Hepatitis (plural: hepatitides) is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. Hepatitis may occur with limited or no symptoms, but often leads to jaundice, poor appetite and malaise. Hepatitis is acute when it lasts less than six months and chronic when it persists longer. The condition can be self-limiting (healing on its own) or can progress to fibrosis (scarring) and cirrhosis.
Viral hepatitis is the most common cause of hepatitis worldwide. Other common causes of non-viral hepatitis include toxic and drug-induced, alcoholic, autoimmune, fatty liver, and metabolic disorders. Less commonly some bacterial, parasitic, fungal, mycobacterial and protozoal infections can cause hepatitis. Additionally, certain complications of pregnancy and decreased blood flow to the liver can induce hepatitis. Cholestasis (obstruction of bile flow) due to hepatocellular dysfunction, biliary tract obstruction, or biliary atresia can result in liver damage and hepatitis.
Non-alcoholic fatty liver disease (NAFLD) is one cause of a fatty liver, occurring when fat is deposited (steatosis) in the liver not due to excessive alcohol use. It is related to insulin resistance and the metabolic syndrome and may respond to treatments originally developed for other insulin-resistant states (e.g. diabetes mellitus type 2) such as weight loss, metformin and thiazolidinediones. Non-alcoholic steatohepatitis (NASH) is the most extreme form of NAFLD, and is regarded as a major cause of cirrhosis of the liver of unknown cause.
Most patients with NAFLD have few or no symptoms. Patients may complain of fatigue, malaise, and dull right-upper-quadrant abdominal discomfort. Mild jaundice may be noticed although this is rare. More commonly NAFLD is diagnosed following abnormal liver function tests during routine blood tests. By definition, alcohol consumption of over 20 g/day (about 25 ml/day of net ethanol) excludes the condition.
Common findings are elevated liver enzymes and a liver ultrasound showing steatosis. An ultrasound may also be used to exclude gallstone problems (cholelithiasis). A liver biopsy(tissue examination) is the only test widely accepted as definitively distinguishing NASH from other forms of liver disease and can be used to assess the severity of the inflammationand resultant fibrosis.
Non-invasive diagnostic tests have been developed, such as FibroTest, that estimates liver fibrosis, and SteatoTest, that estimates steatosis, however their use has not been widely adopted. Apoptosis has been indicated as a potential mechanism of hepatocyte injury as caspase-cleaved cytokeratin 18 (M30-Apoptosense ELISA) in serum/plasma is often elevated in patients with NASH; however, as the role of oncotic necrosis has yet to be examined it is unknown to what degree apoptosis acts as the predominant form of injury.
Other diagnostic tests are available. Relevant blood tests include erythrocyte sedimentation rate, glucose, albumin, and renal function. Because the liver is important for making proteins used in coagulation some coagulation related studies are often carried out especially the INR (international normalized ratio). Blood tests (serology) are usually used to rule out viral hepatitis (hepatitis A, B, C and herpes viruses like EBV or CMV), rubella, and autoimmune related diseases. Hypothyroidism is more prevalent in NASH patients which would be detected by determining the TSH.
It has been suggested that in cases involving overweight patients whose blood tests do not improve on losing weight and exercising that a further search of other underlying causes be undertaken. This would also apply to those with fatty liver who are very young or not overweight or insulin-resistant. In addition those whose physical appearance indicates the possibility of a congenital syndrome, have a family history of liver disease, have abnormalities in other organs, and those that present with moderate to advanced fibrosis or cirrhosis.
A large number of treatments for NAFLD have been studied. While many appear to improve biochemical markers such as alanine transaminase levels, most have not been shown to reverse histological abnormalities or reduce clinical endpoints:
- Treatment of nutrition and excessive body weight:
- Nutritional counseling: Diet changes have shown significant histological improvement. Specifically, avoiding food containing high-fructose corn syrup and trans-fats is recommended.
- Weight loss: gradual weight loss may improve the process in obese patients; rapid loss may worsen NAFLD. Specifically, walking or some form of aerobic exercise at least 30–45 minutes daily is recommended. The negative effects of rapid weight loss are controversial: the results of a meta-analysis showed that the risk of progression is very low.
- A recent meta-analysis presented at the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) reported that weight-loss surgery leads to improvement and or resolution of NASH in around 80% of patients.
- Insulin sensitisers (metformin and thiazolidinediones) have shown efficacy in some studies.
- ursodeoxycholic acid and lipid-lowering drugs, have little benefit.
- Vitamin E: Vitamin E can improve some symptoms of NASH and was superior to insulin sensitizer in one large study. In the Pioglitazone versus Vitamin E versus Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis (PIVENS) trial, for patients with NASH but without diabetes mellitus, the use of very high dosages of vitamin E (800 IU/day) for four years was associated with a significantly higher rate of improvement than placebo (43% vs. 19%) in the primary outcome. The primary outcome was an improvement in certain histological features as measured by biopsy—but it did not improve fibrosis. Pioglitazone, an insulin sensitizer, improved some features of NASH but not the primary outcome, and resulted in a significant weight gain (mean 4.7 kilograms) which persisted after pioglitazone was discontinued.
- Statin: Improvements in liver biochemistry and histology in patients with NAFLD through treatment with statins have been observed in numerous cases, although these studies were carried out on a relatively small sample of patients. Statins have also been recommended for use in treating dyslipidemia for patients with NAFLD.
- Modest wine drinking: In a study using the NHANES III dataset, it has been shown that mild alcohol consumption (one glass of wine a day) reduces the risk of NAFLD by half.
The prevalence of non-alcoholic fatty liver disease ranges from 9 to 36.9% of the population in different parts of the world. Approximately 20% of the United States population suffers from non-alcoholic fatty liver, and the prevalence of this condition is increasing. The prevalence of non-alcoholic fatty liver disease is higher in Hispanics, which can be attributed to high rates of obesity and type 2 diabetes in Hispanic populations. Non-alcoholic fatty liver disease is also more common among men than women in all age groups until age 60, where the prevalence between sex equalize. This is due to the protective nature of estrogen.