Aa
HR: In Response to Your Question
*****How did your GI justify not to try to determine where you stand with your liver disease?
He was really insistent that with such a low viral load the chances of finding significant fibrosis were low and not worth the risk associated with biopsy. He really hit the risks of biopsy hard and I feel he even overstated them as I understand them. He said that even if we found significant fibrosis what would we do? Drive my already low viral load down lower and then maybe not even then see a decrease in ALT? Again, not worth the risk associated with biopsy.
Well, ok, I wasn't sure I agreed but I allowed that to stand for the moment and then asked about fibroscan. I didn't even ask if *he* would order one. I asked, given that I thought Dr. Gish might have one available in our area, if I should pursue it...leaving open the idea that I would pursue it on my own out of pocket. That was when he said, "This wasn't tested on people like you." That was when I said, "But if it just measures elasticity then why would the source of damage matter." We know how he replied.
At this point I think I will have to pursue fibroscan on my own or switch doctors. I do not understand his reluctance to look at my liver. He was very willing to do a follow-up on my MRI for suspected hemangioma with another MRI when I thought ultrasound was more standard and cheaper. He agreed to more frequent LFTs.
Forgot to mention that I asked about a "smoldering" hepatitis and my doctor was really dismissive. He said, "There is no such thing as smoldering hepatitis. That is some layman's term and not a medical term. There is active hepatitis and inactive hepatitis and your's is inactive."
Sidebar if you've time- I borrowed my anti-fibrotic regimen from your advice to the Hep C board. Is there any reason why this would not be suitable for my situation?
And I knew I should have paid more attention in my Far East politics class.
My doctor seemed slightly annoyed with me and said, "I know you really like all of these studies..."
He was really insistent that with such a low viral load the chances of finding significant fibrosis were low and not worth the risk associated with biopsy. He really hit the risks of biopsy hard and I feel he even overstated them as I understand them. He said that even if we found significant fibrosis what would we do? Drive my already low viral load down lower and then maybe not even then see a decrease in ALT? Again, not worth the risk associated with biopsy.
Well, ok, I wasn't sure I agreed but I allowed that to stand for the moment and then asked about fibroscan. I didn't even ask if *he* would order one. I asked, given that I thought Dr. Gish might have one available in our area, if I should pursue it...leaving open the idea that I would pursue it on my own out of pocket. That was when he said, "This wasn't tested on people like you." That was when I said, "But if it just measures elasticity then why would the source of damage matter." We know how he replied.
At this point I think I will have to pursue fibroscan on my own or switch doctors. I do not understand his reluctance to look at my liver. He was very willing to do a follow-up on my MRI for suspected hemangioma with another MRI when I thought ultrasound was more standard and cheaper. He agreed to more frequent LFTs.
Forgot to mention that I asked about a "smoldering" hepatitis and my doctor was really dismissive. He said, "There is no such thing as smoldering hepatitis. That is some layman's term and not a medical term. There is active hepatitis and inactive hepatitis and your's is inactive."
Sidebar if you've time- I borrowed my anti-fibrotic regimen from your advice to the Hep C board. Is there any reason why this would not be suitable for my situation?
And I knew I should have paid more attention in my Far East politics class.
My doctor seemed slightly annoyed with me and said, "I know you really like all of these studies..."
Go ahead, stevenNYer, don't hold back, have fun!
I have requoted your "Elmer Fudd looked. Bugs Bunny looked. Porky Pig looked. Daffy Duck looked. All no luck. Sorry....couldn't help myself....hahahaha.” several times and each time I had a good laugh at myself with my 全息自灸疗法 (Whole Rest Self Curing Method).
Maybe this is one way our forum helps us deal with HBV: LAUGH!!!
I have requoted your "Elmer Fudd looked. Bugs Bunny looked. Porky Pig looked. Daffy Duck looked. All no luck. Sorry....couldn't help myself....hahahaha.” several times and each time I had a good laugh at myself with my 全息自灸疗法 (Whole Rest Self Curing Method).
Maybe this is one way our forum helps us deal with HBV: LAUGH!!!
That's our cajim who claims to be so utterly humorless that his wife threatens to leave him for a mini-car stuffed with clowns.
"Only my wife would have spanked me twice as hard..."
It took all my will power...but okay...I'll be good and say, "no comment"...LOL
It took all my will power...but okay...I'll be good and say, "no comment"...LOL
Oh, CoWriter, you are awesome! If I had half your strength, my doc would have given me all the tests I wanted! Only my wife would have spanked me twice as hard because I would have invaded twice the authority space of the doc!
Steven...thank you for the welcome. Congrats on being UND!
cajim.....there's nothing wrong with educating your doctor. I would make a copy of the latest info and tell him, "It's written by the top hepatologists in the NATION....it's brand new so I figured you wouldn't have it yet and made you a copy (smile). I highlighted the important stuff " (you know, in case he doesn't read all of it).
Regarding testing for genotype, instead of asking him why he's not going to test for it, I would make it impossible for him to say no. I'm female, so I would say......
I need my genotype tested. The median age of HBeAg clearance is more than 40 years for genotype C, so most females infected with HBV of this genotype are more likely to be HBeAg positive during the childbearing years.
So if I have genotype C, that makes me more likely to infect my offspring at birth. And if that happened because my genotype wasn't tested, I would be very upset.
(and I could sue him for refusing to test me and he knows that). I would be the patient from hell....LOL
"Expert Insight Into: Clearance of Hepatitis B e Antigen in Patients with Chronic Hepatitis B and Genotypes A, B, C, D, and F"
George KK Lau, MD, Univ of Hong Kong
More than 350 million people worldwide are chronically infected with hepatitis B virus (HBV). Numerous studies have investigated the mode of transmission of HBV, seeking to better determine the roles of horizontal or vertical transmission among populations. For example, researchers would like to know why perinatal transmission of HBV appears to be common in China, South Korea, and Southeast Asia, while in Africa, central Asia, and the Mediterranean region, perinatal transmission occurs less frequently.
This study suggests that the mode of transmission of HBV is not likely related to ethnicity or environmental factors but rather to the particular genotype of the HBV found in the region. The findings may be important for designing effective vaccine strategies in different geographic areas.
This prospective cohort study was performed in Alaska Native people, who have one of the highest rates of chronic HBV infection in the world. A total of 1158 Alaska Native persons infected with HBV were tested serially for hepatitis B e antigen (HBeAg) and were genotyped. Individuals in the study were identified during a hepatitis B vaccination campaign conducted between 1983 and 1987, and the cohort has been followed for a median of 20.5 years. Every 6 months, individuals were contacted by mail and reminded to visit the clinic to have their blood drawn. As of January 1, 2007, the mean age of participants was 43.7 years.
For individuals who were initially HBeAg positive, the researchers analyzed the initial and final HBeAg-positive specimens, time to clearance, age at clearance, and subsequent HBeAg results. In individuals who were initially HBeAg negative, the investigators analyzed subsequent HBeAg results only.
In this population, five hepatitis B virus genotypes were found. A total of 150 individuals had genotype A, 44 had genotype B, 74 had genotype C, 656 had genotype D, and 233 had genotype F. One person was identified with genotype H and was omitted from further analysis. On the initial screen, 507 individuals were HBeAg positive and 650 were HBeAg negative.
The study revealed that among individuals who were initially HBeAg positive, those with genotype C HBV were more likely than those with other genotypes to be positive on initial and final specimens (P <.001 for each). In addition, time to HBeAg clearance was longer in these individuals (P <.001). It also took longer for people with genotype C to clear HBeAg: the age at which 50% of persons cleared HBeAg was <20 years for those infected with genotypes A, B, D, and F, compared with 47.8 years for those infected with genotype C (P <.001) (see Figure). In addition, in persons who reverted to HBeAg-positive status after losing HBeAg, those with genotypes C and F were more likely to revert to a positive HBeAg state (P <.001). Therefore, these individuals may develop more liver disease and hepatocellular carcinoma over their lifetimes.
Figure. Age at Which 50% of Persons Cleared HBeAg, by Genotype.
In persons initially HBeAg negative, 86% remained negative throughout the study. But those with genotype C HBV were less likely than those with other genotypes to remain HBeAg negative (P <.078).
The authors conclude that their results suggest that viral genotype may have a strong effect on mode of HBV transmission and on patient outcome. For example, genotype C may be responsible for most perinatal transmissions, because seroconversion from HBeAg occurs decades later than in other genotypes. Because the median age of HBeAg clearance was more than 40 years for genotype C, most females infected with HBV of this genotype were likely to be HBeAg positive during their childbearing years, therefore making them more likely to infect their offspring at birth. In contrast, the median age of HBeAg clearance was less than 20 years for HBV genotypes A, B, D, and F, meaning that only a minority of these individuals would be HBeAg positive during their childbearing years and would be less likely to infect their offspring at birth.
Antiviral therapies for HBV are designed to inhibit transmission and prevent chronic disease. The authors suggest that timing of treatments may be guided by genotype. They recommend that in geographic areas where genotype C is predominant, HBV vaccination should be initiated at birth to avoid maternal transmission.
Reference
Livingston SE, Simonetti JP, Bulkow LR, et al. Clearance of hepatitis B e antigen in patients with chronic hepatitis B and genotypes A, B, C, D, and F. Gastroenterology. 2007;133:1452-1457.
cajim.....there's nothing wrong with educating your doctor. I would make a copy of the latest info and tell him, "It's written by the top hepatologists in the NATION....it's brand new so I figured you wouldn't have it yet and made you a copy (smile). I highlighted the important stuff " (you know, in case he doesn't read all of it).
Regarding testing for genotype, instead of asking him why he's not going to test for it, I would make it impossible for him to say no. I'm female, so I would say......
I need my genotype tested. The median age of HBeAg clearance is more than 40 years for genotype C, so most females infected with HBV of this genotype are more likely to be HBeAg positive during the childbearing years.
So if I have genotype C, that makes me more likely to infect my offspring at birth. And if that happened because my genotype wasn't tested, I would be very upset.
(and I could sue him for refusing to test me and he knows that). I would be the patient from hell....LOL
"Expert Insight Into: Clearance of Hepatitis B e Antigen in Patients with Chronic Hepatitis B and Genotypes A, B, C, D, and F"
George KK Lau, MD, Univ of Hong Kong
More than 350 million people worldwide are chronically infected with hepatitis B virus (HBV). Numerous studies have investigated the mode of transmission of HBV, seeking to better determine the roles of horizontal or vertical transmission among populations. For example, researchers would like to know why perinatal transmission of HBV appears to be common in China, South Korea, and Southeast Asia, while in Africa, central Asia, and the Mediterranean region, perinatal transmission occurs less frequently.
This study suggests that the mode of transmission of HBV is not likely related to ethnicity or environmental factors but rather to the particular genotype of the HBV found in the region. The findings may be important for designing effective vaccine strategies in different geographic areas.
This prospective cohort study was performed in Alaska Native people, who have one of the highest rates of chronic HBV infection in the world. A total of 1158 Alaska Native persons infected with HBV were tested serially for hepatitis B e antigen (HBeAg) and were genotyped. Individuals in the study were identified during a hepatitis B vaccination campaign conducted between 1983 and 1987, and the cohort has been followed for a median of 20.5 years. Every 6 months, individuals were contacted by mail and reminded to visit the clinic to have their blood drawn. As of January 1, 2007, the mean age of participants was 43.7 years.
For individuals who were initially HBeAg positive, the researchers analyzed the initial and final HBeAg-positive specimens, time to clearance, age at clearance, and subsequent HBeAg results. In individuals who were initially HBeAg negative, the investigators analyzed subsequent HBeAg results only.
In this population, five hepatitis B virus genotypes were found. A total of 150 individuals had genotype A, 44 had genotype B, 74 had genotype C, 656 had genotype D, and 233 had genotype F. One person was identified with genotype H and was omitted from further analysis. On the initial screen, 507 individuals were HBeAg positive and 650 were HBeAg negative.
The study revealed that among individuals who were initially HBeAg positive, those with genotype C HBV were more likely than those with other genotypes to be positive on initial and final specimens (P <.001 for each). In addition, time to HBeAg clearance was longer in these individuals (P <.001). It also took longer for people with genotype C to clear HBeAg: the age at which 50% of persons cleared HBeAg was <20 years for those infected with genotypes A, B, D, and F, compared with 47.8 years for those infected with genotype C (P <.001) (see Figure). In addition, in persons who reverted to HBeAg-positive status after losing HBeAg, those with genotypes C and F were more likely to revert to a positive HBeAg state (P <.001). Therefore, these individuals may develop more liver disease and hepatocellular carcinoma over their lifetimes.
Figure. Age at Which 50% of Persons Cleared HBeAg, by Genotype.
In persons initially HBeAg negative, 86% remained negative throughout the study. But those with genotype C HBV were less likely than those with other genotypes to remain HBeAg negative (P <.078).
The authors conclude that their results suggest that viral genotype may have a strong effect on mode of HBV transmission and on patient outcome. For example, genotype C may be responsible for most perinatal transmissions, because seroconversion from HBeAg occurs decades later than in other genotypes. Because the median age of HBeAg clearance was more than 40 years for genotype C, most females infected with HBV of this genotype were likely to be HBeAg positive during their childbearing years, therefore making them more likely to infect their offspring at birth. In contrast, the median age of HBeAg clearance was less than 20 years for HBV genotypes A, B, D, and F, meaning that only a minority of these individuals would be HBeAg positive during their childbearing years and would be less likely to infect their offspring at birth.
Antiviral therapies for HBV are designed to inhibit transmission and prevent chronic disease. The authors suggest that timing of treatments may be guided by genotype. They recommend that in geographic areas where genotype C is predominant, HBV vaccination should be initiated at birth to avoid maternal transmission.
Reference
Livingston SE, Simonetti JP, Bulkow LR, et al. Clearance of hepatitis B e antigen in patients with chronic hepatitis B and genotypes A, B, C, D, and F. Gastroenterology. 2007;133:1452-1457.
Thanks, zellyf. My wife thought I could have done better. I will try to be more careful with my next doctor.
cajim: So sorry to hear about that exchange but what you did was absolutely correct. Doctors are just human and prone to the same character flaws as the rest of us: hubris, stubbornness and sometime just plain old meanness. Good luck finding a better doctor. You might ask on the HCV board for references in your area.
I think your analysis of my doctor is quite accurate.
I am looking for another doctor in the Kaiser system. Will keep you updated.
Thank you for the pat on the shoulder. We all need it.
Best.
I am looking for another doctor in the Kaiser system. Will keep you updated.
Thank you for the pat on the shoulder. We all need it.
Best.
CoWriter: Always happy to see new people here trying to help others. Welcome. For some of us regulars, after learning the basics of our disease, we try to ask our doctor to consider our UNIQUE presentation. Unfortunately, from our experiences we've learned that this task is not easy. Doctors don't like to deviate from standard practice. I think there are a couple of main reason for this. The first is as Cajim mentioned, an ego thing. Some may find it hard to accept that their patients know more than them. And the second is liability, hence the "I follow the standard guideline for your treatment." And with this, I know I am lucky that my own doctor was willing to listen to what I have to say. Years from now, maybe in hindsight, I may be wrong. But I won't regret my decision on treatment because with the current research, it's what I feel comfortable with.
Cajim: I sorry to hear your recent experience. You doctor forgot the art of compassion.
Cajim: I sorry to hear your recent experience. You doctor forgot the art of compassion.
"Expert Insight Into: Management of Hepatitis B: Summary of a Clinical Research Workshop"
The past 40 years of hepatitis B virus (HBV) research have produced significant advances in the understanding of the viral life cycle, its pathogenesis and natural history, control of transmission through lifestyle modifications and vaccination, and antiviral treatment. Despite these advances, however, the burden of disease remains high and much is still unknown about the disease and its management.
What are the important elements in evaluation of patients?
Which patients should be treated?
Which agents or combination of agents should be used and for how long?
What factors should be considered when deciding whether to continue, discontinue, or switch antiviral therapy?
What are the important elements in evaluation of patients?
The degree of HBV disease activity is determined by biochemical, virologic, serologic, and histologic measurements, ie, serum alanine aminotransferase (ALT), HBV DNA, seroconversion to anti-HBs or anti-HBe, and fibrosis on liver biopsy, respectively. Of these measurements, ALT, HBV DNA, and antibody/antigen status are the key components in clinical evaluation of patients at the time of initial evaluation and when monitoring for response to therapy.
The matrix of these measurements identifies the disease phase of a particular patient, and this phase identification informs treatment as well as prognosis (See Table). Viral and disease factors, such as elevated ALT levels, the presence of HBeAg, and higher HBV DNA levels predict the development of hepatocellular carcinoma (HCC), with higher HBV DNA levels having the strongest association.
Patient medical history also provides important diagnostic and prognostic information. Patient factors, such as male gender, advanced age, cigarette smoking, and alcohol use, are risk factors for HCC. In addition, co-morbid conditions, such as immunosuppression due to HIV coinfection or cancer treatment, will influence treatment decisions.
Table. Phases of Chronic Hepatitis B
Which patients should be treated?
Immune control of HBV replication plays an important role in determining the outcome of HBV infection. For example, most immune competent adults are able to clear newly acquired HBV through the action of their own immune system and thus avoid the progression from acute to chronic HBV. In contrast, in a subset of adults, as well as in the majority of infants and young children, acute infection progresses to chronic.
In principle, antiviral therapy is indicated in patients who are at risk of liver disease progression, including those in the HBeAg-positive or –negative chronic HBV phase (See Table). Patients in the immune tolerance phase have a minimal degree of liver disease, despite high levels of HBV DNA, and usually are not candidates for antiviral therapy. In the inactive carrier phase, the host immune system is able to adequately suppress HBV, making it unnecessary to institute antiviral treatment.
Apart from the immunologic phases of HBV infection, a number of clinical characteristics may necessitate antiviral therapy. Patients with cirrhosis with or without hepatic decompensation, liver transplant recipients and patients subject to immune suppression (eg, transplant recipients and patients undergoing chemotherapy) must be considered for antiviral therapy. Other special populations, including pregnant women, HIV-coinfected individuals, and children, require unique considerations when determining candidacy for treatment.
Which agents or combination of agents should be used and for how long?
Six antiviral agents are now approved in the United States for the treatment of chronic HBV: standard interferon, peginterferon, lamivudine, telbivudine, adefovir dipivoxil, and entecavir. Three others are progressing in clinical trials: emtricitabine, clevudine, and tenofovir disoproxil fumarate. Peginterferon, which has largely replaced the use of standard interferon, has a defined duration of 12 months. In contrast, the nucleoside analogs are typically long-term and continuous.
All approved agents have shown benefit in phase III clinical trials using biochemical, virologic, and histologic endpoints. Loss of HBsAg and HBeAg are more common in the first year of treatment with peginterferon compared with nucleoside analogs. After the first year, however, nucleoside analogs produce higher response rates (ie, decreased HBV DNA levels, normalization of ALT, and improvement in histology) compared with peginterferon. Despite the long-term duration of nucleoside analogs, fewer adverse effects are associated with their use.
Combination therapy may offer the potential advantage of more potent antiviral activity and lower rates of resistance compared with monotherapy. No well-controlled clinical trials, however, have compared combination therapy with each of the agents as monotherapy. The findings from three small studies in treatment-naive patients suggest that two nucleoside analogs in combination are no more potent than the more potent of the single agents. Reduced rates of resistance have been associated with combination therapy but the duration of these studies was too short for this to be measured. Combination therapy using two nucleoside analogs has, however, been supported by several studies in the setting of lamivudine resistance.
The potency of nucleoside-analog–only combination therapy may be limited by the fact that the agents are directed against one target, HBV polymerase. Combining peginterferon with a nucleoside analog has shown promise of additive antiviral activity.
What factors should be considered when deciding whether to continue, discontinue, or switch antiviral therapy?
Response to therapy is considered complete and durable with loss of HBsAg and seroconversion to anti-HBs. Other endpoints of therapy, such as seroconversion to anti-HBe or undetectability of HBV DNA, may be less durable. A sustained response is one that lasts 6 months after stopping therapy, but even patients with sustained response should be monitored for response durability.
Suboptimal response to therapy, as well as viral resistance and breakthrough, are reasons to switch antiviral therapy. Molecular testing is the surest way to detect resistance but is impractical in the clinical setting. Instead, clinical parameters may be used to identify the emergence of resistance: HBV DNA levels rising more than 1 log from a previous nadir in a compliant patient on treatment indicates virologic resistance or breakthrough; a rise in ALT levels to twice the upper limit of normal plus a rise in HBV DNA levels in a patient with previously normal ALT levels indicates clinical resistance or biochemical breakthrough.
As clinical trials extend for longer periods of time, more is learned about the differences in resistance patterns among the nucleoside analogs. Adefovir and tenofovir are effective against lamivudine-resistant strains. Adefovir resistance, however, may be more common with pre-existing lamivudine resistance, and tenofovir may become the agent of choice in this setting. Emtricitabine and lamivudine are similar in rates and patterns of resistance. Although telbivudine has lower rates of resistance than lamivudine, they remain higher than other approved therapies. Resistance to entecavir has been shown to develop in <1% of nucleoside-naive patients after 1 and 2 years. Strains that do develop resistance to entecavir are sensitive to adefovir.
The past 40 years of hepatitis B virus (HBV) research have produced significant advances in the understanding of the viral life cycle, its pathogenesis and natural history, control of transmission through lifestyle modifications and vaccination, and antiviral treatment. Despite these advances, however, the burden of disease remains high and much is still unknown about the disease and its management.
What are the important elements in evaluation of patients?
Which patients should be treated?
Which agents or combination of agents should be used and for how long?
What factors should be considered when deciding whether to continue, discontinue, or switch antiviral therapy?
What are the important elements in evaluation of patients?
The degree of HBV disease activity is determined by biochemical, virologic, serologic, and histologic measurements, ie, serum alanine aminotransferase (ALT), HBV DNA, seroconversion to anti-HBs or anti-HBe, and fibrosis on liver biopsy, respectively. Of these measurements, ALT, HBV DNA, and antibody/antigen status are the key components in clinical evaluation of patients at the time of initial evaluation and when monitoring for response to therapy.
The matrix of these measurements identifies the disease phase of a particular patient, and this phase identification informs treatment as well as prognosis (See Table). Viral and disease factors, such as elevated ALT levels, the presence of HBeAg, and higher HBV DNA levels predict the development of hepatocellular carcinoma (HCC), with higher HBV DNA levels having the strongest association.
Patient medical history also provides important diagnostic and prognostic information. Patient factors, such as male gender, advanced age, cigarette smoking, and alcohol use, are risk factors for HCC. In addition, co-morbid conditions, such as immunosuppression due to HIV coinfection or cancer treatment, will influence treatment decisions.
Table. Phases of Chronic Hepatitis B
Which patients should be treated?
Immune control of HBV replication plays an important role in determining the outcome of HBV infection. For example, most immune competent adults are able to clear newly acquired HBV through the action of their own immune system and thus avoid the progression from acute to chronic HBV. In contrast, in a subset of adults, as well as in the majority of infants and young children, acute infection progresses to chronic.
In principle, antiviral therapy is indicated in patients who are at risk of liver disease progression, including those in the HBeAg-positive or –negative chronic HBV phase (See Table). Patients in the immune tolerance phase have a minimal degree of liver disease, despite high levels of HBV DNA, and usually are not candidates for antiviral therapy. In the inactive carrier phase, the host immune system is able to adequately suppress HBV, making it unnecessary to institute antiviral treatment.
Apart from the immunologic phases of HBV infection, a number of clinical characteristics may necessitate antiviral therapy. Patients with cirrhosis with or without hepatic decompensation, liver transplant recipients and patients subject to immune suppression (eg, transplant recipients and patients undergoing chemotherapy) must be considered for antiviral therapy. Other special populations, including pregnant women, HIV-coinfected individuals, and children, require unique considerations when determining candidacy for treatment.
Which agents or combination of agents should be used and for how long?
Six antiviral agents are now approved in the United States for the treatment of chronic HBV: standard interferon, peginterferon, lamivudine, telbivudine, adefovir dipivoxil, and entecavir. Three others are progressing in clinical trials: emtricitabine, clevudine, and tenofovir disoproxil fumarate. Peginterferon, which has largely replaced the use of standard interferon, has a defined duration of 12 months. In contrast, the nucleoside analogs are typically long-term and continuous.
All approved agents have shown benefit in phase III clinical trials using biochemical, virologic, and histologic endpoints. Loss of HBsAg and HBeAg are more common in the first year of treatment with peginterferon compared with nucleoside analogs. After the first year, however, nucleoside analogs produce higher response rates (ie, decreased HBV DNA levels, normalization of ALT, and improvement in histology) compared with peginterferon. Despite the long-term duration of nucleoside analogs, fewer adverse effects are associated with their use.
Combination therapy may offer the potential advantage of more potent antiviral activity and lower rates of resistance compared with monotherapy. No well-controlled clinical trials, however, have compared combination therapy with each of the agents as monotherapy. The findings from three small studies in treatment-naive patients suggest that two nucleoside analogs in combination are no more potent than the more potent of the single agents. Reduced rates of resistance have been associated with combination therapy but the duration of these studies was too short for this to be measured. Combination therapy using two nucleoside analogs has, however, been supported by several studies in the setting of lamivudine resistance.
The potency of nucleoside-analog–only combination therapy may be limited by the fact that the agents are directed against one target, HBV polymerase. Combining peginterferon with a nucleoside analog has shown promise of additive antiviral activity.
What factors should be considered when deciding whether to continue, discontinue, or switch antiviral therapy?
Response to therapy is considered complete and durable with loss of HBsAg and seroconversion to anti-HBs. Other endpoints of therapy, such as seroconversion to anti-HBe or undetectability of HBV DNA, may be less durable. A sustained response is one that lasts 6 months after stopping therapy, but even patients with sustained response should be monitored for response durability.
Suboptimal response to therapy, as well as viral resistance and breakthrough, are reasons to switch antiviral therapy. Molecular testing is the surest way to detect resistance but is impractical in the clinical setting. Instead, clinical parameters may be used to identify the emergence of resistance: HBV DNA levels rising more than 1 log from a previous nadir in a compliant patient on treatment indicates virologic resistance or breakthrough; a rise in ALT levels to twice the upper limit of normal plus a rise in HBV DNA levels in a patient with previously normal ALT levels indicates clinical resistance or biochemical breakthrough.
As clinical trials extend for longer periods of time, more is learned about the differences in resistance patterns among the nucleoside analogs. Adefovir and tenofovir are effective against lamivudine-resistant strains. Adefovir resistance, however, may be more common with pre-existing lamivudine resistance, and tenofovir may become the agent of choice in this setting. Emtricitabine and lamivudine are similar in rates and patterns of resistance. Although telbivudine has lower rates of resistance than lamivudine, they remain higher than other approved therapies. Resistance to entecavir has been shown to develop in <1% of nucleoside-naive patients after 1 and 2 years. Strains that do develop resistance to entecavir are sensitive to adefovir.
Perhaps HR can tell us wheher that's the info he was refering to. It comes from a site that teaches doctors how to treat Hep B.
Check out the topics in the advanced program, some of them pertain to you (like the one on genotypes).
The first article says patients with a persistently normal serum ALT, irrespective of HBeAg status, are also at risk for the development of cirrhosis and hepatocellular carcinoma, especially if their HBV DNA is > 4 logs.
The second article says that the degree of HBV disease activity should be determined by checking ALT, HBV DNA, seroconversion to anti-HBs or anti-HBe, AND LIVER BIOPSY. (maybe it can help you convince your doctor). It also talks about combination therapy like HR mentioned.
"Expert Insight Into: Hepatitis B Viral Factors in HBeAg-Negative Carriers with Persistently Normal Serum Alanine Aminotransferase Levels"
(George KK Lau, MD, Department of Medicine, Li Ka Shing Faculty of Medicine
The University of Hong Kong).
Recent large-scale cohort studies in Taiwan showed that chronic hepatitis B virus (HBV) patients with a persistently normal serum ALT (PNALT) level, irrespective of HBeAg status, were also at risk for the development of cirrhosis and hepatocellular carcinoma (HCC), suggesting that persistent HBV viremia may cause subclinical yet continuous disease activity. Among the findings was an association between patients with high-normal ALT levels and HBV DNA viral load levels of >4 logs and a higher risk for HCC, compared with individuals with a lower viral load.
Table. Baseline Characteristics of 414 HBeAg-Negative HBV Carriers with Low-Normal and High-Normal Alanine Aminotransferase.
________________________________________________________________________
Total Alanine Aminotransferase P-
Low-Normal High-Normal value
Age (years, mean +/- SD) 39 ± 10 37 ± 10 41 ± 10 <.001
_________________________________________________________________________
10-year categories of age: <.001
< 30 years 77 (18.6%) 48 (27.3%) 29 (12.2%)
30-39 years 134 (32.4%) 58 (33%) 76 (31.9%)
40-49 years 133 (32.1%) 49 (27.8%) 84 (35.3%)
≥ 50 years 70 (16.9%) 21 (11.9%) 49 (20.6%)
_________________________________________________________________________
ALT 20 ± 8 13 ± 4 25 ± 6 <.001
_________________________________________________________________________
Log10 HBV DNA levels 4.7 ± 1.5 4.3 ± 1.4 5.0 ± 1.5 <.001
(copies/mL)*
_________________________________________________________________________*The percentage was based on those patients with detectable HBV DNA.
(Adapted from Lin C-L, et al. Hepatology. 2007;45:1193-1198, with permission from John Wiley & Sons).
Among the 414 participants, baseline ALT levels were at low-normal levels (<0.5 x ULN) in 176 (42.5%), while 238 (57.5%) had high-normal levels. The overall prevalence of precore A1896 mutant was 72.4%, and 28.2% for basal core promoter T1762/A1764.
When data on low-normal and high-normal ALT levels were compared, the results revealed that high-normal ALT levels were present largely in older people; mean age, 37 versus 41 years, respectively (P10 4 copies/mL were present in 148 (62.2%) patients with high-normal ALT levels, compared with just 83 (47.2%) patients with low-normal ALT levels (P10 4 copies/mL) compared with younger patients: 63.4% versus 47.5%, respectively (P< .001). Importantly, the basal core promoter T1762/A1764 mutant was present in a greater number of older rather than younger patients: 36.5% versus 24.2%, respectively (P = .01).
Factors found to be associated with high-normal ALT levels on multivariate analysis were:
* Male gender: odds ratio 1.82 (95% CI, 1.10–3.01 [P = .019])
* Increasing age (groups 30–39 years [P = .016]; 40–49 years [P 50 years [P = .002])
* Serum HBV DNA levels (>104 copies/mL): OR 1.83 (95% CI, 1.07–3.13 [P = .027])
The investigators were able to follow 89 patients for more than 1 year, with a mean follow-up period of 30 +/- 16 months (range 12–77 months). They found that of the 76 patients with detectable HBV DNA levels at baseline, 12 subsequently went from low- to high-normal ALT levels at last follow-up. Further, the baseline serum HBV DNA levels were significantly higher in those 12 patients than in the 15 patients with persistent low-normal ALT.
The authors note that because HBeAg-negative patients with PNALT levels "are not a homogeneous group," individuals with high-normal serum ALT levels share some of the viral factors/characteristics that have been associated with adverse long-term outcomes.
Reference:
Lin CL, Liao LY, Liu CJ, et al. Hepatitis B viral factors in HBeAg-negative carriers with persistently normal serum alanine aminotransferase levels. Hepatology. 2007;45:1193-1198.
Check out the topics in the advanced program, some of them pertain to you (like the one on genotypes).
The first article says patients with a persistently normal serum ALT, irrespective of HBeAg status, are also at risk for the development of cirrhosis and hepatocellular carcinoma, especially if their HBV DNA is > 4 logs.
The second article says that the degree of HBV disease activity should be determined by checking ALT, HBV DNA, seroconversion to anti-HBs or anti-HBe, AND LIVER BIOPSY. (maybe it can help you convince your doctor). It also talks about combination therapy like HR mentioned.
"Expert Insight Into: Hepatitis B Viral Factors in HBeAg-Negative Carriers with Persistently Normal Serum Alanine Aminotransferase Levels"
(George KK Lau, MD, Department of Medicine, Li Ka Shing Faculty of Medicine
The University of Hong Kong).
Recent large-scale cohort studies in Taiwan showed that chronic hepatitis B virus (HBV) patients with a persistently normal serum ALT (PNALT) level, irrespective of HBeAg status, were also at risk for the development of cirrhosis and hepatocellular carcinoma (HCC), suggesting that persistent HBV viremia may cause subclinical yet continuous disease activity. Among the findings was an association between patients with high-normal ALT levels and HBV DNA viral load levels of >4 logs and a higher risk for HCC, compared with individuals with a lower viral load.
Table. Baseline Characteristics of 414 HBeAg-Negative HBV Carriers with Low-Normal and High-Normal Alanine Aminotransferase.
________________________________________________________________________
Total Alanine Aminotransferase P-
Low-Normal High-Normal value
Age (years, mean +/- SD) 39 ± 10 37 ± 10 41 ± 10 <.001
_________________________________________________________________________
10-year categories of age: <.001
< 30 years 77 (18.6%) 48 (27.3%) 29 (12.2%)
30-39 years 134 (32.4%) 58 (33%) 76 (31.9%)
40-49 years 133 (32.1%) 49 (27.8%) 84 (35.3%)
≥ 50 years 70 (16.9%) 21 (11.9%) 49 (20.6%)
_________________________________________________________________________
ALT 20 ± 8 13 ± 4 25 ± 6 <.001
_________________________________________________________________________
Log10 HBV DNA levels 4.7 ± 1.5 4.3 ± 1.4 5.0 ± 1.5 <.001
(copies/mL)*
_________________________________________________________________________*The percentage was based on those patients with detectable HBV DNA.
(Adapted from Lin C-L, et al. Hepatology. 2007;45:1193-1198, with permission from John Wiley & Sons).
Among the 414 participants, baseline ALT levels were at low-normal levels (<0.5 x ULN) in 176 (42.5%), while 238 (57.5%) had high-normal levels. The overall prevalence of precore A1896 mutant was 72.4%, and 28.2% for basal core promoter T1762/A1764.
When data on low-normal and high-normal ALT levels were compared, the results revealed that high-normal ALT levels were present largely in older people; mean age, 37 versus 41 years, respectively (P10 4 copies/mL were present in 148 (62.2%) patients with high-normal ALT levels, compared with just 83 (47.2%) patients with low-normal ALT levels (P10 4 copies/mL) compared with younger patients: 63.4% versus 47.5%, respectively (P< .001). Importantly, the basal core promoter T1762/A1764 mutant was present in a greater number of older rather than younger patients: 36.5% versus 24.2%, respectively (P = .01).
Factors found to be associated with high-normal ALT levels on multivariate analysis were:
* Male gender: odds ratio 1.82 (95% CI, 1.10–3.01 [P = .019])
* Increasing age (groups 30–39 years [P = .016]; 40–49 years [P 50 years [P = .002])
* Serum HBV DNA levels (>104 copies/mL): OR 1.83 (95% CI, 1.07–3.13 [P = .027])
The investigators were able to follow 89 patients for more than 1 year, with a mean follow-up period of 30 +/- 16 months (range 12–77 months). They found that of the 76 patients with detectable HBV DNA levels at baseline, 12 subsequently went from low- to high-normal ALT levels at last follow-up. Further, the baseline serum HBV DNA levels were significantly higher in those 12 patients than in the 15 patients with persistent low-normal ALT.
The authors note that because HBeAg-negative patients with PNALT levels "are not a homogeneous group," individuals with high-normal serum ALT levels share some of the viral factors/characteristics that have been associated with adverse long-term outcomes.
Reference:
Lin CL, Liao LY, Liu CJ, et al. Hepatitis B viral factors in HBeAg-negative carriers with persistently normal serum alanine aminotransferase levels. Hepatology. 2007;45:1193-1198.
I hope you succeed. I already blew it: Yesterday my wife and I went to see my GI doctor. The first sentence he said was " How come we have this appointment again? I thought you had already accepted my advice to look for another doctor...I have my treatment plan which will not be changed because my patients have read this and that from internet forums...I follow the standard guideline in your treatment, Baraclude, 1.0mg daily...(I asked, "What to do when resistance shows, will you replace or add?")...I will add, that's called rescue therapy...(I asked, "What is the reason for not testing my gynotype?")...I will not repeat my answer a second time!"
Well, hope you smoothe the doc's feather much better than me.
Well, hope you smoothe the doc's feather much better than me.
I really tried to be soft spoken and phrase everything as a question. Really. I reminded myself of it before I went in even. I don't know. I will certainly keep your good advice in mind for next time.
From my experience with my doctor, I think some doctors have a big ego. They feel authority threatened when their patients ask too many questions. My wife repeatedly reminded me to act dump so that the doctor can enjoy his authority and doesn't feel threatened.
Could you have shown so much that you know that your GI doctor felt threatened?
Maybe some of the deplomacy techniques that you learned in your poli sci training could find good use with your GI doctor.
What do you think?
Could you have shown so much that you know that your GI doctor felt threatened?
Maybe some of the deplomacy techniques that you learned in your poli sci training could find good use with your GI doctor.
What do you think?
Thanks, CoWriter, as HR said I think the discussion that pertains to this case wasn't done in a forum where it was recorded for posterity. But, interesting stuff nonetheless.
Here's Dr Lai's presentation from the 2006 Meeting in Boston. However, there have been some changes in the last couple of years, so you may want to check out the more recent info.....
"Hepatitis B Advanced Certificate Program III. Bridging Cultural Differences to Improve HBV Treatment." (includes 19 topics, June 2008)
http://www.projectsinknowledge.com/cp/1802/index.cfm?thspage=curriculum&jn=1802
Dr Lai. Refining the HBV Treatment Paradigm (see fifth topic) "Duration of Therapy. How long do you treat?"
http://www.projectsinknowledge.com/Init/G/1752/1752_dkp_0607.swf
Part 3..."Spotlight on New and Investigational Agents"
Dr Lai discusses 2-year results from the phase III GLOBE trial comparing telbivudine and lamividine in patients with chronic hepatitis B virus infection.
http://www.newsmakersinmedicine.com/Hepatology/index.cfm
Abstract, Dr Lai.
"Hepatitis B Surface Antigen loss in antiviral treated patients with HBEAG(+) chronis Hepatitis B (CHB) infection: Observations from antiviral-naive patients treated with Entecavir (ETV) or Lamivudine (LVD)"
http://www.newsmakersinmedicine.com/Hepatology/abstracts/992.pdf
Abstract, Dr Lai (Page 2)
"Telbivudine Globe Trial: Maximal Early HBV Suppression is Predictive of Optimal Two-Year Efficacy i Nucleoside-treated Hepatitis B Patients"
http://www.newsmakersinmedicine.com/Hepatology/abstracts/110.pdf
Well, that would explain why I've been having a devilish hard time trying to find it.
Dr. Gish is an in-network doctor for me. Whether he has the machine or not, I think I might make an appointment to see him and get his opinion.
Thanks, HR, your input is truly appreciated.
Dr. Gish is an in-network doctor for me. Whether he has the machine or not, I think I might make an appointment to see him and get his opinion.
Thanks, HR, your input is truly appreciated.
MEDICAL PROFESSIONAL
Dr. Lai's presentation was in one of the industry sponsored satellite meetings, so there is no way you can obtain a written representation of what was said, unfortunately. It was not too well received - despite the fact that his data/graphs were quite convincing - , because it went beyond the common simplified algorithms and beliefs. But it is from these meetings and hundreds of papers and dozens of presentation that one has to form an opinion that embraces all the critical variations that exist in hepatitis B.
To clarify, I also lean towards the opinion that your liver damage is rather mild. But it might not be and there is no easy way of knowing other than the methods mentioned.
I think that Dr. Gish has not received his fibroscan machine yet, but I am not sure.
To clarify, I also lean towards the opinion that your liver damage is rather mild. But it might not be and there is no easy way of knowing other than the methods mentioned.
I think that Dr. Gish has not received his fibroscan machine yet, but I am not sure.
Thank you, HR, I will look for Dr. Lai's presentation again. Do you think it behooves me to bring them to his attention or do you think I'm better suited pursuing this line of reasoning with a hepatologist?
I will bump up yesterday's thread. Steven suggested I consolidate my remarks into this one for you.
Cheers and thank you again!
I will bump up yesterday's thread. Steven suggested I consolidate my remarks into this one for you.
Cheers and thank you again!
MEDICAL PROFESSIONAL
MRI is quite capable to distinguish between HCC and hemangiomas, better than US. The ALTs give no clue.
There are dozens shades of gray between "active' and inactive hepatitis. There are plenty of patients with near normal ALTs, which nevertheless have progression of fibrosis. The progression of fibrosis has its own, independent factors from the "activity" of the hepatitis, albeit they are linked in a rough sense.
The dangers of a biopsy are very small compared with the dangers of an unappreciated progressed state of liver fibrosis.
While the VL is very low, it could still be lowered by 3 or more logs - unknown into the depth of current "UND" limits and the ALTs - if caused by chronic HBV - are likely to normalize.
If your Gi would have listened to the emphatic presentation by Dr. Lai regarding Asians with a "low' VL and their unrecognized risk in quite a few cases, he would possibly think differently. Lai challenged the common simplified thinking and pointed to the now existing ability to prevent further progression using the potent antivirals and to the need to look into the true state of affairs using a biopsy in order not to miss the cases that can be helped. This was 2 years ago at the Boston AASLD.
The antifibrotic regimen is good for any form of fibrosis, its major problem lies in its cost.
There are dozens shades of gray between "active' and inactive hepatitis. There are plenty of patients with near normal ALTs, which nevertheless have progression of fibrosis. The progression of fibrosis has its own, independent factors from the "activity" of the hepatitis, albeit they are linked in a rough sense.
The dangers of a biopsy are very small compared with the dangers of an unappreciated progressed state of liver fibrosis.
While the VL is very low, it could still be lowered by 3 or more logs - unknown into the depth of current "UND" limits and the ALTs - if caused by chronic HBV - are likely to normalize.
If your Gi would have listened to the emphatic presentation by Dr. Lai regarding Asians with a "low' VL and their unrecognized risk in quite a few cases, he would possibly think differently. Lai challenged the common simplified thinking and pointed to the now existing ability to prevent further progression using the potent antivirals and to the need to look into the true state of affairs using a biopsy in order not to miss the cases that can be helped. This was 2 years ago at the Boston AASLD.
The antifibrotic regimen is good for any form of fibrosis, its major problem lies in its cost.
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