Using Hydroxychloroquine to Treat Nonalcoholic Steatohepatitis

February 28, 2023 updated by: National Taiwan University Hospital

Nonalcoholic steatohepatitis (NASH) is a serious type of nonalcoholic fatty liver disease (NAFLD), which is characterized by lobular inflammation and apoptosis resulting from hepatic steatosis in the absence of excessive alcohol consumption. If NASH are not controlled well, it will advance to liver fibrosis, cirrhosis, and even hepatocellular carcinoma. However, there is no approved treatments currently.

The investigators aim to clarify whether hydroxychloroquine relieves nonalcoholic steatohepatitis by reviewing medical records from our out-patient-clinic patients who accept the treatment of hydroxychloroquine (Plaquenil®).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Nonalcoholic steatohepatitis (NASH) is a serious type of nonalcoholic fatty liver disease(NAFLD), which is characterized by lobular inflammation and apoptosis resulting from hepatic steatosis in the absence of excessive alcohol consumption. If NASH are not controlled well, it will advance to liver fibrosis, cirrhosis, and even hepatocellular carcinoma. However, there is no approved treatments currently.

According to guidance of American Association for the Study of Liver Diseases (AASLD) and a few studies, vitamin E and pioglitazone are two potential pharmacologic therapies for NASH. They have some therapeutic effects; however, they also have some safety concerns. Therefore, those two drugs have not been wildly used in clinical practices. In addition to vitamin E and pioglitazone, many drugs are being tested in clinical trials. However, promising results have not been revealed yet.

Recent clinical and experimental data suggested that hydroxychloroquine (HCQ) might improve metabolic profiles in patients or animals with obesity-related metabolic disorders. HCQ might also relieve liver inflammation in experimental animals with steatohepatitis. As an inhibitor of endocytosis and autophagy with therapeutic effects in autoimmune disorders, it is reasonable to speculate that HCQ might also relieve liver inflammation in patients with steatohepatitis. Therefore, HCQ has been anecdotally prescribed to patients with steatohepatitis in our clinic. Excitingly, almost all those with HCQ treatment had immediate reduction of their liver enzyme levels, indicating instant relief of their steatohepatitis. Effects of HCQ were similar in those with negative anti-nuclear antibody (ANA) compared to those with weakly positive ANA, suggesting that those are specific steatohepatitis-targeting rather than autoimmune-targeting effects from HCQ.

Thus, the investigators aim to clarify whether HCQ relieves nonalcoholic steatohepatitis by reviewing medical records from our out-patient-clinic patients who accept the treatment of hydroxychloroquine (Plaquenil®).

Study Type

Observational

Enrollment (Anticipated)

150

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 Locations

  • Taiwan
      • Taipei, Taiwan
        • Recruiting
        • National Taiwan University Hospital
      • Taipei, Taiwan
        • Recruiting
        • Graduate Institute of Pharmacology, College of Medicine, National Taiwan University

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Study population are collected from our out-patient-clinic patients who accept the treatment of hydroxychloroquine.

Description

screen out our targeted group：patients with nonalcoholic steatohepatitis

  1. The investigators have made a request to Information Technology Office of National Taiwan University Hospital, and this request is about the list of our out-patient-clinic patients who accept the treatment of hydroxychloroquine.
  2. Collect and review the medical records, ultrasound and blood tests of patients in the abovementioned list and screen out those with nonalcoholic steatohepatitis based on the following criteria.

Inclusion criteria： Our patients who taking hydroxychloroquine and match the following criteria

A. Patients with fatty liver, based on the abdominal ultrasound report of which the date is the closest to the initial date of using HCQ.

B. Alanine aminotransferase (ALT) level of 2.5 and 0.5 month prior to hydroxychloroquine treatment > 41 U/L

C. With ALT result which is tested in 3 months after using HCQ.

D. The initial date of taking HCQ is prior to September, 26, 2022, which is the date we got the list from Information Technology Office of National Taiwan University Hospital.

Exclusion criteria： Our exclusion criteria can be separated into loose exclusion criteria and strict exclusion criteria.

Loose exclusion criteria：patients who match the following criteria will be excluded from the above group.

A. Diseases of the biliary tract：the abdominal ultrasound report indicated the patient with stones in the biliary tract, or the patient with jaundice or his total bilirubin > 2.0 mg/dl

B. Viral hepatitis： Hepatitis B Virus (HBV) Viral Load + or Hepatitis C Virus (HCV) Viral Load +

C. Alcoholic steatohepatitis： History of drinking alcohol or aspartate aminotransferase /alanine aminotransferase (AST/ALT) > 1.5 and γ-glutamyltransferase (GGT) > two times of normal levels (2X)

D. Autoimmune hepatitis： anti-nuclear antibody (ANA)1:80+ (above) or mitochondrial antibody (AMA) + or liver kidney microsome antibody (anti-LKM) + or smooth muscle antibody (anti-SMA) +

E. Wilson's disease：ceruloplasmin < 20 mg/dl

Strict exclusion criteria：patients who had ever had viral hepatitis or was being infected by virus (HBV, HCV infection：hepatitis B surface antigen positive (HBsAg+) or hepatitis B core antibody positive (HBc stands for hepatitis B core antigen, anti-HBc+ stands for hepatitis B core antibody) or anti-HCV Ab+) will be further excluded from the above group.

The definition of months：used in the criteria evaluation and the data analysis

Before patients used HCQ：

negative 0.5 month：During the periods from one month prior to the date of initial use of HCQ to that date, we define the date which is the closest to 0.5 month as -0.5 month.

negative 2.5 months：During the periods from four months to one month prior to the date of initial use of HCQ, we define the date which is the closest to 2.5 months as -2.5 months.

negative 5.5 months：During the periods from seven months to four months prior to the date of initial use of HCQ, we define the date which is the closest to 5.5 months as -5.5 months.

After patients used HCQ： 0.75 months：During the periods that patients used HCQ for 0-1.5 months, we define the date which is the closest to 0.75 months as 0.75 months.

3 months：During the periods that patients used HCQ for 1.5-4.5 months, we define the date which is the closest to 3 months as 3 months.

6 months：During the periods that patients used HCQ for 4.5-7.5 months, we define the date which is the closest to 6 months as 6 months.

9 months：During the periods that patients used HCQ for 7.5-10.5 months, we define the date which is the closest to 9 months as 9 months.

12 months：During the periods that patients used HCQ for 10.5-13.5 months, we define the date which is the closest to 9 months as 12 months.

Then, in addition to the above-mentioned criteria, we will record the following two things separately.

The first one is hemochromatosis. Hemochromatosis may also cause hepatitis, but the prevalence of this disease in Taiwan is very low. Thus, we do not list hemochromatosis in the exclusion criteria.

The second one is drug-induced hepatitis. We do not list suspected drug-induced hepatitis in the exclusion criteria since drug-induced hepatitis may not be accurately confirmed based on our current medical records. However, if we find patients using drugs which may be related to hepatitis, we will record their information separately, including the duration of using these drugs and the ALT levels after stopping using it.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To observe whether patients' alanine aminotransferase (ALT) levels were significantly decreased after using hydroxychloroquine (by statistically analyzing patients' ALT levels before and after using HCQ)
Time Frame: during the period of one year after taking hydroxychloroquine
Comparing patients' alanine aminotransferase (ALT) levels before using hydroxychloroquine with those after using hydroxychloroquine, to observe whether ALT levels were significantly decreased (by statistically analyzing patients' ALT levels before and after using HCQ).
during the period of one year after taking hydroxychloroquine

Collaborators and Investigators

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

Sponsor

National Taiwan University Hospital

Collaborators

National Taiwan University

Investigators

  • Study Director: Chung-Jui Huang, Master, Graduate Institute of Pharmacology, College of Medicine, National Taiwan University
  • Principal Investigator: Feng-Chiao Tsai, Doctor, Graduate Institute of Pharmacology, College of Medicine, National Taiwan University

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)

June 10, 2022

Primary Completion (Anticipated)

July 1, 2025

Study Completion (Anticipated)

July 1, 2025

Study Registration Dates

First Submitted

February 8, 2023

First Submitted That Met QC Criteria

February 8, 2023

First Posted (Actual)

February 17, 2023

Study Record Updates

Last Update Posted (Actual)

March 2, 2023

Last Update Submitted That Met QC Criteria

February 28, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 202206002RINB

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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