Saturday, August 23, 2014

HCV Weekend Reading: Fatty Liver Disease

HCV Weekend Reading: Fatty Liver Disease 

Good afternoon folks, welcome to this edition of weekend reading, today the topic is fatty liver disease.

So sit back and listen to Dr. Joe Galati, interview NY Times reporter, Anahad O’Connor about this serious liver disease and the detrimental effect it has on the liver.

If you haven't read it yet, an article written by O'Connor for the NY Times offers a clear understanding of the condition, including the rise of fatty liver disease in children.

Also in today's post, is an interesting research paper which examines if Non-Alcoholic steatohepatitis (NASH) is associated with HCV disease progression in persons afflicted with both conditions. Finally, an update on Galectin Therapeutics’ drug GR-MD-02 to treat NASH.

In addition, an article over at Healio, published in the July/August issue of "HCV Next" written by Alia Hasham, MD and Thomas C. Mahl, MD., discuss factors associated with fibrosis progression  in persons with fatty liver and HCV.

The Patient with NAFLD and Chronic HCV
In the absence of significant alcohol consumption, non-alcoholic fatty liver disease is now becoming a more frequent, concomitant diagnosis in HCV patients, and insulin resistance has emerged as a key underlying pathogenic feature. NAFLD includes a spectrum of disease, ranging from nonalcoholic steatohepatitis (NASH) to steatosis, with a prevalence of approximately 10% and 30% respectively, in the general population.
The cumulative effects of HCV and NAFLD could have important clinical implications and may accelerate fibrosis progression, increase risk for hepatocarcinogenesis and impair response to antiviral therapy. However, with the introduction of newer anti-HCV agents, including direct-acting antivirals (DAAs), the presence of hepatic steatosis may have less impact on treatment response, and interventions directed at lifestyle modifications, with improvements in insulin sensitivity, could represent an important therapeutic focus. 
Read the article here...

Your Health First Radio

 
In order to gain a better perspective of fatty liver disease; Non-alcoholic fatty liver disease (NAFLD) and Non-Alcoholic steatohepatitis (NASH) an overview is provided by; The Canadian Liver Foundation

What is a fatty liver?

A fatty liver is the result of the excess fat in liver cells. Fatty tissue slowly builds up in the liver when a person’s diet exceeds the amount of fat his or her body can handle. A person has a fatty liver when fat makes up at least 5% of the liver 1. Simple fatty liver can be a completely benign condition and usually does not lead to liver damage. However, once there is a buildup of simple fat, the liver becomes vulnerable to further injury, which may result in inflammation and scarring of the liver 2.

What is Non-alcoholic fatty liver disease (NAFLD)?


NAFLD is a progressive complex of liver disease which starts with fat accumulation in the liver without excessive alcohol consumption. It is strongly associated with metabolic syndrome (obesity + insulin resistance + dyslipidemia)

What is NASH?

NASH stands for Non-Alcoholic steatohepatitis and it represents the more severe end of the spectrum of non-alcoholic fatty liver disease. Steatohepatitis means fatty liver with inflammation, in other words, ongoing damage similar to alcoholic liver disease but in this case it occurs in people who do not drink alcohol or drink minimally 13.

NASH differs from the simple accumulation of fat in the liver, which is a completely benign condition. Up to 20% of adults with NASH develop cirrhosis and up to 11% may experience liver-related deaths. Many individuals develop chronic liver failure and require liver transplantation. The prevalence of NASH is 2-6% in the general population.

Fatty Liver Disease and Hepatitis C
Fatty liver disease has become a serious health problem in the last decade, affecting close to 20 percent of Americans and is estimated to surpass hepatitis C as the leading case of liver transplants by 2020.

A research article published in the current issue of Journal Of Hepatitis Research, titled; Non-Alcoholic Steatohepatitis (NASH) Influences the Disease Progression of Chronic Hepatitis C (CH-C): Histopathological Study of Liver Biopsies in 400 Cases with CH-C., authored by Matsumoto T, Fukuhara K, Yaginuma R, Ikejima K, Morizane T, suggest NASH, the more severe form of NAFLD,  may have an influence on disease progression in people who also have chronic hepatitis C.

In short the authors wrote;
The liver biopsies were performed in Juntendo Hospital or Juntendo University Nerima Hospital. The examined cases were 400 Japanese adults (229 males and 171 females) with ages ranging from 21 to 78 years (mean: 51 years). None of the cases had a past history taking alcohol.

A histological study of the association of NASH in Chronic Hepatitis C (CH-C) in a large number of cases has been performed to date in three studies, including the present study, and the present study involves the largest number of examined cases. The incidence of NASH in CH-C ranged from 9 to 18.3% in the studies (Table 6). These results indicate that the incidence of NASH in CH-C is about 10 to 20%.



The previous two studies [2-4], and the present study showed that patients with NASH had a more advanced stage than those without NASH. In the present study, the likelihood ratio for stage (fibrosis) indicated that, when being NASH-positive, the odds of having a more progressed stage is 1.76 times higher than on being NASH-negative.

Thus, the possibility of an increase in fibrosis due to the association of NASH was considered. However, we thought that this hypothesis needs to be investigated by the examination of repeated liver biopsies in the same patients, but such a study had not been published. Thus, we performed the evaluation of liver changes in the cases of Chronic Hepatitis C (CH-C) with NASH in repeated liver biopsies. Subsequently, three cases of advanced stages (F3 or F4) of CH-C with NASH showed increasing fibrosis from early (F1) to advance (F3) stages in long intervals (9, 12, and 18 years). This indicated that the association of NASH causes an increase of fibrosis with long intervals.

On the other hand, one case with a short interval (2 years) was in an advanced stage (F3) in the first liver biopsy. Thus, the change in liver fibrosis by the association of NASH in short intervals could not be clarified in the present study.

Although the proportion of the increase of fibrosis by CH-C or NASH in CH-C cases with NASH has not been studied, the present study demonstrated that the increase occurred in the same proportion by both CH-C and NASH in two cases, and, in one case, the increase mainly occurred due to CH-C and partly due to NASH.

These indicated that the importance of treatment of both CH-C and NASH in CH-C cases with NASH. Our previous study reported that hepatic steatosis is a predictor of a poor response to interferon α-2b and ribavirin therapy in patients with CH-C [9]. So, we think that a new treatment method is needed in patients with CH-C with NASH.

As an interesting finding in this study, the two cases (case no. 2 and 4) with disease progression from early to advanced stages had fibrosis due to both CH-C and NASH, but no association of NASH was found in the initial biopsy. Until now, it has been reported that chronic infection of HCV leads to NASH [10-12]. Thus, in the two cases, HCV induced NASH and disease progression occurred due to the interaction between HCV infection and the NASH state induced by HCV.

In conclusion, the present study confirmed that the association of NASH influences the disease progression of CH-C, and it is the first to demonstrate that the disease progression is caused by both CH-C and NASH equally or CH-C mainly. These findings are useful for the treatment of CH-C with NASH.

Download The Full Text Article, here

Research
New Mouse Model Points to Therapy for Liver Disease 
Aug 19, 2014

Of Interest

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