Hepatitis C and Related Conditions Quiz

Chronic Hepatitis & Liver Cirrhosis

• HCV is a single-stranded RNA virus similar to flaviviruses
• Seven major genotypes of HCV have been identified
• Genotype 4 is most common in Egypt
• Transmission modes include blood-borne infections
• Injection drug use is the leading cause of transmission, with over 60% of cases
• Body piercings, tattoos, and hemodialysis are risk factors
• Sexual and mother-to-child transmission are rare
• Multiple sexual partners increase risk of both HCV and HIV infection
• Incubation period for hepatitis C is 6-7 weeks
• Acute illness is often mild, usually asymptomatic
• Occasionally, fever, right upper quadrant pain, nausea, vomiting, and jaundice are observed
• Significantly elevated transaminase levels
• High rate of chronic hepatitis (greater than 80%) is a characteristic feature
• In pregnant patients, serum aminotransferase levels usually normalize despite persistent viremia then increase again post-partum

Acute Hepatitis C

• The incubation period for hepatitis C is 6–7 weeks
• Acute illness is often mild and usually asymptomatic
• Fever, right hypochondrial pain, nausea, vomiting, and jaundice are observed occasionally
• Significantly elevated transaminase levels
• High rate of chronic hepatitis (greater than 80%) is a characteristic feature
• In pregnant patients, serum aminotransferase levels typically normalize despite persistent viremia then increase again post-partum

Lab Diagnosis

• HCV antibodies are detected using enzyme immunoassay (EIA)
• Diagnosis is confirmed with PCR for HCV RNA
• Presence of anti-HCV antibodies without HCV RNA suggests recovery from prior infection

Course of Acute and Chronic Hepatitis C

• A graph demonstrates the fluctuating levels of jaundice, symptoms, ALT, anti-HCV, and HCV RNA (PCR) over time (months and years)

Complications

• Mixed cryoglobulinemia and membranoproliferative glomerulonephritis
• Autoimmune thyroiditis
• Lymphocytic sialadenitis
• Idiopathic pulmonary fibrosis
• Sporadic porphyria cutanea tarda
• Monoclonal gammopathies
• Type 2 diabetes mellitus
• 20-30% or more increased risk of B-cell non-Hodgkin lymphoma
• Genotype 1 is associated with end-stage renal disease risk
• Hepatic steatosis is common and associated with HCV infection
• HCV infection in pregnancy can lead to premature birth and intrahepatic cholestasis

Treatment of Acute Hepatitis C

• Direct-acting antivirals (DAAs), such as a 6-week course of ledipasvir and sofosbuvir are effective
• DAAs can prevent chronic hepatitis in acute genotype 1 hepatitis C patients who do not spontaneously clear the infection within 3 months
• Drug treatment is particularly recommended for individuals who inject drugs

Chronic Hepatitis C

• Most infections are initially asymptomatic (75%)
• Chronic hepatitis may progress to cirrhosis in 25% of cases within 20 years
• Patients may experience insidious fatigue and elevated transaminases, with incidental diagnosis during routine checkups

Diagnosis

• Elevated transaminases
• Positive HCV antibodies
• Positive PCR for HCV

Treatment of Chronic Hepatitis C

• Treatment strategies for chronic hepatitis C are described

HCV Virus

• The HCV virus is a 9.6kb RNA virus
• The virus has different proteins: NS3/NS4A Protease Inhibitors; NS5A Inhibitors; and NS5B Polymerase Inhibitors
• Corresponding medications are mentioned (e.g., Ledipasvir, Sofosbuvir)

Patient Cured

• The patient is considered cured when HCV RNA is negative 3 months after treatment, this is known as sustained virological response

Prognosis

• Chronic hepatitis progresses slowly in many cases and develops in up to 85% of individuals with acute hepatitis C.
• Cirrhosis can develop in up to 30% of those with chronic hepatitis C
• Risk of cirrhosis and hepatic decompensation is higher in patients coinfected with HBV or HIV
• Patients with cirrhosis have a 3-5% per year risk of hepatocellular carcinoma (HCC)

Hepatitis D

• HDV is an RNA virus requiring HBV for replication
• Co-infection with HBV is generally similar in severity to acute hepatitis B alone
• Superinfection with HDV has a worse prognosis, often leading to acute liver failure or rapid progression to cirrhosis
• Diagnosis involves detecting antibodies to hepatitis D antigen (anti-HDV) and, where available, hepatitis D antigen itself (HDAg) or HDV RNA in serum.

Hepatitis E

• HEV is a 27- to 34-nm RNA hepevirus in the Hepeviridae family.
• A major cause of acute hepatitis in Central and Southeast Asia.
• Transmission is primarily through the fecal-oral route
• Should be considered in patients experiencing acute hepatitis after travel to endemic areas

Hepatitis E (continued)

• The illness is generally self-limiting (no chronic carrier state)
• Some cases of genotype 3 HEV have been reported to cause chronic hepatitis, especially in transplant recipients taking tacrolimus.
• Diagnosis is usually made through IgM anti-HEV tests in serum. The tests might have varying levels of accuracy

Liver Disease Progression

• Diagram illustrates healthy liver to acute hepatitis to recovery to chronic hepatitis to cirrhosis to liver cancer.

Serologic Diagnosis of Hepatitis B

• Table shows various markers (HBsAg, Anti-HBs, HBc-IgM, HBc-IgG, HBeAg, Anti-HBe, HBV DNA) and their correlation with disease stages.

Acute Hepatitis B

• Graph shows the fluctuating levels of HBsAg, HBV DNA (PCR), IgM Anti-HBc, Anti-HBc, and HBsAb over time (months)

Hepatitis B Treatment

• HBeAg-negative chronic hepatitis treatment is indicated if ALT > 2 x ULN and HBV DNA > 2000 IU/mL
• HBeAg-positive chronic hepatitis treatment is indicated if HBV DNA > 20,000 IU/mL and ALT > 2 x ULN.

Hepatitis B Treatment (continued):

• Compensated cirrhosis with detectable HBV DNA warrants antiviral therapy, regardless of HBeAg status or ALT levels.
• Acute liver failure or decompensated cirrhosis necessitates immediate antiviral therapy initiation.
• Patients on immunosuppressive therapy should receive antiviral treatment before starting immunosuppression.
• Pregnant women with high viral loads (> 2 x 10⁵ IU/mL) should begin therapy during late second or early third trimester

Hepatitis B Treatment (continued):

• Patients with hepatocellular carcinoma (HCC) should use a nucleo(s)tide analog (tenofovir or entecavir)
• Treatment is recommended for people with significant fibrosis (≥ F2), based on FibroScan value >7 kPa, or based on clinical cirrhosis criteria and FibroScan value > 12.5 kPa
• Treatment should not depend only on HBV DNA or ALT levels

Treatment Aim

• Suppress viral replication
• Decrease inflammatory damage to liver
• Prevent or reverse complications (e.g., cirrhosis)

Treatment Aim (continued):

• Reduce risk of hepatocellular carcinoma
• Current therapy for chronic hepatitis B does not eradicate the virus and has limited long-term efficacy.

Drug Therapy

• List of medications (PegInterferon Alfa-2a, Tenofovir alafenamide, Tenofovir fumarate, and Entecavir), including dosages and routes of administration

Hepatitis B Vaccine

• Plasma-derived and recombinant vaccines use the HBsAg to create anti-HBs response for immunity, with an effectiveness rate > 95%.
• Vaccination is recommended for infants at birth and at 1-2 and 6-18 months. Adults should be vaccinated as well if at high risk (including dialysis patients, health care workers)

Hepatitis B Vaccines (continued)

• The recommended schedule for adult vaccination includes a primary dose followed by repeated doses at one and six months after the initial dose.

Postexposure Prophylaxis for Hepatitis B

• Hepatitis B immune globulin (HBIG) provides passive immunization
• Vaccination is also advised in those at increased risk of infection

Liver Cirrhosis

• It's a histological diagnosis marked by advanced fibrosis, structural changes (nodules), and vascular alterations
• Chronic liver inflammation leads to stellate cell activation and endothelial damage
• Activated stellate cells produce collagen (fibrosis) and lead to vascular and organ contractions

Liver Cirrhosis (continued)

• Clinical manifestations stem from the loss of liver function, causing portal hypertension and HCC

Clinical Presentation of Liver Cirrhosis

• Patients may report early satiety, increased abdominal girth, weight gain, and respiratory distress
• Physical exam may show abdominal distension, bulging flanks with shifting dullness, fluid wave, and a palpable liver/spleen. (more sensitive)

Clinical Presentation (continued)

• General stigmata of cirrhosis are often present (spider angiomata, palmar erythema), associated with portal hypertension manifestations

Investigations for Liver Cirrhosis

• Laboratory tests may reveal elevated or normal transaminase levels, high bilirubin levels (with biphasic pattern), low albumin, and elevated alpha-fetoprotein in cirrhosis and HCC.
• Viral markers can be screened.
• Autoimmune markers (antimitochondrial antibodies), LKM antibody, soluble liver antigen may be screened, along with metabolic markers like hemochromatosis and Wilson's disease.

Investigations (continued)

• Imaging, such as ultrasound, can identify irregular surface, dilated portal vein, or splenomegaly
• CT scans and endoscopy provide further assessment for focal lesions or esophageal/gastric varices.

Ascites

• Pathogenesis arises from elevated hydrostatic pressure (portal hypertension); renal sodium retention due to sympathetic activation of the renin-angiotensin-aldosterone system; and low oncotic pressure (hypoalbuminemia)

Treatment of Ascites

• Dietary sodium restriction (limit to under 2g/day)
• Diuretics (spironolactone and furosemide) are employed
• Goal of diuretic therapy is increased urinary sodium (> 78 mmol/day), a urinary sodium/potassium ratio greater than 1, or a maximum weight loss of 0.5 kg/day (1.0 kg/day in edema).

Refractory Ascites

• This describes persistent ascites despite adequate sodium restriction and diuretic therapy.
• Serial large-volume paracentesis (LVP), potentially with albumin infusions (6-8g/L), may be employed
• Transjugular intrahepatic portosystemic shunt (TIPS) might be considered for suitable patients
• Liver transplantation may be considered in some cases.

Spontaneous Bacterial Peritonitis (SBP)

• Occurs in approximately 10% of hospitalized cirrhotic patients with ascites.
• Potential sequela of ascites, with mortality ranging from 10-20% during hospitalization.
• Mortality risk is predicted by worsening renal function.

SBP (continued)

• Recurrence rate within 1 year is approximately 70%.
• Median survival is about 9 months after SBP development.

Complications of Liver Cirrhosis

• Included conditions include hepatorenal syndrome (HRS), hepatic encephalopathy, hepatocellular carcinoma(HCC), and spontaneous bacterial peritonitis (SBP).

SBP Risk Factors

• Upper gastrointestinal hemorrhage, ascitic fluid protein concentration ( < 1g/dL), a history of previous SBP episodes are risk factors.

SBP Clinical Presentation

• Possible clinical signs include worsening jaundice, encephalopathy, or renal failure.
• Some patients may also experience chills, fever, and generalized abdominal pain; however, a significant portion of cirrhosis and SBP cases do not present with fever or leukocytosis.

SBP Diagnosis

• Diagnosis is made when ascitic fluid demonstrates polymorphonuclear cell (PMN) counts of 250/mm3 or above
• PMN count >1000/mm3 suggests bowel perforation

SBP Treatment

• Empiric antibiotic treatment with cefotaxime or ceftriaxone is used.
• Albumin infusion (1.5 g/kg body weight on Day 1, 1.0 g/kg on Day 3) following diagnosis.

SBP Long-Term Prophylaxis

• Long-term use of fluoroquinolones or trimethoprim-sulfamethoxazole might be used in patients successfully recovering from an episode of SBP.

Hepatorenal Syndrome (HRS)

• HRS is a renal dysfunction related to advanced liver disease and portal hypertension.
• Characterized by oliguria, azotemia, reduced urine sodium excretion.

Hepatic Encephalopathy

• Neurologic/psychiatric disturbances related to acute or chronic liver insufficiency and/or portosystemic shunting.
• It can span from disorientation/ asterixis to coma, which are graded according to West Haven Criteria (WHC)
• Failure of liver function to clear intestinal toxins (e.g., ammonia).

Hepatic Encephalopathy: Precipitating Factors

• Diuretics
• High protein meals
• Electrolyte imbalances
• Gastrointestinal hemorrhage

Hepatic Encephalopathy Treatment

• Supportive measures involving treating precipitating causes, lactulose, rifaximin, and chronic protein restriction.

Test your knowledge on hepatitis C, its genotypes, transmission modes, symptoms, and treatment options. This quiz covers clinical aspects and management strategies for hepatitis C and its complications. Perfect for medical students and healthcare professionals.