What is the difference between NAFLD and NASH?,

Non alcoholic fatty liver disease (NAFLD) .,

NAFLD is actually a term for a wide range of conditions characterised by the build-up of fat in the liver cells of people who do not drink alcohol excessively. At one end of this range is simple fatty liver, or steatosis. This is the stage where fat is first detected in the liver cells and is generally regarded as benign (harmless). ,

, Non alcoholic steatohepatitis (NASH) is a significant development in NAFLD. ,,

 This is a more aggressive condition that may cause scarring to the liver and can progress to cirrhosis. Cirrhosis causes irreversible damage to the liver and is the most severe stage in NAFLD. ., In simple terms it may be easiest to think of NAFLD as having the following stages: 1. fatty liver 2. a form of hepatitis known as non alcoholicsteatohepatitis (NASH) 3. fibrosis 4. cirrhosis .,

 Alcohol NAFLD is almost the same as alcoholic liver disease (ALD) and shares the same stages, with alcoholic hepatitis occurring in place of steatohepatitis (NASH). ,

, In practical terms the only difference between the two conditions – NAFLD and ALD – is that the latter is caused by drinking too much and the former by all other causes. ., NAFLD can affect a wide range of people. In general, the older you are the more chance there is that you may have the condition. NAFLD is typically seen in people aged around 50 and more commonly in men than women. It is hard to be precise about how many people have some form of NAFLD but it is estimated that one in five people (20%) in the UK have the earliest stages of NALFD, or steatosis. ,,.

 People most at risk of NAFLD are those who: .,
are obese
have insulin resistance, associated with diabetes
have hypertension (high blood pressure)
have hyperlipidaemia (too much cholesterol and triglyceride in their blood)
are taking certain drugs prescribed for other conditions
have been malnourished, starved or given food intravenously. ,.

Non alcoholic steatohepatitis (NASH) Non alcoholic steatohepatitis (NASH) is a more advanced form of NAFLD in which there is inflammation in and around the fatty liver cells. .

, This may cause swelling of your liver and discomfort or pain around it. If you place your right hand over the lower right hand side of your ribs it will cover the area of your liver. With intense, on-going inflammation a build up of scar tissue may form in your liver. This process is known as fibrosis, and can lead to cirrhosis. .

, NASH is now considered to be one of the main causes of cirrhosis. .,

 Cirrhosis is usually the result of long-term, continuous damage to the liver. This is where irregular bumps, known as nodules, replace the smooth liver tissue and the liver becomes harder. The effect of this, together with continued scarring from fibrosis, means that the liver will run out of healthy cells to support normal functions. This can lead to complete liver failure. NASH should be distinguished from acute fatty liver disease, which may occur during pregnancy or with certain drugs or toxins (poisons). This condition is very rare and may lead rapidly to liver failure. /,

 HCV-induced Steatosis l,

On average steatosis is about two and half times more common in people with HCV than in the general population, so it is clear that the presence of the virus in the body can actually trigger steatosis. Biopsy samples in people with HCV who have steatosis tend to show that fat accumulates around the portal areas, rather than in the middle of the lobules of the liver, as is usually the case Non Alcoholic Fatty Liver Disease (NAFLD) which point to the virus being the trigger rather than other factors.

For people with genotype 3 though, the link between steatosis and the virus has now been definitively established. Up to 80% of people with genotype 3 have moderate to severe steatosis. It seems that that there is a complex interaction between the core protein of the genotype 3 strand of the virus and liver cells that leads to steatosis. This interaction is not seen in other genotypes. It also seems that the severity of steatosis in these patients is directly related to their viral load. The higher the viral load the greater the amount of steatosis. This link has not been observed in other genotypes.

Surprisingly people with genotype 3, who achieve sustained virologic response (SVR) through treatment, have a marked decrease in and sometimes a complete resolution of steatosis. If they then relapse steatosis then reappears. People with other genotypes conversely show no improvement in the level of steatosis after successful treatment. ,.;

What does it Mean If I Have Hepatitis C And NAFLD ?

Steatosis In HCV/ Metabolic and Hepatic

There are two discrete forms of steatosis that may be found in patients infected with hepatitis C virus (HCV). Metabolic steatosis can coexist with HCV, regardless of genotype, in patients with risk factors such as obesity, hyperlipidemia, and insulin resistance. The second form of hepatic steatosis in HCV patients is a result of the direct cytopathic effect of genotype 3 viral infections. There have been proposed mechanisms for this process but it remains elusive. Both categories of steatosis tend to hasten the progression of liver fibrosis and therefore prompt recognition and management should be initiated in patients with HCV and steatosis.

The authors review the current understanding of the relationship between hepatitis C infection and hepatic steatosis and discuss future research directions.

Please Continue Reading

What About HCV Therapy and NASH

Steatosis and HCV treatment

There is increasing evidence that steatosis can reduce the effects of treatment. Some retrospective studies have shown that people with steatosis were less likely to achieve a sustained virologic response (SVR) even when taking into account other factors that might induce steatosis. One study found that sustained virologic response rates were 18-32% lower in people with steatosis compared to people without steatosis after adjusting for other co-factors that affect treatment such as genotype, fibrosis score, and viral load level.

.In the International Journal of Collaborative Research on Internal Medicine & Public Health Vol. 1 No. 9 (November 2009) a study of 89 (naive) or never treated before patients took part in a study to evaluate the effect of steatosis and non alcoholic steatohepatitis (NASH) on treatment response treating with Pegylated Interferon α 2a and Ribavirin.

, All patients were given a biopsy prior to treatment.

Results: Forty-five (50.6%) out of 89 Chronic Hepatitis C patients had associated NAFLD among and 11 patients encounter "superimposed steatohepatitis" (NASH). , superimposed steatohepatitis are independently associated with advanced fibrosis , After treatment a "virologic reponse" was achieved in 61 cases (68.54%) overall. , VIROLOGICAL RESPONSE: reduction in viral replication in response to treatment. In HCV, a complete virological response means that a person's HCV RNA becomes undetectable with treatment.

, As for the group of patients with NAFLD the end of treatment response was significantly lower only (51%). The Group not affected by NAFLD and treated with the same treatment had a 86.36% virological response.

The overall end treatment virologic response was achieved in 61 cases (68.54%) while 28 cases (31.46%) were nonresponders.

 In summary, hepatic steatosis is detected in nearly one half of studied patients with CHC,
even when confounding factors such as overweight, diabetes mellitus or alcohol intake were
excluded. Irrespective of its grade, NFALD in hepatitis C is associated with a more severe
disease and reduced response rate to combined antiviral therapy. Moreover, most of CHC
patients with associated NASH were nonresponders: raising a question about the value of
screening NASH prior to initiation of antiviral therapy.

Click here To view the entire 2009 study and all the variables


Treatment for Steatosis

There is currently no treatment for steatosis. However, there are strategies to help reduce the amount of fat in the liver. It is becoming evident that diet, exercise, and maintaining a healthy weight are important strategies to help reduce and possibly eliminate steatosis.
A recent study found that HCV patients who participated in a diet and exercise program for three months lowered their grade of steatosis and, remarkably, their fibrosis score.

Treatment and Genotype 3

Hepatitis C virus genotypes 2 and 3 are both responsive to antiviral treatment, they have been regarded as similar. However, recent evidence has shown there may be differences between these two genotypes with regard to their clinical features and possibly responses to combined interferon and ribavirin therapy.

.As demonstrated in recent studies considering rapid virologic response (RVR) as a criterion for shortening treatment from the standard 24 weeks to 12 or 16 weeks in patients with genotype  2 or  3, the reason for lower response in geno 3 versus genotype 2 patients may be a lower response rate in patients without an RVR. As a consequence, treatment longer than the currently recommended 24 weeks may be required for patients with genotype 3 but not for those with genotype  2 in the absence of an RVR. Whether this lower sensitivity to treatment in a subgroup of patients with genotype 3 may be attributed to viral heterogeneity or other associated cofactors is not yet known.

New Drug Telaprevir

/Telaprevir Monotherapy Is Potent against HCV Genotype 2 but Not 3 Best Results when Combined with Interferon/ribavirin

Genotype 3 patients, SVR rates were lower overall : G3 telaprevir alone: SVR 50%; G3 telaprevir/pegylated interferon/ribavirin: SVR 67%; G3 pegylated interferon/ribavirin: SVR 44%. ,

 Therapy response to interferon-based regimen in patients with HCV genotype 3 infection is negatively affected by increasing age, suggesting that elderly patients (> 50 years old) with geno 3 infection may need longer duration of therapy." /

,There is increasing evidence that steatosis can reduce the effects of treatment. Some retrospective studies have shown that people with steatosis were less likely to achieve a sustained virologic response (SVR) even when taking into account other factors that might induce steatosis. One study found that sustained virologic response rates were 18-32% lower in people with steatosis compared to people without steatosis after adjusting for other co-factors that affect treatment such as genotype, fibrosis score, and viral load level. /

Diet and Excercise:

A recent study found that HCV patients who participated in a diet and exercise program for three months lowered their grade of steatosis and, remarkably, their fibrosis score. ;./.

The Study

In this study we show that, besides alcohol consumption, an unbalanced diet is an important factor of HCV evolution and nonresponse to antiviral treatment. Specific nutritional education and severe alcohol restrictions might, synergistically, improve the response to antiviral therapy..

Link : The Impact of Diet on Liver Fibrosis and on Response to Interferon Therapy in Patients With HCV-Related Chronic Hepatitis

Preventive Care in Chronic Liver Diseases.

Thomas R. RileyMilton S. Hershey Medical CenterHershey, PA

Introduction:

Chronic liver disease is the tenth leading cause of death in the United States (US) with over 25,000 deaths annually, according to federal statistics. There are an estimated 4 million known cases of hepatitis C in the US, some of which present with cirrhosis or will eventually become cirrhotic (1). Our current ability to treat hepatitis C and eliminate the infection has been improving with the advent of long acting interferons. After treatment, however, there will continue to be about 40-50% with continued evidence of chronic infection.

The natural history of HCV is a progression from hepatitis to cirrhosis over many years, often twenty to fifty years. With an inability to cure the primary disease process in this non-responder group, it becomes important to prevent further insults thus optimizing the length of time between hepatitis to cirrhosis. Once cirrhosis occurs nothing currently can be done to reverse the process. Those with early cirrhosis (Child’s A) may live on average 10 to 15 years before death or liver transplantation (2). Preventive strategies can be used to maximize this time. This review will discuss preventive care methods that have been shown to be effective or have scientific rationale in the setting of chronic liver diseases both in the hepatitis and cirrhotic stages.

Continue Reading............


Link Between Nonalcoholic Steatohepatitis and Liver Cancer Confirmed in New Study

ScienceDaily (May 26, 2010) — A study conducted by researchers at the Cleveland Clinic finds that patients suffering from cirrhosis preceded by nonalcoholic steatohepatitis are at an equal risk of developing hepatocellular carcinoma than those who develop cirrhosis resulting from hepatitis C virus (HCV).

Results of this study appear in the June issue of Hepatology, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases (AASLD).

The incidence of hepatocellular carcinoma (HCC) doubled in the United States between 1983 and 2002. It is currently considered the third leading cause of cancer deaths. The increasing incidence of HCC parallels the obesity epidemic. An estimated two-thirds of obese people have some form of fatty liver, including nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis and subsequently HCC. According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NASH affects 2% to 5% of Americans and ranks as one of the major causes of cirrhosis in the U.S., behind HCV and alcoholic liver disease.

The Cleveland Clinic team, led by Nizar N. Zein, M.D., evaluated a total of 510 patients, 315 with liver cirrhosis secondary to chronic HCV infection and 195 with NASH-induced cirrhosis, to compare the incidence of NASH-cirrhosis to HCV-cirrhosis, and to identify HCC risk factors in each group. Over a median follow-up time of 3.2 years after cirrhosis diagnosis, the yearly cumulative incidence of HCC was 2.6% per year in patients with NASH-cirrhosis compared to 4.0% per year in those with HCV-cirrhosis. These figures suggest that NASH carries a risk of HCC that rivals the risk in patients with HCV-cirrhosis.

Results indicate three factors that are statistically significant in the development of HCC within the NASH-cirrhosis group. An older age at time of cirrhosis diagnosis and a higher BMI were negatively associated with the development of HCC. Among the NASH population, researchers found that patients who reported any lifetime alcohol consumption were 3.6 times more likely to develop HCC than those who had no exposure to alcohol.

"The most significant factor recognized in this study was that of alcohol intake," said Dr. Zein. "Our study supports emerging data that alcohol intake, even in 'social' quantities, may potentially increase the risk of HCC development in NASH- and HCV-cirrhotic patients compared with non-drinkers."

The Cleveland Clinic study established that NASH-induced cirrhosis is a much greater risk factor for HCC than previously thought. A related study offers an explanation as to why NASH often progresses to liver cancer.

Continue Reading......................................

http://www.sciencedaily.com/releases/2010/05/100525090556.htm