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Clinical Management and Treatment of Viral Hepatitis Co-infections

Every person with HCV/HIV co-infection should receive DAA therapy to eradicate HCV, regardless of liver fibrosis stage. Cure of HCV infection substantially reduces the risk for hepatic and extrahepatic complications and eliminates onward HCV transmission. 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 for Persons with Viral Hepatitis/HIV Co-infection

Screening at Baseline

  1. HCV should be screened for 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 which is not mandatory if pangenotypic drugs are to be used. Alternatively, HCV core-antigen testing can be performed to establish chronic HCV infection. Persons engaging in activities associated with increased risk of HCV transmission(iv) should be tested for HCV infection every 3 to 6 months. Persons 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 persons with ongoing risk behavior for HCV re-infection after successful treatment or spontaneous clearance at 3 to 6-monthly intervals
  2. All persons should be screened for HAV and HBV. Persons 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 with detectable viremia
  3. HDV antibodies should be screened for in all HBsAg positive persons                  
  4. Persons 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 persons 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. liver stiffness, liver biopsy, serum fibrosis markers(v), see Table on cut-off values of non-invasive tests for the detection of advanced fibrosis and cirrhosis). Staging of fibrosis should identify patients with compensated advanced chronic liver disease (cACLD) and among them those with clinically significant portal hypertension (CSPH) see Liver Cirrhosis: Classification and Surveillance
  6. Treatment with non-selective beta blockers (NSBBs propranolol, nadolol or carvedilol) should be considered for the prevention of decompensation in patients with CSPH. Carvedilol is the preferred NSBB in compensated cirrhosis, since it is more effective at reducing hepatic venous pressure gradient (HVPG)

Screening for Complications

  1. HCC screening every 6 months (see Liver Cirrhosis: Management) is indicated in
    a) all cirrhotic patients (irrespective of viral clearance for HCV or viral suppression for HBV)
    b) non-cirrhotic HBV (irrespective of HBV suppression) in persons with one of the following: family history of HCC; Asian/African ethnicity, HDV-co-infection, age >45 years, Caucasian patients with PAGE-B score ≥10
    c) consider HCC screening for persons with advanced fibrosis, regardless of etiology, based on individual risk assessment (e.g. family history of HCC)

End Stage Liver Disease (ESLD)

  1. Persons with HIV and 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 Surveillance and Liver Cirrhosis: Management
  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 persons improves overall survival
  3. Persons with HCC or a MELD-score > 12(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)
  4. Renal complications are frequent, see Kidney Disease: Definition, Diagnosis and Management

Vaccination, see Immunisation in Persons with HIV

  1. Persons 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 persons with low CD4 count (< 200 cells/μL) and ongoing HIV replication, ART should be initiated first, prior to respective vaccination. The use of the more immunogenic vaccine Heplisav B should be evaluated where available. Heplisav B may be used for primary immunization to reach better responses. Because of the lack of randomized data on the impact of immunisation in isolated anti-HBc IgG positive persons (HBsAg negative, anti-HBc positive and anti-HBs negative profile), vaccination should be discussed on an individual level. However, if anti-HBc results are not available, HBV vaccination is recommended in all HBsAg negative persons
  2. In persons vaccinated for HBV with insufficient response (anti-HBs < 10 IU/L), re-vaccination should be considered. The use of the more immunogenic vaccine Heplisav B should be evaluated where available (off-label). Double-dose Engerix (40 μg) at 3-4 time points (months 0, 1, 2 and 6) 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 ART 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 Opioid 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. If HCV is diagnosed during pregnancy, treatment should be discussed, taking into consideration the possibility to reduce MTCT, the limited safety data, and the risk of loss to follow-up after delivery. HBV therapy should be continued throughout pregnancy.

 

  1. Screening intervals to detect recently acquired HCV infection should be adapted to individual risk assessments and local epidemiology as described in the Recommendations on recently acquired and early chronic hepatitis C in MSM from the European treatment network for HIV, hepatitis and global infectious diseases consensus panel
  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 HCV-RNA 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-on-treatment-of-hepatitis-c-2020/, free registration needed to get access) and Liver Cirrhosis: Management
  6. MELD calculation, see Liver Cirrhosis: Management