Hepatitis Introduction Hepatitis A Risk Factors: a) Poor hygiene b) Contact with infected people c) Anal-oral contact d) Travelling to endemic places e) Use of needles (very rare) Hep A • Has 4 genotypes • Resistant to bile salts since it is not enveloped • Resistant towards cold, hot (not very high temp), detergent and acid • Inactivated by formalin, chlorine and >38.5C • It can survive in a dry environment from 2 hours to 60 days Transmission • Main transmission: Fecal-oral • Sexual
• Use of needles, blood transfusion (very rare)
Natural History • S&S develop 15-50 (mean 25-30 days) after infection • 1-2 weeks after S&S develops, the feces is infectious Viremia: 3 days – 5 weeks post-infection Detected in feces: 1-5 weeks PI Clinical manifestations: 2-8 weeks PI Inrease in AST/ALT: 2 weeks PI, peak 4 weeks IgM anti HAV: 1 week PI IgG anti HAV: 3 weeks PI Clinical Symptoms Signs • Chills • Cough • Myalgia • Arthralgia • Diarrhea • Constipation • Urticaria • Pruritus • Skin Rash Symptoms • Fever • Bradycardia • Icteric • Lymphadenopathy • Hepatosplenomegaly Lab • Increase in SGPT is more than increase in SGOT • Increase in biliruin, Gamma-GT, AP, PT Treatment • Symptomatic: antipyretic, antiemetic • Enough hydration • Adequate nutrition
Indication for hospitalization:
• Not enough food intake due to massive vomitting • Dehydration • Signs of liver failure: encephalopathy, coagulopathy Minimalizing Risk of Infection • Adult 2 weeks before and 2 weeks after onset • Kids and Immunocompromised lasts up to 6 months after onset Hep A • Hepatitis A tends to be more symptomatic in adults; therefore, paradoxically, as the frequency of HAV infection declines, the likelihood of clinically apparent, even severe, HAV illnesses increases in the susceptible adult population Hepatitis B Transmission Natural History Phases of Infections Hep B Covalently closed circular DNA (ccc) enables Hep B to directly cause HCC without the cirrhotic phase Progression of Dz Lab • Seroconversion: HbeAg (-) and anti-Hbe (+) • Active replication of virus has diminished tremendously • Seroconversion HbeAg is used to judge clinically the improvement in chronic Hep B Lab • Anti-Hbc to diagnose whether someone is currently having an acute infection or not Lab • DNA Hep B the most accurate way to know the viral load • This way, we can predict whether the patient is going to develop a full blown cirrhosis or HCC Treatment Hepatitis C Transmission Lab • Anti HCV shows that someone has been infected before • No protection effect • Formed 7-8 weeks post infection Lab • HCV RNA to know the presence & quantity of virus in the body • Formed 7-10 days post infection Treatment Goal • Therapy goal CURE Treatment Hepatitis D • Hepatitis D Co-infection with Hepatitis B Ascites • Ascites is present when there is accumulation of free fluid in the peritoneal cavity. • Small amounts of ascites are asymptomatic, but with larger accumulations of fluid (> 1 L) there is abdominal distension, fullness in the flanks, shifting dullness on percussion and, when the ascites is marked, a fluid thrill. • Other features include eversion of the umbilicus, herniae, abdominal striae, divarication of the recti and scrotal oedema. Dilated superficial abdominal veins may be seen if the ascites is due to portal hypertension Diagnosis • USG best means of detecting ascites • Paracentesis obtain fluid • SAAG differentiate between exudate or transudate • <25 g/L usually cirrhotic patient transudate Treatment • Sodium and water retention • Diuretics • Paracentesis • TIPS • Peritoneo-venous shunt Hepatic Encephalopathy • Hepatic encephalopathy is a neuropsychiatric syndrome caused by liver disease. • As it progresses, confusion is followed by coma. • Features include changes of intellect, personality, emotions and consciousness, with or without neurological signs. The degree of encephalopathy can be graded from 1 to 4, depending on these features, and this is useful in assessing response to therapy • When an episode develops acutely, a precipitating factor may be found Signs and symptoms • The earliest features are very mild and easily overlooked but, as the condition becomes more severe, apathy, inability to concentrate, confusion, disorientation, drowsiness, slurring of speech and eventually coma develop. Convulsions sometimes occur. Examination usually shows a flapping tremor (asterixis), inability to perform simple mental arithmetic tasks or to draw objects such as a star (constructional apraxia), and, as the condition progresses, hyper-reflexia and bilateral extensor plantar responses. • Hepatic encephalopathy rarely causes focal neurological signs; if these are present, other causes must be sought. Fetor hepaticus, a sweet musty odour to the breath, is usually present but is more a sign of liver failure and portosystemic shunting than of hepatic encephalopathy. Rarely, chronic hepatic encephalopathy (hepatocerebral degeneration) gives rise to variable combinations of cerebellar dysfunction, Parkinsonian syndromes, spastic paraplegia and dementia Pathophysiology • Patof Ammonia overload Diagnosis • Diagnosis made clinically • In doubt EEG diffuse slowing of the normal alpha waves with eventual development of delta waves Treatment • Lactulose (15–30 mL 3 times daily) is increased gradually until the bowels are moving twice daily. It produces an osmotic laxative effect, reduces the pH of the colonic content, thereby limiting colonic ammonia absorption, and promotes the incorporation of nitrogen into bacteria. • Rifaximin (400 mg 3 times daily) is a well-tolerated, non-absorbed antibiotic that acts by reducing the bacterial content of the bowel and has been shown to be effective. It can be used in addition, or as an alternative, to lactulose if diarrhoea becomes troublesome Histology of Liver Cirrhosis • Cirrhosis is characterised by diffuse hepatic fibrosis and nodule formation • Worldwide, the most common causes are chronic viral hepatitis, prolonged excessive alcohol consumption and NAFLD. Cirrhosis is the most common cause of portal hypertension and its complications. Pathophysiology Types of Cirrhosis • Cirrhosis is a histological diagnosis • It evolves over years as progressive fibrosis and widespread hepatocyte loss lead to distortion of the normal liver architecture that disrupts the hepatic vasculature, causing portosystemic shunts. • Cirrhosis can be classified histologically into: – Micronodular cirrhosis, characterised by small nodules about 1 mm in diameter and typically seen in alcoholic cirrhosis. – Macronodular cirrhosis, characterised by larger nodules of various sizes. Areas of previous collapse of the liver architecture are evidenced by large fibrous scars. Management • Treat underlying causes • Endoscopy every 2 years Portal Hypertension The normal hepatic venous pressure gradient (difference between the wedged hepatic venous pressure and free hepatic venous pressure, see below) is 5–6 mm Hg. Clinically significant portal hypertension is present when the gradient exceeds 10 mm Hg and risk of variceal bleeding increases beyond a gradient of 12 mm Hg Clinical Feature • The clinical features result principally from portal venous congestion and collateral vessel formation • Splenomegaly is a cardinal finding Pathophysiology • Increased portal vascular resistance leads to a gradual reduction in the flow of portal blood to the liver and simultaneously to the development of collateral vessels, allowing portal blood to bypass the liver and enter the systemic circulation directly. • Portosystemic shunting occurs, particularly in the gastrointestinal tract and especially the distal oesophagus, stomach and rectum, in the anterior abdominal wall, and in the renal, lumbar, ovarian and testicular vasculature. Diagnosis • Usually clinically • Measure WHVP • Endoscopy • USG • CT & MRI Management • Prevention of acute bleeding beta blocker Hepatocellular Carcinoma (Hepatoma) • Cirrhosis is present in 75–90% of individuals with HCC and is an important risk factor for the disease. The risk is between 1% and 5% in cirrhosis caused by hepatitis B and C • The risk is four times higher in HBeAg-positive individuals than in those who are HBeAg- negative • Risk is higher in men as they age HCC • Macroscopically, the tumour usually appears as a single mass in the absence of cirrhosis, or as a single nodule or multiple nodules in the presence of cirrhosis. It takes its blood supply from the hepatic artery and tends to spread by invasion into the portal vein and its radicals
• Can be caused by aflatoxin
Clinical Presentation • Two types of presentation: 1. Underlying Cirrhosis Deterioration in their liver function with worsening ascites and/or jaundice or variceal hemorrhage Symptoms: weight loss, anorexia, abdominal pain, hepatomegaly, right hypochondrial mass 2. Screening of patients at risk of HCC Lab • AFP 60% increase • Imaging: a) USG focal liver lesion b) CT w/ contrast GOLD STANDARD Barcelona Clinic Liver Cancer Staging Primary Biliary Cirrhosis (PBC) & Primary Sclerosing Cholangitis (PSC) • Both present early with fatigue and pruritus • Autoimmune disease • PSC Men, PBC Women Alcoholic Liver Disease • A threshold of 14 units/week in women and 21 units/week in men is generally considered safe. The risk threshold for developing ALD is variable but begins at 30 g/day of ethanol • Risk factors: Drinking pattern, gender, genetics and nutrition Pathophysiology Treatment • Nutrition • Corticosteroids • Pentoxifylline • Liver Transplantation Non-Alcoholic Fatty Liver Disease (NAFLD) • Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of liver disease encompassing simple fatty infiltration (steatosis), fat and inflammation (non- alcoholic steatohepatitis, NASH) and cirrhosis, in the absence of excessive alcohol consumption (typically a threshold of < 20 g/day for women and < 30 g/day for men is adopted) Pathophysiology Natural History Lab • Increase in AST & ALT • USG appears ‘bright’ • Liver biopsy gold standard Management • Lifestyle • HMG-CoA reductase inhibitor • Tocoferol