Letters To The Editor

To the Editor: I much enjoyed the important article by Drs. Lipold, Batur, and Kagan on whether there is a time limit for systemic menopausal hormone therapy.¹ The simple answer is no. The authors did a good job of reviewing the factors to consider in terms of contraindications and precautions when prescribing menopausal hormone therapy.

An important part of the discussion regarding stopping hormone therapy is the recent evidence from Finland that has shown increased risks of myocardial infarction and stroke, especially in women under age 60, when taken off hormone therapy.² This fact is quite ironic, as many clinicians are trying to rush to get women off hormone therapy in order to protect the heart, when the evidence does not suggest this. Just as with other hormone-deficiency conditions, the status needs to be periodically reviewed, and doses may need to be adjusted. However, after age 60 or 65, women do not automatically start producing the sex hormone that they have been deficient in. While menopause is not a definite endocrinopathy, it is a potential endocrinopathy; and for some women, such as young women who are oophorectomized, it is an absolute endocrinopathy.

The International Menopause Society has published updated guidelines emphasizing that new data and reanalysis of older data show that for most women the benefits of menopausal hormone therapy are much greater than the risks, particularly when started within a few years of menopause.³

To the Editor: I much enjoyed the important article by Drs. Lipold, Batur, and Kagan on whether there is a time limit for systemic menopausal hormone therapy.¹ The simple answer is no. The authors did a good job of reviewing the factors to consider in terms of contraindications and precautions when prescribing menopausal hormone therapy.

An important part of the discussion regarding stopping hormone therapy is the recent evidence from Finland that has shown increased risks of myocardial infarction and stroke, especially in women under age 60, when taken off hormone therapy.² This fact is quite ironic, as many clinicians are trying to rush to get women off hormone therapy in order to protect the heart, when the evidence does not suggest this. Just as with other hormone-deficiency conditions, the status needs to be periodically reviewed, and doses may need to be adjusted. However, after age 60 or 65, women do not automatically start producing the sex hormone that they have been deficient in. While menopause is not a definite endocrinopathy, it is a potential endocrinopathy; and for some women, such as young women who are oophorectomized, it is an absolute endocrinopathy.

The International Menopause Society has published updated guidelines emphasizing that new data and reanalysis of older data show that for most women the benefits of menopausal hormone therapy are much greater than the risks, particularly when started within a few years of menopause.³

To the Editor: I much enjoyed the important article by Drs. Lipold, Batur, and Kagan on whether there is a time limit for systemic menopausal hormone therapy.¹ The simple answer is no. The authors did a good job of reviewing the factors to consider in terms of contraindications and precautions when prescribing menopausal hormone therapy.

An important part of the discussion regarding stopping hormone therapy is the recent evidence from Finland that has shown increased risks of myocardial infarction and stroke, especially in women under age 60, when taken off hormone therapy.² This fact is quite ironic, as many clinicians are trying to rush to get women off hormone therapy in order to protect the heart, when the evidence does not suggest this. Just as with other hormone-deficiency conditions, the status needs to be periodically reviewed, and doses may need to be adjusted. However, after age 60 or 65, women do not automatically start producing the sex hormone that they have been deficient in. While menopause is not a definite endocrinopathy, it is a potential endocrinopathy; and for some women, such as young women who are oophorectomized, it is an absolute endocrinopathy.

The International Menopause Society has published updated guidelines emphasizing that new data and reanalysis of older data show that for most women the benefits of menopausal hormone therapy are much greater than the risks, particularly when started within a few years of menopause.³

In Reply: We would like to thank Dr. Thacker for her interest in our article on the clinical considerations regarding optimal duration of hormone therapy.¹ We agree that the simple answer to whether there is there a time limit for systemic menopausal hormone therapy is no, emphasizing an individualized approach to each patient. After appropriate counseling and shared decision-making, some women may elect a short duration of therapy while others prefer longer-term use.

As Dr. Thacker mentioned, Mikkola et al² performed an observational study of more than 300,000 Finnish women who discontinued hormone therapy. Data on the number of deaths in this group were gathered from a national database and compared with the expected number of deaths in the background population; 30% of the listed causes of death were confirmed by autopsy. In women who had started hormone therapy before age 60, the risk of cardiac death was elevated within the first year after stopping it (standardized mortality ratio [SMR] 1.74; 95% confidence interval [CI] 1.37–2.19), as was the risk of stroke (SMR 2.59, 95% CI 2.08–3.19). This was not true in women who started hormone therapy at age 60 and older. These findings are consistent with our contemporary understanding that for many women younger than age 60 the benefits of hormone therapy outweigh the risks.

The study had several important limitations:

• A healthy-woman bias may have contributed to the reduction in cardiovascular risk.
• No dates for the myocardial infarctions or strokes were available, and the dates hormone therapy was discontined potentially had a 3-month error.
• No data were available on important confounding factors such as smoking, body mass index, blood pressure, lipid levels, and family history.
• Hormone therapy users were compared with an age-standardized background population, which also included hormone therapy users.
• Long-term follow-up data were also perplexing: although more women than expected died of stroke or coronary heart disease within the first year of stopping hormone therapy, after 1 year, significantly fewer women died of these conditions than expected, regardless of how long they had been on hormone therapy before stopping.

These observations highlight the need for long-term, randomized, prospective controlled studies that adequately assess all long-term outcomes (cardiovascular events, mortality, cancer, fracture) in women who initiate hormone therapy before age 60 and within 10 years of menopause, including long-term follow-up after discontinuation. Though future randomized controlled trials will be beneficial to help guide women to a more balanced understanding of long-term hormone therapy and the risks of discontinuation, the current evidence supports continuing hormone therapy in women who derive a net benefit.

In Reply: We would like to thank Dr. Thacker for her interest in our article on the clinical considerations regarding optimal duration of hormone therapy.¹ We agree that the simple answer to whether there is there a time limit for systemic menopausal hormone therapy is no, emphasizing an individualized approach to each patient. After appropriate counseling and shared decision-making, some women may elect a short duration of therapy while others prefer longer-term use.

As Dr. Thacker mentioned, Mikkola et al² performed an observational study of more than 300,000 Finnish women who discontinued hormone therapy. Data on the number of deaths in this group were gathered from a national database and compared with the expected number of deaths in the background population; 30% of the listed causes of death were confirmed by autopsy. In women who had started hormone therapy before age 60, the risk of cardiac death was elevated within the first year after stopping it (standardized mortality ratio [SMR] 1.74; 95% confidence interval [CI] 1.37–2.19), as was the risk of stroke (SMR 2.59, 95% CI 2.08–3.19). This was not true in women who started hormone therapy at age 60 and older. These findings are consistent with our contemporary understanding that for many women younger than age 60 the benefits of hormone therapy outweigh the risks.

The study had several important limitations:

• A healthy-woman bias may have contributed to the reduction in cardiovascular risk.
• No dates for the myocardial infarctions or strokes were available, and the dates hormone therapy was discontined potentially had a 3-month error.
• No data were available on important confounding factors such as smoking, body mass index, blood pressure, lipid levels, and family history.
• Hormone therapy users were compared with an age-standardized background population, which also included hormone therapy users.
• Long-term follow-up data were also perplexing: although more women than expected died of stroke or coronary heart disease within the first year of stopping hormone therapy, after 1 year, significantly fewer women died of these conditions than expected, regardless of how long they had been on hormone therapy before stopping.

These observations highlight the need for long-term, randomized, prospective controlled studies that adequately assess all long-term outcomes (cardiovascular events, mortality, cancer, fracture) in women who initiate hormone therapy before age 60 and within 10 years of menopause, including long-term follow-up after discontinuation. Though future randomized controlled trials will be beneficial to help guide women to a more balanced understanding of long-term hormone therapy and the risks of discontinuation, the current evidence supports continuing hormone therapy in women who derive a net benefit.

In Reply: We would like to thank Dr. Thacker for her interest in our article on the clinical considerations regarding optimal duration of hormone therapy.¹ We agree that the simple answer to whether there is there a time limit for systemic menopausal hormone therapy is no, emphasizing an individualized approach to each patient. After appropriate counseling and shared decision-making, some women may elect a short duration of therapy while others prefer longer-term use.

As Dr. Thacker mentioned, Mikkola et al² performed an observational study of more than 300,000 Finnish women who discontinued hormone therapy. Data on the number of deaths in this group were gathered from a national database and compared with the expected number of deaths in the background population; 30% of the listed causes of death were confirmed by autopsy. In women who had started hormone therapy before age 60, the risk of cardiac death was elevated within the first year after stopping it (standardized mortality ratio [SMR] 1.74; 95% confidence interval [CI] 1.37–2.19), as was the risk of stroke (SMR 2.59, 95% CI 2.08–3.19). This was not true in women who started hormone therapy at age 60 and older. These findings are consistent with our contemporary understanding that for many women younger than age 60 the benefits of hormone therapy outweigh the risks.

The study had several important limitations:

• A healthy-woman bias may have contributed to the reduction in cardiovascular risk.
• No dates for the myocardial infarctions or strokes were available, and the dates hormone therapy was discontined potentially had a 3-month error.
• No data were available on important confounding factors such as smoking, body mass index, blood pressure, lipid levels, and family history.
• Hormone therapy users were compared with an age-standardized background population, which also included hormone therapy users.
• Long-term follow-up data were also perplexing: although more women than expected died of stroke or coronary heart disease within the first year of stopping hormone therapy, after 1 year, significantly fewer women died of these conditions than expected, regardless of how long they had been on hormone therapy before stopping.

These observations highlight the need for long-term, randomized, prospective controlled studies that adequately assess all long-term outcomes (cardiovascular events, mortality, cancer, fracture) in women who initiate hormone therapy before age 60 and within 10 years of menopause, including long-term follow-up after discontinuation. Though future randomized controlled trials will be beneficial to help guide women to a more balanced understanding of long-term hormone therapy and the risks of discontinuation, the current evidence supports continuing hormone therapy in women who derive a net benefit.

To the Editor: Thanks for the concise review of obstructive sleep apnea (OSA) in the January 2016 issue.¹ I offer the following comments and questions:

1. Risk factors for OSA include large neck circumference, which in Table 1 is defined as larger than 40 cm (15.75 inches), which would include shirt collar sizes 16 and above. In the second paragraph of the text, large neck circumference is defined as greater than 17 inches in men, which would include collar sizes above 17. The definition of a large neck as larger than 40 cm must obviously be more sensitive for predicting OSA, and the definition of greater than 17 inches more specific. Which do the authors use in clinical practice?

2. The American Academy of Sleep Medicine is quoted as recommending home OSA screening “if direct monitoring of the response to non-[continuous positive airway pressure] treatments for sleep apnea is needed.”² However, the need for direct monitoring would seem to be a contraindication to home testing rather than an indication. If this statement is correct as written, would the authors explain why and how specific non-CPAP treatments for OSA are more amenable to monitoring at home than in the sleep lab?

3. Patients with Parkinson disease are at risk for both OSA and hypotension, making them generally an exception to the association of OSA with hypertension.³

4. The home overnight OSA test often consists of a pulse oximeter worn for 8 hours at night, taped to a finger.⁴ This simple, inexpensive test for OSA detects episodes of apnea or hypopnea that result in arterial desaturation. Is it beneficial to also document episodes of apnea or hypopnea that do not result in arterial desaturation? These episodes are included in the 17% false-negative rate for home OSA testing mentioned in the text. Are these episodes important clinically, other than for prognosis in patients who may go on to develop apneic episodes severe enough to cause desaturation?

5. Lastly, the authors may wish to comment on the importance of diagnosing and treating OSA in patients who plan to have elective surgery under general anesthesia, which can lead to profound sleep apnea in the recovery room, with associated morbidity and death.⁵

To the Editor: Thanks for the concise review of obstructive sleep apnea (OSA) in the January 2016 issue.¹ I offer the following comments and questions:

1. Risk factors for OSA include large neck circumference, which in Table 1 is defined as larger than 40 cm (15.75 inches), which would include shirt collar sizes 16 and above. In the second paragraph of the text, large neck circumference is defined as greater than 17 inches in men, which would include collar sizes above 17. The definition of a large neck as larger than 40 cm must obviously be more sensitive for predicting OSA, and the definition of greater than 17 inches more specific. Which do the authors use in clinical practice?

2. The American Academy of Sleep Medicine is quoted as recommending home OSA screening “if direct monitoring of the response to non-[continuous positive airway pressure] treatments for sleep apnea is needed.”² However, the need for direct monitoring would seem to be a contraindication to home testing rather than an indication. If this statement is correct as written, would the authors explain why and how specific non-CPAP treatments for OSA are more amenable to monitoring at home than in the sleep lab?

3. Patients with Parkinson disease are at risk for both OSA and hypotension, making them generally an exception to the association of OSA with hypertension.³

4. The home overnight OSA test often consists of a pulse oximeter worn for 8 hours at night, taped to a finger.⁴ This simple, inexpensive test for OSA detects episodes of apnea or hypopnea that result in arterial desaturation. Is it beneficial to also document episodes of apnea or hypopnea that do not result in arterial desaturation? These episodes are included in the 17% false-negative rate for home OSA testing mentioned in the text. Are these episodes important clinically, other than for prognosis in patients who may go on to develop apneic episodes severe enough to cause desaturation?

5. Lastly, the authors may wish to comment on the importance of diagnosing and treating OSA in patients who plan to have elective surgery under general anesthesia, which can lead to profound sleep apnea in the recovery room, with associated morbidity and death.⁵

To the Editor: Thanks for the concise review of obstructive sleep apnea (OSA) in the January 2016 issue.¹ I offer the following comments and questions:

1. Risk factors for OSA include large neck circumference, which in Table 1 is defined as larger than 40 cm (15.75 inches), which would include shirt collar sizes 16 and above. In the second paragraph of the text, large neck circumference is defined as greater than 17 inches in men, which would include collar sizes above 17. The definition of a large neck as larger than 40 cm must obviously be more sensitive for predicting OSA, and the definition of greater than 17 inches more specific. Which do the authors use in clinical practice?

2. The American Academy of Sleep Medicine is quoted as recommending home OSA screening “if direct monitoring of the response to non-[continuous positive airway pressure] treatments for sleep apnea is needed.”² However, the need for direct monitoring would seem to be a contraindication to home testing rather than an indication. If this statement is correct as written, would the authors explain why and how specific non-CPAP treatments for OSA are more amenable to monitoring at home than in the sleep lab?

3. Patients with Parkinson disease are at risk for both OSA and hypotension, making them generally an exception to the association of OSA with hypertension.³

4. The home overnight OSA test often consists of a pulse oximeter worn for 8 hours at night, taped to a finger.⁴ This simple, inexpensive test for OSA detects episodes of apnea or hypopnea that result in arterial desaturation. Is it beneficial to also document episodes of apnea or hypopnea that do not result in arterial desaturation? These episodes are included in the 17% false-negative rate for home OSA testing mentioned in the text. Are these episodes important clinically, other than for prognosis in patients who may go on to develop apneic episodes severe enough to cause desaturation?

5. Lastly, the authors may wish to comment on the importance of diagnosing and treating OSA in patients who plan to have elective surgery under general anesthesia, which can lead to profound sleep apnea in the recovery room, with associated morbidity and death.⁵

In Reply: We thank Dr. Keller for his thorough reading of our article.¹

Regarding the predictive value of neck circumference for obstructive sleep apnea, (OSA), neck circumference is one of many tools to screen for OSA. If neck circumference greater than 38 cm is applied without other predictors (such as the presence of snoring, daytime sleepiness, or elevated body mass index), it provides only a 58% sensitivity and 79% specificity.² It is less an issue of inches vs collar size vs centimeters than of combining circumference with other parameters (as in the STOP-BANG questionnaire) before proceeding with a sleep study. The senior author of our article (G.R.) uses 38 cm.

With respect to home vs sleep lab monitoring, the question was beyond the scope of the paper and outside our expertise, as we are both general internists. The home venue recommendations in this instance were taken directly from the American Academy of Sleep Medicine.³ We would rely on consultation with a sleep specialist before ordering home monitoring to determine the potential success of non-CPAP interventions for OSA.

As for Parkinson disease as an exception to OSA and hypertension, we wrote in the paper, “Untreated OSA is associated with a number of conditions.”¹ Yes, resistant hypertension is prominent in today’s epidemic of obesity, diabetes, and OSA, but not everyone with coronary artery disease, atrial fibrillation, or heart failure—as in persons with Parkinson disease—has hypertension. The associated conditions in our paper are more typical of a general medical practice, but we agree that Parkinson disease is associated with OSA. Patients with hypertension and OSA are more prevalent because the clinical risk factors for OSA and hypertension are common to both conditions.⁴

In adults, apnea is considered present when the airflow drops by 90% or more from the pre-event baseline. Hypopnea in adults is present when the airflow drops by 30% or more of the pre-event baseline for 10 or more seconds in association with either 3% or greater arterial oxygen desaturation or an electroencephalographic arousal.⁵ Studies have shown that episodes of hypopnea with 2% oxygen desaturation are associated with an increased prevalence of metabolic impairment.⁶ A higher degree of desaturation, ie, more than 4%, was associated with increased prevalence of self-reported cardiovascular disease.⁷ But the significance of episodes of hypopnea without arterial desaturation is not well known to us and was beyond the scope of our article.

Our article was primarily focused on screening for OSA in ambulatory clinical practice and was not intended as a comprehensive review of screening in different settings of patient care. As to the importance of recognizing OSA in patients undergoing elective surgery under general anesthesia, we agree that screening is important to reduce the risk of postoperative adverse respiratory events in patients with a high pretest probability of OSA. In a recent study by Seet et al,⁸ patients with high STOP-BANG questionnaire scores (≥ 3) had higher rates of intraoperative and early postoperative adverse events than those with low scores (< 3). The risk of adverse events correlated with higher scores, and  patients with a STOP-BANG score of 5 or more had a five times greater risk of unexpected intraoperative and early postoperative adverse events, whereas those with a STOP-BANG score of 3 or more had a one in four chance of an adverse event. We recommend polysomnography for patients with a STOP-BANG score of 5 or more before elective surgery.

In Reply: We thank Dr. Keller for his thorough reading of our article.¹

Regarding the predictive value of neck circumference for obstructive sleep apnea, (OSA), neck circumference is one of many tools to screen for OSA. If neck circumference greater than 38 cm is applied without other predictors (such as the presence of snoring, daytime sleepiness, or elevated body mass index), it provides only a 58% sensitivity and 79% specificity.² It is less an issue of inches vs collar size vs centimeters than of combining circumference with other parameters (as in the STOP-BANG questionnaire) before proceeding with a sleep study. The senior author of our article (G.R.) uses 38 cm.

With respect to home vs sleep lab monitoring, the question was beyond the scope of the paper and outside our expertise, as we are both general internists. The home venue recommendations in this instance were taken directly from the American Academy of Sleep Medicine.³ We would rely on consultation with a sleep specialist before ordering home monitoring to determine the potential success of non-CPAP interventions for OSA.

As for Parkinson disease as an exception to OSA and hypertension, we wrote in the paper, “Untreated OSA is associated with a number of conditions.”¹ Yes, resistant hypertension is prominent in today’s epidemic of obesity, diabetes, and OSA, but not everyone with coronary artery disease, atrial fibrillation, or heart failure—as in persons with Parkinson disease—has hypertension. The associated conditions in our paper are more typical of a general medical practice, but we agree that Parkinson disease is associated with OSA. Patients with hypertension and OSA are more prevalent because the clinical risk factors for OSA and hypertension are common to both conditions.⁴

In adults, apnea is considered present when the airflow drops by 90% or more from the pre-event baseline. Hypopnea in adults is present when the airflow drops by 30% or more of the pre-event baseline for 10 or more seconds in association with either 3% or greater arterial oxygen desaturation or an electroencephalographic arousal.⁵ Studies have shown that episodes of hypopnea with 2% oxygen desaturation are associated with an increased prevalence of metabolic impairment.⁶ A higher degree of desaturation, ie, more than 4%, was associated with increased prevalence of self-reported cardiovascular disease.⁷ But the significance of episodes of hypopnea without arterial desaturation is not well known to us and was beyond the scope of our article.

Our article was primarily focused on screening for OSA in ambulatory clinical practice and was not intended as a comprehensive review of screening in different settings of patient care. As to the importance of recognizing OSA in patients undergoing elective surgery under general anesthesia, we agree that screening is important to reduce the risk of postoperative adverse respiratory events in patients with a high pretest probability of OSA. In a recent study by Seet et al,⁸ patients with high STOP-BANG questionnaire scores (≥ 3) had higher rates of intraoperative and early postoperative adverse events than those with low scores (< 3). The risk of adverse events correlated with higher scores, and  patients with a STOP-BANG score of 5 or more had a five times greater risk of unexpected intraoperative and early postoperative adverse events, whereas those with a STOP-BANG score of 3 or more had a one in four chance of an adverse event. We recommend polysomnography for patients with a STOP-BANG score of 5 or more before elective surgery.

In Reply: We thank Dr. Keller for his thorough reading of our article.¹

Regarding the predictive value of neck circumference for obstructive sleep apnea, (OSA), neck circumference is one of many tools to screen for OSA. If neck circumference greater than 38 cm is applied without other predictors (such as the presence of snoring, daytime sleepiness, or elevated body mass index), it provides only a 58% sensitivity and 79% specificity.² It is less an issue of inches vs collar size vs centimeters than of combining circumference with other parameters (as in the STOP-BANG questionnaire) before proceeding with a sleep study. The senior author of our article (G.R.) uses 38 cm.

With respect to home vs sleep lab monitoring, the question was beyond the scope of the paper and outside our expertise, as we are both general internists. The home venue recommendations in this instance were taken directly from the American Academy of Sleep Medicine.³ We would rely on consultation with a sleep specialist before ordering home monitoring to determine the potential success of non-CPAP interventions for OSA.

As for Parkinson disease as an exception to OSA and hypertension, we wrote in the paper, “Untreated OSA is associated with a number of conditions.”¹ Yes, resistant hypertension is prominent in today’s epidemic of obesity, diabetes, and OSA, but not everyone with coronary artery disease, atrial fibrillation, or heart failure—as in persons with Parkinson disease—has hypertension. The associated conditions in our paper are more typical of a general medical practice, but we agree that Parkinson disease is associated with OSA. Patients with hypertension and OSA are more prevalent because the clinical risk factors for OSA and hypertension are common to both conditions.⁴

In adults, apnea is considered present when the airflow drops by 90% or more from the pre-event baseline. Hypopnea in adults is present when the airflow drops by 30% or more of the pre-event baseline for 10 or more seconds in association with either 3% or greater arterial oxygen desaturation or an electroencephalographic arousal.⁵ Studies have shown that episodes of hypopnea with 2% oxygen desaturation are associated with an increased prevalence of metabolic impairment.⁶ A higher degree of desaturation, ie, more than 4%, was associated with increased prevalence of self-reported cardiovascular disease.⁷ But the significance of episodes of hypopnea without arterial desaturation is not well known to us and was beyond the scope of our article.

Our article was primarily focused on screening for OSA in ambulatory clinical practice and was not intended as a comprehensive review of screening in different settings of patient care. As to the importance of recognizing OSA in patients undergoing elective surgery under general anesthesia, we agree that screening is important to reduce the risk of postoperative adverse respiratory events in patients with a high pretest probability of OSA. In a recent study by Seet et al,⁸ patients with high STOP-BANG questionnaire scores (≥ 3) had higher rates of intraoperative and early postoperative adverse events than those with low scores (< 3). The risk of adverse events correlated with higher scores, and  patients with a STOP-BANG score of 5 or more had a five times greater risk of unexpected intraoperative and early postoperative adverse events, whereas those with a STOP-BANG score of 3 or more had a one in four chance of an adverse event. We recommend polysomnography for patients with a STOP-BANG score of 5 or more before elective surgery.

To the Editor: In the article by Drs. Singh et al in your June issue, I was surprised that the role of hepatitis delta wasn’t mentioned as a potential cause of acute liver failure. My understanding is that this peculiar virus can only infect those with hepatitis B surface antigenemia, but when it does, it results in far more serious liver injury, including acute liver failure in some.

To the Editor: In the article by Drs. Singh et al in your June issue, I was surprised that the role of hepatitis delta wasn’t mentioned as a potential cause of acute liver failure. My understanding is that this peculiar virus can only infect those with hepatitis B surface antigenemia, but when it does, it results in far more serious liver injury, including acute liver failure in some.

To the Editor: In the article by Drs. Singh et al in your June issue, I was surprised that the role of hepatitis delta wasn’t mentioned as a potential cause of acute liver failure. My understanding is that this peculiar virus can only infect those with hepatitis B surface antigenemia, but when it does, it results in far more serious liver injury, including acute liver failure in some.

In Reply: We thank Dr. Homler for bringing hepatitis D as a potential cause of acute liver failure to our attention.

Hepatitis D virus, first described in the 1970s, requires the hepatitis B surface antigen (HBsAg) capsid to enter the hepatocyte and, thus, can only cause liver injury when the patient is also infected simultaneously with hepatitis B virus.¹ Hepatitis D virus can cause either coinfection (presence of immunoglobulin M anti-HB core antibody with or without HBsAg) or superinfection (presence of HBsAg without immunoglobulin M anti-HB core antibody) with hepatitis B virus. In India, coinfection has been reported to be the cause of acute liver failure in about 4% of all patients, and superinfection in 4.5%.²

While simultaneous treatment for hepatitis D and B viruses with pegylated interferon and any of the agents used for treatment of hepatitis B has been successful in treating chronic hepatitis, it has not been proven useful in patients with acute liver failure, and liver transplant remains the only treatment option.³

In Reply: We thank Dr. Homler for bringing hepatitis D as a potential cause of acute liver failure to our attention.

Hepatitis D virus, first described in the 1970s, requires the hepatitis B surface antigen (HBsAg) capsid to enter the hepatocyte and, thus, can only cause liver injury when the patient is also infected simultaneously with hepatitis B virus.¹ Hepatitis D virus can cause either coinfection (presence of immunoglobulin M anti-HB core antibody with or without HBsAg) or superinfection (presence of HBsAg without immunoglobulin M anti-HB core antibody) with hepatitis B virus. In India, coinfection has been reported to be the cause of acute liver failure in about 4% of all patients, and superinfection in 4.5%.²

While simultaneous treatment for hepatitis D and B viruses with pegylated interferon and any of the agents used for treatment of hepatitis B has been successful in treating chronic hepatitis, it has not been proven useful in patients with acute liver failure, and liver transplant remains the only treatment option.³

In Reply: We thank Dr. Homler for bringing hepatitis D as a potential cause of acute liver failure to our attention.

Hepatitis D virus, first described in the 1970s, requires the hepatitis B surface antigen (HBsAg) capsid to enter the hepatocyte and, thus, can only cause liver injury when the patient is also infected simultaneously with hepatitis B virus.¹ Hepatitis D virus can cause either coinfection (presence of immunoglobulin M anti-HB core antibody with or without HBsAg) or superinfection (presence of HBsAg without immunoglobulin M anti-HB core antibody) with hepatitis B virus. In India, coinfection has been reported to be the cause of acute liver failure in about 4% of all patients, and superinfection in 4.5%.²

While simultaneous treatment for hepatitis D and B viruses with pegylated interferon and any of the agents used for treatment of hepatitis B has been successful in treating chronic hepatitis, it has not been proven useful in patients with acute liver failure, and liver transplant remains the only treatment option.³