Viral Hepatitis Co-infection, Overview

Clinical Management and Treatment of Viral Hepatitis Co-infections in PLWH

Every person with HCV/HIV co-infection should receive DAA therapy to eradicate HCV, regardless of liver fibrosis stage in the context of faster liver fibrosis progression in co-infected persons and the availability of DAAs with excellent tolerability and efficacy. DAAs achieve similar cure rates and tolerability in HCV/HIV co-infected compared to HCV mono-infected persons. Therefore, treatment indication and regimens are the same as in HCV mono-infected persons. All persons with HBV/HIV co-infection should receive ART including TDF or TAF, unless history of tenofovir intolerance. All HBsAg-positive persons should be screened for Hepatitis Delta (HDV).

General Recommendations

General Recommendations for Persons with Viral Hepatitis/HIV Co-infection

Screening at Baseline

  1. PLWH should be screened for HCV at time of HIV diagnosis and annually thereafter(i). Screening should use an anti-HCV antibody test(ii). A positive result should be followed by HCV-RNA(iii) and genotype determination. Alternatively, HCV core-antigen testing can be performed to establish chronic HCV infection. PLWH engaging in activities associated with increased risk of HCV transmission(iv) should be tested for HCV infection every 3 to 6 months. PLWH suspected of recently acquired primary HCV infection with a negative anti-HCV antibody test should be tested for HCV-RNA. HCV-RNA or HCV core-antigen testing is also recommended in PLWH with ongoing risk behavior for HCV re-infection after successful treatment or spontaneous clearance at 3 to 6-monthly intervals
  2. PLWH should be screened for HAV and HBV. PLWH who are anti-HBc positive and HBsAg negative, in particular those with elevated liver transaminases, should be screened for HBV-DNA in addition to HBsAg to rule out occult HBV infection
  3. HDV antibodies should be screened for in all HBsAg positive persons                  
  4. PLWH with viral hepatitis co-infection should be assessed for concurrent causes of liver disease such as alcohol consumption, cardiac disease, renal impairment, autoimmunity, genetic or metabolic liver diseases (e.g. genetic haemochromatosis, diabetes mellitus or obesity) and drug-induced hepatotoxicity
  5. Status of liver damage should be assessed in all PLWH with viral hepatitis co-infection with a complete blood count, ALT, AST, GGT, ALP, hepatic synthetic function (e.g. coagulation, albumin, cholinesterase) and staging of fibrosis (e.g. FibroScan, liver biopsy, serum fibrosis markers(v), see Table on cut-off values of non-invasive tests for the detection of significant fibrosis and cirrhosis

Screening for Complications

  1. HCC screening is indicated in all cirrhotic HBV or HCV co-infected PLWH (even if HCV infection has been cured and HBV replication is medically suppressed) in a setting where treatment for HCC is available. Although the cost-effectiveness of HCC screening in persons with F3 fibrosis is uncertain, surveillance may be considered based on an individual risk assessment, see page 52. In HBV-positive non-cirrhotics, HCC screening should follow current HCC EASL guidelines. Risk factors for HCC in this population include family history of HCC, ethnicity (Asians, Africans), HDV and age > 45 years. EASL guidelines propose using the PAGE-B score in Caucasians to assess the HCC risk, however this score has not been validated in PLWH, see Assessment of PLWH at Initial & Subsequent Visits, Viral Hepatitis Co-infection, Cancer: Screening Methods, and Liver Cirrhosis: Management
  2. Screening for oesophageal varices upon diagnosis of cirrhosis in co-infected persons is also indicated (every 2-3 years thereafter according to presence of ongoing liver disease if negative for oesophageal varices at initial screening), see Liver Cirrhosis: Classification and Surveillance

End Stage Liver Disease (ESLD)

  1. PLWH with liver cirrhosis require the same measures for the treatment of oesophageal varices, hepatorenal syndrome, hepatic encephalopathy or ascites as HIV-negative persons, see Liver Cirrhosis: Classification and SurveillanceLiver Cirrhosis: Management, and Diagnosis and Management of Hepatorenal Syndrome (HRS)
  2. Persons with viral hepatitis/HIV co-infection suffering from ESLD warrant particular attention in the management of liver insufficiency, see Dose Adjustment of ARVs for Impaired Hepatic Function. ART in cirrhotic PLWH improves overall survival
  3. PLWH with HCC or a MELD-score > 15(vi), CD4 count > 100 cells/μL and options for efficacious and durable ART should be evaluated for liver transplantation (OLTX), see Solid Organ Transplantation (SOT) in PLWH
  4. Renal complications are frequent, see Kidney Disease: Definition, Diagnosis and Management, and Diagnosis and Management of Hepatorenal Syndrome (HRS)

Vaccination

(see Vaccination)

  1. PLWH lacking anti-HAV IgG antibodies or anti-HBs antibodies should be offered vaccination for the respective virus to prevent infection regardless of their CD4 count. The response to the HBV vaccine is influenced by the CD4 count and level of HIV-VL. In PLWH with low CD4 count (< 200 cells/μL) and ongoing HIV replication, ART should be initiated first, prior to respective vaccination. Because of the lack of data on the impact of immunisation in isolated anti-HBc IgG positive persons (HBsAg negative, anti-HBc positive and anti-HBs negative profile), vaccination is not recommended in this population. However, if anti-HBc results are not available, HBV vaccination is recommended in all HBs-Ag negative persons
  2. In PLWH vaccinated for HBV with insufficient response (anti-HBs < 10 IU/L), re-vaccination should be considered. Double-dose (40 μg) at 3-4 time points (months 0, 1, 6 and 12) may help to improve response rates to the HBV vaccine. Persons who fail to seroconvert after HBV vaccination and remain at risk for HBV should have annual serological tests for evidence of HBV infection. TDF based cART has been associated with prevention of HBV infection in these persons and ART including TDF or TAF is recommended

Prevention/Support

  1. Psychiatric, psychological, social and medical support should be made available to persons with alcohol intake to stop drinking
  2. Substitution therapy (opioid replacement therapy) in persons with active drug use as a step towards cessation of active drug use should be encouraged. Help provided (e.g. through needle and syringe exchange programs) reduces the risk of re-infection including parenteral viral transmission (harm reduction strategy), see Drug Dependency and Drug Addiction
  3. Since HBV and HIV, and occasionally HCV, are transmitted sexually, adequate counselling including the use of condoms is advisable. Information on the risk of HCV transmission due to mucosal traumatic sexual practices associated with a high likelihood of blood contact or ongoing IDU, “chemsex” (sex under the influence of recreational drugs taken predominantly intravenously immediately before and/or during sexual contacts), should be provided and risk reduction should be discussed
  4. In women of childbearing age, HCV treatment should be initiated prior to conception because of limited safety data in pregnancy, and to reduce the risk of MTCT of HCV

Notes:

  1. Screening intervals to detect recently acquired HCV infection should be adapted to individual risk assessments and local epidemiology as described in the European AIDS Treatment Network (NEAT) consensus conference statement, www.neat-id.org
  2. Anti HCV-Antibodies: turn positive 1-6 months after infection; late seroconversions have been described; may rarely be lost due to immunosuppression
  3. There is no standard conversion formula for converting the amount of HCVRNA reported in copies/mL to the amount reported in IU/mL. The conversion factor ranges from about one to five HCV-RNA copies per IU/ mL
  4. Risk for percutaneous HCV transmission by sharing equipment for injection drug use; risk for mucosal HCV transmission including fisting, receptive condomless anal intercourse, sharing equipment during nasally administered drug use, sharing sex toys, sharing anal douching equipment, and engaging in sexual intercourse causing rectal trauma with bleeding; the presence of ulcerative sexually transmitted infections (STIs) increases the risk of HCV transmission
  5. Serum fibrosis markers include APRI, FIB-4, Hyaluronic acid, Fibrometer, Fibrotest, Forns, Hepascore and other indices. The combination of blood biomarkers, of liver stiffness measurement and blood tests or repeated assessments may improve accuracy (https://easl.eu/publication/easl-recommendations-treatment-of-hepatitis-c) and Cut-off Values of Non-invasive Tests for the Detection of Significant Fibrosis and Cirrhosis. For HCC, see General Recommendation for Persons with Viral Hepatitis/HIV Co-infection, Cancer: Screening Methods and Liver Cirrhosis: Management
  6. MELD calculation, see Liver Cirrhosis: Management