Chronic Hepatitis & Liver Cirrhosis PDF

Chronic hepatitis &Liver cirrhosis Acute hepatitis C HCV is a single-stranded RNA virus with properties similar to those of flaviviruses. Seven major genotypes of HCV have been identified. Genotype 4 is the most prevalent in Egypt Modes of transmission: blood born Over 60% o...

Chronic hepatitis &Liver cirrhosis Acute hepatitis C HCV is a single-stranded RNA virus with properties similar to those of flaviviruses. Seven major genotypes of HCV have been identified. Genotype 4 is the most prevalent in Egypt Modes of transmission: blood born Over 60% of cases are transmitted by injection drug use(addicts) Body piercing, tattoos, hemodialysis are risk factors. The risk of sexual and maternal–neonatal transmission is low Having multiple sexual partners may increase the risk of HCV infection, and HIV coinfection Symptoms and Signs The incubation period for hepatitis C: 6–7 weeks, Clinical illness is often mild, usually asymptomatic or subclinical Sometimes fever, right hypochondrial pain, nausea, vomiting, jaundice, markedly elevated transaminases. Characterized by waxing and waning aminotransferase elevations and a high rate (greater than 80%) of chronic hepatitis. Inpregnant patients with chronic hepatitis C, serum aminotransferase levels frequently normalize despite persistence of viremia, only to increase again after delivery. Lab diagnosis Detection of HCV antibodies by enzyme immunoassay (EIA). Diagnosis confirmed by PCR for HCV RNA. anti-HCV antibodies without HCV RNA in the serum, suggesting recovery from HCV infection in the past. Course of acute and chronic hepatitis C Complications mixed cryoglobulinemia and membranoproliferative glomerulonephritis autoimmune thyroiditis, lymphocytic sialadenitis, idiopathic pulmonary fibrosis, sporadicporphyria cutanea tarda, monoclonal gammopathies, and type 2 diabetes mellitus. Complications 20–30% or more increased risk of B-cell non-Hodgkin lymphoma, genotype 1) is associated with an increased risk of end-stage renal disease. Hepatic steatosis is a particular feature of infection with HCV that’s why whenever found I ultrasound viral markers should be asked for. HCV infection during pregnancy is associated with preterm birth and intrahepatic cholestasis of pregnancy Treatment of acute hepatitis C Treatment Direct acting antivirals A 6-week course of ledipasvir and sofosbuvir has been shown to prevent chronic hepatitis in patients with acute genotype-1 hepatitis C and lack of spontaneous clearance after 3 months. Treatment of acute hepatitis C may be cost effective and is particularly recommended in people who inject drugs. Chronic hepatitis C Most chronic infection is initially asymptomatic (75%), chronic hepatitis progresses to cirrhosis after 20 years in 25% of cases. Patientsmay have insidious fatigue and raised transaminases and might be discovered accidently during routine check up Diagnosis Elevated transaminases Positive HCV antibodies Positive PCR for HCV.  TREATMENT OF CHRONIC HEPATITIS C When you do consider the patient cured? The patient is considered cured when HCVRNA is negative 3 months after end of treatment and this is called sustained virological response Prognosis Chronichepatitis, which progresses slowly in many cases, develops in as many as 85% of all persons with acute hepatitis C. Ultimately, cirrhosis develops in up to 30% of those with chronic hepatitis C; the risk of cirrhosis and hepatic decompensation is higher in patients coinfected with both HCV and HBV or HIV. Patients with cirrhosis are at risk for hepatocellular carcinoma at a rate of 3– 5% per year. Hepatitis D HDV is a defective RNA virus that causes hepatitis only in association with HBV infection Infection (blood borne)is either co-infection or superadded infection Inco-infection, the infection is generally similar in severity to acute hepatitis B alone. Superinfection carries a worse short-term prognosis, often resulting in acute liver failure or progresses rapidly to cirrhosis. The diagnosis of hepatitis D is made by detection of antibody to hepatitis D antigen (anti-HDV) and, where available, hepatitis D antigen (HDAg) or HDV RNA in serum. Hepatitis E Hepatitis E HEV is a 27- to 34-nm RNA hepevirus (in the Hepeviridae family) that is a major cause of acute hepatitis throughout Central and Southeast Asia Mode of transmission feco-oral It should be considered in patients with acute hepatitis after a trip to an endemic area. In rare cases, hepatitis E can be mistaken for drug-induced liver injury. Acute fulminant hepatitis, acute hepatitis during pregnancy Hepatitis E Illness generally is self-limited (no carrier state), but instances of chronic hepatitis with rapid progression to cirrhosis attributed to HEV genotype 3 have been reported in transplant recipients (particularly when tacrolimus rather than cyclosporine is used as the main immunosuppressant) and, rarely, in persons with HIV infection, preexisting liver disease, or cancer undergoing chemotherapy. The diagnosis of acute hepatitis E is made most readily by testing for IgM antiHEV in serum, although available tests may not be reliable. Treatment Indications for treatment HBeAg-negative chronic hepatitis hepatitiѕ B e antigen (ΗΒеAg)-negative chronic hераtitis (ALT >2 x ULN and НBV DNA >2000 international units/mL) HBeAg positive (immune active phase) For hераtitiѕ B e antigen (НBеAg)-positive patients without cirrhosis, treatment should be initiated when the НBV DNA is >20,000 international units/mL (>105 copies/mL) and the ALT is >2 x ULN Treatment Indications for treatment Compensated cirrhosis and detectable НΒV DNA should be treated with antiviral therapy regardless of the НΒeAg status or the serum ALT level Acute liver failure or decompensated cirrhosis secondary to ΗBV should initiate antiviral therapy as soon as possible. Treatment Indications for treatment Patients receiving immunosuppressive therapy Antiviral therapy should be administered to most patients with chronic HΒV before initiating immunosuppressive therapy, regardless of the НΒV DNA or aminotransferase levels. Such patients are at risk for ΗBV reactivation. Pregnant patients (indications same as non pregnant) However, to prevent transmission to their child, pregnant patients with high viral loads (>2 x 105 international units/mL) should initiate therapy in the late second or early third trimester, even if the aminotransferase levels are normal. Treatment Indications for treatment Patients with hepatocellular carcinoma All patients with HCC should be treated with a nucleos(t)ide analog (eg, tenofovir or entecavir) as this might reduce the risk of HCC recurrence, and improve the prognosis of HBV-related HCC after curative therapy. Transient elastography by FibroScan Treatment is recommended with evidence of significant fibrosis (≥F2) based on TE (FibroScan®) value >7 kPa or evidence of cirrhosis (F4) based on clinical criteria with TE (FibroScan ®) value of >12.5 kPa, regardless of HBV DNA or ALT levels Treatment aim: Suppress viral replication and decrease viral load Decrease ongoing hepatic injury Prevent or reverse complications of cirrhosis Reduce risk of hepatocellular carcinoma Induction of long-term suppression of HBV-DNA levels represents the main end point of all current treatment strategies Current therapy for chronic hepatitis B does not eradicate hepatitis B virus and has limited long-term efficacy Drug therapy: Peginterferon Peginterferon Alfa-2a : Adults: 180 mcg subcutaneously once weekly for 48 weeks. Nucleotide analogue Tenofovir Tenofovir alafenamide Oral tablet; Adults: 25 mg PO once daily. Tenofovir fumarate Oral tablet; Adults: 300 mg PO once daily. Nucleoside analogue Entecavir: oral tablets 0.5 mg and 1 mg tab Drugs Peginterferon alfa-2a peginterferon alfa-2a 180 μg/wk only Child A, side effects Antinucleos(t)ides: Entecavir 0.5, 1mg Lamivudine 100 mg Adefovir, tenofovir, Telbivudine HBV vaccine Plasma-derived and recombinant HBV vaccines use HBsAg to stimulate the production of anti-HBs in noninfected individuals. The vaccines are highly effective, with a greater than 95% rate of seroconversion. Vaccine administration is recommended for all infants and for adults at high risk of infection (eg, those receiving dialysis, healthcare workers). The recommended vaccination schedule for infants is an initial vaccination at the time of birth (ie, before hospital discharge), repeat vaccination at 1-2 months, and another repeat vaccination at 6-18 months. The recommended vaccination schedule for adults is an initial vaccination, a repeat vaccination at 1 month, and another repeat vaccination at 6 months Postexposure prophylaxis Hepatitis B immune globulin (HBIG) is derived from plasma. It provides passive immunization for individuals who describe recent exposure to a patient infected with HBV. Recommendations for postexposure prophylaxis for contacts of patients positive for HBsAg are as follows Perinatal exposure - HBIG plus vaccination at time of birth (90% effective) Sexual contact with an acutely infected patient - HBIG plus vaccination Sexual contact with a chronic carrier - Vaccination Liver cirrhosis Liver Cirrhosis Cirrhosis is a histological diagnosis characterized by advanced (bridging) fibrosis, and architectural (nodule formation) and microvascular distortion. Pathophysiology Chronic hepatic inflammation and injury result in and hepatic stellate cell activation and endothelial cell damage Activatedstellate cells produce collagen (fibrosis), with subsequent vascular and organ contractions Its clinical features relate to loss of synthetic function, portal hypertension and HCC Clinical picture Manifestations of portal hypertension ( Portal vein pressure of greater than 8 mm Hg) Esophageal varices Ascites Splenomegaly GIT congestion, nausea and dyspepsia Manifestations of liver cell dysfunction Jaundice, encephalopathy, white nails, gynecomastia, palmar erythema, spider angioma, oedema lower limbs Investigations Laboratory Transaminases may be elevated or normal Bilirubin high biphasic Albumin is low, alpha feto protein is high in cirrhosis and in HCC Viral markers Autoimmune (antimitochondrial antibodies, LKM ab, soluble liver antigen Metabolic causes heamochromatosis increase serum iron Wilsons disease increase urinary coppor and serum ceruloplasmin Investigations Imaging Ultrasound irregular surface, dilated portal vein, splenomegaly CT triphasic If there is focal lesion by ultrasound characteristic features Endoscopy Esophageal varices, gastric varices Ascites Pathogenesis in cirrhosis includes elevated hydrostatic pressure from sinusoidal/portal hypertension, renal sodium retention secondary to sympathetic activation of renin- angiotensin-aldosterone system, and reduced oncotic pressure caused by hypoalbuminemia Clinical Presentation Patients may complain of early satiety, increased abdominal girth, weight gain, or respiratory distress Physical examination can reveal abdominal distention, bulging flanks, shifting dullness (most sensitive), fluid wave (least sensitive), or ballotable liver/spleen. General stigmata of cirrhosis are often present, including spider angiomata and palmar erythema Palmar erythema Spider angioma Diagnosis Abdominal ultrasound with Doppler can detect small amounts of intraperitoneal fluid and evaluate for portal vein thrombosis or Budd-Chiari syndrome Diagnostic paracentesis with ascitic fluid analysis is indicated in all patients with new-onset ascites and most patients with ascites who are admitted to the hospital Routine ascitic fluid testing includes cell count with differential, total protein, and albumin  Ifinfection suspected, also order gram stain, culture, and sensitivity Serum-ascites albumin gradient (SAAG) SAAG = serum albumin − ascitic albumin SAAG 1.1 g/dL or greater predicts portal hypertension with 97% accuracy Ascitic total protein is usually low in cirrhosis If ascitic total protein greater than 2.5 g/dL and SAAG greater than or equal to 1.1 g/dL, consider a cardiac etiology. If ascitic total protein greater than 2.5 g/dL and SAAG less than 1.1 g/dL, the differential is peritoneal carcinomatosis and tuberculous peritonitis. Treatment Restrict dietary sodium to less than 2 g/day Diuretics spironolactone 100 mg and furosemide 40 mg taken orally once a day Spironolactone blocks the action of aldosterone on mineralocorticoid receptors in the distal tubule and collecting duct of the kidney nephron, resulting in an inhibition of sodium reabsorption and potassium excretion Loop diuretics (e.g., furosemide) inhibit the reabsorption of sodium, potassium, and chloride in the ascending limb of the loop of Henle Goals of diuretic therapy: 24-hour urinary sodium greater than 78 mmol, spot urine sodium/potassium ratio greater than 1, or maximum weight loss of 0.5 kg/day (1.0 kg/day in patients with edema) Treatment Refractory ascites is defined as persistent ascites despite adequate sodium restriction and maximum-dose diuretics (i.e., spironolactone 400 mg/day and furosemide 160 mg/day), or intolerance of diuretic therapy Serial large-volume (i.e., 5 L or greater) paracenteses (LVP) may be necessary. Albumin infusion of 6 to 8 g/L of ascites removed may improve survival TIPS in carefully selected patients can offer superior control of ascites compared with serial LVP Liver transplantation should be considered in patients with refractory ascites Spontaneous bacterial peritonitis Present in approximately 10% of hospitalized patients with cirrhosis, spontaneous bacterial peritonitis (SBP) is the most important potential sequela of ascites Mortality is 10% to 20% during the same hospitalization, and is predicted by worsening renal function Approximately 70% recurrence rate within 1 year of infection Median survival is 9 months after development of SBP Complications of liver cirrhosis Hepatorenal syndrome Hepatic encephalopathy Hepatocellular carcinoma Spontaneous bacterial peritonitis Spontaneous bacterial peritonitis Risk factors for SBP include upper gastrointestinal hemorrhage, ascitic fluid protein concentration less than 1 g/dL, and a previous episode of SBP Clinical Presentation Suspect SBP in cirrhotic patients with worsening jaundice, encephalopathy, or renal failure Fever, chills, and generalized abdominal pain can be seen; 33% of patients with cirrhosis and SBP will not have a fever or leukocytosis Spontaneous bacterial peritonitis Diagnosis Diagnosis is made when ascitic fluid polymorphonuclear (PMN) cell count is 250/mm3 or higher. PMN count greater than 1000/mm3 suggests bowel perforation. Treatment Cefotaxime and ceftriaxone are the empiric antibiotics of choice Albumin infusion, 1.5 g/kg body weight on day 1 of diagnosis and 1.0 g/kg on day 3 Spontaneous bacterial peritonitis Long-term prophylaxis with a fluoroquinolone or trimethoprim- sulfamethoxazole is indicated in patients who recover from an episode of SBP Hepatorenal syndrome (HRS) is a class of renal failure that occurs in advanced liver disease and portal hypertension Hallmarks are oliguria, azotemia, and reduced urinary sodium excretion. Hepatic Encephalopathy Defined as neurologic or psychiatric disturbances associated with acute or chronic liver insufficiency and/ or portosystemic shunting West Haven Criteria (WHC) severity grading for hepatic encephalopathy Overt HE spans from disorientation/asterixis to coma, corresponding to WHC grades 2 to 4 Covert HE includes minimal and grade 1 HE Failure of liver to clear intestinal toxins (e.g., ammonia), which then accumulate in the systemic circulation, eventually migrating into the brain Ammonia forms glutamine in astrocytes, causing cellular swelling, which precipitates cerebral edema and impairs cognition Hepatic Encephalopathy Precipitating factors Diuretics Heavy protein meal Disturbed electrolytes Gastrointestinal heamorrhage Treatment Lactulose, rifaximin, chronic protein restriction, treat precipitating cause