Minimal Hepatic Encephalopathy: Effect of H. pylori infection and small intestinal bacterial overgrowth treatment on clinical outcomes

Abstract

The effect Helicobacter pylori (Hp) infection and small intestinal bacterial over growth (SIBO) in minimal hepatic encephalopathy (MHE) is not well understood. The aim of the study was to determine the effect of eradication of Hp infection and SIBO treatment on MHE in patients with cirrhosis. Patients with cirrhosis were enrolled and MHE was determined by psychometric tests and critical flicker frequency analysis. Hp infection and SIBO were assessed by urea breath and Hydrogen breath tests respectively in patients with cirrhosis and in healthy volunteers. Patients with Hp infection and SIBO were given appropriate treatment. At six weeks follow-up, presence of Hp infection, SIBO and MHE status was reassessed. Ninety patients with cirrhosis and equal number of healthy controls were included. 55 (61.1%) patients in the cirrhotic group were diagnosed to have underlying MHE. Among cirrhotic group, Hp infection was present in 28 with MHE (50.9%) vs. in 15 without MHE (42.8%) (p = 0.45). Similarly, SIBO was present in 17 (30.9%) vs. 11 (31.4%) (p = 0.95) in patients with and without MHE respectively. In comparison with healthy controls, patients with cirrhosis were more frequently harboring Hp and SIBO (47.7% vs. 17.7% (p < 0.001) and 31.1% vs. 4.4% (p < 0.001) respectively. On follow-up, all patients showed evidence of eradication of Hp and SIBO infection. Treatment of SIBO significantly improved the state of MHE in cirrhotics, however eradication of Hp infection did not improve MHE significantly. Additionally, patients with low Model for End-Stage Liver Disease (MELD) score and belonging to Child class B had significantly better improvement in MHE. A large number of patients with cirrhosis had either active Hp infection or SIBO with or without MHE, compared to healthy controls. Treatment of SIBO significantly improved MHE in patients with cirrhosis, whereas eradication of Hp did not affect the outcome of MHE in these patients. Hepatic encephalopathy (HE) is a frequent complication of chronic liver disease (CLD) 1. HE can be precipitated by various factors like gastrointestinal bleeding, sepsis, azotemia, drugs (e.g. sedatives, diuretics), electrolyte imbalance and constipation. The most relevant substance considered in the pathogenesis of HE is ammonia, although the exact mechanisms of its neurotoxic effects are still under study 2. A substantial number of patients with advanced CLD have minimal hepatic encephalopathy (MHE), which is the earliest stage in the spectrum of HE. One study reported the occurrence of MHE to be as high as 50%in patients with CLD 3. MHE, by definition, has no obvious clinical manifestations and is characterized by neurocognitive impairment in attention, vigilance and integrative function 4. It develops in patients with significant liver function impairment or with porto-systemic shunting. MHE is associated not only with impaired daily functioning and quality of life, but is also considered as an occupational and public health hazard i.e. patient may be unfit to drive a car, operate a machiner...

Identification of minimal hepatic encephalopathy based on dynamic functional connectivity

“…As we know, MHE has the potential to progress into OHE, which can cause irreversible brain damage (Tapper et al, 2020). Studies have shown that MHE can be reversed by prompt treatment (Abid et al, 2020;Butterworth & McPhail, 2019;Nardone et al, 2016); therefore, it is important to diagnose and treat MHE before major neurological damage occurs. Currently, various neuropsychological tests are used as the diagnostic standard for MHE, but they are easily affected by age, education level, and mental state.…”

Helicobacter pylori infection and small intestinal bacterial overgrowth–more than what meets the eye

“…While the “test and treat” strategy[ 13 ] for H. pylori infection in patients with dyspepsia has been validated, no clear recommendations currently exist for testing/treating SIBO in patients with H. pylori infection. Several extra gastrointestinal conditions appear to be associated with both SIBO[ 15 - 18 ] and H. pylori infection[ 19 - 21 ] and dysbiosis due to the attempted treatment for H. pylori infection may be related to the microbiome-mediated pro-inflammatory state. It is therefore important to recognize the signs and symptoms of H. pylori infection and treat the infection as well as the associated dysbiosis bearing in mind that persistence of gastrointestinal symptoms despite eradication of H. pylori infection could suggest coexisting SIBO.…”

“…Several studies have reported an association between SIBO, H. pylori infection and a variety of pathologies (Figure 1 ). In comparison trials, both SIBO and H. pylori infection appear more common in cirrhosis[ 15 ], Fabry’s disease[ 16 ] and Parkinson's disease[ 17 ]. Independent reviews of H. pylori infection and SIBO show overlapping higher incidence in patients with diabetes mellitus, metabolic syndrome, hepatic encephalopathy, chronic urticaria, psoriasis and rosacea when compared to the general population[ 18 - 21 ].…”

“…Independent reviews of H. pylori infection and SIBO show overlapping higher incidence in patients with diabetes mellitus, metabolic syndrome, hepatic encephalopathy, chronic urticaria, psoriasis and rosacea when compared to the general population[ 18 - 21 ]. In patients with cirrhosis and hepatic encephalopathy, the eradication of SIBO appears to improve encephalopathic symptoms; however, the treatment of H. pylori infection does not[ 15 ]. Inversely, the treatment of H. pylori infection has been documented to improve chronic spontaneous urticaria[ 18 ] and rosacea[ 19 ] but the treatment of SIBO has not.…”

Comparison of current and emerging strategies for treating hepatic encephalopathy.

“…6 Many therapeutic agents have been used for the treatment of these complications of end-stage liver disease. 7 These medications reduce the formation of ammonia by reducing its absorption from the gastrointestinal tract. The aggravating factors like electrolyte imbalances, constipation and gastrointestinal hemorrhage are also corrected.…”