Etiopathogenesis of Anemia in Chronic Liver Disease
Etiopathogenesis of Anemia in Chronic Liver Disease
Anemia is the most common complication of liver cirrhosis and is seen in 75% of cases. The
 etiology of anemia in liver disease is diverse and often multi-factorial. Given the diverse
 and sometimes multifactorial etiology of cirrhosis, it is difficult to determine the exact
 cause of anemia in these groups of patients. The most common type of anemia encountered in
 liver cirrhosis is normocytic normochromic anemia, attributable to the chronic inflammatory
 state. The key question in management of anemia in patients with liver disease which specific
 factor needs to be corrected to restore hemoglobin levels and improve overall clinical status
 and improve severity scores.
Common causes of anemia include acute and chronic blood loss due to upper gastrointestinal
 (GI) bleeding, malnutrition, hemolysis, hypersplenism secondary to portal hypertension, and
 impaired coagulation. Alcohol causes anemia by its direct bone marrow toxicity, vitamin B12
 and folate deficiency due to poor oral intake, and intestinal malabsorption. Treatment
 related anemia is seen in patients with chronic hepatitis C virus infection receiving
 ribavirin and interferon. Hepatitis associated aplastic anemia, characterized by pancytopenia
 and hypocellular bone marrow, is an entity seen concurrently with or within 6 months of
 infection with hepatotropic viruses such as hepatitis B, hepatitis C and Epstein-Barr virus.
 Acute and chronic blood loss from varices, portal hypertensive gastropathy and gastric antral
 vascular ectasia can give rise to iron-deficiency anemia, in which the picture is one of
 microcytic hypochromic anemia. Another common hematological abnormality seen in liver
 cirrhosis is macrocytosis. The causes of macrocytosis in liver cirrhosis are also multi
 factorial. Vitamin B12 and folate deficiency is also frequently seen in liver cirrhosis,
 particularly of alcoholic origin, due to malnutrition and increased intestinal permeability,
 and gut dysbiosis.

 Patients with cirrhosis patients have a high incidence of sepsis which can trigger
 decompensation and may result in prolonged hospital stay and increased mortality. Many
 studies have estimated that about 30%-50% admissions of patients with cirrhosis have sepsis.
 Of those who don't have sepsis at presentation, about 15% patients admitted to hospital
 develop sepsis during the hospital stay. After infection develops, the patient may develop
 acute kidney injury (AKI), shock, encephalopathy or disseminated intravascular coagulation
 (DIC) further decreasing the chances of survival. Sepsis and the associated cytokines have a
 myelosuppressive effect and prevent the erythron from making blood cells. This results in an
 increase in ferritin as an inflammatory biomarker and alters iron metabolism by affecting the
 production of hepcidin in the liver. The worsening of anemia in patients with sepsis is well
 documented, and this is further impacted using drugs like antibiotics which trigger
 inflammation mediated suppression of the erythron and other hematopoietic precursors like
 megakaryocytes and leucoblasts.

 In the study, after taking informed consent, participants will be evaluated for etiology of
 chronic liver disease with proper history, clinical examination and investigations which will
 include viral markers (HbsAg, Anti-HCV, Total anti-Hbc, AIH markers (Anti-nuclear antibody/
 anti-smooth muscle antibody/anti- liver kidney microsomal antibody), serum ceruloplasmin,
 non-alcoholic fatty liver disease (NAFLD) work up and radiological investigations for
 cirrhosis. The severity of cirrhosis will be determined by Child-Pugh's and MELD/MELD-Na
 score.

 To evaluate for anemia, following results would be noted: Complete hemogram with RBC indices,
 reticulocyte count and peripheral blood smear, RFT, LFT, INR, iron studies - serum iron,
 ferritin, total iron binding capacity and %transferrin saturation, serum vitamin B12, folate
 levels. Workup for hemolysis would include lactate dehydrogenase, serum haptoglobin, direct
 coombs test and plasma hemoglobin. Upper GI endoscopy findings will also be noted to evaluate
 the contribution of gastrointestinal blood loss in causing anemia.
Inclusion Criteria:

 1. Age 18-75 years

 2. Either gender

 3. Patients with chronic liver disease with anemia (Hemoglobin in Non-pregnant women (18
 years of age and above) <12g/dl and in men <13g/dl

 Exclusion Criteria:

 1. Those who do not consent to participate in the study

 2. Renal dysfunction (S. Creatinine ≥ 2mg/dL)

 3. Pregnancy/Lactation

 4. Post liver transplant patients

 5. HIV infection

 6. Patients who are on psychoactive drugs, like sedatives or antidepressants

 7. Patients with uncontrolled sepsis

 8. Patients who are too sick to carry out the protocol

 9. Patients with ongoing active bleeding

 10. Patients with known primary hematological disorders