AIH_PBC Flashcards
What is Autoimmune Hepatitis (AIH)?
a chronic and progressive inflammatory disease of the liver
What are the key characteristics of AIH?
It is characterized by the presence of positive autoantibodies and elevated serum levels of IgG.
Who is more commonly affected by AIH, men or women?
Women are more commonly affected than men.
more common in children
What is the typical disease course of AIH?
can range from subclinical or acute forms to fulminant hepatic failure.
what is pathogenesis of autoimmune hepatitis?
combination of genetic predisposition, altered immunological processes, and environmental factors
What are the key pathological processes in autoimmune hepatitis?
Hepatocellular necrosis (death of liver cells) and fibrosis (scarring of the liver).
How does the immune system contribute to the pathogenesis of autoimmune hepatitis?
environmental factors can trigger an altered immune response, leading to progressive chronic inflammation, hepatic necrosis, activation of hepatic stellate cells (which produce collagen), fibrogenesis, and ultimately cirrhosis.
What is the clinical importance of genetic screening in autoimmune hepatitis?
Genetic screening has limited clinical importance at this time.
What are the four main criteria used in the diagnosis of autoimmune hepatitis?
Specific autoantibodies (at least one)
Clinical signs and symptoms
Blood tests (AST, ALT, high IgG level)
Histologic findings (interface hepatitis)
What other hepatic diseases should be ruled out before diagnosing autoimmune hepatitis?
Viral hepatitis (A, B, C, D, E, EBV, CMV), drug-induced liver injury, hemochromatosis, Wilson disease, alpha-1-antitrypsin deficiency.
Can drug-induced liver injury mimic autoimmune hepatitis?
DILI can have features of autoimmune hepatitis. Some medications associated with this are minocycline, nitrofurantoin, statins, and anti-TNFα agents.
What are the main autoantibodies associated with autoimmune hepatitis?
ANA (antinuclear antibody)
ASMA (antismooth muscle antibody)
Anti-LKM1 (anti-liver kidney microsomal antibody)
AAA (antiactin antibody)
What autoantibodies are characteristic of AIH type I and AIH type II?
AIH type I: ANA and/or ASMA/AAA
AIH type II: Anti-LKM1
What percentage of patients with AIH have negative autoantibodies?
20 %
What percentage of AIH patients have positive ANA at presentation?
80 %
Are ANA pathognomonic for AIH?
No, they can also be found in other conditions like primary sclerosing cholangitis, chronic B or C hepatitis, and NASH (non-alcoholic steatohepatitis).
Do antibody levels correlate with disease severity or treatment response?
No, they do not correlate with disease severity and are not used for evaluating treatment response.
Describe the range of clinical manifestations in autoimmune hepatitis.
They can vary widely, from asymptomatic forms to decompensated cirrhosis or even fulminant liver failure.
Why is taking a thorough medical history important in evaluating for autoimmune hepatitis?
Because AIH can be associated with other autoimmune diseases, such as autoimmune thyroiditis, rheumatoid arthritis, hemolytic anemia, immune thrombocytopenia, ulcerative colitis, diabetes type I, Sjögren syndrome, vitiligo, and celiac sprue.
What are some common symptoms of autoimmune hepatitis?
Fatigue, dark urine, right upper quadrant pain, anorexia, and joint pain.
What are some possible physical examination findings in autoimmune hepatitis?
The examination can be normal, or it may reveal hepatomegaly (enlarged liver), splenomegaly (enlarged spleen), scleral icterus (yellowing of the eyes), ascites (fluid accumulation in the abdomen), spider angiomas (small, dilated blood vessels on the skin), and encephalopathy (brain dysfunction).
What is a typical finding in blood tests regarding aminotransferases in autoimmune hepatitis?
Elevation in aminotransferases (AST and ALT). In severe forms, these levels can be more than 10 times the upper limit of normal (ULN).
What is a typical finding in blood tests regarding IgG levels in autoimmune hepatitis?
High levels of IgG are seen in 85% of patients.
What are the typical findings in blood tests regarding cholestasis enzymes (such as alkaline phosphatase and bilirubin) in autoimmune hepatitis?
They are usually normal or only slightly elevated.
What other blood test abnormalities may be present in autoimmune hepatitis, especially in cases with cirrhosis?
Prolonged prothrombin time (PT), hypoalbuminemia, thrombocytopenia, leukopenia, and anemia.
What is the characteristic histologic finding in autoimmune hepatitis?
Interface hepatitis, which is a process of inflammation of the hepatic parenchyma (liver tissue) at its junction with portal tracts.
What type of inflammatory infiltrate is typically seen in the portal areas in autoimmune hepatitis?
A lymphoplasmacytic infiltrate, which consists of lymphocytes and plasma cells.
What type of liver cell death is often observed in autoimmune hepatitis?
Centrilobular necrosis, which is the death of liver cells around the central vein of the liver lobule.
What is the purpose of histopathologic examination in autoimmune hepatitis?
It is useful to** exclude other causes **of hepatitis, to grade the severity of inflammation, and to stage the degree of fibrosis.
What are the main objectives of treatment for autoimmune hepatitis?
To improve symptoms
To control the inflammation
To obtain biochemical remission (normalization of AST, ALT, IgG)
To prevent disease progression
To determine fibrosis regression
What is the first-line treatment for autoimmune hepatitis?
Corticosteroids, such as prednisone.
What are the common prednisone regimens used in autoimmune hepatitis?
Prednisone 40-60 mg/day alone
Prednisone 20-40 mg/day in combination with Azathioprine 1-2 mg/kg/day
How should corticosteroid therapy be monitored and adjusted?
Monitor hepatic blood tests regularly.
Taper the doses gradually to obtain remission with minimal doses of corticosteroids (5-10 mg/day).
What are some potential side effects of corticosteroids?
Osteopenia, osteoporosis, diabetes mellitus, hypertension, depression, anxiety, Cushing syndrome, peptic ulcer disease (PUD), glaucoma, cataracts.
What is Budesonide, and how does it compare to prednisone?
Budesonide is another corticosteroid that can be used in autoimmune hepatitis.
It has fewer side effects than prednisone.
What are the limitations of Budesonide in autoimmune hepatitis?
It is not recommended in patients with cirrhosis or severe forms of AIH.
Can Budesonide be used in combination with other medications?
Yes, it can be used in association with Azathioprine.
What is the typical dosage of Azathioprine (AZA) used in autoimmune hepatitis?
50-100 mg per day.
When is it recommended to start AZA in relation to corticosteroid therapy?
It is recommended to start AZA 2 weeks after initiating corticosteroid therapy.
Is AZA used as monotherapy for the induction of remission in autoimmune hepatitis?
No, it is not used as monotherapy for induction of remission.
What are the potential side effects of AZA?
Leukopenia, thrombocytopenia (may require dose reduction or discontinuation), nausea, vomiting, pancreatitis.
What are the treatment options for AIH without cirrhosis or acute severe forms of AIH?
Budesonide + AZA
Prednisone + AZA
What is the treatment approach for AIH with cirrhosis or acute severe AIH?
Do NOT use Budesonide.
Consider Prednisone + AZA.
What is the treatment approach for patients with fulminant hepatic failure and high suspicion of AIH?
Start corticosteroid therapy without waiting for histologic results.
When should liver transplantation be considered in severe AIH?
If there is no improvement in liver tests or if the clinical status worsens after 1-2 weeks of corticosteroid treatment.
What defines AIH with fulminant liver failure, and what is the preferred treatment?
The presence of hepatic encephalopathy at presentation defines AIH with fulminant liver failure. Liver transplantation has been shown to have better survival rates compared with corticosteroid therapy alone.
How long should treatment be continued in patients with AIH?
Stopping treatment can be considered in patients with normal AST, ALT, and IgG for at least 2 years.
Is long-term remission without treatment possible in AIH?
Yes, but it is possible only in a few cases. Careful follow-up is very important.
What other medications might be considered for autoimmune hepatitis?
Mycophenolate mofetil
Calcineurin inhibitors (Cyclosporine)
Biologic treatment: Rituximab, Infliximab
In what situations would these other therapeutic options be considered?
In patients with no response to standard treatment, incomplete response, or intolerance to standard treatment.
What is the recommendation regarding family planning in women with autoimmune hepatitis?
It is recommended to maintain biochemical remission for at least a year before pregnancy.
What medications can be used to treat autoimmune hepatitis during pregnancy?
Prednisone and/or Azathioprine. Mycophenolate mofetil is NOT recommended during pregnancy.
What screening is recommended for pregnant women with cirrhosis due to autoimmune hepatitis?
Screening for esophageal varices.
When is bone densitometry recommended in patients with autoimmune hepatitis?
In all patients with AIH and risk factors for osteoporosis, and it should be repeated at 2-3 years in patients treated with corticosteroids.
What should be done regarding vitamin D in patients with autoimmune hepatitis?
Determine serum levels of vitamin D and use supplements with calcium and vitamin D when necessary.
When should bisphosphonate therapy be considered in patients with autoimmune hepatitis?
In patients with AIH and osteoporosis.
What should be checked regarding hepatitis B virus (HBV) in patients with autoimmune hepatitis?
Check for HBsAg, HBsAb, and HBcAb due to the risk of HBV reactivation with immunosuppressive therapy.
What is the key characteristic of PBC?
Progressive chronic inflammation affecting the epithelial cells of the small and medium intrahepatic bile ducts.
What is the main consequence of the bile duct damage in PBC?
Cholestasis, which is the impairment of bile flow.
What happens in untreated cases of PBC?
They can develop cirrhosis, which is the irreversible scarring of the liver.
What is the typical age range for the diagnosis of PBC?
40-50 years old, although it can occur between 15 and 93 years of age.
What is the primary mechanism driving the pathogenesis of PBC?
An autoimmune response where the immune system mistakenly attacks and damages the bile ducts within the liver.
What is the consequence of the immune attack on bile ducts in PBC?
Destruction of bile ducts leads to a decrease in biliary excretion.
What effect do accumulated bile salts have on hepatocytes (liver cells)?
They have toxic effects on hepatocytes, leading to liver cell damage and inflammation.
What are the long-term consequences of chronic cholestasis and inflammation in PBC?
They can lead to the development of fibrosis (scarring) in the liver.
What other autoimmune diseases are commonly associated with PBC?
Hashimoto’s thyroiditis, Sjögren’s syndrome/sicca complex, celiac disease, and systemic sclerosis.
Why is it crucial to obtain a detailed medical history, including medication and supplement use, in patients with suspected PBC?
Because certain medications and supplements can cause drug-induced liver injury, which can mimic PBC.
What percentage of patients with drug-induced liver injury (DILI) have a cholestatic pattern that can resemble PBC?
30 %
Primary biliary cholangitis – Clinical findings
Asymptomatic (50%);
Fatigue and pruritus – the most frequent symptoms;
Sicca symptoms (dry eyes and mouth);
Right upper quadrant pain;
Jaundice (poor prognostic sign) – late finding;
Other symptoms of hepatic decompensation: ascites, peripheral edema, gastrointestinal bleeding,
encephalopathy;
Physical examination: can be normal, excoriations from itching, xanthelasmas, hepatomegaly,
splenomegaly;
Primary biliary cholangitis – Laboratory
findings
Cholestatic pattern;
Alkaline phosphatase is elevated out of proportion compared to aminotransferases (!! Can have other
sources);
GGT, 5-nucleotidase;
Autoantibodies – antimitochondrial antibodies (AMA) – 95% of PBC patients;
Alkaline phosphatase levels do not correlate with disease severity;
AMA levels do not correlate with disease severity;
Absence of AMA does not exclude the diagnosis of PBC;
ANA can be present too (30% of PBC patients);
Ig M levels are often elevated;
Bilirubin level is high in advanced disease;
Primary biliary cholangitis – Histologic
findings
Stage 1 – florid bile duct lesion (a bile duct at the center of a dense lymphocytic infiltrate);
Stage 2 – loss of normal bile ducts, extension of inflammation in the hepatic parenchyma;
Stage 3 – bridging fibrosis of the portal triads;
Stage 4 – cirrhosis;
Primary biliary cholangitis – Diagnosis
Cholestatic pattern;
AMA;
Compatible histologic findings;
PBC should be suspected in patients with persistent cholestasis and symptoms like
fatigue/pruritus;
Hepatic biopsy is NOT mandatory for diagnosis (the antibodies are highly specific);
Primary biliary cholangitis – Differential
diagnosis
NASH, alcoholic steatohepatitis;
Infiltrative malignant disorders;
Infiltrative benign disorders (sarcoidosis, amyloidosis);
DILI
Sepsis;
Viral hepatitis with cholestatic pattern;
Vascular diseases (Budd-Chiari syndrome);
Secondary biliary cholangitis;
Primary sclerosing cholangitis;
What is the first-line imaging modality in patients with suspected PBC?
Abdominal ultrasound.
What is the purpose of abdominal ultrasound in PBC?
To exclude obstructive causes of cholestasis, such as gallstones or bile duct obstruction, and to evaluate for gallbladder pathology.
What is MRCP, and what is its role in PBC?
MRCP stands for magnetic resonance cholangiopancreatography.
It is a non-invasive imaging technique that visualizes the biliary tree and pancreatic ducts.
In PBC, it can help identify stenosis (narrowing) and dilatations (widening) of the intrahepatic and extrahepatic bile ducts, which are characteristic features of primary sclerosing cholangitis (PSC) and can sometimes be seen in PBC.
When is endoscopic ultrasound useful in the evaluation of PBC?
When there is a high suspicion of bile stones or other **extrahepatic obstructive lesions **that may not be clearly visualized on MRCP or ultrasound.
What are the complications associated with cholestasis in PBC?
Malabsorption
Steatorrhea (fatty stools)
Dyslipidemia (abnormal blood lipid levels)
Low levels of fat-soluble vitamins (A, D, K, E)
What bone-related complications can occur in PBC?
Osteopenia (decreased bone density) and osteoporosis (weak and brittle bones).
What complications can arise from cirrhosis in advanced PBC?
Ascites (fluid accumulation in the abdomen)
Esophageal varices (enlarged veins in the esophagus)
Gastrointestinal bleeding
Hepatic encephalopathy (brain dysfunction)
What is the first-line therapy for PBC?
Ursodeoxycholic acid (UDCA).
What are the benefits of UDCA in PBC?
Slows down disease progression in patients with early-stage PBC.
Has rare side effects.
What is the typical dosage of UDCA for PBC?
13-15 mg/kg/day.
How does UDCA work in PBC?
Increases transport of biliary acids.
Decreases the toxic effect of biliary acids on hepatocytes.
Decreases apoptosis (programmed cell death) rate of biliary epithelial cells.
Has an antioxidant effect.
What medication is used for patients with an inadequate response to UDCA?
Obeticholic acid.
What are some other therapeutic options for PBC?
Colchicine, methotrexate, budesonide.
What is the only effective treatment for advanced PBC with liver failure?
Liver transplant.
Primary biliary cholangitis – Management of
associated complications
Pruritus – Cholestyramine, Rifampin;
Fatigue – look for other causes like anemia, hypothyroidism, sleep disorders;
Sicca syndrome – artificial tears;
Bone densitometry should be done every 3 years in patients with PBC and osteopenia;
Supplements with calcium and vitamin D;
Bisphosphonates can be used, but with care in patients with esophageal varices;
Screening of esophageal varices;
Screening of hepatocellular carcinoma;
What is primary sclerosing cholangitis (PSC)?
PSC is a progressive inflammatory, sclerosing (scarring), and obliterative (blocking) disease of the extrahepatic or intrahepatic bile ducts, or both.
Which bile ducts are affected in PSC?
Medium-sized and large extrahepatic or intrahepatic bile ducts, or both.
What percentage of patients with PSC have inflammatory bowel disease (IBD)?
70-90% of patients with PSC have IBD, especially ulcerative colitis.
What other condition can be associated with PSC?
Multifocal fibrosclerosis syndromes, such as retroperitoneal, mediastinal, and periureteral fibrosis.
What are the late-stage complications of PSC?
Complete biliary obstruction
Secondary biliary cirrhosis
Portal hypertension
Bleeding varices
Liver failure
Cholangiocarcinoma (cancer of the bile ducts)
How do patients with PSC typically present?
Often asymptomatic.
In what scenario should PSC be suspected in patients with inflammatory bowel disease (IBD)?
In patients with IBD who have a persistent and unexplained elevation in serum alkaline phosphatase for more than 6 months.
What are some symptoms that can occur in PSC?
Right upper quadrant abdominal pain, pruritus (itching), jaundice, and acute cholangitis (inflammation of the bile ducts).
What are the typical laboratory findings in PSC?
Cholestatic pattern, including elevated alkaline phosphatase and slightly elevated transaminases (AST and ALT).
What should be considered if a patient with suspected PSC has positive ANA or ASMA?
The possibility of an** overlap syndrome**, which is a condition with features of both PSC and autoimmune hepatitis (AIH).
What are the characteristic imaging findings in PSC?
Multifocal stricturing (narrowing) with normal and/or dilated areas of the intrahepatic or extrahepatic bile ducts, or both.
What is MRCP, and what is its role in PSC?
MRCP stands for magnetic resonance cholangiopancreatography.
It is a non-invasive imaging technique that visualizes the biliary tree and pancreatic ducts.
In PSC, it is the preferred imaging modality to evaluate the extent and severity of bile duct strictures.
What is ERCP, and when might it be used in PSC?
ERCP stands for endoscopic retrograde cholangiopancreatography.
It is an invasive procedure that involves inserting an endoscope into the duodenum and injecting contrast dye into the bile ducts.
It may be used in PSC for diagnostic purposes when MRCP is inconclusive or for therapeutic interventions, such as dilating strictures or placing stents.
What is the most common distribution of bile duct strictures in PSC?
The majority of patients (85%) have both intrahepatic and extrahepatic bile duct strictures.
What are the less common distributions of bile duct strictures in PSC?
15% of patients have only intrahepatic bile duct strictures.
2-4% have only extrahepatic bile duct strictures.
What is the characteristic histologic finding in PSC?
Fibrous obliteration of small bile ducts with concentric replacement by connective tissue in an “onion-skin” pattern.
What is the recommendation regarding colonoscopy in patients with PSC?
All patients diagnosed with PSC should undergo a full colonoscopy with biopsies, even in the absence of IBD symptoms.
What is the recommendation regarding bone density examination in PSC?
All newly diagnosed PSC patients should undergo a bone density examination.
How are major bile duct strictures managed in PSC?
Endoscopic dilatation with or without stenting.
What is the treatment for advanced PSC?
Liver transplant.
What are overlap syndromes in the context of autoimmune liver disease?
They are variants of autoimmune liver disease where serologic and clinical characteristics are mixed with those of other chronic liver disorders, often immune-mediated.
What characterizes the overlap syndrome between autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC)?
Presence of anti-mitochondrial antibodies (AMA) with histological features of AIH.
Treatment is typically the same as for AIH.
What is the term for the overlap syndrome with ANA or ASMA and histological features of PBC?
Autoimmune cholangitis.
What characterizes the overlap syndrome between AIH and primary sclerosing cholangitis (PSC)?
Serology (autoantibodies) of AIH but imaging findings characteristic of PSC.
