Portal hypertension is commonly caused by cirrhosis and results in a hepatic venous pressure gradient over 10 mmHg, increasing risk of variceal bleeding. Clinical features include splenomegaly, abdominal wall varices, and esophageal/gastric varices which can cause life-threatening bleeding. Management focuses on primary and secondary prevention of variceal bleeding through beta-blockers, band ligation, TIPSS, and antibiotics for associated sepsis risk.
Some slides are taken from different textbooks of medicine like Davidson, Kumar and Clark and Oxford, and some from other presentations made by respected tutors. I'm barely responsible for compilation of various resources per my interest. These resources are free for use, and I do not claim any copyright. Hoping knowledge remains free for all, forever.
Some slides are taken from different textbooks of medicine like Davidson, Kumar and Clark and Oxford, and some from other presentations made by respected tutors. I'm barely responsible for compilation of various resources per my interest. These resources are free for use, and I do not claim any copyright. Hoping knowledge remains free for all, forever.
Approach to Management of Upper Gastrointestinal (GI) BleedingArun Vasireddy
Upper gastrointestinal bleeding is gastrointestinal bleeding in the upper gastrointestinal tract, commonly defined as bleeding arising from the esophagus, stomach, or duodenum. Blood may be observed in vomit (hematemesis) or in altered form in the stool (melena). Depending on the severity of the blood loss, there may be symptoms of insufficient circulating blood volume and shock. As a result, upper gastrointestinal bleeding is considered a medical emergency and typically requires hospital care for urgent diagnosis and treatment. Upper gastrointestinal bleeding can be caused by peptic ulcers, gastric erosions, esophageal varices, and some rarer causes such as gastric cancer.
The initial assessment includes measurement of the blood pressure and heart rate, as well as blood tests to determine hemoglobin concentration. In significant bleeding, fluid replacement is often required, as well as blood transfusion, before the source of bleeding can be determined by endoscopy of the upper digestive tract with an esophagogastroduodenoscopy. Depending on the source, endoscopic therapy can be applied to reduce rebleeding risk. Specific medical treatments (such as proton pump inhibitors for peptic ulcer disease) or procedures (such as TIPS for variceal hemorrhage) may be used. Recurrent or refractory bleeding may lead to need for surgery, although this has become uncommon as a result of improved endoscopic and medical treatment.
Seminar present the Upper Gastrointestinal Bleeding problems
Edited by : Dr. Inzar Yassen & Dr. Ammar L. Aldwaf
in Hawler Medical Uni. collage of medicine in 14/01/2014
Iraq - Kurdistan - Erbil
June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...Levi Shapiro
Letter from the Congress of the United States regarding Anti-Semitism sent June 3rd to MIT President Sally Kornbluth, MIT Corp Chair, Mark Gorenberg
Dear Dr. Kornbluth and Mr. Gorenberg,
The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
harassment and intimidation at the Massachusetts Institute of Technology (MIT). Failing to act decisively to ensure a safe learning environment for all students would be a grave dereliction of your responsibilities as President of MIT and Chair of the MIT Corporation.
This Congress will not stand idly by and allow an environment hostile to Jewish students to persist. The House believes that your institution is in violation of Title VI of the Civil Rights Act, and the inability or
unwillingness to rectify this violation through action requires accountability.
Postsecondary education is a unique opportunity for students to learn and have their ideas and beliefs challenged. However, universities receiving hundreds of millions of federal funds annually have denied
students that opportunity and have been hijacked to become venues for the promotion of terrorism, antisemitic harassment and intimidation, unlawful encampments, and in some cases, assaults and riots.
The House of Representatives will not countenance the use of federal funds to indoctrinate students into hateful, antisemitic, anti-American supporters of terrorism. Investigations into campus antisemitism by the Committee on Education and the Workforce and the Committee on Ways and Means have been expanded into a Congress-wide probe across all relevant jurisdictions to address this national crisis. The undersigned Committees will conduct oversight into the use of federal funds at MIT and its learning environment under authorities granted to each Committee.
• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
• The Committee on Oversight and Accountability is investigating the sources of funding and other support flowing to groups espousing pro-Hamas propaganda and engaged in antisemitic harassment and intimidation of students. The Committee on Oversight and Accountability is the principal oversight committee of the US House of Representatives and has broad authority to investigate “any matter” at “any time” under House Rule X.
• The Committee on Ways and Means has been investigating several universities since November 15, 2023, when the Committee held a hearing entitled From Ivory Towers to Dark Corners: Investigating the Nexus Between Antisemitism, Tax-Exempt Universities, and Terror Financing. The Committee followed the hearing with letters to those institutions on January 10, 202
Approach to Management of Upper Gastrointestinal (GI) BleedingArun Vasireddy
Upper gastrointestinal bleeding is gastrointestinal bleeding in the upper gastrointestinal tract, commonly defined as bleeding arising from the esophagus, stomach, or duodenum. Blood may be observed in vomit (hematemesis) or in altered form in the stool (melena). Depending on the severity of the blood loss, there may be symptoms of insufficient circulating blood volume and shock. As a result, upper gastrointestinal bleeding is considered a medical emergency and typically requires hospital care for urgent diagnosis and treatment. Upper gastrointestinal bleeding can be caused by peptic ulcers, gastric erosions, esophageal varices, and some rarer causes such as gastric cancer.
The initial assessment includes measurement of the blood pressure and heart rate, as well as blood tests to determine hemoglobin concentration. In significant bleeding, fluid replacement is often required, as well as blood transfusion, before the source of bleeding can be determined by endoscopy of the upper digestive tract with an esophagogastroduodenoscopy. Depending on the source, endoscopic therapy can be applied to reduce rebleeding risk. Specific medical treatments (such as proton pump inhibitors for peptic ulcer disease) or procedures (such as TIPS for variceal hemorrhage) may be used. Recurrent or refractory bleeding may lead to need for surgery, although this has become uncommon as a result of improved endoscopic and medical treatment.
Seminar present the Upper Gastrointestinal Bleeding problems
Edited by : Dr. Inzar Yassen & Dr. Ammar L. Aldwaf
in Hawler Medical Uni. collage of medicine in 14/01/2014
Iraq - Kurdistan - Erbil
June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...Levi Shapiro
Letter from the Congress of the United States regarding Anti-Semitism sent June 3rd to MIT President Sally Kornbluth, MIT Corp Chair, Mark Gorenberg
Dear Dr. Kornbluth and Mr. Gorenberg,
The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
harassment and intimidation at the Massachusetts Institute of Technology (MIT). Failing to act decisively to ensure a safe learning environment for all students would be a grave dereliction of your responsibilities as President of MIT and Chair of the MIT Corporation.
This Congress will not stand idly by and allow an environment hostile to Jewish students to persist. The House believes that your institution is in violation of Title VI of the Civil Rights Act, and the inability or
unwillingness to rectify this violation through action requires accountability.
Postsecondary education is a unique opportunity for students to learn and have their ideas and beliefs challenged. However, universities receiving hundreds of millions of federal funds annually have denied
students that opportunity and have been hijacked to become venues for the promotion of terrorism, antisemitic harassment and intimidation, unlawful encampments, and in some cases, assaults and riots.
The House of Representatives will not countenance the use of federal funds to indoctrinate students into hateful, antisemitic, anti-American supporters of terrorism. Investigations into campus antisemitism by the Committee on Education and the Workforce and the Committee on Ways and Means have been expanded into a Congress-wide probe across all relevant jurisdictions to address this national crisis. The undersigned Committees will conduct oversight into the use of federal funds at MIT and its learning environment under authorities granted to each Committee.
• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
• The Committee on Oversight and Accountability is investigating the sources of funding and other support flowing to groups espousing pro-Hamas propaganda and engaged in antisemitic harassment and intimidation of students. The Committee on Oversight and Accountability is the principal oversight committee of the US House of Representatives and has broad authority to investigate “any matter” at “any time” under House Rule X.
• The Committee on Ways and Means has been investigating several universities since November 15, 2023, when the Committee held a hearing entitled From Ivory Towers to Dark Corners: Investigating the Nexus Between Antisemitism, Tax-Exempt Universities, and Terror Financing. The Committee followed the hearing with letters to those institutions on January 10, 202
Embracing GenAI - A Strategic ImperativePeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
Synthetic Fiber Construction in lab .pptxPavel ( NSTU)
Synthetic fiber production is a fascinating and complex field that blends chemistry, engineering, and environmental science. By understanding these aspects, students can gain a comprehensive view of synthetic fiber production, its impact on society and the environment, and the potential for future innovations. Synthetic fibers play a crucial role in modern society, impacting various aspects of daily life, industry, and the environment. ynthetic fibers are integral to modern life, offering a range of benefits from cost-effectiveness and versatility to innovative applications and performance characteristics. While they pose environmental challenges, ongoing research and development aim to create more sustainable and eco-friendly alternatives. Understanding the importance of synthetic fibers helps in appreciating their role in the economy, industry, and daily life, while also emphasizing the need for sustainable practices and innovation.
Unit 8 - Information and Communication Technology (Paper I).pdfThiyagu K
This slides describes the basic concepts of ICT, basics of Email, Emerging Technology and Digital Initiatives in Education. This presentations aligns with the UGC Paper I syllabus.
Model Attribute Check Company Auto PropertyCeline George
In Odoo, the multi-company feature allows you to manage multiple companies within a single Odoo database instance. Each company can have its own configurations while still sharing common resources such as products, customers, and suppliers.
Francesca Gottschalk - How can education support child empowerment.pptxEduSkills OECD
Francesca Gottschalk from the OECD’s Centre for Educational Research and Innovation presents at the Ask an Expert Webinar: How can education support child empowerment?
Read| The latest issue of The Challenger is here! We are thrilled to announce that our school paper has qualified for the NATIONAL SCHOOLS PRESS CONFERENCE (NSPC) 2024. Thank you for your unwavering support and trust. Dive into the stories that made us stand out!
The French Revolution, which began in 1789, was a period of radical social and political upheaval in France. It marked the decline of absolute monarchies, the rise of secular and democratic republics, and the eventual rise of Napoleon Bonaparte. This revolutionary period is crucial in understanding the transition from feudalism to modernity in Europe.
For more information, visit-www.vavaclasses.com
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
Macroeconomics- Movie Location
This will be used as part of your Personal Professional Portfolio once graded.
Objective:
Prepare a presentation or a paper using research, basic comparative analysis, data organization and application of economic information. You will make an informed assessment of an economic climate outside of the United States to accomplish an entertainment industry objective.
Instructions for Submissions thorugh G- Classroom.pptxJheel Barad
This presentation provides a briefing on how to upload submissions and documents in Google Classroom. It was prepared as part of an orientation for new Sainik School in-service teacher trainees. As a training officer, my goal is to ensure that you are comfortable and proficient with this essential tool for managing assignments and fostering student engagement.
2. Portal hypertension
Portal hypertension frequently complicates cirrhosis but has other
causes. The normal hepatic venous pressure gradient is 5–6 mmHg.
Clinically significant portal hypertension is present when the
gradient exceeds 10 mmHg and risk of variceal bleeding increases
beyond a gradient of 12 mmHg. Extrahepatic portal vein obstruction
is the usual source of portal hypertension in childhood and
adolescence, while cirrhosis causes at least 90% of cases of portal
hypertension in adults in developed countries. Schistosomiasis is the
most common cause of portal hypertension worldwide but is
infrequent outside endemic areas, such as Egypt
3.
4. Clinical features
Splenomegaly is a cardinal finding and a diagnosis of portal
hypertension is unusual when splenomegaly cannot be detected
clinically or by ultrasonography.
Collateral vessels may be visible on the anterior abdominal wall and
occasionally several radiate from the umbilicus to form a ‘caput
medusae’
The most important collateral vessel formation occurs in the
oesophagus and stomach, as this can be a source of severe
bleeding. Rectal varices also cause bleeding and are often mistaken
for haemorrhoids).
Fetor hepaticus results from portosystemic shunting of blood, which
allows mercaptans to pass directly to the lungs.
5. Ascites occurs as a result of renal sodium retention and portal
hypertension.
The most important consequence of portal hypertension is variceal
bleeding, which commonly arises from oesophageal varices or from
gastric varices. Drugs capable of causing mucosal erosion, such as
salicylates and NSAIDs, can also precipitate bleeding. Variceal
bleeding is often severe, and recurrent if preventative treatment is
not given.
6.
7. Investigations
ØThe diagnosis is often made clinically.
ØPortal venous pressure measurements are rarely needed.
Ø Thrombocytopenia is common due to hypersplenism, and platelet
counts are usually in the region of 100 ×109 /L; values below 50×109
/L are uncommon.
ØLeucopenia occurs occasionally but anaemia is seldom attributed
directly to hypersplenism.
ØEndoscopy is the most useful investigation to determine whether
gastro-oesophageal varices are present. When cirrhosis is
diagnosed, endoscopy should be performed to screen for
oesophageal varices (and repeated every 2–3 years if initially
absent).
ØUltrasonography often shows features of portal hypertension, such
as splenomegaly and collateral vessels, and can sometimes indicate
the cause, such as cirrhosis or portal vein thrombosis.
Ø CT and magnetic resonance angiography can identify the extent of
portal vein clot and check hepatic vein patency
8. Management
qAcute upper gastrointestinal haemorrhage from gastro-
oesophageal varices is a common manifestation of chronic liver
disease.
qThe mortality following a variceal bleed has improved to around
15% overall but is still about 45% in those with poor liver function
(i.e. Child–Pugh C).
qThe management of portal hypertension is largely focused on the
prevention and/or control of variceal haemorrhage. It is important to
remember, though, that bleeding can also result from peptic
ulceration, which is more common in patients with liver disease than
in the general population..
9.
10. • Primary prevention of variceal bleeding
If non-bleeding varices are identified at endoscopy, β-adrenoceptor
antagonist (β-blocker) therapy with propranolol or nadolol or
carvidolol is effective in reducing portal venous pressure.
Administration of these drugs at doses that reduce the heart rate by
25% has been shown to be effective in the primary prevention of
variceal bleeding.
The efficacy of β-blockers in primary prevention is similar to that of
prophylactic banding
11. Management of acute variceal bleeding
The priority in acute bleeding is to restore the circulation,. However,
restrictive transfusion (aiming for a haemoglobin level >70g/L) is
associated with better outcomes. The source of bleeding should
always be confirmed by endoscopy because about 20% of patients
are bleeding from non-variceal lesions.
All patients with cirrhosis and gastrointestinal bleeding should
receive prophylactic broad-spectrum antibiotics, such as
intravenous cephalosporin because sepsis is common and
treatment with antibiotics improves survival. The measures used to
control acute variceal bleeding include vasoactive medications (e.g.
terlipressin), endoscopic therapy (banding), balloon tamponade and
TIPSS.
12. • Pharmacological reduction of portal venous pressure:
Terlipressin is a synthetic vasopressin analogue that, in contrast to
vasopressin. It reduces portal blood flow and/or intrahepatic
resistance and hence brings down portal pressure. It lowers
mortality in the setting of acute variceal bleeding. Caution is needed
in patients with severe ischaemic heart disease or peripheral
vascular disease because of the drug’s vasoconstrictor properties.
In countries where terlipressin is not available, octreotide is a
frequently used alternative.
13. • Variceal ligation (‘banding’) :
This is the most widely used initial treatment and is undertaken, if
possible, at the time of diagnostic endoscopy. It stops variceal
bleeding in over 90% of patients and can be repeated if bleeding
recurs. Banding is repeated every 2–4 weeks until all varices are
obliterated. Band ligation has fewer side-effects than sclerotherapy.
Prophylactic acid suppression with proton pump inhibitors may
reduce the risk of secondary bleeding from banding-induced
ulceration. In the case of gastric varices, banding is less effective
and so endoscopic therapy relies on injection of agents such as
thrombin or cyanoacrylate.
14. • Balloon tamponade This technique employs a tube, which consists
of two balloons that can be positioned in the fundus of the stomach
and in the lower oesophagus, respectively).. This technique may be
used in the event of life-threatening haemorrhage if early
endoscopic therapy is not available or is unsuccessful.
Endotracheal intubation prior to tube insertion reduces the risk of
pulmonary aspiration.
15.
16. • TIPSS :This technique uses a stent placed between the portal vein
and the hepatic vein within the liver to provide a portosystemic
shunt and reduce portal pressure. coagulation deficiencies may
require correction with fresh frozen plasma, and antibiotic cover is
provided. is an effective treatment for both oesophageal and gastric
varices. Hepatic encephalopathy occurs in up to a third of patients
following TIPSS.
17. • Portosystemic shunt surgery Surgery prevents recurrent
bleeding but carries a high mortality and often leads to
encephalopathy. In practice, portosystemic shunts are now
reserved for when other treatments have not been successful.
• Oesophageal transection Rarely, surgical transection of the
varices may be performed as a last resort when bleeding cannot
be controlled by other means but operative mortality is high.
18.
19. Secondary prevention of variceal bleeding
• Beta-blockers are used as a secondary measure to prevent
recurrent variceal bleeding. Following successful endoscopic
therapy, patients should be entered into an oesophageal banding
programme with repeated sessions of therapy at 2–4-week intervals
until the varices are obliterated. There is some evidence that early
TIPSS after successful endoscopic therapy may improve survival in
selected patients with advanced liver disease
20. Alcohol-related liver disease
• Alcohol is one of the most common causes of chronic liver disease
worldwide, with consumption continuing to increase in some
countries. Excessive alcohol consumption produces a spectrum of
effects on the liver. Almost all heavy drinkers will have alcohol-
related fatty liver, but only a minority will develop clinically
significant liver disease (alcoholic hepatitis or cirrhosis).
21.
22. What are the risk factors of alcohol-related
liver disease (ALD):
• Amount of alcohol consumed. In the UK, a ‘unit’ of alcohol contains
8 g of ethanol. The current UK guidelines recommend drinking less
than 14 units of alcohol per week. The threshold of alcohol
consumption required to develop liver disease around 30 g/day (25–
30 units/week) of ethanol.
• Drinking pattern. it is generally thought that liver damage is more
likely to occur in continuous rather than intermittent or ‘binge’
drinkers, as this pattern gives the liver a chance to recover.
23. • Sex. Women who drink heavily are at higher risk of developing
cirrhosis than men.
• Genetics. Genetic factors predispose to both alcohol use disorders
and risk of disease progression. The patatin-like phospholipase
domain-containing 3 (PNPLA3) gene is an important susceptibility
gene for cirrhosis in both ALD and NAFLD
24. • Nutrition. Being either obese or underweight increases mortality in
alcohol-related liver disease. Ethanol itself produces 7 kcal/g (29.3
kJ/g) and may contribute to weight gain. Excess alcohol
consumption is also frequently associated with nutritional
deficiencies such as thiamine and folate deficiency.
• Coexistent liver disease. Patients with coexistent chronic hepatitis
C or NAFLD who drink heavily have accelerated disease
progression compared with non-drinkers.
25. Clinical features
Three types of ALD are recognised :
Alcohol-related fatty liver disease (AFLD):
usually presents with an incidental finding of elevated
transaminases or an echogenic liver on ultrasound. It is generally
asymptomatic, has a good prognosis and steatosis usually
disappears within 3 months of abstinence.
26. Alcoholic hepatitis (AH):
presents with rapid onset jaundice in the context of recent heavy
alcohol use, tender hepatomegaly and features of the systemic
inflammatory response syndrome. Unlike other types of hepatitis, the
ALT level is only mildly raised (< 300) and may even be normal, but
the AST/ALT ratio is often greater than 1.5–2. Cirrhosis may coexist
in patients with acute alcoholic hepatitis.
Even if they abstain, it may take up to 6 months for jaundice to
resolve.
27. • Alcoholic cirrhosis :
Palmar erythema, spider naevi and gynaecomastia are more
common in alcoholic cirrhosis than in cirrhosis of other aetiologies.
Alcoholic cirrhosis often presents with a serious complication, such
as variceal haemorrhage or ascites, and only half of such patients
will survive for 5 years from presentation.
28.
29. Investigations
• The clinical history from patient, relatives and friends is important to
establish alcohol misuse duration and severity.
• macrocytosis in the absence of anaemia, may suggest and support
a history of alcohol misuse.
• A raised GGT is commonly seen in alcohol-related fatty liver and
generally falls within 2–6 weeks of abstinence.
• Carbohydrate-deficient transferrin (CDT) is also a serum biomarker
of recent alcohol excess.
• The extent of fibrosis can be assessed using either serum fibrosis
markers or transient elastography.
• A liver biopsy is occasionally required if there is diagnostic
uncertainty.
30. • In alcoholic hepatitis, a number of prognostic scoring systems are
available. The prothrombin time (PT) and bilirubin are used to
calculate a ‘modified discriminant function’ (mDF), also known as
the Maddrey score, which enables the clinician to assess prognosis
(serum bilirubin in µmol/L is divided by 17 to convert to mg/dL):
DF = [4.6 × Increase in PT (sec)] + Bilirubin (mg/dL
Avalue over 32 implies severe disease.
A second scoring system, the Glasgow Alcoholic Hepatitis Score,
uses the age, white cell count and renal function, in addition to PT
and bilirubin, to assess prognosis . A score of 9 or more identifies an
even higher risk group.
31.
32. Management
üCessation of alcohol consumption is the single most important
treatment and prognostic factor. Life-long abstinence is the best
advice.
ü Nutrition :
Nutrition is very important, and calorie intake correlates with
survival in severe alcoholic hepatitis.
üDrug therapy:
The optimal treatment of severe alcoholic hepatitis (Maddrey’s
discriminative score > 32) has been widely debated. The study
showed no effect of pentoxifylline on survival. There was a
borderline reduction in 28-day mortality with prednisolone.
Prednisolone was associated with increased rates of sepsis and
gastrointestinal bleeding. If the bilirubin has not fallen 7 days after
starting glucocorticoids, the drugs are unlikely to reduce mortality
and should be stopped.
33. üLiver transplantation :
ALD is a common indication for liver transplantation in
Europe and the United States. The outcome of
transplantation for ALD is good, with survival rates similar
to other indications and if the patient remains abstinent
there is no risk of disease recurrence.
34. Non-alcoholic fatty liver disease
vIncreasingly sedentary lifestyles and changing dietary patterns
mean that the prevalence of obesity and insulin resistance has
increased worldwide, and so fat accumulation in the liver is a
common finding during abdominal imaging studies and on liver
biopsy.
vNAFLD includes a spectrum of progressive liver disease. The
majority will have fatty infiltration alone (steatosis) but a minority
(10%–20%) will develop accompanying inflammation (non-alcoholic
steatohepatitis, NASH) and/or fibrosis, and may progress to
cirrhosis and primary liver cancer. NAFLD is considered by many to
be the hepatic manifestation of the ‘metabolic syndrome’ as it is
strongly associated with obesity, type 2 diabetes, dyslipidaemia and
hypertension.
35. Pathophysiology
The initiating events in NAFLD are typically based on the
development of obesity and insulin resistance, leading to increased
hepatic free fatty acid . This imbalance between the rate of
import/synthesis and the rate of export/catabolism of fatty acids in
the liver leads to the development of steatosis. This may be an
adaptive response through which hepatocytes store potentially toxic
lipids that causing steatosis that then progresses to NASH or
fibrosis.
36.
37. Clinical features
NAFLD is frequently asymptomatic, although it may be associated
with fatigue and mild right upper quadrant discomfort.
It is commonly identified as an incidental biochemical abnormality
during routine blood tests or as a fatty liver on abdominal imaging.
patients may present late in the natural history of the disease with
complications of cirrhosis and portal hypertension, such as variceal
haemorrhage, or with hepatocellular carcinoma.
The average age of NAFLD cirrhosis patients is currently 50–60
years; however, the emerging epidemic of childhood obesity means
that NAFLD is present in increasing numbers of younger patients.
NAFLD is also associated with polycystic ovary syndrome and
obstructive sleep apnoea.
38. Investigations
ØIt is important to assess alcohol consumption as a contributory
factor and check for medications that cause fatty liver, such as
tamoxifen, amiodarone and corticosteroids.
Ø Investigations should exclude other coexistent liver diseases
(including viral, autoimmune and inherited causes).
Ø Biochemical tests There is no single diagnostic blood test for
NAFLD. Serum GGT is often raised. ALT and AST may be normal or
modestly raised, usually less than twice the upper limit of normal.
ALT levels fall as hepatic fibrosis increases and the normal AST :
ALT ratio of < 1 reverses as advanced fibrosis develops. low-titre
antinuclear antibody and elevated ferritin levels.
39. Imaging:
Ultrasound is most often used and provides a qualitative assessment
of hepatic fat content, as the liver appears ‘bright’ due to increased
echogenicity. CT, MRI or MR spectroscopy offer greater sensitivity
for detecting lesser degrees of steatosis,
Transient elastography :
Transient elastography (TE) is often used to assess those with
indeterminate fibrosis scores.
40. • Liver biopsy Although it is frequently not required for either
diagnosis or staging, liver biopsy remains the ‘gold standard’
investigation for diagnosis and assessment of degree of
inflammation and extent of liver fibrosis. The histological changes
seen in NAFLD are identical to those described in ALD. The
definition of NASH is based on a combination of three lesions
(steatosis, hepatocellular injury and inflammation).
41. Management:
• Non-pharmacological treatment: lifestyle interventions to promote
weight loss and improve insulin sensitivity through dietary changes
and physical exercise. Sustained weight reduction of 7%–10% is
associated with significant improvement in histological and
biochemical NASH severity.
42. • Pharmacological treatment :
No pharmacological agents are currently licensed specifically for
NAFLD therapy.
Treatment directed at coexisting metabolic disorders, such as
dyslipidaemia and hypertension,
Specific insulin-sensitising agents, in particular glitazones, may help
selected patients.
high-dose vitamin E (800U/day) have been tempered by evidence
that high doses may be associated with an increased risk of prostate
cancer and all-cause mortality, which has limited its use.
Obeticholic acid, a farnesoid X receptor agonist, appears to improve
fibrosis in non-cirrhotic NASH in an interim analysis but the trial is
ongoing.
44. Autoimmune hepatitis
• Autoimmune hepatitis (AIH) is a disease of immune-mediated injury
targeting hepatocytes, which can present either as an acute severe
hepatitis or chronic hepatitis leading to cirrhosis.
• It is a lifelong disease which often runs a relapsing and remitting
course. It can develop at any age, with peaks around the second and
sixth decades. It is more common in women with a 5:1
predominance.
45. Clinical features
• Some patients may be asymptomatic, with a raised ALT detected on
blood tests.
• The onset of symptoms is usually insidious, with fatigue, anorexia
and arthralgia.
• In about one-quarter of patients the onset is acute, resembling viral
hepatitis, but resolution does not occur.
• Signs of chronic liver disease, especially spider naevi and
hepatosplenomegaly, can be present. Approximately 25% of
patients will have cirrhosis at diagnosis, and some will progress to
cirrhosis despite treatment.
46.
47. Investigations
üThere is no single diagnostic test for autoimmune hepatitis.
üLiver enzymes typically show raised ALT and AST, although these
fluctuate.
üSerological tests for autoantibodies are often positive. The most
frequently seen is high titre of antinuclear and/or antismooth
muscle antibodies, typically associated with raised IgG levels.
üDisease characterised by the presence of anti-liver–kidney
microsomal (LKM) antibodiesis typically seen in paediatric
populations and can be more resistant to treatment than ANA-
positive disease.
üMore recently, anti-soluble liver antigen (anti-SLA) has been
described typically in adult patients, often with aggressive disease
and lacking autoantibodies of other specificities
48. ü Elevated serum IgG levels are an important diagnostic and
treatment response feature if present, but the diagnosis is still
possible in the presence of normal IgG levels.
ü If the diagnosis of autoimmune hepatitis is suspected, liver biopsy
should be performed both to confirm the diagnosis before
commencing long-term immunosuppression and to stage any liver
fibrosis. It typically shows an abundance of lymphocytes and
plasma cells around the portal tracts.
49. Management
§ Treatment with glucocorticoids is life-saving in autoimmune
hepatitis, particularly during exacerbations of active and
symptomatic disease. prednisolone (30–40 mg/day) is given orally;
the dose is then gradually reduced as the patient and LFTs improve.
Budesonide may be used in non-cirrhotic patients if steroid side-
effects are problematic. Maintenance therapy is usually with
azathioprine (1–2 mg/kg daily), although introduction of this is often
delayed by around a month to allow the liver enzymes to settle in
case it causes drug-induced hepatotoxicity. Maintenance
azathioprine can be used as monotherapy, or may be combined with
low-dose prednisolone (ideally, below 5 mg/day)
§ However, in case series, mycophenolate mofetil (MMF) appears
effective in patients who are azathioprine-intolerant, but less so in
azathioprine non-responders. Similarly, tacrolimus appears helpful
in refractory disease.
50. The aims of treatment are to achieve resolution of symptoms and to
completely control inflammatory activity to prevent progressive
fibrosis, especially in younger patients or those with cirrhosis.
Disease activity (indicated by rising ALT and IgG levels) should be
monitored regularly. Maintenance treatment is required for at least 3
years and is often continued long term, as relapse rates are high if
immunosuppression is withdrawn
51. Primary biliary cholangitis
• Primary biliary cholangitis is a chronic, progressive cholestatic liver
disease that predominantly affects women aged 30 and over.
• It is characterised by granulomatous inflammation of the portal
tracts, leading to progressive damage and eventually loss of the
small and middle-sized bile ducts. This, in turn, leads to fibrosis and
cirrhosis of the liver. There is a strong female-to-male
predominance of 9:1.
52. Clinical features
PBC may be detected incidentally on routine blood tests, but
systemic symptoms such as fatigue and generalised itch are
common.
Although there may be right upper abdominal discomfort. Bone pain
or fractures can rarely result from osteomalacia (fat-soluble vitamin
malabsorption) or, more commonly, from osteoporosis.
Xanthomatous deposits occur in a minority, especially around the
eyes. Scratch marks may be found in patients with severe pruritus.
53. • Associated diseases Autoimmune and connective tissue
diseases occur with increased frequency in PBC,
particularly the sicca syndrome, systemic sclerosis,
coeliac disease and thyroid diseases. Hypothyroidism
should always be considered in patients with fatigue
54. Diagnosis and investigations
vThe LFTs show a pattern of cholestasis.
vHypercholesterolaemia is common and worsens as disease
progresses but appears not to be associated with increased
cardiovascular risk.
vAMA is present in over 95% of patients; when it is absent, the
diagnosis should not be made without obtaining histological
evidence and considering cholangiography (typically MRCP) to
exclude other biliary disease. Due to the peripheral nature of the
ducts affected by PBC, the biliary tree should appear normal on
imaging.
v Fibrosis stage should be assessed, usually using transient
elastography.
v Liver biopsy is necessary only if there is diagnostic uncertainty.
55. Management
The hydrophilic bile acid ursodeoxycholic acid (UDCA), at a dose of
13–15 mg/kg daily, improves bile flow, improves LFTs, may slow down
histological progression
Obeticholic acid (OCA) is a second-generation bile acid therapeutic
that improves alkaline phosphatase in more than half of patients who
did not respond to or tolerate UDCA,.
Bezafibrate, a peroxisome proliferator-activated receptor-alpha
(PPARα) agonist used predominantly to treat hyperlipidaemia.
Liver transplantation should be considered once liver failure has
developed and may also be indicated in patients with intractable
pruritus.
Serum bilirubin remains the most reliable marker of declining liver
function.
56. • Pruritus:
This is the main symptom requiring treatment. The cause is
unknown. First-line treatment is colestyramine, which probably acts
by binding potential pruritogens in the intestine and increasing their
excretion in the stool. Colestyramine may bind other drugs in the gut
(most obviously UDCA) and adequate spacing should be used
between drugs.. Alternative treatments include rifampicin as
required with close monitoring of LFTs), naltrexone (an opioid
antagonist)plasmapheresis may be used.
57. Fatigue:
may reflect intracerebral changes due to cholestasis. Unfortunately,
once depression, hypothyroidism and coeliac disease have been
excluded, there is currently no specific treatment. The impact on
patients’ lives can be substantial.
Malabsorption:
Prolonged cholestasis is associated with steatorrhoea and
malabsorption of fat-soluble vitamins, which should be replaced as
necessary.
Bone disease :
Osteopenia and osteoporosis are common and treatment started
with replacement calcium and vitamin D3 . Bisphosphonates should
be used if there is evidence of osteoporosis. Osteomalacia is rare.
58. Primary sclerosing cholangitis
Primary sclerosing cholangitis (PSC) is an immune-mediated
cholestatic liver disease characterised by multifocal stricturing of
the larger bile ducts of the extra- and/or intrahepatic biliary tree,
often in association with inflammatory bowel disease. This is also
associated with progressive hepatic fibrosis which can lead to
cirrhosis and portal hypertension, along with an increased risk of
various cancers (cholangiocarcinoma, gallbladder, colon). PSC is
twice as common in men as women. Most patients present at age 25–
40 years.
59. The generally accepted diagnostic criteria are:
generalised beading and stenosis of the biliary system on
cholangiography .
absence of choledocholithiasis (or history of bile duct surgery)
exclusion of bile duct cancer, by prolonged follow-up.
60.
61. Clinical features
ØThe diagnosis is often made incidentally when persistently raised
serum ALP is discovered in an individual with ulcerative colitis.
ØPatients may present with episodes of biliary obstruction, or with
symptoms of cirrhosis or portal hypertension.
Ø Common symptoms include fatigue, intermittent jaundice, weight
loss, right upper quadrant abdominal pain and pruritus.
ØAttacks of acute cholangitis are uncommon and usually follow
biliary instrumentation.
62. Investigations
ØBiochemical screening usually reveals a cholestatic pattern of LFTs. Modest
elevations in serum transaminases are usually seen, whereas hypoalbuminaemia
and clotting abnormalities are found at a late stage only.
Øserum AMA is absent.
ØThe key investigation is MRCP, which is usually diagnostic and reveals multiple
irregular stricturing and dilatation.
Ø ERCP should be reserved for therapeutic interventions.
ØOn liver biopsy, the characteristic early features of PSC are periductal ‘onion
skin’ scaring fibrosis.
Øall patients diagnosed with PSC should undergo an initial colonoscopy, even in
the absence of bowel symptoms
63.
64.
65. Management
üThere is no cure for PSC but management of cholestasis and its
complications and specific treatment of the disease process are
indicated.
üUDCA is widely used, although the evidence to support this is
limited.
üOverall, the median time from diagnosis to death or transplant is
around 20 years.
ü Prognosis is worse insymptomatic patients, possibly reflecting a
later disease stage at diagnosis.
66. Cancer screening :
Patients with PSC should have annual ultrasound scans to assess for
gallbladder polyps, to aid early detection of gallbladder cancer.
Patients with PSC and colitis should undergo annual colonoscopy to
screen for colorectal cancer.
Management of complications:
Broad-spectrum antibiotics (e.g. cipro oxacin) should be given for
acute attacks of cholangitis. If a dominant stricture is associated
with either jaundice or infection, ERCP may be performed for
sampling to exclude cholangiocarcinoma and to relieve the
obstruction,. Fat-soluble vitamin replacement is necessary in
jaundiced patients. Metabolic bone disease (usually osteoporosis) is
a common complication that requires treatment
67. Surgical treatment:
Surgical resection of the extrahepatic bile duct and biliary
reconstruction have a limited role in the management of non-
cirrhotic patients with dominant extrahepatic disease. Liver
transplantation is the only surgical option in patients with advanced
liver disease. Cholangiocarcinoma is a contraindication to
transplantation.