An Overview on Diagnosis and Management of Non-alcoholic Fatty Liver Disease

Abdalrahman Fadulalseed Wedaatella¹, Rahaf Abdulrahman Almehery², Ranaa Mohammed Al Namar², Aishah Saeed M Shmashir², Amro Musa Alam Alhouda³, Anas Ameen Fallatah⁴, Ali Abdalla Ali Osman⁵, Noor Hassan A Alazmi⁶, Mohammed Ahmed M Hurubi⁷*, Zainab Abdullah Al Khuraidah⁸, Esraa Ahmed Akili⁹

¹Department of Family Medicine, Nawan Primary health care center, Nawan, KSA.

²Faculty of Medicine, King Khalid University, Abha, KSA.

³Department of Family Medicine, Aljereen Primary health care center, Albaha, KSA.

⁴Department of Preventive Medicine/ Infectious Diseases Control, Makkah, KSA.

⁵Dr. Hala Essa Binladen Hospital, Alhamra, Jeddah, KSA.

⁶Department of Emergency, Gurayat General Hospital, Gurayat, KSA.

⁷Department of Family Medicine, Primary Health Care Center Haroob, Jazan, KSA.

⁸Department of Renal Dialysis, Qatif Central Hospital, Qatif, KSA.

⁹Faculty of Medicine, Ibn Sina National College, Jeddah, KSA.

*Email: [email protected]

ABSTRACT

Non-alcoholic fatty liver disease (NAFLD) is difficult to define, has intricate pathogenesis, has a high outbreak, and few acquiesced treatments are available. Thus, this condition has posed a great challenge in our time. The non-alcoholic fatty liver disorder is correlated with obesity and insulin resistance and is emerging as the most ordinary form of chronic liver disorder in grown-ups and kids alike. The Pubmed, NCBI, Medline, Cochrane databases, and Embase were searched for patients' studies with nonalcoholic fatty liver disorder. Management options, Incidence, and causes were all investigated. NAFLD is a quickly rising reason for a chronic liver disorder. It is a complicated condition that encounters multiple challenges in its management and assessment. If it's not treated on time, hepatic steatosis may progress to NASH and eventually liver cirrhosis. Controlling this illness requires a multidisciplinary technique. We hope that treatment options for advanced stages of the condition will meliorate in the next decade.

Key words:Liver cirrhosis, Non-alcoholic fatty liver disease (NAFLD), Non-alcoholic steatohepatitis (NASH), Diagnosis

INTRODUCTION

Nonalcoholic fatty liver disorder(NAFLD) has increased in pandemic proportions, in addition to the increased obesity prevalence and other risk factors for metabolic syndrome [1, 2], and is predicted to evolve into a major index for graft of liver in ten years [3]. NAFLD is described by anomalous fat preservation (macrovesicular steatosis) in more than 5% of hepatocytes in the liver without secondary reasons e.g. drugs or alcohol. The two classifications of NAFLD are non-alcoholic fatty liver disorder (NAFL) and non-alcoholic steatohepatitis (NASH). The worse form of NAFLD is NASH in which liver deterioration and inflammation happen in addition to fat preservation in the presence of the liver in NAFL. With more liver compensation, NASH is possible to lead to liver sarcoidosis and ultimately to cirrhosis, which can lead to liver graft or even death. It is evaluated that 20 to 30 percent of grown-ups living in advanced countries and consuming Western foods have NAFLD, 2 to 5 percent have extreme liver damage (NASH), and 1 to 2 percent of the total Grown-ups are at risk for the illness progress to Cirrhosis NASH [4]. To achieve the most beneficial treatment intervention, it is important to be able to recognize which patients are most in jeopardy of cirrhosis development. Any degree, of liver fibrosis, is a criterion for predicting adverse results. Type 2 diabetes (T2DM), older age, and fatness are also correlated with advanced NASH and fibrosis [4].

This study aims to discuss the characteristics, presentation, and treatment of the non-alcoholic fatty liver disorder.

MATERIALS AND METHODS

These keys were used in the mesh ("Non-Alcoholic Fatty Liver Disease" [mesh]) and "Signs and Symptoms" [mesh]) or "Management" [mesh] and the PubMed database was used to choose articles according to the inclusion criteria, the articles were chosen based on the liability of one of the following topics: Non-alcoholic fatty liver disease, Non-alcoholic fatty liver disease features, and management. Exclusion criteria were all other articles that did not have one of these topics as their main endpoint.

About 90 articles were selected as the most relevant articles out of 1202 articles indexed in the last 2 decades and their complete texts were assessed. 31 of the articles out of 90 were included after a complete review. Additional research and publications were found using reference lists of known and related studies. specialists' unanimity recommendation and thoughts on relevant issues have been added to assist physicians working in assessing the simplest and most practical schizophrenia.

RESULTS AND DISCUSSION

The global rate prevalence of NAFL is about 20%, whereby Africa has 13%, North America and Europe have 23%, and 32% in the Middle East [5]. Oscillations of Geographic are based on known distinction in severity and incidence, especially the high frequency of NAFLD-related genetic danger types [6] as well as the lower NASH risk for specific society’s e.g. blacks, and the higher rate in Hispanics [7]. Agedness is a risk aspect for NAFLD and is more regular in men.

Nevertheless, proof suggests that NAFLD [8, 9] is growing in overweight children and juveniles. Compared to grown-ups, they have a higher rate of advancement to cirrhosis and the development of liver cancer (HCC), which leads to higher mortality and the need for graft [10]. NAFLD patients are closely associated with central obesity (51%), metabolic syndrome (43%), type 2 diabetes (23%), and dyslipidemia (69%). The condition prevalence has risen from 15% in 2005 to 25% - an almost pandemic ratio - in 2010, in line with the rising rate of obesity [5]. The fibrosis existence is the most essential predictor of negative results in NAFLD rather than NASH’s histological markers [11]. Fatality from all causes remains a threat even in very early fibrosis, and this threat increases with fibrosis progression.

Risk factors

Age

 The threat of developing NAFLD increases with age, although age is not a barrier to the progression of the condition. The reason for risen hepatic steatosis with agedness may be connected to the higher incidence of metabolic syndrome as well as insulin resistance [12]. Peaks appear in men 40-49 years old and in women 50 years old [13].

Gender

Males are more at stake for NAFLD than females. In a multinational study (USA), 79% of Asian patients with NAFLD were male, while only 44% were Caucasian [14]. The prevalence of NAFLD is higher in men (13.3% in men and 2.7%, in women in China, 21.6% in men, and 11.2% in Korean women [15]).

Ethnicity and genetics

Compared to other populations, Spaniards are more predisposed to NAFLD and insulin resistance, then Asians [14]. Ethnic distinctions in NAFLD prevalence are considered to be associated not only with a strong genetic predisposition but also with various ways of life and eating habits.

Diabetes mellitus

One of the main threat factors for NAFLD is diabetes mellitus. Regardless, diabetes is uncommon in NAFLD patients who present with elevated transaminase levels, even though NAFLD is very regular in patients with diabetes mellitus.

Obesity

Another main threat aspect for NAFLD is fatness. Investigations have displayed a parallel increase in NAFLD with an increase in BMI [16].

Central obesity

Central fatness is associated with visceral heaviness, which is closely linked to NAFLD and insulin resistance. NAFLD occurs in lean and obese central patients and increases the risk with the addition of general fatness. The data also show that despite having a lower BMI, visceral adipose tissue is higher in patients with NAFLD [17].

Metabolic syndrome

NAFLD is currently believed an essential symptom of metabolic syndrome (MS) and is a central pathogen of insulin resistance. The extra ingredients of metabolic syndrome raise the threat of fatty liver disorder and show the highest threat in patients with complete metabolic syndrome.

Moreover, multiple emerging threat factors have been reported in Western populations, e.g. sleep apnea, polycystic ovary syndrome, hypogonadism hypothyroidism, and obstructive.

Symptoms and signs

Influential and demoralized weariness, autonomic nervous system dysfunction, and excessive daytime drowsiness have been ascribed to underlying liver disorder. Patients with NAFLD are unlikely to encounter any physical symptoms, while patients with NASH are more likely to have developed scarring (cirrhosis), enlarged blood vessels beneath the skin, ascites (inflammation of the abdomen), red and yellow palms (yellow color of skin and eyes), and an enlarged spleen.

In patients with NAFLD, tiredness shows a strong association with sleepiness in the daytime and autonomic dysfunction. Indeed, studies have proved the existence of autonomic dysfunction in patients with early-stage NAFLD [18], and that worsening exhaustion is associated with worsening of autonomic symptoms [19]. Other symptoms, such as syncope and dizziness, can lead to NAFLD with many clinical outcomes, including cognitive impairment, falls, and fall injuries. Indeed, analyses recommended that a history of falls is regular in 43% NAFLD [20] because they are the result of autonomic nervous system dysfunction.

Patients with NAFLD also have concerns about concentration and memory. Investigations prove that 50% of NAFLD patients show mild mental symptoms, and up to 46% show moderate or severe cognitive impairment [19]. Yet, in the early stages of NAFLD, cognitive impairment has nothing to do with hepatic encephalopathy because there is no positive association between cognitive symptoms and indicators of the severity of liver damage.

Diagnosis

NAFLD can be diagnosed with imaging equipment such as computed tomography (CT), ultrasound, or magnetic resonance imaging (MRI), but a liver biopsy is necessary to detect NASH and the presence/location of its features such as inflammation, hepatocyte ballooning, early fibrosis, and Mallory-Denk bodies.

Identification of hepatic steatosis without a secondary underlying reason (such as alcohol and steatogenic drugs) is essential for the correct diagnosis of NAFLD, followed by a threat assessment for the possible existence of significant NASH and fibrosis [21]. This test is generally done in response to elevated liver transaminases, but this method is restricted because many patients with early NAFLD show regular liver function results. Thus, it should be evaluated in high-risk patients such as those with type 2 diabetes. Ultrasound is not sensitive enough to detect steatosis of less than 20%, regardless of transaminase levels [22].

The existence or absence of significant fibrosis is a critical prognostic feature in NAFLD, and the assessment of fibrosis in another non-invasive manner is another significant unmet need for NASH diagnosis. Numerous imaging algorithms based on imaging and clinical data have been developed to assess fibrosis, but it seems that they are only able to detect advanced fibrosis without showing much use in the early stages [23]. Yet, a newer approach that examines collagen circulation using stable isotope labeling of new collagen [24] is promising in treatment trials in which current tests are not sensitive to light changes.

Treatment

Treatment is divided into two categories: targeting steatosis or progression pathogenesis.

Obesity, dyslipidemia, and insulin resistance are always key factors in the development of hepatic steatosis. Losing weight or drug therapy for insulin resistance/dyslipidemia are factors in decreasing steatosis. In particular, losing weight has been observed to enhance liver chemistry, steatosis, inflammatory changes, necrosis, and fibrosis [25], but rapid losing weight may change and worsen the condition. Obesity surgery has also been victorious in many investigations [25], and it seems to be the only treatment with lasting effects on NASH. Medication should include thiazolidinedione, pioglitazone, rosiglitazone, metformin, statins, and fibric acid derived.

Oxidative stress/inflammation is important in NASH pathogenesis, and antioxidants e.g vitamin E are likely to lower TGF-β pro fibrinogen levels, improve histology, and inhibit liver star cell activation. Pentoxifylline TNF-α is a proinflammatory cytokine that produces excess cytokines that are absorbed by inflammatory cells, leading to liver cell collapse and induction of fibrogenesis. This cytokine is increased in NASH [26].

CONCLUSION

NAFLD is the most important chronic liver condition. NAFLD rates in patients with fatness and type 2 diabetes are increasing. It is a complicated disease that faces multiple challenges in its diagnosis and management. If it's not treated on time, hepatic steatosis may advance to NASH and eventually liver cirrhosis. Doctors need to become more aware of this situation through better screening of potential threat factors to cope with the burden of the disease.

ACKNOWLEDGMENTS : None

CONFLICT OF INTEREST : None

FINANCIAL SUPPORT : None

ETHICS STATEMENT : None