POWERPOINT PRESENTATION BRIEF FOR NEUTROSEC

“LIVER DISEASES. KILLING ME SOFTLY”

Slide 3. Overview
Slide 4. The Liver: This slide only outlines some of the major functions of the liver. Please note
that these functions are more than what is listed. Of particular interest are detoxification,
metabolism of drugs and foods, production of bile and clotting factors.

Slide 5. Liver Toxicity: The liver has been generally described as the “chemical factory” of the
body. Besides producing many different biochemicals for the body, almost every substance that
enters the body through the mouth (e.g. food, drugs, alcohol), through the nose (e.g. inhaled
substances, smoke, environmental chemicals), by injection, infusion and other means, usually
pass through the liver for metabolism and other physiological processes. Thus the liver is
exposed to varied impacts/risks/injuries from these substances. Many of these substances are
toxic. Thus they can harm the cells of the liver. Examples are
 Alcohol: this accounts for more than 50% of all cases of toxicity
 Drugs: These refer to both prescribed medicines, self-medication and abused medicines.
They are responsible for more than 50% of acute liver disease. Examples include
hepatotoxicity due to overdose of acetaminophen (also called Paracetamol) &
idiosyncratic liver injury caused by other drugs.
 Chemicals (industrial fumes, vehicle exhaust fumes and many other chemicals)
 Auto-immune disorders: An example is autoimmune hepatitis, an inflammatory disease
which occurs when the body’s immune system suddenly perceives liver cells as foreign
bodies and begins to attack them. Though the exact cause is unknown, genetic and
environmental factors are the major suspects, acting over time to trigger the disease. If
not diagnosed and treated on time, it can lead to cirrhosis and eventually, liver failure.
 Infections (especially by viruses)

Slide 6. Liver Disease: This slide gives a simple definition of “liver diseases” and how it occurs. It
also gives specific examples of the common types of liver diseases, namely:
• Alcoholic Liver Disease (ALD)
• Non Alcoholic Liver Disease (NALD)
• Drug-Induced Liver Injury (DILI)
• Fatty Liver Disease
• Viral Hepatitis
• Liver Cirrhosis
Slide 7. Epidemiology: The slide gives a global picture of the impact of liver disease on quality
of life around the world. Specifically, it shows that non-alcoholic steatohepatitis (NASH) is
driven largely by obesity and has a global prevalence as high as 35%. In Nigeria, the statistics
are even more disturbing - chronic liver disease accounts for 16.7% of gastroenterology OPD
consultations and 7.9% of medical admissions.
Slide 8. Risk Factors: This slide just gives a general view of all the factors that play critical roles
in the pathogenesis of liver diseases. Specific mention of a few risk factors is essential here, in
case a rep has to answer related questions during a CM.
- Family History: Inherited liver diseases are a group of metabolic and genetic defects that
typically cause early chronic liver diseases. Most of these liver diseases are due to a
defect of an enzyme/transport protein that alters a metabolic pathway and exerts a
pathogenic role mainly in the liver. The prevalence is variable, but most are rare
pathologies. (Manuela Scorza et al. Genetic Diseases That Predispose to Early Liver
Cirrhosis. Int’l J Hepatol. Vol. 2014, Article ID 713754 )
- Cigarette Smoking: Smoking causes a variety of adverse effects on organs that have no
direct contact with the smoke itself, e.g. liver. The adverse effects of smoking on the
liver are:
i. Direct or indirect toxic effects by chemical substances with cytotoxic potential which
increase inflammation and fibrosis.
ii. Immunological effects: It also increases the production of pro-inflammatory
cytokines (Interleukin 1 & 6, and TNF- α) which are involved in liver injury.
iii. Oncogenic (cancer) effects: Smoking produces chemicals with cancer potential that
increase the risk of hepatocellular carcinoma (HCC) in patients with viral hepatitis.
(Abdel-Rahman El-Zayadi, Heavy Smoking and Liver. World J Gastroenterol. 2006;12(38): 6098–6101)

- Starvation: Starvation causes liver cell injury and death, leading to a rise in
aminotransferases. Malnutrition-induced hepatitis is common among individuals with
anorexia nervosa, especially as body mass index (BMI) decreases. While the hepatitis of
anorexia nervosa can reach severe levels, an increase in food intake and a return to a
healthy body weight often quickly lead to normalization of elevated aminotransferases
caused by starvation. (Rosen E et al. Hepatic Complications of Anorexia Nervosa. Dig Dis Sci.
2017;62(11):2977-2981)
- Parenteral Nutrition: A type of liver disease called Parenteral Nutrition-Associated Liver
Disease (PNALD) occurs in patients receiving IV feeding. In fact, there are 3 types of liver
disorders associated with parenteral nutrition: steatosis, cholestasis, and gallbladder
stones. Factors that contribute to this disease include
i. History of IV feeding
ii. Sepsis
iii. Bacterial overgrowth
iv. Prematurity/low birth weight.
v. Excessive calorie intake
 vi. Choline deficiency, etc.
(Kumpf VJ. Parenteral nutrition-associated liver disease in adult and pediatric patients. Nutr Clin
Pract. 2006; 21(3):279-90)

- Obesity: Obesity is associated with an increased risk of nonalcoholic fatty liver disease
(NAFLD). Steatosis, the major feature of NAFLD, occurs when the rate of hepatic fatty
acid uptake from plasma and fresh fatty acid synthesis is greater than the rate of fatty
acid oxidation and removal (as triglyceride) from the liver. (Elisa Fabbrini et al. Obesity and
NAFLD: Biochemical, Metabolic and Clinical Implications. Hepatology. 2010 Feb; 51(2): 679–689)

Slide 9. Risk Factors - Alcohol: This slide intends to throw more light on alcohol as one of the
two most commonly cited risk factors for liver disease (the other one being drugs). Usually, high
levels of nutritional deficiencies and malnutrition are found in alcoholic patients. Therefore, it
was previously thought that those deficiencies were responsible for the high prevalence of liver
disease in alcoholic patients. However, studies now show that alcohol itself is the major cause,
through direct toxic effects of Acetaldehyde (metabolite of alcohol) & generation of free
radicals or ROS.
The impact of alcohol on the development and progression of alcoholic liver disease depends
on the type of alcohol consumed, amount consumed and pattern of consumption. For instance,
concentrated wines and spirits have a high percentage of alcohol than red wine. Thus the small
the alcohol content, the lower the risk of alcohol-induced damage. Heavy drinkers are at a high
risk than occasional drinkers. Drinking on empty stomach carries a higher risk because uptake is
faster and blood levels of alcohol is also higher.
Slide 10. Risk Factor (Alcohol): This slide intends to draw attention to a trend of indirect alcohol
intake among men and women in Nigeria – intake of alcoholic herbal mixtures. These are
actively marketed for fancy indications such as “man power”, “sexual prowess”, etc. They
contain ingredients that are usually no disclosed on the outer packs. The only features are the
bitter taste, dark color of the content and alcoholic components. Studies have shown that these
mixtures (most of which are marketed as alcoholic bitters) exposes consumers to multiple liver
toxins. They are fast gaining popularity among male consumers and consumption is driven
more by the alcohol content than the herbal benefits.
Medical literature in Nigeria on Herb-induced liver injury has documented the toxic effects of
alcohol (consumed directly or in alcoholic herbal mixtures).
- an independent determinant of the progression of chronic liver disease
- a major cause of liver cirrhosis in about 80% of patients

Slide 11. Risk factors (Medications): Drug induced liver injury is another cause of liver disease
and refers to liver injury from xenobiotics, herbs, or medications that lead to liver dysfunction.
A xenobiotic is a chemical substance found within an organism that is not naturally produced or
expected to be present within the organism; or a chemical foreign to or not produced by an
organism. Over 1,000 drugs are known to induce liver toxicity, including many prescribed
medicines. Examples are Acetaminophen (Paracetamol), some antibiotics (including
Amoxicillin-Clavulanate) and immunosuppressant drugs.
Studies have also shown that use of certain drugs on very chronic basis exposes the patients to
toxicity arising from chronic drug use. In particular, there are growing concerns about the safety
of herbal medicines because of their association with complications, (e.g. liver damage) and a
high incidence of morbidity & mortality in active and chronic consumers of alcoholic herbal
mixtures.

Slide 12. Pathophysiology: This slide serves to simplify the otherwise complicated process of
liver disease development and progression. The process is broken down into 3 stages: Contact
with toxin, Fibrosis and Cirrhosis
i. Contact with toxic factor (alcohol, drugs, chemical, etc.): The liver will respond by
way of inflammation (hepatitis) or infiltration of liver cells with fat (steatosis) or
both. Because these changes are not permanent and the ability of the liver to
regenerate its own tissues has not been lost, the liver can regenerate the damaged
tissues and reverse the changes. However, with continued exposure to the toxic
factor, injury can progress to fibrosis and cirrhosis.
ii. Fibrosis: Fibrosis is generally defined as the thickening and scarring of connective
tissue, usually as a result of injury. At the stage, liver cells (hepatocytes) begin to die
(necrosis). Necrosis stimulates immune cells to release cytokines and growth factors,
which in turn stimulate the production of collagen, fibronectin & proteoglycans. The
combination of collagen, fibronectin and proteoglycan form a matrix which build up
to form a scar tissue. Usually the liver also has a homeostatic process of handling
this matrix formation and this is by degradation of the produced collagen. But when
a liver is going through fibrosis and matrix formation, the process of collagen break
down is impaired. Thus scar tissue formation continues unchallenged Fibrosis
occurs when collagen formation is faster than its break down & removal
Slide 13. Cirrhosis: This is the late stage of liver scarring (fibrosis) of the liver. It is a chronic
disease of the liver marked by cell degenerations, inflammation, and fibrous thickening of
tissue. At this stage, scar tissue replaces healthy liver cells. Also, the usual smooth liver texture
becomes nodular, compromise blood flow & cause liver dysfunction. Consequently, either of the
following event take place:

- Liver is scarred but may still be able cope & function (compensated cirrhosis)
- Liver is extensively scarred & unable to function (decompensated cirrhosis).
Slide 14. Pathophysiology: Self explanatory
Slide 15. Treatment Approach: The major underlying factors in liver disease (excluding viral
infections) include
a) Oxidative stress, due to ROS.
b) Deficiency of glutathione (GSH).
c) Loss of cell membrane integrity.
d) Deficiency of nutrients.
Therefore, treatment approach must consider addressing these gaps. In other word, treatment
must be tailored towards reducing the generation of free radicals (or Reactive Oxygen Species),
increasing production of glutathione, which is the body’s major scavenger of free radicals,
maintenance of the functions of the liver cell membrane and provision of specific nutrients
which the liver needs for optimal function.

Slide 16. Treatment Principles: This slide takes us through the thinking behind treatment. It
justifies the inclusion of key ingredients in the treatment offering. For a fact, all the ingredients
in Neutrosec are nutritional in nature. This suggests the critical nature of nutrition in the
management of liver diseases and maintenance of liver functions.
It emphasizes that methyl group donation is key in major biochemical reactions in the liver
which lead to the production of glutathione and health of liver cells. Thus the presence or
absence of these methyl donors (Methionine, Choline and Folate) will impact liver health; for
instance, deficiency of these important methyl donors to predispose the liver necrosis of
hepatocyte, development of fibrosis, and appearance of foci of carcinomas (liver cancer).

Slide 17. Hepatoprotection - Methionine, SAMe & Liver Disease: This slide simply outlines the
importance of Methionine and its metabolite (SAMe). Methionine is a precursor to SAMe, while
SAMe is a precursor to glutathione. The slide generally lists the major benefits of SAMe to the
liver
- Restoration of glutathione deposits & prevention of oxidative stress
- Regulation of liver cell growth and differentiation
- Maintenance of the integrity of liver cell membranes, thus protecting the liver
- Alteration of the process of fibrosis, thus restoring liver function.
Summary is that the presence of methionine convers all the above benefits on the liver,
thus protecting the liver and restoring its functions.

Slide 18. Hepatoprotection - Choline, Phosphatidylcholine and Liver Disease: The slide throws light
on the important roles that nutritional choline plays in liver functions and the consequence of its
deficiency. Choline is necessary for the formation of phosphatidylcholine. Phosphatidylcholine is
important for solubilizing bile salts. It is also a major component of liver cell membrane. Poor hepatic
choline/phosphatidylcholine availability promotes the steatosis that characterizes nonalcoholic fatty
liver disease (NAFLD). That means when we eat diet that is low in choline long term, the risk of
developing liver disease increases.

Slide 19. Hepatoprotection – Vitamins and Liver Disease: This slide presents the importance
of vitamins in the maintenance of liver functions. Folate deficiency may arise from
- Poor folate intake
- Mal-absorption
- Low liver uptake/ storage
- Increased urinary excretion
In any case, folate deficiency encourages liver disease progression Also, chronic deficiencies of
Vitamin B12 increases the risk of liver disease. Low levels of Folate and B12 are associated with
fibrosis. This calls for regular intake of dietary sources of these nutritional factors.

Slides 20 and 29 are self-explanatory.

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Friday Enaholo