Non-alcoholic fatty liver disease overview: Difference between revisions

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==Differentiating Non-alcoholic fatty liver disease from Other Diseas ==
==Differentiating Non-alcoholic fatty liver disease from Other Diseas ==
* NAFLD must be differentiated from Auto Immune Hepatitis,α1-antitrypsin deficiency,Wilson disease and Hereditary hemochromatosis.


==Epidemiology and Demographics==
==Epidemiology and Demographics==

Revision as of 16:15, 14 December 2017

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Non-Alcoholic Fatty Liver Disease Microchapters

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Overview

Historical Perspective

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Causes

Differentiating Non-Alcoholic Fatty Liver Disease from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

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Ultrasound

Other Imaging Findings

Other Diagnostic Studies

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Editor in Chief: Elliot Tapper, M.D., Beth Israel Deaconess Medical Center, C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vamsikrishna Gunnam M.B.B.S [2]

Overview

Nonalcoholic fatty liver disease [NAFLD] is due to the deposition of extra fat in liver cells that is not caused by alcohol. It is normal for the liver to contain some fat. However, when there is more than 5 -10 percent of the liver’s weight is fat, then it is called a fatty liver (steatosis).NAFLD is marked by inflammation that can progress to irreversible damage.NAFLD is similar to the damage caused by alcohol consumption in most of the cases. It is estimated that in united states approximately 80 to 100 million people are affected with NAFLD. Reflecting the obesity worldwide now NAFLD has become one of the leading cause of chronic liver disease. NAFLD most commonly affects people in the age group 2-19 and 40-50 years.It is most commonly seen in Hispanic population when compared to Caucasian and African American populations.

Historical Perspective

  • First introduced in 1980, NAFLD is a quite new concept. [1]
  • It is divided into non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) primarily based on histologic findings.
  • Biopsies of NAFL may also display macrovesicular steatosis with lobular and periportal irritation however do now not display cellular injury and fibrosis (steatohepatitis), which characterizes NASH. [2]
  • NAFL has in large part been taken into consideration benign, but recent cohort studies display a high hazard for development to NASH in as much as 44% on serial biopsies at 5 years.
  • NASH reasons modern fibrosis which could result in cirrhosis and hepatocellular cancer (HCC).

Classification

  • Based on histology it is classified into the non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH).NAFL mostly considered as a benign condition but recent studies show it can progress to NASH up to 44%. The more severe form of NAFLD is called non-alcoholic steatohepatitis (NASH).[3]
  • One of the leading cause for cirrhosis in adults in united states is NASH. Almost 25 percent of adults with NASH may lead to cirrhosis.
  • On the other hand, NASH progress to fibrosis that can lead to cirrhosis and hepatocellular cancer (HCC).[4]
  • Rate of progression does not correlate with body mass index (BMI) or hyperlipidemia

Pathophysiology

  • The exact pathogenesis of NAFLD is not fully understood, But It is thought that pathophysiology of NAFLD is multifactorial that includes numerous genetic, dietary, metabolic and hormonal factors.
  • According to the 2 hit hypothesis NAFLD is described as follows
    • The first hit resulting in increased fat accumulation especially triglycerides within the hepatocyte and increases the risk of liver injury.
    • On the second hit inflammatory cytokines causes mitochondrial dysfunction and oxidative stress which in turn lead to steatohepatitis and/or fibrosis.[5].
  • Free fatty acids (FFA) play very crucial role in damaging the liver indirectly by either undergoing β-oxidation or are esterified with glycerol to form triglycerides, leading to hepatic fat accumulation.
  • Now there is new evidence that FFA is directly causing the liver damage by increasing the oxidative stress by upregulation of TNF-alpha expression via a lysosomal pathway.

[6]

  • Oxidative stress inhibits the replication process in the mature hepatocytes, Results in the proliferation of progenitor (oval ) cell population and later they differentiate into hepatocyte-like cells. Now both the oval and hepatocyte-like cells play a very important role in the process of fibrosis and hepatocellular carcinogenesis.[5]
  • Alterations in MTP/apoB synthesis and secretion have been implicated as one of the potential mechanisms in the pathogenesis of NAFLD which in turn leads to a decreased capacity for lipid export
  • Normally triglycerides are transported from the liver in the form of VLDL particles which are then formed by the incorporation of triglyceride into apolipoprotein B (apoB) by microsomal transfer protein (MTP).[7]

Causes

Differentiating Non-alcoholic fatty liver disease from Other Diseas

  • NAFLD must be differentiated from Auto Immune Hepatitis,α1-antitrypsin deficiency,Wilson disease and Hereditary hemochromatosis.

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

  • NASH may progress to fibrosis and, later, to cirrhosis.
  • Studies of serial liver biopsies estimate a 26-37% rate of hepatic fibrosis and 2-15% rate of cirrhosis in less than 6 years. [16][17][18]
  • In 2001, NASH represented 2.9% of the indications of liver transplantation.[19]
  • The impact of NAFLD is manifest at each step along the spectrum of the disease.
  • Studies in the United States and Sweden have revealed that both simple steatosis as well as steatohepatitis significantly reduce life expectancy, even when the diagnosis is made in children.[20][21]
  • patients with NAFLD when high NAFLD fibrosis score (NFS) and a high fibrosis-4 (FIB-4) score have increased the risk of developing Hepatocellular cancer, colorectal cancer in males, and breast cancer in females.[22]
  • Esophageal varices.
  • Hepatic failure leads to encephalopathy.

Diagnosis

Diagnosis Criteria

 
Incidental finding of Fatty liver on ultrasound
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Check for persistently raised LFTs
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ask the patient for significant alcohol intake
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NO
 
 
 
YES
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Diagnose NAFLD
 
 
 
Consider other
alcoholic related diseases


Monitor severity of the disease


 
 
 
 
 
Offer Enhanced Liver Fibrosis Test (ELF)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(>10.51) ELF Positive
 
 
 
(<10.51) ELF Negative
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Indicating advanced fibrosis and risk of progression to cirrhosis
 
 
 
Typically Benign -- Advanced fibrosis unlikely
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Refer the patient to Heptologist
 
 
 
 
  • On negative ELF test offer retest for every 3 years for adults and 2 years for children.

History and Symptoms

Usually, NAFLD [Nonalcoholic fatty liver disease] presents with no or few symptoms and sighs but when it does it shows the following[23]

  • Hepatomegaly
  • Patient presents with fatigue
  • Abdominal swelling (ascites)
  • Enlarged breasts in men ( due to decreased estrogen clearance by liver damage )
  • Pain in the upper right abdomen
  • Yellowing of the skin and eyes (jaundice)
  • Splenomegaly
  • The disease may present first with cirrhosis and/or the complication of portal hypertension.

Physical Examination

Laboratory Findings

  • Elevated liver function tests are common. Typically, one finds a 2-4 fold elevation of the ALT above normal limit and an ALT/AST ratio of greater than 1.[24] This ratio is imperfect, as AST tends to rise with the degree of fibrosis.[25]
  • Furthermore,high ALT values within the reference range (less than 40 IU) are still predictive of NAFLD/NASH.[26]
  • Another blood test that can be elevated is the ferritin.
  • Typically, and except in very advanced disease, the liver's synthetic function is intact with normal albumin and INR.
  • When considering NAFLD, other tests are generally performed, including those for associated conditions (e.g. glucose, hemoglobin A1C) and those to distinguish this disease from viral hepatitis. Additionally, autoimmune causes are ruled out with serology.
  • TSH is warranted, as hypothyroidism is more prevalent in NASH patients.[27]

Imaging Findings

  • Imaging is often ordered in the workup of suspected NAFLD.
  • Ultrasound, and computed tomography have sensitivities between 93-100%, but 62-76% positive predictive values. Problematically, ultrasound of fatty liver reveals a hyperechoic echotexture - a so-called 'bright liver' - that can often be indistinguishable from fibrosis and generally cannot reliably delineate NAFLD from NASH.[28]
  • Computed tomography, is less sensitive, rarely detecting steatosis when fatty infiltration is less than 33%, but is potentially more specific.[29] Statistics are similar for MRI, however using advanced MR techniques, some groups have been able to both quantify steatosis and differentiate steatohepatitis from steatosis.[30][31]
  • Transient elastography, an enhanced form of ultrasound that measures the stiffness of your liver. Liver stiffness indicates fibrosis or scarring.

Other Diagnostic Studies

  • A biopsy of the liver is still considered the gold standard in diagnosis.
  • This is especially true for those patients with elevated liver enzymes for whom a non-invasive workup is inconclusive; 34% of these patients, in one series, were found to have NASH.[32]
  • Classically, biopsy reveals macrovesicular steatosis, inflammation, ballooning degeneration, zone 3 perivenular/periportal/perisinusoidal fibrosis and, finally, mallory bodies.[33][34]

Medical Therapy

  • Trials are presently being conducted to optimize treatment of NASH. No standard treatment has yet emerged as the gold standard.
  • General recommendations include improving metabolic risk factors - weight loss, treating diabetes, managing lipids - and reducing alcohol intake.
  • Moringa Oleifera (MO), a plant from the family Moringacea is a major crop in Asia and Africa, the leaves of these plant have been studied extensively and it has shown to be beneficial in NAFLD and in prevention and alleviation of NAFLD.[35]
  • Very recently treatment with probiotics shown very significant decrease in the inflammation of the liver without any adverse side effects. [36][37]

Surgery

Primary Prevention

There are some ways to prevent NAFLD,

  • Eating a healthy diet is the first and very important step. Eat food that is rich in vegetables, fruits and healthy fats.
  • Exercise on regular basis.
  • Maintain a healthy weight.
  • Alcohol cessation, If Patient drinks.
  • Take medications under the guidance of physician when needed, don't take unnecessary medications

Secondary Prevention

References

  1. ↑ Vizuete J, Camero A, Malakouti M, Garapati K, Gutierrez J (2017). "Perspectives on Nonalcoholic Fatty Liver Disease: An Overview of Present and Future Therapies". J Clin Transl Hepatol. 5 (1): 67–75. doi:10.14218/JCTH.2016.00061. PMC 5411359. PMID 28507929.
  2. ↑ Zhao ZH, Liu XL, Fan JG (2017). "[Research on the natural history of non-alcoholic fatty liver disease should be taken seriously]". Zhonghua Gan Zang Bing Za Zhi (in Chinese). 25 (2): 81–84. PMID 28297791.
  3. ↑ "American Liver Foundation - Non-Alcoholic Fatty Liver Disease".
  4. ↑ "Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: implications for prognosis and clinical management. - PubMed - NCBI".
  5. ↑ 5.0 5.1 Dowman JK, Tomlinson JW, Newsome PN (2010). "Pathogenesis of non-alcoholic fatty liver disease". QJM. 103 (2): 71–83. doi:10.1093/qjmed/hcp158. PMC 2810391. PMID 19914930.
  6. ↑ Feldstein AE, Werneburg NW, Canbay A, Guicciardi ME, Bronk SF, Rydzewski R, Burgart LJ, Gores GJ (2004). "Free fatty acids promote hepatic lipotoxicity by stimulating TNF-alpha expression via a lysosomal pathway". Hepatology. 40 (1): 185–94. doi:10.1002/hep.20283. PMID 15239102.
  7. ↑ "Apolipoprotein synthesis in nonalcoholic steatohepatitis - Charlton - 2002 - Hepatology - Wiley Online Library".
  8. ↑ "Nonalcoholic Fatty Liver Disease".
  9. ↑ Sung KC, Jeong WS, Wild SH, Byrne CD (2012). "Combined influence of insulin resistance, overweight/obesity, and fatty liver as risk factors for type 2 diabetes". Diabetes Care. 35 (4): 717–22. doi:10.2337/dc11-1853. PMC 3308286. PMID 22338098.
  10. ↑ "Nonalcoholic fatty liver disease".
  11. ↑ "Nonalcoholic Fatty Liver Disease".
  12. ↑ "Nonalcoholic Fatty Liver Disease & NASH | NIDDK".
  13. ↑ McCullough, AJ. Thiazolidinediones for NASH. NEJM 2006;355(22):2361-2363.
  14. ↑ Ong JP et al. Epidemiology and Natural History of NAFLD and NASH. Clin Liver Dis 11 (2007) 1–16
  15. ↑ Ruhl CE, Everhart JE. Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the united states. Gastroenterology 2003;124(1):71–9.
  16. ↑ Adams LA, Sanderson S, Lindor KD, et al. The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies. J Hepatol 2005;42(1):132–8.
  17. ↑ Harrison SA, Torgerson S, Hayashi PH. The natural history of nonalcoholic fatty liver disease:a clinical histopathological study. Am J Gastroenterol 2003;98(9):2042–7.
  18. ↑ Ekstedt M, Franzén LE, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006;44:865-73.
  19. ↑ Charlton M et al. Frequency of Nonalcoholic Steatohepatitis as a Cause of Advanced Liver Disease. Liver Transpl 2001;7:608-614
  20. ↑ Adams et al. The Natural History of Nonalcoholic Fatty Liver Disease: A Population-Based Cohort Study. GASTROENTEROLOGY 2005;129:113–121
  21. ↑ Feldstein AE et al. The natural history of non-alcoholic fatty liver disease in children: a follow-up study for up to 20 years. Gut 2009;58:1538–1544
  22. ↑ Kim GA, Lee HC, Choe J, Kim MJ, Lee MJ, Chang HS, Bae IY, Kim HK, An J, Shim JH, Kim KM, Lim YS (2017). "Association between non-alcoholic fatty liver disease and cancer incidence rate". J. Hepatol. doi:10.1016/j.jhep.2017.09.012. PMID 29150142.
  23. ↑ "Nafld".
  24. ↑ Powell et al. The Natural History of Nonalcoholic Steatohepatitis: A Follow-up Study of Forty-two Patients for Up to 21 YearsHEPATOLOGY 1990; 11: 74-80
  25. ↑ Sorbi et al. The Ratio of Aspartate Aminotransferase to Alanine Aminotransferase: Potential Value in Differentiating Nonalcoholic Steatohepatitis From Alcoholic Liver DiseaseAm J Gastroenterol 1999;94:1018–1022
  26. ↑ Chang Y et al. Higher Concentrations of Alanine Aminotransferase within the Reference Interval Predict Nonalcoholic Fatty Liver Disease. Clinical Chemistry 2007;53(4):686–692
  27. ↑ Liangpunsakul S, Chalasani N. Is hypothyroidism a risk factor for non-alcoholic steatohepatitis? J Clin Gastroenterol 2003;37:340-3. PMID 14506393
  28. ↑ MIshra P et al. Abdominal Ultrasound for Diagnosis of Nonalcoholic Fatty Liver Disease (NAFLD). Am J Gastroenterol 2007;102:2716–2717).
  29. ↑ Saadeh et al. The Utility of Radiological Imaging in Nonalcoholic Fatty Liver Disease. GASTROENTEROLOGY 2002;123:745–750
  30. ↑ Taouli B et al. Advanced MRI Methods for Assessment of Chronic Liver Disease. AJR 2009; 193:14–27.
  31. ↑ McPherson S et al. Magnetic resonance imaging and spectroscopy accurately estimate the severity of steatosis provided the stage of fibrosis is considered. J Hepatol. 2009;51(2):389-97
  32. ↑ Skelly et al. Findings on liver biopsy to investigate abnormal liver function tests in the absence of diagnostic serology. J Hepatol 2001;35:195-9
  33. ↑ Angula P. Nonalcoholic Fatty Liver Disease. NEJM. 2002 346(16):1221-31
  34. ↑ Brunt EM, Janney CG, Di Bisceglie AM et al. Nonalcoholic steatohepatitis: A proposal for grading and staging the histological lesions. Am. J. Gastroenterol. 1999; 94(9):2467-2474
  35. ↑ Vergara-Jimenez M, Almatrafi MM, Fernandez ML (2017). "Bioactive Components in Moringa Oleifera Leaves Protect against Chronic Disease". Antioxidants (Basel). 6 (4). doi:10.3390/antiox6040091. PMID 29144438.
  36. ↑ Manzhalii E, Virchenko O, Falalyeyeva T, Beregova T, Stremmel W (2017). "Treatment efficacy of a probiotic preparation for non-alcoholic steatohepatitis: a pilot trial". J Dig Dis. doi:10.1111/1751-2980.12561. PMID 29148175.
  37. ↑ Das N, Sikder K, Ghosh S, Fromenty B, Dey S (2012). "Moringa oleifera Lam. leaf extract prevents early liver injury and restores antioxidant status in mice fed with high-fat diet". Indian J. Exp. Biol. 50 (6): 404–12. PMID 22734251.

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