Patient A is 19 years of age and a college sophomore who presented to her physician's office with mild jaundice. The patient reports being in good health until a week before, at which time she began having flu-like symptoms of headache, low-grade fever, nausea, loss of appetite, and malaise. She self-treated the fever with acetaminophen. The symptoms persisted. Upon awakening this morning, she noticed that her eyes were yellow. She therefore contacted her physician's office.

In response to her physician's questions, she indicated that her urine has been darker than usual and she has been experiencing joint pain for the last three days. She also acknowledged that her stools have been lighter than usual.

Her medical history is positive for mild exercise-induced asthma, for which she uses a prophylactic bronchodilating inhaler. Her only other routine medication is a daily vitamin/mineral supplement. She reports no surgeries. Family history is positive for cardiovascular disease (father and both sets of grandparents) and breast cancer (mother).

Other significant history includes that she was immunized against hepatitis B at 12 years of age and she recently participated in a two-week mission trip to Central America. Although she was very cautious about the foods she ingested during the mission trip, the patient indicated that a primary recreational activity after the day's work was to swim in the lagoon near the village. The lagoon was fed both by the stream in which the natives washed their clothes and the adjacent bay. Rainfall averaged 2–3 inches per day. Patient A returned to the United States five weeks ago.

Physical examination revealed a well-developed, well-nourished female who was alert and oriented. Her temperature was 99.7°F; other vital signs were within normal limits. Abnormal physical findings included mild icterus of sclera and skin, abdominal tenderness, hepatomegaly, and palpable spleen. Results of laboratory tests are indicated in Table 2.

Patient B is a paramedic, 48 years of age. Laboratory work obtained during his annual physical examination reveals hyperlipidemia; CBC, glucose, BUN, and electrolytes were within normal range. With the exception of his weight (15 lbs heavier than indicated for his height), his exam identifies no abnormalities.

After two months of a diet and exercise program, his cholesterol level is 256. Therefore, his physician elects to begin a lipid-lowering agent. A baseline liver profile is drawn prior to initiation of the medication. Because the patient is in a profession that is high-risk for bloodborne pathogen exposure, an HCV antibody test with reflex to qualitative HCV RNA is ordered. The liver profile reveals an AST of 226 Units/L and an ALT of 282 Units/L. HCV antibody and qualitative HCV RNA are both positive.

The physician reviews Patient B's history and medications. He has been a paramedic for 25 years. He was immunized against HBV in 1988. During his career, he has experienced several exposures to blood (usually blood splashes, but also two needlesticks from IV needles), most before the advent of Standard Precautions. His most recent exposure was two years ago. An HIV test six months post-exposure was negative. He does not recall hepatitis testing being performed at that time.

Patient B's surgical history includes a hernia repair in childhood and removal of skin lesions three times in the past eight years. He has had no transfusions. He is the widowed father of two teenage children. His wife died six years ago from ovarian cancer.

The patient has never smoked. He drinks about six beers per week and rarely drinks hard liquor. He denies any history of illegal drug use. Although the patient has no current prescription medications, he uses several herbal preparations including garlic, ginkgo, and an antioxidant preparation. The patient takes ibuprofen for pain, consuming 6 to 10 tablets (200 mg each) per month.

Although alcohol consumption and herbal antioxidants can both cause liver inflammation, the degree of his liver inflammation is much higher than would be expected from limited use of these two factors. The patient is diagnosed with chronic HCV infection.

In order to evaluate the extent of liver damage and determine an appropriate treatment plan, the physician orders an HCV RNA quantitative PCR and genotype as well as a PT. A gastroenterology specialist is consulted for further evaluation and possible liver biopsy and to co-manage the patient. The PT is within normal range. The liver biopsy reveals chronic inflammatory infiltration of the portal areas with minimal fibrosis. Genotype identifies the virus as type 3. HCV RNA viral load is 350,000 phages/cc.

Treatment options appropriate for HCV genotype 3, and the timing of therapy in relation to biopsy findings and anticipated progression of disease are discussed with Patient B. He is advised to eat a nutritious, balanced diet and abstain completely from alcohol. Although he is not currently sexually active, the patient is educated about the low but present risk of sexual transmission of HCV and how to minimize the risk of transmission. A test for HAV antibody is found to be negative. Immunization against HAV is also recommended, as acquiring an acute case of HAV in a patient with pre-existing chronic hepatitis can be much more serious that either condition alone. Because of uncertainty as to how recently he acquired the infection, the decision is made to defer treatment for three to four months while monitoring the course of the infection.

Four months after the initial diagnosis, there has been no improvement in Patient B's liver function tests: the ALT is 356 Units/L and AST is 418 Units/L. The HCV RNA remains detectable in the blood, and the viral load has increased to 450,000 phages/cc. He is advised to begin antiviral treatment; therapeutic options are discussed in relation to efficacy, potential drug interactions, and cost reimbursement priorities, bearing in mind that he is a treatment-naïve patient with no evidence of cirrhosis. The recommended course of therapy is the 12-week, two-drug oral regimen of sofosbuvir (400 mg) and velpatasvir (100 mg) for a duration of 12 weeks (reported SVR rate: 95% in clinical trials for genotype 3).

On treatment, the patient experiences transient nausea and persistent mild fatigue, but is compliant with the recommended duration of therapy. At 12 weeks, the ALT and AST are both within normal range and HCV RNA is undetectable. Treatment is discontinued and Patient B is asked to return in three months, six months, and one year after cessation of therapy to repeat HCV viral load and confirm a sustained virologic response.

Patient C is a man, 32 years of age, with a history of injection drug use, who participated in a free HIV testing day. His screening test was found to be positive. A confirmatory test conducted at the health department was also positive. He has therefore been referred to the Infectious Disease Clinic of a large university medical center for follow up.

During his first visit, the patient indicates that he injected drugs off and on beginning at 19 years of age. His first two experiences with rehabilitation failed, but he has been "clean" for two years, since his best friend died of an overdose. He reports that he also snorted cocaine occasionally during the years he used injected drugs.

The patient's medical history includes a hospitalization for a motorcycle accident at age 24, with surgery on his right leg both on that admission and again about a year later. He received 2 units of blood during the first admission. The patient denies a history of heart disease, neurologic disorders, or endocrine disorders. He has had pneumonia both in adolescence and again last year.

The patient's parents are living and in good health. Grandparents all have hypertension, and maternal grandmother has type 2 diabetes. The patient smokes 1/2 to 1 pack of cigarettes per day and consumes two or three drinks per day. The patient's current medications include acetaminophen or ibuprofen as needed for leg pain and paroxetine for anxiety and depression.

Physical examination reveals no acute distress. Vital signs are within normal limits, and sclerae are non-icteric. Oral cavity is free from thrush and leukoplakia. Cervical lymph nodes are palpable but moveable and nontender. Heart sounds are normal; lungs are clear. Abdomen is soft; both liver and spleen are palpable. Neurologic exam is normal. The patient has full function in upper extremities and left leg; right leg has a slight decrease in strength and a moderate decrease in range of motion.

Initial laboratory tests ordered by the nurse practitioner (NP) include an HIV PCR viral load, a CD4 count, a CBC, a chemistry panel, and a liver profile. Because of the high incidence of HCV and/or HBV coinfection in persons whose HIV was acquired percutaneously, the NP also orders a hepatitis profile. Baseline tuberculosis testing is also recommended for persons with HIV who are entering care. Therefore, a T-SPOT interferon gamma release assay is also ordered. The patient is instructed to return in 72 hours to review lab results and formulate a treatment plan.

Upon his return, all results except the HIV PCR are available. His CD4 count is 246. Hematocrit is 44%, hemoglobin 15 gm/dL, and WBC is 3,800. The liver profile reveals an alkaline phosphatase of 143 Units/mL, AST 358 Units/L, ALT 383 Units/L, total bilirubin 1.2 mg/dL, and albumin 2.8 gm/dL. The remainder of the chemistry panel is unremarkable. Hepatitis profile is positive for HBsAg, HBeAg, and total anti-HBc. The anti-HAV, anti-HCV and anti-HBc IgM are negative. The PPD is negative.

The NP informs Patient C that he is coinfected with HIV and HBV and instructs him about the problems associated with HIV/HBV coinfection. He is given HAV and pneumococcal immunizations and options for antiretroviral therapy are discussed. Because of its effectiveness against both HIV and HBV, a medication regimen including tenofovir with lamivudine or tenofovir with emtricitabine should be utilized. A third medication for HIV viral suppression should be added, with consideration of the hepatotoxicity profile of the medication. After discussing available options with limited hepatotoxicity, an integrase inhibitor is selected as the third active agent in the combination. A single tablet medication containing bictegravir, emtricitabine, and tenofovir alafenamide in a once daily formulation was therefore selected to treat both HIV and HBV.

Information is provided to Patient C regarding safe sex practices. He is also instructed to abstain from alcohol and to use ibuprofen (or no more than 2 g acetaminophen in 24 hours) for pain control. The NP also orders a PT to be drawn; in addition, the patient is referred to hepatology for a liver biopsy to be performed in order to evaluate the progression of the liver disease. The patient is scheduled for a follow-up visit in four weeks, with a repeat HIV PCR performed at that time. In the interim, his baseline HIV PCR is found to be 123,000.

Upon his return to the office, Patient C is advised that the liver biopsy revealed periportal inflammation with focal necrosis and bridging fibrosis. PT is 15.6 seconds (control: 12 seconds). These findings indicate severe, advanced liver disease and the guarded prognosis. Because of the severity of his liver disease, he is not a good candidate for PegIFN therapy. The patient's current HIV status precludes his being a transplant candidate at the time. The recommended treatment plan for Patient C is to maximize his HIV suppression while minimizing his continued liver damage. If he is compliant with his therapy, he should be able to maintain a fairly good quality of life for three years or more. Prolonging the time until liver failure also provides the opportunity to improve immunocompetency. Some liver transplant centers now accept HIV-positive patients, provided that HIV viral loads are undetectable and CD4 counts are sufficiently high (usually >500). Patient C's future, therefore, depends upon his tolerance of the regimen, his compliance with the treatment plan, and his body's response to therapy.

The patient will initially be followed on a monthly basis. The viral load will be checked one month after the initiation of therapy, then every three months thereafter. Liver profile, CBC, and amylase will be assessed after one month, then bimonthly. After three months, HIV and HBV quantitative PCRs will be measured. If both are well suppressed, follow-up will be extended to every two to three months. If the patient's liver function significantly deteriorates, supportive therapy for end-stage liver disease will be instituted.