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Pentoxifylline vs. Prednisolone: A Comparison of Efficacy in the Treatment of Severe Alcoholic Hepatitis in Adult Patients

Ashley A Hilliker

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Abstract

Background:\nAlcoholic hepatitis is a chronic, inflammatory liver disease that is on the rise in the United States. Traditionally, the progression of severe alcoholic hepatitis has been slowed with a 28-day course of prednisolone. However, since corticosteroids such as prednisolone have been associated with increased risk of infection and multiple unpleasant side effects, newer research is aimed at using pentoxifylline (PTX) as an alternative treatment. PTX has been shown to have a better safety profile than prednisolone, but its effectiveness in the treatment of severe alcoholic hepatitis is in question. Therefore, the aim of this systematic review is to further evaluate the efficacy of PTX as compared to prednisolone in the treatment of severe alcoholic hepatitis in adult patients.\nMethods:\nAn exhaustive search using MEDLINE-Ovid, MEDLINE-Pub-Med, Web of Science, and Up-To-Date was performed using the terms: pentoxifylline, corticosteroids, and alcoholic hepatitis. Animal studies, articles published over ten years ago, and articles written in non-English languages were excluded from the search. Only randomized-controlled trials were considered for review. All articles were assessed for quality using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria.\nResults:\nThree studies met criteria and were used in this systematic review. The STOPAH trial, an RCT by Thursz et al found that PTX is less effective than Prednisolone at treating severe alcoholic hepatitis in adults in the prevention of mortality at 28 days (P < 0.06). In a small, RCT by Park et al, it was found that PTX is not inferior nor superior to prednisolone in the treatment of severe alcoholic hepatitis. A third RCT by De et al indicated that PTX was superior to prednisolone in the regards to survival at 3 months (P<0.05).\nConclusion:\nThe overall quality of evidence supporting the use of PTX rather than prednisolone in the treatment of severe alcoholic hepatitis in adult patients is low. Although there is indication that PTX may be a safer alternative or perhaps equivalent to prednisolone in select patients, there is a lack of evidence from good RCTs to support this theory. Based on the results discussed in this systematic review, further investigation with larger, longer RCTs is warranted.

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Background:\nAlcoholic hepatitis is a chronic, inflammatory liver disease that is on the rise in the United States. Traditionally, the progression of severe alcoholic hepatitis has been slowed with a 28-day course of prednisolone. However, since corticosteroids such as prednisolone have been associated with increased risk of infection and multiple unpleasant side effects, newer research is aimed at using pentoxifylline (PTX) as an alternative treatment. PTX has been shown to have a better safety profile than prednisolone, but its effectiveness in the treatment of severe alcoholic hepatitis is in question. Therefore, the aim of this systematic review is to further evaluate the efficacy of PTX as compared to prednisolone in the treatment of severe alcoholic hepatitis in adult patients.\nMethods:\nAn exhaustive search using MEDLINE-Ovid, MEDLINE-Pub-Med, Web of Science, and Up-To-Date was performed using the terms: pentoxifylline, corticosteroids, and alcoholic hepatitis. Animal studies, articles published over ten years ago, and articles written in non-English languages were excluded from the search. Only randomized-controlled trials were considered for review. All articles were assessed for quality using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria.\nResults:\nThree studies met criteria and were used in this systematic review. The STOPAH trial, an RCT by Thursz et al found that PTX is less effective than Prednisolone at treating severe alcoholic hepatitis in adults in the prevention of mortality at 28 days (P < 0.06). In a small, RCT by Park et al, it was found that PTX is not inferior nor superior to prednisolone in the treatment of severe alcoholic hepatitis. A third RCT by De et al indicated that PTX was superior to prednisolone in the regards to survival at 3 months (P<0.05).\nConclusion:\nThe overall quality of evidence supporting the use of PTX rather than prednisolone in the treatment of severe alcoholic hepatitis in adult patients is low. Although there is indication that PTX may be a safer alternative or perhaps equivalent to prednisolone in select patients, there is a lack of evidence from good RCTs to support this theory. Based on the results discussed in this systematic review, further investigation with larger, longer RCTs is warranted.

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Available abstract

Background:\nAlcoholic hepatitis is a chronic, inflammatory liver disease that is on the rise in the United States. Traditionally, the progression of severe alcoholic hepatitis has been slowed with a 28-day course of prednisolone. However, since corticosteroids such as prednisolone have been associated with increased risk of infection and multiple unpleasant side effects, newer research is aimed at using pentoxifylline (PTX) as an alternative treatment. PTX has been shown to have a better safety profile than prednisolone, but its effectiveness in the treatment of severe alcoholic hepatitis is in question. Therefore, the aim of this systematic review is to further evaluate the efficacy of PTX as compared to prednisolone in the treatment of severe alcoholic hepatitis in adult patients.\nMethods:\nAn exhaustive search using MEDLINE-Ovid, MEDLINE-Pub-Med, Web of Science, and Up-To-Date was performed using the terms: pentoxifylline, corticosteroids, and alcoholic hepatitis. Animal studies, articles published over ten years ago, and articles written in non-English languages were excluded from the search. Only randomized-controlled trials were considered for review. All articles were assessed for quality using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria.\nResults:\nThree studies met criteria and were used in this systematic review. The STOPAH trial, an RCT by Thursz et al found that PTX is less effective than Prednisolone at treating severe alcoholic hepatitis in adults in the prevention of mortality at 28 days (P < 0.06). In a small, RCT by Park et al, it was found that PTX is not inferior nor superior to prednisolone in the treatment of severe alcoholic hepatitis. A third RCT by De et al indicated that PTX was superior to prednisolone in the regards to survival at 3 months (P<0.05).\nConclusion:\nThe overall quality of evidence supporting the use of PTX rather than prednisolone in the treatment of severe alcoholic hepatitis in adult patients is low. Although there is indication that PTX may be a safer alternative or perhaps equivalent to prednisolone in select patients, there is a lack of evidence from good RCTs to support this theory. Based on the results discussed in this systematic review, further investigation with larger, longer RCTs is warranted.

Key concepts: Alcoholic hepatitis, Medicine, Pentoxifylline, Prednisolone, Randomized controlled trial, Internal medicine, Alcoholic liver disease, Hepatitis

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Pentoxifylline vs. Prednisolone: A Comparison of Efficacy in the Treatment of Severe Alcoholic Hepatitis in Adult Patients — Research Paper | ScholarLens