💡 TLDR Primary Care - Deep Dive (#095)

In this issue:

✅ Summarized HCV guidelines

🧠 Review the common signs and symptoms of hepatitis C

⭐ Review the updated options for treatment

📈 And more!

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DEEP DIVE

Hepatitis C

This week, we'll explore the latest clinical guidelines on hepatitis C virus infection, a viral liver disease caused by the hepatitis C virus (HCV). Diagnostic methods such as HCV antibody testing and HCV RNA PCR tests serve as cornerstones for HCV screening, with positive results indicating current or past infection. Liver function tests and imaging studies like ultrasound elastography (FibroScan) aid in assessing liver damage, while HCV genotyping helps tailor treatment decisions based on the viral genotype.

Recognizing hepatitis C symptoms promptly is crucial for initiating treatment and preventing disease progression. While many individuals with acute HCV infection are asymptomatic, chronic HCV infection can lead to symptoms such as fatigue, jaundice, abdominal pain, dark urine, and unexplained weight loss. Long-term, chronic infection may result in severe liver complications such as cirrhosis, liver failure, and hepatocellular carcinoma.

Treatment strategies for hepatitis C have evolved significantly with the advent of direct-acting antivirals (DAAs), which offer high cure rates, shorter treatment durations, and fewer side effects compared to previous interferon-based therapies. Current guidelines recommend DAAs such as sofosbuvir, velpatasvir, and glecaprevir/pibrentasvir, with treatment regimens typically lasting 8 to 12 weeks, depending on the patient's HCV genotype, treatment history, and presence of cirrhosis.

Monitoring for adverse effects and treatment efficacy is essential throughout the therapeutic course. Regular follow-up includes viral load testing to confirm sustained virologic response (SVR), indicating the patient is cured of HCV. Managing potential drug interactions and comorbid conditions, such as HIV or substance use disorders, is also crucial to comprehensive care.

Guidelines on the evaluation and management of hepatitis C virus infection are from the American Association for the Study of Liver Diseases (AASLD 2024), the World Federation for Ultrasound in Medicine and Biology (WFUMB 2024), and the Centers for Disease Control and Prevention (CDC 2023), among others.

For a full review of hepatitis C guidelines, head over to Pathway. We’ll cover some key takeaways below (with the recommendation strength in parentheses). 

1. Screening and Diagnosis:

• Obtain one-time, routine opt-out HCV testing in all persons ≥ 18 years of age. (B)
• Obtain annual HCV testing in:
  • all persons injecting drugs
  • male patients with HIV having unprotected sex with men
  • men having sex with men taking pre-exposure prophylaxis. (B)
• Obtain prenatal HCV testing as part of routine prenatal care of each pregnancy. (B)
• Recognize that as per the most updated classification, there are seven genotypes of HCV based on their nucleotide variability in HCV sequences recovered from multiple geographic regions. 
  • Genotype 1: the most widely dispersed worldwide, 60% to 70% of isolates from the United States are subtype 1a or 1b
  • Genotype 2: widely dispersed but most diverse in central and west Africa
  • Genotype 3: widely distributed but most diverse in Asia, linked to illicit drug use
  • Genotype 4: Northern Africa and the Middle East. 
  • Genotype 5: South Africa
  • Genotype 6: Southeast Asia. 
  • Genotype 7: Central Africa (Congo). (E)

2. Diagnostic Investigations:

• Obtain quantitative or qualitative nucleic acid testing directly following a positive HCV antibody serological test result for the detection of HCV RNA as the preferred strategy to diagnose viremic infection. (B)
• Consider obtaining HCV genotyping if it would alter treatment recommendations. (B)
• Obtain imaging-based noninvasive liver disease assessment tests to detect significant fibrosis, advanced fibrosis, and cirrhosis in adult patients with chronic HCV infection. (B)
• Obtain simple blood-based noninvasive liver disease assessments, such as APRI or FIB-4 Index, as an initial test to detect significant fibrosis, advanced fibrosis, and cirrhosis in adult patients with chronic HCV infection undergoing fibrosis staging before initiating antiviral therapy. (B)
• Obtain ultrasound elastography to exclude significant fibrosis and diagnose cirrhosis in patients with chronic HCV infection. (B)
• Assess all patients for kidney disease (with urinalysis and eGFR) at the time of HCV infection diagnosis. (B)
• Recognize that a liver biopsy is not routine, but it may help determine the severity of the disease. 
  • Other indications for a liver biopsy include:
    • uncertain diagnosis
    • presence of another liver disorder
    • immunocompromised patient. (E)
• Inform patients with positive hepatitis C antibodies and negative HCV-RNA results that they do not have evidence of current (active) HCV infection but are not protected from reinfection. (B)

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3. Medical Management:

• Initiate any of the following pangenotypic direct-acting antiviral regimens in all adult, adolescent, and ≥ 3 years old pediatric patients with chronic hepatitis C infection, regardless of the disease stage:
  • sofosbuvir/daclatasvir for 12 weeks
  • sofosbuvir/velpatasvir for 12 weeks
  • glecaprevir/pibrentasvir for 8 weeks. (B)
• Discontinue direct-acting antiviral therapy in patients with an increase in ALT ≥ 10-fold from baseline at any time during treatment (especially with signs or symptoms of liver inflammation or increasing conjugated bilirubin, ALP, or INR). (B)
• Recognize that the standard regimens are anywhere from 12 weeks to 24 weeks with or without ribavirin based on the genotype, treatment experience, and presence or absence of cirrhosis. (E)
• Recognize that Genotype 1, the most common genotype present in the United States, has four different treatments approved, two of which require only a single pill per day. 
• For example, the combination of sofosbuvir and ledipasvir in a single pill and the combination of grazoprevir and elbasvir in a single pill. (E)

🧠 Ask Pathway AI:

1. What is the likelihood of hepatitis C transmission in different populations of at risk people?

2. How often should patients with HCV be screened for liver cancer?

3. What is the rate of cure in patients undergoing treatment for HCV?

4. Specific Circumstances:

• Obtain testing for hepatitis C virus in all infants and children born to pregnant patients with current (detectable HCV-RNA) or probable (reactive anti-HCV testing while HCV-RNA results are not available) HCV infection. (E)
• Administer vaccination against hepatitis A and hepatitis B in all susceptible patients with HCV infection. (B)
• Administer vaccination against pneumococcal infection in all patients with cirrhosis. (B)
• Recognize the prognosis of HCV:
  • Only 10-15% of patients infected with HCV have a self-limited infection; in all others, the infection is progressive. 
  • About 20% will develop cirrhosis within two decades, and another 1 to 5% will develop liver cancer within three decades. 
  • The progression of the disease is more common in heavy users of alcohol, cirrhotics, and those with a coexisting HBV infection. 
  • Individuals who have an undetectable viral load generally have a decreased risk of developing cirrhosis and death. (E)

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