Wednesday, July 1, 2015

New Hepatitis C Treatment Causes Dangerous Reactivation of Hepatitis B in Coinfected Patients

by Christine M. Kukka

Coinfected patients treated with new, successful hepatitis C antivirals drugs face a potentially life-threatening reactivation of their hepatitis B infection—even if their hepatitis B is resolved or inactive.
Up to 30 percent of people infected with hepatitis C are also infected with hepatitis B. In these coinfected patients, hepatitis C becomes the “dominant” virus in the liver and suppresses hepatitis B to barely detectable levels. When the new antiviral drugs, including sofosbuvir (Solvadi) are used, hepatitis B can resurge as hepatitis C retreats.

In the past, hepatitis C treatment used the antiviral ribavirin and pegylated interferon. While ribavirin targeted only hepatitis C, the interferon treatment helped the immune system fight both hepatitis C and B.

Today’s fast-acting hepatitis C treatment contains only antivirals that target only hepatitis C. Once hepatitis C is eradicated, doctors are finding a few cases where coinfected patients quickly experience a dangerous reactivation of their hepatitis B infection, even if they had “inactive” or resolved hepatitis B.

This discovery is significant, according to a report published in the current issue of the journal of Clinical Infectious Diseases, because current hepatitis C treatment guidelines, “do not offer specific guidance on treatment and monitoring of patients coinfected with hepatitis B.”

As a result, doctors don’t know they should be looking for hepatitis B reactivation in patients treated with sofosbuvir and simeprevir. However, coinfected patients may be among the first treated with the new drugs by doctors and Veterans Administration clinics because coinfections can produce more serious liver damage that requires treatment.

The journal article reports on two coinfected patients treated with sofosbuvir and simeprevir. One patient achieved undetectable hepatitis C viral load within four weeks, but seven weeks after starting treatment he developed jaundice and abdominal pain. Doctors at Emory University School of Medicine discovered he had a sudden reactivation of hepatitis B. His hepatitis B viral load, which had been very low before treatment, jumped into the millions and blood tests revealed severe liver damage.

Doctors stopped treatment and started him on the hepatitis B antiviral tenofovir (Viread), which quickly controlled the hepatitis B flare. After 28 weeks, the patient’s hepatitis B remained under control and he remained cured of hepatitis C.

In the second reported case, a patient who had cleared a hepatitis B infection and had hepatitis B surface antibodies, was treated with the same antivirals. This time, doctors monitored his hepatitis B and C viral load every two weeks. As expected, the hepatitis C virus disappeared while the hepatitis B viral load rapidly rose. This time, doctors added tenofovir to the ongoing treatment and 12 weeks later the patient tested undetectable for both viruses.

Researchers urged doctors to screen hepatitis C patients for signs of past or current hepatitis B infections before starting the new treatment, and to monitor hepatitis B viral load during treatment.

Tuesday, June 30, 2015

dlDNA marks progression of HBV-related liver disease

The level of serum duplex-linear DNA (dlDNA) increases markedly with liver disease progression and development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection, suggests research published in Gut.

Viral dlDNA has been shown to be the primary precursor of HBV DNA integration into host chromosomes, a process that can have oncogenic consequences, explain the researchers, adding that their main result “supports the notion that dlDNA may play a role in HCC oncogenesis and suggests that therapeutic reduction of dlDNA may reduce the risk of HCC development.”

Using a peptide nucleic acid-mediated quantitative real-time polymerase chain reaction clamping assay developed for the purpose of detecting dlDNA, the proportion of serum dlDNA relative to total HBV DNA was found to be a median of 7.24% in the 143 chronic HBV patients.


Hepatic ALT flares linked to HBsAg clearance

Hepatic alanine aminotransferase (ALT) flares are associated with rapid decline and greater annual reductions of hepatitis B surface antigen (HBsAg) in patients with chronic hepatitis B virus (HBV) infection who achieve HBsAg seroclearance, say Japanese researchers.

Of the 392 HBsAg-positive chronic HBV patients included in this study, 50 achieved HBsAg seroclearance during the median follow-up of 14 years, reports the team from the Nagasaki University Graduate School of Biomedical Sciences in Hepatology Research.

When patients were categorised on the basis of rapidity of seroclearance, the 22 patients who achieved HBsAg seroclearance within 5 years of HBsAg levels reaching 2 log IU/mL had a significantly higher maximum ALT level than the 28 who achieved seroclearance more than 5 years after reaching this threshold, at 487 IU/L versus 146 IU/L (p=0.03).


Monday, June 29, 2015

TE accurate in diagnosing subclinical cirrhosis in patients at risk for HBV-related HCC

Researchers in Korea used transient elastography and found it to be useful in identifying subclinical cirrhosis among patients at risk for hepatitis B virus infection-related hepatocellular carcinoma who did not have evidence of cirrhosis, according to study data.

“We showed that [transient elastography] can identify patients with [subclinical cirrhosis] who are at increased risk of developing [hepatocellular carcinoma] in [chronic hepatitis B] patients without clinical evidence of [liver stiffness],” the researchers wrote. “The concept of [transient elastography]-defined [subclinical cirrhosis] might help the physician to modify the management and surveillance strategies for [chronic hepatitis B] patients and also activate following studies in this field.”

Researchers, including Seung Up Kim, MD, PhD, and Kwang-Hyub Han, MD, department of internal medicine, Yonsei University College of Medicine, Seoul, Korea, analyzed data of 2,876 patients without clinical cirrhosis who underwent transient elastography (TE) examinations between April 2006 and December 2012. Subclinical cirrhosis (SCC) was defined as a non-clinical cirrhosis with a liver stiffness (LS) of at least 13 kPa.

Saturday, June 27, 2015

ASCO 2015: Does Hepatocellular Carcinoma Differ in People with Hepatitis B and C? | Liver Cancer/HCC

Liver cancer patients with hepatitis B at a large U.S. cancer center appeared to have worse disease status than those with hepatitis C, including larger tumors and more extensive liver involvement, according to research presented at the American Society of Clinical Oncology (ASCO) annual meeting this month in Chicago. Prognosis for the 2 groups was similar, however.

Over years or decades chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection can lead to serious liver disease including cirrhosis and hepatocellular carcinoma (HCC), a type of primary liver cancer. HCC is a major cause of cancer death worldwide, and hepatitis B and C are leading risk factors. But it is not well understood how liver cancer outcomes differ for people with HBV (a DNA virus in the Hepadnavirus family that integrates its genetic material into host cells) versus HCV (an RNA virus in the Flavivirus family). - ASCO 2015: Does Hepatocellular Carcinoma Differ in People with Hepatitis B and C? | Liver Cancer/HCC

Friday, June 26, 2015

Bristol-Myers Squibb Co Undergoes Major US Busines...

Bristol-Myers Squibb Co (NYSE:BMY) announced Thursday it will be halting early-stage discovery work in virology research, including hepatitis B and HIV. The company will be laying off around 100 employees as it shuts down two research centers.

"Consistent with the evolution of the company's R&D strategic focus, which was announced in 2013, the Discovery organization will discontinue its research efforts in virology. This includes early research in hepatitis B (HBV) and HIV...Approximately 100 Discovery positions will be eliminated as a result of these changes,” the company stated.

Bristol-Myers, however, noted that ongoing development work on advanced virology treatments including HIV attachment inhibitor BMS-663068, the HIV maturation inhibitor BMS-955176, beclabuvir and the anti-PD-L1 compound BMS-936559, will continue. Also, the company’s marketed virology drugs such as Baraclude (entecavir), Reyataz (atazanavir)/Evotaz (atazanavir and cobicistat), Sustiva (efavirenz), Atripla (efavirenz/emtricitabine/tenofovir disoproxil fumarate), Daklinza (daclatasvir) and Sunvepra (asunaprevir), will not be affected by the consolidation.

Thursday, June 25, 2015

Intradermal HBV vaccine safe, effective for intramuscular nonresponders

HealthDay News -- For intramuscular hepatitis B virus vaccine nonresponders, intradermal vaccine administration seems efficacious and safe, according to a study published in the Journal of Gastroenterology and Hepatology.

About 5% to 10% of people fail to develop a protective immune response to hepatitis B virus (HBV) vaccination, which has important implications for health care workers, families living in households with people that have HBV, and others who may be at increased risk of exposure to HBV.

So Or Kalchiem-Dekel, MD, from the Soroka University Medical Center in Israel, and colleagues designed a prospective case series to examine efficacy, safety, and durability of intradermal vaccine administration in those who have not responded well to intramuscular HBV vaccine.