Non-alcoholic fatty liver disease natural history, complications and prognosis
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2]
Overview
If left untreated non-alcoholic fatty liver disease may progress to fibrosis and, later 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. Common complications of NAFLD include fibrosis, cirrhosis, internal bleeding, encephalopathy. The presence of fibrosis and cirrhosis associated with a particularly poor prognosis among patients with NAFLD.
Natural History, Complications and Prognosis
Natural History
- The symptoms of NAFLD usually develop in the 40th decade of life, and usually asymptomatic at first.
- After following NAFLD patients for long-term the outcome of the disease is as follows
- If left untreated, patients with NAFLD may progress to develop hepato-cellular carcinoma (HCC). But it is directly propotional to the degree of fibrosis and advanced cirrhosis
- Children who are positive with NAFLD are also prone to short lifespan when compared to general population.[1]
NAFLD with normal liver enzymes
Two cohort studies suggest no increased risk of cirrhosis among patients with steatosis by imaging but normal liver transaminases"
- NAFLD with normal liver enzyme levels (n = 41,461) after 6 years of monitoring.[2]
- NAFLD with normal liver enzyme levels (n = 3,522) after 8 years of monitoring[3].
NAFLD with high FIB-4
In a cohort study of uncertain duration, 8% of patients had a high FIB-4 and 3% had one of cirrhosis, hepatocellular carcinoma, and liver transplantation[4].
NAFLD with any fibrosis
The NIH Cohort found that any state of Fibrosis increases overall mortality or liver transplantation[5].
Complications
- Common complications of NAFLD include:[6][7]
- Fibrosis
- Cirrhosis. Amon patients with both hepatic steatosis and elevated liver function tests, the incidence rate of cirrhosis is 3.37 (95% CI: 2.34-4.86) per 1000 1000 person-years.
- Internal bleeding
- Encepholopathy
Non-alcoholic fatty liver disease, especially if with cirrhosis, may be associated with thrombocytopenia[8][9].
Prognosis
- In a cohort study of patient who had biopsy-proven NAFLD, 6% developed death, hepatocellular carcinoma, or death with 5 years[10].
- The rate of ESLD (fibrosis stage 3/4 with symptoms) among patients with fibrosis stage 1/2 over 20 years is per Nasr et al[11]:
- 11% (6 of 53) (Supplementary table 1)
- 25% (4 of 16) (Supplementary table 1)
- Histology is the most reliable means to grade the severity of the disease and thus estimate prognosis.
A simulation study has estimated prognoses[14]
Prognosis estimated based on treatment
Randomized controlled trials have been executed of:
- Semaglutide[15]:
- "An improvement in fibrosis stage occurred in 43% of the patients in the 0.4-mg group and in 33% of the patients in the placebo group (P=0.48)" over 6 years of treatment.
Assuming that
- The 14% improvement above found be Newsome et al[15] would be significant in larger trials
- An improvement in fibrosis state has the same clinical significance as regression from advanced fibrosis (stage 3 or 4) to non-advanced fibrosis (Stage 1 or 2)
The reduction in progression to end-stage liver disease (ESLD; fibrosis stage 3 or 4 with symptoms) by treating is 1.4% over twenty years. The estimate is based on:
10% (the absolute reduction in advanced fibrosis due to treatment according to Newsome et al[15]) x 14% (approximate absolute increase in risk of ESLD from fibrosis 3/4 versus fibrosis 1/2 per Nasr et al[11])
Thus, the number needed to treat (NNT) is about 70 (100/1.4).
References
- ↑ Calzadilla Bertot L, Adams LA (2016). "The Natural Course of Non-Alcoholic Fatty Liver Disease". Int J Mol Sci. 17 (5). doi:10.3390/ijms17050774. PMC 4881593. PMID 27213358.
- ↑ Huang YH, Chan C, Lee HW, Huang C, Chen YJ, Liu PC; et al. (2023). "Influence of Nonalcoholic Fatty Liver Disease With Increased Liver Enzyme Levels on the Risk of Cirrhosis and Hepatocellular Carcinoma". Clin Gastroenterol Hepatol. 21 (4): 960–969.e1. doi:10.1016/j.cgh.2022.01.046. PMC 9349477 Check
|pmc=
value (help). PMID 35124270 Check|pmid=
value (help). - ↑ Natarajan Y, Kramer JR, Yu X, Li L, Thrift AP, El-Serag HB; et al. (2020). "Risk of Cirrhosis and Hepatocellular Cancer in Patients With NAFLD and Normal Liver Enzymes". Hepatology. 72 (4): 1242–1252. doi:10.1002/hep.31157. PMC 8318072 Check
|pmc=
value (help). PMID 32022277 Check|pmid=
value (help). - ↑ Schreiner AD, Zhang J, Moran WP, Koch DG, Livingston S, Bays C; et al. (2023). "Real-World Primary Care Data Comparing ALT and FIB-4 in Predicting Future Severe Liver Disease Outcomes". J Gen Intern Med. 38 (11): 2453–2460. doi:10.1007/s11606-023-08093-8. PMID 36814048 Check
|pmid=
value (help). - ↑ Angulo P, Kleiner DE, Dam-Larsen S, Adams LA, Bjornsson ES, Charatcharoenwitthaya P; et al. (2015). "Liver Fibrosis, but No Other Histologic Features, Is Associated With Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease". Gastroenterology. 149 (2): 389–97.e10. doi:10.1053/j.gastro.2015.04.043. PMC 4516664. PMID 25935633.
- ↑ Chacko KR, Reinus J (2016). "Extrahepatic Complications of Nonalcoholic Fatty Liver Disease". Clin Liver Dis. 20 (2): 387–401. doi:10.1016/j.cld.2015.10.004. PMID 27063276.
- ↑ Vanni E, Marengo A, Mezzabotta L, Bugianesi E (2015). "Systemic Complications of Nonalcoholic Fatty Liver Disease: When the Liver Is Not an Innocent Bystander". Semin Liver Dis. 35 (3): 236–49. doi:10.1055/s-0035-1562944. PMID 26378641.
- ↑ Rivera-Álvarez M, Córdova-Ramírez AC, Elías-De-La-Cruz GD, Murrieta-Álvarez I, León-Peña AA, Cantero-Fortiz Y; et al. (2021). "Non-alcoholic fatty liver disease and thrombocytopenia IV: its association with granulocytopenia". Hematol Transfus Cell Ther. doi:10.1016/j.htct.2021.06.004. PMID 34312112 Check
|pmid=
value (help). - ↑ Panke CL, Tovo CV, Villela-Nogueira CA, Cravo CM, Ferreira FC, Rezende GFM; et al. (2020). "Evaluation of thrombocytopenia in patients with non-alcoholic fatty liver disease without cirrhosis". Ann Hepatol. 19 (1): 88–91. doi:10.1016/j.aohep.2019.05.011. PMID 31575467.
- ↑ Mózes FE, Lee JA, Vali Y, Alzoubi O, Staufer K, Trauner M; et al. (2023). "Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis". Lancet Gastroenterol Hepatol. doi:10.1016/S2468-1253(23)00141-3. PMID 37290471 Check
|pmid=
value (help). - ↑ 11.0 11.1 Nasr P, Ignatova S, Kechagias S, Ekstedt M (2018). "Natural history of nonalcoholic fatty liver disease: A prospective follow-up study with serial biopsies". Hepatol Commun. 2 (2): 199–210. doi:10.1002/hep4.1134. PMC 5796332. PMID 29404527.
- ↑ Jepsen P, Grønbæk H (2011). "Prognosis and staging of non-alcoholic fatty liver disease". BMJ. 343: d7302. doi:10.1136/bmj.d7302. PMID 22102440.
- ↑ Suman, A.; Khullar, V.; Limaye, A. (2016). "Complications of Non-Alcoholic Fatty Liver Disease". Journal of Hepatology. 64 (2): S473. doi:10.1016/S0168-8278(16)00798-4. ISSN 0168-8278.
- ↑ Chhatwal J, Dalgic OO, Chen W, Samur S, Bethea ED, Xiao J; et al. (2022). "Analysis of a Simulation Model to Estimate Long-term Outcomes in Patients with Nonalcoholic Fatty Liver Disease". JAMA Netw Open. 5 (9): e2230426. doi:10.1001/jamanetworkopen.2022.30426. PMC 9471976 Check
|pmc=
value (help). PMID 36098969 Check|pmid=
value (help). - ↑ 15.0 15.1 15.2 Newsome PN, Buchholtz K, Cusi K, Linder M, Okanoue T, Ratziu V; et al. (2021). "A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis". N Engl J Med. 384 (12): 1113–1124. doi:10.1056/NEJMoa2028395. PMID 33185364 Check
|pmid=
value (help).