In patients with a negative HCV RNA test, no further action is required for patients with no risk exposures. In patients with ongoing risk behaviors, at least annual HCV testing (HCV antibody test with reflex to HCV RNA) should be conducted; in addition, risk-reduction resources and support should be provided (Table 1). Patients with a positive HCV antibody test, but undetectable HCV RNA likely experienced a past infection. Patients who have detectable HCV RNA should be informed that they have an active HCV infection and could benefit from further evaluation and curative treatment. 

Pretreatment tele-video evaluation

A pretreatment visit should be scheduled as soon as possible after a detectable HCV RNA by PCR is received. The objectives of this visit are two-fold: (1) to obtain relevant signs and symptoms, clinical history, and laboratory tests, determine fibrosis stage, whether or not referral to specialist is warranted, and identify factors that may impact HCV treatment, and (2) to educate the patient about HCV, its modes of transmission and reinfection, and treatment expectations, alongside connecting them with support services to reduce high risk behaviors.³⁷ In the event an in-person visit is not feasible, a telemedicine appointment with video conferencing is recommended in order to inspect for stigmata of cirrhosis and other extra-hepatocellular manifestations. 

Physical examination

Key stigmata of cirrhosis and extra-hepatic manifestations can be reasonably assessed via telemedicine through visual examination of signs of portal hypertension and cirrhosis. For instance, the eyes (e.g., jaundice); the skin and nails, especially palms, hands, and face (e.g., erythema, jaundice, purpura, spider hemangiomas, temporal wasting); the abdomen (e.g., ascites and gynecomastia); and general demeanor (e.g., fatigue, coordination, orientation, response latency) are all signs that can be seen via video conferencing (Table 2). Inquiring about fatigue, changes in the mental state or gait, and any other symptoms the patient may be having can also provide insight into possible encephalopathy or other complications. Most patients with cirrhosis are asymptomatic, and will not exhibit these signs until end stage of disease. 

Blood work and fibrosis assessment

Laboratory evaluation should be comprehensive to minimize the need for multiple lab visits. Laboratory tests to assess liver and kidney function, and co-infection with HIV and HBV should be performed, if they have not been performed in the past 6 months (Table 2).³⁷ HCV genotype testing can be performed but is not necessary or recommended with the use of pan-genotypic DAAs.¹¹ Patients who would benefit from a referral to a specialist, whether for HCV treatment or for specialist co-management include previous HCV infection, cirrhosis, HBV or HIV coinfection, low platelets, known or suspected HCC, current pregnancy, renal impairment, and uncontrolled comorbidities (Figure 1). Other laboratory tests may be required by the individual’s insurance carrier for approval and thus should be considered for inclusion in the initial blood work to minimize the treatment delays.

Severity of liver disease and fibrosis assessment should be determined for every patient with HCV who is being considered for treatment. The AASLD and Infectious Diseases Society of America (IDSA) guidelines recommend assessment of liver disease severity either by directed physical exam, blood-based tests, or transient elastography.³⁷ Several serology-based tests can be employed to accurately assess the degree of fibrosis in patients with chronic HCV infection (Table 2).³⁷ Patients with blood tests indicating advanced fibrosis (e.g., Fibrosis-4 [FIB-4] score of >3.25, AST-to-platelet ratio index [APRI] >1.5, FibroTest^TM/Fibrosure^® > 0.58, and FibroMeter^TM >0.786) may be treated in the PCP setting in the absence of decompensated cirrhosis.^11–14 Patients with advanced fibrosis should additionally undergo a complete abdominal ultrasound and alpha-fetoprotein (AFP) to exclude hepatocellular carcinoma (HCC) and to assess for signs of portal hypertension. Those with decompensated cirrhosis (e.g., any signs of portal hypertension, hepatic encephalopathy, ascites, and/or edema evident during the physical exam conducted by telemedicine) or platelet levels less than 100,000/mL should be co-managed or referred to a specialist (Figure 1).

Studies have supported that patients with compensated cirrhosis and HCV infection can be appropriately treated in the PCP setting, while patients with decompensated cirrhosis or hepatocellular carcinoma (HCC) should be referred to a specialist with expertise in liver transplantation and cancer treatment.^{22–25,27,32} We recommend that non-specialists develop relationships with expert HCV specialists who can offer guidance on specific management questions. An example of such collaboration is The National Clinician Consultation Center at the University of California, San Francisco; offers free phone and online consultation from national experts, as well as a variety of materials, including online HCV educational courses. Another option for support is participation in Project ECHO’s telementoring program, which offers a mentor/collaborative care relationship with specialists.

Patient education and counseling

Once a patient receives a confirmatory positive HCV RNA and has agreed to set up a telemedicine visit, we recommend discussing best contact number and alternate contact information; patient portal registration, if available; and mobile and/or broadband internet access to help identify patient preference in communication, as well as uncover any potential barriers. Of note, programs are available to offer more affordable devices and broadband plans to low-income consumers (Table 4).

The AASLD/IDSA guidelines recommend that patient education and harm reduction interventions be offered over the entire HCV care continuum to reduce the risk of liver disease progression and to prevent HCV transmission.³⁷ Videos, patient brochures, and other patient educational materials are available online (Table 4). Of note, patients may prefer to view these materials in private due to their sensitive subject matter and associated stigma. Assessing for ongoing substance use disorder, educating patients regarding its effect on worsening of fibrosis, and connecting patients with appropriate supportive services are important to the long-term management of HCV patients in order to target harm reduction services and gauge risk for reinfection. Persons who actively inject drugs should be prioritized for HCV treatment, as they are likely to transmit HCV to others, and curative treatment can prevent transmission. Moreover, treatment of opioid use disorder can be initiated concurrently with HCV treatment,¹⁴ as no drug-drug interactions have been reported between methadone or buprenorphine and the pan-genotypic direct-acting antiviral (DAA) regimens in the treatment algorithm (Table 3).^14,15

Finally, discussions with patients about expectations for their course of treatment are integral to patient engagement and treatment success. These discussions should include the process of obtaining the medication from a specialty pharmacy, any potential for drug interactions, the importance of adherence, and the need for blood work to confirm cure once treatment is complete.

Optional on-treatment follow-up tele-visit

Treatment: Aside from those whose short life expectancy cannot be improved by HCV therapy or liver transplantation, all patients with HCV infection should be treated, including persons who use drugs and/or alcohol.] We recommend the use of one of two highly effective, pan-genotypic therapies for HCV treatment, each included in the algorithm: Glecaprevir/Pibrentasvir (GLE/PIB) and Sofosbuvir/Velpatasivir (SOF/VEL). Each of these therapies demonstrates SVR12 cure rates of ≥ 95% in registration trials and real-world experience, and they share similar safety profiles.^14–18 A comparison of the two treatments is provided in Table 3.

Of note, hepatic impairment and potential drug interactions may direct the decision between the two treatments and will determine the type of monitoring or dose duration modifications that may be necessary. Protease inhibitors, such as glecaprevir in GLE/PIB, are contraindicated in those with suspected/history of decompensated liver disease (Child-Turcotte Pugh Class B or C).⁴⁵ We recommend the use of specialty pharmacies, as they typically offer assistance with the prior authorization process and with access to patient financial assistance programs.

Monitoring

It is important to observe that AASLD recommends, and our expert panel is in agreement, that no laboratory monitoring is required during HCV treatment. Recent findings from a multinational, minimal monitoring (MINMON) study (n= 400) have shown that minimal monitoring, (no pre-treatment genotyping, no scheduled on-treatment clinic or labs, and telemedicine touchpoint at Weeks 4 and 22) and 84-days supply of SOF/VEL provided at start of treatment resulted in 95% SVR rate (95% CI, 92.4, 96.7).¹⁷ Other minimal monitoring studies have reported similar results.^17,18 Unique instances that may require special laboratory monitoring include a patient taking warfarin; and then international normalized ration (INR) should be monitored periodically.³⁷ Patients with diabetes are not at risk of hypoglycemia due to DAAs and in fact may exhibit improvements in insulin resistance with eradication of HCV.¹⁷ Some clinicians may choose to order additional labs during treatment for cirrhotic patients or those with secondary causes of liver disease.

Touchpoints, such as an electronic portal, bidirectional text messaging with reminders, telephone, and/or video conferencing, are encouraged throughout the treatment course. These touchpoints can support medication adherence; monitor for adverse events and any drug interactions potentially arising from new medications started after the pre-treatment visit; and connect patients with support services if needed.³⁷A meta-analysis of touchpoint effectiveness conducted by Thakkar and colleagues showed that text messaging was associated with a two-fold increase in medication adherence in adults with chronic diseases.¹⁷ Frequency of these touchpoints, as well as type of communication pathway should be individualized based on the needs of each patient, especially those who may have social and/or psychological barriers that may require other supportive services. Providers can also coordinate care with patient navigators, nurse coordinators, social workers, and pharmacists to take an active role in tracking and monitoring patients through the HCV care continuum. A video conference appointment can be used in the event a patient experiences side effects, skin findings, swelling, or other issue that may require a physical examination. 

HCV RNA by PCR and an ALT should be collected at least 12weeks after treatment completion to document HCV cure (SVR12). Undetectable viral load at 12 weeks after completion of treatment confirms eradication. Presence of viral load may be indicative of recurrent viremia (post-treatment virologic relapse or HCV re-infection). In either case, an HCV infection is present, and the patient should undergo another course of HCV treatment tailored to the patient’s circumstances.³⁷

Post-cure follow-up tele-visit

A telemedicine appointment should be scheduled after SVR12 results are received to provide positive reinforcement toward achieving SVR12, as well as to emphasize measures to avoid re-infection and further liver damage. In non-cirrhotic and/or low-stage fibrosis (F0 and F1) patients, no further liver workup is necessary; however, patients with intermediate stage of fibrosis (F2) and/or ongoing concern for progression of fibrosis, should undergo annual fibrosis assessment. For patients with advanced fibrosis or cirrhosis (fibrosis stage F3 and F4), HCC surveillance (a liver ultrasound with AFP) is recommended every 6months. Telemedicine platforms can be employed to improve HCC surveillance [60] (currently only 24% of patients receiving HCC surveillance according to the guidelines),¹⁷ such as patient reminder/recall systems, patient education, and other population health outreach strategies.⁶⁰

All patients should be reminded that re-infection is possible with repeat exposure to HCV infected blood. In addition, patients should be educated that the HCV antibody test will always remain positive if tested in the future – and does not protect from reinfection. Annual testing with HCV RNA by PCR is recommended in those who continue behaviors associated with risk of HCV infection, such as people who inject drugs and unprotected sex.³⁷ Patients should be linked to community-based harm reduction services, such as syringe service programs (SSPs), treatments for substance use and mental health disorders, and support services for food insecurity and homelessness. Addressing these risks will reduce the likelihood of HCV reinfection and the acquisition of other infections, such as HIV and other sexually transmitted infections.¹⁴

Syringe service programs are of particular interest as they can significantly impact HCV transmission. It is estimated that a complete mitigation of shared needles could prevent 43% of all HCV cases globally and 77% of cases in North America by 2030.¹⁷ Providing long-term care for HCV patients through telemedicine can preserve privacy, lessen the fear of discussing sensitive subjects, be less burdensome on patients, and improve outcomes. A randomized trial of patients with substance use disorders found that those receiving telephone-based continuing care had higher rates of abstinence over 2years, and that their care cost less than a standard continuing care or relapse prevention program.¹⁸