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As 2015 came to a close, the world’s leading hepatologists, scientists, and other healthcare professionals gathered in San Francisco to discuss the latest liver disease research and treatment outcomes.
The American Liver Foundation attended this international conference, known as The Liver Meeting, which is organized by the American Association for the Study of Liver Diseases (AASLD). We had a correspondent onsite to help bring the latest liver news to you. We hope that you followed us on Facebook, twitter and other social media, during this conference for timely updates.
Today, we are pleased to provide readers of our e-newsletter, Liver Lowdown, with a few highlights from The Liver Meeting.
Several of the presentations at the conference demonstrated that too many Americans are still unaware of the liver’s role, their risks of liver disease, and the importance of maintaining good liver health.
In a recent survey (commissioned by Intercept Pharmaceuticals) a whopping 42% of respondents believe that a person can live without a liver or were unsure.
The survey also found that liver disease ranks low on American’s list of health concerns.
• 45% of survey respondents were concerned about heart disease,
• 40% of women surveyed said that they were concerned about breast cancer, and
• nearly one-third of male respondents expressed a concern about prostate cancer.
However, less than 20% of respondents expressed a concern about liver disease. This is surprising since some studies suggest that as many as two in ten adults in the U.S. may have nonalcoholic fatty liver disease.
Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) took center stage at the conference. Scientists reported on potential new screening tools and therapies for treating the condition.
Nonalcoholic Fatty Liver Disease, the most common liver disease in the western world, is characterized by a build-up of excessive fat in the liver. In recent years, the prevalence of NAFLD has grown proportionally with the rise in obesity, sedentary lifestyle, fast-food diets and diabetes.
NAFLD may develop into the more serious nonalcoholic steatohepatitis (NASH).NASH causes inflammation and accumulation of fat and fibrous (scar) tissue in the liver. Like NAFLD, nonalcoholic steatohepatitis is often a silent disease. Patients with NASH are at high risk of developing cirrhosis and liver cancer.
NAFLD can sometimes be reversed with treatment of the conditions that contribute to its development – including weight management, as well as control of diabetes, high cholesterol, and high triglycerides. However, there is currently no cure for NASH, and it is fast becoming one of the leading reasons for liver transplants.
One of the big announcements at the Liver Meeting was newly published guidelines for the management of NAFLD and NASH by the American Association for the Study of Liver Disease (AASLD) and the American College of Gastroenterology (ACG). To learn more about these protocols, please click on the link below. http://www.gastro.org/journals-publications/gastroenterology/NAFLD_Guideline_6-12.pdf
At present, the only way to definitely assess the state of liver destruction is by examining liver cells taken with a biopsy. To increase the rate of testing, a non-invasive way of evaluating the progression of NAFLD to NASH is necessary. Japanese researchers are looking into the presence of two sugar molecules (glycobiomarkers) that can be found in blood tests as a non-invasive way to distinguish NAFLD from NASH and to facilitate diagnosis of NASH.
Currently, there is no approved drug therapy for treating NAFLD/NASH. However, research presented at the Liver Meeting suggests that such treatments may be down the road.
• Researchers announced the design of a phase 3 trial to evaluate the benefits of Elafibranor on NASH Patients. In a phase 3 trial, the drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
• Another promising treatment is Obeticolic Acid (OCA), an investigational drug that is being studied in NASH patients. In a trial sponsored by the National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK), treatment with once daily 25 mg OCA was shown to reverse fibrosis in a significant proportion of biopsy-proven NASH patients, as observed by repeat liver biopsy at the end of the double-blind treatment phase (week 72). Research presented at The Liver Meeting 2015 suggested that baseline characteristics and changes in clinical parameters may be helpful in predicting histological response to OCA therapy in adults with NASH and further evaluation with larger patient numbers is warranted.
Dr. Rohit Loomba of the University of California in San Diego, presented a study demonstrating that parents, children, and siblings (first-degree relatives) of patients with advanced fibrosis (NAFLD-cirrhosis) are at 12 times higher risk of developing the condition than the control group was. Dr. Loomba, a member of the ALF National Board of Directors and National Medical Advisory Committee recommends that all first-degree relatives of patients with NAFLD-cirrhosis should be screened.
Hepatitis C remained a hot topic at this year’s Liver Meeting. Researchers reported on several Phase III clinical trials for both new drugs and drug combinations.
The AASLD also issued an important statement at the Liver Meeting, recommending early treatment of chronic HCV infection before the development of severe liver disease to improve overall survival rates. In its statement, the AASLD said:
Over the past two-plus years, the Food and Drug Administration has approved multiple new treatments for hepatitis C virus (HCV) that offer nearly universal cure rates with minimal side effects. It is a remarkable success story for medical science. Unfortunately, many insurers – both private and public – are delaying access to new HCV treatments to patients until their disease has progressed and the liver is further damaged. There is no medical evidence to justify that position and much to justify treating all patients.
• A new once-daily pill combining two different drugs to treat genotypes 1-6 chronic Hepatitis C infection is now in testing and could soon give physicians a bigger arsenal of drugs with which to treat patients. The pill combines sofosbuvir (SOF), an already approved drug, with the drug, velpatasvir (VEL). SOF/VEL has the potential to simplify treatment and eliminate the need for HCV genotype testing.
The researchers reported on the results of their patient study in which these two drugs were tested in patients with the six different subtypes of Hepatitis C infection and cirrhosis. Some of the patients suffering from advanced (decompensated) cirrhosis took the drug for 12 weeks along with ribivarin (RBV), others for 24 weeks.
This study generated high interest at the meeting because testing has already gone through 3 stages, all that is needed to gather information to present a drug for approval. It is also of interest since prior decomp studies have used low dose RBV. This design may be able to see if researchers can achieve the same efficacy with 24 weeks and no RBV to allow an option to those who cannot tolerate the 3rd drug.
Findings: The cure rate for the patients with advanced cirrhosis, who received SOF/VEL plus RBV for 12 weeks, was 94 percent. Those who received SOF/VEL without RBV for 12 weeks and 24 weeks achieved SVR12 rates of 83 percent and 86 percent, respectively. The patients with HCV infection, who had early stage cirrhosis, achieved cure rates of 98 percent within 12 weeks.
Update: This fixed-dose product has been filed as a treatment for HCV genotypes 1-6 on the strength of four phase III trials. The FDA is due to deliver a verdict on the application by June 28, 2016.
• Also presented at the conference were interim results of treatment plans using combinations of the drugs daclatasvir (DCV)/or sofosbuvir (SOF) with or without ribavirin (RBV), have shown promising results in the treatment of HCV genotype (GT) 3.
Genotype 3 has not only been a harder to treat genotype, it also tends to progress more rapidly to fibrosis and cirrhosis, One potentially groundbreaking study evaluated the effectiveness and safety of DCV and SOF with RBV for 12 and 16 weeks among patients with advanced fibrosis or cirrhosis. The results of the study showed that 88% of the patients with advanced fibrosis and 96% of the patients with cirrhosis were effectively cured at 4 weeks. Another preliminary analysis showed that DCV and SOF, with or without RBV, led to high SVR12 rates (above 90%) in HCV GT3-infected patients, regardless of cirrhosis status. The use of RBV did not affect efficacy outcomes. A third study of DCV’s usefulness analyzed patients in a treatment program in France. DCV and SOF, with or without RBV treatments, demonstrated high 12-week cure rates in GT3 patients with advanced liver disease. The optimal treatment duration was found to be 24 weeks in cirrhotic patients.
• Two studies on potential treatment for chronic genotype (GT) 4 HCV infection yielded positive findings. Genotype 4 is the most common variant of HCV in the Middle East and Africa, particularly Egypt. In these two studies, an integrated analysis was conducted of data from treatment-naïve and treatment-experienced patients enrolled in studies in the U.S. and Egypt. In each study, subjects were randomized 1: 1 to received either 12 or 24 weeks of sofosbuvir (SOF) (400 mg daily) plus ribavirin (RBV) (1000-1200 mg daily). The researchers concluded that SOF and RBV for 24 weeks resulted in a 91% 12-week cure rate in Egyptian patients with HCV GT4 infection. The combined safety and efficacy data support the use of this interferon-free regimen. In addition, the data suggest a shorter treatment duration of 12 weeks may be of benefit for some patients, such as treatment-naïve patients without cirrhosis. It is worth noting that this treatment program is not the current standard of care. AASLD and ISDA guidelines recommend Harvoni for 12 weeks or PrO +RBV for 12 weeks.
• Several studies tested the effectiveness of various treatment regimens using the drugs grazoprevir (GZR) and elbasvir (EBR) and demonstrated high rates of success. In one study, more than 90% of the patient population, all of whom had no prior treatment experience and all of whom had genotype (GT) 1 hepatitis – the most common form of Hepatitis C found in the Americas, Europe, and some parts of Asia, tested free of the disease after treatment periods of 8 or 12 weeks. After 8 weeks, 90% of the treatment-naïve patients taking GZR and EBR with RBV achieved cure rates of 90%. Those taking GZR and EBR without RBV achieved cure rates of almost 94%. After 12 weeks the cure rates rose to around 91% and 98%, respectively.
Other studies reported that the drugs later and final stage clinical trials showed that the 12-18 week regimens of GZR/EBR were highly effective and safe for patients with HCV GT 1 and 4, and 6 (found in Hong Kong, Macau and Vietnam) infections, including some patient populations with complicating illnesses like HIV. At 12 weeks, treatment-experienced patients taking GZR and EBR with RBV achieved cure rates of 89%. Those taking GZR and EBR without RBV achieved cure rates of 91%.
Additionally, at 16 weeks, treatment-experienced patients taking GZR and EBR with RBV achieved cure rates of 94%. Those taking GZR and EBR without RBV achieved cure rates of 100%. In the study of the patients living with both HCV and HIV, 12-week cure rates were 95% at 12 weeks and 94% at 24 weeks, with the same patients were uncured at 24 weeks as they were at 12 weeks. The difference in percentage is due to patients who did not remain in the study for various reasons.
Other Hepatitis C Updates: Since The Liver Meeting, the U.S. Food and Drug Administration (FDA) has accepted a supplemental New Drug Application (sNDA) and granted priority review for VIEKIRA PAK® (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets) without ribavirin (RBV) in patients with genotype 1b (GT1b) chronic hepatitis C virus (HCV) and compensated cirrhosis (Child-Pugh A). The current dosing recommendation for patients with GT1b and compensated cirrhosis is to administer RBV with VIEKIRA PAK for 12 weeks. The FDA grants priority review designation to investigational therapies that treat a serious condition and, if approved, would provide a significant improvement in safety or effectiveness.
The Centers for Disease Control and Prevention (CDC) estimates that in the United States, over 3 million people are chronically infected with HCV.2 Genotype 1 is the most common HCV in the U.S.3 Of the total U.S. population with GT1 HCV infection, approximately 77 percent are genotype 1a (GT1a) and 23 percent are GT1b.3
UC Irvine Health researchers have developed a cost-effective one-step test that screens, detects and confirms hepatitis C virus (HCV) infections using a urine sample. Dr. Ke-Quin Hu, director of hepatology services, presented these findings at the conference, pointing out that current blood-based HCV testing requires two steps and can be expensive and inconvenient, and is not widely available or affordable globally. “For the first time, we can use urine specimens for one-step screening and diagnosing of HCV infection,” said Hu.
Hepatitis C, among other liver diseases, increases a person’s risk of developing primary liver cancer. Because the new direct acting anti-viral drugs are effectively curing hepatitis C, researcher are beginning to address concerns about whether or not a person who has been cured of HCV infection is still at higher risk of developing cancer. A large study presented at the meeting found that the risk after cure remains elevated at 0.3% higher per year, or 1 patient in 300. The risk was elevated in patients who were of older age, Hispanic or had cirrhosis or diabetes.
Most adult exposure to HBV resolves and does not require therapy. However, there is a very high risk of chronic disease when exposure occurs in early childhood, especially at the time of birth. Chronic hepatitis B increases the risk for cirrhosis and liver cancer. Unfortunately, babies born with HBV have a 90 % chance of developing chronic hepatitis B. This risk decreases if the infant is given immunoglobulin and vaccinated against HBV within 12 hours after birth. To curb the spread of the virus, researchers have looked at additional ways to prevent transmission from mother to infant.
Researchers highlighted a study in which 200 pregnant Chinese women with chronic-HBV infection were treated with Tenofovir (Viread). The treatment began at 30-32 weeks gestation. The treated women were less likely to pass the virus to their babies, and there were no dangerous side effects reported. Because of these results, the researchers suggest that TDF therapy should be strongly considered for in certain cases and started at gestation week 30-32.
While treatment of HBV during pregnancy remains controversial, some researchers feel that such treatment may be needed to reduce the global burden of HBV and liver cancer.
Primary Biliary Cholangitis (PBC) previously known as Primary Biliary Cirrhosis is a slow- advancing liver disease; its cause are unknown. PBC is characterized by inflammation in the liver and scarring of the bile ducts, eventually leading to cirrhosis, and other complications, including cancer. This disease occurs primarily in women.
Potential New Treatment on the Horizon
• Obeticolic Acid (OCA), mentioned above in studies in NASH, is also being evaluated in PBC patients. At the AASLD meeting, attendees learned about the results of recent studies. For example, some patients who had been on the drug for four and a half years showed improvement in blood tests evaluating their liver status. The results of this study indicate that OCA can be a long-term treatment for PBC. The most common serious side effect reported by patients has been pruritus (itching).
Since The Liver Meeting ALF recently learned that leading medical centers in the United States are beginning to enroll adults aged 18 – 75 years with PSC in a Phase 2 clinical study of an experimental treatment, obeticholic acid (OCA).
This study in PSC will also evaluate OCA’s effect on liver biochemistry, including alkaline phosphatase (ALP), and safety. Patients in the trial will receive obeticholic acid or a placebo for 24 weeks during the trial, to see if OCA improves ALP in patients with PSC, versus the placebo alone.
After this phase of the trial is complete, the long-term safety extension phase of the trial will begin and last for a further 24 months. This phase of the trial is designed specifically to evaluate the safety and tolerability of using OCA on a long-term basis.
For more information about this or other studies, you can speak to your doctor or go to www.ClinicalTrials.gov.
Liver Transplants continue to be a last option for many patients with advanced liver disease. Allocating liver organs for transplant remains a complex but important issue. A tool in use to determine prognosis and prioritize receipt of available organs is called MELD (Model for End-Stage Liver Disease). The tool takes into account several signs of liver function. One study presented at the meeting addressed the gender discrepancies in selecting patients for transplant.
• Researchers from the Mayo Clinic and Stanford suggest that women are 8% less likely than are men to be selected for receipt of a transplant. This is because women generally have lower muscle mass and will show a lesser presence of a blood chemical known as creatnine. This chemical is incorporated into the total MELD score, so women often achieve a lower MELD score, which may hinder the consideration of women for transplants. Researchers who conducted the study suggested that a more accurate assessment tool may include glomerular filtration, GFR, the rate of filtered fluid through the kidney.
Liver cirrhosis is often a development from ALD (Alcoholic Liver Disease) and/or NAFLD (Non-Alcoholic Fatty Liver Disease). Researchers at the meeting presented evidence that even a month’s abstinence from alcohol reduced the risk factors for NAFLD. After a month of abstinence, 94 participants showed changes in insulin resistance and other known markers of NAFLD. Participants were tested at baseline and after one month.
The effects of coffee on the liver have been of interest to researchers in recent years, several of them have shown a hepatoprotective benefit from coffee. Researchers from Australia presented evidence that showed more than 2 cups of coffee reduce certain complications of liver disease, particularly in patients with HCV. The researcher noted there are 1000 substances in coffee and it could be a combination of substances which might be at work.
The mission of the American Liver Foundation is to facilitate, advocate and promote education, support and research for the prevention, treatment and cure of liver diseases.
You can find out more about our work and information about liver disease on our website, www.liverfoundation.org. And please call our national toll-free Helpline, 1-800- GO-LIVER (1-800-465-4837).
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