Hepatitis C is not just a liver disease. Geri Hirsch RN-NP, MSN February 2014

Transcription

1 Hepatitis C is not just a liver disease Geri Hirsch RN-NP, MSN February 2014

2 Disclosures Merck Janssen Vertex Abbvie Roche

3 This Talk Meets the Following CAHN Standards 1. Provides competent and professional care. 2. Performs and/or refines client assessment. 3. Administers and/or monitors therapeutic interventions. 4. Manages rapidly changing situations. 5. Intervenes with the teaching/coaching function. 6. Monitors and ensures the quality of health care practices. 7. Practices within organizational and professional practice structures.

4 This Talk Meets the Following CAHN Competencies Viral Hepatitis 3a.6 Understand available anti-viral therapies used to treat adult clients with chronic hepatitis B, C and or D infection (pre and post liver transplant) 3a.7 Describe tests that are used to monitor a client during therapy for chronic hepatitis B, C and D (pre and post liver transplant) 4.2 Participate in the dissemination of new knowledge in hepatology nursing

5 Introduction Hepatitis C virus (HCV) is an infectious disease that often remains asymptotic and unrecognized until complications of the virus arise. The extra hepatic manifestations(ehm) of the virus, which first bring patients into contact with the medical profession. EHMs can be the dominant feature, while hepatic disease is mild. Recognized in the 1990s several syndromes and conditions have now been linked to hepatitis C, other still emerging

6 Introduction Established conditions with a proven pathophysiological and epidemiology e.g cryoglobulinaemia. Consistently been found to be seen in patients with HCV the underlying cause of these conditions is not clearly understood e.g porphyria cutanea tarda. Other autoimmune conditions are commonly seen in the patients with HCV nephropathies, - the exact interplay between virus and resulting clinical condition is not clear. clinicians have to have a high index of suspicion and a knowledge of the extra hepatic manifestations of HCV in order to not only treat the manifestation but also in initiated timely therapies for the underlying

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8 Case Study Mr. PR is a 54 yr old male presented to ER with a 2 week history for shortness of breath (SOB). No prior history of SOB; saw family doctor CXR congestive heart failure with interstitial edema Treated as out patient lasix,ventolin, atrovent. Patient worsen as an outpatient went to emergency department.

9 Past Medial History Motor vehicle accident (MVA) 17 years ago; multiple fractures requiring surgery and transfusions Residual short tem memory loss and unable to work. Initial HCV diagnosis was in Only HCV care was immunization for hepatitis A and B. No allergies Medications Lasix, atrovent, ventolin and diazepam

10 Supports Lives at home with wife (she is unable to work provides care to spouse) Quit smoking 2 weeks prior to admission to hospital Consumes 12 beers on the weekend only Denies high risk behavior Physical Exam B/P 190/110, heart rate 88, oriented to time place and person Few crackes at the lung bases, normal S1, S2 and JVP, Abdominal exam normal and no edema or skin rashes

11 Laboratory findings Urea 17, creatinine 244, Hgb 90, plts 119,00,24 hour urine 2 grams protein,creatinine clearance 30 ml/min, AST/ALT normal Hepatitis B surface antigen, HIV and Hepatitis A IgM-ve HCV RNA PCR +ve, genotype 2a/c Abdominal Ultrasound bilateral renal cyst and medical renal disease EKG abnormal with T wave inversion in lateral leads and non specific q waves ( no prior EKGs) Wall motion study - suggestive of prior infarct and enlarged right atrium and tricuspid regurgitation CAT head significant atrophy gien patient s age no acute issues

12 Crygobulins positive Kidney biopsy membranoproliferative glomerulonephritis and a necrotizing vasculitis.

13 Discussion HCV often asymptomatic EHM are common Approximately 75% of patients will develop an EHM during their illness Common symptoms reported: Fatigue, arthagias, paresthesia, myalgias, puritis, sicca symptoms

14 T Pathophysiology of EHM of HCV It is thought that extrahepatic tissues serve as a reservoir for the hepatitis virus Like other viruses, the HCV has developed an ability to evade detection by the immune system leads to chronic inflammation, tissue damage and immune-complex aggregation, activating autoimmune phenomena. In cryoglubulinaemia the B-cell lymphoproliferation is the initial immune-cascade trigger. The HCV tropism allows the lymphocytes to serve as host and reservoir and activates lymphocytes and subsequently leads to immunoglobulin production

15 Cryoglobulinaemia One the most common and closely linked extrahepatic HCV manifestations and is most often a mixed cryoglobulinaemia of type 2 or 3. Considered a lymphoproliferative disorder, thought to result from chronic stimulation and over production of B cells producing immunoglobulin. characterised by these abnormal blood-borne protein, which precipitate and aggregate into gel-like substances at reduced temperatures, normally aggregate below 37 C. [ cryoglobulins aggregate and form gel-like substances cause clinical signs and complications through occluding vessels and inflicting target organ damage.

16 Cryoglobulinaemia Symptoms relate to the organ affected and can range from joint pain, muscle pain, acute kidney injury and glomerulonephritis, or more commonly manifesting as a vasculitic syndrome. Critical ischemia can result with loss of limbs, particularly digits. Other non-specific symptoms including lethargy,arthralgia and pruritus in up to 18% of patients. Up to 50% of patients remain relatively asymptomatic until a critical assault on an organ occurs

17 Cryoglobulinaemia 1 st presentation of cryoglobulinaemia investigating for the cause would include a hepatitis screen. Other investigations: urinalysis, (may show haematuria, complement assay, which is low, cryoglobulin levels Rheumatoid factor is often positive Biopsies typically show a leukoclastic vasculitis, which usually involves the mediumsized vessels. An important manifestation of cryoglobulinaemia is a peripheral neuropathy which has been reported in up to 90% of patents Most cases involve a sensory impairment similar to the diabetic neuropathy, and a similar glove stocking distribution The condition can be made worse by interferon therapy, which is an important issue to consider in managing the underling HCV. A biopsy typically shows axonal damage and an epineural vasculitic infiltrate

18 Cryoglobulinaemia Therapy is targeted at treating the underlying HCV and reducing or eradicating viral load immune-targeted therapy. most studied and used regimes include cyclophosphamide along with steroid therapy with the aim of suppressing antibody production and cryoglobulin production (mixed results.) A major concern /drawback of this therapy is the risk of allowing HCV viral replication and the most recent review of therapy does not endorse cyclophosphamide therapy. Targeted therapies such as rituximab have shown greater promise and has been shown to rapidly reduce antibody and cryoglobulin levels. Severe cases, or those involving major organs, warrant early corticosteroid therapy and immunosuppression therapy and may include plasmapheresis. Treating the underlying HCV remains the cornerstone of preventing both hepatic and extrahepatic complications

19 Glomerulonephritis Defined as an inflammatory process which, in the case of hepatitis C. due to immune dysregulation and an ineffective response by the body to deal with the HCV. most common glomerulonephritis associated with HCV-related cryoglobulinaemia is membranoproliferative glomerulonephritis (MPGN). The pathophysiology of HCV-related glomerulonephritis is thought to involve deposition of immune complexes, anti-hcv immunoglobulin and an IgM subtype rheumatoid factor.

20 Glomerulonephritis Presentation 80% hypertension with moderate renal insufficiency. 20% 35% nephrotic syndrome ( > 3 grams of protien excretion ) 25% nephritic ( < 3 grams of protien excretion ). 10% of patients present with rapidly deteriorating renal function

21 Glomerulonephritis Treatment aggressive hypertensive therapy (renin-angiotensin system blockade. ) Ace inhibitors, angiotensin receptor blockers and diuretics. Patients often have high lipid and triglyceride levels and managing coronary risk factors have been proven to be beneficial Treating the underlying HCV infection has not only been shown to clear the virus successfully but also in preventing or limiting renal damage. Dual therapy with interferon and ribavirin has been shown to reduce viral load, proteinuria but has mixed success in improving glomerular filtration and creatinine levels, studies have consistently shown that commencing antiviral therapy stabilises renal function. Caution has to be taken in using ribavirin at full dose as clearance is related to renal function.

22 Glomerulonephritis In patients rapidly progressive glomerulonephritis and nephritic syndrome, early aggressive therapy is crucial. Plasma exchange is used in order to remove circulating cryoglobulins and hence reducing the insult on organs and tissues. Cyclophosphamide has been used to suppress B cell function during the acute phase of the illness by reducing cryoglobulin production (more recent studies no longer recommended as first-line therapy. Rituximab first line in treating nephritic syndrome and glomerulonephritis. The rationale behind this research is the impact that the CD20 targeted antibody has on selectively targeting B cells, the driving force in cryoglobulinaemias. Small studies have shown mixed benefits in reducing proteinuria and stabilising renal function, but may increase sepsis improving renal disease, paradoxically increases circulating viral load, which has been shown in cyclophosphamide, [ but not yet shown in rituximab.

23 Case Study Treatment in Hospital Plasmapheresis 3 times a week Line sepsis staph infection, ICU admission Prednisone 40 mg a day Meds up discharge Valium 20 mg at bedtime Adalat XL 180 mg a day Hydrochlorthazide 25 mg a day Atrovent 2 puffs 4 times a day Ventolin puffer 1-2 puffs every 4 hours as needed Metoptolol 100 mg 2 times a day Perindopril 2 mg a day Multivits Calcoun 500 mg a day Etidronate 400 mg a day

24 Case Study Outpatient Seen in clinic,weaning off prednisone, educate regarding hepatitis C Weaned of prednisone started treatment Peg interferon alfa 2a and Ribavirin 200mg daily once prednisone was down to 10 mg/day ( treatment for 48 weeks) Week 12 ve Emotional outbust and sexually aggressive behavior

25 Case Study Follow- up Achieved SVR Creatinine range No protienuria Aggressive behavior continued- seen traumatic brain injury team despite medications patient aggressive behavior continues,

26 Summary and Conclusions HCV is typically associated with liver dysfunction and progression to cirrhosis, clinical presentation remains diverse and sometimes unexpected. Clinicians have to have a high index of suspicion and a knowledge of the EHM of HCV in order to not only treat the manifestation, but in initiated timely therapies for the underlying HCV

27 References Franco Dammacco, M.D., and Domenico Sansonno, M.D., Therapy for Hepatitis C Virus Related Cryoglobulinemic Vasculitis.NEJM, 2013; 369: September 12, 2013 Sterling RK, Bralow S.,Extrahepatic manifestations of hepatitis C virus.curr Gastroenterol Rep Feb;8(1):53-9.