Etiopathogenesis of Anemia in Chronic Liver Disease

September 26, 2021 updated by: Madhumita Premkumar, Postgraduate Institute of Medical Education and Research

Assessment of Role of Iron Metabolism, Nutritional Deficiency, Gastrointestinal Loss, and Chronic Inflammation in the 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.

Study Overview

Status

Recruiting

Conditions

Detailed Description

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.

Study Type

Observational

Enrollment (Anticipated)

125

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • India
      • Chandigarh, India, 160012
        • Recruiting
        • PGIMER
        • Principal Investigator:
          • Dr. Madhumita Premkumar, MD, DM
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

All patients with chronic liver disease attending outpatient department of hepatology, admitted under hepatology department or emergency services

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Chronic liver disease with anemia
All patients with anemia as diagnosed by WHO criteria in patients with liver disease of any etiology.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Etiologies of anemia in patients with liver disease
Time Frame: 1 month
Determine the prevalence of various etiologies of anemia in patients with liver disease
1 month
Correlation with liver disease severity
Time Frame: 1 month
Association of liver disease severity as measured by MELD, MELD Na and CTP scores with severity of anemia
1 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Postgraduate Institute of Medical Education and Research

Investigators

  • Principal Investigator: Madhumita Premkumar, MD, DM, Postgraduate Institute of Medical Education and Research

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2020

Primary Completion (Anticipated)

December 30, 2021

Study Completion (Anticipated)

December 31, 2021

Study Registration Dates

First Submitted

November 4, 2020

First Submitted That Met QC Criteria

November 4, 2020

First Posted (Actual)

November 10, 2020

Study Record Updates

Last Update Posted (Actual)

September 28, 2021

Last Update Submitted That Met QC Criteria

September 26, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IM/2020/1624

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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