ABCs of Viral Hepatitis What Primary Care Physicians Need to Know

Transcription

1 ABCs of Viral Hepatitis What Primary Care Physicians Need to Know Dr Kenny C.P. Sze Associate Consultant Division of Gastroenterology Department of General Medicine

2 Outline and Keypoints Hepatitis A Recap; remember vaccination Hepatitis B When to refer; other management measures Hepatitis C Where are we (Singapore) now with Interferon free therapy?

3 Hepatitis A

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5 Hepatitis A Transmission: Faecal-oral incl. contaminated food/water, direct contact with infected patient Incubation: 2-6 weeks Symptoms: Fever, myalgia, fatigue LOA, N+V, abdo pain Icterus/urine+stool discolouration Complications: Majority of cases self-limiting (ALF 0.35% cases) Rarely ALF (higher risk of with pre-existing chronic liver disease eg. >40% with HCV)

6 Diagnosis/Management Hepatitis A IgM Acute infection Usually associated with markedly deranged LFTs Hepatitis A Ab total (or IgG) Immunity (either from past exposure or vaccination) Supportive care Majority of cases self-limiting Contact precautions (prevent transmission) Prevention Vaccination; esp. patients with chronic liver disease!

7 Hepatitis B

8 Hepatitis B Transmission: Blood borne (including mother to child); sexual contact Incubation: 1-6 months Symptoms: No symptoms Fever, myalgia, fatigue LOA, N+V, abdo pain Icterus/urine+stool discolouration Complications: ALF uncommon (0.1 to 0.5%) Fibrosis, cirrhosis, decompensation (long term) Hepatocellular carcinoma Extrahepatic manifestations

9 How to diagnose HBV / interpret serology? Past Exposure Infection Immunity Anti-HBc IgM Anti-HBc IgG HBsAg Anti-HBs Interpretation Early acute HBV infection Acute HBV infection or Acute flare of chronic infection Refer for GE evaluation Chronic HBV infection Exposure but resolved HBV infection Prior vaccination No exposure or immunity

10 Known HBV Disease phases/when to refer? Risk of progressive fibrosis & cirrhosis Refer GE to consider antiviral therapy to prevent damage

11 What is the purpose of HBV Therapy? Goal Induce immunologic control / cure or suppress viral replication, in order to prevent: Hepatic complications: Cirrhosis Decompensation Hepatocellular carcinoma Extrahepatic manifestations and related morbidity/mortality E.g. Polyarteritis nodosa, glomerulonephritis (membraneous/membranoproliferative GN) End point Virological suppression HBeAg loss/anti-hbe seroconversion HBsAg loss /anti-hbs seroconversion (rare)

12 What treatments are available? Pegylated interferon Side effects common Constitutional Neuropsychiatric Haematologic Infective Decompensation Variable off treatment response rates eag positive Anti-HBe seroconvsersion ~30% to 50% sag loss 3-7% eag negative Sustained off treatment response <20% sag loss 3-12% Depending on various factors including eag status, viral load, ALT level, genotype Finite therapy 48 weeks, frequent monitoring for toxicity required Nucleos(t-)ide analogues Minimal/uncommon side effects High virological suppression rates Generally in excess of 90%-95% Extemely rare/no resistance with newer agents Entecavir and Tenofovir Low off treatment response rates eag positive Anti-HBe seroconversion ~ 20% sag loss 0-3% eag negative Sustained off treatment response <5% sag loss very rare Indefinite therapy duration Risk of flare off therapy

13 Other management considerations HCC screen AASLD/EASL: surveillance 6 monthly (US with/without AFP) if Men 40 Women 50 Anyone with advanced fibrosis/cirrhosis or family history of HCC Additionally MOH suggests at least 12 monthly (US with AFP) for anyone with HBV Check for other blood borne viruses (HCV, HIV) Family/sexual contact screening + vaccination, precautions against transmitting to others Alcohol abstinence Vaccination for HAV (if no immunity) GE referral for females of childbearing years with plan for pregnancy To evaluate risks of vertical transmission and risk reduction measures

14 Hepatitis C

15 Hepatitis C Transmission: Blood-borne Incubation: days Symptoms: Often asymptomatic Associated with fatigue, impaired QOL Extra-hepatic manifestations (PCT, vasculitis) Complications: Liver related: Fibrosis, cirrhosis, decompensation, HCC Extra-hepatic: Insulin resistance/dm, Cryoglobulinaemic vasculitis, ITP, PCT, lymphoma

16 How to diagnose HCV? HCV Ab (1 st line) Exposure HCV RNA Ongoing infection If Ab positive If suspect acute infection, or immunocompromised HCV Ab positive, but RNA negative Retest RNA 3 months after to confirm no infection/cleared infection

17 Who needs referral/treatment? All patients with HCV should be referred and considered for treatment Especially if: Cirrhosis or significant fibrosis Clinically significant extra-hepatic manifestations E.g. cryoglobulinaemic vasculitis, porphyria cutanea tarda, NH lymphoma Those at risk of transmitting to others E.g. women of child-bearing age who wish to get pregnant; haemodialysis pts Treatment not recommended if limited life expectancy due to non-liver related comorbidities

18 What is the purpose of HCV Therapy? Goal Cure HCV in order to prevent: Hepatic complications: Cirrhosis Decompensation Hepatocellular carcinoma Extrahepatic manifestations and related morbidity/mortality End point Sustained virologic response Undetectable RNA at week 12 (SVR12) or 24 (SVR24) after end of treatment

19 What treatments are available? Pegylated interferon/ribavirin (PEG/RBV) Side effects common Constitutional Neuropsychiatric Haematologic Infective Decompensation Prolonged therapy and frequent monitoring weeks Frequent clinical and laboratory monitoring Low SVR rates Between 50% (GT1) to 60-80% (GT2/3) Lower with cirrhosis, unfavourable IL28b genotypes Direct acting antivirals (DAAs +/- RBV) Minimal side effects Mostly similar to placebo Few cases of decompensation (3D regime) Drug-drug interactions need to be considered RBV related AE needs to be considered Shorter therapy, less monitoring Generally 12 weeks (sometimes 24 weeks, but occ. as little as 8 weeks) Relatively little clinical and laboratory monitoring Very high SVR rates Generally in excess of 90 to 95% Lower in certain subgroups e.g. decompensated cirrhosis (60-80%, but still far superior SVR and AE profile than PEG/RBV)

20 Interferon-free DAA regimes Asunaprevir/Daclatasvir Yes No No No No

21 Interferon-free DAA regimes in Singapore Asunaprevir/Daclatasvir Yes No No No No

22 Treatment durations PEG/RBV naïve or experienced DAA naïve No cirrhosis NB: Cirrhotic / decompensated patients may require Addition of Ribavirin Longer therapy (24weeks)

23 DAA DDIs

24 How much does it cost? DAA regimes vary (+/- ribavirin) Asunaprevir/Daclatasvir Paritaprevir/ritonavir/Ombitasvir/Dasabuvir Ledipasvir/Sofosbuvir Sofosbuvir/Daclatasvir Costs vary with regime and duration Range from approximately $30,000 to $180,000

25 National Foundation of Digestive Disease Treatment Access Program (NFDD TAP) Reduced prices for those who are: Singapore citizen or PR, and, subsidised patients of restructured hospitals Requires evaluation by MSW and approval by NFDD Treatment regime to be determined by respective hospital policies and guidelines

26 National Foundation of Digestive Disease Treatment Access Program (NFDD TAP) Drug Dose Qty per bottle/box Selling price per bottle under NFDD Tap ($) Minimum ordering quantity Asunaprevir 100mg BD bottle Daclatasvir 60mg OM 28 3, (when dispensed with Asunaprevir) 1 box Daclatasvir 60mg OM 28 4, box Sofosbuvir 400mg OM 28 15, bottle Sofosbuvir, Ledipasvir 400mg/90mg (1 tab) OM Paritaprevir, ritonavir, Ombitasvir, Dasabuvir 28 19, bottle 1 packet daily 28 daily packs 13, pack

27 National Foundation of Digestive Disease Treatment Access Program (NFDD TAP) Drug Dose Qty per bottle/box Selling price per bottle under NFDD Tap ($) Minimum ordering quantity Asunaprevir 100mg BD bottle Daclatasvir 60mg OM 28 3, (when dispensed with Asunaprevir) 1 box Daclatasvir 60mg OM 28 4, box Sofosbuvir 400mg OM 28 15, bottle Sofosbuvir, Ledipasvir 400mg/90mg (1 tab) OM Paritaprevir, ritonavir, Ombitasvir, Dasabuvir Expensive But Curative 28 19, bottle 1 packet daily 28 daily packs 13, pack

28 Other management considerations HCC screen if advanced fibrosis/cirrhosis Check for other blood borne viruses (HBV, HIV); precautions against transmitting to others Family/sexual contact screening Alcohol abstinence Vaccination of HAV/HBV (if no immunity)

29 Summary / Take home messages Hepatitis A Remember vaccination Hepatitis B Phases of disease / when to refer Treatment approaches available HCC screen BBV screen Family/sexual contact screen + vaccination; precautions against transmission to others Alcohol abstinence Remember vaccination Hepatitis C BBV screen Family/sexual contact screen; precautions against transmission to others Alcohol abstinence Remember vaccination Direct acting anti-virals (DAAs) now available in Singapore