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Kembara Xtra - Medicine - Non Alcoholic Fatty Liver
Nonalcoholic fatty liver (NAFL), nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis are among the range of fatty liver illnesses that are not brought on by other factors (such as alcohol consumption).
The most prevalent chronic liver disease in industrialized countries like the United States; up to 90% of patients with mild, asymptomatic aminotransferase elevations that aren't brought on by alcohol, viral hepatitis, or drugs have this condition.
NAFL is a reversible disease in which hepatocytes develop enormous vacuoles of triglyceride fat.
- Fat deposits in cells without hepatocellular damage (no hepatocyte ballooning, necrosis, or fibrosis) were found in liver biopsies.
- Low risk of developing cirrhosis or liver failure if ALT and AST levels are normal or 3 to 4 times upper limit values
- Another name: steatosis
ALT and AST elevated, typically 3 to 4 times ULN - 30% with NASH may progress to fibrosis over 5 years and may progress to cirrhosis, liver failure, and rarely hepatocellular cancer. Liver biopsy: fatty deposits in cells with hepatocellular injury (ballooning, acute/chronic inflammation, fibrosis); may be histologically indistinguishable from alcoholic steatohepatitis.
Cirrhosis with current or past histologic evidence of steatosis or steatohepatitis is referred to as NASH cirrhosis.
Epidemiology The most prevalent chronic liver disease in Western developed nations
Predominant age: 40s to 50s; can occur in minors; predicted to become the most common reason for liver transplantation by 2030; predominant sex: male = female
Incidence
NAFLD prevalence estimates range greatly, from 31 to 86 cases per 10,000 person-years to 29 cases per 100,000 person-years.
Prevalence
Estimate from the United States: 10–40%
Present in 69-87% of people with type 2 diabetes mellitus, 90% of people who are morbidly obese (BMI 40), 58–74% of obese people, and 50% of people with dyslipidemia (1).
PATHOPHYSIOLOGY AND ETIOLOGY
The main cause is believed to be insulin resistance, which increases triglyceride production, hepatic absorption of fatty acids, and lipolysis. The term metabolic-associated fatty liver disease (MAFLD) is the preferred renaming of this disorder on a global scale.
NAFL: an abnormal buildup of triglycerides in the liver and a compromised capacity to eliminate fatty acids
NASH: Multiple hit theory of steatohepatitis that links genetic causes, oxidative stress damage, insulin resistance, and hormones produced by adipose tissue to inflammation of the liver parenchymal cells.
Genetics: largely unknown, some familial clustering, and higher heritability; NAFL: more first-degree relatives have cirrhosis than matched controls; NASH: 18% of cases have a first-degree relative who is affected.
Obesity (BMI > 30), visceral obesity (waist > 102 cm for males or > 88 cm for women), hypertension, high triglyceride and low high-density lipoprotein (HDL) values, metabolic syndrome are risk factors.
Severe weight loss (starvation, bariatric surgery) Organic solvent exposure (e.g., chlorinated hydrocarbons, toluene); vinyl chloride; hypoglycin A Gene for hemochromatosis/other conditions with increased iron stores Protein-calorie malnutrition; total parenteral nutrition (TPN) >6 weeks
Smoking Drugs: various chemotherapy regimens, nucleoside analogues, tetracycline, glucocorticoids, tamoxifen, methotrexate, amiodarone, antiretroviral medicines for HIV, valproic acid, and fialuridine
Age-related increases in prevalence, severity, advanced fibrosis, and mortality; cholecystectomy history;
pregnant women's issues
In the third trimester, acute fatty liver of pregnancy is a rare but significant condition. Preeclampsia is linked to 50% of cases.
Child Safety Considerations
Pediatric NAFLD - With a prevalence of 9.6%, pediatric NAFLD is becoming more common, paralleling the growth in kid obesity.
- Vitamin E may be beneficial
Reye syndrome is a fatty liver disease with encephalopathy that typically occurs after a viral infection.
Prevention
Limit alcohol consumption to two units per day for men and one unit per day for women.
Maintain a healthy BMI.
Avoid hepatotoxic drugs for diabetes treatment and prevention.
Pneumococcal and yearly influenza vaccinations Immunization against HAV and HBV if not already immune
Accompanying Conditions
obesity in the central region, high blood pressure, type 2 diabetes, insulin resistance, high cholesterol, preeclampsia during pregnancy, heart arrhythmias and CVD, hypothyroidism, and hypogonadism; OSA
Diagnoses: NAFLD should be taken into consideration in patients with asymptomatic aminotransferase increases. Routine screening is not advised because to the absence of effective medication treatments and the questionable long-term advantages of screening.
NAFLD cannot be distinguished from other chronic liver diseases by any history or laboratory characteristics.
Risk factors, such as metabolic syndrome or obesity, raise the index of suspicion. Cryptogenic cirrhosis may appear. Noninvasive biomarkers of steatosis/fibrosis are not sufficiently accurate.
The gold standard diagnostic test is a liver biopsy, however it should only be used if the results will alter care.
HISTORY: Usually asymptomatic; possible exhaustion and/or abdominal fullness; nebulous right upper quadrant pain; past medical history; past alcohol consumption; past family history.
clinical assessment
Liver pain, mild to severe hepatomegaly, splenomegaly, and in more severe cases, cutaneous stigmata of chronic liver disease or portal hypertension (such as palmar erythema, spider angiomata, ascites), as well as jaundice, may all be present.
Differential diagnosis includes: hepatitis caused by viruses, alcohol-related liver disease, drug- or toxin-induced hepatitis, autoimmune hepatitis, celiac disease, muscle disease if a non-hepatic cause of increased enzymes is possible, hemochromatosis, Wilson disease, lipodystrophy, and others.
Laboratory Results
The following are necessary for a diagnosis of NAFLD: Imaging or histological evidence of hepatic steatosis
No history of heavy alcohol use; no competing factors to account for hepatosteatosis; no concurrent causes to account for chronic liver disease
ALT and AST levels may be raised in the initial tests (lab, imaging).
Non-specific enzyme abnormalities may exist or may be normal with advanced cirrhosis. If alcohol-induced, these are often AST/ALT 1.
- The degree of fibrosis is NOT correlated with the level of enzyme increase.
Lipid abnormalities: high total cholesterol, elevated LDL, elevated triglycerides, decreased HDL; if cirrhosis is present: decreased serum albumin, elevated PT, thrombocytopenia; elevated alkaline phosphatase; total/direct bilirubin; elevated ferritin (1.5 times normal);
Serum tests for hepatitis serologies, anti-smooth muscle antibody, ANA, serum gammaglobulin, celiac, 1-antitrypsin, iron, copper, and liver disease to rule out other causes
Ultrasound (US) is the primary imaging technique: Liver fat seems to be hyperechogenic.
Tests in the Future & Special Considerations
By assessing liver stiffness, several modalities can aid in the noninvasive quantification of fibrosis, but no modality can reliably distinguish between simple steatosis and steatohepatitis.
Serum biomarkers include the improved liver fibrosis panel, FibroTest, and HepaScore. Clinical decision aids include the NAFLD fibrosis score, FIB-4 index, and APRI score.
Imaging techniques include magnetic resonance elastography (MRE), vibration controlled transient elastography (VCTE) or FibroScan, and acoustic radiation force impulse (ARFI).
Liver biopsy is the gold standard for diagnosis and prognosis, and it must be likely that management will change before the biopsy.
Interpretation of Tests
The NAFLD activity score (NAS), which ranges from 0 to 8, is used to grade diagnosis based on three histologic features: steatosis (0–3), inflammation (0–3), and hepatocyte ballooning (0–2). With scores under 5, NASH is quite likely.
Activity in Steatosis Stages of fibrosis range from 0 to 4, depending on the degree of fibrosis.
Early management of metabolic risk factors is prioritized, as NAFLD is linked to increased cardiovascular morbidity and death.
General Actions
The only therapy with solid proof of benefits and safety for persons who are overweight or obese is weight loss. Aim for consistent weight loss of 5 to 10% of your body weight.
20 to 45 minutes of aerobic exercise performed three to five times per week together with calorie restriction or other dietary changes Strict diabetes management Treat the components of the metabolic syndrome—obesity, dyslipidemia, and hypertension.
Avoid or use alcohol in moderation.
Avoid using drugs that are hepatotoxic.
There is currently no drug that is categorically effective in treating NAFL or NASH. Among the promising agents are:
- Thiazolidinediones (pioglitazone): can be used in patients with and without type 2 diabetes mellitus, improves liver histology, but only when biopsy-proven NASH.
- GLP-1 receptor agonists (exenatide and liraglutide); vitamin E 400 to 800 IU daily; long-term safety issues at high doses; only use with biopsy-proven NASH and individuals without diabetes.
Early research suggests that type 2 diabetic mellitus and NASH individuals can benefit.
The drug pentoxifylline Agents that demonstrated +/- benefit
- Ursodeoxycholic acid - Metformin
– Statins
- Probiotics - Omega-3 fatty acids - Obeticholic acid (a bile acid derivative)
Aspirin and coffee/caffeine
QUESTIONS FOR REFERENCE
If you have chronic AST/ALT increases, advanced liver fibrosis (stage F3 or above), or liver biopsy-proven fibrosis, consult a hepatologist.
Surgical Techniques
NAFLD is not a contraindication for bariatric treatments in suitable obese patients. Data are lacking to conclusively determine the advantages and disadvantages of surgery in the management of NASH patients.
NAFLD is the second most prevalent reason for liver transplantation, yet 80–100% of patients will experience NAFLD recurrence in the transplanted liver.
Follow-up Annual LFT monitoring Surveillance with US or CT to assess for disease progression every two to three years or earlier if rising metabolic risk factors
Routine liver biopsies are not advised, but if fibrosis advancement is suspected, they may be repeated five years after the initial biopsy.
Hepatic fibrosis staging is the best indicator of death in patients with histologically proven NAFLD. It is still unknown whether to screen for hepatocellular cancer in noncirrhotic NAFLD.
Low in simple carbs, saturated and trans fats, and alcohol (light/moderate consumption may have a preventive or aggravating effect).
extensive coaching on long-term modifications to one's diet, exercise routine, and alcohol consumption.
Prognosis
Only NASH has been shown to proceed within the NAFLD spectrum, with the potential to cause cirrhosis, hepatocellular carcinoma, cholangiocarcinoma, and/or liver failure.
Up to 20% of people can develop cirrhosis. Transplantation is successful, however NASH frequently recurs after transplant due to persistent risk factors. Up to 42% of patients develop hepatocellular carcinoma without cirrhosis.
Complications
Progressive disease can result in decompensated cirrhosis, portal hypertension, ascites, encephalopathy, bleeding varices, and hepatorenal or hepatopulmonary syndromes, among other consequences.
Nonalcoholic fatty liver (NAFL), nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis are among the range of fatty liver illnesses that are not brought on by other factors (such as alcohol consumption).
The most prevalent chronic liver disease in industrialized countries like the United States; up to 90% of patients with mild, asymptomatic aminotransferase elevations that aren't brought on by alcohol, viral hepatitis, or drugs have this condition.
NAFL is a reversible disease in which hepatocytes develop enormous vacuoles of triglyceride fat.
- Fat deposits in cells without hepatocellular damage (no hepatocyte ballooning, necrosis, or fibrosis) were found in liver biopsies.
- Low risk of developing cirrhosis or liver failure if ALT and AST levels are normal or 3 to 4 times upper limit values
- Another name: steatosis
ALT and AST elevated, typically 3 to 4 times ULN - 30% with NASH may progress to fibrosis over 5 years and may progress to cirrhosis, liver failure, and rarely hepatocellular cancer. Liver biopsy: fatty deposits in cells with hepatocellular injury (ballooning, acute/chronic inflammation, fibrosis); may be histologically indistinguishable from alcoholic steatohepatitis.
Cirrhosis with current or past histologic evidence of steatosis or steatohepatitis is referred to as NASH cirrhosis.
Epidemiology The most prevalent chronic liver disease in Western developed nations
Predominant age: 40s to 50s; can occur in minors; predicted to become the most common reason for liver transplantation by 2030; predominant sex: male = female
Incidence
NAFLD prevalence estimates range greatly, from 31 to 86 cases per 10,000 person-years to 29 cases per 100,000 person-years.
Prevalence
Estimate from the United States: 10–40%
Present in 69-87% of people with type 2 diabetes mellitus, 90% of people who are morbidly obese (BMI 40), 58–74% of obese people, and 50% of people with dyslipidemia (1).
PATHOPHYSIOLOGY AND ETIOLOGY
The main cause is believed to be insulin resistance, which increases triglyceride production, hepatic absorption of fatty acids, and lipolysis. The term metabolic-associated fatty liver disease (MAFLD) is the preferred renaming of this disorder on a global scale.
NAFL: an abnormal buildup of triglycerides in the liver and a compromised capacity to eliminate fatty acids
NASH: Multiple hit theory of steatohepatitis that links genetic causes, oxidative stress damage, insulin resistance, and hormones produced by adipose tissue to inflammation of the liver parenchymal cells.
Genetics: largely unknown, some familial clustering, and higher heritability; NAFL: more first-degree relatives have cirrhosis than matched controls; NASH: 18% of cases have a first-degree relative who is affected.
Obesity (BMI > 30), visceral obesity (waist > 102 cm for males or > 88 cm for women), hypertension, high triglyceride and low high-density lipoprotein (HDL) values, metabolic syndrome are risk factors.
Severe weight loss (starvation, bariatric surgery) Organic solvent exposure (e.g., chlorinated hydrocarbons, toluene); vinyl chloride; hypoglycin A Gene for hemochromatosis/other conditions with increased iron stores Protein-calorie malnutrition; total parenteral nutrition (TPN) >6 weeks
Smoking Drugs: various chemotherapy regimens, nucleoside analogues, tetracycline, glucocorticoids, tamoxifen, methotrexate, amiodarone, antiretroviral medicines for HIV, valproic acid, and fialuridine
Age-related increases in prevalence, severity, advanced fibrosis, and mortality; cholecystectomy history;
pregnant women's issues
In the third trimester, acute fatty liver of pregnancy is a rare but significant condition. Preeclampsia is linked to 50% of cases.
Child Safety Considerations
Pediatric NAFLD - With a prevalence of 9.6%, pediatric NAFLD is becoming more common, paralleling the growth in kid obesity.
- Vitamin E may be beneficial
Reye syndrome is a fatty liver disease with encephalopathy that typically occurs after a viral infection.
Prevention
Limit alcohol consumption to two units per day for men and one unit per day for women.
Maintain a healthy BMI.
Avoid hepatotoxic drugs for diabetes treatment and prevention.
Pneumococcal and yearly influenza vaccinations Immunization against HAV and HBV if not already immune
Accompanying Conditions
obesity in the central region, high blood pressure, type 2 diabetes, insulin resistance, high cholesterol, preeclampsia during pregnancy, heart arrhythmias and CVD, hypothyroidism, and hypogonadism; OSA
Diagnoses: NAFLD should be taken into consideration in patients with asymptomatic aminotransferase increases. Routine screening is not advised because to the absence of effective medication treatments and the questionable long-term advantages of screening.
NAFLD cannot be distinguished from other chronic liver diseases by any history or laboratory characteristics.
Risk factors, such as metabolic syndrome or obesity, raise the index of suspicion. Cryptogenic cirrhosis may appear. Noninvasive biomarkers of steatosis/fibrosis are not sufficiently accurate.
The gold standard diagnostic test is a liver biopsy, however it should only be used if the results will alter care.
HISTORY: Usually asymptomatic; possible exhaustion and/or abdominal fullness; nebulous right upper quadrant pain; past medical history; past alcohol consumption; past family history.
clinical assessment
Liver pain, mild to severe hepatomegaly, splenomegaly, and in more severe cases, cutaneous stigmata of chronic liver disease or portal hypertension (such as palmar erythema, spider angiomata, ascites), as well as jaundice, may all be present.
Differential diagnosis includes: hepatitis caused by viruses, alcohol-related liver disease, drug- or toxin-induced hepatitis, autoimmune hepatitis, celiac disease, muscle disease if a non-hepatic cause of increased enzymes is possible, hemochromatosis, Wilson disease, lipodystrophy, and others.
Laboratory Results
The following are necessary for a diagnosis of NAFLD: Imaging or histological evidence of hepatic steatosis
No history of heavy alcohol use; no competing factors to account for hepatosteatosis; no concurrent causes to account for chronic liver disease
ALT and AST levels may be raised in the initial tests (lab, imaging).
Non-specific enzyme abnormalities may exist or may be normal with advanced cirrhosis. If alcohol-induced, these are often AST/ALT 1.
- The degree of fibrosis is NOT correlated with the level of enzyme increase.
Lipid abnormalities: high total cholesterol, elevated LDL, elevated triglycerides, decreased HDL; if cirrhosis is present: decreased serum albumin, elevated PT, thrombocytopenia; elevated alkaline phosphatase; total/direct bilirubin; elevated ferritin (1.5 times normal);
Serum tests for hepatitis serologies, anti-smooth muscle antibody, ANA, serum gammaglobulin, celiac, 1-antitrypsin, iron, copper, and liver disease to rule out other causes
Ultrasound (US) is the primary imaging technique: Liver fat seems to be hyperechogenic.
Tests in the Future & Special Considerations
By assessing liver stiffness, several modalities can aid in the noninvasive quantification of fibrosis, but no modality can reliably distinguish between simple steatosis and steatohepatitis.
Serum biomarkers include the improved liver fibrosis panel, FibroTest, and HepaScore. Clinical decision aids include the NAFLD fibrosis score, FIB-4 index, and APRI score.
Imaging techniques include magnetic resonance elastography (MRE), vibration controlled transient elastography (VCTE) or FibroScan, and acoustic radiation force impulse (ARFI).
Liver biopsy is the gold standard for diagnosis and prognosis, and it must be likely that management will change before the biopsy.
Interpretation of Tests
The NAFLD activity score (NAS), which ranges from 0 to 8, is used to grade diagnosis based on three histologic features: steatosis (0–3), inflammation (0–3), and hepatocyte ballooning (0–2). With scores under 5, NASH is quite likely.
Activity in Steatosis Stages of fibrosis range from 0 to 4, depending on the degree of fibrosis.
Early management of metabolic risk factors is prioritized, as NAFLD is linked to increased cardiovascular morbidity and death.
General Actions
The only therapy with solid proof of benefits and safety for persons who are overweight or obese is weight loss. Aim for consistent weight loss of 5 to 10% of your body weight.
20 to 45 minutes of aerobic exercise performed three to five times per week together with calorie restriction or other dietary changes Strict diabetes management Treat the components of the metabolic syndrome—obesity, dyslipidemia, and hypertension.
Avoid or use alcohol in moderation.
Avoid using drugs that are hepatotoxic.
There is currently no drug that is categorically effective in treating NAFL or NASH. Among the promising agents are:
- Thiazolidinediones (pioglitazone): can be used in patients with and without type 2 diabetes mellitus, improves liver histology, but only when biopsy-proven NASH.
- GLP-1 receptor agonists (exenatide and liraglutide); vitamin E 400 to 800 IU daily; long-term safety issues at high doses; only use with biopsy-proven NASH and individuals without diabetes.
Early research suggests that type 2 diabetic mellitus and NASH individuals can benefit.
The drug pentoxifylline Agents that demonstrated +/- benefit
- Ursodeoxycholic acid - Metformin
– Statins
- Probiotics - Omega-3 fatty acids - Obeticholic acid (a bile acid derivative)
Aspirin and coffee/caffeine
QUESTIONS FOR REFERENCE
If you have chronic AST/ALT increases, advanced liver fibrosis (stage F3 or above), or liver biopsy-proven fibrosis, consult a hepatologist.
Surgical Techniques
NAFLD is not a contraindication for bariatric treatments in suitable obese patients. Data are lacking to conclusively determine the advantages and disadvantages of surgery in the management of NASH patients.
NAFLD is the second most prevalent reason for liver transplantation, yet 80–100% of patients will experience NAFLD recurrence in the transplanted liver.
Follow-up Annual LFT monitoring Surveillance with US or CT to assess for disease progression every two to three years or earlier if rising metabolic risk factors
Routine liver biopsies are not advised, but if fibrosis advancement is suspected, they may be repeated five years after the initial biopsy.
Hepatic fibrosis staging is the best indicator of death in patients with histologically proven NAFLD. It is still unknown whether to screen for hepatocellular cancer in noncirrhotic NAFLD.
Low in simple carbs, saturated and trans fats, and alcohol (light/moderate consumption may have a preventive or aggravating effect).
extensive coaching on long-term modifications to one's diet, exercise routine, and alcohol consumption.
Prognosis
Only NASH has been shown to proceed within the NAFLD spectrum, with the potential to cause cirrhosis, hepatocellular carcinoma, cholangiocarcinoma, and/or liver failure.
Up to 20% of people can develop cirrhosis. Transplantation is successful, however NASH frequently recurs after transplant due to persistent risk factors. Up to 42% of patients develop hepatocellular carcinoma without cirrhosis.
Complications
Progressive disease can result in decompensated cirrhosis, portal hypertension, ascites, encephalopathy, bleeding varices, and hepatorenal or hepatopulmonary syndromes, among other consequences.
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