HEPATOLOGY Flashcards

Question

What are the predictors of poor prognosis for acute liver failure?

Answer 1

Encephalopathy Extrahepatic organ failure - particularly AKI Indeterminate aetiology Subacute ALF Certain biochemical markers

Answer 2

clinical criteria that are used to select patients to undergo emergency liver transplantation

Answer 3

Arterial pH: < 7.3 after resuscitation and > 24 h since ingestion Lactate: > 3 mmol/L after resuscitation OR The 3 following criteria: Hepatic encephalopathy ≥ grade 3 Serum creatinine > 300 umol/L INR > 6.5

Answer 4

INR: > 6.5 OR 3 out of 5 following criteria: Aetiology: indeterminate aetiology hepatitis, drug-induced hepatitis Age: < 10 years or > 40 years Jaundice: Interval jaundice-encephalopathy > 7 days Bilirubin: > 300 umol/L INR: > 3.5

Answer 5

Manage in ICU at a transplant centre Medications to reverse any poisonings Liver transplant Managing organ systems - fluid resuscitation, intubation and entail action, nutrition, manage GI bleeds, sort metabolic abnormalities, manage AKI, sort imbalance of coagulation, sepsis 6, management of raised ICP

Answer 6

Sepsis Hypoglycaemia Raised ICP Bleeding AKI

Answer 7

Grade 3 - 30% Grade 4 - 70%

Answer 8

Inflammation of the liver

Answer 9

Alcoholic hepatitis Non alcoholic fatty liver disease (steatohepatitis) Viral hepatitis (hep viruses, CMV, EBV) Autoimmune hepatitis Drug induced hepatitis (e.g. paracetamol overdose) Ischaemic hepatitis

Answer 10

Hepatitis may be asymptomatic or could present with non-specific symptoms: Abdominal pain Fatigue Pruritis (itching) Muscle and joint aches Nausea and vomiting Jaundice Fever (viral hepatitis) RUQ pain, Hepatomegaly

Answer 11

Deranged LFTs - high AST/ALT with a proportionally less of a rise in ALP Raised bilirubin

Answer 12

ALT, AST, GGT, ALP are enzymes found within the liver. Hepatocellular injury will typically cause elevated transaminases (AST/ALT) that are released into the serum as a result of liver cell injury or death

Answer 13

Hepatitis A (relatively rare in UK)

Answer 14

Raised AST and ALT with a proportionally less of a rise in ALP Biliary - predominant rise in GGT and ALP

Answer 15

RNA picornavirus Incubation period is 2-4 weeks

Answer 16

Transmitted via faecal oral route Can also be spread with men who have sex with men or IV drug users

Answer 17

Prodromal flu-like stage RUQ pain, tender hepatomegaly, nausea, vomiting, anorexia and jaundice. It can cause cholestasis which presents with dark urine (bilirubin excreted in urine) and pale stools (bilirubin doesnt manage to enter gut) and moderate hepatomegaly.

Answer 18

It resolves without treatment in around 1-3 months.

Answer 19

it is commonly a mild self-limiting illness Good oral hydration, rest, avoid alcohol, antiemetics, chlorphenamine for pruritus, stay home, avoid unnecessary contact, avoid unprotected sex for 7 days after onset of jaundice, analgesia Notifiable disease so notify public health

Answer 20

Vaccination against hepatitis A isn't routinely offered in the UK because the risk of infection is low for most people Those at increased risk: - close contacts of someone with hep A - people planning to travel/live in parts of the world where hepatitis A is widespread - people who inject illegal drugs - you have chronic liver disease - you have clotting disorders - men who have sex with men - people who may be exposed to hepatitis A through their job e.g. sewage workers, institutions where levels of personal hygiene may be poor, people working with monkeys, apes and gorillas

Answer 21

There would be a development of jaundice, asterixis, confusion, GI bleeds, ascites or bruising. This is because ALF is defined as abnormal transaminases, development of coagulopathy and hepatic encephalopathy within 28 weeks of disease onset

Answer 22

Liver injury - check ALT, AST, ALP, GGT Liver function - check bilirubin, albumin and INR

Answer 23

Those travelling to endemic areas High risk sex, multiple partners Factor VIII and factor IX deficiencies Lab or sewage workers IVDU

Answer 24

Incubation: Hepatitis A as a relatively long incubation period that may last from 2 - 6 weeks (mean 28-30 days). Prodromal: Early part of the disease, characterised by fever, joint pain and rash. Flu-like symptoms may be present Icteric: In addition to jaundice, the icteric phase is characterised by anorexia, abdominal pain and change in bowel habit. Convalescent: Recovery phase as the body returns to normal and symptoms subside. Symptoms like malaise may last months.

Answer 25

Hep A is thought to increase the risk of miscarriage or pre-term labour when it occurs in the 2nd or 3rd trimester Breastfeeding is not known to transmit the virus

Answer 26

Post infection fatigue and feeling ill for months - common with hep A and B (a functional disease)

Answer 27

Initial dose 4-6 weeks before travel Provides protection for 12 months Booster 6-12 months later Provides immunity for 10 years (often considered life-long)

Answer 28

Enveloped DNA virus Belongs to the family of hepadnaviridae Incubation period is 6-20 weeks

Answer 29

It is transmitted by direct contact with blood or bodily fluids, such as during sexual intercourse or sharing needles (i.e. IV drug users or tattoos). It can also be passed through sharing contaminated household products such as toothbrushes or contact between minor cuts or abrasions. It can also be passed from mother to child during pregnancy and delivery (known as “vertical transmission”).

Answer 30

Most people fully recover from the infection within 2 months, however 10% go on to become chronic hepatitis B carriers. In these patients the virus DNA has integrated into their own DNA and so they will continue to produce the viral proteins.

Answer 31

Surface antigen (HBsAg) – active infection E antigen (HBeAg) – marker of viral replication and implies high infectivity Core antibodies (HBcAb) – implies past or current infection Surface antibody (HBsAb) – implies vaccination or past or current infection Hepatitis B virus DNA (HBV DNA) – this is a direct count of the viral load

Answer 32

We can measure IgM and IgG versions of the HBcAb. IgM implies an immediate response to an active infection and will give a high titre with an acute infection and a low titre with a chronic infection. IgG indicates a past infection where the HBsAg is negative. (surface antigen is cleared but they have a clear immune response to a previous infection)

Answer 33

Indicates viral load Where the HBeAg is present it implies the patient is in an acute phase of the infection where the virus is actively replicating. The level of HBeAg correlates with their infectivity. If the HBeAg is higher, they are highly infectious to others. When they HBeAg is negative but the hepatitis B e antibody is positive this implies they have been through a phase where the virus was replicating and but the virus has now stopped replicating and they are less infectious.

Answer 34

All babies in the UK born on or after 1 August 2017 are given 3 doses of hepatitis B-containing vaccine as part of the NHS routine vaccination schedule. These doses are given at 8, 12 and 16 weeks of age. It involves injecting the hepatitis B surface antigen (hepatitis B surface antibodies form against this and this is checked to ensure vaccine has worked)

Answer 35

Most acute cases are self-limiting Notifiable disease so it must be reported If profound acute hepatitis or even fulminant hepatic failure then urgent admission and assessment should be sorted. Screen for other blood born viruses (hepatitis A and B and HIV) and other STD Refer to gastroenterology, hepatology or infectious diseases for specialist management Notify Public Health Stop smoking and alcohol Education about reducing transmission and informing potential at risk contacts Testing for complications: FibroScan for cirrhosis and ultrasound for hepatocellular carcinoma Antiviral therapy can be used to slow the progression of the disease and reduce infectivity only in chronic cases! Liver transplantation for end-stage liver disease

Answer 36

Acute and chronic

Answer 37

cirrhosis and hepatocellular carcinoma

Answer 38

No evidence of jaundice

Answer 39

failure to clear the virus after acute infection. Defined as persistence of serum hepatitis B surface antigen (HBsAg) for >6 months

Answer 40

Perinatal transmission 90% Risk of progression to chronic infection has an inverse relationship with age.

Answer 41

subclinical hepatitis Anicteric hepatitis Icteric hepatitis Fulminant hepatic failure (rare)

Answer 42

Because for pt who clear the virus, HBV can persist at low levels and so can reactivate in the presence of immunosuppression

Answer 43

Phase 1 - HBeAg +ve chronic infection - minimal liver inflammation and high viral replication Phase 2 - HBeAg +ve chronic hepatitis - moderate-severe liver inflammation and accelerate progression to fibrosis. Usually occurs many years after first phase. May skip this phase Phase 3 - HBeAg -ve chronic infection - significant viral suppression and absence of significant liver disease. Favourable prognosis if minimal liver injury developed before immune clearance. Fibrosis may be present on biopsy despite low levels of HBV DNA. Phase 4 - HBeAg -ve negative chronic hepatitis - moderate to severe liver inflammation, low rate of spontaneous clearance and genetic mutations in the HBV genome that impair expression of HBeAg. Phase 5 - HBsAg negative phase - recovery.

Answer 44

Patients will be asymptomatic and unlikely to be identified unless blood tests are taken for an alternative problem. Patients will not realise they are infected. If acquired during adulthood, very low risk of chronic hepatitis B.

Answer 45

Typically presents with a non-specific illness in the absence of jaundice. Malaise Anorexia Nausea Fever Right upper quadrant pain Vomiting

Answer 46

Features similar to anicteric hepatitis but also present with jaundice.

Answer 47

A clinical syndrome of severe liver function impairment, which causes hepatic coma and the decrease in synthesizing capacity of liver, and develops within eight weeks of the onset of hepatitis.

Answer 48

Majoritively asymptomatic Fatigue, RUQ pain, anorexia, nausea, fever, vomiting, jaundice Exacerbations which may mimic acute hepatitis B Complications of chronic hepatitis e.g. cirrhosis, hepatocellular carcinoma Cirrhosis findings - stigmata of chronic liver disease Decompensated cirrhosis - ascites, encephalopathy, jaundice, coagulopathy and GI bleeds

Answer 49

Skin rash, arthritis, arthralgia, glomerulonephritis, polyarteritis nodosa, Cryoglobulinaemia, and papular acrodermatitis

Answer 50

IgG anti-HBC positive Anti-HBS positive or negative HBsAg positive

Answer 51

IgG Anti-HBc (-), Anti-HBs (+), HBsAg (-)

Answer 52

Entecavir, peginterferon alfa, tenofovir alafenamide, and tenofovir disoproxil

Answer 53

RNA flavivirus Incubation period 6-9 weeks

Answer 54

Parenteral Permucosal Vertical

Answer 55

1 in 4 fights off the virus and makes a full recovery 3 in 4 it becomes chronic

Answer 56

liver cirrhosis and associated complications and hepatocellular carcinoma

Answer 57

Screen for other blood born viruses (hepatitis A and B and HIV) and other sexually transmitted diseases Refer to gastroenterology, hepatology or infectious diseases for specialist management Notify Public Health (it is a notifiable disease) Stop smoking and alcohol Education about reducing transmission and informing potential at risk contacts Testing for complications: FibroScan for cirrhosis and ultrasound for hepatocellular carcinoma Antiviral treatment with direct acting antivirals (DAAs) is tailored to the specific viral genotype. They successfully cure the infection in over 90% of patients. They are typically taken for 8 to 12 weeks Liver transplantation for end-stage liver disease

Answer 58

After exposure to the hepatitis C virus only around 30% of patients will develop features such as: a transient rise in serum aminotransferases / jaundice fatigue arthralgia

Answer 59

defined as the persistence of HCV RNA in the blood for 6 months.

Answer 60

heumatological problems: arthralgia, arthritis eye problems: Sjogren's syndrome cirrhosis hepatocellular cancer cryoglobulinaemia: typically type II porphyria cutanea tarda, especially if there are other factors such as alcohol abuse Glomerulonephritis Non-Hodgkin lymphoma

Answer 61

sustained virological response (SVR), defined as undetectable serum HCV RNA six months after the end of therapy

Answer 62

a combination of protease inhibitors (e.g. daclatasvir + sofosbuvir or sofosbuvir + simeprevir) with or without ribavirin are used

Answer 63

haemolytic anaemia, cough. Women should not become pregnant within 6 months of stopping ribavirin as it is teratogenic

Answer 64

Single stranded RNA virus that is transmitted parenterally It can only survive in patients who also have a hepatitis B infection as its an incomplete RNA virus. It attaches itself to the HBsAg to survive and cannot survive without this protein There are very low rates in the UK.

Answer 65

Hepatitis D increases the complications and disease severity of hepatitis B.

Answer 66

There is no specific treatment for hepatitis D. It is a notifiable disease and Public Health need to be notified of all cases.

Answer 67

Co-infection: Hepatitis B and Hepatitis D infection at the same time. Superinfection: A hepatitis B surface antigen positive patient subsequently develops a hepatitis D infection.

Answer 68

associated with high risk of fulminant hepatitis, chronic hepatitis status and cirrhosis.

Answer 69

RNA hepevirus Incubation period 3-8 weeks

Answer 70

Faecal oral route

Answer 71

Mild illness

Answer 72

the virus is cleared within a month and no treatment is required. Can only cause chronic disease in immunocompromised individuals

Answer 73

Central and South-East Asia, North and West Africa, and in Mexico

Answer 74

carries a significant mortality (about 20%) during pregnancy

Answer 75

It’s currently in development but is not yet in widespread use

Answer 76

Acute - <6 months, causes nausea, vomiitng, RUQ pain, jaundice and hepatomegaly Chronic - >6 months, sometimes asymptomatic, fever, fatigue, anorexia, extrahepatic symptoms, may not have hepatomegaly but may have a lower margin that feels irregular if there is cirrhosis

Answer 77

6-monthly abdominal ultrasound and alpha-fetoprotein

Answer 78

Paracetemol overdose

Answer 79

Greater elevation in AST than ALT Associated with reduced albumin and protein levels due to reduced hepatic synthetic function

Answer 80

Human normal immunoglobulin (HNIG) Hepatitis A vaccine may be used

Answer 81

if the person exposed is a known responder to the HBV vaccine then a booster dose should be given if they are a non-responder (anti-HBs < 10mIU/ml 1-2 months post-immunisation) they need to have hepatitis B immune globulin (HBIG) and a booster vaccine

Answer 82

monthly PCR - if seroconversion then interferon +/- ribavirin

Answer 83

The acute onset of symptomatic hepatitis due to heavy alcohol consumption

Answer 84

>100g per day for 15-20 years (about 88 units a week)

Answer 85

A spectrum of conditions that result from alcohol mediated liver damage Alcoholic fatty liver -> alcoholic hepatitis -> cirrhosis (irreversible)

Answer 86

9 per 100,000 in those under 75

Answer 87

It can be metabolised by alcohol dehydrogenase in the cytosol. Uses the conversion of NAD+ to NADH. (most common) It can be metabolised by catalase in peroxisome It can be metabolised by CYP2E1 All 3 lead to the conversion of alcohol to acetaldehyde

Answer 88

Jaundice Anorexia Fever Tender hepatomegaly Others - abdo pain, ascites, muscle wasting, confusion, asterixis, tremor, bruising, stigmata of chronic liver disease The pt may also have the features of alcohol withdrawal

Answer 89

FBC U&Es LFTs Bone profile CRP Magnesium Coagulation Non-invasive liver screen to determines the possible cause of liver disease Liver ultrasound with Doppler Liver biopsy in cases of severe alcoholic hepatitis where steroid treatment is being considered Septic screen Endoscopy - varices CT/MRI be be used

Answer 90

AST/ALT ratio >2 Elevated bilirubin Elevated GGT Elevated neutrophil count Elevated INR Low albumin due to reduced synthetic function Elevated prothrombin time due to reduce synthetic function U&Es may be deranged in hepatorenal syndrome

Answer 91

Steatosis Neutrophil infiltration Hepatocytes ballooning Fibrosis Cholestasis Mallory-denk bodies

Answer 92

eosinophilic accumulations of proteins within the cytoplasms of hepatocytes. No pathological role in disease but a marker of alcohol-induced liver disease.

Answer 93

Maddrey discriminant function Model for end-stage lover disease Glasgow alcoholic hepatitis score

Answer 94

Patients with mild-to-moderate alcoholic hepatitis are usually managed conservatively with good nutrition, attention to adequate hydration and managing alcohol withdrawal. It is important to screen for underlying chronic liver disease, but the mainstay of treatment is alcohol cessation. Patients with severe alcoholic hepatitis can be extremely unwell with multi-organ failure and require referral to an ICU. Corticosteroids are often given

Answer 95

stratifies patients already receiving steroids for alcoholic hepatitis treatment for 7 days to predict which will not improve and should be considered for other management strategies

Answer 96

Hepatic encephalopathy Systemic infection: including spontaneous bacterial peritonitis GI bleeding: variceal bleeding (oesophageal/rectal) Coagulopathy and thrombocytopaenia Ascites Multi-organ failure

Answer 97

not regularly drink more than 14 units per week for both men and women. If drinking 14 units in a week, this should be spread evenly over 3 or more days and not more than 5 units in a day.

Answer 98

breast, mouth and throat.

Answer 99

Jaundice Hepatomegaly Spider Naevi Palmar Erythema Gynaecomastia Bruising – due to abnormal clotting Ascites Caput Medusae – engorged superficial epigastric veins Asterixis – “flapping tremor” in decompensated liver disease

Answer 100

Used to check the elasticity of the liver by sending high frequency sound waves into the liver. It helps assess the degree of cirrhosis.

Answer 101

Chronic inflammation damaged liver cells and they are then replaced with scar tissue which tends to form nodules. This fibrosis affects the structure and blood flow through the liver, which causes increased resistance in the vessels leading in to the liver = portal hypertension

Answer 102

Alcoholic liver disease Non Alcoholic Fatty Liver Disease Hepatitis B Hepatitis C Others: autoimmune hepatitis, primary biliary cirrhosis, haemochromatosis, Wilson’s disease, alpha 1 anti trypsin deficiency, cystic fibrosis, drugs e.g. amiodarone or methotrexate

Answer 103

Type 1 - typically women with peak incidence at 16-30 years. Acute presentations are rare Types 2 - seen more commonly in children with average age presentation at 10. Female predominance. More aggressive with 80% developing cirrhosis.

Answer 104

Type 1 - ANA, Anti-smooth muscle antibodies (anti-actin) And raised IgG is typical Ttype 2 - Anti-liver/kidney microsomal type 1 antibodies (LKM1) Type 3 - Soluble liver-kidney antigen

Answer 105

Anti-liver kidney microscopes 1 Anti-liver cytosol antigen type 1

Answer 106

Scoring systems Routine bloods Non-invasive liver screen Liver imaging Liver biopsy

Answer 107

High dose steroids and other immunosuppressants e.g. azathioprine Liver transplantation may be required in end stage liver disease but the disease can recur in transplanted livers

Answer 108

Jaundice – caused by raised bilirubin Hepatomegaly – however the liver can shrink as it becomes more cirrhotic Splenomegaly – due to portal hypertension Spider Naevi – these are telangiectasia with a central arteriole and small vessels radiating away Palmar Erythema – caused by hyperdynamic cirulation Gynaecomastia and testicular atrophy in males due to endocrine dysfunction Bruising – due to abnormal clotting Ascites Caput Medusae – distended paraumbilical veins due to portal hypertension Asterixis – “flapping tremor” in decompensated liver disease

Answer 109

FBC - hyponatraemia due to fluid retention U&Es - for hepatorenal syndrome LFTS - ALT, AST, ALP and bilirubin will all be deranged Albumin and prothrombin time Noninvasive liver screen Alpha fetoprotein every 6 months to check for hepatocellular carcinoma Enhanced liver fibrosis blood test if its available

Answer 110

Ultrasound and alpha-fetoprotein - to check for hepatoceullar carcinoma

Answer 111

Nodularity of the surface of the liver A “corkscrew” appearance to the arteries with increased flow as they compensate for reduced portal flow Enlarged portal vein with reduced flow Ascites Splenomegaly

Answer 112

Child-Pugh score

Answer 113

The factors included are bilirubin, albumin, INR, ascites and encephalopathy Each score is given 1,2 or 3 so the minimum score is 5 and maximum is 15 The score then indicates the severity of the cirrhosis and prognosis

Answer 114

NICE recommend retesting every 2 years in patients at risk of cirrhosis: Hepatitis C Heavy alcohol drinkers Diagnosed alcoholic liver disease Non alcoholic fatty liver disease and evidence of fibrosis on the ELF blood test Chronic hepatitis B (although they suggest yearly for hep B)

Answer 115

Model for End-stage liver disease score Stratifies severity of end-stage liver disease and helps guide referral for liver transplant Should be used every 6 months in pt with compensated cirrhosis

Answer 116

High protein, low sodium diet

Answer 117

Malnutrition Portal hypertension, varices, variceal bleeding Ascites and spontaneous bacterial peritonitis Hepatorenal syndrome Hepatic encephalopathy Hepatocellular carcinoma

Answer 118

Cirrhosis affects metabolism of proteins in the liver and reduces the amount of protein produced It disrupts the liver’s ability to store glucose as glycogen

Answer 119

Liver cirrhosis increases the resistance of blood flow in the liver. As a result, there is increased back-pressure into the portal system. This is called “portal hypertension”.

Answer 120

This back-pressure causes the vessels at the sites where the portal system anastomoses with the systemic venous system to become swollen and tortuous = varices Gastro-oesophageal junction, ileocaecal junction, rectum and anterior abdominal wall via the umbilical vein

Answer 121

Varices at the anterior abdominal wall via the umbilical vein The portosystemic shunt causes the round ligament to re-chanell, allowing blood from the portal system to pass into the abdominal veins = veins dilate

Answer 122

Propranolol to reduce portal hypertension Elastic band ligation at 2 weekly intervals until all varices have been eradicated Injection of sclerosant (second line to ligation) TIPS if above are all unsuccessful in preventing further episodes

Answer 123

Transjugular Intra-hepatic portosystemic shunt - inserting a wire into the jugular vein under X-ray guidance down the vena cava and into the liver via the hepatic vein. They then make a connection between hepatic vein and portal vein and put a stent in place to allow blood to flow directly from the portal vein to the hepatic vein and relieve the pressure in he portal system and varices

Answer 124

Resuscitation - Terlipressin, correct any coagulopathy, prophylactic broad spectrum antibiotics, consider intubation and intensive care Urgent endoscopy - elastic band ligation or injection of sclerosant Sengstaken-Blakemore tube if endoscopy fails

Answer 125

Abnormal accumulation of fluid in the abdomen/peritoneal cavity In men, no fluid should be present. In women, up to 20 mls may be considered normal depending on the timing of their menstrual cycle.

Answer 126

Cirrhosis -> The increased pressure in the portal system causes fluid to leak out of the capillaries in the liver and bowel and into the peritoneal cavity. The drop in circulating volume caused by fluid loss into the peritoneal space causes a reduction in blood pressure entering the kidneys. The kidneys sense this lower pressure and release renin, which leads to increased aldosterone secretion and reabsorption of fluid and sodium in the kidneys. Cirrhosis causes a transudative, meaning low protein content, ascites.

Answer 127

Transudate: due to the ultrafiltration of plasma (i.e. removal of fluid). It does not contain large proteins and only few cells. Exudate: due to leakage of whole contents of plasma (i.e. fluid, cells and proteins). Largely due to an inflammatory process.

Answer 128

Serum-ascites albumin gradient <11g/L or a gradient >11g/L

Answer 129

Liver disorders - cirrhosis, alcoholic liver disease, ALF, liver mets Cardiac - right heart failure, constrictive pericarditis Others - Budd-Chiari syndrome, portal vein thrombosis, veno-occlusive disease, myxoedema

Answer 130

Hypoalbuminaemia - nephrotic syndrome, severe malnutrition Maliganncy - peritoneal carcinomatosis Infection e.g. tuberculous peritonitis Others - pancreatitis, bowel obstruction, biliary ascites, postoperative lymphatic leak, serositis

Answer 131

Reduce dietary sodium Fluid restriction is sodium <125mmol/L Aldosterone antagonists - spironolactone Paracentesis (ascetic tap or drain) Prophylactic antibiotics to reduce risk of SBP TIPS may be considered Consider transplantation in refractory ascites

Answer 132

This occurs in around 10% of patients with ascites secondary to cirrhosis and can have a mortality of 10-20%.

Answer 133

an infection developing in the ascitic fluid and peritoneal lining without any clear cause (e.g. not secondary to an ascitic drain or bowel perforation).

Answer 134

Can be asymptomatic so have a low threshold for ascitic fluid culture Fever Abdominal pain Deranged bloods (raised WBC, CRP, creatinine or metabolic acidosis) Ileus Hypotension

Answer 135

Escherichia coli Klebsiella pnuemoniae Gram positive cocci (such as staphylococcus and enterococcus)

Answer 136

Take an ascitic culture prior to giving antibiotics Usually treated with an IV cephalosporin such as cefotaxime

Answer 137

Hypertension in the portal system leads to dilation of the portal blood vessels, stretched by large amounts of blood pooling there. This leads to a loss of blood volume in other areas of the circulation, including the kidneys. This leads hypotension in the kidney and activation of the renin-angiotensin system. This causes renal vasoconstriction, which combined with low circulation volume leads to starvation of blood to the kidney. This leads to rapid deteriorating kidney function

Answer 138

fatal within a week or so unless liver transplant is performed.

Answer 139

functional impairment of the liver cells prevents them metabolising the ammonia into harmless waste products. Secondly, collateral vessels between the portal and systemic circulation mean that the ammonia bypasses liver altogether and enters the systemic system directly. (Ammonia is produced by intestinal bacteria when they break down proteins!)

Answer 140

Acutely, it presents with reduced consciousness and confusion. It can present in a more chronically with changes to personality, memory and mood.

Answer 141

Lactulose to promote excretion of ammonia And consider Rifaximin to reduce number of ammonia-producing bacteria

Answer 142

Serum albumin - ascitic fluid albumin

Answer 143

Direct spread - bacterial translocation across the bowel wall Haematogenous spread - bacteria enter ascites via the bloodstream

Answer 144

SBP: >250/mm3 of WCC, predominantly neutrophils, cultures positive Culture negative SBP: >250/mm3 of WCC, predominantly neutrophils, cultures negative Bacterascites: <250/mm3 of WCC, culture-positive (suggests early-stage SBP or colonisation) Secondary bacterial peritonitis: multiple organisms on culture, seen in 5%. Suggestive of intra-abdominal pathology (e.g. perforation).

Answer 145

Non-alcoholic fatty liver disease (30% of adults in the uk have it) It’s expected to become the leading indication for liver transplantation in the near future

Answer 146

Non alcoholic fatty liver (aka simple steatosis) Non-alcoholic steatohepatitis (steatosis coexisting with hepatocellular injury and inflammation = NASH) Fibrosis Cirrhosis

Answer 147

Strongly linked to obesity and metabolic syndrome Poor diet and low activity levels Type 2 diabetes or impaired glucose regulation Hyperlipidaemia Middle age onwards Smoking Hypertension Sudden weight loss/starvation Obstructive sleep apnoea Endocrine e.g. PCOS, hypothyroidism FHx Higher risk in Hispanic and asian people

Answer 148

USS Hep B and C serology Autoantibodies for autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis Immunoglobulins for autoimmune hepatitis and primary biliary cirrhosis Caeruloplasmin for Wilson’s disease Alpha 1 anti-trypsin levels for alpha 1 anti-trypsin deficiency Ferritin and transferrin saturation for hereditary haemochromatosis

Answer 149

LFTs, FBC, clotting, hep B and C viral serology, autoantibodies, ferritin serum caeruloplasmin, alpha-1 antitrypsin deficiency, HbA1c, lipid profile. Renal function test, TFTs Assess persons risk of CVD Liver USS to confirm hepatic steatosis Enhanced liver fibrosis blood test if available NAFLD fibrosis score if not available Fibroscan is 3rd line and should be performed if ELF or NAFLD fibrosis score indicates fibrosis

Answer 150

Drug treatment - amiodarone or tamoxifen Hep C virus infection PCOS

Answer 151

Portal hypertension Variceal haemorrhage Liver failure Hepatocellular carcinoma Sepsis Hypertension, CKD, impaired glucose regulation, type 2 diabetes Cardiovascular disease

Answer 152

a non-invasive blood test that measures three direct markers of fibrosis: hyaluronic acid (HA) procollagen III amino-terminal peptide (PIIINP) tissue inhibitor of matrix metalloproteinase 1 (TIMP-1)

Answer 153

No treatment but advise pt that the aim of management is to reduce the risk of progression of NAFLD Lifestyle modification - diet, physical activity, regular exercise, weight loss, minimal alcohol, optimally manage comorbidities Pioglitazone may be used off-label in NASH Vitamin E supplementation for non-diabetic pt with NASH

Answer 154

If they are at high risk of advanced liver fibrosis If there are signs of advanced liver disease on examination If there is uncertainty about the diagnosis

Answer 155

paracetamol sodium valproate, phenytoin MAOIs halothane anti-tuberculosis: isoniazid, rifampicin, pyrazinamide statins alcohol amiodarone methyldopa nitrofurantoin

Answer 156

combined oral contraceptive pill antibiotics: flucloxacillin, co-amoxiclav, erythromycin* anabolic steroids, testosterones phenothiazines: chlorpromazine, prochlorperazine sulphonylureas fibrates rare reported causes: nifedipine

Answer 157

methotrexate methyldopa amiodarone

Answer 158

Nonalcoholic fatty liver disease Excess fat in the liver. It’s defined as >5% of hepatocytes containing fat It requires exclusion of a significant alcohol intake (>30g/day in men and >20g a day in women) whic would be suggestive of alcohol-related liver disease

Answer 159

A group of risk factors associated with an increased risk of CVD and stroke Abdominal obesity - waist circumference >94cm in men or >80 cm in women Hypertension (>130/85 or treated for hypertension) Impaired fasting blood glucose (>5.6mmol/L or treated for type 2 diabetes mellitus) High triglycerides (>1/7mmol/L serum level) Low HDL cholesterol (<1.0mg/dl men or <1.3mmol/L in women)

Answer 160

Insulin resistance -> promotes increased breakdown of peripheral adipose tissue + increased synthesis of triglycerides + increased uptake of fatty acids -> accumulation of toxic lipids in the liver -> hepatic steatosis The accumulation of fat within the liver can promote inflammatory changes, liver injury and eventually scarring leading to fibrosis and in its most severe form cirrhosis

Answer 161

Typically asymptomatic Non-specific RUQ pain Fatigue Hepatomegaly Obesity Hypertension Stigmata of chronic liver disease Features of decompensated cirrhosis - jaundice, ascites, bruising, encephalopathy

Answer 162

15 per 100,000 Most common in women Type 1 has a 4:1 female predominance Type 2 has a 10:1 female predominance Affects all ages and ethnicities

Answer 163

Environmental trigger in a genetically predisposed individual Genetics: Dysfunctional Treg cell response. HLA DR3 and HLA DR4 Other genes Precipitants: Herbal chemicals, drugs or viral infections include hep A and human herpes viruses)

Answer 164

Interface hepatitis (i.e. between the lobules of hepatocytes and portal tracts) Lymphoplasmacytic infiltrates into portal tracts and extending to lobules Hepatocytes necrosis usually in periportal area (may see bridging necrosis where necrosis extends between terminal venues and portal tracts) Hepatic rosette formation (pseudoacini which are glandlike formations develop due to chronic inflammation)

Answer 165

The presence autoimmune hepatitis with another autoimmune liver disease (PBC or PSC)

Answer 166

Autoimmune hepatitis and PBC are female predominant. PSC is male predominant. Can all present asymptmatically. Autoimmune hepatitis can be acute or chronic. PBC can present with marked fatigue and Pruritis. PSC can present with features of cholangitis AIH has raised ALT/AST (liver picture). PBC and PSC have raised ALP and GGT (cholestatic picture) AIH has raised IgG. PBC has raised IgM Autoantibodies in AIH are ANA, SMA and LKM. In PBC its AMA. AIH and PBC have excellent prognoses. PSC once symptomatic will have a need for transplant within 15 years at 50% of cases

Answer 167

an iron storage disorder that results in excessive total body iron and deposition of iron in tissues

Answer 168

Mutations in human haemachromatosis protein gene on chromosome 6. This genetic mutations is autosomal recessive and is important in regulating iron metabolism. Variants in this gene lead to excess iron absorption by enterocytes and ultimately, iron overload in vital organs. There is also non-HFE haemachromatosis which is rare. Caused by other genetic variants. Acquired haemachromatosis is often due to frequent transfusions of RBCs or excessive intake of iron

Answer 169

It may be as low as 1% in women and 28% in men This means the vast majority of pt with abnormal gene will not develop HH

Answer 170

About 4g of iron with 3G stored in haemoglobin of RBC

Answer 171

1mg iron lost a day from desquamation of GI cells each day 15-40mg lost with each menstrual cycle We required 1-2mg of dietary iron a day

Answer 172

Iron is absorbed from the upper gastrointestinal tract and enters the body via the ferroportin receptor on the basolateral surface. It is then transferred within the body by carrier protein transferrin. Transferrin is able to transport iron from body stores to tissues by interacting with the transferrin receptor. Once in tissue, iron is stored as ferritin that is a readily available soluble iron store. A small amount of ferritin is found within the serum and can be measured. Many immune cells of the reticuloendothelial system can also store large sums of iron in the form of ferritin - this is why its known as an acute phase reactant

Answer 173

Hepcidin - a protein made by the liver This inhibits the efflux of iron from enterocytes and the reticuloendothelial system by induced degradation of ferroportin

Answer 174

Genetic variants in HFE gene -> reduced levels of hepcidin -> increased absorption of iron to 2-4mg a day -> increased stores of iron -> increased serum ferritin and transferrin saturation -> iron deposition in key organs which causes major dysfunction

Answer 175

Secondary hypothyroidism - Chronic tiredness, weakness, cold intolerance, constipation, weight gain Type 2 diabetes mellitus - polyuria, polydypsia, weight loss Joint pain from chronic arthropathy Pigmentation - bronze/slate-grey Hair loss Secondary hypogonadism - Erectile dysfunction and amenorrhoea Cognitive symptoms (memory and mood disturbances) Chronic liver disease stigmata Cardiomyopathy -> HF symptoms Early symptms are typically fatigue, ED and arthralgia

Answer 176

Usually after the age of 40 when iron overload becomes enough to cause sympotms

Answer 177

menstruation acts to regularly eliminate iron from the body.

Answer 178

Liver Heart Pituitary gland - affects sex hormone and TSH production Pancreas Joints Skin

Answer 179

Second and third metacarpophalangeal joints

Answer 180

FBC, LFTs Serum ferritin Transferrin saturation (determines whether high ferritin is caused by iron overload or high ferritin due to inflammation) If serum ferritin and transferrin saturation are high… Genetic testing for HFE variants (and rarer genetic variants if not positive) CT abdomen MRI / Liver biopsy with perl’s stain can establish iron concentration in parenchymal cells HbA1c for diabetes X-rays for joint arthropathy

Answer 181

Type 1 Diabetes Liver Cirrhosis Iron deposits in the pituitary and gonads lead to endocrine and sexual problems - hypogonadism, impotence, amenorrhea, infertility) Cardiomyopathy Hepatocellular Carcinoma Hypothyroidism Arthropathy

Answer 182

Weekly venesection (about 500ml of blood which is about 350mg of iron) Alternatively iron chelation therapy e.g. deferasirox Monitor FBC weekly , serum ferritin monthly and transferring saturation 1-3 monthly Avoid alcohol Genetic counselling Monitoring and treating complications

Answer 183

the excessive accumulation of copper in the body and tissues

Answer 184

a mutation in the “Wilson disease protein” on chromosome 13. The Wilson disease protein is also known as “ATP7B copper-binding protein” and is responsible for various functions, including the removal of excess copper in the liver. Genetic inheritance is autosomal recessive.

Answer 185

Most patients with Wilson disease present with one or more of: Hepatic problems (40%) Neurological problems (50%) Psychiatric problems (10%)

Answer 186

Copper deposition in the liver leads to chronic hepatitis and eventually liver cirrhosis

Answer 187

The most common neurologic symptoms of WD are movement disorders including tremor, dystonia, parkinsonism, ataxia and chorea which are associated with dysphagia, dysarthria and drooling

Answer 188

Can range from mild depression to full psychosis

Answer 189

Chronic hepatitis Neurological and psychiatric features Kayser-fleischer rings in Cornea Haemolytic anaemia Renal tubular acidosis Osteopenia

Answer 190

Brown circles surrounding the iris caused by deposition of copper in Descemet’s corneal membrane Can eventually be seen by the naked eye but proper assessment is made using slit lamp examination

Answer 191

serum caeruloplasmin Slit lamp examination for Kayser-Fleischer rings Liver biopsy for liver copper content is definitive gold standard test 24 hour urine copper assay Scoring systems Serum copper Genetic analysis of ATP7B gene

Answer 192

This is the protein that carries copper in the blood. It can be falsely normal or elevated in cancer or inflammatory conditions. It is also not specific to Wilson disease.

Answer 193

Treatment is with copper chelation using: Penicillamine Trientene

Answer 194

10-25 Children usually present with liver disease whereas the first sign of disease in young adults is often neurological diseases

Answer 195

Untreated Wilson’s disease is fatal. The majority of patients die due to liver complications, though a minority will die from neurological complications. Prognosis is dependent, in part, on time of diagnosis, with those diagnosed and treated early having better long-term outcomes. Specialist treatment and adherence to therapy is key to improving survival.

Answer 196

An abundant enzyme produced by the liver and acts as a protease inhibitor Inhibits neutrophil elastase enzyme

Answer 197

Autosomal recessive with co-dominant expression (both alleles are expressed but the clinical phenotype is only seen with inheritance of 2 abnormal genes) defect in the SERPINA1 gene that codes for A1AT on chromosome 14. There are many genetic mutations that can affect the gene and each mutation refers to an allele which is subsequently linked to a letter code which described their electrophoretic mobilities such as the 3 major ones… M (medium), S (slow) or Z (very slow). M allele is normal and is found in >95% of the general population S allele is found in 2-3% of the population Z allele is the most severe and is found in 1% of the population

Answer 198

Liver cirrhosis after 50 Bronchiectasis and emphysema - in pt who are young and non-smokers

Answer 199

The mutant alpha-1-antitrypsin protein gets trapped in the liver/can’t leave, builds up, and causes liver damage which can progress to cirrhosis over time It can also lead to hepatocellular carcinoma

Answer 200

The lack of a normal, functioning alpha-1-antitrypsin protein leads to an excess of neutrophil elastase that attack the connective tissue in the lungs. Elastase breaks down elastin which is vital for the integrity of alveoli. This leads to bronchiectasis and emphysema over time.

Answer 201

Pt with COPD who are young, non-smokers or have a positive FHx, those with chronic liver disease and adult-onset asthma with poor response to bronchodilators

Answer 202

Underrecognised conditions with >1 million carriers of the abnormal AAT gene Most common in white Northern Europeans M=F Bimodal distribution in clinical presentation - neonates it causes hepatitis and children it causes decompensated cirrhosis, its most commonly seen in 5th decade of life with features of liver or lung disease

Answer 203

PiMM - homozygous for normal alleles PiZZ - homozygous for abnormal Z allele (only has 10% normal A1AT levels) PiSZ - compound heterozygous, 2 abnormal recessive alleles, variable phenotype PiMZ - heterozygous - only 1 abnormal gene so unlikely to have the clinical phenotype

Answer 204

PiZZ (likely to only have 10% normal A1AT levels so good chance of manifesting disease) There is an 80-100% chance of developing COPD with PiZZ

Answer 205

15% of adult pt will develop cirrhosis and 75% will hae respiratory problems Dyspnoea, cough, wheeze, ankle swelling Jaundice, bruising, spider naevi, palmar erythema, hepatomegaly, ascites, leuconychia, confusion, asterixis, cachexia

Answer 206

Low serum-alpha 1-antitrypsin (screening test of choice) Spirometry and other pulmonary function tests will show an obstructive picture Chest X-ray/CT to look for emphysema and bronchiectasis LFTs Others to consider: Phenotyping and genotyping Gene sequencing Liver USS and possibly liver biopsy Abdominal CT (Family members should also be investigated)

Answer 207

By using an acid-Schiff-positive staining (this stain is also used for glycogen storage disease)

Answer 208

Normal is 0.9-1.9g/L Minimum amount is about 0.8g/L (Patients with PiZZ usually have levels <0.3)

Answer 209

Stop smoking to slow down emphysema Stop drinking alcohol completely if signs of chronic liver disease Nutritional support, pulmonary rehabilitation and seasonal vaccinations COPD management - beta agonists, Muscarinic antagonists and steroids. Organ transplant for end-stage liver/lung disease Monitoring for complications e.g. hepatocellular carcinoma

Answer 210

Patients with established cirrhosis need regular surveillance for hepatocellular carcinoma with 6-monthly liver ultrasound and alpha-fetoprotein (AFP) monitoring

Answer 211

Trials are ongoing into the use of intravenous human alpha-1-antitrypsin therapy (e.g. Zemaira) to treat AATD. However, in the UK this is currently not recommended by NICE

Answer 212

Aka hepatic vein thrombosis A condition where there is obstruction to the venous outflow of the liver owing to occlusion of the hepatic vein. It can be caused by occlusion or partial occlusion to any, or all, of the 3 major hepatic veins It usually seen in the context of underlying haematological disease or another procoagulant condition

Answer 213

abdominal pain: sudden onset, severe ascites → abdominal distension tender hepatomegaly (It can present acutely with this + nausea and vomiting) (It can also present chronically with hepatomegaly, mild jaundice, ascites, negative hepatojugular reflux and splenomegaly)

Answer 214

obstruction due to a predominantly venous process (e.g. thrombosis, phlebitis)

Answer 215

obstruction due to external compression or invasion of the hepatic veins/IVC (e.g. tumour)

Answer 216

also known as veno-occlusive disease. It specifically refers to obstruction of the hepatic sinusoids and small hepatic venules.

Answer 217

This describes several conditions that result in hepatic congestion due to cardiac or pericardial disease. Commonly the result of right-sided heart failure, tricuspid regurgitation or constrictive pericarditis

Answer 218

a very specific condition where there is membranous obstruction in the IVC that predisposes to thrombosis. A thick fibrous band or web may develop blocking flow through the IVC. More frequently seen in Asian countries (e.g. Japan). Usually a milder version of BCS.

Answer 219

Myeloproliferative disorders (cause 50%) combined oral contraceptive pill (20%) Malignancy (10%) thrombophilia: activated protein C resistance, antithrombin III deficiency, protein C & S deficiencies pregnancy Infection and benign liver lesions

Answer 220

Occlusion increases the pressure in hepatic sinusoids, which reduces blood flow, causes dilatation and leads to interstitial fluid accumulation. When the lymphatic capacity for clearing the interstitial fluid is exceeded, it passes through the liver capsule and causes ascites. This global increase in pressure reduces portal flow and leads to hypoxic damage to hepatocytes. Due to poor portal flow, portal vein thrombosis may be seen in 10-20% of cases. As the condition progresses there is centrilobar necrosis (cell damage around the central veins in the liver architecture). This area is known as zone 3. Rapid progression to acute liver failure, or slow progression of fibrosis, depends on the speed of occlusion.

Answer 221

Acute occlusion: patients at risk of acute liver failure that can result in death within 2-3 weeks. Subacute occlusion: more insidious onset over months compared to acute occlusion. Less severe due to collateral venous formation in portal and hepatic venous systems. At risk of rapid progression of fibrosis. Chronic occlusion: development of chronic liver disease with features of portal hypertension. Usually present with complications of cirrhosis (e.g. ascites, encephalopathy)

Answer 222

The clinical features of BCS are highly variable. Up to 15% of patients may be asymptomatic, which is usually due to hepatic venous collaterals (patency of the last remaining hepatic vein) Other pt: Acute liver failure characterised by ascites, encephalopathy, jaundice and coagulopathy Abdominal pain Ascites Nausea and vomiting Bruising GI bleeding Hepatomegaly Distended abdominal veins

Answer 223

Doppler ultrasound: first-line investigation. CT/MRI: used if doppler ultrasound is not available, to confirm the diagnosis following ultrasound or when ultrasound is negative but the suspicion is still high. Venography: involves transvenous insertion of a catheter via the internal jugular or femoral vein. Contrast is then injected to visualis the hepatic venous system once accessed. May be used if CT/MRI are inconclusive or to plan for therapeutic interventions. Considered the gold-standard.

Answer 224

FBC U&E LFTs Bone profile CRP Coagulation Non-invasive liver screen Imaging to assess for underlying malignancy or tumour causing extrinsic compression Thrombophilia screen Haematological screen to assess for myeloproliferative disorders Liver biopsy maybe

Answer 225

They should be referred to a specialist liver unit with access to interventional radiology and transplant services. Treat underlying obstruction - medical management, interventional radiology, TIPSS and Oliver transplantation Treat any consequences of portal hypertension e.g. varices and ascites Treat underlying condition

Answer 226

Systemic anticoagulation - LMWH

Answer 227

Angioplasty with or without stenting Catheter directed thrombolysis

Answer 228

Acute forms of BCS with acute liver failure is usually fatal without liver transplantation. The use of TIPSS and liver transplantation has improved outcomes with 75% survival at 5 years. Without treatment life expectancy is 3 years after first symptoms Follow-up is important because patients are at risk of developing hepatocellular carcinoma following an episode of BCS.

Answer 229

progressive liver dysfunction for six months or longer

Answer 230

Alcohol Viruses Inherited conditions (AAT deficiency, Wilson’s disease, hereditary haemochromatosis) Metabolic - NAFLD and NASH Autoimmune Biliary - PBC and PSC Vascular - ischaemic hepatitis, BCS, congestive hepatopathy Drug-induced liver injury Cryptogenic (no known cause)

Answer 231

Chronic liver disease may result from repeated insults that cause inflammation or cholestasis. Excess deposition of fat in the liver can also promote an inflammatory response, which is seen in conditions like non-alcoholic fatty liver disease. Over time, chronic damage can lead to fibrosis where the normal liver architecture is replaced by fibrotic tissue and regenerative nodules. If the aetiological factor is removed or treated then some reversibility in liver function can occur depending on the extent of fibrosis. If fibrogenesis continues then the end result is cirrhosis, which describes irreversible liver remodeling that is associated with significant morbidity and mortality.

Answer 232

Compensated and decompensated cirrhosis

Answer 233

patients are typically asymptomatic as a small amount of residual function allows the liver to continue carrying out normal function despite extensive damage.

Answer 234

in this state the liver no longer has the capacity to carry out its normal functions, which results in multiple complications. If the insult is removed, the liver may 'recompensate' over time to a state of compensated cirrhosis. Characterised by coagulopathy, jaundice, encephalopathy, ascites and GI bleeding

Answer 235

Child-Pugh score

Answer 236

A way to grade the severity of cirrhosis using the clinical and biochemical features of decompensated cirrhosis: encephalopathy, ascites, bilirubin, albumin and INR It puts your diagnosis into class A (5-6), class B (7-9) or class C (10-15). The different classes reflect the severity of cirrhosis and provide an estimated one year survival. Class A: mild disease, one year survival 100% Class B: moderate disease, one year survival 80% Class C: severe disease, one year survival 45%

Answer 237

Early clinical features are usually non-specific. They include anorexia, lethargy, weight loss, hepatomegaly, nausea or disturbed sleep pattern. As patients develop more advanced disease, stigmata of chronic liver disease develop.

Answer 238

Caput medusa Splenomegaly Palmar erythema Dupuytren’s contracture Leuconychia Gynaecomastia Spider naevi

Answer 239

Encephalopathy (confusion +asterixis) Ascites Jaundice GI bleeding Coagulopathy

Answer 240

Liver biopsy - gold standard but high risk of complications so reservied for specific cases LFTs (although cannot be used to exclude cirrhosis) - likely to see hyperbilirubinaemia, raised INR and low albumin FBC - low platelets supportive of portal hypertension Transient elastography - US to measure sound wave velocity and indicate the degree of fibrosis USS, CT or MRI

Answer 241

Ask about alcohol intake, metabolic risk, hepatitis risk, hepatotoxic medications, FHx, previous jaundice, travel history USS and other imaging If <40 then check serum copper and caeruloplasmin LFTs, FBC, renal function, coagulation tests Virology - hep B, hep C , CMV< EBV Biochemistry - alpha-1-antitrypsin, HbA1c, blood glucose, iron studies, alpha-fetoprotein (tumour marker) Immunology - autoantibodies and coeliac, immunoglobulins

Answer 242

Liver fibrosis -> increased pressure in portal system -> splenomegaly -> hypersplenism (Other causes - alcohol effects on bone marrow or DIC)

Answer 243

Remove aetiological factor e.g. alcohol cessation, stopping meds, anti-viral therapies Diet - healthy, balanced diet as malnutrition is common, cutting down on salt and reduce oedema/ascites Meds - diuretics, hypotensive agents, prescription creams to ease skin itching Manage major complications Liver transplantation

Answer 244

Hepatic encephalopathy Ascites Hyponatraemia Gastrointestinal bleeding (i.e. variceal bleed) Bacterial infections (i.e. SBP) Acute kidney injury Hepatocellular carcinoma Hepatorenal syndrome Hepatopulmonary syndrome Acute-on-chronic liver failure

Answer 245

Caused by hyperammonaemia One theory - portal hypertension, causes shunting of ammonia away from the liver into the systemic circulation at portosystemic collaterals -> encephalopathy

Answer 246

First-line treatments: involves laxatives (i.e. lactulose 15-20 mls QDS) to maintain bowel motions. Should aim for 2-3 bowel motions per day - this is because constipation is the main driver of encephalopathy Second-line treatments: involves the long-term use of antibiotics (i.e. rifaximin) to reduce the proportion of ammonia-producing colonic bacteria.

Answer 247

It develops due to a combination of portal hypertension and loss of oncotic pressure due to hypoalbuminaemia. Due to widespread vasodilatation and underperfusion of the kidneys, the RAAS is active leading to excess water and sodium reabsorption that exacerbates ascites.

Answer 248

Aldosterone antagonists which may be combined with loop diuretics Paracentesis

Answer 249

Lower oesophagus Upper anal canal Umbilicus Bare area of the liver Retroperitoneum

Answer 250

Infection in ascitic fluid. It is defined as a predominantly neutrophilic ascitic white cell count (WCC) >250/mm3.

Answer 251

Antibiotics: Follow local guidance, should not be delayed, ascitic tap should be obtained prior. Human albumin solution: Helps to prevent the development of acute kidney injury and hepatorenal syndrome. Prophylaxis: Patients at risk of, or following confirmed, SBP should be managed with long-term prophylactic antibiotics (e.g. rifaximin).

Answer 252

United Kingdom model for end-stage liver disease (UKELD) score

Answer 253

Serum creatinine Sodium Bilirubin INR The minimum criteria for listing a patient for liver transplantation is a score ≥ 49, which represents a 9% one-year mortality without a transplant Other indications for liver transplantation, outside the UKELD score, are based on the presence of hepatocellular carcinoma with specific criteria and variant syndromes (e.g. diuretic resistant ascites).

Answer 254

6th most frequently diagnosed cancer 3rd leading cause of cancer-released deaths Incidence is highest in Asia due to burden of viral hepatitis M:F 3:1

Answer 255

Cirrhosis is the largest risk factor (up to 1/3rd of pt will deve;op it in their lifetime) Chronic hep B even in the absence of cirrhosis Hep c usually with advanced fibrosis or cirrhosis Others - hep D, aflatoxin, betel nut chewing (common in Asia), alcohol, smoking, NAFLD, AAT deficiency, hereditary haemachromatosis, androgenic steroids and a weak association with the contraceptive pill

Answer 256

A mycotoxin produced by certain moulds Can contaminate food products

Answer 257

Chronic liver injury -> necrosis -> hepatocytes regeneration -> regenrative nodules can lead to hyperplasia -> dysplasia -> maliganncy

Answer 258

Because it can integrate its own DNA material into the host genome and promote replication

Answer 259

Due to cirrhosis nearly always being present in HCV

Answer 260

Bones, lymph nodes and lungs (via the hepatic or portal veins)

Answer 261

Many pt are asymptomatic features of liver failure/cirrhosis (may present as de compensated liver disease) Constitutional symptoms - fever, anorexia, night sweats, weight loss, fatigue Localised symptoms - abdo pain, hepatomegaly, RUQ mass, jaundice Paraneoplastic syndromes

Answer 262

Hypoglycaemia (due to tumours high metabolic rate or, rarely, secretion of insulin-like growth factor) Erythrocytosis (due to secretion of EPO) Hypercalcaemia (due to secretion of parathyroid-hormone related peptide) Dermatological conditions e.g. dermatomyositis

Answer 263

There are 2 ways to make a formal diagnosis… Imaging - CT or MRI using imaging criteria Histology - liver biopsy or surgical specimen (Also do routine liver biochemistry, FBC, U&Es, alpha-fetoprotein, USS)

Answer 264

Liver Imaging Reporting and Data System (LIRaDS)

Answer 265

a focal nodule >1cm with early enhancement on the arterial phase with rapid washout of contrast on the portal venous phase of a three-phase contrast scan

Answer 266

Pain Bleeding Needle track seeding (implantation of tumour cells along the tract created by an instrument when trying to take a sample) Infection Injury to a nearby organ e.g. Perforation of gallbladder

Answer 267

surgical resection in early disease Liver transplantation Radio frequency ablation Transarterial chemoembolisation For more advanced disease… Multikinase inhibitors e.g. Sorafenib

Answer 268

Assesses the suitability of pt for lover transplant with cirrhosis and hepatocellular carcinoma It has three components: Tumour size: A single lesion < 5 cm, OR, up to 3 lesions each < 3cm Invasion: no evidence of macrovascular invasion Other features: No extrahepatic features Patients who meet the Milan criteria have a < 10% recurrence rate and 5-year survival of 70%.

Answer 269

Stage 0-A: > 5 years Stage B: > 2.5 years Stage C: > 1 year Stage D: ~ 3 months Overall 5-year survival for all stages is only 15%

Answer 270

>12g Doses of >150mg/kg associated with serious or fatal adverse effects Doses <75mg/kg are unlikely to cause toxicity unless staggered

Answer 271

The ingestion of a potentially toxic dose of paracetamol within 1 hour or less. Serious toxicity is unlikely if a patient has ingested <75 mg/kg. If a patient has ingested > 75 mg/kg, are symptomatic, or need urgent psychiatric assessment, hospital admission is warranted.

Answer 272

This refers to excessive ingestion of paracetamol over a period longer than one hour, usually in the context of self-harm. Serious toxicity may occur in patients who have ingested > 150 mg/kg in any 24 hour period. Rarely, toxicity may occur for ingestions between 75-150 mg/kg. Doses consistently < 75 mg/kg in any 24 hour period are unlikely to be toxic. However, if paracetamol above the recommended daily dose (4g/24 hours in adults) is ingested for the two preceding days or more, the risk increases. All patients that have taken a staggered overdose should be referred to hospital for assessment.

Answer 273

As a staggered overdose

Answer 274

Once ingested, paracetamol reaches peak concentration at 4 hours with an average half life of 2 hours. This may be significantly increased in the presence of hepatic dysfunction.

Answer 275

Paracetamol is primarily metabolised in the liver via conjugation with the addition of glucuronide to form a water soluble metabolite that can be excreted in the urine

Answer 276

When there is excess paracetamol ingestion, such as with overdose, conjugation in the liver become saturated and paracetamol is converted into the metabolite N-acetyl-p-benzoquinoneimine (NAPQI). NAPQI has a short half-life and is usually conjugated by the addition of glutathione, which is then renally excreted. When glutathione stores are depleted, excess NAPQI binds to hepatocellular proteins and results in oxidative damage, mitochondrial dysfunction and ultimately hepatocellular injury. Anything that effects glutathione reserves may increase the risk of severe hepatotoxicity such as fasting, excess alcohol consumption and certain drugs

Answer 277

Pt may be completely asymptomatic in the early stages. They may have nausea, vomiting and abdominal pain Around 12-36 hours following the overdose pt typically experience abdominal pain At 48-72 hours pt develop clinical features due to hepatic necrosis - RUQ pain, nausea, vomiting, jaundice, AKI, hepatic encephalopathy Rarely, patients who have taken a significant overdose with very high plasma paracetamol concentrations may develop early metabolic acidosis, raised lactate and possibly coma.

Answer 278

History FBC U&Es LFTs Bone profile Blood gas BG Paracetemol levels Salicylates levels (always request in acute overdose) Nomogram

Answer 279

A paracetemol ingestion graph It plots paracetemol concentration against time from ingestion If paracetemol concentration lies on or above the treatment line, then NAC should be administered This is use for patient paracetamol over 1 hour or less and presented within 8 hours

Answer 280

It determines whether treatment with N-acetylcysteine (NAC) is needed

Answer 281

IV NAC Standard 21 hour regimen which is based on the pt weight

Answer 282

First infusion at 1 hour - 200mls 5% dextrose or 0.9% NaCl with 150mg/kg of NAC Second infusion at 4 hour - 500mls 5% dextrose or 0.9% NaCl with 50mg/kg of NAC Third infusion at 16 hour -1000mls 5% dextrose or 0.9% NaCl with 100mg/kg of NAC

Answer 283

Take bloods in to look for signs of hepatic impairment If there is any evidence of significant deranged LFTs or abnormal renal function. The patient should be discussed with the liver transplant centre.

Answer 284

It’s a precursor to glutathione so it increases glutathione concentration so more can bind to NAPQI

Answer 285

Anaphylactic reactions (30% of pt)

Answer 286

nausea, vomiting, urticarial rash, angioedema, tachycardia, and bronchospasm. Shock is uncommon.

Answer 287

Temporary stop of infusion Consider chlorpromazine and nebulised salbutamol Once reaction has settles and slowly restart the infusion with the first bag over 2 hours

Answer 288

If plasma paracetemol concentration is on or above the line on a nomogram Any staggered overdose If any doubt over time of paracetemol ingestion patients who present > 24 hours if they are clearly jaundiced or have hepatic tenderness, their ALT is above the upper limit of normal

Answer 289

Consider - activated charcoal may help reduce absorption of the drug 4 hours post ingestion check bloods, paracetemol levels and assess nomogram. If at risk then give IV NAC

Answer 290

Arterial pH < 7.3, 24 hours after ingestion or all of the following: prothrombin time > 100 seconds creatinine > 300 µmol/l grade III or IV encephalopathy

Answer 291

vasoactive mediators cause splanchnic vasodilation which in turn reduces the systemic vascular resistance. This results in 'underfilling' of the kidneys. This is sensed by the juxtaglomerular apparatus which then activates the RAAS, causing renal vasoconstriction which is not enough to counterbalance the effects of the splanchnic vasodilation.

Answer 292

Type 1 is rapidly progressive and has a very poor prognosis Type 2 is slowly progressive and prognosis is poor but pt may liver for longer

Answer 293

Liver transplantion is ideal but pt are often too unwell to have surgery and there’s a shortage of donors Vasopressin analogues e.g. Terlipressin, to cause vasoconstriction of splanchnic ciruclation Volume expansion with 20% albumin TIPPS

Answer 294

AKI in pt with liver disease It represents the end-stage of a reduction in kidneys perfusion induced by increasingly severe hepatic injury Diagnosis of exclusion

Answer 295

Ground-glass hepatocytes with flat, hazy and uniformly dull appearing cytoplasms

Answer 296

Portal vein thrombosis Arteriovenous fistula Increased splenic blood flow or splenic vein thrombosis

Answer 297

Cirrhosis Schistomiasis Polycystic liver disease Metastatic maligannt disease Drugs Veno-occlusive disease Sarcoidosis Massive fatty change Nodular regenerative hyperplasia Alcoholic hepatitis

Answer 298

Budd-chiari syndrome Veno-occlusive disease Severe right sided HF or constrictive pericarditis (very rare now)

Answer 299

Usually asymptomatic and only present with splenomegaly Complications can cause haematemesis or meleana, ascites and encephalopathy

Answer 300

Portal hypertension Hypoalbuminaemia Na+ and water retention due to peripheral arterial vasodilation All can occur at once

Answer 301

A rare disorder affecting children up to the age of 15 characterised by an acute, life-threatening, non-inflammatory encephalopathy and fatty degeneration of the liver with minimal or no clinical signs of liver involvement. In classic Reye's syndrome, there is a severe but self-limiting disturbance of mitochondrial structure and associated enzymatic disturbances usually lasting about six days. This is accompanied by an intense, acute catabolic state associated with cerebral oedema in the absence of encephalitis or meningitis. The pathogenesis of Reye's syndrome is unclear but it appears to involve mitochondrial dysfunction that inhibits oxidative phosphorylation and fatty-acid beta-oxidation in a virus-infected, sensitised host. The host has usually been exposed to mitochondrial toxins, most commonly salicylates (e.g. aspirin use). Histologically the mitochondria are seen to become swollen and reduced in number. The liver and kidney are both affected. Changes in the brain result in cerebral oedema and increased intracranial pressure (ICP). A rare complication of common viral infections

Answer 302

a group of inherited diseases that result from a lack of, or abnormal functioning of, one of the enzymes involved in the conversion of glucose to glycogen or the breakdown of glycogen back into glucose. Because there are a number of different enzymes involved in glycogen production and breakdown, there are a number of different glycogen storage disorders If the enzyme problem is with one of the enzymes involved in glycogen production (synthesis), this causes reduced amounts of normal glycogen to be produced and sometimes abnormal glycogen being produced. If the enzyme problem is with one of the enzymes involved in glycogen breakdown back into glucose, this can lead to hypoglycaemia and a build-up of glycogen in your muscles and liver.

Answer 303

a clinical syndrome of severe liver function impairment, which causes hepatic coma and the decrease in synthesizing capacity of liver, and develops within eight weeks of the onset of hepatitis.

Answer 304

A pus-filled pocket of fluid within the liver

Answer 305

Staph aureus in children E.coli in adults

Answer 306

Drainage Amoxicillin + ciprofloxacin + metronidazole

Answer 307

Due to the dual blood supply via hepatic artery and portal vein

Answer 308

Hepatic artery occlusion - arteriosclerosis, thrombosis, emboli, hepatic artery aneurysm, polyarteritis nodes, sickle cell disease Others - shock, trauma, hypercoagulable state, eclampsia, complications of anaesthesia

Answer 309

Liver ischaemia Obstruction to hepatic vascular inflow - Portal vein thrombosis, hepatic artery thrombosis, presinusoidal causes of vascular obstruction Obstruction to hepatic vascular outflow - Budd-chiari syndrome (hepatic vein thrombosis), thrombosis of retrohepatic inferior vena cava and vasoocclusive disease Obstruction to blood flow through the liver - Sickle cell disease, DIC, intrasinuoidal malignancy, infection

Answer 310

A potentially life-threatening condition in which some small veins in the liver are obstructed Also called sinusoidal obstruction syndrome

Answer 311

Stellate cells store retinoids in their resting state and contain the intermediate filament, desmin. When activated (to myofibroblasts), they are contractile and regulate sinusoidal blood flow. Under appropriate conditions, stellate cells can also produce proteases that degrade the extracellular matrix, leading to reversal of fibrosis. The balance between collagen production and degradation is critical to the progression of liver scarring and cirrhosis development/resolution

Answer 312

Endothelin and nitric oxide play a major role in modulating stellate cell contractility. Stellate cells are activated by a wide variety of inflammatory cytokines

Answer 313

Reduce dietary sodium Fluid restriction may be requires if Na+ is <125mmol/L Aldosteron antagonists Drainage if tense ascites with albumin cover Prophylactic antibiotics to reduce risk of SBP TIPS may be considered in some patients

Answer 314

Albumin administration reduces paracentesis-Induced Circulatory Dysfunction and renal failure

Answer 315

Human albumin solution - A solution containing protein derived from plasma, serum, or normal placentas

Answer 316

Apoptotic hepatocytes which are acidophilic globule of cells that represent a dying hepatocytes surrounded by normal parenchyma (necrosis of individual hepatocytes)

Answer 317

Hepatitis (viral, autoimmune or drug)

Answer 318

Necrosis of a minute cluster of hepatocytes. Macrophages and lymphocytes tend to accumulate around them in an effort to localise the damage.

Answer 319

Hepatitis (viral, autoimmune, drug)

Answer 320

Necrosis involving a particular zone of the acinus Zone 3 is most typically affected

Answer 321

Zone 1 is periportal cells (closest to portal vessels so best oxygenated) Zone 2 is mid lobular cells Zone 3 is pericentral cells (closest to central vein where oxygenation is poor)

Answer 322

Zone 1 hepatocytes are specialized for oxidative liver functions e.g. gluconeogenesis, β-oxidation of fatty acids and cholesterol synthesis zone III cells are more important for glycolysis, lipogenesis and cytochrome P-450-based drug detoxification (here there is the highest concentration of CYP2E1 and thus are most sensitive to NAPQI production in acetaminophen toxicity)

Answer 323

Portal vessel - autoimmune hepatitis, haemochromatosis, biliary cirrhosis Central vein - NAFLD, drug/alcohol induced toxicity, parasite infection

Answer 324

It is characterized by inflammation extending from the portal tract (PT) into the periportal zone, with necrosis of periportal hepatocytes and disruption of the limiting plate (A type of zonal necrosis)

Answer 325

Hepatitis (viral, autoimmune, drug)

Answer 326

necrosis involving multiple lobules E.g. in localised ischaemic injury

Answer 327

Inferior portion of oesophagus Superior portal of the anal canal Round ligament of the liver (previous umbilical cord)

Answer 328

>5-10mm/Hg

Answer 329

When blood is diverted away from the portal venous system and backs up into the systemic veins (Less blood gets to liver -> decreased liver function and blood detoxification which causes a build up of toxic metabolites e.g. ammonia)

Answer 330

Blood backs up into the spleen causing congestive splenomegaly which leads to hypersplenism = anaemia, leukopenia and thrombocytopenia

Answer 331

Portal hypertension causes endothelial cells to release more NO -> arteries dilate -> hypotension -> stimulates release of aldosterone -> kidneys retain sodium and water -> fluid gets pushed a crossed tissues = ascites

Answer 332

Ascites (distended abdomen) Bleeding (secondary to oesophageal varices) Caput medusae Diminished liver function (jaundice, hepatic encephalopathy, bleeding etc) Enlarged spleen (anaemia, thrombocytopenia and leukopenia)

Answer 333

Take a hepatic venous pressure gradient measurement (catheter is inserted into IVC and then into portal vein to measure the difference in pressures) Liver USS to look for cirrhosis CT or MRI to look for ascites, cirrhosis and splenomegaly FBC, liver enzymes, serology OGD to look for oesophageal varices

Answer 334

Beta blockers can decrease portal venous pressured Diuretics and sodium restriction for ascites Manage oesophageal varices and prevent bleeding again with TIPPS (creates an internal bypass between portal and hepatic vein= relieves pressure)

Answer 335

A rare lung complication of liver disease It’s hypoxaemia due to dilated intrapulmonary vasculature = somehow causes a ventilation-perfusion mismatch Causes SOB, clubbing, spider angioma, cyanosis, low blood o2 sats

Answer 336

Chronic obstruction to flow within portal venous system = portal vein pressure builds up

Answer 337

Type 1 is a rapid onset hepatorenal syndrome (less than two weeks). This typically occurs following an acute event such as an upper GI bleed. Type 2 is a more gradual decline in renal function and is generally associated with refractory ascites

Answer 338

Alcohol is converted to acetaldhyde by alcohol dehydrogenase using the conversion of NAD+ to NADH. This also produces reactive oxygen species. As NADH levels increase, more fatty acids are produced As NAD+ levels decrease, less fatty acid oxidation Both lead to more fat production in the liver

Answer 339

Production of acetaldhyde from alcohol causes production of ROS Reactive oxygen species can damage proteins, including DNA Acetaldehyde can also inhibit anything they bind to and this causes acetaldhyde adducts to form = immune system recognises these as foreign = neutrophil clear up = destruction of hepatocytes by neutrophilic infiltration At this point you may get painful hepatomegaly and neutrophil leukocytosis

Answer 340

Mallory bodies - Damaged intermediate filaments in the cytoplasm of hepatocytes

Answer 341

ALT exceeding AST

Answer 342

Yellow fever Dengue fever Lassa fever Ebola

Answer 343

Spread by aedes mosquitos Common in tropical and subtropical areas of Africa and South America

Answer 344

2-14 days incubation may cause mild flu-like illness lasting less than one week classic description involves sudden onset of high fever, rigors, nausea & vomiting. Bradycardia may develop. A brief remission is followed by jaundice, haematemesis, oliguria if severe jaundice, haematemesis may occur

Answer 345

Acidosis In one study, 95% of patients with an arterial pH <7.30 who didn't receive a liver transplant died

Answer 346

Pneumococcal one off vaccine

Answer 347

Human Normal Immuniglobulin or hep A vaccine

Answer 348

If the person is a known responder to the HBV vaccine then give a booster dose If they are a non-responder then give hep B immune globulin and a booster vaccine

Answer 349

monthly PCR - if seroconversion then interferon +/- ribavirin