GOING BEYOND THE LIVER IN NAFLD/NASH: THE HEPATOLOGIST'S/ENDOCRINOLOGIST’S PERSPECTIVE

I listened to the above conference today. There is another conference this Saturday:

https://www.eventbrite.com/e/lets-smash-nash-ddw-2022-symposium-registration-336102861707

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The biggest take away from this is that the prevalence of this disease is gargantuan. The market is simply immense.

The benefits of eradicating this from one's life, improves liver health, reduces potential diabetes complications leading to less potential for cardiovascular disease. In addition, it leads to reduced possibility for liver disease, for hepatitis, for cirrhosis and for hepatocellular carcinoma and therefore for metastasis.

Patients will lose weight as all the liver fat dissipates. No more swollen bellies.

Here are some things I found interesting:

NAFLD and NASH prevalence to exceed 30 million cases by 2030.

The only real sign is extended belly. Sure there are labs and other markers.

NAFLD and NASH sit in the transition zone between Diabetes (which leads to CardioVascular Disease) and Liver Disease (Cirrhosis, Hepatitis), (which leads to Chronic Kidney Disease, CVD and HepatoCellular Carcinoma and other cancers).

Massive prevalence of NAFLD & NASH in Diabetes population. NAFLD increases risk of death in CVD.

About 25% of population has either NAFLD or NASH, (Think Type II Diabetes, Fat, hepatocyte ballooning, inflammation with or without fibrosis). 25% of that are NASH cases, (1/8 population), NASH leads to Cirrhosis, (Stage 4 hepatic fibrosis with or without fat and inflammation). Cirrhosis leads to liver failure. Liver failure leads to HepatoCellular Carcinoma, (Fat, Ballooning, Inflammation, Scarring and mutation).

NAFLD may progress over 14 years. NASH may progress over 7 years.

The best predictor of mortality is degree of Fibrosis, (Scarring).

NASH is an indication for liver transplant. Primary cause of chronic liver disease.

NASH characterized by hepatic steatosis, inflammation and ballooned hepatocytes with or without presence of fibrosis.

Biomarkers should be developed for specific patient groups for timely detecting of fibrosis.

The progression:

Normal liver >> Isolated Steatosis >> NASH >> Fibrosis >> Cirrhosis

NASH is driven by Insulin Resistance, common in Metabolic Syndrome X. 80% of obese individuals have NAFLD. Insulin Resistance is toxic to the liver. Cell membranes destroyed. Necrotic inflammation. Transition from NAFLD to NASH.

Resmetirom is the only potential drug which may get approved. It is a selective thyromimetic.

Liver is in a hypothyroid state.

Treatment is very passive:

Treat the metabolic syndrome, modifying cardiovascular risk factors, diabetes control. Lose weight, Assess annual liver function tests, re-assess in a few years. Remember NASH is interim/transition between Diabetes and Liver Disease (Hepatitis).

Use FibroScan to gauge. (This is European Lecture and therefore their treatment protocol). Measurement is directly related to tissue stiffness, (fibrosis). The stiffer, the faster the wave progresses. Quick test, 5 minutes. limited by obesity and operator.

Liver Biopsy is "Gold Standard" to diagnose NASH, but it's imperfect.

Sustained weight loss of >10% leads to fibrosis regression of 45% and very high improvement in steatosis, and NASH scoring. 230 >> 207 lbs indefinitely.

"Because of the slow progression of NASH, the FDA recommends liver histological improvement as endpoints reasonably likely to predict clinical benefit to support accelerated approval."

NASH Resolution would be the resolution of steatohepatitis on overall histopathologic reading and No Worsening of liver Fibrosis

and

Fibrosis Improvement would be an improvement of 1 or greater fibrosis stage and No worsening of steatohepatitis.

Bariatric surgery very effective in resolving NASH after 5 years. 84% effective.

In non-diabetic patients, some doctors prescribe Vitamin E, not to exceed 800 iu daily. Most doctors are not treating. Some are using Pioglitazone, but it is not approved.