NASH is a disease similar to alcoholic hepatitis in histology which has no relationship with alcohol abuse.1,2
Primary NASH is related to insulin resistance and its phenotypic manifestations like mainly overweight/obesity, visceral adiposity, type 2 diabetes, hypertriglyceridemia, and hypertension.3-5
Secondary NASH is rare, is not associated with insulin resistance or the metabolic syndrome, and is related to variable medical or surgical conditions or drug intake.1,3,4
NASH associated with intestinal bypass surgery was reported mainly in bariatric surgery performed before early 1980s.1,6-12
From the 1950s to early 1980s, the jejunoileal bypass was the most common malabsorptive operation in which the proximal jejunum was anastomosed to the distal ileum.6,12
A common variant form of jejunoileal bypass is jejunocolic bypass.6
Since these types of surgery have rarely been performed in Korea, we were not able to find a case of NASH caused by intestinal bypass surgery in Korean literatures. In our case, unlike the cases in Western countries, jjejunocolic bypass was not performed to reduce weight, but to relieve symptoms related to intestinal adhesion.
The pathogenesis of NASH after bypass surgery is thought to be different from that of primary NASH associated with the metabolic syndrome, but the exact mechanism is not clear. Rapid weight loss after surgery, protein-calorie malnutrition, decreased carnitine concentrations, essential fatty acid deficiency and stimulation of TNF by bacterial overgrowth have been reported as possible etiologic factors.1
The relation between NASH and SIBO is unclear. However, there are some reports which described relationship between NASH and SIBO.13-15
SIBO was combined up to 50% of patients with NASH caused by intestinal bypass surgery.13,14
SIBO might play a role in the pathogenesis of NASH by affecting intestinal permeability and serum endotoxin. A slower small intestinal transit time and higher bacterial concentration of proximal small intestine was reported in an experimental model of NASH in rats and treatment with antibiotics accelerated the transit time, decreased TNF-α and lowered the severity of NASH.16
The control of bacterial growth in small intestine is maintained by action of the immune system, gastric acid, pancreatic enzymes, small intestinal motility, and the ileocecal valve.17-19
The jejunocolic bypass can result in disruption of these mechanisms and it can be cause of SIBO.17-19
The symptoms related to SIBO include bloating, diarrhea, weight loss, weakness, and neuropathy.18,20
SIBO generally cause a malabsorption syndrome including cobalamine (vitamin B12), fat-soluble vitamin (vitamin A, D, E, and K), fat, carbohydrate, and iron.18
Edema of lower extremities is caused by more complicated causes such as anemia, malnutrition, hypoproteinemia, and vitamin B12 deficiency.21
Hypoproteinemia and hypoalbuminemia are related to amino acid uptake impairment by SIBO itself or protein losing enteropathy associated with SIBO.18,22,23
The gold standards for the diagnosis of SIBO are considered direct culture of jejunal aspirates.17,20,21,24
There is no consensus in literature on the positive culture cut value for bacterial overgrowth, these cut values range from >104
However, this test is rarely performed in clinical practice, because of invasiveness, possible contamination, and low reproducibility.17,20
Breath tests have been performed as non-invasive tests for diagnosis of SIBO. The most commonly used test for SIBO are hydrogen breath tests using glucose or lactulose.18,20
The positive lactulose hydrogen breath test is defined as early hydrogen peak (>10 ppm) occurring at least 15 minutes before the later prolonged peak or double peak (first peak before 90 minutes and second peak after at least 15 minutes from first peak).24,25
Therapeutic trials of antibiotics can be an alternative diagnostic strategy of SIBO.19
The treatment of SIBO includes treating the underlying disease, eradicating overgrowth, nutritional support.17-19,21
When surgical correction of the clinical condition associated with SIBO is not possible, management is based on antibiotic therapy.
The patient presented in the case, who had no risk factors for primary NASH, has undergone jejunocolic bypass surgery for the purpose of controlling symptoms related to small bowel adhesion. Rapid weight loss and malnutrition was not evident which excludes them as the cause of NASH in this case. Although the majority of intestinal bypass surgery associated with NASH is jejuno-ileal bypass, there is one reported case that is related to jejunocolic bypass in the literature.7
The pitting edema related to hypoalbuminemia was relieved by antibiotic treatment in our case. The hypoalbuminemia can be either related to SIBO itself or protein losing enteropathy caused by SIBO.22
Although a negative result in the technetium labeled (99m
Tc) human serum albumin scintigraphy cannot exclude protein loosing enteropathy due to its variable sensitivity (66% to 96%),26
the cause of hypoproteinemia and hypoalbuminemia in our case favored SIBO itself.
It is reported that SIBO and NASH can be improved when underlying cause is corrected, but there are some cases of NASH which does not resolve after surgical bypass correction.1
In our case, both NASH and SIBO improved dramatically after repair operation.
In conclusion, we report a case of NASH caused by SIBO after jejunocolic bypass surgery, resolved dramatically after surgical correction, with a review of literature.