COMMENT FROM THE EDITOR Hepatology Articles in CGH: 2013 in Review ontributions related to liver disease in Clinical Gastroenterology and Hepatology (CGH) have been steadily growing. In 2013, 23 articles were accepted and 5 of these were accompanied by editorials. The quality of the studies and the breadth of topics are gratifying to see. What follows is a brief summary of these studies broadly categorized into groups, the goal being to review new insights and to stimulate investigators to expand submissions of clinically focused work in liver disease to CGH.
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Noninvasive Liver Disease/Hepatic Fibrosis Markers Six studies addressed aspects of the growing experience with noninvasive detection of liver disease and cirrhosis/fibrosis. Gara et al demonstrated the utility of transient elastography in predicting cirrhosis relative to the aspartate aminotransferase to platelet ratio index and liver biopsy in a population with chronic hepatitis C virus infection.1 Wong et al identified normal elastography values in a large Asian control population,2 and Koehler et al validated the use of the fatty liver index (a simple anthropometric and laboratory algorithm) in predicting ultrasonographydocumented fatty liver in a large elderly European population.3 Macaluso et al quantified the effects of body mass index and liver stiffness on the accuracy of ultrasonographic detection of steatosis in hepatitis C virus infection.4 Raman et al demonstrated differences in fecal microbiome and volatile organic compounds in patients with nonalcoholic fatty liver disease (NAFLD) relative to healthy controls expanding
on the proposed link between gut bacteria profiles and NAFLD.5 Finally, Hanouneh et al used a mass spectrometry approach to identify novel volatile compounds that distinguish patients with alcoholic hepatitis from those with other causes of decompensation and from healthy controls.6
Systematic Reviews Five systematic reviews covering a broad range of topics were included. Singh et al contributed 2 systematic reviews and meta-analyses of noninvasive techniques for evaluating cirrhosis. The first evaluated studies of the accuracy of spleen stiffness measurements in detecting esophageal varices and found significant limitations for this test,7 and the second showed that studies of liver stiffness measurements may be useful in predicting risk of decompensation, hepatocellular carcinoma and mortality in cirrhosis.8 White et al reviewed epidemiological studies linking NAFLD to hepatocellular carcinoma and also found limitations but noted a lower risk of hepatocellular carcinoma in NAFLD cirrhosis compared to hepatitis C virus cirrhosis.9 Wang et al reviewed studies of outcomes of liver transplantation in nonalcoholic steatohepatitis and found similar 1-, 3-, and 5-year survival relative to other etiologies of liver disease, but noted an increased risk of cardiovascular complications in those transplanted for nonalcoholic steatohepatitis.10 Awai et al reviewed studies of liver ultrasonography and magnetic resonance imaging for detecting and grading steatosis in children and found ultrasonography to be inadequate and magnetic resonance to be promising.11
Clinical Reviews We published several clinical reviews in the Perspective section of
Clinical Gastroenterology and Hepatology 2014;12:352–354
the journal. Mehta et al reviewed the current state of knowledge regarding the pathogenesis and treatment of muscle cramps in cirrhosis12 and Northrup et al provided a guide for clinicians regarding coagulation in liver disease.13 Finally, Rossi and Navarro provided a clinical perspective on herbal and dietary supplement induced liver injury.14
Disease Modifiers Two studies evaluated factors that may influence liver disease progression or recurrence. Yu et al analyzed data from the hepatitis C antiviral long-term treatment against cirrhosis (HALT-C) trial and observed a strong direct association between dietary cholesterol intake measured by food frequency questionnaires and risk of liver disease progression.15 Finkenstedt et al evaluated LT donor and recipient rs738409 PNPLA3 genotypes and found that rs738409-G allele status in recipients, but not donors, was associated with a significantly increased risk of graft steatosis over time.16 This result supports the finding that effects of PNPLA3 on hepatic steatosis are mediated outside the liver.
Detection, Management, and Outcomes Six studies evaluated various aspects of liver disease detection, management, and outcomes. Clark et al studied the national Alpha-1 Foundation database and compared alanine aminotransferase levels in those with and without liver disease.17 They found that alanine aminotransferase elevations were a poor predictor of the presence of liver disease. Murali et al assessed a large cohort of patients with pregnancy-specific liver disease and found that total bilirubin level and International Normalized Ratio levels
COMMENT FROM THE EDITOR, continued were comparable to Model for EndStage Liver Disease in predicting early mortality.18 McMahon et al performed a longitudinal populationbased cohort study of Alaska natives with hepatitis B e antigen–negative chronic hepatitis B virus infection.19 Twenty-five percent of these patients developed immune active hepatitis B virus although the risk of advanced fibrosis was low if alanine aminotransferase values remained less than twice normal and hepatitis B virus DNA levels were less than 20,000 IU/mL. Kanwal et al found that 40% of hepatitis C patients with favorable IL28B genoptypes in a Veterans Affairs cohort had contraindications to interferon-based therapies.20 Jorgensen et al undertook a longitudinal analysis of a cohort of Nordic patients transplanted for PSC and found that immunosuppression with cyclosporine and azathioprine had protective effects on the activity of inflammatory bowel disease.21 Wigg et al performed a pilot randomized controlled trial of a chronic disease management program in patients with cirrhosis and found better outpatient attendance but minimal effects on hospital admission rates, disease severity, and quality of life.22
Drug-Induced Injury Ghabril et al evaluated 6 cases of liver injury after administration of tumor necrosis factor alpha antagonists from the U.S. Drug-Induced Liver Injury Network and reviewed 28 prior published reports.23 They found a predominance of females and of an autoimmune phenotype in the cases and a generally good prognosis after drug discontinuation.
Conclusions 2013 was an exciting year for liver disease studies in CGH, and we
are appreciative of all manuscripts submitted. A number of opportunities for increasing submissions to CGH related to liver disease are present. Studies of noninvasive disease/fibrosis markers highlight the promise and challenges of decreasing reliance on invasive techniques in the diagnosis of liver disease and bring forward the validation and implementation of novel technologies for evaluating the presence and type of liver disease. Further studies in these areas are needed. Systematic reviews and meta-analyses dealing with focused clinical questions on disease mechanisms, diagnostics, and therapies are welcome. Moreover, studies on factors that influence liver disease severity and progression are likely to provide novel opportunities to understand pathogenesis and for treatment and are also areas of high priority. Finally, clinical trials of novel diagnostics and therapeutic agents as well as comparative effectiveness studies and studies evaluating the efficacy, effectiveness, and implementation of management strategies in healthcare systems are of particular interest. We encourage investigators to expand submissions of clinically focused work in liver disease to CGH in the New Year. MICHAEL B. FALLON The University of Texas Health Science Center at Houston Division of Gastroenterology Hepatology and Nutrition Houston, Texas
References 1. Gara N, Zhao X, Kleiner DE, et al. Discordance among transient elastography, aspartate aminotransferase to platelet ratio index, and histologic assessments of liver fibrosis in patients with chronic hepatitis C. Clin Gastroenterol Hepatol 2013;11:303–308.
2. Wong GLH, Chan HLY, Choi PCL, et al. Association between anthropometric parameters and measurements of liver stiffness by transient elastography. Clin Gastroenterol Hepatol 2013;11: 295–302. 3. Koehler EM, Schouten JNL, Hansen BE, et al. External validation of the fatty liver index for identifying nonalcoholic fatty liver disease in a population-based study. Clin Gastroenterol Hepatol 2013; 11:1201–1204. 4. Macaluso FS, Maida M, Cammà C, et al. Body mass index and liver stiffness affect accuracy of ultrasonography in detecting steatosis in patients with chronic hepatitis C virus genotype 1 infection. Clin Gastroenterol Hepatol 2013 Oct 7. [Epub ahead of print]. 5. Raman M, Ahmed I, Gillevet PM, et al. Fecal microbiome and volatile organic compound metabolome in obese humans with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2013; 11:868–875. 6. Hanouneh IA, Zein NN, Cikach F, et al. The breathprints in patients with liver disease identify novel breath biomarkers in alcoholic hepatitis. Clin Gastroenterol Hepatol 2013 Sep 10. [Epub ahead of print]. 7. Singh S, Eaton JE, Murad MH, et al. Accuracy of spleen stiffness measurement in detection of esophageal varices in patients with chronic liver disease: systematic review and meta-analysis. Clin Gastroenterol Hepatol 2013 Sep 18. [Epub ahead of print]. 8. Singh S, Fujii LL, Murad MH, et al. Liver stiffness is associated with risk of decompensation, liver cancer, and death in patients with chronic liver diseases: a systematic review and metaanalysis. Clin Gastroenterol Hepatol 2013;11:1573–1584. 9. White DL, Kanwal F, El-Serag HB. Association between nonalcoholic fatty liver disease and risk for hepatocellular cancer, based on systematic review. Clin Gastroenterol Hepatol 2012;10: 1342–1359. 10. Wang X, Li J, Riaz DR, et al. Outcomes of liver transplantation for nonalcoholic steatohepatitis: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2013 Sep 25. [Epub ahead of print].
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COMMENT FROM THE EDITOR, continued 11. Awai HI, Newton KP, Sirlin CB, et al. Evidence and recommendations for imaging liver fat in children, based on systematic review. Clin Gastroenterol Hepatol 2013 Sep 30. [Epub ahead of print]. 12. Mehta SS, Fallon MB. Muscle cramps in liver disease. Clin Gastroenterol Hepatol 2013;11:1385–1391. 13. Northup PG, Caldwell SH. Coagulation in liver disease: a guide for the clinician. Clin Gastroenterol Hepatol 2013; 11:1064–1074. 14. Rossi S, Navarro VJ. Herbs and liver injury: a clinical perspective. Clin Gastroenterol Hepatol 2013 Aug 4. [Epub ahead of print]. 15. Yu L, Morishima C, Ioannou GN. Dietary cholesterol intake is associated with progression of liver disease in patients with chronic hepatitis C: analysis of the hepatitis C antiviral long-term treatment against cirrhosis trial. Clin Gastroenterol Hepatol 2013;11:1661–1666. 16. Finkenstedt A,AuerC,GlodnyB,et al.Patatinlike phospholipase domain-containing protein
354
3 rs738409-G in recipients of liver transplants is a risk factor for graft steatosis. Clin Gastroenterol Hepatol 2013;11:1667–1672. 17. Clark VC, Dhanasekaran R, Brantly M, et al. Liver test results do not identify liver disease in adults with a1antitrypsin deficiency. Clin Gastroenterol Hepatol 2012;10:1278–1283. 18. Murali AR, Devarbhavi H, Venkatachala PR, et al. Factors that predict 1-month mortality in patients with pregnancyspecific liver disease. Clin Gastroenterol Hepatol 2014;12:109–113. 19. McMahon BJ, Bulkow L, Simons B, et al. Relationship between level of hepatitis B virus DNA and liver disease: a population-based study of hepatitis B e antigen–negative persons with hepatitis B. Clin Gastroenterol Hepatol 2013 Sep 11. [Epub ahead of print]. 20. Kanwal F, White DL, Tavakoli–Tabasi S, et al. Many patients with interleukin 28B genotypes associated with response to therapy are ineligible for treatment
because of comorbidities. Clin Gastroenterol Hepatol 2013 Aug 23. [Epub ahead of print]. 21. Jørgensen KK, Lindström L, Cvancarova M, et al. Immunosuppression after liver transplantation for primary sclerosing cholangitis influences activity of inflammatory bowel disease. Clin Gastroenterol Hepatol 2013;11: 517–523. 22. Wigg AJ, McCormick R, Wundke R, et al. Efficacy of a chronic disease management model for patients with chronic liver failure. Clin Gastroenterol Hepatol 2013;11:850–858. 23. Ghabril M, Bonkovsky HL, Kum C, et al. Liver injury from tumor necrosis factor-a antagonists: analysis of thirty-four cases. Clin Gastroenterol Hepatol 2013;11: 558–564.
Conflicts of interest The author discloses no conflicts. http://dx.doi.org/10.1016/j.cgh.2014.01.001
C
Noninvasive Liver Disease/Hepatic Fibrosis Markers Six studies addressed aspects of the growing experience with noninvasive detection of liver disease and cirrhosis/fibrosis. Gara et al demonstrated the utility of transient elastography in predicting cirrhosis relative to the aspartate aminotransferase to platelet ratio index and liver biopsy in a population with chronic hepatitis C virus infection.1 Wong et al identified normal elastography values in a large Asian control population,2 and Koehler et al validated the use of the fatty liver index (a simple anthropometric and laboratory algorithm) in predicting ultrasonographydocumented fatty liver in a large elderly European population.3 Macaluso et al quantified the effects of body mass index and liver stiffness on the accuracy of ultrasonographic detection of steatosis in hepatitis C virus infection.4 Raman et al demonstrated differences in fecal microbiome and volatile organic compounds in patients with nonalcoholic fatty liver disease (NAFLD) relative to healthy controls expanding
on the proposed link between gut bacteria profiles and NAFLD.5 Finally, Hanouneh et al used a mass spectrometry approach to identify novel volatile compounds that distinguish patients with alcoholic hepatitis from those with other causes of decompensation and from healthy controls.6
Systematic Reviews Five systematic reviews covering a broad range of topics were included. Singh et al contributed 2 systematic reviews and meta-analyses of noninvasive techniques for evaluating cirrhosis. The first evaluated studies of the accuracy of spleen stiffness measurements in detecting esophageal varices and found significant limitations for this test,7 and the second showed that studies of liver stiffness measurements may be useful in predicting risk of decompensation, hepatocellular carcinoma and mortality in cirrhosis.8 White et al reviewed epidemiological studies linking NAFLD to hepatocellular carcinoma and also found limitations but noted a lower risk of hepatocellular carcinoma in NAFLD cirrhosis compared to hepatitis C virus cirrhosis.9 Wang et al reviewed studies of outcomes of liver transplantation in nonalcoholic steatohepatitis and found similar 1-, 3-, and 5-year survival relative to other etiologies of liver disease, but noted an increased risk of cardiovascular complications in those transplanted for nonalcoholic steatohepatitis.10 Awai et al reviewed studies of liver ultrasonography and magnetic resonance imaging for detecting and grading steatosis in children and found ultrasonography to be inadequate and magnetic resonance to be promising.11
Clinical Reviews We published several clinical reviews in the Perspective section of
Clinical Gastroenterology and Hepatology 2014;12:352–354
the journal. Mehta et al reviewed the current state of knowledge regarding the pathogenesis and treatment of muscle cramps in cirrhosis12 and Northrup et al provided a guide for clinicians regarding coagulation in liver disease.13 Finally, Rossi and Navarro provided a clinical perspective on herbal and dietary supplement induced liver injury.14
Disease Modifiers Two studies evaluated factors that may influence liver disease progression or recurrence. Yu et al analyzed data from the hepatitis C antiviral long-term treatment against cirrhosis (HALT-C) trial and observed a strong direct association between dietary cholesterol intake measured by food frequency questionnaires and risk of liver disease progression.15 Finkenstedt et al evaluated LT donor and recipient rs738409 PNPLA3 genotypes and found that rs738409-G allele status in recipients, but not donors, was associated with a significantly increased risk of graft steatosis over time.16 This result supports the finding that effects of PNPLA3 on hepatic steatosis are mediated outside the liver.
Detection, Management, and Outcomes Six studies evaluated various aspects of liver disease detection, management, and outcomes. Clark et al studied the national Alpha-1 Foundation database and compared alanine aminotransferase levels in those with and without liver disease.17 They found that alanine aminotransferase elevations were a poor predictor of the presence of liver disease. Murali et al assessed a large cohort of patients with pregnancy-specific liver disease and found that total bilirubin level and International Normalized Ratio levels
COMMENT FROM THE EDITOR, continued were comparable to Model for EndStage Liver Disease in predicting early mortality.18 McMahon et al performed a longitudinal populationbased cohort study of Alaska natives with hepatitis B e antigen–negative chronic hepatitis B virus infection.19 Twenty-five percent of these patients developed immune active hepatitis B virus although the risk of advanced fibrosis was low if alanine aminotransferase values remained less than twice normal and hepatitis B virus DNA levels were less than 20,000 IU/mL. Kanwal et al found that 40% of hepatitis C patients with favorable IL28B genoptypes in a Veterans Affairs cohort had contraindications to interferon-based therapies.20 Jorgensen et al undertook a longitudinal analysis of a cohort of Nordic patients transplanted for PSC and found that immunosuppression with cyclosporine and azathioprine had protective effects on the activity of inflammatory bowel disease.21 Wigg et al performed a pilot randomized controlled trial of a chronic disease management program in patients with cirrhosis and found better outpatient attendance but minimal effects on hospital admission rates, disease severity, and quality of life.22
Drug-Induced Injury Ghabril et al evaluated 6 cases of liver injury after administration of tumor necrosis factor alpha antagonists from the U.S. Drug-Induced Liver Injury Network and reviewed 28 prior published reports.23 They found a predominance of females and of an autoimmune phenotype in the cases and a generally good prognosis after drug discontinuation.
Conclusions 2013 was an exciting year for liver disease studies in CGH, and we
are appreciative of all manuscripts submitted. A number of opportunities for increasing submissions to CGH related to liver disease are present. Studies of noninvasive disease/fibrosis markers highlight the promise and challenges of decreasing reliance on invasive techniques in the diagnosis of liver disease and bring forward the validation and implementation of novel technologies for evaluating the presence and type of liver disease. Further studies in these areas are needed. Systematic reviews and meta-analyses dealing with focused clinical questions on disease mechanisms, diagnostics, and therapies are welcome. Moreover, studies on factors that influence liver disease severity and progression are likely to provide novel opportunities to understand pathogenesis and for treatment and are also areas of high priority. Finally, clinical trials of novel diagnostics and therapeutic agents as well as comparative effectiveness studies and studies evaluating the efficacy, effectiveness, and implementation of management strategies in healthcare systems are of particular interest. We encourage investigators to expand submissions of clinically focused work in liver disease to CGH in the New Year. MICHAEL B. FALLON The University of Texas Health Science Center at Houston Division of Gastroenterology Hepatology and Nutrition Houston, Texas
References 1. Gara N, Zhao X, Kleiner DE, et al. Discordance among transient elastography, aspartate aminotransferase to platelet ratio index, and histologic assessments of liver fibrosis in patients with chronic hepatitis C. Clin Gastroenterol Hepatol 2013;11:303–308.
2. Wong GLH, Chan HLY, Choi PCL, et al. Association between anthropometric parameters and measurements of liver stiffness by transient elastography. Clin Gastroenterol Hepatol 2013;11: 295–302. 3. Koehler EM, Schouten JNL, Hansen BE, et al. External validation of the fatty liver index for identifying nonalcoholic fatty liver disease in a population-based study. Clin Gastroenterol Hepatol 2013; 11:1201–1204. 4. Macaluso FS, Maida M, Cammà C, et al. Body mass index and liver stiffness affect accuracy of ultrasonography in detecting steatosis in patients with chronic hepatitis C virus genotype 1 infection. Clin Gastroenterol Hepatol 2013 Oct 7. [Epub ahead of print]. 5. Raman M, Ahmed I, Gillevet PM, et al. Fecal microbiome and volatile organic compound metabolome in obese humans with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2013; 11:868–875. 6. Hanouneh IA, Zein NN, Cikach F, et al. The breathprints in patients with liver disease identify novel breath biomarkers in alcoholic hepatitis. Clin Gastroenterol Hepatol 2013 Sep 10. [Epub ahead of print]. 7. Singh S, Eaton JE, Murad MH, et al. Accuracy of spleen stiffness measurement in detection of esophageal varices in patients with chronic liver disease: systematic review and meta-analysis. Clin Gastroenterol Hepatol 2013 Sep 18. [Epub ahead of print]. 8. Singh S, Fujii LL, Murad MH, et al. Liver stiffness is associated with risk of decompensation, liver cancer, and death in patients with chronic liver diseases: a systematic review and metaanalysis. Clin Gastroenterol Hepatol 2013;11:1573–1584. 9. White DL, Kanwal F, El-Serag HB. Association between nonalcoholic fatty liver disease and risk for hepatocellular cancer, based on systematic review. Clin Gastroenterol Hepatol 2012;10: 1342–1359. 10. Wang X, Li J, Riaz DR, et al. Outcomes of liver transplantation for nonalcoholic steatohepatitis: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2013 Sep 25. [Epub ahead of print].
353
COMMENT FROM THE EDITOR, continued 11. Awai HI, Newton KP, Sirlin CB, et al. Evidence and recommendations for imaging liver fat in children, based on systematic review. Clin Gastroenterol Hepatol 2013 Sep 30. [Epub ahead of print]. 12. Mehta SS, Fallon MB. Muscle cramps in liver disease. Clin Gastroenterol Hepatol 2013;11:1385–1391. 13. Northup PG, Caldwell SH. Coagulation in liver disease: a guide for the clinician. Clin Gastroenterol Hepatol 2013; 11:1064–1074. 14. Rossi S, Navarro VJ. Herbs and liver injury: a clinical perspective. Clin Gastroenterol Hepatol 2013 Aug 4. [Epub ahead of print]. 15. Yu L, Morishima C, Ioannou GN. Dietary cholesterol intake is associated with progression of liver disease in patients with chronic hepatitis C: analysis of the hepatitis C antiviral long-term treatment against cirrhosis trial. Clin Gastroenterol Hepatol 2013;11:1661–1666. 16. Finkenstedt A,AuerC,GlodnyB,et al.Patatinlike phospholipase domain-containing protein
354
3 rs738409-G in recipients of liver transplants is a risk factor for graft steatosis. Clin Gastroenterol Hepatol 2013;11:1667–1672. 17. Clark VC, Dhanasekaran R, Brantly M, et al. Liver test results do not identify liver disease in adults with a1antitrypsin deficiency. Clin Gastroenterol Hepatol 2012;10:1278–1283. 18. Murali AR, Devarbhavi H, Venkatachala PR, et al. Factors that predict 1-month mortality in patients with pregnancyspecific liver disease. Clin Gastroenterol Hepatol 2014;12:109–113. 19. McMahon BJ, Bulkow L, Simons B, et al. Relationship between level of hepatitis B virus DNA and liver disease: a population-based study of hepatitis B e antigen–negative persons with hepatitis B. Clin Gastroenterol Hepatol 2013 Sep 11. [Epub ahead of print]. 20. Kanwal F, White DL, Tavakoli–Tabasi S, et al. Many patients with interleukin 28B genotypes associated with response to therapy are ineligible for treatment
because of comorbidities. Clin Gastroenterol Hepatol 2013 Aug 23. [Epub ahead of print]. 21. Jørgensen KK, Lindström L, Cvancarova M, et al. Immunosuppression after liver transplantation for primary sclerosing cholangitis influences activity of inflammatory bowel disease. Clin Gastroenterol Hepatol 2013;11: 517–523. 22. Wigg AJ, McCormick R, Wundke R, et al. Efficacy of a chronic disease management model for patients with chronic liver failure. Clin Gastroenterol Hepatol 2013;11:850–858. 23. Ghabril M, Bonkovsky HL, Kum C, et al. Liver injury from tumor necrosis factor-a antagonists: analysis of thirty-four cases. Clin Gastroenterol Hepatol 2013;11: 558–564.
Conflicts of interest The author discloses no conflicts. http://dx.doi.org/10.1016/j.cgh.2014.01.001
