Hepatitis C

Hepatitis C virus

https://meditropics.com/650-2/

Ankur Verma

Post graduate resident, department of medicine , LHMC

 

It’s is a major cause of chronic liver disease and a major health problem in india and worldwide.it is classified in family flaviviridae and under genus hepaciviridae; found as lipoviral particle, virion bind to IgG, free virion in blood contains ssRNA forming structural proteins – core protein, E1 and E2 glycoprotein and nonstructural proteins P7, NS3, NS4A, NS4B, NS5B. It is having a prevalence of  0.7% in india with maximum infection by genotype 3 and genotype 1.

Lipoviral particle is most infectious form and the lifecycle start with binding of the particle to liver cell followed by endocytosis, uncoating and fusion to translation to processing and replication, assembly, maturation and release. For replication there is formation of membranous web.

Hepatitis c virus can cause acute hepatitis, of which 55-89% develops chronic hepatitis, of which 2-24% develops cirrhosis over 20 yrs. Patient develops hepatic decompensation 3% per year and HCC 1-4% per year. There are extra hepatic manifestations of hepatitis C of which proved are lichen planus, autoimmune thyroiditis, B-cell NHL, mixed cryoglobulinemia.

Diagnosis of hepatitis c virus is done by detection of the reactivity of anti-HCV antibodies and later detection of HCV RNA levels, if RNA levels are detected it is diagnosed as current infection. Testing is done in individuals of >17 years of age with opt out testing, less than 18 years with increased risk of HCV, prenatal HCV testing, testing of individuals with high risk periodically and annually done in persons using inject drugs, men who having sex with men taking PrEP, HIV infected man having unprotected sex with man, solid organ donor or recipient.

There are some high risk group have been defined like with risk activities like persons doing injection drug use, intranasal illicit, use of glass crack pipe, men having sex with men and those with risk exposure like patients on hemolysis, parenteral exposure, needle stick injury, child born to infected woman transfusion or organ transplant.

Therapy is started in patients all patients with acute and chronic HCV infection and goal of the therapy is to achieve sustained virological response (SVR). Before starting treatment preliminary test required are CBC, INR, hepatic function, KFT, cirrhosis assessment. Based upon the the test patient treatment has been divided as

  1. Patients those are treatment naïve adults without cirrhosis – in this category patients have chronic hepatitis c and have not received treatment and are started on glecaprevir(300mg)/pibrentasvir(120mg) for a duration of 8 weeks or sofosbuvir(400mg)/velpatasvir(100mg) for a duration of 12 weeks. In these patients monitoring for hypoglycemia and INR in patient on warfarin therapy is required. And SVR is done at 12 week of therapy.
  2. Treatment naïve with compensated cirrhosis – HCV positive with child pugh A and have not received any treatment, for them with genptype 1-6 started on glecaprevir(300mg) /pibrentasvir(120mg) for 8 weeks and for genotype 1,2,4-6 sofosbuvir (400mg)/ velpatasvir (100mg) for 12 weeks before starting genotype 3 on sofosbuvir (400mg)/ velpatasvir (100mg) for 12 weeks RAS is done and if Y93H is positive we have to add ribavirin weight based and if ribavirin ineligible than continue for 24 weeks.
  3. Treatment in decompensated HCV positive – started on sofosbuvir/ velpatasvir +ribavirin for 12 weeks or sofosbuvir/ ledipasvir and low dose ribavirin for 12 weeks. If ribavirin ineligible than continue for 24 weeks.

This patient should be monitored for hepatic profile and drug to be discontinued if there is > 10 fold increase in ALT, <10 fold increase in alt with symptoms and deranged INR and bilirubin and <10 fold in ALT levels with persistent elevation after 2weeks of observation.

Those patients who has achieved SVR

  1. Assess HCV reoccurance annually
  2. If cirrhosis present UGI endoscopy to be done
  3. If liver disease is present with normal SVR look for other cause
  4. More frequent monitor of CBC if therapy includes ribavirin

Those patients who has not achieved SVR

  1. Assess every 6 to 12 hrly with CBC and INR
  2. Surveillance for HCC every 6 month
  3. Surveillance of varices in cirrhotic patients

Retreatment in patients with prior failure of therapy

Sofosbuir-based treatment failures, with or without compensated cirrhosis

Sofosbuvir (400mg)/velpatasvir(100mg)/voxilaprevir(100mg) with genotype 3 add weight based ribavirin

Alternative regimen – glecaprevir/pibrentasvir

Multiple DAA treatment failure (all genotype)

Glecaprevir (300mg)/pibrentasvir(120mg) plus daily sofosbuvir(400mg) and weight based ribavirin for 16 weeks.

Or

Sofosbuvir(400mg)/velpatasvir(100mg)/voxilaprevir plus weight ribavirin for 24 weeks   

HIV and HCV medication interaction

          Elbasvir(50mg)/grazoprevir(100mg)

          Glecaprevir(300mg)/pibrentasvir(120mg)

          Sofosbuvir(400mg)/velpatasvir(100mg)

          Ledipasvir(90mg)/sofosbuvir(400mg)

Sofosbuvir(400mg)/velpatasvir(100mg)/voxilaprevir(100mg)

In HCV postive patients with HCV no dose adjustment is required and during postpartum period breast feeding is not contraindicated.

There is a key population (PWID, MSM, individuals in correactional centres) screening is done annually, counselling and testing for HIV PrEP is done.

Management in acute hepatitis is with same regimen as we have used in chronic hepatitis, treatment is started without waiting for spontaneous resolution. During the treatment patient should avoid alcohol and hepatotoxic drugs.