Non-alcoholic fatty liver disease natural history, complications and prognosis: Difference between revisions
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{{Non alcoholic fatty liver disease}} | {{Non alcoholic fatty liver disease}} | ||
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==Overview== | ==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, Complications and Prognosis== | ||
{{see also|Non-alcoholic fatty liver disease Noninvasive scores}} | |||
===Natural History=== | ===Natural History=== | ||
*The symptoms of NAFLD usually develop in the 40th decade of life, | *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 | *After following NAFLD patients for long-term the outcome of the disease is as follows | ||
**1) Patients with [[Non-alcoholic fatty liver disease|NAFLD]] has overall high morbidity and mortality rate and the common cause of death in NAFLD patients is cardiovascular disease. | **1) Patients with [[Non-alcoholic fatty liver disease|NAFLD]] has overall high [[morbidity]] and [[mortality]] rate and the common cause of death in NAFLD patients is cardiovascular disease. | ||
**2) Patients with [[NASH]] has more liver-related mortality rate | **2) Patients with [[NASH]] has more liver-related mortality rate | ||
* If left untreated, | * 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.<ref name=" | * Children who are positive with NAFLD are also prone to short lifespan when compared to general population.<ref name="pmid27213358">{{cite journal| author=Calzadilla Bertot L, Adams LA| title=The Natural Course of Non-Alcoholic Fatty Liver Disease. | journal=Int J Mol Sci | year= 2016 | volume= 17 | issue= 5 | pages= | pmid=27213358 | doi=10.3390/ijms17050774 | pmc=4881593 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27213358 }} </ref> | ||
Patients progress about 1 stage per 7 years<ref name="pmid24768810">{{cite journal| author=Singh S, Allen AM, Wang Z, Prokop LJ, Murad MH, Loomba R| title=Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies. | journal=Clin Gastroenterol Hepatol | year= 2015 | volume= 13 | issue= 4 | pages= 643-54.e1-9; quiz e39-40 | pmid=24768810 | doi=10.1016/j.cgh.2014.04.014 | pmc=4208976 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24768810 }} </ref>. | |||
==== 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.<ref name="pmid35124270">{{cite journal| author=Huang YH, Chan C, Lee HW, Huang C, Chen YJ, Liu PC | display-authors=etal| title=Influence of Nonalcoholic Fatty Liver Disease With Increased Liver Enzyme Levels on the Risk of Cirrhosis and Hepatocellular Carcinoma. | journal=Clin Gastroenterol Hepatol | year= 2023 | volume= 21 | issue= 4 | pages= 960-969.e1 | pmid=35124270 | doi=10.1016/j.cgh.2022.01.046 | pmc=9349477 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=35124270 }} </ref> | |||
* NAFLD with normal liver enzyme levels (n = 3,522) after 8 years of monitoring<ref name="pmid32022277">{{cite journal| author=Natarajan Y, Kramer JR, Yu X, Li L, Thrift AP, El-Serag HB | display-authors=etal| title=Risk of Cirrhosis and Hepatocellular Cancer in Patients With NAFLD and Normal Liver Enzymes. | journal=Hepatology | year= 2020 | volume= 72 | issue= 4 | pages= 1242-1252 | pmid=32022277 | doi=10.1002/hep.31157 | pmc=8318072 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32022277 }} </ref>. | |||
==== 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<ref name="pmid36814048">{{cite journal| author=Schreiner AD, Zhang J, Moran WP, Koch DG, Livingston S, Bays C | display-authors=etal| title=Real-World Primary Care Data Comparing ALT and FIB-4 in Predicting Future Severe Liver Disease Outcomes. | journal=J Gen Intern Med | year= 2023 | volume= 38 | issue= 11 | pages= 2453-2460 | pmid=36814048 | doi=10.1007/s11606-023-08093-8 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=36814048 }} </ref>. | |||
==== NAFLD and fatty liver index ==== | |||
The fatty liver index (FLI) is based on the following findings from a cohort study<ref name="pmid17081293">{{cite journal| author=Bedogni G, Bellentani S, Miglioli L, Masutti F, Passalacqua M, Castiglione A | display-authors=etal| title=The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population. | journal=BMC Gastroenterol | year= 2006 | volume= 6 | issue= | pages= 33 | pmid=17081293 | doi=10.1186/1471-230X-6-33 | pmc=1636651 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17081293 }} </ref>: | |||
{| class="wikitable" | |||
|+ Parameters of the fatty liver index<ref name="pmid17081293"/> | |||
! Parameter !! Regression coefficient] | |||
|- | |||
| Log<sub>e</sub> (triglycerides, mg*dL<sup>-1</sup>) || style="text-align: right;"| 0.953 | |||
|- | |||
| BMI (kg*m<sup>2-1</sup>)|| style="text-align: right;"| 0.139 | |||
|- | |||
| Log<sub>e</sub> (GGT, U*L<sup>-1</sup>) || style="text-align: right;"| 0.718 | |||
|- | |||
| Waist circumference (cm) || style="text-align: right;"| 0.053 | |||
|- | |||
| Constant || style="text-align: right;"| -15.745 | |||
|} | |||
This leads to the equation: | |||
FLI = (e <sup>0.953*loge (triglycerides) + 0.139*BMI + 0.718*loge (ggt) + 0.053*waist circumference - 15.745</sup>) / (1 + e <sup>0.953*loge (triglycerides) + 0.139*BMI + 0.718*loge (ggt) + 0.053*waist circumference - 15.745</sup>) * 100 | |||
Or the equation may be expressed as: | |||
* e<sup>y</sup> / (1 + e<sup>y</sup>) × 100 | |||
* Note that in both the numerator and denominator the exponent is: y = 0.953 × ln(triglycerides, mg/dL) + 0.139 × BMI + 0.718 × ln (GGT, U/L) + 0.053 × waist circumference, cm – 15.745 | |||
This equation has been used to prognosticate<ref name="pmid38350680">{{cite journal| author=Kim KS, Hong S, Han K, Park CY| title=Association of non-alcoholic fatty liver disease with cardiovascular disease and all cause death in patients with type 2 diabetes mellitus: nationwide population based study. | journal=BMJ | year= 2024 | volume= 384 | issue= | pages= e076388 | pmid=38350680 | doi=10.1136/bmj-2023-076388 | pmc=10862140 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=38350680 }} </ref>. | |||
Online calculators are available: | |||
* Diagnosis of fatty liver. [https://www.mdcalc.com/calc/10001/fatty-liver-index MDCALC] | |||
* Distinguishing alchoholic and nonalcoholic fatty liver disease, [https://www.mayoclinic.org/medical-professionals/transplant-medicine/calculators/the-alcoholic-liver-disease-nonalcoholic-fatty-liver-disease-index-ani/itt-20434726 Mayo Clinic] | |||
==== NAFLD with any fibrosis ==== | |||
The NIH Cohort found that any state of Fibrosis increases overall mortality or liver transplantation<ref name="pmid25935633">{{cite journal| author=Angulo P, Kleiner DE, Dam-Larsen S, Adams LA, Bjornsson ES, Charatcharoenwitthaya P | display-authors=etal| title=Liver Fibrosis, but No Other Histologic Features, Is Associated With Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease. | journal=Gastroenterology | year= 2015 | volume= 149 | issue= 2 | pages= 389-97.e10 | pmid=25935633 | doi=10.1053/j.gastro.2015.04.043 | pmc=4516664 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25935633 }} </ref>. | |||
*Common complications of NAFLD include: | ==== NAFLD imaging ==== | ||
**Fibrosis | Elastography can help determine prognosis<ref name="pmid38512249">{{cite journal| author=Lin H, Lee HW, Yip TC, Tsochatzis E, Petta S, Bugianesi E | display-authors=etal| title=Vibration-Controlled Transient Elastography Scores to Predict Liver-Related Events in Steatotic Liver Disease. | journal=JAMA | year= 2024 | volume= | issue= | pages= | pmid=38512249 | doi=10.1001/jama.2024.1447 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=38512249 }} </ref>. | ||
** | |||
**Internal bleeding | ===Complications=== | ||
*Common complications of NAFLD include:<ref name="pmid27063276">{{cite journal| author=Chacko KR, Reinus J| title=Extrahepatic Complications of Nonalcoholic Fatty Liver Disease. | journal=Clin Liver Dis | year= 2016 | volume= 20 | issue= 2 | pages= 387-401 | pmid=27063276 | doi=10.1016/j.cld.2015.10.004 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27063276 }} </ref><ref name="pmid26378641">{{cite journal| author=Vanni E, Marengo A, Mezzabotta L, Bugianesi E| title=Systemic Complications of Nonalcoholic Fatty Liver Disease: When the Liver Is Not an Innocent Bystander. | journal=Semin Liver Dis | year= 2015 | volume= 35 | issue= 3 | pages= 236-49 | pmid=26378641 | doi=10.1055/s-0035-1562944 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26378641 }} </ref> | |||
**[[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 | **Encepholopathy | ||
[[Non-alcoholic fatty liver disease]], especially if with cirrhosis, may be associated with [[thrombocytopenia]]<ref name="pmid34312112">{{cite journal| author=Rivera-Álvarez M, Córdova-Ramírez AC, Elías-De-La-Cruz GD, Murrieta-Álvarez I, León-Peña AA, Cantero-Fortiz Y | display-authors=etal| title=Non-alcoholic fatty liver disease and thrombocytopenia IV: its association with granulocytopenia. | journal=Hematol Transfus Cell Ther | year= 2021 | volume= | issue= | pages= | pmid=34312112 | doi=10.1016/j.htct.2021.06.004 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=34312112 }} </ref><ref name="pmid31575467">{{cite journal| author=Panke CL, Tovo CV, Villela-Nogueira CA, Cravo CM, Ferreira FC, Rezende GFM | display-authors=etal| title=Evaluation of thrombocytopenia in patients with non-alcoholic fatty liver disease without cirrhosis. | journal=Ann Hepatol | year= 2020 | volume= 19 | issue= 1 | pages= 88-91 | pmid=31575467 | doi=10.1016/j.aohep.2019.05.011 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31575467 }} </ref>. | |||
===Prognosis=== | ===Prognosis=== | ||
* Histology is the most reliable means to grade the severity of the disease and thus estimate prognosis | * In a cohort study of patient who had biopsy-proven NAFLD, 6% developed death, hepatocellular carcinoma, or death with 5 years<ref name="pmid37290471">{{cite journal| author=Mózes FE, Lee JA, Vali Y, Alzoubi O, Staufer K, Trauner M | display-authors=etal| title=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. | journal=Lancet Gastroenterol Hepatol | year= 2023 | volume= | issue= | pages= | pmid=37290471 | doi=10.1016/S2468-1253(23)00141-3 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=37290471 }} </ref>. | ||
* The | |||
* Depending on the extent of the fibrosis and cirrhosis at the time of diagnosis, the prognosis may vary.<ref name=" | In a cohort of patients with steatosis by imaging but did not have liver biopsies, after 8 years of follow-up, liver function tests predicted clinical outcomes only if LFTs abnormal<ref name="pmid32022277">{{cite journal| author=Natarajan Y, Kramer JR, Yu X, Li L, Thrift AP, El-Serag HB | display-authors=etal| title=Risk of Cirrhosis and Hepatocellular Cancer in Patients With NAFLD and Normal Liver Enzymes. | journal=Hepatology | year= 2020 | volume= 72 | issue= 4 | pages= 1242-1252 | pmid=32022277 | doi=10.1002/hep.31157 | pmc=8318072 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32022277 }} </ref>. | ||
* | |||
* 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<ref name="pmid29404527">{{cite journal| author=Nasr P, Ignatova S, Kechagias S, Ekstedt M| title=Natural history of nonalcoholic fatty liver disease: A prospective follow-up study with serial biopsies. | journal=Hepatol Commun | year= 2018 | volume= 2 | issue= 2 | pages= 199-210 | pmid=29404527 | doi=10.1002/hep4.1134 | pmc=5796332 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29404527 }} </ref>: | |||
** 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. | |||
** The presence of [[fibrosis]] and [[cirrhosis]] is associated with a particularly poor prognosis among patients with NAFLD. <ref name="pmid22102440">{{cite journal| author=Jepsen P, Grønbæk H| title=Prognosis and staging of non-alcoholic fatty liver disease. | journal=BMJ | year= 2011 | volume= 343 | issue= | pages= d7302 | pmid=22102440 | doi=10.1136/bmj.d7302 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22102440 }} </ref> | |||
** Depending on the extent of the [[fibrosis]] and [[cirrhosis]] at the time of diagnosis, the prognosis may vary.<ref name="SumanKhullar2016">{{cite journal|last1=Suman|first1=A.|last2=Khullar|first2=V.|last3=Limaye|first3=A.|title=Complications of Non-Alcoholic Fatty Liver Disease|journal=Journal of Hepatology|volume=64|issue=2|year=2016|pages=S473|issn=01688278|doi=10.1016/S0168-8278(16)00798-4}}</ref> | |||
A simulation study has estimated prognoses<ref name="pmid36098969">{{cite journal| author=Chhatwal J, Dalgic OO, Chen W, Samur S, Bethea ED, Xiao J | display-authors=etal| title=Analysis of a Simulation Model to Estimate Long-term Outcomes in Patients with Nonalcoholic Fatty Liver Disease. | journal=JAMA Netw Open | year= 2022 | volume= 5 | issue= 9 | pages= e2230426 | pmid=36098969 | doi=10.1001/jamanetworkopen.2022.30426 | pmc=9471976 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=36098969 }} </ref> | |||
==== Prognosis estimated based on treatment ==== | |||
Randomized controlled trials have been executed of: | |||
* Semaglutide<ref name="pmid33185364">{{cite journal| author=Newsome PN, Buchholtz K, Cusi K, Linder M, Okanoue T, Ratziu V | display-authors=etal| title=A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. | journal=N Engl J Med | year= 2021 | volume= 384 | issue= 12 | pages= 1113-1124 | pmid=33185364 | doi=10.1056/NEJMoa2028395 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=33185364 }} </ref>: | |||
** "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<ref name="pmid33185364"/> 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<ref name="pmid33185364"/>) | |||
x | |||
14% (approximate absolute increase in risk of ESLD from fibrosis 3/4 versus fibrosis 1/2 per Nasr et al<ref name="pmid29404527"/>) | |||
Thus, the number needed to treat (NNT) is about 70 (100/1.4). | |||
==References== | ==References== |
Latest revision as of 23:53, 21 March 2024
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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]
Patients progress about 1 stage per 7 years[2].
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.[3]
- NAFLD with normal liver enzyme levels (n = 3,522) after 8 years of monitoring[4].
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[5].
NAFLD and fatty liver index
The fatty liver index (FLI) is based on the following findings from a cohort study[6]:
Parameter | Regression coefficient] |
---|---|
Loge (triglycerides, mg*dL-1) | 0.953 |
BMI (kg*m2-1) | 0.139 |
Loge (GGT, U*L-1) | 0.718 |
Waist circumference (cm) | 0.053 |
Constant | -15.745 |
This leads to the equation: FLI = (e 0.953*loge (triglycerides) + 0.139*BMI + 0.718*loge (ggt) + 0.053*waist circumference - 15.745) / (1 + e 0.953*loge (triglycerides) + 0.139*BMI + 0.718*loge (ggt) + 0.053*waist circumference - 15.745) * 100
Or the equation may be expressed as:
- ey / (1 + ey) × 100
- Note that in both the numerator and denominator the exponent is: y = 0.953 × ln(triglycerides, mg/dL) + 0.139 × BMI + 0.718 × ln (GGT, U/L) + 0.053 × waist circumference, cm – 15.745
This equation has been used to prognosticate[7].
Online calculators are available:
- Diagnosis of fatty liver. MDCALC
- Distinguishing alchoholic and nonalcoholic fatty liver disease, Mayo Clinic
NAFLD with any fibrosis
The NIH Cohort found that any state of Fibrosis increases overall mortality or liver transplantation[8].
NAFLD imaging
Elastography can help determine prognosis[9].
Complications
- Common complications of NAFLD include:[10][11]
- 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[12][13].
Prognosis
- In a cohort study of patient who had biopsy-proven NAFLD, 6% developed death, hepatocellular carcinoma, or death with 5 years[14].
In a cohort of patients with steatosis by imaging but did not have liver biopsies, after 8 years of follow-up, liver function tests predicted clinical outcomes only if LFTs abnormal[4].
- 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[15]:
- 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[18]
Prognosis estimated based on treatment
Randomized controlled trials have been executed of:
- Semaglutide[19]:
- "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[19] 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[19]) x 14% (approximate absolute increase in risk of ESLD from fibrosis 3/4 versus fibrosis 1/2 per Nasr et al[15])
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.
- ↑ Singh S, Allen AM, Wang Z, Prokop LJ, Murad MH, Loomba R (2015). "Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies". Clin Gastroenterol Hepatol. 13 (4): 643-54.e1-9, quiz e39-40. doi:10.1016/j.cgh.2014.04.014. PMC 4208976. PMID 24768810.
- ↑ 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). - ↑ 4.0 4.1 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). - ↑ 6.0 6.1 Bedogni G, Bellentani S, Miglioli L, Masutti F, Passalacqua M, Castiglione A; et al. (2006). "The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population". BMC Gastroenterol. 6: 33. doi:10.1186/1471-230X-6-33. PMC 1636651. PMID 17081293.
- ↑ Kim KS, Hong S, Han K, Park CY (2024). "Association of non-alcoholic fatty liver disease with cardiovascular disease and all cause death in patients with type 2 diabetes mellitus: nationwide population based study". BMJ. 384: e076388. doi:10.1136/bmj-2023-076388. PMC 10862140 Check
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value (help). PMID 38350680 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.
- ↑ Lin H, Lee HW, Yip TC, Tsochatzis E, Petta S, Bugianesi E; et al. (2024). "Vibration-Controlled Transient Elastography Scores to Predict Liver-Related Events in Steatotic Liver Disease". JAMA. doi:10.1001/jama.2024.1447. PMID 38512249 Check
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value (help). - ↑ 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
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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
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value (help). - ↑ 15.0 15.1 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). - ↑ 19.0 19.1 19.2 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).