Hepatitides and alcoholic liver disease Flashcards
What family does the hepatitis A virus belong to?
Picornaviridae
What is the structure of the hepatitis A virus?
Small, non-enveloped with ss + sense RNA
What is the route of hepatitis A transmission?
Fecal-oral
What is the course of hepatitis A infection?
- Incubation (2-6w)
- Prodrome (1-2w)
- Icteric phase (2w)
- Resolution of symptoms
What are the clinical features of the prodromal phase of hepatitis A infection?
RUQ pain Hepatomegaly Fever Malaise Anorexia N+V
What are the clinical features of the icteric phase of hepatitis A infection?
Jaundice
Dark urine
Pale stools
Pruritis
How do you diagnose hepatitis A infection?
Bloods - transaminases - bilirubin - HAV RNA - antiHAV IgM - antiHAV IgG Liver biopsy
What will you see on liver biopsy in a hepatitis A infection?
Periportal inflammation Hepatocyte swelling Ballooning degeneration Bridging necrosis Councilman bodies
Which hepatitis viruses are fecal-oral?
HAV
HEV
Vowels = bowels
What family does the hepatitis E virus belong to?
Hepeviridae
What is the structure of the hepatitis E virus?
Non-enveloped with ss + sense RNA
What is the route of hepatitis E transmission?
Fecal-oral transmission
In which region is hepatitis A commonly found?
Tropical
Subtropical
In which region is hepatitis E commonly found?
Equatorial
Developing countries
What is the course of hepatitis E infection?
- Incubation (2-8w)
- Prodrome (1-2w)
- Icteric phase (2w)
- Resolution of symptoms
What are the clinical features of the prodromal phase of hepatitis E infection?
RUQ pain Hepatomegaly Fever Malaise Anorexia N+V
What are the clinical features of the icteric phase of hepatitis E infection?
Jaundice
Dark urine
Pale stools
Pruritis
How do you diagnose hepatitis E infection?
Bloods - transaminases - bilirubin - HEV RNA - antiHEV IgM - antiHEV IgG Liver biopsy
What will you see on liver biopsy in a hepatitis E infection?
Patchy necrosis
Which group is most at risk for fulminant hepatitis in hepatitis E infection?
Pregnant women (incr mortality of both mother and fetus)
Do affected hepatitis E patients become carriers?
No
Which hepatitides can have chronic sequelae?
HBV
HCV
HDV
Consonants = chronic
Discuss the treatment of hepatitis E infection
Self-limiting
Supportive care
Which hepatitides have vaccinations available?
HAV
HBV
What family does the hepatitis B virus belong to?
Hepadnaviridae
What is the structure of the hepatitis B virus?
Enveloped, circular, partially ds DNA
What is the route of hepatitis B transmission?
Parenteral
Sexual
MTC
Which groups are at risk of parenteral hepatitis B transmission?
IVDUs HCWs Hemodialysis patients Blood transfusion recipient Organ transplant recipient
What is the replication cycle of HBV?
- After entering the host cell’s nucleus, reverse transcriptase completes the positive strand of the virus’s partially double-stranded relaxed circular DNA (rcDNA).
- The rcDNA is converted to covalently closed circular DNA
- The cccDNA is then transcribed into viral mRNA by host RNA polymerase.
- The viral mRNA leaves the nucleus and is translated into HBV core proteins and new reverse transcriptase in the cytoplasm.
- Viral mRNA and reverse transcriptase are packaged into a capsid, where viral mRNA is then reverse-transcribed into viral rcDNA.
- New viral DNA genomes are enveloped and leave the cell as progeny virions.
What is the pathophysiology of hepatocyte destruction in acute HBV infection?
HBV-derived peptides on HBV infected hepatocytes are detected by lymphocytes which activate CD8+ T cells that attack the hepatocytes
What is the pathophysiology of hepatocellular carcinoma in chronic HBV infection?
Persistent inflammation
HBV DNA integration into the host genome
What is the course of hepatitis B infection?
- Incubation (1-6m)
- Clinical course varies significantly
- serum sickness-like syndrome
- subclinical hepatitis
- symptomatic hepatitis
- fulminant hepatitis
When can serum sickness-like syndrome in acute HBV infection develop?
1-2w post infection
What are the clinical features of serum sickness-like syndrome in acute HBV infection?
Rash
Myalgia
Arthalgia
Fever
What are the clinical features of symptomatic hepatitis in acute HBV infection?
Fever Myalgia Arthalgia Skin rash Fatigue Anorexia Nausea RUQ pain Jaundice
When does hepatitis B infection become chronic?
If the infection persists for more than 6 months with the detection of HBsAg
Which HBV antigen is the first evidence of infection?
HBsAg
Which HBV antigen indicates carrier state?
Continued HBsAg after 6mo
Which HBV antigen indicates active viral replicatoin?
HBeAg
Which HBV antibody indicates resolved infection or immunity?
Anti-HBsAg (with no HBsAg present)
Which HBV antibody indicates recent HBV infection
Anti-HBcAg IgM
Which HBV antibody indicates chronic HBV infection?
Anti-HBcAg IgG
Which HBV antibody indicates long-term clearance of HBV?
Anti-HBeAg
How do you screen for HBV infection and how do you confirm HBV infection?
Screen - HBsAg, anti-HBcAg IgM
Confirm - HBV DNA, HBeAg
What additional laboratory studies should you perform in a patient with confirmed HBV infection?
Transaminases Ferritin Bilirubin Albumin INR Cholinesterase
What will you see on liver biopsy in an acute hepatitis B infection?
Councilman bodies
Bridging necrosis
What will you see on liver biopsy in a chronic hepatitis B infection?
Periportal infiltrates
Piecemeal necrosis
Ground glass hepatocytes
Which histology finding is pathognomic for chronic HBV?
Ground glass hepatocytes
What are extrahepatic manifestations of hepatitis B infection?
Polyarteritis nodosa
Glomerulonephritis
Aplastic anemia
Discuss your management of hepatitis B infection
Lifestyle changes (weight, alcohol, medications) Acute - supportive care Chronic - nucleoside/nucleotide analogues (tenofovir) - pegylated interferon alpha End-stage liver disease - transplant
Name contraindications for tenofovir
Kidney disease (AKI, CKD) Bone disease (osteomalacia, osteoporosis) Fanconi syndrome
Name contraindications for pegylated interferon alpha
Decompensated cirrhosis
Psychiatric conditions
Pregnancy
What is the structure of hepatitis D virus?
Defective ss RNA
What does the hepatitis D virus require to enter host cells?
HBsAg coat of HBV
What is the incubation period of HDV coinfection?
1-6mo
What is the incubation period of HDV super infection?
2-8w
Define acute liver failure
Rapidly worsening liver function resulting in coagulopathy and hepatic encephalopathy in individual without preexisting liver disease or cirrhosis
Name causes of acute liver failure
Viral hepatitis
Substances (acetominophen, halothane)
Toxins (aflatoxin)
What investigations should you perform in acute liver failure?
Transaminases Bilirubin Coagulopathy studies FBC (platelets) Viral serology Toxicology screening
Discuss your management of acute liver failure
Address underlying cause
Early transfer to a transplant center
Name complications of HBV infection
Short-term - HDV infection - acute liver failure Long-term - liver cirrhosis - hepatocellular carcinoma - extrahepatic manifestations - post-hepatitis syndrome
Which glomerulonephritis is more common as a extrahepatic manifestation of HBV infection?
Membranous glomerulonephritis
Membranoproliferative type I is less common
Define acute hepatitis C infection
HCV infection that develops during the first 6 months following the exposure
Define chronic hepatitis C infection
HCV infection that persists beyond the first 6 months following the exposure
Do the majority of HCV infections resolve or progress?
85% become chronic - majority of acute infections are asymptomatic
What family does the hepatitis C virus belong to?
Flaviviridae
What is the structure of the hepatitis C virus?
Enveloped,+ sense ss RNA
What is the route of hepatitis C transmission?
Parenteral
Sexual
Perinatal
What is the incubation period for hepatitis C infection?
2w-6mo
What is the clinical presentation of acute hepatitis C infection?
Asymptomatic
Symptomatic
- same as other acute viral hepatitis
What is the clinical presentation of chronic hepatitis C infection?
Liver cirrhosis
What are the extrahepatic manifestations of chronic hepatitis C infection?
- Hematological
- mixed cryoglobulinemia
- B cell non-Hodgkin lymphoma
- ITP
- autoimmune hemolytic anemia - Renal
- membranoproliferative glomerulonephritis
- membranous glomerulonephritis - Dermatological
- porphyria cutanea tarda
- lichen planus - Endocrine
- DM
- autoimmune thyroiditis - Vascular
- leukocytoclastic vasculitis
How do you diagnose HCV infection?
ELISA (antibodies) and confirm with PCR (HCV RNA)
Discuss the management of HCV infection
2 x DAA (ledipasvir + sofosbuvir)
Interferon + ribavirin
What are the adverse effects of interferon and ribavirin combination?
Arthalgia Thrombocytopenia Leukopenia Anemia Depression Teratogenic
Can pregnant women with HBV/HCV deliver vaginally and/or breastfeed?
Yes
Which sex does autoimmune hepatitis affect predominantly?
Females
Name the clinical features of autoimmune hepatitis
Fatigue
Abdominal pain
Weight loss
Jaundice (if acute liver failure)
How do you diagnose autoimmune hepatitis?
ANA
ASMA
Liver biopsy
Give a differential diagnosis for autoimmune hepatitis
Viral hepatitis
Primary sclerosing cholangitis
Primary biliary cirrhosis
Alcohol-related hepatotoxicity
Discuss the management of autoimmune hepatitis
Azathioprine
Prednisone
What are the 3 stages of alcoholic liver disease?
Alcoholic fatty liver
Alcoholic hepatitis
Alcohol-related cirrhosis
What are the laboratory findings in alcoholic fatty liver disease?
AST>ALT
Incr GGT
Incr CDT
Macrocytic anemia
What are the laboratory findings in alcoholic hepatitis?
AST:ALT>2 Macrocytic anemia Thrombocytosis Incr GGT Incr ALP
Which histological finding is associated with alcoholic liver disease?
Mallory bodies
What is the etiology of NAFLD and NASH?
DM II
Obesity