Hepatitis Nursing CE Course for APRNs

rris, 2019, 2020).

Risk Factors/Protective Features

                Individuals traveling to countries with food and water supply contaminated by fecal matter are at risk of contracting HAV. More specifically, HAV is endemic in areas of Central and South America, Asia, Africa, the Middle East, and the Western Pacific. In addition, individuals in areas with unsafe water or food, inadequate sanitation, poor personal hygiene, and those engaging in oral-anal sex have a higher risk of contracting HAV. Overcrowded living conditions increase the risk for HAV (CDC, 2021a; WHO, 2022b; Hinkle & Cheever, 2018).

Children, particularly young and not toilet trained, contract the virus more often, although they have fewer signs and symptoms than adults. Facilities such as preschools, childcare centers, and other institutions housing young children are at risk for outbreaks; in turn, the children’s families are at risk of contracting HAV. Outbreaks in the younger population are typically due to frequent hand-to-mouth contact and poor hygiene. Patients with developmental disabilities are also at higher risk of contracting HAV (Hinkle & Cheever, 2018; Hoffman & Sullivan, 2020; Norris, 2019, 2020).

 

Signs and Symptoms

                The signs and symptoms of HAV depend on its phase. Many individuals may have few to no symptoms. Individuals who have HAV may experience fever, chills, malaise, nausea, jaundice, anorexia, and abdominal discomfort. Dark urine, pruritis, diarrhea, vomiting, urticaria, cough, splenomegaly, and acholic stools occur within a few days of illness. Objective findings may include hepatomegaly (or hepatosplenomegaly when the spleen is also affected) within those first few days. Splenomegaly results from the increased vascular pressure that occurs with liver disease. Symptoms of splenomegaly include abdominal discomfort in the left upper quadrant, left shoulder pain, abdominal bloating or distension, and a feeling of fullness with decreased appetite. Between days 4 and 30, patients may present with increased serum albumin and jaundice. Jaundice occurs in 70% of HAV cases. Once the jaundice peaks, the other symptoms resolve (Hinkle & Cheever, 2018; Hoffman & Sullivan, 2020; Lai & Chopra, 2022; Norris, 2019).

Signs and symptoms are typically found in individuals over the age of 5, while those in early childhood have been found not to experience many signs and symptoms of hepatitis A. The disease is self-limited as the virus sheds in several weeks; signs and symptoms typically resolve within two months. Unlike other hepatitis viruses, HAV does not typically result in chronic illness or fulminant liver failure. In less than 1% of individuals, HAV causes acute fulminant hepatitis, liver failure, or death (CDC, 2021a; Lai & Chopra, 2022; Norris, 2019, 2020).

Diagnosis

             A laboratory examination occurs following the collection of health history and physical assessment. Acute HAV infection is confirmed by detecting serum immunoglobulin M (IgM) anti-HAV antibodies; serum IgG may be present if a prior infection occurred. IgM is the first immunoglobulin produced during infection, and levels peak early and decline in 3 to 6 months. In contrast, IgG levels increase after one month and remain elevated, demonstrating long-term immunity following the resolution of an illness or effective vaccination. IgG is the most prevalent immunoglobulin in the blood and extracellular fluid (Lai & Chopra, 2022; Norris, 2019, 2020; Scanlon & Sanders, 2019; WHO, 2022d).

Hepatitis B 

             HBV is a double-stranded DNA virus that has HBV DNA and DNA polymerase. The virus contains a hepatitis B surface antigen (HBsAg), whereas the core of the virus has a protein called the hepatitis B core antigen (HBcAg). The content within the core contributes to viral replication, which injures the liver and causes dysfunction; this also increases the risk of developing hepatitis D. HBV can cause the patient to develop chronic hepatitis, cirrhosis, and hepatic necrosis and serve as a disease carrier. The virus is found in infected blood, serum, and body fluids. HBV is transmitted through the oral, sexual, or percutaneous routes (e.g., needle injection). The incubation period for HBV is 45 to 60 days; the virus stays in the serum for a longer period, thus increasing the risk of transmission (Hepatitis B Foundation, 2022; Hoffman & Sullivan, 2020; Norris, 2019).

Risk Factors/Protective Features

              Although vaccination is widely available and is effective 98% of the time, global HBV cases are the most prevalent and on the rise. Global HBV cases have increased by 1.5 million annually, with 296 million individuals living with HBV. Asia and Africa have the highest number of individuals living with HBV (WHO, 2022c).

Infants born to mothers with HBV are at risk of contracting the virus due to the blood exchange between mother and child. If an infant is infected with HBV from the mother, they have a 90% risk of being a disease carrier. In addition, anyone who may have an exchange of bodily fluids is at risk for developing HBV, including individuals who have unprotected sex or inject drugs. It may also be transmitted via accidental needle sticks, unsterile medical and dental equipment, and sharing personal care items such as razors and toothbrushes. Healthcare workers are an at-risk population due to potential exposure to blood and blood products. However, the screening of blood products has reduced the transmission of HBV in healthcare settings (Hepatitis B Foundation, 2022; Hinkle & Cheever, 2018; Norris, 2019, 2020).

Signs and Symptoms

                Unlike HAV, HBV patients may not experience signs and symptoms for a significant period. Many people with HBV are silent carriers, unknowingly infecting others. HBV symptoms include malaise, jaundice, dark urine, nausea, vomiting, and abdominal pain. Fever is infrequent; hepatomegaly, splenomegaly, enlarged cervical lymph nodes, and jaundice may occur. If the disease continues to impact the liver, the risk of developing hepatocarcinoma, cirrhosis, or liver failure increases (Hinkle & Cheever, 2018; WHO, 2022c).

Diagnosis

             HBV can be diagnosed if the surface antigen, HBsAg, is found in the serum. Specifically, the diagnosis of HBV occurs when HBsAg levels are greater than 2% in the serum. HBsAg may be detected before the onset of symptoms and during active symptoms. Levels typically decline in 3 to 6 months. Elevated levels beyond 6 months indicate that the acute disease is transitioning to a chronic state. Initially, IgM is elevated; over time, IgM declines, and IgG levels increase in the serum. Screening may also include a liver ultrasound (Hepatitis B Foundation, 2022; Hoffman & Sullivan, 2020; Norris, 2019, 2020; WHO, 2022b).

 

Hepatitis C 

             Hepatitis C is caused by HCV and has an incubation period of up to 26 weeks. HCV is a single-stranded and genetically unstable virus that alters the hepatocyte during endocytosis. The virus is composed of a single RNA strand and appears similar to flaviviruses. This instability has allowed it to develop at least six different genotypes and approximately 70 subtypes. HCV genotypes are 1 (1a and 1b), 2, 3, 4, 5, and 6. Approximately 75% of individuals with HCV in the United States have either genotype 1a or 1b, while 10% to 20% of affected Americans have either genotype 2 or 3 (American Liver Foundation, 2022; Kish et al., 2017; Norris, 2019, 2020).

HCV’s genetic instability has made it challenging to develop effective treatment and vaccination. The disease can be short-term or long-term, and the individual may be asymptomatic until a secondary illness occurs. Secondary conditions, such as cirrhosis or liver cancer, occur because of the stress on the liver from HCV (CDC, 2020; Hoffman & Sullivan, 2020; Norris, 2020).

Risk Factors/Protective Features

                HCV is transmitted by exchanging bodily fluids via sexual intercourse, needles for tattoos or injections, body piercings, and from mother to child during birth. HIV is a common co-infection, particularly if an individual acquires HCV through drug use. Blood transfusions can be a source of HCV in nations that do not screen donated blood products for the virus (Office of Infectious Disease and HIV/AIDS Policy, 2020; Norris, 2019, 2020).

Signs and Symptoms

             The signs and symptoms of HCV are nondescript, with many patients overlooking them and not seeking treatment. Patients may experience malaise, right upper quadrant pain, and nausea. Jaundice is not as common in HCV as with other hepatitis viruses. Untreated HCV can trigger a domino effect leading to cirrhosis, hepatocellular carcinoma, and end-stage liver disease (Kish et al., 2017; Norris, 2020).

Diagnosis

             Approximately 40% of individuals infected with HCV know they have the disease. Therefore, collecting a blood sample to test for the virus is key to earlier treatment and preventing poor long-term outcomes. As previously described, specimens are analyzed for the presence of HCV antibodies; if the antibody screen is reactive, the specimen will also be tested for HCV RNA. The testing can be completed by an enzyme immunoassay or enhanced chemiluminescence immunoassay test; if positive, a polymerase chain reaction (PCR) test should be conducted to confirm the diagnosis (CDC, 2020; Kish et al., 2017).

A positive test can occur in patients 6 to 8 weeks following exposure to the virus. HCV testing is recommended at least once after age 18 and during every pregnancy. The rates of HCV have quadrupled from 2010 to 2018 due to increased injection drug use (Office of Infectious Disease and HIV/AIDS Policy, 2020; Norris, 2020).

 

Hepatitis D 

                For someone to acquire the hepatitis D virus (HDV), they must have HBV; without it, the virus is incomplete. HDV is part of the Deltaviridiae family and contains RNA. HDV can have severe long-term implications, as HBV furthers liver inflammation and places the individual at risk for the most severe form of hepatitis, hepatocellular carcinoma, and death. The incubation period for HDV is 2 to 8 weeks (Hoffman & Sullivan, 2020; Norris, 2020; WHO, 2022c;).

Risk Factors/Protective Features

                Individuals who contract HDV have previously or simultaneously acquired HBV as well. As such, vaccination against HBV is protective and preventative against HDV. Individuals who inject drugs or receive hemodialysis are at risk of contracting HDV. Maternal-to-fetal virus transfer is rare compared to the other forms of viral hepatitis (Norris, 2020; WHO, 2022c).

Signs and Symptoms

                HDV has similar signs and symptoms to HBV. However, patients infected with HDV are more likely to develop fulminant and chronic liver failure and cirrhosis than those with HBV alone (Hinkle & Cheever, 2018; Norris, 2020).

Diagnosis

             HDV is diagnosed when HDV antibodies or HDV RNA is found in the serum. Specifically, the serum will contain anti-HDV IgG and IgM, and HDV RNA (Norris, 2020; Scanlon & Sanders, 2019; WHO, 2022d).

 

Hepatitis E 

                Hepatitis E virus (HEV) is a single-stranded, unenveloped virus; the disease has four genotypes. Only types 1 and 2 are seen in humans, whereas 3 and 4 are found in animals. Like HAV, HEV is transmitted via the fecal-oral route. The disease is found in contaminated water sources in areas with poor sanitation. Genotype 1 is associated with contaminated water and is thus more common in humans than genotype 2. Genotype 3 tends to be found in undercooked meat, such as pork and animal liver. The incubation period is 2 to 8 weeks. The disease tends to stay acute; however, long-term HEV occurs in immunocompromised individuals, such as HIV, cancer, and organ transplant recipients. The transition from acute to chronic disease occurs in 2% of patients with HEV (Hinkle & Cheever, 2018; Hoffman & Sullivan, 2020; Norris, 2020; WHO, 2022e).

Risk Factors/Protective Features

                HEV is like HAV in terms of at-risk populations. However, pregnant women with HEV have a more severe illness and risk developing fulminant liver failure. A pregnant patient contracting HEV in the second and third trimesters poses a more significant risk. Approximately 20% to 25% of pregnant patients in the third trimester with HEV die from the disease (Norris, 2020; WHO, 2022e).

Although HEV rarely causes chronic disease, those with a compromised immune system are at a higher risk of developing a chronic form of the disease, morbidity, and mortality. Severe disease leading to the loss of life occurs in 2% of HEV cases. HEV is found most frequently in East and South Asia (Norris, 2019; WHO, 2022e).

Signs and Symptoms

             The signs and symptoms of HEV are similar to HAV. Initially, the patient will likely experience nausea, vomiting, and anorexia. As the infection progresses, patients can develop jaundice, amber or tea-colored urine, and pale stools (Hinkle & Cheever, 2018; Norris, 2020; WHO, 2022e).

Diagnosis

                HEV appears clinically like other hepatitis viruses. As such, it is essential to identify whether an endemic is occurring and if water has been contaminated. Serum tests are conducted to determine whether anti-HEV IgM antibodies are present. Reverse transcriptase polymerase chain reaction (RT-PCR) can detect HEV in the serum or stool (WHO, 2022e).

 

Chronic Viral Hepatitis

             Patients with hepatitis for longer than 3 to 6 months are deemed to have chronic viral hepatitis. HBV, HCV, and HDV place the patient at risk for chronic hepatitis due to hepatocellular injury and inflammation (Hinkle & Cheever, 2018; Norris, 2020).  

Risk Factors/Protective Features

                In patients with HBV, HCV, or HDV, developing chronic hepatitis is a risk despite treatment. HCV has the highest rates of chronic viral hepatitis due to a lack of treatment in patients who have been asymptomatic for years. Eighty-five percent of individuals with HCV are likely to transition to chronic viral hepatitis. Patients who are older, male, immunocompromised, drink alcohol, and/or take hepatotoxic medications are at greater risk of developing chronic hepatitis. Approximately 25% of individuals with chronic hepatitis will develop associated conditions, such as cirrhosis or liver cancer; typically, this occurs within 20 to 30 years of diagnosis (Hoffman & Sullivan, 2020; Norris, 2019).

Signs and Symptoms

             The signs and symptoms of chronic viral hepatitis vary and do not suggest a specific disease outcome. Typically, patients report fatigue, decreased appetite, and jaundice. If the patient develops liver failure, they are likely to experience thrombocytopenia, oliguria, ascites, edema, and changes in mentation associated with hepatic encephalopathy (Hoffman & Sullivan, 2020; Norris, 2020).

Diagnosis

                A patient may be asymptomatic, and a workup for chronic hepatitis may be initiated due to an elevated liver function panel. In individuals with chronic hepatitis, elevated AST and ALT levels will occur; however, the severity of the disease is based on the precipitating virus (Norris, 2020).

Treatment/Management of Hepatitis

 

Nonpharmacological Management

Fecal-Oral Route Transmission-Based Hepatitis

Patients experiencing hepatitis caused by fecal-oral route transmission are commonly treated utilizing nonpharmacological management. Treatment for HAV and HEV is individualized based on the patient's symptoms and lab values; there is no specific recommended treatment regimen. Patients require supportive care, which includes promoting good health and reducing the risk of further trauma to the liver. The patient and family or other close contacts should be educated on proper sanitation and bathroom hygiene to prevent the spread of disease. The provider should review the patient’s medication list and determine if any hepatotoxic medications should be discontinued during the illness (Grossman & Porth, 2014; Hinkle & Cheever, 2018; Hoffman & Sullivan, 2020; National Institutes of Health [NIH], 2019; WHO, 2022a).

Patients should be encouraged to rest and maintain nutrition. The patient must have optimum nutrition to support immune function. Fluid and electrolyte status must be assessed and balanced, especially if the patient is experiencing excessive nausea, vomiting, and diarrhea. Due to the risk of dehydration, oral fluids should be encouraged and transitioned to intravenous if unsuccessful. For patients experiencing anorexia, small, frequent high-calorie snacks instead of large meals can help maintain caloric intake; a high-calorie diet is advised due to the liver’s inability to store glycogen. In addition, high-quality hand hygiene should be encouraged to prevent infection spread (Grossman & Porth, 2014; Hinkle & Cheever, 2018; Hoffman & Sullivan, 2020; NIH, 2019; WHO 2022a).

Bodily Fluid/Percutaneous Transmission-Based Hepatitis           

There are universal recommendations for the nonpharmacological management of hepatitis viruses transmitted via bodily fluids or percutaneously (HBV, HCV, and HDV). Patients should be encouraged to hydrate and consume a diet low in fat and high in fruits, vegetables, and whole grains. The liver creates and releases bile, which emulsifies dietary fat. Vitamin supplements may be helpful. Patients should avoid alcohol, tobacco, and hepatotoxic medications (Hoffman & Sullivan, 2020).

It is recommended that patients with hepatitis are monitored at least every 6 to 12 months. Patients should be educated on the importance of maintaining appointments with all providers, including hepatologists and/or gastroenterologists. It is crucial to assess and address any psychosocial issues due to changes in the patient’s life, such as anxieties related to being hospitalized, missing work, and avoiding sexual contact. Patients should be educated on strategies to prevent the transmission of the disease to others (American Liver Foundation, 2022; Hepatitis B Foundation, 2022; Hinkle & Cheever, 2018).

A liver transplant may be required if the disease worsens and causes end-stage hepatic failure. A transplant will not cure underlying hepatitis (usually HBV or HCV); however, it will prevent disease progression. HCV is a leading cause of liver failure necessitating a transplant. Since 80% of liver cancers are due to chronic HBV or HCV infections, all patients should be screened for liver cancer. Hepatocellular carcinoma is the most common type of liver cancer and is caused by chronic HBV in 44% to 55% of patients. Liver cancer screening consists of serum alpha-fetoprotein (AFP), ultrasound of the liver, computed tomography (CT), or magnetic resonance imaging (MRI) and should be completed at least every 6 months (American Society of Clinical Oncology, 2022; Hoffman & Sullivan, 2020; Norris, 2019: Sachar et al., 2021).

 

Pharmacological Prevention and Management

HAV

             There are no specific medications indicated for the treatment of HAV, so management focuses on symptom management and supportive care. HAV vaccines are available for individuals 12 months and older to prevent infection. However, if an infant travels, they may receive one HAV vaccine at 6 months. Children and adults may be given the Vaqta or Havrix vaccines as a two-dose series. For a three-dose vaccination series, providers may opt to administer Twinrix. For travelers, immune globulin, GamaSTAN, has been approved as a prophylactic treatment. IgG may be given following exposure to HAV (CDC, 2021a; Norris, 2019, 2020). 

 

HBV

             The HBV vaccination series is intended to prevent the acquisition and spread of the virus. HBV vaccination is highly effective, preventing viral acquisition in at least 98% of recipients. The vaccinations are given intramuscularly (IM) in the deltoid muscle or the anterolateral aspect of the thigh. The deltoid is the recommended administration site for adults. Administration in alternative sites, such as dorsogluteal or ventrogluteal, is related to decreased immunogenicity. Infants should receive their first HBV vaccination dosage within 24 hours of birth, followed by two to three other doses given at least four weeks apart. The vaccine can also be administered within 7 days of exposure for post-exposure prophylaxis (Hepatitis B Foundation, 2022; Norris, 2020; WHO, 2022b).

             Patients with HBV may require pharmacological treatment with interferons and nucleoside analogs. Interferons work by mimicking the body's naturally produced interferons. Approved interferons include interferon alfa 2b (Intron A) and peginterferon alfa 2a (Pegasys). Nucleoside analogs work by interfering with HBV replication. Nucleoside analogs approved to treat HBV include lamivudine (Epivir-HBV), adefovir dipivoxil (Hepsera), tenofovir disoproxil fumarate (Viread), entecavir (Baraclude), and tenofovir alfenamide (Vemlidy). These medications can slow the progression of the disease, preventing cirrhosis and liver cancer; however, there is a risk of hepatotoxicity with nucleoside analogs. See Table 1 for more information on these medications, dosing, adverse effects, and contraindications (Lok, 2019; WHO, 2022b).

Table 1

Medications to Treat HBV 

Drug	Dose	Adverse Effects	Contraindications and Considerations
Interferons
Interferon alfa 2b (Intron A)	For adults: 30 to 35 international units (IU) administered IM or subcutaneously (subQ) every week for 16 weeks; dosing is divided into 5 million IU administered daily, or 10 million IU administered 3 times weekly For children 1 to 17 years: 3 million IU/m2 subQ 3 times a week for the 1st week, then 6 million to 10 million IU/m2 administered three times weekly for 16 to 24 weeks	Depression, difficulty concentrating, drowsiness, fatigue, insomnia, angina, arrhythmia, edema, rhinitis, nasal congestion, anorexia, diarrhea, dry mouth, dyspepsia, nausea, vomiting, impotence, amenorrhea, arthralgia, dyspnea, alopecia, rash, and flulike syndrome	Autoimmune hepatitis or decompensated liver disease Use cautiously in patients with a history of cardiovascular or pulmonary disease, depression, coagulation disorders, or renal impairment
Peginterferon alfa 2a (Pegasys)	For adults: 180 mcg subQ once weekly for 48 weeks For children 3 and older: 180 mcg/1.73 m2 x body surface area (BSA) subQ once weekly for 48 weeks; use with ribavirin (Virazole); maximum dose is 180 mcg weekly	Depression, anxiety, dizziness, insomnia, headaches, nervousness, blurred vision, abdominal pain, nausea, vomiting, diarrhea, dry mouth, weight loss, cough, dyspnea, alopecia, pruritus, dermatitis, eczema, injection-site reaction, flulike syndrome, neutropenia, thrombocytopenia, and anemia May inhibit growth in children	If a pediatric patient turns 18 during treatment, continue the pediatric dose until completion Contraindicated in patients with autoimmune hepatitis Use cautiously in patients with a history of depression or anxiety Use cautiously in patients with a baseline neutrophil count < 1,5000 /mm3, baseline platelet count < 90,000 /mm3, baseline Hbg < 10 g/dL, or CrCl < 50 mL/minute Use cautiously in patients with hypertension, an autoimmune disease, pulmonary disease, colitis, pancreatitis, and thyroid disease
Nucleoside Analogs
Lamivudine (Epivir-HBV)	For adults: 100 mg orally once daily For children ages 2 to 17: 3 mg/kg orally once daily; maximum dose is 100 mg daily	Dizziness, fatigue, headaches, insomnia, neuropathy, depression, anorexia, diarrhea, nausea, vomiting, abdominal pain, pancreatitis, cough, arthralgia, myalgia, anemia, neutropenia, thrombocytopenia, hepatotoxicity, and lactic acidosis	The optimal treatment duration has not been determined lamivudine (Epivir) is used for HIV infection and lamivudine (Epivir-HBV) is used for HBV Monitor bilirubin, serum lipase, creatinine kinase (CK), and alanine transaminase (ALT) Use cautiously in patients with decreased renal function Use only when an alternative antiviral is not available or appropriate Use cautiously in patients (especially children) with a history or increased risk of pancreatitis
Adefovir dipivoxil (Hepsera)	For adults and children over 12: 10 mg orally daily Adjust the dose based on creatinine clearance (CrCl): for a CrCl of 30 to 45 mL/minute: 10 mg orally every other day (48 hours) for a CrCl of 10 to 29 mL/minute: 10 mg orally every 3 days (72 hours) if the patient receives hemodialysis, administer 10 mg orally every 7 days after a dialysis treatment	Headaches, abdominal pain, diarrhea, nausea, vomiting, flatulence, pruritis, renal failure, hepatic failure, severe hepatomegaly with steatosis, and lactic acidosis	Conduct HIV antibody testing prior to initiating treatment Use cautiously in older adults due to decreased liver and kidney function Use cautiously in combination with nephrotoxic drugs or in patients with an increased risk of developing hepatic disease
Tenofovir disoproxil fumarate (Viread)	For adults and children older than 2 that weigh ≥ 35 kg: 300 mg orally once daily 10 to < 35 kg: 8 mg/kg orally once daily; maximum dose 300 mg	Headaches, fever, peripheral neuropathy, insomnia, dizziness, depression, anxiety, fatigue, nausea, vomiting, dyspepsia, abdominal pain, hyperglycemia, weight loss, back pain, pneumonia, pruritus, diaphoresis, and neutropenia	Monitor weight and adjust the dose as needed Use cautiously in patients at risk for decreased hepatic or renal function Contraindicated with use with other nephrotoxic drugs
Entecavir (Baraclude)	For adults and children over 16 with no history of nucleoside treatment: 0.5 mg orally once daily; must be taken at least 2 hours after a meal and at 2 hours before eating the next meal Adjust the dose based on creatinine clearance (CrCl): for a CrCl of 30 to 50 mL/minute: 0.25 mg once daily or 0.6 mg every other day for a CrCl of 10 to 30 mL/minute: 15 mg once daily or 0.5 mg every 72 hours for a CrCl < 10 mL/minute; or if the patient is undergoing dialysis: 0.05 mg once daily or 0.5 mg every 72 hours For children ages 2 to 16 that weigh at least 10 kg, dosing is weight-based: > 30 kg: 0.5 mg (1 tablet of 10 mL) once daily 26 to 30 kg: 0.45 mg (9 mL) once daily 23 to 26 kg: 0.4 (8 mL) once daily 20 to 23 kg: 0.35 (7 mL) once daily 17 to 20 kg: 0.3 mg (6 mL) once daily 14 to 17 kg: 0.25 mg (5 mL) once daily 11 to 14 kg: 0.2 mg (4 mL) once daily 10 to 11 kg: 0.15 mg (3 mL) once daily	Fatigue, dizziness, headaches, diarrhea, nausea, vomiting, dyspepsia, hematuria, lactic acidosis, and hepatomegaly	Contraindicated for use in patients that have a concurrent infection with HBV and HIV that are not being treated with highly active antiretroviral therapy (HAART) Use cautiously in patients with decreased renal or hepatic function or those that have a history of a liver transplant
Tenofovir alfenamide (Vemlidy)	For adults and children older than 12: 25 mg orally once daily	Headaches, abdominal pain, cough, fatigue, nausea, diarrhea, dyspepsia, arthralgia, and lactic acidosis	Medication should be administered with food Monitor liver function tests and CK levels Use cautiously in patients with renal or hepatic impairment Contraindicated in patients with a CrCl < 15 mL/minute

(Woods, 2023)

HCV

             Currently, a vaccination for HCV is not available. Patients with HCV should be administered oral antivirals; the direct-acting antiviral medications can cure HCV in 8 to 12 weeks in 95% of individuals and prevent further complications such as cirrhosis and liver cancer. However, many patients must take these medications for at least 6 months or longer. Medications for HCV vary depending on the strain of the virus, viral load, presence of liver damage in the body, any previous treatment for HCV, and other concurrent infections (American Liver Foundation, 2022; Hoffman & Sullivan, 2020; Office of Infectious Disease and HIV/AIDS Policy, 2020).

             Traditional and effective medications, ribavirin (Virazole) and peginterferon alfa 2a (Pegasys), have been used for several years; however, interferon has numerous exclusion criteria, making many individuals ineligible. As such, newer treatments have evolved, though many require multiple medications and the use of ribavirin (Virazole). Sofosbuvir/velpatasvir (Epclusa) must be given with ribavirin (Virazole). Glecaprevir/pibrentasvir (Mavyret) and sofosbuvir/velpatasvir/voxilaprevir (Vosevi) are used to manage all HCV genotypes with treatment ranging from 8 to 12 weeks. The medications work at various points in the HCV viral replication cycle. Examples of genotype-specific medications include sofosbuvir (Sovaldi) and ledipasvir/sofosbuvir (Harvoni) for genotype 1a, sofosbuvir (Solvaldi) plus ribavirin (Virazole) for genotypes 2, 3, and 4, and ledipasvir/sofosbuvir (Harvoni) for genotypes 5 and 6. The most common side effects are headache and fatigue; however, some medications can cause anemia. The provider should assess serum laboratory data, changes in the patient’s physical assessment, and potential risk for drug resistance (see Table 2; American Liver Foundation, 2022; Kish et al., 2017; Lagging et al., 2018).

Table 2

Medications to Treat HCV 

Drug	Dose	Adverse Effects	Contraindications
Interferon alfa 2b (Intron A)	3 million IU administered IM or subQ three times weekly; if after 16 weeks ALT levels have normalized, continue treatment for 18 to 24 months; if ALT levels have not normalized after 16 weeks or HCV RNA levels continue to be elevated, treatment should be discontinued	See Table 1	Not to be combined with ribavirin (Virazole) in those patients with a CrCl < 50 mL/minute
Ribavirin (Virazole)	When used in combination with interferon alfa-2b (Intron A): Adults weighing > 75 kg: 1,200 mg orally daily divided into two doses for 24 to 48 weeks Adults weighing ≤ 75 kg: 1,000 mg orally daily divided into two doses (400 mg in the morning and 600 mg in the evening) for 24 to 48 weeks Children older than 3 that weigh > 73 kg: 1,200 mg orally divided into two doses Children older than 3 that weigh 60 to 73 kg: 1,000 mg divided into two doses (400 mg in the morning and 600 mg in the evening) Children older than 3 that weigh 47 to 59 kg: 800 mg orally daily in 2 divided doses Children older than 3 that weigh < 47 kg: 15 mg/kg/day orally in 2 divided doses When used in combination with peginterferon alfa-2b (Pegasys): Adults with genotype 1 or 4 that weigh ≥ 75 kg: 1,200 mg orally daily divided into two doses for 48 weeks < 75 kg: 1,000 mg orally daily divided into two doses for 48 weeks Adults with genotype 2 or 3: 800 mg orally daily divided into two doses for 24 weeks Adolescents and children older than 5 with genotype 2 or 3: ≥ 75 kg: 1,200 mg orally daily divided into two doses 60 to 74 kg: 1,000 mg orally daily divided into two doses (400 mg in the morning and 600 mg in the evening)  47 to 59 kg: 800 mg orally daily in 2 divided doses 34 to 46 kg: 600 mg orally daily in 2 divided doses (200 mg in the morning and 400 mg in the evening) 23 to 33 kg: 400 mg orally daily in 2 divided doses Treatment in children with genotypes 2 and 3 should last 24 weeks and all other genotypes 48 weeks	Fatigue, dizziness, headaches, insomnia, agitation, depression, anxiety, memory impairment, aggressive and hostile behavior, suicidal and homicidal ideation, bradycardia, cardiac arrest, blurred vision, dry mouth, anorexia, diarrhea, nausea, vomiting, dyspepsia, constipation, menstrual changes, anemia, leukopenia, neutropenia, thrombocytopenia, hepatomegaly, hyperbilirubinemia, growth retardation in children, dyspnea, cough, alopecia, pruritus, eczema, diaphoresis, and flulike illness	Should not be used as monotherapy for the treatment of HCV Contraindicated in pregnant individuals and those who have a pregnant partner; extreme care should be taken to prevent pregnancy for at least 6 months after treatment cessation Use cautiously in patients with cardiac disease due to an increased risk of myocardial infarction Use cautiously in patients with decreased hepatic or renal function
peginterferon alfa 2a (Pegasys)	For adults with HCV and HIV-1 infections who have not been previously treated with interferon alfa: 180 mcg subQ once weekly; when used in combination with ribavirin (Virazole), treatment duration is 48 weeks HCV infection with compensated hepatic disease in individuals not previously treated with interferon alfa, in combination with other antiviral drugs: Adults with genotypes 1 or 4: 180 mcg subQ once weekly for 48 weeks when used with ribavirin (Virazole) Adults with genotypes 2 or 3: 180 mcg subQ once weekly for 24 weeks when used with ribavirin (Virazole) Children older than 5: 180 mcg/1.73 m2 x BSA subQ once weekly; for genotypes 2 or 3, continue treatment for 24 weeks; for any other genotype, continue treatment for 48 weeks	See Table 1	See Table 1
Sofosbuvir/ velpatasvir (Epclusa)	For patients with HCV genotypes 1, 2, 3, 4, 5, or 6 without cirrhosis when used in with ribavirin (Virazole): Adults and children older than 6 that weigh at least 30 kg: 400 mg/100 mg orally once daily for 12 weeks Children older than 6 that weigh 17 to <30 kg: 200 mg/50 mg orally once daily for 12 weeks Children older than 3 that weigh at least 30 kg: 400 mg/100 mg orally once daily for 12 weeks Children older than 3 that weigh 17 to < 30 kg: 200 mg/ 50 kg orally once daily for 12 weeks Children older than 3 that weigh < 17 kg: 150 mg/37.5 mg orally once daily for 12 weeks	Fatigue, insomnia, irritability, depression, headaches, nausea, diarrhea, anemia, and CK elevation	Do not use antacids within 4 hours of taking sofosbuvir/ velpatasvir (Epclusa) Monitor lipase, CK, bilirubin, and Hgb levels May cause symptomatic bradycardia when taken with amiodarone (Pacerone)
Glecaprevir/ pibrentasvir (Mavyret)	Numerous dose adjustments are recommended based on the patient's laboratory results, previous treatments, and concurrent infections. For patients with HCV genotypes 1, 2, 3, 4, 5, or 6 that are treatment naïve without cirrhosis: Adults and children older than 3 that weigh at least 45 kg: 300 mg/120 mg orally once daily for 8 weeks Children 3 or older that weigh 30 to < 40 kg: 250 mg/100 mg orally once daily for 8 weeks Children 3 or older that weigh 20 to < 30 kg: 200 mg/80 mg orally once daily for 8 weeks Children 3 or older that weigh < 20 kg: 150 mg/60 mg orally once daily for 8 weeks	Headaches, fatigue, nausea, vomiting, diarrhea, and pruritis	Should be taken with food to minimize gastrointestinal (GI) effects Contraindicated in patients with moderate to severe hepatic failure Should not be combined with atazanavir (Reyataz) or rifampin (Rifadin) Prior to initiating treatment, patients should be tested for current or prior HBV infection
sofosbuvir/ velpatasvir/ voxilaprevir (Vosevi)	For adults: 400 mg/100 mg/100 mg orally once daily for 12 weeks	Insomnia, headaches, depression, fatigue, diarrhea, and nausea	Should be taken with food Monitor lipase, CK, and bilirubin levels Before initiating treatment, patients should be tested for current or prior HBV infection Contraindicated in patients with moderate to severe hepatic failure; use cautiously in patients at risk for hepatic injury, such as those with a history of chronic alcohol abuse
sofosbuvir (Sovaldi)	HCV genotype 1 or 4 without HIV co-infection: 400 mg orally once daily in combination with peginterferon alfa 2a (Pegasys) and ribavirin (Virazole) for 12 weeks; for patients that cannot receive interferon dose is 400 mg orally once daily with ribavirin (Virazole) for 24 weeks HCV genotype 2 with or without HIV infection: Adults and children older than 3 that weigh ≥ 35 kg: 400 mg orally once daily with ribavirin (Virazole) for 12 weeks Children older than 3 that weigh 17 to < 35 kg: 200 mg orally once daily with ribavirin (Virazole) for 12 weeks Children older than 3 that weigh < 17 kg: 150 mg orally once daily with ribavirin (Virazole) for 12 weeks HCV genotype 3 with or without HIV infection: Adults and children older than 3 that weigh ≥ 35 kg: 400 mg orally once daily with ribavirin (Virazole) for 24 weeks Children older than 3 that weigh 17 to < 35 kg: 200 mg orally once daily with ribavirin (Virazole) for 24 weeks Children older than 3 that weigh < 17 kg: 150 mg orally once daily with ribavirin (Virazole) for 24 weeks For adults and children older than 3 years with HCV and hepatocellular carcinoma who are awaiting a liver transplant: 400 mg orally once daily with ribavirin (Virazole) for 48 weeks or until transplantation occurs	Headaches, insomnia, irritability, nausea, diarrhea, anemia, pruritis, flulike illness, and neutropenia	Contraindicated for use with amiodarone (Pacerone) and hypericum perforatum (St. John's Wort) Monitor serum CK, bilirubin, lipase, Hgb, neutrophil, and platelet counts Use cautiously in patients with a CrCl < 30 mL/minute
ledipasvir/ sofosbuvir (Harvoni)	For patients with HCV genotype 1 that are treatment naïve without cirrhosis: Adults and children older than 3 that weigh at least 35 kg: 90 mg/400 mg orally once daily for 12 weeks Children older than 3 weighing 17 to < 35 kg: 45 mg/200 mg orally once daily for 12 weeks Children older than 3 weighing < 17 kg: 33.75 mg/150 mg orally once daily for 12 weeks For patients with HCV genotypes 4, 5, or 6 that are treatment naïve without cirrhosis: Adults and children older than 3 that weigh at least 35 kg: 90 mg/400 mg orally once daily for 12 weeks Children 3 or older that weigh 17 to < 35 kg: 45 mg/ 200 mg orally once daily for 12 weeks Children 3 or older that weigh < 17 kg: 33.75 mg/150 mg orally once daily for 12 weeks	Fatigue, headaches, insomnia, dizziness, irritability, depression, nausea, vomiting, diarrhea, hyperbilirubinemia, increased lipase levels, myalgia, cough, and dyspnea	Monitor serum lipase, bilirubin, and CK levels Use with amiodarone (Pacerone) may cause symptomatic bradycardia, leading to cardiac arrest or the need for pacemaker placement Prior to initiating treatment, patients should be tested for current or prior HBV infection

(Woods, 2023)

HDV

             There is no specific treatment for HDV as it is treated with and like HBV. As such, patients receive interferon and antivirals. It is worth noting that the recurrence of HDV is high even when interferon is appropriately administered. The interferon should be administered for at least 48 weeks. Preventing HBV will assist in preventing HDV. Therefore, it is recommended that all receive the HBV vaccination series. However, there is no specific vaccination for HDV (Hinkle & Cheever, 2018; Hoffman & Sullivan, 2020; Norris, 2019, 2020).

HEV

             Treating a patient with HEV is based on the patient’s symptoms. Unfortunately, there is no readily available vaccination for HEV. However, WHO identified that an HEV vaccine is available and licensed in China, though unavailable in other countries. If a patient is given a medication to treat HEV, the medication of choice is typically ribavirin (Virazole), especially in the immunocompromised population. However, medication therapy is not frequently used as the disease is usually self-limited (Hoffman & Sullivan, 2020; WHO, 2022e).

Chronic Viral Hepatitis

                Medications to treat the precipitating virus (i.e., HBV or HCV) will be used to manage chronic viral hepatitis (see Tables 1 and 2). For instance, patients with HBV may take interferons and/or nucleotide analog agents (Norris, 2020).

 

Evidence-Based Practice

             By 2030, the WHO seeks to abolish HBV; this goal is contingent upon promoting greater education, awareness, and prevention using the HBV vaccination series. Postpartum and pediatric APRNs are well-poised to educate new parents on the HBV vaccination series. Hepatitis causes loss of time at work and school; APRNs are in a great position to promote health and wellness in preventing and caring for patients with hepatitis (Hinkle & Cheever, 2018; Seto et al., 2018).

The care of patients with any hepatitis diagnosis may range from patient education to caring for a patient with severe life-threatening liver damage secondary to either acute or chronic hepatitis. A common goal among healthcare workers is to reduce the risk and incidence of hepatitis, and education is paramount to that endeavor. Patient education is essential in various settings and includes educating individuals or groups regarding known risk factors and modes of transmission. Education should also include promoting available vaccines for HAV and HBV, demonstrating appropriate hygiene practices, avoiding contaminated water and food, explaining the risks of travel to certain areas, and what to do if there is potential exposure. Currently, 48 out of 50 states mandate HBV vaccination as a requirement to enroll in daycare, pre-K, school, or some combination; about half of all states have a similar mandate for HAV vaccination (Hoffman & Sullivan, 2020; Immunize.org, 2021b, 2021c).

Public health campaigns should focus on the risk of IV drug use, safer sexual practices, and strategies to decrease blood and body fluids transmission. All healthcare professionals must collaborate to educate patients and work towards an improved standard of care involving needlesticks, sharps incidents, and other possible sources of contamination for caregivers. Since patients with hepatitis are often cared for by their families, education should include safety precautions to prevent transmission to family members, caregivers, and friends (Ignatavicius et al., 2018).

Patients with hepatitis are vulnerable to fatigue and need adequate rest in the hospital and while recovering at home. Rest is required to decrease metabolic demands and promote more substantial blood flow to the hepatic system to heal and restore liver tissue. The provider may limit the patient’s activity level based on liver enzyme testing results. The amount of activity can be increased if lab results improve, but the activity level should be limited again if liver function tests worsen. Patients should be encouraged to rest when they feel tired, pace themselves, and learn to prioritize activities to accomplish their most vital tasks first (Ignatavicius et al., 2018).

The provider may make referrals to other agencies or case management to assist the patient with medication costs, home health/public health for support at home, and others that might benefit the patient. Patients, particularly those with chronic HCV, often experience lapses in quality care along the continuum of health care. In particular, researchers found patients with a history of substance abuse were less likely to be prescribed treatment and have follow-ups (Reader et al., 2020).

Future Research

 

Artificial Intelligence: Predicting Disease Outcomes

                The University of Florida has begun research using four artificial intelligence (AI) algorithms to predict HCV. The algorithms use machine learning to determine success versus failure for treatment options. Machine learning considers patients’ comorbidities and lifestyle factors, such as alcohol consumption and smoking (Bennett, 2022).

             AI has the potential to assist in diagnosing and treating hepatitis patients. The researchers recommend using AI to explore incidences of hepatitis complications, such as hepatic encephalopathy and hepatocellular carcinoma. It is recommended that further research using machine and deep learning in AI is needed to enhance earlier diagnosis and care of the hepatitis patient. Artificial intelligence has the potential to identify at-risk HCV patients 2 to 3 years before initial diagnosis or onset of signs and symptoms (Doyle et al., 2020; Liu et al., 2021; Shergill, 2021).

HBV Cure

In addition to preventing HBV, there is a global push to cure the virus. A cure requires complete seroconversion of HBV. The International Coalition to Eliminate HBV (ICE-HBV) has a team of more than 50 scientists researching a cure for HBV. The goal is to slow or stop cellular division from occurring. Researchers predicted that a cure for HBV is likely to come from multiple medications that address the episomal covalently closed DNA, the existence of HBV DNA within the large human genome, the large antigen load, and the exhausted immune response within the liver (Fanning et al., 2019; Lee et al., 2021; Revill et al., 2019).

Research also suggests that a cure for HBV may come from a direct attack on the core protein. Core protein allosteric modulators (CpAMs) may be able to prevent DNA replication. Other scientists concur that CpAMs are promising as a possible HBV cure (Schlicksup et al., 2018; Viswanathan et al., 2020).

New Goals

WHO seeks to combat the morbidity and mortality caused by hepatitis through encouraging vaccination, diagnostic testing, administration of medications, and education. The goal is to reduce new infections by 90% and deaths by 65% between 2016 and 2030. To accomplish this, all stakeholders, such as providers, nurses, patients, and families, must be on board and actively engaged in activities to screen for and treat the illness. APRNs have an excellent opportunity to contribute to the decrease and possible cessation of hepatitis through health promotion (WHO, 2022a).

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