HBV Advocate Blog: Doctors Explain Which Medical Guidelines They Follow, Or Ignore

There are three sets of hepatitis B treatment guidelines available worldwide (from America, Asia and Europe) and sometimes they agree, and often they conflict.

Confronted with varying treatment recommendations, a team of expert doctors from the University of Michigan Health System in Ann Arbor detailed which they followed when caring for their own patients in the January 2014 issue of the journal of Clinical Gastroenterology and Hepatology.

All three guidelines give guideposts forwhen antiviral treatment should begin—when ALT levels are elevated indicating liver cell damage, or viral load is high, or when a liver biopsy uncovers fibrosis or cirrhosis. But there is much gray area and little consensus about exactly how high viral load or ALT levels should be to trigger treatment, or when to perform a liver biopsy. For example:

When do these doctors start treatment? When patients have moderate (compensated) cirrhosis, they follow American guidelines but they don't wait for HBV DNA to reach 20,000 IU/mL. They start treating when HBV DNA is much lower (at 2,000 IU/mL) because of the risk of liver cancer in these cirrhotic patients.

In non-cirrhotic patients, they follow American guidelines and start treatment when HBV DNA levels exceed 20,000 IU/mL and ALT levels are greater than twice the upper limits of normal.

For patients in the gray zone, with moderately elevated viral loads and ALT levels, the doctors recommend liver biopsies to determine the true health of their livers, especially if patients are 40 or older.

When do they order a liver biopsy? All guidelines agree that neither treatment nor a biopsy is needed in patients with normal ALT and low viral load. These doctors order a biopsy when patients have slightly elevated ALT levels, especially in patients age 40 or older. (European guidelines recommend a biopsy in these patients once they reach age 30.) Treatment is recommended if moderate to severe inflammation and/or fibrosis is found.

If patients have high viral load, even though their ALT levels are normal (called the immune-tolerant stage), the doctors would not treat or biopsy until the patient reached age 40, when liver damage and cancer risks increase.

Do they treat pregnant women with high viral loads to prevent infection of newborns? European and Asian guidelines promote treating women with high viral loads with antivirals to prevent mother-to-child infection.

"We defer treatment in women who have plans to be pregnant unless they have active or advanced liver disease," they wrote. "We discuss the benefits and risks of ... antiviral treatment with women who have HBV DNA level(s) greater than (10 million) IU/mL during the second trimester of pregnancy.

"We recommend starting antiviral treatment around week 30 if the patient agrees and (we) prefer tenofovir (Viread)…. We stop treatment immediately after delivery and emphasize the importance of monitoring for postpartum flares. We discuss the potential risk of exposing the infant to the antiviral medication if treatment is continued, but we do not advise against breastfeeding."

How often do these doctors monitor their patients? They monitor patients under age 30 in the immune-tolerant stage every six to 12 months and older patients every three to six months. "We monitor HBeAg-negative patients every three months over a one-year period before determining they are truly in the inactive carrier phase, at which time we decrease monitoring to every 6 to 12 months."

What treatments do these doctors use? Pegylated interferon and the antivirals tenofovir and entecavir are recommended as first treatments by the American guidelines and the doctors follow their recommendations. However, despite their good experience with interferon, fewer than 10% of their patients select interferon. "We are more enthusiastic in recommending interferon to young patients, particularly those who are hesitant to commit to a long duration of treatment and young women who are planning to start a family within the next two to three years," they wrote.

When it comes to antivirals, they believe entecavir and tenofovir are equally effective. "We prefer entecavir in patients who are at increased risk of (kidney damage) such as patients with decompensated cirrhosis, older patients, and patients with hypertension or diabetes. We prefer tenofovir in young women who might become pregnant during the course of treatment," they wrote.

They avoid prescribing lamivudine, telbivudine, and adefovir because of their higher rates of drug resistance. "In addition, we systematically have switched patients from adefovir to tenofovir because tenofovir is more potent. For patients taking lamivudine plus adefovir because of prior lamivudine resistance, we have switched them to tenofovir if they have undetectable HBV DNA levels or to the combination pill Truvada (containing the antiviral emtricitabine plus tenofovir). We have switched most patients taking lamivudine to tenofovir, except for a few who had been on lamivudine for many years with undetectable HBV DNA levels because the risk of antiviral drug resistance in these patients is very low."

When do the doctors stop antiviral treatment? These doctors continue antiviral treatment indefinitely in those who have cirrhosis and in many older patients (older than 60) unless they clear HBsAg.

For HBeAg-positive patients without cirrhosis, the doctors won't stop treatment until 12 months after the patients have achieved HBeAg seroconversion in order to "consolidate" the HBeAg loss.

In HBeAg-negative patients, they stop treatment after HBsAg loss, but this has occurred in only one patient they have treated in the past five years.

"We have, however, discontinued treatment in several patients who can no longer afford or are no longer willing to commit to long-term treatment if they have completed at least five years of treatment with undetectable HBV DNA levels in the past three years," they reported. "Although all patients experienced virologic relapse after treatment was stopped, most patients continue to have low HBV DNA levels and normal ALT levels and have not required resumption of treatment."

"Guidelines provide an evidence-based framework for managing patients; however, management of individual patients must be flexible, taking into account the patient's preference and other medical or psychosocial conditions, evolution in knowledge over time, and the provider's experience," they concluded.