Clinical trial NCT00689546: Acute Viral Hepatitis and Diabetes Mellitus
Official title: Natural Course of Acute Icteric Viral Hepatitis in Type II Diabetes Mellitus Patients and Non-Diabetic Patients:A Pilot Cohort Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Acute Viral Hepatitis
Diabetes Mellitus
Lead sponsor: All India Institute of Medical Sciences
Sponsor class: OTHER
First posted: 2008-06-03
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All consecutive patients of acute viral hepatitis attending the OPD of Department of Gastroenterology and Endocrinology, All India Institute of Medical Sciences (AIIMS) will be candidates for the inclusion in the study.

Brief summary: It has been observed that several of patients having prolonged or complicated course of acute viral hepatitis have underlying diabetes. It is possible that with impaired hepatocyte regenerating capacity, these patients run a more prolonged and complicated course.

We hypothesize that acute hepatitis infection has a prolonged and complicated course among diabetic patients.

Detailed description: Acute viral hepatitis is usually a self limited condition characterizes by typical course of prodrome followed by an icteric phase. In some cases the course may be protracted or complicated by the development of cholestatic phase or acute liver failure . The development of complicated course depends on a number of factors such as the type of virus and a variety of host factors including age of infection, immune status of the host and condition of the underlying liver before the onset of hepatitis.

Patients who have an underlying chronic liver disease or cirrhosis have increased risk of development of decompensation and liver related death when they develop superinfection with some hepatotropic viruses.

Vento etal demonstrated in their classical study that superinfection with hepatitis A on chronic liver disease is associated with high risk of decompensation and death. In India, since most of the adult population including those with chronic liver disease has been shown to have protective antibodies against HAV, this infection is rarely a problem in them.

Hepatitis E virus (HEV) has demonstrated to be the most common cause of acute hepatitis, acute liver failure and subacute liver in India. There is now enough data to suggest that HEV superinfection is also the commonest cause of acute decompensation of chronic liver disease in Indian subcontinent.

Many of these patients do not have any signs and symptoms of preexisting liver disease and it is the liver failure secondary to HEV superinfection which bring to light the underlying chronic liver disease.

World over, as well as in developing countries nonalcoholic fatty liver disease (NAFLD) is fast emerging as an important causes of chronic liver disease. Obesity and diabetes are two most important risk factors for NAFLD.It has been estimated that there would be about 366 million diabetes in the world by 2030.Of these 79.4 million will be in India.

Diabetes has been proposed as a risk factor for both chronic liver disease and HCC.The spectrum of liver involvement ranges from fatty liver, steatohepatitis, and fibrosis to cirrhosis. Even among patients with NASH, presence of diabetes is annotated with advanced stage of fibrosis . There is some suggestion that diabetic patients who develop acute viral hepatitis may have a prolonged course. Liver regeneration capacity has been demonstrated to be impaired among animal and human with fatty liver after partial resection. It is therefore possible that diabetic by of having NAFLD may have poor regenerating capacity leading to prolonged course of hepatitis.

It has been an observation in our unit that most of the patients who present with acute on chronic liver failure or subacute hepatic failure have diabetes. Whether it is simply a co-existence of two commonly occurring diseases (diabetes with a prevalence of 10% in Indian population and hepatitis E which is endemic(1) in our country) or the presence of acute hepatitis E in a diabetic patients some how produces a worse outcome as compared to hepatitis E in a non-diabetic patients. There fore it is important to find out the natural course of the two commonly occurring diseases when they occur together or separately.

We hypothesize that acute hepatitis infection has a prolonged and complicated course among diabetic patients.

Eligibility criteria: Inclusion Criteria:

* All patients between the ages of 18 to 70 years

Exclusion Criteria:

* Recent intake of drugs known to cause acute hepatitis
* History of alcohol ingestion \>40mg/day
* Suspected ischemic hepatitis
* Illness causing acute hepatitis such as Malaria hepatits, enteric hepatitis, Leptospirosis, septecemia
* HIV.
* Associated co morbidities, which can affect survival such as cardiovascular disease and diabetic nephropathy.
* Recent intake of drugs known to cause acute hepatitis
* History of alcohol ingestion \>40mg/day
* Suspected ischemic hepatitis
* Malaria hepatits, enteric hepatitis, Leptospirosis, septecemia
* Co infection with HIV.
* Comorbidities which affect survival such as CAD and diabetic nephropathy.
* Gestational diabetes
* Pregnant female
* Cirrhosis

Primary outcomes:
measure: Duration of icteric hepatitis.
Secondary outcomes:
measure: Development of complications
measure: Mortality
Other outcomes:
Locations:
city: New Delhi
country: India
facility: All India Institute Of Medical Sciences
state: Delhi
Study officials:
affiliation: All India Institiute Of Medical Sciences
name: Subrat Acharya, DM
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hamid SS, Atiq M, Shehzad F, Yasmeen A, Nissa T, Salam A, Siddiqui A, Jafri W. Hepatitis E virus superinfection in patients with chronic liver disease. Hepatology. 2002 Aug;36(2):474-8. doi: 10.1053/jhep.2002.34856.
citation: Monga R, Garg S, Tyagi P, Kumar N. Superimposed acute hepatitis E infection in patients with chronic liver disease. Indian J Gastroenterol. 2004 Mar-Apr;23(2):50-2.
citation: Ramachandran J, Eapen CE, Kang G, Abraham P, Hubert DD, Kurian G, Hephzibah J, Mukhopadhya A, Chandy GM. Hepatitis E superinfection produces severe decompensation in patients with chronic liver disease. J Gastroenterol Hepatol. 2004 Feb;19(2):134-8. doi: 10.1111/j.1440-1746.2004.03188.x.
citation: Vento S, Garofano T, Renzini C, Cainelli F, Casali F, Ghironzi G, Ferraro T, Concia E. Fulminant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis C. N Engl J Med. 1998 Jan 29;338(5):286-90. doi: 10.1056/NEJM199801293380503.
citation: Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004 May;27(5):1047-53. doi: 10.2337/diacare.27.5.1047.
citation: Behrns KE, Tsiotos GG, DeSouza NF, Krishna MK, Ludwig J, Nagorney DM. Hepatic steatosis as a potential risk factor for major hepatic resection. J Gastrointest Surg. 1998 May-Jun;2(3):292-8. doi: 10.1016/s1091-255x(98)80025-5.