Reversing Advanced Fibrosis Caused by NASH

Experts consider the potential to reverse fibrosis in patients with nonalcoholic steatohepatitis by utilizing recommended management strategies and referring to currently available clinical practice guidelines.


Norman Sussman, MD: Can we reverse fibrosis? The answer is, yes. Studies have shown that patients who improve their metabolic profile can see NASH [nonalcoholic steatohepatitis] completely disappear. In fact, about half of them will see their fibrosis improve to the point that the liver will function completely normal. It is important to recognize that once people have developed cirrhosis, they are still at risk for liver cancer. But all the other features, all the other disease burden, can be improved simply by improving metabolic syndrome.

In terms of reducing fibrosis, some companies are now working on medications that we hope will increase the rate at which patients are able to dissolve their scar tissue.

Mazen Noureddin, MD: We need to increase education for patients as well as primary care physicians and clinicians from some other specialties, such as endocrinology and even gastroenterology. Many patients are not aware of what advanced fibrosis means. They end up in our clinics. They sit down in front of us, we do 1 or 2 noninvasive tests or even a liver biopsy, and we tell them they have advanced fibrosis or cirrhosis. A lot of them will not understand. They will be surprised. And then we explain that the sequence of that to them, such as progression to cirrhosis, and eventually decompensated liver disease, liver failure, and cancer. This all comes as a surprise for them.

Therefore, 1 of the huge tasks we face with these patients who come to us is providing them with education, education, education. A lot of these patients come to us overweight [obese], as well as with uncontrolled diabetes, uncontrolled high blood pressure. We tell them, “Your metabolic syndrome and nonalcoholic fatty liver disease with advanced fibrosis need to be controlled.” We advise them to go to their primary care physician or endocrinologist for management to control the diabetes as well as the hypertension.

Many programs have nutritionists. They teach patients how to lose weight via different strategies. It’s 1 of the most effective methods to help nonalcoholic fatty liver disease. However, once patients get to advanced fibrosis, it is probably important to add another thing to their lifestyle. There are a few medications that are recommended by the American Association for the Study of Liver Diseases as well as the European Association for the Study of the Liver that we sometimes prescribe to patients. Some have adverse effects, and some are not very effective for fibrosis. Therefore, new therapies are needed.

Another thing that we educate them about once they have advanced fibrosis is that they are at risk of cancer. Some patients start with hepatocellular carcinoma screening, which we do, on average, every 6 months. As I mentioned, weight loss is a very good strategy at a baseline, and for advanced fibrosis you probably want to add other things. But the problem with weight loss is that many patients have been the same way for many years. Some of them are initially successful. However, the overall success rate has not been overwhelming. Therefore, the search for new medications to reverse advanced fibrosis has been crucial.

Viviana Figueroa Diaz, MD: Once the patients have risk factors for NASH, it’s good to screen them for fatty liver disease. That could be from a primary care provider, or if a primary care provider finds an imaging result suggestive of fatty liver disease, it’s OK to even refer the patient to a gastroenterologist or a hepatologist. The most important part is not only to assess for fibrosis but also to use our tools to motivate the patient to stick to lifestyle modifications.

Right now, it’s a partnership. Most of the work is on the patient. We don’t have a pill, per se, right now. There is a lot of research going on regarding therapeutic options with pharmacotherapy, but right now what we have is lifestyle modification. Part of that is on the patient, but we also have to motivate and guide the patient. One of the things we shouldn’t be doing is saying, “You need to lose weight,” and that’s it. That gives the patient no resources. You really have to work on diet counseling, exercise counseling, goals for their diabetes, weight goals. That drives the patient a little better, in regard to achieving their lifestyle modifications.

Mazen Noureddin, MD: The American Association for the Study of Liver Diseases and the European Association for the Study of the Liver manage the disease similarly. There’s a slight difference in recommendations for screening. For instance, the European authority recommends screening for those at high risk, such as patients with diabetes and patients at age 55. The American Association for the Study of Liver Diseases has not yet recommended screening. However, with a more cost-effective analysis in the future, everyone feels that this will happen. Nowadays, both societies recommend vitamin E and pioglitazone to these patients, and usually they recommend starting with a liver biopsy to diagnose NASH. We feel that this is going to change in the future. We feel are going to target more F2 individuals, or advanced fibrosis patients, to reverse their disease. Vitamin E and pioglitazone have done well, however they have some adverse effects and have not shown to be very effective in reversing fibrosis in the trials that they have been involved in.

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