APIK Journal of Internal Medicine

: 2021  |  Volume : 9  |  Issue : 3  |  Page : 139--145

Nonalcoholic fatty liver disease: New epidemic

Rajkumar P Wadhwa, Deven Shrikant Gosavi, Aathira Ravindranath 
 Department of Gastroenterology and Hepatology, Apollo BGS Hospital, Mysore, Karnataka, India

Correspondence Address:
Dr. Rajkumar P Wadhwa
Department of Gastroenterology, Apollo BGS Hospitals, Adichunchungiri Road, Kuvempunagar, Mysore - 570 023, Karnataka


The global obesity epidemic has dramatically increased the prevalence of nonalcoholic fatty liver disease (NAFLD), such that it is the most common cause of chronic liver disease in Western nations. NAFLD is an important cause of liver disease in India also. The prevalence of NAFLD in India is around 9%-32% of general population with higher prevalence in those with overweight or obesity and those with diabetes or prediabetes. NAFLD is an important cause of unexplained rise in hepatic transaminases, cirrhosis, and hepatocellular carcinoma. The spectrum of abnormalities which the term NAFLD encompasses is isolated fatty liver, nonalcoholic steatohepatitis (NASH), and cirrhosis. The pathogenesis of NAFLD/NASH is complex and includes the development of insulin resistance, accumulation of excess lipids in the liver, mitochondrial dysfunction, and cell damage, and development of necroinflammation. Diagnosis is usually incidental during the evaluation for unrelated abdominal symptoms, elevated transaminases without any other explanation. Imaging modalities such as ultrasound are useful to diagnose the presence of excessive fat deposition in the liver but are not useful in differentiating simple steatosis from NASH. Liver biopsy may be useful in making this distinction, especially in those with risk factors for significant liver disease. Treatment modalities include weight reduction and exercise, metformin, Vitamin E, pentoxifylline, and saroglitazar and are effective in normalizing transaminases or in improving hepatic steatosis and inflammation in Indian patients with NAFLD. Randomized controlled treatment trials involving large number of patients with histological end point are required to assess the efficacy of different modalities.

How to cite this article:
Wadhwa RP, Gosavi DS, Ravindranath A. Nonalcoholic fatty liver disease: New epidemic.APIK J Int Med 2021;9:139-145

How to cite this URL:
Wadhwa RP, Gosavi DS, Ravindranath A. Nonalcoholic fatty liver disease: New epidemic. APIK J Int Med [serial online] 2021 [cited 2022 Sep 26 ];9:139-145
Available from: https://www.ajim.in/text.asp?2021/9/3/139/321661

Full Text


Serendipitous discovery of fatty liver during routine evaluation has a larger connotation nowadays as obese and diabetic patients could develop histological steatohepatitis similar to that seen with alcohol-induced liver disease.[1] The term nonalcoholic fatty liver disease (NAFLD) was coined to include all the various manifestations of excessive lipid deposition in the liver which include simple steatosis (isolated fatty liver [IFL]), nonalcoholic steatohepatitis (NASH), and cirrhosis. NASH is a more advanced stage of NAFLD and has a higher risk of progressing to cirrhosis or hepatocellular carcinoma (HCC).[1] Even in the absence of alcohol intake, patients who have one or more components of the metabolic syndrome with insulin resistance, develop hepatic steatosis due to increased lipolysis and increased delivery of fatty acids from adipose tissue to liver.[2] In most cases, steatosis remains stable without any further cellular damage. However, some develop hepatic oxidative stress and recruitment of various cytokines, leading to hepatic inflammation and/or fibrosis and thus to NASH, and subsequently complications such as cirrhosis and HCC. Primary NAFLD is usually associated with insulin resistance or metabolic syndrome, whereas secondary NAFLD is caused by intake of certain drugs, surgery, or total parenteral nutrition.[3]


Prevalence of NAFLD is rising in concert with rising rates of obesity and diabetes mellitus, with an estimated 33.8% of the population meeting criteria for obesity and 10.6% for Type 2 diabetes mellitus (T2DM).[4] Prevalence estimates vary widely depending on the information available in a given population, and the diagnostic criteria that are used to establish the diagnosis (liver biochemistry, imaging, and liver biopsy). A recent meta-analysis has shown the global prevalence of NAFLD among patients with T2DM was 55.48%.[59] (95% confidence interval [CI] 47.26%–63.67%), with regional prevalence of 51.77% in the United States (95% CI: 31.33%–71.64%), 56.83% in Latin America (95% CI: 34.05%–76.98%), 67.97% in Europe (95% CI: 62.07%–72.98%), 52.04% in East Asia (95% CI: 45.37%–58.55%), 57.87% in South Asia (95% CI: 52.87%–62.68%), 67.29% in West Asia (95% CI: 60.39%–73.61%), and 30.39% in Africa (95% CI: 11.64%–67.09%). The Dallas heart study used magnetic resonance spectroscopy in more than 2200 adults to identify a 31% prevalence of NAFLD in a cohort of asymptomatic persons.[5],[6] The largest study to date using ultrasound (US), followed by hepatic histology was in a cohort of asymptomatic middle-aged patients from San Antonio, Texas, and revealed a 46% prevalence of NAFLD and a 12.2% prevalence of NASH.[7] Recent data indicate that NAFLD may have male preponderance with a later peak in prevalence in women suggesting a relationship to sex hormones and menopause.[8],[9] NAFLD can occur at all ages including childhood, though the highest prevalence is described in those between 40 and 50 years of age. A comparison of data in 12,715 patients 12–19 years of age, obtained from the National Health and Examination Surveys from 1988 to 1994 and 2007–2010, demonstrated an increase in the prevalence of pediatric NAFLD from 3.9% to 10.7%.[10] NAFLD is considered to be the hepatic manifestation of the metabolic syndrome as defined by the presence of 3 or more of the following: abdominal obesity, hypertriglyceridemia, low high-density lipoprotein levels, hypertension, and an elevated fasting plasma glucose. NAFLD, and specifically NASH, is often associated with diabetes mellitus, which is associated with a 60% to 76% frequency of NAFLD and a 22% frequency of NASH.[7],[11],[12] However, some studies have shown that it may even occur in the absence of obesity or diabetes.[13],[14] Urbanization and associated changes, such as sedentary lifestyle and fat-rich diet, and a higher inherited tendency for diabetes mellitus make Indians more prone to metabolic syndrome or insulin resistance and its manifestations such as NAFLD and NASH.[15],[16],[17],[18] In Indians, risk factors associated with NAFLD were age >40 years, male gender, central obesity, high body mass index (BMI) (>25), elevated fasting blood sugar, and high aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels.[19] The allelic variant rs738409 (I148M) in PLPLA3 gene located on chromosome 22q13 and known to encode adiponutrin, a 481–amino acid protein that mediates triacylglycerol synthesis and was shown to be associated with increased hepatic steatosis as well as inflammation.[20],[21] A meta-analysis demonstrated an odds ratio of 3.26 (95% CI: 2.14–4.95) for NASH and 3.25 (95% CI: 2.86–3.70) for hepatic fibrosis for persons with the I148M SNP.[22] Apolipoprotein C3 gene (APOC3) regulates plasma TG concentrations, and 2 SNPs (rs2854117 and rs2854116) that affect the insulin response element in the gene were found to be associated with NAFLD in a study of Asian Indian men of normal weight.[23]


The 2-hit hypothesis proposed by Day et al. in 1988 provides a framework for our current understanding of the increasingly complicated steps that lead to hepatic steatosis, steatohepatitis, and fibrosis.[24] Dysregulation of fatty acid metabolism leads to steatosis, which is associated with several cellular adaptations and altered signaling pathways that render hepatocytes vulnerable to a second hit which may be one or more environmental or genetic perturbations that cause hepatocyte necrosis and inflammation.

Mechanisms of steatosis

Lipid accumulation in the liver results from an imbalance between overall calorie intake and systemic calorie utilization. Based on studies using radiolabelled precursors, 59% of triglyceride synthesis in human NAFLD results from uptake of adipose-derived nonesterified fatty acids (NEFA) while de novo lipogenesis accounts for about 26% and dietary sources for 15%.[25] Incorporation of NEFA into triglycerides and their contribution to steatosis depends on the activity of acyl CoA: diacylglycerol acyltransferase 1.[26] However, the other sources of fatty acids are also significant. Compared to normal, de novo lipogenesis is increased from 5% to 15%–25%, and spill-over from intestinal-derived chylomicrons is increasingly recognized and may also be a source of additional oxidative stress.[27],[28],[29]

Opposing the accumulation of liver fat, VLDL secretion is increased in NAFLD but plateaus at a hepatic triglyceride content of 10%, indicating limited compensation for high circulating NEFA.[30] Moreover, the secretion of apo B100, a key component of normal VLDL, is impaired in human NAFLD and may correlate with the secretion of a larger VLDL particle with greater triglyceride relative to its apoB100 content.[31],[32]

Mitochondrial dysfunction

The mitochondria seem to be both a source as well as a target of pro-oxidant free radicals (superoxide and hydroxyl radicals) responsible for the cellular damage which is a distinguishing feature of NASH.[33],[34] Mitochondrial morphological changes evident in NASH are swelling and intramitochondrial crystals. The crystalline structures may be phase transitions of cristae phospholipid bilayers.[35] Impaired function of the mitochondria is due to dysfunction of components of the electron transport chain as well as overexpression of uncoupling protein.[36],[37]

Lipid peroxidation in nonalcoholic steatohepatitis

Mitochondrial damage and generation of free radicals result in oxidative stress and lipid peroxidation.[38] In addition, cytochrome p450 (omega-oxidation) or peroxisomal fatty acid oxidation may contribute to it. Superoxide dismutase metabolizes free radicals to hydrogen peroxide which decays to hydroxyl radicals that are highly reactive and damage membrane fatty acids, proteins, and DNA through direct binding until detoxified by glutathione. Injury to the fatty acids produces lipid peroxidation giving rise to another free radical and a lipid hydroperoxide. Oxidative injury to the phospholipid monolayer which contains insulin- sensitive lipases, and to the endoplasmic reticulum (ER) may be lead to the development of cellular ballooning, impaired disposal of toxic-free fatty acids, and hepatic insulin resistance.[39]

Autophagy, lysosomes, fatty acid-induced injury, and apoptosis

Disposal of accumulated and presumably injured fat droplets involves the process of lysosome-mediated autophagy.[40] Impaired autophagy of small fat droplets, as well as diminished fatty acid-binding protein may contribute to accumulation of free fatty acids.[41] Free fatty acids, in turn, alter lysosomal permeability, leading to release of cathepsins (lysosomal proteases), which are associated with changes in mitochondrial permeability. This contributes to release of mitochondrial cytochrome C which activates caspases, leading to further activation of apoptosis pathways.

Endoplasmic reticulum stress, activation of inflammation, fibrosis, and cell death

Activation of caspase 3 leads to fragmentation of cytokeratin-18 (CK-18) which contributes to formation of Mallory–Denk bodies, seen best in ballooned hepatocytes, and to CK-18 fragments detectable in blood.[42] ER stress, along with accumulation of free fatty acids and cell death, induces proinflamatory cytokines such as interleukin 8, through activation of transcription factors such as nuclear factor kappa B and c-Jun N-terminal kinase. Activity in these pathways leads to accumulation of inflammatory infiltrates and activation of collagen-producing hepatic stellate cells characterized by transition from a Vitamin A-rich quiescent cell to a proliferating myofibroblast. Progression of fibrosis may also depend on an altered repair process with impaired hepatocyte replication and increased activity of hepatic progenitor cells, leading to a ductular reaction in the portal tracts.[43]

Role of gut dysbiosis

The term “dysbiosis” refers to disruption of the normal gut microbiota. It can result from various dietary, environmental, immunological factors, exposure to antibiotics as well as alterations in bile flow, gastric pH, or intestinal dysmotility. Gut dysbiosis has been linked to a variety of disorders such as inflammatory bowel disease and NAFLD. Microbial population has shown both qualitative and quantitative changes in people with NAFLD. Such alterations could lead to changes in the gut-liver axis metabolism. Dysbiosis inhibits secretion of fasting-induced adipose factor (FIAF), which in turn inhibits endothelial lipoprotein lipase, which is responsible for releasing triglycerides from circulating chylomicrons and VLDL.[60] Decreased circulating FIAF levels result in transactivation of hepatic lipogenic enzymes by carbohydrate-responsive element-binding protein and sterol regulatory element-binding protein 1c (SREBP-1c). The net effect is increased triglyceride storage in adipocytes and liver. Lipopolysaccharide stimulates Toll-like receptor 4 (TLR4) on endothelial cells and TLR9 on dendritic cells. This activation induces inflammasomes and proinflammatory cytokines, which induce NAFLD progression. It can also result in increased endogenous alcohol production, which increases intestinal permeability with disruption of tight junctions (zona occludins), allowing endotoxins and ethanol to have direct effects on the liver.[60] The intestinal microbiota converts dietary phosphatidylcholine to choline and to hepatotoxic trimethylamine. Reduced availability of dietary choline inhibits VLDL excretion from the liver-inducing steatosis.


Clinical features

Most patients with NAFLD are asymptomatic. Some patients may describe a vague right upper quadrant pain, fatigue, and malaise. A detailed history should be taken to rule out other causes of liver disease, especially alcohol consumption (consumption of <20–40 g of alcohol per day). Presentation of NAFLD in an Indian study was dyspepsia (n = 37), malaise or fatiguability (n = 36), and incidental detection of raised transaminases and fatty liver on sonogram (n = 22).[44] Anthropometry may reveal overweight or obesity. Hepatomegaly is commonly seen but often is difficult to appreciate on physical examination because of obesity. Stigmata of chronic liver disease, such as splenomegaly, spider telangiectasias, and ascites, are limited to those with cirrhosis.

Biochemical investigations

Mild (2–4 fold) elevation of serum ALT and AST levels with the AST/ALT ratio being <1 is seen in most patients. Serum alkaline phosphatase level was slightly elevated in one-third of patients.[45] Serum bilirubin, serum albumin, and prothrombin time are normal unless cirrhosis has developed. Elevated serum ferritin level may be found and is a marker of advanced disease. Low-titer (<1:320) antinuclear antibodies may be present in 25% of cases, but other markers of autoimmune hepatitis are negative.[45] An important thing to remember is that clinical and laboratory findings may not correlate with the histologic severity of NAFLD, and the entire histologic spectrum of NAFLD, including cirrhosis, can be seen in patients with normal or near-normal serum aminotransferase levels.[45] Insulin resistance can be measured by the quantitative insulin sensitivity check index test or the homeostasis model assessment test both of which are derived from the euglycemic hyperinsulinaemic clamp test with mathematical modeling of fasting insulin and glucose levels.


Imaging is usually obtained for the evaluation of unexplained liver biochemical abnormalities or if NAFLD is suspected clinically. US shows a “bright” liver of increased echogenicity, consistent with hepatic steatosis.[45] Fatty liver also can be documented by abdominal computed tomography (CT) (a fatty liver is lower in density than the spleen) and by magnetic resonance imaging, with which fat appears bright on T1-weighted imaging. US and CT had sensitivity rates of 100% and 93%, respectively, for detecting hepatic fat involving >33% of the liver, with positive predictive values of 62% and 76%, respectively.[45] Newer US-based modalities such as transient elastography (Fibroscan) uses a low amplitude shear wave that propagates through the liver parenchyma. The speed at which the wave moves is correlated with liver stiffness and is primarily useful to detect liver fibrosis. Another US-based modality is acoustic radiation force impulse elastography.

Liver biopsy

As discussed previously, the diagnosis of a fatty liver can be made by imaging alone but IFL and NASH cannot be differentiated, for which histology is necessary. The distinction between NASH and IFL is critical because patients with NASH are at risk of progression to cirrhosis.[45] An Indian study showed that female gender, BMI, waist-to-hip ratio, hypercholesterolemia, and LDL levels were found to be independent predictors of disease severity in patients with NASH.[46] The presence of these characteristics might justify the risk of doing a liver biopsy in view of the potential benefits to be accrued by treatment. The typical histological features of NAFLD/NASH are macrovesicular steatosis, lobular neutrophilic inflammation, Mallory bodies, ballooning degeneration, lipogranuloma, and pericellular fibrosis predominantly in the perivenular regions, i.e., zone 3 of the hepatic acinus.[45] NAFLD Activity Score (NAS) combines the unweighted sum of scores for steatosis, lobular inflammation, and hepatocellular ballooning on a scale of 0–8.[45] A score of 0–2 is most suggestive of “not-NASH,” and a score of 5 or greater suggests that NASH is present. It is primarily a research tool.


There are several serum markers which would reflect the inflammation in the liver in order to distinguish between IFL and NASH. CK-18 is released by the action of caspases and is a marker for apoptosis. It has been evaluated as a marker for NASH.[45] A meta-analysis demonstrated sensitivity and specificity rates of 78% and 87%, respectively. It is not commercially available. CK-18 fragments and soluble FaS are molecules involved in and produced during the cascade of apoptosis. A combination of these two markers was assessed in a study of NAFLD patients, these markers demonstrated a sensitivity of 88% and a specificity of 89% for distinguishing NASH from the absence of NASH.[45] M65 ELISA which measures both cleaved and uncleaved CK-18 has demonstrated a sensitivity of 100% and specificity of 80% for the combination. Another such marker is terminal peptide of procollagen III (PIIINP).

Scoring systems

Development of Clinical Scoring Systems are an attempt to differentiate between IFL and NASH/Cirrhosis. These consist of clinical or laboratory variables ranging from readily available tests such as serum liver zenzyme levels and the platelet count, to surrogate markers of necroinflammation or fibrosis, such as apolipoprotein A-1 or tissue inhibitor of metalloproteinase 1 levels. A few of these include FibroSURE (FibroTest), Fibrometer, NAFLD fibrosis score, Fib-4, AST-to-platelet ratio index, BARD, European Liver Fibrosis Score, NASHTest, and AST/ALT ratio. These tests are best at predicting either absent or advanced fibrosis (cirrhosis) and are less helpful for estimating intermediate stages of fibrosis.

Natural history

The prognosis in patients with IFL is favorable, with little potential for histologic or clinical progression. Patients with IFL are thought to have mortality rates similar to that of the general population. Development of NASH is predictive of a reduced life expectancy from cardiovascular, malignancy, or liver-related causes. The finding of NASH with fibrosis suggests a worse prognosis compared with NASH without fibrosis. Rates of fibrosis progression are quite variable, and no clinical or laboratory data appear to predict the disease course reliably. 80% of patients with NAFLD have stable IFL, whereas 20% go on to develop NASH. Cirrhosis then develops in approximately 11% of patients with NASH in 15 years. Approximately 31% of cirrhotic patients decompensate over 8 years of follow up. Furthermore, approximately 7% of cirrhotic patients can develop HCC over 6.5 years.[45] The factors that predict progression of fibrosis include the presence of diabetes mellitus, severe insulin resistance, cigarette smoking, weight gain >5 kg, and rising serum ALT and AST levels.


The optimal therapy for NAFLD has not been established. Although improvements in metabolic parameters, liver enzyme levels, or steatosis on imaging are readily determined in clinical trials, histologic improvement in steatosis, inflammation, and fibrosis is the ultimate goal of treatment. A 2-point improvement in the NAS, with 1 of the points coming from a reduction in hepatocyte ballooning degeneration, may indicate a successful intervention.[45] Improvement in fibrosis (which is not part of the NAS) is also desirable, although it is difficult to conduct trials of adequate length to allow improvement in fibrosis. Standard treatment of NAFLD has consisted of weight loss, removal of potentially offending drugs and toxins, and control of associated metabolic disorders.[45]

Lifestyle modification

The goal of lifestyle modification is to achieve weight loss and improve physical conditioning. Dietary modification and physical exercise are its main components. The goal is to achieve a weight loss of 7%–10% of body weight. For this, the most important modality is to reduce daily calories by 500–750 kcal. This alone has been shown to improve the histological features of NASH. Elimination or significant reduction in saturated fatty acids and high fructose corn syrup (for western countries) from diet is another measure. Omega-3 fatty acid supplementation may decrease hepatic steatosis and improve TG levels. Caffeinated coffee intake (approximately 2–3 cups/day) has been found to have a protective effect against hepatic fibrosis in retrospective studies.[47] This protective effect has been observed not only in NAFLD but also alcoholic liver disease as well as chronic hepatitis C. Moderate exercise 4–5 times weekly for 30–45 min each time and resistance training three times weekly with a total exercise time of 45 min improves insulin resistance, liver enzyme levels, and steatosis by imaging. However, there is a lack of data on its effect on NASH histopathology.[45]


Pharmacological intervention could be considered in patients with active or progressive disease who fail lifestyle modification.

Antidiabetes medications

Metformin reduces hyperinsulinemia and improves hepatic insulin sensitivity, reduces hepatomegaly and hepatic steatosis in animal studies, but human studies have not demonstrated good results.[48] The use of metformin is currently not recommended as a therapy for NAFLD or NASH. Thiazolidinediones (TZDs) are potent PPAR-γ agonists. In adipocytes, PPAR-γ decreases lipolysis and FFA release. TZDs improve insulin resistance by increasing glucose disposal in muscle and decreasing hepatic glucose output. Treatment with rosiglitazone and pioglitazone has shown an improvement in insulin resistance, normalization of liver biochemical test levels, and histologic improvement with low rates of hepatotoxicity.[49],[50] However, treatment with TZDs is associated with weight gain. Furthermore, it needs to be taken for a long time (at least 6 months–2 years) to demonstrate a beneficial effect. Increased risk of heart failure (Rosiglitazone–FDA black box warning) and osteoporosis has also been observed. In view of these issues, their use should be limited to patients with Stage 2 fibrosis or greater who have failed to improve with dietary measures and exercise. Saroglitazar is a dual PPAR-α/γ agonist approved (in India) for treatment of diabetic dyslipidemia and has been shown to lead to a significant improvement in transaminases, liver stiffness measurement, and FibroScan values in NAFLD patients.[61] Incretin mimetics have shown preliminary promise for the treatment of NASH. Exenatide and liraglutide are glucagon-like protein-1 receptor agonists that improve insulin sensitivity and serum glucose levels and promote modest weight loss. Exenatide in particular has shown promise in animal models and human pilot trials.[51] SGLT2 inhibitors (canagliflozin, luseogliflozin) have been shown to have a significant reduction in ALT, body weight, and the fatty liver index in NAFLD patients.[62] The impact of SGLT2 inhibitor on liver histology is not confirmed.

Farnesoid X receptor agonist

FXR activation has been demonstrated to reduce hepatic glucogenesis, lipogenesis, and steatosis in animal models. Obeticholic acid (OCA) is a synthetic variant of natural bile acid chenodeoxycholic acid. A phase 2 RCT in Japan (FLINT-J trial) showed that high doses of OCA (40 mg/day) significantly resolved NASH compared with placebo (38 vs. 20%, P = 0.049). An international, phase 3 study (REGENERATE study) is now ongoing.

Weight loss medications

None of this class of medications have been proven to be useful.

Cytoprotective and antioxidant agents

As discussed in the pathogenesis, oxidative stress, its resultant cell damage, and inflammation play a major role in the development of NASH. Hence, a potential role has been considered for antioxidant agents. Vitamin E 800–1000 IU daily improves NASH when used for 2 years, but there is no improvement in fibrosis.[45] It may increase the risk of prostate cancer. It is recommended as a first-line therapy in nondiabetic adults with biopsy-proved NASH. Pentoxifylline is has been shown to inhibit proinflammatory cytokines, including tumour necrosis factor-alpha, leading to reduced production of reactive oxygen species. Studies have shown varying degrees of histologic improvement as well as improved serum liver enzyme levels and reduced insulin resistance.[52]

Lipid-lowering agents

Because patients with NASH often have coexisting hyperlipidemia, the use of lipid-lowering agents has been studied as a potential dual-target therapy to address both conditions. Statins, which inhibit HMG-CoA reductase, have shown modest benefit in pilot trials.[53] Larger trials without the surrogate end points of serum liver enzyme levels and improved hepatic steatosis have also suggested a benefit.[54] For now, statins can be recommended to treat concomitant hyperlipidemia in patients with NASH, but further study is needed before statins can be recommended as primary therapy for NASH. Ezetimibe is another lipid-lowering agent that has shown benefit in improving hepatic histology in one pilot trial in 24 patients with NAFLD.[55]

Bariatric surgery

RYGB, LAGB, sleeve gastrectomy improves or resolves NASH in 60%–80% of cases; likely improves fibrosis.[45]

Liver transplantation

NASH cirrhosis is one of the most common indications for liver transplantation. An increased rate of cardiovascular events in patients with NASH cirrhosis undergoing liver transplantation has been reported, particularly in the perioperative period, as compared with patients who are transplanted for alcoholic cirrhosis.[56] As a result, the 30-day mortality following liver transplantation is higher for patients with NASH cirrhosis, however, 1–3-year mortality rates are similar to those for other indications for liver transplantation.[57] The majority of patients has recurrent steatosis 5 years after transplantation, although cirrhosis has been reported to develop in only 5%.[58] Hepatic steatosis in donor grafts is common (30%–50% of potential graft livers).[45] Grafts with <30% steatosis are acceptable for use, and those with more than 60% fat are generally considered unacceptable. Those with an intermediate degree of steatosis (30%–60%) are evaluated on a case-by-case and center-dependent basis.[45]

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Conflicts of interest

There are no conflicts of interest.


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