Chronic Liver Disease Lectures (PDF)

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Chronic Liver Disease 1 and 2: Cause and Clinical Features Department of Medicine Professor John Ryan Hepatology Consultant LEARNING OUTCOMES C...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Chronic Liver Disease 1 and 2: Cause and Clinical Features Department of Medicine Professor John Ryan Hepatology Consultant LEARNING OUTCOMES CLD 1: Medical Conditions Causing Chronic Liver Disease Define chronic liver disease and cirrhosis List the causes of chronic liver disease and cirrhosis Describe how each cause leads to development of chronic liver disease and cirrhosis Outline the common symptoms and signs in each cause of chronic liver disease and cirrhosis Develop a differential diagnosis for what has caused cirrhosis in a patient Outline the overarching principles of investigations and management in each cause of chronic liver disease and cirrhosis. CLD 2: Clinical Features Define chronic liver disease and cirrhosis Explain the pathophysiology of chronic liver disease and cirrhosis List the cardinal symptoms and signs of chronic liver disease and cirrhosis Explain how each symptom and sign is caused in chronic liver disease and cirrhosis Develop a differential diagnosis for chronic liver disease and cirrhosis Outline the overarching principles of investigations and management in chronic liver disease and cirrhosis DEFINITIONS Chronic liver disease (CLD) is a progressive deterioration of liver functions for more than six months, which includes synthesis of clotting factors, other proteins, detoxification of harmful products of metabolism, and excretion of bile. The time to disease is a relative rather than absolute distinction. Acute Liver Injury: Short course, usually a more rapid, severe onset of symptoms Chronic Liver Disease: Longer course (>6 months), a more gradual, insidious onset of symptoms Some causes of liver disease can present with either an acute (eg. Hepatitis A tends to be acute only) or chronic presentation (eg. Haemochromatosis very rarely acute), and some can progress from acute to chronic (acute alcoholic hepatitis to chronic alcoholic liver disease). ACUTE LIVER CHRONIC LIVER DISEASE INJURY Chronic Alcoholic Liver Alcoholic hepatitis Disease (ALD) Paracetamol Fatty liver disease overdose Hepatitis B and C Hepatitis A and E Haemochromatosis Ischaemic hepatitis  Chronic Liver Disease is a continuous process of inflammation, destruction, and regeneration of liver parenchyma, which can lead to fibrosis and cirrhosis if the underlying cause is not addressed​ Fibrosis is the deposition of extracellular matrix (ECM) in response to chronic liver injury by any cause. Fibrosis can be reversible in the initial stage of development. The transition point to irreversible fibrosis is still not completely understood.​ ​ Cirrhosis is a final stage of chronic liver disease that results in disruption of liver architecture, the formation of widespread nodules, vascular reorganization, neo-angiogenesis, and deposition of an extracellular matrix PATHOPHYSIOLOGY PATHOPHYSIOLOGY The injury pathway is initiated by hepatic stellate cells (HSC). HSC are usually dormant cells found in the space between sinusoids and hepatocytes. While quiescent, they play a role in Vitamin A metabolism. In response to liver injury, HSCs are activated, and transform into fibroblasts and upregulate the expression of inflammatory receptors. This pro-inflammatory phase makes the liver cells responsive to inflammatory cytokines, and leads to progressive activation of more HSC cells, resulting in the accumulation of ECM and fibrosis. Healthy Liver (for Cirrhotic Liver transplantation) PATHOPHYSIOLOGY: PORTAL HYPERTENSION The liver receives 25% of the cardiac output (between 800-1200mls/min). Hepatic sinusoids are specialised capillaries, which receive this considerable blood volume. In cirrhosis, sinusoidal endothelial cells (SECs), which line the hepatic sinusoids, produce excess nitric oxide (NO) vasodilator, and endothelin-1 (ET-1) vasoconstrictor, leading to blood vessel constriction and high pressures within the liver vascular bed. This is termed portal hypertension. Due to back pressure, the splanchnic (abdominal) circulation also sees an increase in NO leading to dilation of blood vessels, activating the renin-angiotensin-aldosterone system (RAAS), and resulting in water and sodium retention, increasing blood volume, creating a hyperdynamic circulation. Portal hypertension (increased pressure in the portal vein) and hyperdynamic circulation (increased blood volume in the portal system) PATHOPHYSIOLOGY: PORTAL HYPERTENSION Portal hypertension: As the resistance to blood flow increases within the portal circulation (in this case due to the upstream fibrosis), the pressure backs up and tries to find alternative routes back to the heart, around the obstruction. Due to the venous anatomy, this pressure can back up into: - Gastro-oesophageal veins: Oesophageal varices (increasing the risk of life- threatening variceal bleeding) - Splenic vein: Splenomegaly - Umbilical veins: Caput medusae - Rectal veins: Haemorrhoids DECOMPENSATION The natural history of cirrhosis is characterised by a stable 'compensated' period, followed by periods of acute 'decompensation'. A common cause for GI acute medical admissions, complex medical needs, high risk of in hospital death. Def: Acute deterioration in liver function in a patient with cirrhosis, characterised by the development of one of the following complications: 1. Jaundice (impaired excretion of bilirubin leading to accumulation in skin and mucous membranes) 2. Ascites (most common complication of cirrhosis, accumulation of fluid in the abdomen due to portal hypertension) 3. Hepatic Encephalopathy: a range of neurological symptoms, exact mechanism unknown but thought to be secondary to build up of toxins crossing the BBB, including ammonia 4. Variceal Haemorrhage: Oesophageal varices can rupture, leading to life-threatening haemorrhage with a high mortality rate. SIGNS AND SYMPTOMS WHAT DO YOU SEE? SYMPTOMS- CAUSES Symptom Cause Fatigue and weakness Catabolic state given inflammation, malnutrition, poor diet of ALD Nausea and Vomiting Poor gastric emptying, increased acid production, ascites causing mechanical nausea Pruritis Excess bilirubin deposited in skin Jaundice Circulating unconjugated bilirubin. Bleeding Reduced clotting factors produced, platelets consumed due to splenomegaly Weight gain Fluid retention and third spacing, given hyperdynamic state, reduced albumin production Confusion Encephalopathy due to reduced ammonia excretion, B12 deficiency due to alcohol Wernicke's Fever/ Abdominal pain Subacute bacterial peritonitis due to ascites Upper GI Bleed: Haematemesis, Oesophageal Varices due to portal hypertension malaena SIGNS- CAUSES Signs Causes Reduced GCS/Asterixis Hepatic Encephalopathy due to reduced excretion of ammonia Jaundice Hepatocyte damage reducing conjugation of bilirubin Bruising/Petechiae Reduced clotting factor synthesis, consumptive thrombocytopaenia Ascites Due to RAA system activation, salt and fluid retention, splanchnic arterial dilation, portal hypertension, reduced oncotic pressure due to reduced albumin synthesis Splenomegaly/Caput Portal hypertension medusae Peripheral oedema Reduced albumin production Pallor Anaemia of chronic disease, B12 deficiency, iron deficiency CAUSES OF CHRONIC LIVER DISEASE Overlapping causes are common: eg. HCV with ALD or NAFLD METABOLIC DYSFUNCTION- ASSOCIATED STEATOTIC LIVER DISEASE Leading cause of chronic liver disease in Ireland and the Western World  Steatosis: accumulation of lipid droplets within hepatocytes METABOLIC DYSFUNCTION- ASSOCIATED STEATOTIC LIVER DISEASE Leading cause of chronic liver disease in Ireland and the Western World  Metabolic Syndrome: A cluster of conditions which indicate a high risk of cardiovascular disease: - Insulin resistance - Central Obesity 'apple shaped' - Hypertension METABOLIC DYSFUNCTION- - Hyperlipidaemia ASSOCIATED Associated Conditions: STEATOTIC - MASLD - Sleep apnoea LIVER DISEASE - Gout: Hyperuricaemia - PCOS: Polycystic Ovarian Syndrome - Erectile Dysfunction Leading cause of chronic liver disease in Ireland and the Western World Causes a mild chronic disease, i.e. the majority of deaths are secondary to MI Affects approximately 1/3 of Irish individuals and stroke. (large number undiagnosed) High High Sedenta calorie saturate ry intake d fat lifestyle  Nomenclature: Previously termed 'Non-Alcoholic Fatty Liver Disease' or NAFLD. While out ruling alcohol is a key component of making this diagnosis, the METABOLIC DYSFUNCTION- name is stigmatising, and therefore has been recently changed. ASSOCIATED Other terms: STEATOTIC NASH: Non-Alcoholic Steatohepatitis LIVER DISEASE - Infers inflammation secondary to the fatty infiltration Leading cause of chronic liver disease MASLD is a diagnosis of exclusion: in Ireland and the Western World - Fatty liver on ultrasound - Absence of alcohol excess - Features of metabolic syndrome - Need to out-rule all other potential causes Treatment: Life-style modification: diet, exercise, ALCOHOLIC LIVER DISEASE Major public health issue, both in Ireland and worldwide  Ethanol ALCOHOLIC - CNS depressant which produces euphoria and behavioural excitation at low levels, drowsiness, ataxia, slurred speech, stupor, and coma at higher LIVER intoxication levels. DISEASE Impact of Alcohol on Liver - Ethanol is metabolised by ADH (alcohol dehydrogenase) in hepatocytes - ADH-catalyzed ethanol oxidation uses nicotinamide adenine dinucleotide (NAD +) as a cofactor, generating reduced NAD+ (NADH) and acetaldehyde. The latter compound is highly reactive and toxic. Impact of Alcohol on Brain - Alcohol use leads to cerebellar disfunction, resulting in classic intoxifcation symptoms of ataxia, broad based gait, slurred speech. - Chronic use: cerebellar wasting can lead to chronic cerebellar ataxia and can be seen on neuroimaging in chronic alcoholism. - Acute Withdrawal: due to changes to neurotransmitter channels that occur in alcoholism, abrupt withdrawal can lead to seizures. Cerebellar Atrophy Clinical features of Alcoholic Liver Disease: - Features of CLD - Extra-hepatic manifestations: o Nervous system: Symmetric peripheral neuropathy. Withdrawal: Thiamine deficiency complications: Wernicke's encephalopathy, korsakoff's psychosis. o Pancreatitis o Cardiomyopathy ALCOHOLIC Diagnosis: LIVER DISEASE - Documentation of regular alcohol consumption - Clinical or biochemical features suggestive of liver injury Memory Aid: - LFT pattern: Scotch is o AST: ALT ratio >1.5 stronger than o Elevated GGT Limoncello - Exclusion of alternative causes of liver disease - Liver biopsy: Histology shows steatosis, hepatocellular injury, fibrosis or cirrhosis AST > ALT Management: - Alcohol cessation and avoidance of risks (Alcohol withdrawal seizures, Wernicke's, Korsakoffs) - Addiction support - Screening for and management of cirrhosis complications (variceal bleeding, ascites, SBP, hepatic encephalopathy, HCC) - Nutritional support - Avoidance of other causes of liver injury ALCOHOL WITHDRAWAL Thiamine AKA. Vitamin B1. Key role in cerebral metabolism. Deficiency can cause neuronal cell death, classically seen in the mammillary bodies (hypothalamus). Deficiency is classically associated with alcohol use disorder, poor dietary intake, impaired intestinal absorption, reduced hepatic storage. Wernicke-Korsakoff syndrome is a disease spectrum, with Wernicke's representing the acute phase, progressing to Korsakoff in the chronic stage, if the thiamine deficiency is not reversed. Wernicke's encephalopathy Acute, life-threatening neurological condition caused by thiamine deficiency characterized by a clinical triad: 1. Ophthalmoplegia with nystagmus, 2. Ataxia 3. Confusion Korsakoff Psychosis Neuropsychiatric disorder associated with memory disturbances, confabulation, emotional disturbances. Management: Thiamine supplementation: Intravenous Pabrinex (vit B+C), switching to oral thiamine tablets for long term management.  VIRAL HEPATITIS HAV HBV HCV HEV Type RNA DNA RNA RNA Incubation period (days) 15-50 50-180 14-84 15-60 Acute vs chronic liver disease Acute Acute Chronic Acute, rarely Chronic chronic in immunocom promised Can cause cirrhosis and No Yes Yes No primary hepatocellular carcinoma Vaccine available Yes Yes No No  Risk Factors (key questions on history taking): Intravenous drug injectors Approximately 70% of people who inject drugs in Ireland have HCV Sexually transmitted: multiple sexual partners/unprotected sex HEPATITIS C Tattoos Blood transfusion (Irish Blood Transfusion Scandal) ssRNA virus Haemodialysis 80-90% of infections become Vertical transmission (mother to baby) chronic Travel to endemic areas: Egypt Risk of cirrhosis and HCC Health care workers Curable Preventable? No No vaccine currently exists Curable: Yes Direct Acting Antivirals, eg. sofosbuvir 99% chance of cure with an 8-week course of DAA tablets Modes of transmission: Similar to HCV Highly infectious Very environmentally stable: can remain active on surfaces for up to one week. Hygiene practices are essential HEPATITIS B Remains an important global Preventable? Yes public health issue Vaccination exists Significant morbidity and mortality Curable? No Risk of cirrhosis and HCC Managed by viral suppression with nucleoside analogues: eg. Entacavir, lamivudine Goals of therapy: Prevent disease progression to cirrhosis or HCC. Prevent mother to child transmission Prevent reactivation Prevent HBV-associated extra-hepatic manifestations HAEMOCHROMATOSIS 'BRONZED DIABETES' Named in 1800's 'Chrom' meaning pigmentation, in the 'haem' meaning blood Excess iron is absorbed via the intestine, leading to total-body iron overload. Iron accumulates in multiple organs: Liver (cirrhosis and HCC), heart (cardiomyopathy), pancreas (diabetes), pituitary (pituitary hypogonadism, skeletal (arthralgias/arthritis/osteoporosis). Chronic picture: Manifests years later after significant iron deposition Onset in premenopausal women can be delayed by menstrual loss of blood Symptoms: cirrhosis, diabetes, arthralgias/arthritis/osteoporosis, fatigue, erectile dysfunction/loss of libido/amenorrhoea, ECG abnormalities, bronze skin hyperpigmentation (epidermal iron deposition). HAEMOCHROMATOSIS Ireland has the highest prevalence of hereditary haemochromatosis (HH) in the world 1/5 people in Ireland are gene carriers. Hereditary haemochromatosis is an autosomal recessive condition due to homozygous (ie. 2 copies) mutations in the HFE (H: High, Fe: Iron) gene on chromosome 6. – C282Y (Cysteine to Tyrosine at 282nd amino acid) – H63D (Histidine to Aspartic Acid at amino acid 63) 85% of HH due to C282Y homozygosity Diagnosis: 1. Iron Studies – Pre-menopausal women: Transferrin saturation >45%, ferritin >200 µg/L – Men/ post-menopausal women: Transferrin saturation >50%, ferritin >300µg/L 2. AND genetic testing: HFE genotyping Treatment: – 1st line: Venesection – 2nd line: Iron chelator (inaccessible veins, needle phobia, concomitant anaemia,)  Deferasirox  Wilsons disease (hepatolenticular degeneration) is an autosomal recessive genetic disorder of copper metabolism due to ATP7B mutations on chromosome 13 Impaired biliary copper excretion leads to accumulation of copper in several organs, most notably the liver, brain, and WILSONS DISEASE cornea. Ocular: Kayser fleisher rings (brown-yellow ring at corneo- scleral junction, due to copper deposition in Descemet's membrane). Liver: Cirrhosis, can progress to fulminant liver failure Neurological: Dysarthria, parkinsonism, cerebellar ataxia, dystonia, tremor etc. Psychiatric: mood disorders, psychosis, cognition Other organs: Kidney, heart, joints, endocrine Rare condition, but devastating if missed Can present at any age, but the vast majority between ages 5- 35.  Investigations: WILSONS DISEASE Serum copper (high, >1.6µmol/L) , caeruloplasmin (low, 1.6µmol/L/24hours) Slit lamp ophthalmology exam Treatment: D-Penacillamine: promotes urinary excretion of copper Zinc: interferes with uptake of copper from GI tract Trientine: chelator Rare condition, but devastating if missed PRIMARY BILIARY CHOLANGITIS A form of Autoimmune Liver Disease. (Previously called Primary Biliary Cirrhosis) Characterized by a T-lymphocyte-mediated attack on small intralobular bile ducts. Continuous assault on bile duct epithelial cells leads to their gradual destruction and eventual disappearance. This leads to a cycle of cholestasis and liver fibrosis. Associations: Symptoms: Female (95%) Fatigue Sjogren's syndrome Pruritis Autoimmune thyroid disease Sicca Rheumatoid arthritis Signs and symptoms of CLD Coeliac disease Inflammatory bowel disease The disease is chronic and often progressive, resulting in end-stage liver disease 50% of people are asymptomatic at time of diagnosis PRIMARY BILIARY CHOLANGITIS Diagnosis: - Cholestatic LFT picture: o Alkaline Phosphatase /GGT almost always elevated (generally 3-4x normal)​ o AST, ALT < 200 U/L​ o Raised bilirubin in later stages of disease Xanthelasma - Antimitochondrial Antibody: AMA (hallmark of diagnosis) - Raised cholesterol (leading to xanthoma and xanthelama) - Liver biopsy and histology: chronic non-suppurative, granulomatous, lymphocytic small bile duct cholangitis Treatment - 1st line: Ursodeoxycholic Acid - Benzafibrate - Obeticholic acid Xanthoma - Budesonide PRIMARY SCLEROSING CHOLANGITIS A form of Autoimmune Liver Disease. Primary sclerosing cholangitis A chronic progressive disorder of unknown aetiology that is characterized by inflammation, fibrosis, and stricturing of medium and large ducts in the intrahepatic and/or extrahepatic biliary tree Associations Ulcerative colitis IBD is present in 50-80% of people with PSC PRIMARY SCLEROSING CHOLANGITIS – DIAGNOSIS A form of Autoimmune Liver Disease. Diagnosis: Cholestatic LFTs: Raised ALP and gGT​ History of IBD Imaging: MRCP (magnetic resonance cholangio pancreatography) Beaded Characteristic radiological features usually appearance of make diagnosis: Multifocal, short, annular strictures that bile ducts on alternate with normal or mildly dilated segments. This MRCP results in a "beaded" appearance of the bile duct. Long strictures may also be seen and are concerning for cholangiocarcinoma. Autoantibodies can be supportive Management: Trial UDCA No proven medical therapy Screening for complications - Cholangiocarcinoma (Lifetime risk 7-15%) AUTOIMMUNE HEPATITIS A form of Autoimmune Liver Disease. A chronic, inflammatory disease of the liver that is characterized by circulating autoantibodies and elevated serum globulin levels Challenging to diagnose and manage as it is a rare, and heterogenous disease. Associations Female > Male (4:1) Clinical Features: Broad range of symptoms, from asymptomatic to acute/severe or even fulminant liver disease. Classically: Middle-aged (or teenage) woman, but can occur at any age, in both men and women Fatigue, malaise, weight loss, nausea, pruritis, jaundice, polyarthralgia, oligomenorhhoea. Signs and symptoms of liver disease Risk of progression to HCC  AUTOIMMUNE HEPATITIS Diagnosis: AIH is a clinical diagnosis - Exclusion of other causes of CLD - Hypergammaglobulinaemia - Hepatocellular pattern of LFT derangement: o Elevated ALT, AST - Positive ANA, SMA, Anti-LKM (not disease specific). - Liver Biopsy: Histology shows interface hepatitis with lymphoplasmacytic infiltrate, periportal necrosis, and rosetting of hepatocytes Histologic hallmarks of autoimmune hepatitis. (A) - Excellent response to corticosteroids is telling Depiction of a normal hepatic lobule, note the clear delineation between the connective tissue of the portal triad and the hepatocytes. In autoimmune hepatitis, (B and Treatment: C) lymphocytic infiltrate accumulates in the portal triad. Interface hepatitis (C) occurs when the lymphocytes in the - Prednisolone portal triad invade the limiting plate spilling around the - Azothioprine hepatocytes Source: https://my.clevelandclinic.org/departments/digestive/medica  Alcohol related liver disease​ Non-alcoholic fatty liver disease​ Viral Hepatitis- Hepatitis B, C​ Autoimmune Hepatitis​ Primary Sclerosing Cholangitis​ Primary Biliary cholangitis​ Medication related: Methotrexate, amiodarone​ Hereditary: Haemochromatosis, Wilson's Disease, Alpha 1 Antitrypsin Deficiency​ CHF/Nephrotic syndrome (for oedema) DIFFERENTIAL DIAGNOSIS INVESTIGATIONS AND DIAGNOSIS WHAT ARE LIVER FUNCTION TESTS? Liver enzymes (damage to different ALT/AST parts of the liver): ALT: alanine transaminase AST: aspartate aminotransferase ALP: Alkaline phosphatase ALP/gGT GGT: Gamma-glutamyl transferase Liver function (the liver is doing what it should be doing):​ LFT patterns: Bilirubin​ Hepatocellular/parenchymal damage: Raised Albumin​ transaminases: ALT/AST Cholestatic/obstructive: Raised ALK PHOS/GGT Prothrombin time​ Bilirubin can be raised in either Platelets Alcoholic hepatitis: AST>ALT ratio is >2:1 (AST>ALT: Scotch is stronger than Limoncello) INVESTIGATIONS Bloods Explanation LFTs Raised ALT/AST: indicate hepatocyte damage Raised GGT/ALP: indicate biliary tree injury Raised bilirubin: Visible jaundice when approx >50 Coagulation profile Raised INR, reduced coagulation factor production –measure of liver synthetic function Albumin Reduced- measure of synthetic function FBC Anaemia Thrombocytopenia: Low platelets Viral Hepatitis Screen Hep A, B, C, EBV, CMV, VZV, HIV Autoantibody screen ANA, SMA, Anti-LKM- AIH Anti Smooth muscle Ab- PSC AMA: Anti Mitochondrial Ab-PBC Iron studies and ferritin Raised Ferritin, Fe, and T sat, low TIBC- HFE Caeruloplasmin and serum Reduced in Wilson's copper  INVESTIGATIONS Imaging Explanation Liver Ultrasound Evaluate liver morphology for nodularity or coarse texture of cirrhosis, evaluate for ascites, hepatomegaly/splenomegaly, HCC MRI Liver/ MRCP MRI Liver- higher quality image evaluate for liver tumour/morphology MRCP to evaluate the biliary tree- PSC/PBC OGD To screen/surveillance of oesophageal varices Special Tests Liver elastography Can give a score to evaluate for hepatic (Fibroscan) steatosis and fibrosis Liver Biopsy Gold standard but invasive, may not be required if other investigations suggest CLD/Cirrhosis Fibroscan SCORING SYSTEMS CHILD-PUGH SCORE Estimates cirrhosis mortality Classified A,B or C Composite of Total bilirubin, albumin, INR, ascites and hepatic encephalopathy MELD: Mayo End-Stage Liver Disease (MELD) Serum bilirubin, serum creatinine, and the international normalized ratio (INR) of prothrombin time. MELD is an excellent predictor of 3-month mortality among cirrhotic patients listed for liver transplantation Kings College Criteria: Acute Liver Failure MANAGEMENT Prevention: Alcohol cessation, avoid hepatotoxic medications e.g paracetamol/NSAIDS, weight loss and diet management, DM optimisation for hepatic steatosis, Hep A and B vaccination Pharmacological: Beta Blockers for varices, Lactulose for encephalopathy (increases bacterial uptake of ammonia), Rifaxamin for encephalopathy, Diuretics and low salt diet for ascites and oedema management. Procedures: Paracentesis to drain ascitic fluid, OGD banding of varices, Trans-jugular Intrahepatic Portosystemic Shunt Surgical: Liver transplant definitive management Palliative care: can be involved early for optimisation of symptoms and advanced care planning Paracentesis MEDICAL EMERGENCY: VARICEAL HAEMORRHAGE Rupture of oesophageal varices MORTALITY: overall mortality with each episode of VH remains around 15% to 25% at six weeks Resuscitation ABC: IVC x 2, crystalloid fluids, blood transfusion aiming for Hb 7- 9g/dL Pharmacological Management Somatostatin Terlipressin Sengstaken- Antibiotic prophylaxis Blakemore Tube (Ceftriaxone) Source Control Balloon tamponade, Endoscopy inserted into the Band ligation oesophagus and inflated OR Sengstaken-Blakemore ​Tube to apply manual Long-term pressure to bleeding Blood splurting from Prophylaxis: Non-cardioselective vessel. oesophageal varix, seen beta blockers: propranolol Indicated only in rare on OGD cases of very unstable, uncontrolled  1 2 3 4 5 6 7 8 Case Presentation: 3 A 65 year old gentleman presents to the emergency department with PLANNING MANAGEMENT acute confusion and behavioural disturbance. His past medical history includes haemochromatosis and chronic liver disease. Physical examination demonstrates asterixis, distended abdomen with shifting dullness, caput medusae. Which of the following is an appropriate treatment to address this gentleman's confusion? a. Cefotaxime b. Lactulose c. Lorazepam d. Rifampacin e. Senna  1 2 3 4 5 6 7 8 Case Presentation: A 65 year old gentleman presents to the emergency department with acute 3 PLANNING confusion and behavioural disturbance. His past medical history includes MANAGEMENT chronic liver disease. Physical examination demonstrates asterixis, distended abdomen with shifting dullness, caput medusae. Which of the following is an appropriate treatment to address this gentleman's confusion? a. Cefotaxime b. Lactulose c. Lorazepam d. Rifampacin e. Senna ANSWER: B Lactulose lowers ammonia levels and therefore is indicated for the treatment of hepatic encephalopathy, aim for 3 bowel motions per day. Rifaxamin (not rifampacin) is also indicated, in addition to lactulose. Senna is a stimulant laxative and has no role in ammonia reduction. Lorazepam sedation will not address the underlying cause. Cefotaxime is an antibiotic used for treatment of spontaneous bacterial peritonitis.  1 2 3 4 5 6 7 8 Case Presentation: Section 4: A 55 year old lady is referred to the hepatology service with jaundice Providing Information and hepatocellular derangement of her liver function tests. She is a non drinker, with no metabolic risk factors, normal ferritin. Her AMA and SMA antibodies are positive. The hepatology team prescribes a prolonged tapering course of prednisolone. Select the most appropriate piece of information to discuss with the patient? a. Bone protection should be considered with prolonged steroid use b. Gastric protection is not required with prednisolone c. Patients are at risk of hypotension on steroid therapy d. Steroids do not increase the risk of diabetes e. There is no risk associated with stopping steroids suddenly  1 2 3 4 5 6 7 8 Case Presentation: Section 4: A 55 year old lady is referred to the hepatology service with jaundice Providing Information and hepatocellular derangement of her liver function tests. She is a non drinker, with no metabolic risk factors, normal ferritin. Her AMA and SMA antibodies are positive. The hepatology team prescribes a prolonged tapering course of prednisolone. Select the most appropriate piece of information to discuss with the patient? a. Bone protection should be considered with prolonged steroid use b. Gastric protection is not required with prednisolone c. Patients are at risk of hypotension on steroid therapy d. Steroids do not increase the risk of diabetes e. There is no risk associated with stopping steroids suddenly ANSWER: A The following are amongst the steroid risk: Osteoporosis, gastric ulceration, hypertension, diabetes, adrenal crisis with abrupt