Cirrhosis Flashcards
What are the key pathological processes that define cirrhosis?
Hepato-cellular necrosis
Fibrosis
Nodule formation
What are the major consequences of cirrhosis in the liver?
Disturbance of the hepatic architecture
Hepato-cellular failure
What is the liver’s response to hepatocyte necrosis and hepatic lobule collapse in cirrhosis?
Formation of diffuse septa and nodular regrowth of liver cells.
which part of the liver lobule suffers most ?
the part adjacent to the portal vein
: What is the space of Disse?
A tissue space between hepatocytes and sinusoidal endothelial cells.
What happens in the space of Disse following hepatic injury?
There is an increase in extracellular matrix which contains collagens and fibronectin.
What is another name for the hepatic stellate cell, and where is it located?
Lipocyte, fat-storing cell, Ito cell
Lies in the space of Disse
How does the hepatic stellate cell contribute to fibrogenesis in cirrhosis?
The activation of the stellate cell by cytokines produces expression of α actin and is the principal cell involved in fibrogenesis. The stellate cell becomes contractile.
What happens to sinusoids in cirrhosis, and what is the consequence?
Sinusoids are converted to capillaries, and they lose the endothelial fenestrae.
This impedes metabolic exchange between blood and hepatocytes.
What does sinusoidal stenosis lead to in cirrhosis?
protal hypertension
What are the characteristics of macronodular cirrhosis?
Thick septa and nodules of variable sizes (large).
What is mixed cirrhosis?
Regeneration in a micronodular cirrhosis.
What are the characteristics of micronodular cirrhosis?
Thin regular septa, regenerating small nodules.
What are common symptoms in the clinical history of a patient with cirrhosis?
Fatigue and weight loss
Anorexia and flatulent dyspepsia
Abdominal pain
Jaundice (color of urine and feces)
Swelling of legs or abdomen
Hemorrhage (nose, gums, skin, alimentary tract)
Past health (hepatitis, drugs ingested, blood transfusion, alcohol consumption)
What are some general findings on physical examination in a patient with cirrhosis
Nutrition, fever, fetor hepaticus, jaundice, pigmentation, purpura, finger clubbing, vascular spiders, palmar erythema
white nails, gynecomastia, testicular atrophy, parotid enlargement, Dupuytren’s contracture
What abdominal findings may be present in a patient with cirrhosis?
(ascites, abdominal wall veins, liver, spleen)
What are some nutritional changes that may be observed in cirrhosis, especially alcoholic cirrhosis?
Fat stores and muscle mass are reduced, especially in alcoholic cirrhosis
What other physical findings may be present in a patient with cirrhosis?
Peripheral edema
Neurological signs (mental function, stupor, tremor)
What findings are indicative of portal hypertension?
Splenomegaly and abdominal wall veins collaterals usually indicate portal hypertension
What are some less common complications that can occur in cirrhosis, especially biliary cirrhosis?
Digital clubbing and hypertrophic osteoarthropathy complicate cirrhosis, especially biliary cirrhosis
What hematologic findings are common in cirrhosis?
A mild normocytic or macrocytic, normochromic anemia.
The leukocyte and platelet counts are reduced (hypersplenism).
What happens to prothrombin time in cirrhosis?
The prothrombin time is prolonged and does not return to normal with vitamin K.
What serum biochemical tests are altered in cirrhosis?
Bilirubin is raised.
Albumin values are low.
Gamma-globulin is raised.
Alkaline phosphatase is raised.
Transaminase values are normal or increased.
What serum immunological tests may be performed in cirrhosis?
Smooth muscle, mitochondrial, and nuclear antibodies.
HBs-Ag (Hepatitis B surface antigen).
Anti-HCV (Hepatitis C antibodies).
What urine findings are typical in cirrhosis?
Urobilinogen is present.
Bilirubin is present (in case of jaundice).
Sodium excretion is diminished in the presence of ascites.
What is the role of endoscopy in the context of cirrhosis?
For diagnosis of portal hypertension.
What can hepatic CT scan or ultrasound be used for in patients with cirrhosis?
Diagnosis of ascites.
Splenomegaly.
Space-occupying lesions.
What is the reliability of hepatic CT scan or ultrasound for diagnosing cirrhosis?
not reliable
What are serial imaging and α-fetoprotein levels used for in the management of cirrhosis?
For follow-up and for HCC (hepatocellular carcinoma) diagnosis.
What are some helpful diagnostic points on liver biopsy for cirrhosis?
Absence of portal tracts.
Abnormal vascular arrangements.
The presence of nodules with fibrous septa.
What are the contraindications for a liver biopsy?
Ascites.
Coagulation defect.
What are the clinical manifestations of liver failure in cirrhosis?
Jaundice
Ascites
Encephalopathy
Low serum albumin
Prothrombin deficiency
What are the clinical manifestations of portal hypertension in cirrhosis?
Splenomegaly
Esophageal varices
Hypertensive gastropathy
Abdominal wall veins collaterals
What are the symptoms of compensated cirrhosis?
May be asymptomatic
Can portal hypertension be present in compensated cirrhosis?
Portal hypertension may be present even with normal function tests
What are the physical findings in compensated cirrhosis?
Firm enlargement of the liver with a firm edge
Spleen may be palpable
What do biochemical tests show in compensated cirrhosis?
may be normal
How is the diagnosis of compensated cirrhosis confirmed?
Diagnosis needs to be confirmed by liver biopsy
What are the characteristic signs and symptoms of decompensated cirrhosis?
Patient has ascites and/or jaundice.
Weakness, muscle wasting, weight loss.
Fetor hepaticus may be present.
Spontaneous bruising and epistaxis (nosebleeds), encephalopathy.
Abdominal distension (ascites), edema of the legs.
Biochemical test values are modified.
Gastrointestinal tract bleeding.
What types of chronic liver disease can be caused by excessive chronic alcohol use?
Alcoholic fatty liver
Alcoholic hepatitis
Alcoholic cirrhosis
What effect can chronic alcohol use have on the liver, even without inflammation or necrosis?
Chronic alcohol use can produce fibrosis in the absence of accompanying inflammation and/or necrosis.
What is the typical nodule size in alcoholic cirrhosis?
In alcoholic cirrhosis, the nodules are usually <3 mm in diameter (micronodular).
What change in nodule size may occur with cessation of alcohol in alcoholic cirrhosis?
with cessation of alcohol, larger nodules may form, resulting in a mixed micronodular and macronodular cirrhosis.
What are the most important risk factors involved in the development of alcoholic liver disease?
Quantity and duration of alcohol intake are the most important risk factors.
Are there genetic predispositions for alcohol-induced liver lesions?
Yes, there are genetic predispositions
Are men or women more susceptible to alcoholic liver injury?
Women are more susceptible to alcoholic liver injury when compared to men.
What is the threshold for liver disease in men regarding alcohol intake?
An intake of > 40-60 g/d of alcohol (>21 drinks/week) for 10 years.
What is the threshold for liver disease in women regarding alcohol intake?
10-20 g/d (14 drinks/week).
What are examples of what constitutes “1 drink” in these guidelines?
1 drink = 12 oz beer, 5 oz wine, 1.0 oz malt liquor, 1.5 oz 80 proof “hard liquor”.
What is essential for the diagnosis of alcoholic cirrhosis regarding patient history?
The diagnosis requires an accurate history regarding both amount and duration of alcohol consumption.
What are some nonspecific symptoms of alcoholic cirrhosis?
Right upper quadrant pain, fever (alcoholic hepatitis), nausea and vomiting, diarrhea, anorexia.
What are some physical findings that may be present in alcoholic cirrhosis?
Palmar erythema, parotid enlargement, digital clubbing, Dupuytren’s contracture, muscle wasting.
What specific signs may be present in men with alcoholic cirrhosis?
Men may have decreased body hair and gynecomastia as well as testicular atrophy.
What are the causes of anemia in alcoholic cirrhosis?
From chronic GI blood loss, nutritional deficiencies, hypersplenism, or as a direct suppressive effect of alcohol on the bone marrow.
What might laboratory tests show in compensated alcoholic cirrhosis?
Tests may be normal.
What happens to platelet counts in alcoholic cirrhosis?
Platelet counts are often reduced.
What is Zieve’s syndrome, and in what condition does it occur?
A unique form of hemolytic anemia (with spur (spike) cells and acanthocytes) called Zieve’s syndrome occurs in patients with severe alcoholic hepatitis.
How are serum alanine and aspartate aminotransferases (ALT, AST) affected in alcoholic cirrhosis?
ALT and AST are elevated, with AST levels higher than ALT levels, usually by a 2:1 ratio.
What other laboratory tests are typically elevated in alcoholic cirrhosis?
γ-glutamyl transferase (GGT)
Alkaline phosphatase
Bilirubin
What does leukocytosis indicate in alcoholic hepatitis?
Reflects the severity of liver disease.
Are imaging studies routinely needed in alcoholic liver disease (ALD)?
No, they are not routinely needed.
What can ultrasound, CT scan, and MRI show in alcoholic cirrhosis?
Liver steatosis (fatty liver)
Enlargement of the liver and spleen
Complications of cirrhosis (HCC - hepatocellular carcinoma)
Is a liver biopsy mandatory for the diagnosis of alcoholic liver disease (ALD)?
No, it is not mandatory.
When is a liver biopsy indicated in alcoholic liver disease (ALD)?
Only if the diagnosis is uncertain.
What is the cornerstone of therapy for patients with alcoholic liver disease?
Abstinence is the cornerstone of therapy for patients with alcoholic liver disease.
What else is important in the treatment of alcoholic liver disease, besides abstinence?
Good nutrition and the management of underlying complications (ascites, edema, variceal hemorrhage, or porto-systemic encephalopathy) require specific treatment.
Is acetaminophen use always contraindicated in patients with liver disease?
Acetaminophen use is often discouraged in patients with liver disease.
Is there a generally accepted safe limit for acetaminophen use in patients with liver disease?
However, if no more than 2 g of acetaminophen per day are consumed, there generally are no problems.
What percentage of patients exposed to HCV infection develop chronic hepatitis C?
80%
What percentage of patients with chronic hepatitis C will develop cirrhosis, and over what time frame?
20-30% will develop cirrhosis over 20-30 years.
What type of virus is HCV, and what is the likely mechanism of liver damage?
HCV is a noncytopathic virus, and liver damage is probably immune-mediated.
What are the characteristic features of the liver in cirrhosis due to CHC?
The liver is small and shrunken with characteristic features of a mixed micro- and macronodular cirrhosis.
What percentage of patients exposed to hepatitis B develop chronic hepatitis B?
About 5% of patients exposed to hepatitis B develop chronic hepatitis B.
What percentage of patients with chronic hepatitis B will develop cirrhosis?
20% of those patients will go on to develop cirrhosis.
What are the diagnostic markers for chronic hepatitis B?
Hepatitis B core antigen (AgHBc) and hepatitis B surface antigen (AgHBs) will be positive.
What are the microscopic histological findings in cirrhosis due to chronic viral hepatitis?
Periportal fibrosis
Bridging fibrosis
Portal inflammatory cell infiltrate
Interface hepatitis
Some lobular hepatocellular injury
HCV genotype 3 – steatosis (fatty change)
What are the macroscopic histological findings in cirrhosis due to chronic viral hepatitis?
Micro- and macronodular
How do patients with cirrhosis due to chronic hepatitis C or B typically present?
Patients with cirrhosis due to either chronic hepatitis C or B can present with the usual symptoms and signs of chronic liver disease: fatigue, malaise, vague right upper quadrant pain.
What laboratory tests are used to evaluate cirrhosis due to chronic hepatitis C?
Quantitative HCV RNA testing
Analysis for HCV genotype
What hepatitis B serologies are evaluated in cirrhosis due to chronic hepatitis B?
Hepatitis B serologies to include HBsAg, anti-HBs, HBeAg (hepatitis B e antigen), anti-HBe antibody.
What additional test is used to quantify the viral load in cirrhosis due to chronic hepatitis B?
Quantitative HBV DNA levels.
What antiviral therapies are used for chronic hepatitis B (VHB)?
Lamivudine
Adefovir
Telbivudine
Entecavir
Tenofovir (disoproxil and alafenamide fumarate)
What is the treatment strategy for chronic hepatitis C (VHC)?
Interferon-free therapy; direct antiviral: protease inhibitor + NS 5A inhibitor (required for replication assembly) + NS 5B polymerase inhibitor or Polymerase inhibitor + Ribavirin
What is the success rate of treatment for chronic hepatitis C?
SVR (sustained virologic response): 90-100% for naïve and experienced-treatment patients with compensated cirrhosis.
Besides antiviral therapy, what else is important in the treatment of cirrhosis?
Treatment of complications: esophageal variceal hemorrhage, development of ascites and edema, or encephalopathy.
What is required for the diagnosis of cirrhosis due to AIH?
biopsy shows nothing
Diagnosis requires positive autoimmune markers: antinuclear antibody (ANA) or anti-smooth-muscle antibody (ASMA).
Which patients with cirrhosis due to AIH may benefit from immunosuppressive therapy?
Patients with cirrhosis due to AIH that present active inflammation accompanied by elevated liver enzymes can considerably benefit from the use of immunosuppressive therapy.
What conditions are included under the concept of nonalcoholic fatty liver disease (NAFLD)?
NAFLD is a concept that includes simple steatosis and nonalcoholic steatohepatitis (NASH).
What conditions is NAFLD associated with?
It is associated with metabolic syndrome, obesity, DM (diabetes mellitus), and hyperlipidemia.
Which form of NAFLD can progress to increased fibrosis and cirrhosis?
From NAFLD, only the patients with NASH (nonalcoholic steatohepatitis) can progress to increased fibrosis and cirrhosis.
What has been increasingly recognized about cryptogenic cirrhosis?
It has been increasingly recognized that many patients with cryptogenic cirrhosis in fact have nonalcoholic steatohepatitis.
What is biliary cirrhosis related to?
Related to chronic cholestasis due to:
Congenital or autoimmune processes
External bile duct compression
What does chronic cholestasis produce?
Chronic cholestasis produces hepatocellular necrosis.
What are the two categories of abnormal bile retention, and why is this distinction important?
Intrahepatic and extrahepatic.
Important for therapeutic reasons.
What are the causes of chronic cholestatic syndromes?
Primary biliary cholangitis
Autoimmune cholangitis
Primary sclerosing cholangitis
What are the histopathologic features of chronic cholestasis?
Xanthomatous transformation of hepatocytes; and irregular, so-called biliary fibrosis.
How does congestive heart failure lead to liver damage in cardiac cirrhosis?
The elevated venous pressure transmitted via the inferior vena cava and hepatic veins to the sinusoids of the liver.
Which laboratory values are typically raised in biliary cirrhosis?
Alkaline phosphatase, Bilirubin, GGT are raised.
What pathological changes occur in the liver due to long-term passive congestion and ischemia?
The long-term passive congestion and relative ischemia due to poor circulation, lead to centrilobular hepatocytes necrosis and to pericentral fibrosis.
How are AST and ALT levels affected in cardiac cirrhosis?
AST levels are elevated, and AST is usually > than ALT.
What is hemochromatosis?
An inherited disorder of iron metabolism that results in an increase in hepatic iron deposition.
What can hemochromatosis lead to?
This leads to a portal fibrosis that progresses to cirrhosis, liver failure, and hepatocellular cancer.
What does excessive iron deposition in tissues lead to in hemochromatosis?
organ damage
can include other organs
What does a liver biopsy show in hemochromatosis?
Liver biopsy: iron concentration and hepatic iron index.
What is Wilson’s disease?
young teenager
An inherited disorder of copper homeostasis with failure to excrete excess amounts of copper, leading to an accumulation in the liver and many other tissues: brain (putamen, globus pallidus, caudate and thalamus), eye, kidneys, muscles, etc. (defective function of copper-transporting ATP7B protein).
How is hemochromatosis treated?
Treatment requires regular therapeutic phlebotomy
What neurological manifestations can occur due to copper deposition in the central nervous system in Wilson’s disease?
Parkinson-like movement, tremors, ataxia, dystonia.
What causes chronic liver disease in α1AT deficiency?
Chronic liver disease is due to the accumulation of insoluble mutant protein within hepatocytes: chronic hepatitis, cirrhosis, HCC.
What eye findings can occur in Wilson’s disease?
Deposition in the eye can result in Kayser-Fleischer corneal rings and sunflower cataracts (slit-lamp examination); golden-brown pigment in the outside rim of the cornea - multicolored cataracts
How is Wilson’s disease treated?
Treatment consists of copper-chelating medications (D-Penicillamine, Zinc).
How is α1AT deficiency diagnosed?
Diagnosis is made by determining α1AT levels.
What does a liver biopsy show in α1AT deficiency?
Liver biopsy shows characteristic PAS-positive granules.
What are the treatments for α1AT deficiency?
The only effective treatment is liver transplantation, but sometimes intravenous infusions of AT1.
