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In reply: Alcoholic hepatitis: An important consideration

In Reply: We thank Dr. Mirrakhimov for his interest in our article1 and for his comments on the importance of infection evaluation and treatment in patients with alcoholic hepatitis. We agree with the points he has raised and emphasized several of them in our article. We highlighted the need to evaluate for infections in these patients, as about a quarter of them are infected at the time of presentation.2

Importantly, patients with alcoholic hepatitis frequently have systemic inflammatory response syndrome criteria, which can be related to the overall inflammatory state of the disease itself or can reflect an active bacterial infection. Therefore, clinical monitoring for symptoms and signs of infection is crucial, and screening for infections is warranted on admission as well as repeatedly during the hospital stay for patients who experience clinical deterioration.3 Obtaining blood and urine cultures and performing paracentesis in patients with ascites to evaluate for bacterial peritonitis are required. Indeed, infections are a leading cause of death in patients with severe alcoholic hepatitis, both directly and indirectly by predisposing to multiorgan failure.4

Another factor to consider is the increased susceptibility to infection in these patients treated with corticosteroids. A study by Louvet et al2 showed that nonresponse to corticosteroids is the main factor contributing to the development of infection during treatment with corticosteroids, suggesting that infection is likely a consequence of the absence of improvement in liver function. More recently, results of the Steroids or Pentoxifylline for Alcoholic Hepatitis trial (which evaluated the treatment effect of prednisolone and pentoxifylline in the management of severe alcoholic hepatitis) showed that despite the higher rates of infections in patients treated with prednisolone, the mortality rates attributed to infections were similar across the treatment groups, regardless of whether prednisolone was administered.4

Finally, it is important to emphasize that criteria to initiate empiric antibiotics in patients with alcoholic hepatitis are currently lacking, and the decision to start antibiotics empirically in patients without a clear infection is largely based on the clinician’s assessment.

References
  1. Dugum M, Zein N, McCullough A, Hanouneh I. Alcoholic hepatitis: challenges in diagnosis and management. Cleve Clin J Med 2015; 82:226–236.
  2. Louvet A, Wartel F, Castel H, et al. Infection in patients with severe alcoholic hepatitis treated with steroids: early response to therapy is the key factor. Gastroenterology 2009; 137:541–548.
  3. European Association for the Study of Liver. EASL clinical practical guidelines: management of alcoholic liver disease. J Hepatol 2012; 57:399–420.
  4. Thursz MR, Richardson P, Allison M, et al. Prednisolone or pentoxifylline for alcoholic hepatitis. N Engl J Med 2015; 372:1619–1628.
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Mohannad Dugum, MD
Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic

Nizar Zein, MD
Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic

Arthur McCullough, MD
Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic

Ibrahim Hanouneh, MD
Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic

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Cleveland Clinic Journal of Medicine - 82(6)
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alcoholic hepatitis, infection, Mohannad Dugum, Nizar Zein, Arthur McCullough, Ibrahim Hanouneh
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Mohannad Dugum, MD
Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic

Nizar Zein, MD
Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic

Arthur McCullough, MD
Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic

Ibrahim Hanouneh, MD
Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic

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Mohannad Dugum, MD
Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic

Nizar Zein, MD
Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic

Arthur McCullough, MD
Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic

Ibrahim Hanouneh, MD
Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic

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In Reply: We thank Dr. Mirrakhimov for his interest in our article1 and for his comments on the importance of infection evaluation and treatment in patients with alcoholic hepatitis. We agree with the points he has raised and emphasized several of them in our article. We highlighted the need to evaluate for infections in these patients, as about a quarter of them are infected at the time of presentation.2

Importantly, patients with alcoholic hepatitis frequently have systemic inflammatory response syndrome criteria, which can be related to the overall inflammatory state of the disease itself or can reflect an active bacterial infection. Therefore, clinical monitoring for symptoms and signs of infection is crucial, and screening for infections is warranted on admission as well as repeatedly during the hospital stay for patients who experience clinical deterioration.3 Obtaining blood and urine cultures and performing paracentesis in patients with ascites to evaluate for bacterial peritonitis are required. Indeed, infections are a leading cause of death in patients with severe alcoholic hepatitis, both directly and indirectly by predisposing to multiorgan failure.4

Another factor to consider is the increased susceptibility to infection in these patients treated with corticosteroids. A study by Louvet et al2 showed that nonresponse to corticosteroids is the main factor contributing to the development of infection during treatment with corticosteroids, suggesting that infection is likely a consequence of the absence of improvement in liver function. More recently, results of the Steroids or Pentoxifylline for Alcoholic Hepatitis trial (which evaluated the treatment effect of prednisolone and pentoxifylline in the management of severe alcoholic hepatitis) showed that despite the higher rates of infections in patients treated with prednisolone, the mortality rates attributed to infections were similar across the treatment groups, regardless of whether prednisolone was administered.4

Finally, it is important to emphasize that criteria to initiate empiric antibiotics in patients with alcoholic hepatitis are currently lacking, and the decision to start antibiotics empirically in patients without a clear infection is largely based on the clinician’s assessment.

In Reply: We thank Dr. Mirrakhimov for his interest in our article1 and for his comments on the importance of infection evaluation and treatment in patients with alcoholic hepatitis. We agree with the points he has raised and emphasized several of them in our article. We highlighted the need to evaluate for infections in these patients, as about a quarter of them are infected at the time of presentation.2

Importantly, patients with alcoholic hepatitis frequently have systemic inflammatory response syndrome criteria, which can be related to the overall inflammatory state of the disease itself or can reflect an active bacterial infection. Therefore, clinical monitoring for symptoms and signs of infection is crucial, and screening for infections is warranted on admission as well as repeatedly during the hospital stay for patients who experience clinical deterioration.3 Obtaining blood and urine cultures and performing paracentesis in patients with ascites to evaluate for bacterial peritonitis are required. Indeed, infections are a leading cause of death in patients with severe alcoholic hepatitis, both directly and indirectly by predisposing to multiorgan failure.4

Another factor to consider is the increased susceptibility to infection in these patients treated with corticosteroids. A study by Louvet et al2 showed that nonresponse to corticosteroids is the main factor contributing to the development of infection during treatment with corticosteroids, suggesting that infection is likely a consequence of the absence of improvement in liver function. More recently, results of the Steroids or Pentoxifylline for Alcoholic Hepatitis trial (which evaluated the treatment effect of prednisolone and pentoxifylline in the management of severe alcoholic hepatitis) showed that despite the higher rates of infections in patients treated with prednisolone, the mortality rates attributed to infections were similar across the treatment groups, regardless of whether prednisolone was administered.4

Finally, it is important to emphasize that criteria to initiate empiric antibiotics in patients with alcoholic hepatitis are currently lacking, and the decision to start antibiotics empirically in patients without a clear infection is largely based on the clinician’s assessment.

References
  1. Dugum M, Zein N, McCullough A, Hanouneh I. Alcoholic hepatitis: challenges in diagnosis and management. Cleve Clin J Med 2015; 82:226–236.
  2. Louvet A, Wartel F, Castel H, et al. Infection in patients with severe alcoholic hepatitis treated with steroids: early response to therapy is the key factor. Gastroenterology 2009; 137:541–548.
  3. European Association for the Study of Liver. EASL clinical practical guidelines: management of alcoholic liver disease. J Hepatol 2012; 57:399–420.
  4. Thursz MR, Richardson P, Allison M, et al. Prednisolone or pentoxifylline for alcoholic hepatitis. N Engl J Med 2015; 372:1619–1628.
References
  1. Dugum M, Zein N, McCullough A, Hanouneh I. Alcoholic hepatitis: challenges in diagnosis and management. Cleve Clin J Med 2015; 82:226–236.
  2. Louvet A, Wartel F, Castel H, et al. Infection in patients with severe alcoholic hepatitis treated with steroids: early response to therapy is the key factor. Gastroenterology 2009; 137:541–548.
  3. European Association for the Study of Liver. EASL clinical practical guidelines: management of alcoholic liver disease. J Hepatol 2012; 57:399–420.
  4. Thursz MR, Richardson P, Allison M, et al. Prednisolone or pentoxifylline for alcoholic hepatitis. N Engl J Med 2015; 372:1619–1628.
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Cleveland Clinic Journal of Medicine - 82(6)
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Cleveland Clinic Journal of Medicine - 82(6)
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335-336
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335-336
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