Infections affecting the Liver a resume .pptx

Review on infectious diseases affecting the liver especially endemic in Egypt

1. INFECTIONS & Liver DR A A MOUKHTAR 2024

2. Introduction : The liver contains approximately one-third of the reticuloendothelial system mass in humans. In addition to receiving both the portal and systemic circulation, the liver plays an important role in host defence against invasive microorganisms. However , it can become involved during systemic infections when local or general conditions Favor bacterial colonization.

3. On the other hand, susceptibility to infection is common in patients with chronic liver disease due to impairment of the immune system and to malnutrition. The impact of microbial pathogens on the liver can vary greatly. This Lecture will review involvement of the liver during systemic infections with organisms that are not considered to be primarily hepatotropic.

4. AGENDA

5. Acute non hepatotropic hepatitis Commonest cause for acute hepatitis remains a plethora of hepatotropic viruses (commonly hepatitis A, B and E). In tropical regions , the syndrome of jaundice, elevated transaminases with or without encephalopathy, may also occur due to several non-hepatotropic infections . While many such infections have effective treatment available, the lack of awareness about these infections can lead to unwanted outcomes.

6. Co-infections with more than one tropical agent have been also reported commonly . Systemic sepsis by gram-positive (GP) and gram-negative (GN) bacteria may also lead to jaundice and encephalopathy. Endotoxins (produced by GP and/or GN bacteria) inhibit transport of bile acids and other organic anions across canalicular and sinusoidal membrane and produce intrahepatic cholestasis The failure to control these infectious agents is possibly related to : poor hygienic conditions, inadequate health infrastructure, lack of adequate preventive measures and poor resource allocation for health in these tropical countries

7. Medical personnel often face the challenge of differentiating ALF induced by viral hepatitis from these tropical infections causing jaundice and encephalopathy (so-called ALF mimickers) because the treatment protocol is entirely different for these two conditions. Thus ,

8. Though both these conditions (ALF and ALF mimickers) may have similar clinical presentation (jaundice, elevated transaminases and altered sensorium), subtle difference in history and physical examination along with biochemical /serological markers often makes the distinction between these two conditions easier. The presence of fever along with jaundice, hepatomegaly thrombocytopenia and the absence of coagulopathy often point towards an ALF-mimicking illness rather than ALF. Moreover, some of these illnesses may have very distinctive physical findings, e. g. Eschar in scrub typhus (ST) and Rose spots in enteric fever , Extrahepatic manifestations of TB , Brucellosis , Periorbital pain in Dengue fever Renal failure in leptospirosis etc... Haemolysis in Malaria. The diagnosis can be clinched with easily accessible investigations if one clinically suspects these tropical infections

9. BRUCELLOSIS:

10. Elbehiry , et al ., The Development of Diagnostic and Vaccine Strategies for Early Detection and Control of Human Brucellosis, Particularly in Endemic Areas. Vaccines 2023, 11, 654. https:// doi.org/10.3390/vaccines11030654

11. DENGUE FEVER : Case definition According to the World Health Organization (WHO) 1997 classification, dengue has been traditionally classified into dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS) . DF Fever with at least two features: ocular pain, headache, muscle or joint pains, cutaneous rash, bleeding manifestations, and reduced leukocyte count DHF Fever, thrombocytopenia (≤ 100 × 109/L), bleeding manifestations, and evidence of plasma leakage. DSS DHF with tachycardia or low pulse pressure (< 20 mmHg) or hypotension (systolic blood pressure < 90 mmHg)

12. Leptospirosis Leptospirosis, caused by spirochetes of the genus Leptospira., is one of the most widespread zoonotic infections in the world. Human infection is usually acquired through contact with urine from infected animals, most commonly rodents and other small mammals. Infections usually peak during late summer/early fall in temperate regions and the rainy season in the tropics. The clinical presentation of the disease is variable. Subclinical infection occurs in a majority of cases, which, in general, do not seek medical attention. Symptomatic disease generally consists of biphasic illness which can occur in 2 forms: anicteric and icteric (Weil’s Disease).

13. Jaundice & Red eyes

14. Clinical Features Wide range of severity and clinical features Subclinical infection Self limited systemic illness 90 % Severe potentially fatal illness consisting of Renal failure 15 % Liver failure 15% Pneumonitis >30 to 40% mortality Hemorrhagic diathesis

15. Bimodal illness Leptospiremic/ Septicaemic phase Immune phase/ Leptospiruric Phase Distinction maybe blurred

16. Clinical Features- early (5 -7 days) High fever and chills Severe headache, eyeball pain, photophobia Mental confusion Muscle pain & tenderness (calves and back) Redness in the eyes & conjunctival injection Sore throat Rash- maculopapular

17. Clinical Features- Late (A) Anicteric Variety After 2 to 3 days of seeming recovery New fever Milder myalgias Aseptic meningitis- similar to viral meningitis- clue- Neutrophilic leucocytosis Uveitis ( Iridocyclitis ) Choreoretinitis

18. Clinical Features- Late (B) Icteric Variety Severe Leptospirosis (Weil’s Disease) Jaundice Renal Dysfunction Hemorrhagic Diathesis Mortality 5 to 15 %

19. To Sum Up Clinical Features Bacteraemic Leptospirosis Aseptic Meningitis Icteric Leptospirosis with Renal involvement Pulmonary Syndrome

20. Other Complications Rhabdomyolysis Hemolysis Myocarditis Pericarditis CHF Necrotising Pancreatitis MOF

21. Lab Diagnosis Urine : Sediment (RBCs, WBCs, Casts) & proteinuria Blood Counts : PMN – Leucocytosis , ESR elevation Thrombocytopenia Biochemistry: LFT (Enzymes not very high); KFT Coagulation Profile - Vit K dep factors low CPK MM CSF Abnormalities X Ray Chest- patchy alveolar pattern- lower lobes

22. Lab Diagnosis Antigen Detection : DGI and Silver impregnation staining- urine, CSF Culture (EMJH ) PCR Antibody Detection (second week) IgM & IgG MAT ELISA Indirect Hemagglutination Test Microcapsule Agg test

23. Take Home Messages Leptospirosis is an infectious disease ( zoonosis ) caused by a bacterium. Leptospirosis is transmitted to humans by direct exposure to urine or tissue of an infected animal. Leptospirosis typically progresses through two phases of nonspecific symptoms. Leptospirosis can be diagnosed by culture of infected blood, urine, or spinal fluid, as well as using antibody testing. Animals are also at risk for contracting Leptospirosis. Leptospirosis is treated with antibiotics and is rarely fatal.

24. Differential Diagnosis Acute Febrile Syndrome (Dengue , Malaria, Influenza, Typhus, Mono, Enteric, Hanta ). Jaundice (VH, Yellow Fever, Complicated Malaria). Aseptic Meningitis (.., .., .. )

25. Every jaundice is not viral Hepatitis

26. Granulomatous hepatitis ( infectious causes ).

27. Granulomatous hepatitis Granulomatous hepatitis refers to the presence of granulomas in the liver. It has been attributed to multiple etiologies , with sarcoidosis and primary biliary cholangitis being the most common causes in the US, and tuberculosis worldwide. Granulomas may also be incidental findings, especially with the increased use of computed tomography (CT) and magnetic resonance imaging (MRI), but are most commonly found to be associated with an underlying systemic process. Manifestations may include right upper quadrant abdominal pain and tenderness, elevated alkaline phosphatase and transaminases, hyperbilirubinemia, jaundice, or fevers. Management is directed towards the treatment of the underlying cause.

28. Pathophysiology Due to the rich blood supply and numerous Kupffer cells (stellate sinusoidal macrophages), the liver is a very common site for granuloma formation. Kupffer cells help clear foreign particles by phagocytosis and pinocytosis. When the macrophages are unable to clear the stimulus of inflammation, a further inflammatory process is initiated, resulting in an aggregation of macrophages around the source of the inflammatory stimulus. This aggregation, along with a peripheral cuff of lymphocytes, form an inflammatory focus called a granuloma. Hepatic granulomas may be classified into four main variants, namely, caseating, non-caseating, fibrin-ring, and lipogranulomas .

29. The usual spectrum of Q fever: Febrile illness: Fever, usually accompanied by a headache that plateaus in 2 to 4 days and returns to normal in 5 to 14 days, is the most common outcome of the infection. The fever lasts longer in untreated patients (up to 57 days) and in elderly patients. Atypical pneumonia: It is characterized by nonproductive cough, fever, and minimal auscultatory findings with nonspecific findings on a chest X-ray. Hepatitis: It may present in three ways, including hepatitis without clinical manifestations, hepatitis with hepatomegaly, and hepatitis with granulomas on liver biopsy presenting as prolonged fever of unknown origin. These patients develop fever, abdominal pain (mostly in the right upper quadrant), nausea, vomiting, diarrhea , and anorexia.[5] Cardiac involvement: Myocarditis and pericarditis are seen in some of the patients with Q fever. Myocarditis is one of the major causes of death in these patients.[7] Exanthema associated with fever: Though uncommon, a pink macular or papular rash, may be seen on the trunk in 5% to 21% of patients.[8] Neurological involvement: Q fever may cause encephalitis/meningoencephalitis, lymphocytic meningitis, and peripheral neuropathy.

30. The Liver Abscess :

31. Hepatic abscess   Liver abscesses are purulent collections in the liver parenchyma that result from bacterial, fungal, or parasitic infection . Pyogenic hepatic abscess constitutes about half of all visceral abscesses and 13% of intraabdominal ones. Incidence - increasing while the mortality = stable or decreasing . The trend of increasing incidence may be due to the availability of more sensitive diagnostic tests than in the past (e.g., CT scan) or to the increasing prevalence of predisposing conditions.

32. Microbiology :

33. Microbiology K pneumoniae   have been associated with multiple extra-hepatic complications, including endophthalmitis and central nervous system infections. Enterobacteriaceae are especially prominent when the infection is of biliary origin. A colonic source is usually the initial source of anaerobic infection ( e.g Bacteroids , Fusobacterium sp. ) infection. Staphylococcus aureus   abscesses usually result from hematogenous spread of organisms involved with distant infections, such as endocarditis.  Amebic liver abscess   is most often due to  E histolytica . Liver abscess is the most common extraintestinal manifestation of this infection. Fungal abscesses primarily are due to  Candida albicans  and occur in individuals with prolonged exposure to antimicrobials, hematologic malignancies, solid-organ transplants, and congenital and acquired immune Def.

34. Clinical presentation

35. Clinical presentation

36. Presentation

37. In the case of Echinococcus infection, there is an initial asymptomatic phase in a child. Years later, some of these patients will show clinical symptoms from reactivation of the infection. The clinical manifestations depend on the type, size, and site of the cysts present. Small cysts in non-vital organs can go undetected, but large ones in critical locations can present with signs of compression or rupture. The usual rate of cyst progression is 1 to 5 centimeters in a year. The liver is affected in two-thirds of cases of Echinococcus infection. Symptoms of compression usually start when the diameter is 10 cm and include biliary colic, cholangitis, obstructive jaundice, portal and venous obstruction, Budd-Chiari syndrome, bronchial fistula, If it ruptures, overt peritonitis or anaphylaxis will be present N.B Charcot triad (right upper quadrant pain, jaundice, and fever) is a sign of cholangitis, liver abscess is a differential. Shock ; distress or even overt shock (septic shock or anaphylactic shock in the case of the hydatiform mole rupture). Extra hepatic septic foci : In the case of Klebsiella liver abscesses,can also send septic emboli to the eye, meninges, and brain. Therefore symptoms of these organ systems can be present, and it can last after the liver abscess is drained.

38. DOUBLE TARGET SIGN

39. TREATMENT CHEMOTHERAPY : Start with monotherapy with METRONIDAZOLE (800mg thrice daily for 10 days or 500mg IV QDS) In cases where improvement is not seen within 3 days, alternate chemotherapy or surgical means EMETINE HYDROCHLORIDE : intramuscular or deep subcutaneous injection @ 1mg/kg/day not exceeding 60mg/day ( contraindicated in renal, cardiac and muscular disease) CHLOROQUINE : 1 g (600-mg base) per day for 2 days followed by 500 mg (300-mg base) per day for 2 to 3 week DILOXANATE FUROATE : added after treatment of liver abscess for eradication of intestinal amebiasis

40. TREATMENT ASPIRATION/DRAINAGE: Therapeutic aspiration has not been proved superior or very effective in management of amebic liver abscess Its use has been reserved for the following situations: 1.Amebic serology is inconclusive, delayed, or unavailable, and the main differential diagnosis is a pyogenic liver abscess. 2.A therapeutic trial with antiamebic drugs is deemed inappropriate (as in pregnancy). 3.There is suspicion of secondary infection of the liver abscess; this is estimated to occur in 15% of cases 4. When fever and pain persist for more than 3 to 5 days after starting appropriate therapy, aspiration may provide symptomatic relief. 5. Rupture is suspected to be imminent in an extremely large abscess, especially if pericardial

41. The liver in special situations:

42. Liver in malaria The liver can be infected by all the 4 types of plasmodium. However,  P. falciparum  causes the most serious damage to the liver, with pathological changes of enlarged liver with edema in the color of blue brick or black. The hepatic sinus and the central vein are congested, and the hepatocytes are cloudy and swelling with degeneration. The Kupffer cells proliferate in a large quantity, containing malarial pigment, fragments of erythrocytes with or without plasmodium, and a small quantity of hemosiderin.

43. COVID-19

44. Infections after liver transplant