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Autoimmune Hepatitis


Presentation

Oettinger et al. published a series of 142 children with autoimmune hepatitis [8]. Findings included:

Other symptoms and signs may include:

Pain
  • We report a case with torpid evolution, presented with multiple and deep ulcers in a young patient with autoimmune hepatitis, causing pain and significant disability. We observed complete healing of lesions after two months of successful treatment.[ncbi.nlm.nih.gov]
  • We describe a case of 40-year-old woman who presented to our hospital with symptoms of non-radiating epigastric pain for 4-5 days associated with nausea and vomiting.[ncbi.nlm.nih.gov]
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  • Pyoderma Gangrenosum (PG) is a cutaneous condition, its diagnosis suggested by the presence of a painful cutaneous ulcer showing rapid progression.[ncbi.nlm.nih.gov]
  • A primigravid pa- tient presented at 30 weeks with altered mental status, abdominal pain, vomiting, and epistaxis.[ncbi.nlm.nih.gov]
Weight Loss
  • A 25-year-old woman presented with jaundice, palpitation, and weight loss of 5 kg during a period of 2 weeks.[ncbi.nlm.nih.gov]
  • Cell Transplant Liver Cancer Liver & Biliary Diseases Pancreatic Diseases Pancreatic Cancer Pancreatitis Peptic Ulcer Disease Portal Hypertension Primary Biliary Cirrhosis (PBC) Primary Sclerosing Cholangitis Stomach (Gastric) Cancer Stomach Diseases Weight[nyp.org]
  • Findings included: Jaundice 58% Non specific weakness 57% Anorexia 47% Abdominal pain 38% Paleness 26% Other symptoms and signs may include: General discomfort or uneasiness Abdominal distension Pruritis Diarrhea Edema Weight loss Spider angiomata Hepatomegaly[symptoma.com]
  • Symptoms can develop over weeks or months and are non-specific (tiredness, general fatigue, anorexia, weight loss and joint and muscle pains). On rare occasions AIH develops quickly and symptoms and signs appear rapidly.[royalfree.nhs.uk]
  • As it grows, symptoms may include pain in the upper abdomen on the right side, a lump in the upper abdomen, bloating, loss of appetite, weight loss, weakness, fever and yellow skin and eyes. These symptoms may be caused by other health problems.[bshr.com]
Anorexia
  • Findings included: Jaundice 58% Non specific weakness 57% Anorexia 47% Abdominal pain 38% Paleness 26% Other symptoms and signs may include: General discomfort or uneasiness Abdominal distension Pruritis Diarrhea Edema Weight loss Spider angiomata Hepatomegaly[symptoma.com]
  • Symptoms can develop over weeks or months and are non-specific (tiredness, general fatigue, anorexia, weight loss and joint and muscle pains). On rare occasions AIH develops quickly and symptoms and signs appear rapidly.[royalfree.nhs.uk]
  • […] liver disease, or acute or even fulminant hepatic failure.People usually present with one or more nonspecific symptoms, sometimes of long lasting duration, as fatigue, general ill health, lethargy, weight loss, mild right upper quadrant pain, malaise, anorexia[en.wikipedia.org]
  • […] play roles in pathogenesis ( J Hepatol 2015;62:S100 ) Genetic predisposition: North America / Europe: HLA-DR3 (DRB1*0301) and HLA-DR4 (DRB1*0401) China / Japan: HLA-DR4 (DRB1*0405) Clinical features Most patients have nonspecific symptoms: fatigue, anorexia[pathologyoutlines.com]
  • Anorexia, diarrhoea. Arthralgias. Skin rashes (including acne), hirsutism. Oedema. Amenorrhoea. Chest pain (pleuritis). Weight loss and intense pruritus (unusual). Signs Common findings on physical examination are as follows: Hepatomegaly.[patient.info]
Malaise
  • It starts with acute symptoms in 30% of the cases with jaundice, fever, malaise, liver tenderness, like an acute viral hepatitis.[meddean.luc.edu]
  • Common signs and symptoms associated with this condition include changes in your urine color, malaise, fatigue, itching, reduced appetite and nausea and vomiting.[livestrong.com]
  • […] chronic liver disease, or acute or even fulminant hepatic failure.People usually present with one or more nonspecific symptoms, sometimes of long lasting duration, as fatigue, general ill health, lethargy, weight loss, mild right upper quadrant pain, malaise[en.wikipedia.org]
Infectious Mononucleosis
  • CONTINUE SCROLLING OR CLICK HERE FOR RELATED ARTICLE Reviewed on 12/21/2018 Hepatitis Slideshow Pictures Hepatitis C Quiz Infectious Mononucleosis Slideshow[medicinenet.com]
Vomiting
  • We describe a case of 40-year-old woman who presented to our hospital with symptoms of non-radiating epigastric pain for 4-5 days associated with nausea and vomiting.[ncbi.nlm.nih.gov]
  • A primigravid pa- tient presented at 30 weeks with altered mental status, abdominal pain, vomiting, and epistaxis.[ncbi.nlm.nih.gov]
  • Fatigue Abdominal pain Joint pain Itching (pruritus) Jaundice An enlarged liver Abnormal blood vessels on the skin (spider angiomas) Nausea and vomiting Loss of appetite Skin rashes Dark-colored urine, light colored stools In women, loss of menstruation[columbiasurgery.org]
  • Common initial symptoms can include fatigue, nausea, vomiting, abdominal pain, weight loss, light colored stools, dark colored urine, joint pain, rashes, and loss of menstruation in women.[rarediseases.org]
  • Common signs and symptoms associated with this condition include changes in your urine color, malaise, fatigue, itching, reduced appetite and nausea and vomiting.[livestrong.com]
Abdominal Pain
  • A primigravid pa- tient presented at 30 weeks with altered mental status, abdominal pain, vomiting, and epistaxis.[ncbi.nlm.nih.gov]
  • Common presenting symptoms included jaundice, fatigue, and abdominal pain. The majority of subjects received steroids for induction and AZA for maintenance of remission.[ncbi.nlm.nih.gov]
  • Fatigue Abdominal pain Joint pain Itching (pruritus) Jaundice An enlarged liver Abnormal blood vessels on the skin (spider angiomas) Nausea and vomiting Loss of appetite Skin rashes Dark-colored urine, light colored stools In women, loss of menstruation[columbiasurgery.org]
  • Findings included: Jaundice 58% Non specific weakness 57% Anorexia 47% Abdominal pain 38% Paleness 26% Other symptoms and signs may include: General discomfort or uneasiness Abdominal distension Pruritis Diarrhea Edema Weight loss Spider angiomata Hepatomegaly[symptoma.com]
Palpitations
  • A 25-year-old woman presented with jaundice, palpitation, and weight loss of 5 kg during a period of 2 weeks.[ncbi.nlm.nih.gov]
Jaundice
  • A possibility of DIAIH should be considered in cases of DILI which exhibit overt jaundice, autoantibodies, intense histological inflammation and a long latency period.[ncbi.nlm.nih.gov]
  • All other causes of cholestatic jaundice were ruled out. Her history of recurrent asthma exacerbations, eosinophilia, recurrent sinus infections and positive myeloperoxidase antibodies was suggestive of eosinophilic granulomatosis with polyangiitis.[ncbi.nlm.nih.gov]
  • A 25-year-old woman presented with jaundice, palpitation, and weight loss of 5 kg during a period of 2 weeks.[ncbi.nlm.nih.gov]
  • She had jaundice with no history of viral infections, drug intake, alcohol abuses or exposition to blood products. She was positive for antinuclear antibody, double stranded DNA antibody and LKM 1 antibody.[ncbi.nlm.nih.gov]
  • A 44-year-old female was admitted to our hospital with jaundice, general fatigue and liver dysfunction. Her transaminase levels were elevated, her immunoglobulin G level was 1735 mg/dL and her anti-nuclear titres were 80.[ncbi.nlm.nih.gov]
Hepatomegaly
  • CT Nonspecific, ranging from normal to hepatomegaly and cirrhosis.[radiopaedia.org]
  • Findings included: Jaundice 58% Non specific weakness 57% Anorexia 47% Abdominal pain 38% Paleness 26% Other symptoms and signs may include: General discomfort or uneasiness Abdominal distension Pruritis Diarrhea Edema Weight loss Spider angiomata Hepatomegaly[symptoma.com]
  • Symptoms range from minor to severe can be acute or chronic fatigue abdominal pain joint pain pruritus skin rashes dark-colored urine amenorrhea in women - often an initial complaint Physical exam inspection distended abdomen - ascites jaundice palpation hepatomegaly[step2.medbullets.com]
  • AIH symptoms include: enlarged liver (hepatomegaly) abnormal blood vessels on the skin ( spider angiomas ) abdominal distention (swelling) dark urine pale-colored stools Additional symptoms may include: yellowing of the skin and eyes ( jaundice ) itching[healthline.com]
Recurrent Jaundice
  • Other symptoms may include: Fever Abdominal pain Arthritis Anemia Dry eyes and mouth Recurrent jaundice frequently develops in severe cases Lack of menstrual periods Normally, these symptoms of autoimmune disease develop gradually over the course of weeks[premiermedicalhv.com]
Pruritus
  • Fatigue Abdominal pain Joint pain Itching (pruritus) Jaundice An enlarged liver Abnormal blood vessels on the skin (spider angiomas) Nausea and vomiting Loss of appetite Skin rashes Dark-colored urine, light colored stools In women, loss of menstruation[columbiasurgery.org]
  • Presentation Symptoms range from minor to severe can be acute or chronic fatigue abdominal pain joint pain pruritus skin rashes dark-colored urine amenorrhea in women - often an initial complaint Physical exam inspection distended abdomen - ascites jaundice[step2.medbullets.com]
  • Weight loss and intense pruritus (unusual). Signs Common findings on physical examination are as follows: Hepatomegaly. Jaundice (around 50% of patients). Splenomegaly. Spider angiomata. Ascites. Encephalopathy.[patient.info]
  • 2015;62:S100 ) Genetic predisposition: North America / Europe: HLA-DR3 (DRB1*0301) and HLA-DR4 (DRB1*0401) China / Japan: HLA-DR4 (DRB1*0405) Clinical features Most patients have nonspecific symptoms: fatigue, anorexia, nausea, weight loss, jaundice, pruritus[pathologyoutlines.com]
Hirsutism
  • . • Endocrine changes like cushingoid appearance, acne, hirsutism. • Pulmonary changes like pleurisy,transitory pulmonary infiltrates and collapse. • Acute,recurrent and non- deforming polyarthrits of large joints. • Mild aneamia, leucopenia, thrombocytopenia[de.slideshare.net]
  • Compared to prednisone, it has a relatively safe adverse-effect profile with headache and respiratory infection seen most commonly. 9 Cosmetic changes such as moon face, acne, and hirsutism have been noted. 8 Budesonide is primarily metabolized through[uspharmacist.com]
  • Skin rashes (including acne), hirsutism. Oedema. Amenorrhoea. Chest pain (pleuritis). Weight loss and intense pruritus (unusual). Signs Common findings on physical examination are as follows: Hepatomegaly. Jaundice (around 50% of patients).[patient.info]
  • Common symptoms include the following: Fatigue Upper abdominal discomfort Mild pruritus Anorexia Myalgia Diarrhea Cushingoid features Arthralgias Skin rashes (including acne) Edema Hirsutism Amenorrhea Chest pain from pleuritis Weight loss and intense[emedicine.com]
Arthritis
  • This report confirms the need to monitor liver enzymes carefully in patients using long-term treatment with MTX for psoriasis or rheumatoid arthritis.[ncbi.nlm.nih.gov]
  • Among the autoimmune diseases, rheumatoid arthritis (RA), multiple sclerosis (MS), thyroid disease, primary biliary cirrhosis (PBC) are reported mostly among tobacco-exposed animals.[ncbi.nlm.nih.gov]
  • Pyoderma gangrenosum is associated with a concomitant systemic disease in 50 to 70 % of cases, including inflammatory bowel disease (IBD), rheumatoid arthritis, and lymphoproliferative disorders.[ncbi.nlm.nih.gov]
  • This is the most common form of autoimmune hepatitis, and about half of patients have another form of autoimmune disease such as celiac disease, rheumatoid arthritis, Crohn’s disease, or other.[columbiasurgery.org]
  • People with autoimmune hepatitis also have another autoimmune condition, such as Graves' disease, rheumatoid arthritis or inflammatory bowel disease, states the NDDIC.[livestrong.com]
Arthralgia
  • At the time of diagnosis of AIH, patients presented with arthralgia, abdominal complaints, cutaneous involvement and fatigue as common symptoms. All patients fulfilled the current diagnostic criteria of both, AIH and SLE.[ncbi.nlm.nih.gov]
  • Although patients may present with acute symptoms (eg, arthralgia), about 34% to 45% are asymptomatic and are identified subsequent to abnormal liver function tests such as increased alanine and/or aspartate aminotransferase (generally 2,3 Elevated levels[questdiagnostics.com]
  • The patient will sometimes present with jaundice, fever and right upperquadrant pain and occasionally systemic symptoms such as arthralgias (arthritis), myalgias (muscle aches), polyserositits and thrombocytopenia.[texasliver.com]
  • […] fulminant hepatic failure.People usually present with one or more nonspecific symptoms, sometimes of long lasting duration, as fatigue, general ill health, lethargy, weight loss, mild right upper quadrant pain, malaise, anorexia, nausea, jaundice or arthralgia[en.wikipedia.org]
Dark Urine
  • The patient suffers from non-specific symptoms such as fatigue, dark urine, and discoloration of stools, upper abdominal discomfort or skin rashes.[drfalkpharma.com]
  • urine Mental confusion, which may occur in advanced stages In making a diagnosis of autoimmune hepatitis, your doctor will start by conducting a thorough physical examination and asking about your medical history, including any symptoms you have been[ucsfhealth.org]
  • Symptoms include jaundice, dark urine, fever and flulike symptoms. It can be prevented with hepatitis A vaccine. A virus that causes liver disease and inflammation.[bshr.com]
  • Some people also have symptoms of hepatitis such as fever and jaundice (yellowing of the skin or eyes or dark urine).[nuh.com.sg]
Amenorrhea
  • Presentation Symptoms range from minor to severe can be acute or chronic fatigue abdominal pain joint pain pruritus skin rashes dark-colored urine amenorrhea in women - often an initial complaint Physical exam inspection distended abdomen - ascites jaundice[step2.medbullets.com]
  • Genetic predisposition: North America / Europe: HLA-DR3 (DRB1*0301) and HLA-DR4 (DRB1*0401) China / Japan: HLA-DR4 (DRB1*0405) Clinical features Most patients have nonspecific symptoms: fatigue, anorexia, nausea, weight loss, jaundice, pruritus and amenorrhea[pathologyoutlines.com]
  • Common symptoms include the following: Fatigue Upper abdominal discomfort Mild pruritus Anorexia Myalgia Diarrhea Cushingoid features Arthralgias Skin rashes (including acne) Edema Hirsutism Amenorrhea Chest pain from pleuritis Weight loss and intense[emedicine.com]

Workup

Work up consists of a detailed history and physical examination.

Laboratory Tests

  • Complete blood count
  • Liver function tests
  • Serology for ANAs, SMAs, LKM1, anti-LC1
  • Immunoglobulins and albumen levels
  • Blood profile

Imaging Studies

Test Results

Test results will indicate eosinophilia, raised ANA, ASMA and other increased antibody titres. Blood profile will show increased blood count and a prolonged prothrombin time. Biopsy will show Ag-Ab aggregates in the liver. CT scan will show extrahepatic involvement, if any.

Penicillium
  • Talaromyces marneffei, previously known as Penicillium marneffei, is the most important pathogenic thermally dimorphic fungus causing systemic mycosis in Southeast Asia.[ncbi.nlm.nih.gov]
HLA-DR3
  • For example, HLA DR3 positivity only contributes when other antibodies are negative. This calculator correctly scores such circumstances. Also, it is not possible to check off boxes in an illogical fashion. This calculator is kept at[web.archive.org]
  • Transgenic AIH mice carrying HLA-DR3 showed reduced diversity and total load of gut microbiota.[ncbi.nlm.nih.gov]
  • :80 3 1:80 2 1:40 1 1:40 0 Antimitochondrial antibody Positive -4 Negative 0 Hepatitis viral markers Negative 3 Positive -3 Other etiological factors History of drug usage Yes -4 No 1 Alcohol (average consumption) 25 g/d 2 60 g/d -2 Genetic factors: HLA[medscape.com]
  • Race-, sex-, and age-related differences in incidence The disease is most common in whites of northern European ancestry with a high frequency of HLA-DR3 and HLA-DR4 markers. The Japanese population has a low frequency of HLA-DR3 markers.[emedicine.com]
HLA-DR4
  • (DRB1*0401) China / Japan: HLA-DR4 (DRB1*0405) Clinical features Most patients have nonspecific symptoms: fatigue, anorexia, nausea, weight loss, jaundice, pruritus and amenorrhea Up to 25% of patients are asymptomatic, whereas 25 - 30% have episodes[pathologyoutlines.com]
  • Race-, sex-, and age-related differences in incidence The disease is most common in whites of northern European ancestry with a high frequency of HLA-DR3 and HLA-DR4 markers. The Japanese population has a low frequency of HLA-DR3 markers.[emedicine.com]
  • HLA-DR3 serotype also occurs more commonly in caucasians. 10,11 HLA-DR4 serotype associated disease occurs more commonly in older adults and usually responds well to immunosuppressive therapy and exhibits more extra-hepatic manifestations. 10,11 HLA-DR4[jpma.org.pk]
HLA-B8
  • […] consumption Male Male 35-35 gm/day; female 25-40 gm/day (0 points) Male 50-80 gm/day; female 40-60 gm/day (-2 points) Male 80 gm/day; female 60 gm/day (-1 point) Genetic factors Other autoimmune diseases in patient or first-degree relatives (1 point) HLA[merckmanuals.com]
  • […] include the following: The presence of serologic immune markers (antinuclear antibodies, anti–smooth muscle antibodies, liver-kidney microsomal antibodies) An association with histocompatibility haplotypes common in autoimmune disorders (eg, HLA-B1, HLA-B8[merckmanuals.com]
  • B8, DR3 haplotype has been associated with a number of autoimmune diseases such as AIH, thyroiditis, celiac disease, and myasthenia gravis.[dx.doi.org]
Liver Biopsy
  • Although phenotypic changes in liver biopsy specimens are rare in this condition, the present case could provide clues to the possible pathogenesis of AIH.[ncbi.nlm.nih.gov]
  • Liver biopsy showed prominent interface hepatitis with MS. A drug-lymphocyte stimulation test (DLST) using EE2 was positive.[ncbi.nlm.nih.gov]
  • Twenty eight months after treatment, another liver biopsy was performed, showing almost full remission of the disease, with only mild fibrosis and no significant inflammatory infiltrate.[ncbi.nlm.nih.gov]
  • METHODS: Ultrastructural analyses were performed using liver biopsies from 14 children with clinicopathologically diagnosed AIH.[ncbi.nlm.nih.gov]
  • BACKGROUND: Liver biopsy is the gold standard in evaluating inflammation and fibrosis in autoimmune hepatitis.[ncbi.nlm.nih.gov]

Treatment

Medications

Corticosteroids are the mainstay of treatment. Budesonide has been shown to be more effective in inducing remission than prednisone, and results in fewer adverse effects [9].

Transplantation

Liver transplantation may be required if patients do not respond to drug therapy or when patients present with fulminant liver failure.

Prognosis

Autoimmune hepatitis may advance to cirrhosis [3]. Without treatment, almost 50% of patients will die within five years. Mild liver disease generally has a good prognosis with treatment, however, the more severe the disease, the worst the prognosis. In severe and/or complicated disease, life expectancy is greatly reduced.

Complications

Untreated and uncontrolled autoimmune hepatitis may progress to chronic hepatitis that will then show widely systemic manifestations. Complications include the following:

Etiology

Autoimmune hepatitis is an inflammation of the liver that occurs when immune cells mistake the liver's normal cells for harmful invaders and attack them [3]. The exact cause of the disease is unknown, but a number of factors have been implicated in its development. It may be initiated or triggered by genetic factors, viral infections (eg acute hepatitis A and B, Epstein-Barr virus infection) [4], etc. Some chemical factors such as interferons, etc may also play a role.

Genetic factors are proposed to be the main culprit behind this disease. DR3, DR4, B8, B15 and C4A gene deletions and mutations may lead to the production of autoantibodies. To some point, the body will be able to combat these autoantibodies but when an environmental trigger, such as infection by a virus, etc may cause the threshold of tolerance to be breached, then the disease becomes symptomatic.

Epidemiology

Incidence

0.1-1.2 cases per 100,000 people are estimated to suffer from autoimmune hepatitis in the United States. 6% of all liver transplantations conducted in the US are due to this disease.

Age

It may occur at any age, ranging from infants to old people. Some studies reveal a bimodal age prevalence, with peak incidence first in the mid-second to early-third decade of life and second peak incidence between the late-fourth to seventh decade of life.

Sex

Women are affected more often than men (70% to 80% of patients are women) [2].

Sex distribution
Age distribution

Pathophysiology

Microscopically, clusters of plasma cells in the interface of portal tracts and hepatic lobules are fairly characteristic for autoimmune hepatitis [5]. The salient features [6] include the absence of serologic markers of viral infection, elevated serum IgG and gamma-globulin levels (1-2-3x normal), and high serum titres of autoantibodies.

Subtypes

Type I

It is characterised by presence of positive ANA and ASMA [7] antibodies. Anti-actin antibodies may also be present. Gamma globulin levels are greatly elevated. This type occurs predominantly in elderly patients. HLA associations include DR3, DR4 and B8.

Type II

It is characterised by presence of Anti-LKM (anti-liver kidney microsomal antibody) and P450 IID6 antibodies. It occurs most commonly in young girls , and is very rare in adults. HLA associations include DR3, B14 and C4AQO.

Type III

This subtype occurs most commonly in middle-aged adults and is characterised by elevated levels of cytokeratin 8 and 18. Soluble liver-kidney antigens are also present. HLA association is unclear.

Prevention

  • Sodium butyrate attenuated the injuries and prevented migration of Escherichia coli into the liver.[ncbi.nlm.nih.gov]
  • Periodic screening for autoantibodies would help to prevent delayed diagnosis and would improve patient's quality of life.[ncbi.nlm.nih.gov]
  • Autoimmune hepatitis may occur during the course of systemic lupus erythematosus and an early diagnosis is important for preventing advanced liver disease. Definitive diagnosis of autoimmune hepatitis requires confirmation by means of a liver biopsy.[ncbi.nlm.nih.gov]
  • Physicians need to be aware of these 2 hepatic diseases as diagnosis and appropriate therapy need to occur early in the disease course to prevent progression to advanced liver disease.[ncbi.nlm.nih.gov]
  • Bone density monitoring and interventions to prevent steroid-related bone disease should be implemented throughout the course of the disease.[ncbi.nlm.nih.gov]

References

Article

  1. Krawitt EL: Autoimmune Hepatiti. N Engl J Med 354:54, 2006
  2. McFarlane IG, Heneghan MA. Autoimmunity and the Female Liver. Hepatol Res. April 2004;28(4):171-176. [Medline]
  3. Czaia AJ. Autoimmune Hepatitis. In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger and Fordtran's Gastrointestinal and Liver Disease. 9th edition. Philadelphia. Pa: Saunders Elsevier;2010: Chap 88
  4. Vento S, Cainelli F. Is there a role for viruses in triggering autoimmune hepatitis? Autoimmune Rev. Jan 2004;3(1):61-9
  5. Czaja AJ:Autoimmune Liver Disease. Curr Opin Gastroenterol 23:255, 2007
  6. Robbins and Cotran, Pathologic Basis of Disease. 8th ed. Pa: Saunders Elsevier. Chap 17. pg 855-56
  7. Bogdanos DP, Invernizzi P, Mackay IR, Vergani D (June 2008). Autoimmune Liver Serology:Current Diagnostic and Clinical challenges. World J Gastroenterol. 14(21):3374-3387 doi 10.3748/wjg.14.3374 PMC 2716592 
  8. Oettinger R, Brunnberg A, Gerner P, Wintermeyer P, Jenke A, Wirthe S. Clinical features and biochemical data of Caucasian children at diagnosis of autoimmune hepatitis. J Autoimmune. Feb 2005;24(1):79-84 
  9. Mann MP, Strassburg, CP (2011). Therapeutic Strategies for Autoimmune Hepatitis. Digestive Strategies. Basel, Switzerland. 29(4):411-5. 
  10. Stephen J McPhee, Maxine A Papadakis. Current Medical Diagnosis and Treatment 2009. Pg 596

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Last updated: 2019-07-11 21:09