disease”. They have induced the development of liver cancer associated with obesity in animal models in which this protein has been silenced and “we have seen that the animals do not develop the disease at all: neither liver cancer nor the fat store. It’s amazing,“ said the doctor. Now “we are working on human samples of non-alcoholic fatty liver disease to validate the involvement of these proteins in human pathology”. The researchers are aiming to find targets that control several metabolic pathways at the same time, “because the metabolic alteration does not take place in a single pathway, rather a decompensation takes place, the metabolism becomes unbalanced and various pathways are affected,” she concluded. The liver is the metabolic centre, and if we control the liver we can control many disorders associated with this liver disease”.
Additional information

The Lipids & Liver research group has been recognised as a Consolidated Group by the Department of Education of the Basque Government since 2007. Its research work relating to the Physiopathology of Lipid Metabolism comes within the strategic Health and Life Quality line of the Spanish Ministry of the Economy and Competiveness and of the Basque Government, in the sphere of the Euskampus biomedicine and healthy Ageing and life quality.

The group works in close collaboration with various research groups at the UPV/EHU as well as external ones with which they have had numerous publications in various scientific journals. The group is part of the Biocruces Institute for Health in which it broadens its research to the disorder in humans. It also collaborates with CIC bioGUNE, the University of Santiago de Compostela, other groups in Madrid, the Hospital of Valdecilla (Santander), as well as with the University of South Carolina and Yale University. It also works with an American pharmaceutical company in the quest for treatment targets.