BIOCHEMICAL MARKERS FOR STEATOSIS: A NECESSITY. BUT FOR NOW, BE SATISFIED WITH THE BIOPSY

MARCADORES BIOQUÍMICOS DE ESTEATOSE: UMA NECESSIDADE. MAS POR ENQUANTO FIQUE SATISFEITO COM A BIÓPSIA

Nowadays, non-alcoholic fatty liver disease (NAFLD) is considered one of the most important causes of chronic liver disease in the world. Recent data show a global prevalence of 25%, with a recent increase that follows the current trends of the obesity epidemic¹³. Among obese patients, the prevalence of NAFLD can exceed 90%⁴,¹⁰. NAFLD is a spectrum of disease involving simple hepatic steatosis and nonalcoholic steatosis (NASH) with or without fibrosis or cirrhosis.

Regarding the disease’s natural history, about 20% of patients with hepatic steatosis have NASH. Over time, 20% of those individuals will develop hepatic cirrhosis. Recently, NASH had become the most important indication of liver transplant among women in the United States and is expected to overtake alcoholic liver disease as the leading liver transplant indication for all patients within the next few years. Compared to NAFLD, patients with NASH can develop hepatocellular carcinoma in a 12 times higher rate and have an annual mortality 1.7 times higher⁹.

Liver biopsy is the only method to diagnose NASH. It is histologic demonstrations of hepatic steatosis associated with hepatocyte ballooning degeneration and lobular inflammation. There are some clinical scores for prediction of liver fibrosis; however, these methods were not validated for the obese population and present variable specificity and sensibility in the literature³,¹⁰,¹¹.

De Carli et al.³ evaluated the performance of these noninvasive scores in morbidly obese patients undergoing bariatric surgery. They found that the APRI (AST to platelet ration index) presented the higher specificity (99.61%), predictive positive value (PPV) (85.71%), positive likelihood ratio (PLR) (62.5), and accuracy (0.93). FIB4 was the second test in terms of accuracy (0.9) and PLR (10.53). Udelsman et al.¹¹, in contrast, evaluated liver biopsies of 2465 obese patients and reported that the NAFLD fibrosis score (NFS) performed best in screening out advanced fibrosis, with a sensitivity of 85% and an NPV of 99%.

In that regard, the American Society of Bariatric and Metabolic Surgery (ASBMS) recently proposed an algorithm for screening for advanced liver fibrosis in patients seeking bariatric surgery⁸. According to the authors, it is possible to rule out advanced fibrosis in one-third of the patients undergoing bariatric surgery. In other words, if the score is under the cutoff value of -1.455, they do not to recommend performing a liver biopsy intraoperatively. In patients with indeterminate or high NFS, liver stiffness measure or intraoperative liver biopsy should be considered.

However, we must emphasize that NAFLD is a variable spectrum of disease, which reduces the accuracy of clinical scores and makes it difficult to identify specific markers for screening for the disease. The condition also has a major burden in the public health system due to its natural history and negative outcomes. Therefore, in the context of bariatric surgery, it is very important to screen the patients for advanced fibrosis and cirrhosis, since it may alter the follow-up and treatment after surgery. Intraoperative liver biopsy is relatively safe because it is possible to observe and confirm hemostasis, unlike percutaneous needle biopsy¹². We also believe that the additional operative time (around 5 min) and the cost of processing the specimen do not overcome the potential benefits of an accurate diagnosis.

There are no NASH-specific medications. Weight loss is the first treatment goal if it has the strongest association with histologic improvement¹,². Currently, bariatric surgery is the most effective weight-loss therapy, which plays a crucial role in the management of obese patients with NAFLD and NASH. Studies comparing liver biopsies before and after bariatric surgery have shown substantial improvements in liver histology, including fibrosis regression⁵–⁷.

The NAFLD inflicts a great burden on patients’ and on the health system. As long as we do not find an accurate biochemical marker or clinical score, intraoperative liver biopsy remains the best alternative for an adequate diagnosis in patients undergoing bariatric surgery. It allows the proper follow-up and treatment after the surgery. Routine hepatic biopsy during surgery makes possible to both the physician and the patient to know the real extent of the problem and manage it properly. The high prevalence of NAFLD in this population overcomes any possible complications or extra cost of the procedure.

• Financial source: None
• Editorial Support: National Council for Scientific and Technological Development (CNPq).

REFERENCES

• ¹
  Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328-57. https://doi.org/10.1002/hep.29367
  » https://doi.org/10.1002/hep.29367
• ²
  Chitturi S. Treatment options for nonalcoholic Fatty liver disease. Therap Adv Gastroenterol. 2008;1(3):173-89. https://doi.org/10.1177/1756283X08096951
  » https://doi.org/10.1177/1756283X08096951
• ³
  Carli MA, Carli LA, Correa MB, Junqueira Júnior G, Tovo CV, Coral GP. Performance of noninvasive scores for the diagnosis of advanced liver fibrosis in morbidly obese with nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol. 2020;32(3):420-5. https://doi.org/10.1097/MEG.0000000000001519
  » https://doi.org/10.1097/MEG.0000000000001519
• ⁴
  Feijó SG, Lima JM, Oliveira MA, Patrocínio RM, Moura-Junior LG, Campos AB, et al. The spectrum of nonalcoholic fatty liver disease in morbidly obese patients: prevalence and associate risk factors. Acta Cir Bras. 2013;28(11):788-93. https://doi.org/10.1590/s0102-86502013001100008
  » https://doi.org/10.1590/s0102-86502013001100008
• ⁵
  Lassailly G, Caiazzo R, Buob D, Pigeyre M, Verkindt H, Labreuche J, et al. Bariatric surgery reduces features of nonalcoholic steatohepatitis in morbidly obese patients. Gastroenterology. 2015;149(2):379-88. https://doi.org/10.1053/j.gastro.2015.04.014
  » https://doi.org/10.1053/j.gastro.2015.04.014
• ⁶
  Lima RR, Garcia JHP, Studart MS, Pinheiro FS, Pinto JOG, Sales LA, et al. Accuracy of elastography in the assessment of reduction in liver steatosis and fibrosis in the early postoperative period after bariatric surgery. Arq Bras Cir Dig. 2022;35:e1671. https://doi.org/10.1590/0102-672020220002e1671
  » https://doi.org/10.1590/0102-672020220002e1671
• ⁷
  Mathurin P, Hollebecque A, Arnalsteen L, Buob D, Leteurtre E, Caiazzo R, et al. Prospective study of the long-term effects of bariatric surgery on liver injury in patients without advanced disease. Gastroenterology. 2009;137(2):532-40. https://doi.org/10.1053/j.gastro.2009.04.052
  » https://doi.org/10.1053/j.gastro.2009.04.052
• ⁸
  Mazzini GS, Augustin T, Noria S, Romero-Marrero C, Li N, Hameed B, et al. ASMBS Position Statement on the Impact of Metabolic and Bariatric Surgery on Nonalcoholic Steatohepatitis. Surg Obes Relat Dis. 2022;18(3):314-25. https://doi.org/10.1016/j.soard.2021.11.015
  » https://doi.org/10.1016/j.soard.2021.11.015
• ⁹
  Sheka AC, Adeyi O, Thompson J, Hameed B, Crawford PA, Ikramuddin S. Nonalcoholic Steatohepatitis: a review. JAMA. 2020;323(12):1175-83. https://doi.org/10.1001/jama.2020.2298
  » https://doi.org/10.1001/jama.2020.2298
• ¹⁰
  Silva MBBE, Tustumi F, Dantas ACB, Miranda BCJ, Pajecki D, DE-Cleva R, et al. Obesity and severe steatosis: the importance of biochemical exams and scores. Arq Bras Cir Dig. 2022;34(4):e1626. https://doi.org/10.1590/0102-672020210002e1626
  » https://doi.org/10.1590/0102-672020210002e1626
• ¹¹
  Udelsman BV, Corey K, Hutter MM, Chang DC, Witkowski ER. Use of noninvasive scores for advanced liver fibrosis can guide the need for hepatic biopsy during bariatric procedures. Surg Obes Relat Dis. 2021;17(2):292-8. https://doi.org/10.1016/j.soard.2020.09.037
  » https://doi.org/10.1016/j.soard.2020.09.037
• ¹²
  Vargas C, Jeffers LJ, Bernstein D, Reddy KR, Munnangi S, Behar S, et al. Diagnostic laparoscopy: a 5-year experience in a hepatology training program. Am J Gastroenterol. 1995;90(8):1258-62. PMID: 7639226
• ¹³
  Younossi Z, Anstee QM, Marietti M, Hardy T, Henry L, Eslam M, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2018;15(1):11-20. https://doi.org/10.1038/nrgastro.2017.109
  » https://doi.org/10.1038/nrgastro.2017.109

Publication Dates

• Publication in this collection
  20 Mar 2023
• Date of issue
  2023

History

• Received
  06 Aug 2022
• Accepted
  01 Dec 2022