PBL: liver cirrhosis Flashcards
What is recommend daily limit of alcohol consumption?
2 units for male, 1 unit for female
1 unit = 8g of pure alcohol
* 1 shot, 8 oz beer
Pathophysiology of alcoholic liver disease
- Acetaldehyde produced from the metabolism of ethanol in the liver
- Increased in oxidative stress to the liver –> interrupts oxidation of fatty acids –> promoting fatty acid synthesis –> steatosis
- Toxic and structural alterations of cellular proteins –> damge to hepatocytes –> liver fibrosis
Leading to alcoholic related liver disease
* AFLD (more than 90%)
* Alcoholic hepatitis (10-35%)
* Cirrhosis (10-20%)
What are the clinical features of alcoholic liver disease?
AFLD
* Asymptomatic with abnormal liver enzymes (raised AST and ALT)
* USG shows echogenic liver
Alcoholic hepatitis
* Rapid onset of jaundice in recent heavy alcohol use
* Tender hepatomegaly
* AST elevated, AST/ALT ratio >1.5
* Significant short term mortality from sepsis and renal failure
Cirrhosis
* Stigmata of chronic liver disease e.g. palmar erythema, dupuytrens contracture, spider naevi and gynaecomastia
* Serious complications: esophageal variceal hemorrhage, ascites
* Nodular liver, sizes varies
Ix for alcoholic liver disease?
- CBC, LT
- USG
- Can do transient elastography to assess extent of fibrosis
- Glascow alcoholic hepatitis score can be used to assess the prognosis of alcoholic hepatitis
What is the Mx of alcoholic liver disease?
- ALCHOL CESSATION
- Nutrition (previous poor diet from heavy drinking)
- Severe alcoholic hepatitis: Use Maddrey discriminant function to assess whether patient needs steroids/pentoxifylline
- Liver transplantation: 6 months abstinence of alcohol beforehand (arbitrary number but used to ensure that the liver graft is not wasted if patient resumes drinking after transplantation)
What is the underlying cause of PSC and SS?
Postulated to be a mixture of autoimmune disorder/underlying inflammation and scarring of the intrahepatic and extrahepatic ducts.
In PSC the inflammation and scarring causes narrowing of the bile ducts, leading to impaired bile flow. Bile stasis precipitates infective cholangitis ultimately leading to cholestasis and liver failure.
Immune activation: 50% have elevated IgM, increased IgG fraction autoantibody, 75% have anti-Sm antibodies and 80% have pANCA
Linked with IBD (increased permeability of bacteria into the portal circulation across an inflamed colonic wall may lead to chronic or recurrent cholangitis.
SS
* Pruritis: cholestatic jaundice
* Fatigue
* RUQ discomfort
* Constitutional symptoms: fever and chills, night sweats
What are the blood and imaging Ix done for PSC?
Blood tests
* LFT: increased AST and ALT, increased ALP and GGT (but ALP predominant), conjugated bilrubin increased (as post hepatic obstruction)
* AMA: normally absent in PSC but required to help exclude primary biliary cholangitis
* Serum IgG4: marker of autoimmune pancreatitis but also elevated in PSC. IgG4 associated disease have a more rapidly progressive course and are less responsive to corticosteroids
* Autoantibodies: IgM, IgG4, Hypergammaglobulinemia, pANCA
Imaging tests
* USG abdomen: bile duct wall thickening, focal bile duct dilatation. Gallbladder wall thickening and enlargement, presence of gallstones.
* MRCP 1st line imaging modality due to non invasiveness and diagnostic accuracy
* ERCP (therapeutic + diagnostic): when MRCP contraindicated such as in implanted metal devices. Characteristic multifocal strictures that alternate with dilatation of intrahepatic or extrahepatic bile ducts resulting in beaded appearance of bile duct. Cholangiogram (In PBC the appearance will be normal)
MRCP and ERCP findings of primary sclerosing cholangitis?
Compare it to PBC (primary biliary cirrhosis)
In PBC: cholangiogram will appear normal as there is no strictures present (only microscopic level affected)
What are the causes of secondary sclerosing cholangitis?
Complications of PSC?
- Liver cirrhosis complications
- Acute kidney injury: bile cast nephropathy
- Hepatic osteodystrophy
- Cholangiocarcinoma
- Colorectal cancer
- Hepatocellular carcinoma
- Gallbladder carcinoma
In patient with PSC with declining renal function how do you manage?
- Take off all renal toxic medications (Steroids etc)
- Hydration
- Rule out obstruction (causing hydronephrosis) by abd USG
- Rule out UTI by urine dipstick
- RFT should have already been done (may have underlying bile cast nephropathy)
What is the mechanism of bile cast nephropathy?
cholemic nephropathy
* Direct bile acid/bilirubin toxicity. Excessive serum/urine bile acid and bilirubin can cause direct bile salt induced tubular toxicity. Bile acids/bilirubin also promotes tubulointerstitial inflammation. Bile casts associated with intratubular obstruction
* 2nd hit in patients with other pathology. Acute decompensated liver cirrhosis. Haemodynamic AKI, HRS is exacerbated by bile acid/bilirubin.
Prerenal AKI and ischemic/nephrotoxic ATI/ATN also worsened by excessive urinary bile acids.
What is Tx for bile cast nephropathy?
Does not require renal biopsy for dx (as making a dx will not change treatment)
Principle of treatment: treating the underlying cause of hyperbilirubinemia to prevent kidney injury
* ERCP, tumor resection, PTBD
* Extracorporeal therapies such as haemodialysis and plasma exchange are the other treatment options
Biologics: living liver cells
Non biologic: artificial membranes and absorbents (i.e. plasmapharesis and albumin dialysis)
Mx of PSC?
FU of predisposing conditions?
- Cholangioplasty of dominant strictures is difficult and not commonly done as there is no dominant strictures
- UDCA (limited evidence)
- Fat soluble vitamin suppleemnt
- Pregabalin for pruritis
- Long term prophylactic antibiotics for patients with recurrent cholangitis
- Definitive treatment: orthotropic liver transplantation
FU
* IBD/colorectal cancer: ileocolonoscopy
* Cholangiocarcinom and gallbladder carcinoma: abd USG annually
* Progression of liver disease: LFT, clotting profile, fibrosis staging with transient elastography, screening for fat soluble vitamins (ADEK) deficiencies
Mechanism of ascites in liver cirrhosis?
Appearance of fluid?
Cirrhosis –> portal hypertension causing splanchnic arterial vasodilation. Decreased total systemic vascular resistance –> arterial underfilling. Decreased effective arterial blood volume –> stimulate neurohormonal systems –> increased RAAS –> increased renal tubular absorption of Na –> Na retention –> ascites, edema
Appearance of peritoneal fluid
* Straw (normal)
* Blood stained (rule out traumatic tap by 3 bottle test (uniformly blood stain) or allow to stand (xanthochromia)
* Chylous
Management of biochemical abnormalities in liver cirrhosis?
- HypoNa. Hypovolemic –> fluid replacement. Hypervolemic (i.e. fluid retention) –> diuretics
- Coagulopathy (Platelet/PT): usually no Mx needed baseline –> interventions considered when underoing invasive procedures. Balance between risk of transfusiosn and procedure. Options: TPO-R agonist, FFP, cryoprecipitate, platelet transfusion
- Anemia: ix and Mx per cause of GIB accordingly: highly suggestive of variceal bleeding
Tolvapatan not in HK
What is the grading of hepatic encephalopathy?
What is the Kings criteria for transplantation?
Indications for liver transplantation in hepatic malignancy?
