Treatment of NASH: What Helps

Beyond Weight Loss?

Pembimbing : Dr. Titos Ahimsa, Sp.PD-KGEH

• Handhy Tanara 112016289
 Nonalcoholic Fatty Liver
Alcoholic Liver Disease
Disease (NAFLD)

Nonalcoholic Fatty Liver + Hepatocellular Nonalcoholic

(NAFL) Injury Steatohepatitis (NASH)

Cirrhosis and/or Hepatocellular

Cancer (HCC)
Assessment of Risky Drinking Behavior (12 month)
Recurrent drinking in hazardous situations
• More than once driven a car or other vehicle while
drinking or after having had too much to drink?
• More than once gotten into situations while drinking
or after drinking that increased your chances of getting
hurt (such as swimming, using machinery, walking in a
dangerous area or around heavy traffic, or having
unsafe sex)?
Continued use despite recurrent
interpersonal or social problems
• Continued to drink even though it was causing you
trouble with family or friends?
• Gotten into physical fights while drinking or right after
drinking?
• Given up or cut back on activities that were important
or interesting to you, in order to drink?
Failure to fulfill major role obligations at work, school, or
home
•Had a period when your drinking or being sick from drinking often
interfered with taking care of home or family? Caused job troubles?
School problems?
Recurrent legal problems related to alcohol
•Gotten arrested, been held at a police station, or had any other legal
problems because of drinking?
Health problems
•Found that when the effects of alcohol were wearing off, you had
withdrawal symptoms, such as trouble sleeping, shakiness,
restlessness, nausea, sweating, a racing heart, or a seizure? Or sensed
things that were not there?
•Continued to drink even though it was making you feel depressed or
anxious or adding to another health problem? Or after having had a
memory blackout?
Nonalcoholic Fatty Liver Disease and Related Definitions
 Definitions of NAFLD requires

• There is evidence of hepatic steatosis,

either by imaging or by histology
• There are no causes for secondary
hepatic fat accumulation such as
significant alcohol consumption, use
of steatogenic medication, or
hereditary disorders
NAFLD Should be Suspected In

Individuals with risk factors

Hepatic steatosis on imaging

Abnormal liver enzymes without a competing

etiology for liver disease (such as viral hepatitis,
Wilsons disease or alcoholic liver disease (ALD))
Assessing a Patient with Suspected NAFLD
Confirming the diagnosis

Definitions : Development of liver fibrosis to

Determining the patient’s risk of liver-
related outcomes (cirrhosis, HCC)
the point that there is architectural distortion
with the formation of regenerative nodules,
which results in decreased liver function.
Symptoms : Anorexia, nausea, vomiting,
diarrhea, vague RUQ pain, fatigue, weakness,
fever, jaundice, amenorrhea, impotence,
infertility

Formulating a monitoring and/or treatment

plan based on the patient’s metabolic risk
profile and risk for liver-related outcomes
Hematoxylin-eosin stain of tissue sections from
•Normal human liver
•Nonalcoholic fatty liver (NAFL)
•Nonalcoholic steatohepatitis (NASH)
•NASH with fibrosis
•NASH with cirrhosis

Black arrows indicate steatosis; white arrows show ballooned hepatocytes, a key feature of
steatohepatitis; black arrowheads indicate fibrosis. PT, portal tract.
 Confirmation of NAFLD and Disease Prognostication
Imaging modalities, including sonography,
CT scan and MRI
Prognostication relies on assessing the risk of
progression to cirrhosis,
Disease activity refers to the pathophysiological
engine driving the disease towards cirrhosis
Disease activity is traditionally inferred from the
presence of steatohepatitis and assessment of
NAFLD activity score (NAS),
Disease stage is reliably measured by the fibrosis
stage
The need for a liver biopsy to make these
assessments is a major barrier to the evaluation
• Proof of hepatic steatosis but do not provide prognostic
information
• Inferred from disease activity and stage.
• Disease stage refers to how far the disease has
progressed towards cirrhosis.
• Can only be determined with a liver biopsy.
• F0 (normal liver) through F4 (cirrhosis).
• management of NAFLD patients and has fueled
great interest in alternate approaches.
 Disease Staging

Vibration Controlled Transient

Elastography (VCTE)
• Relatively inexpensive compared to magnetic
resonance elastograstography (MRE), widely Fibrosis-4 (FIB4) index
available
• Provides liver stiffness measurement (LSM), a FIB4<1.45 without fibrosis and/or at
surrogate for hepatic fibrosis. very low risk of liver-related outcomes
• It also provides the continuous attenuation
parameter (CAP), a surrogate for hepatic steatosis.

NAFLD fibrosis score (NFS)

Aspartate Amino Transferase
NFS<1.455 without fibrosis and/or at (AST) to Platelet Ratio Index
very low risk of liver-related outcomes
NAFLD Treatment

•Diet:

•Weight loss generally reduces hepatic steatosis, achieved either by hypocaloric diet alone or in conjunction with
increased physical activity.

•Loss of at least 3 – 5 % of body weight appears necessary to improve steatosis, but a greater weight loss (up to 10
% ) may be needed to improve necroinflammation.

•Patients with NAFLD should not consume heavy amounts of alcohol

NAFLD Treatment

•Vitamin E ( α -tocopherol) daily dose of 800 I U / day

•First-line pharmacotherapy for non-diabetic adults with biopsy-proven NASH (improves liver histology)

•Not yet recommended to treat NASH in diabetic patients, NAFLD without liver biopsy, NASH cirrhosis, or
cryptogenic cirrhosis.

•Pioglitazone

•Pioglitazone can be used to treat steatohepatitis in patients with biopsy-proven NASH.

•Long-term safety and efficacy of pioglitazone in patients with NASH is not established.
NAFLD Treatment

•Pentoxifylline

•Xanthine derivative, is thought to act by reducing the viscosity of blood, allowing it to flow more easily through
partially obstructed areas.

•Almost exclusively for peripheral artery disease

•Liraglutide

•Liraglutide interacts with the GLP-1 receptor and acts to increase insulin and decrease glucagon release.
Classification and Management of Patients With Nonalcoholic Fatty Liver Disease
 Summary
The appropriate monitoring and treatment strategy for a patient with NAFLD depends on
the individual’s metabolic risk profile and their risk of liver-related outcomes.
Weight loss through diet and exercise remains the cornerstone of treatment; bariatric
surgery should be considered in patients who meet criteria.
Management of cardiometabolic risk and adherence to cancer screening guidelines are
essential.
Given the currently available data, vitamin E and pioglitazone, typically used as first-line
agents, should be reserved for those with intermediate-risk NASH.
The pharmacological treatment of NASH is evolving, with several agents currently in the
pipeline for testing.
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