Uncommon Cause of Pulmonary Infiltrates in Patient with Liver Disease דר. מטבייצ' קו אלונה
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1 Uncommon Cause of Pulmonary Infiltrates in Patient with Liver Disease דר. מטבייצ' קו אלונה מחלקת ריאות וטיפול נמרץ נשימתי מרכז רפואי מאיר
2 מק רה ב ת 47, יליד ת אזרביג'אן, שנ ת ע לי ה 1997 צה ב ת ב י לדו ת - IgG HAV חיובי לא ק יב לה תו צ רי דם, ל לא שי מו ש ב סמי ם אין מח ל ת כ בד ב מ שפ ח תה
3 מק רה בבדי קו ת דם בקה ילה positive HCV ביקור ראשון במרפאת כבד רמת RNA HCV פי ברוז יס ביו פסי ה ל לא סימנ י דל ק ת, ל לא הוחל ט ע ל מ ע קב ב ל בד
4 מק רה ביקורת שגרתית : ללא סימני מחלת כבד כרונית, ללא עלית אנזימי כבד מעקב שמרני ע ל יי ת אנזימ י כבד, US בטן תק י ן ל לא שינוי, HCV RNA הוחל טיפול אנטי ווירלי Pegasys Copegus ו- (Pegylated Interferon alfa-2a ).(Ribaverin )
5 DATE HCV RNA TREATMENT <600
6 המ ש ך מ עק ב אמ בו ל טו רי חולשה כללית נכרת, הופעת שיעול יבש, ללא קשיי נשימה, ללא חום סיסטמי צ יל ו ם חזה
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9 מי ק ר ה במחשבה של דלקת ריאות Rulid Zinnat + למשך 10 ימים, ללא שיפור. קושי בנשימה במאמצים בינוניים, שיעול יבש ממשיך מופנית לצילום חוזר. צי ל ו ם חזה בי קור ת
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12 מי ק ר ה ב ע ק בו ת החמרה ב צי ל ום חזה מו פני ת למיו ן מצב יציב, ללא חום, ללא מצוקה נשימתית ריווי חמצן 98% על אוויר חדר ללא הגדלת בלוטות לימפה ריאות נקיות Neut -830,2.14 -WBC לאור התמונה הריאתית אשפוז
13 Pulmonary Function Tests FVC 1.12 liter 37% FEV liter 37% FEV1/FVC 0.86% SAT (RA) - 91% SAT( 2 liter/min O2) - 95%
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17 אב חנ ה מב ד ל ת
18 אבחנה מ בדלת Pulmonary infection - Typical / Atypical pneumonia - Opportunistic infection or tuberculosis BOOP Malignancy (including lymphoma) ILD (including LIP) Drug induced Interstitial Pneumonitis
19 מה ל ך אש פוז 9.06 הופעת קוצר נשימה גם במנוחה, נזקקת לחמצן גם במנוחה, נשימה בועית, ללא חיידקי AF בכיח מתן סטרואידים תוך ורידי ברונכוסקופיה ללא ממצא אנדוברונכאלי. נלקחים שטיפות, הברשות וביופסיות.
20 תוצאות פתולוגיות וציטולוגיות של ברונכוסקופיה 1. שטיפות תאי אפיתל רספירטורי שפירים והיסטיוציטים בודדים Segments 60% Eos 2% Lymphocytes 12% Monocytes 26% Mesothelial - <1% 2. הברשות תאי אפיתל רספירטורי שפירים בקבוצות ותפזורת
21 Transbronchial biopsy קטעי דופן הסמפון ורקמת ריאה פריברונכיאלית, התרחבות ופיברוזיס קלה במחיצות, מאקרופגים אינטרהאלבאולריים. עם מוקדי הסננה צלולרית באינטרסטיציום. ללא גרנולומות, ללא סימני ממאירות. התמונה בכללותה אינה ספציפית. לתרופות. לא ניתן לשל ול תגובה
22 אבחנה מ בדלת Pulmonary infection - Typical / Atypical pneumonia - Opportunistic infection or tuberculosis BOOP Malignancy (including lymphoma) ILD (including LIP) Drug induced Interstitial Pneumonitis
23 Interferon-Ribavirin Induced Pneumonitis
24 World Wide 40 Million 170 Million HIV HEP C
25 Prevalence of Hepatitis C (2002) 1-2% 2 5 % > 10 % Not available 3 % World Population = 170 Million
26 RATIONALE FOR PEGYLATION OF INTERFERONS: WHY DO WE DO IT? Pegylation attachment of an inactive, nontoxic polyethylene glycol moiety to the active conventional interferon molecule Result sustained absorption, higher serum concentration, slower rate clearance, longer half-life more constant therapeutic concentration
27 RATIONALE FOR PEGYLATION OF INTERFERONS: WHY DO WE DO IT? PEG-Interferon PegIFN -2b Interferon 1000 pg/ml Hours
28 PegInterferon + Ribavirin Sustained Virologic Response(SVR) Overall Genotype 1 Genotype 2/3 Interferon 47% 34% 80% Peg 61% 48% 88%
29 SIDE EFFECTS OF IFN TREATMENT Flu-like symptoms Headache Alopecia Fatigue or asthenia Myalgia, arthralgia Fever, chills Nausea Injection-site reaction Leukopenia Thyroiditis Anorexia Diarrhea Psychiatric symptoms Autoimmunity Thrombocytopenia Depression Insomnia
30 SIDE EFFECTS OF RBV TREATMENT Hemolytic anemia Teratogenicity Cough and dyspnea Rash and pruritus Insomnia Anorexia. Chutaputti A. J Gastro-enterol Hepatol. 2000;15(suppl): E156-E163.
31 Peginterferon (PEG) and Ribavirin (RBV) combination combination therapy that are known to cause various side effects in almost 80 % of patients with HCV infection.
32 Pulmonary toxicity rare : - dyspnea (23-26%) - cough (15-17%) - pharyngitis (11-12%) - nonproductive cough, rhinitis (1-10%) - <1% - asthma, pneumonia, sarcoidosis,pleuritis with effusion, BOOP, interstitial pneumonitis
33 Interferon-Ribavirin Induced Pneumonitis Onset at any stage of treatment supporting the idiosyncratic nature of side effect Dry cough, dyspnea, fever, inspiratory crackles Chest X-ray bilaterally patchy infiltrates or opacification HRCT - bilaterally patchy consolidation, ground-glass attenuation
34 Pneumonitis as a consequence of peginterferoncombination therapy for ribavirin hepatitis Dig Dis Sci cases. 12 (48%) males Mean age: 55.2 years. 14 patients - treated with conventional interferon, while 11 patients developed pneumonitis during or after treatment with peginterferon and ribavirin
35 Interferon-Ribavirin Induced Pneumonitis Dig Dis Sci 2009 The most common presenting symptoms of pneumonitis is any combination were dry cough, dyspnea, fever, and fine inspiratory crackles on examination. Chest radiographs usually show bilateral patchy infiltrate or opacification HRCT scans show bilateral patchy consolidation as well as ground-glass attenuation
36 Drug-induced interstitial pneumonitis. Onset: 2-12 weeks of therapy. In most cases, symptoms of pneumonitis are reversible after cessation of combination treatment, again in support of steroids.
37 Treatment options No consensus regarding treatment Three options 1. Stop combination treatment and wait until disease the disease resolved 2. Steroids 3. Azathioprine - in therapy-resistant or relapsing cases (adding to steroids)
38 Mortality Mortality exclusively in patients with peginterferon induced pneumonitis in comparison conventional interferon (7% versus 0%) reason in unclear Patient who died relatively young and had no relevant pulmonary or other severe diseases in their medical history Failure to recognize interferon-associated pulmonary toxicity may result in persistence of pulmonary damage
39 שחרור VC % TLC % RV % PFT קבלה FVC % FVC % FEV % FEV % FEV1/FVC 85% FEV1/FVC 0.86 TLCO 29.9% TLCO/VA 47.5% SAT 96% RA SAT 91% RA 6MWT 312 m
40 PFT follow up 6 weeks VC % TLC % FVC % FEV % FEV1/FVC 0.83 TLCO 56% TLCO/VA 64% SAT 98% RA 6MWT m 4 months VC % TLC % FVC % FEV % FEV1/FVC 0.84 TLCO 56% TLCO/VA 71% SAT 98% RA
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42 Hepatitis C Virus תודה
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