This study reports the acute outcomes in a typical resource-poor setting in Bangladesh. The majority (75%) of subjects were female. Seven (35%) patients in our study were pregnant. Three (42.86%) out of 7 pregnant subjects and 3 (23.08%) out of 13 non-pregnant subjects had worsening of HE. Deterioration of HE was not statistically significantly different between pregnant and non-pregnant subjects (Fisher’s exact = 1.000).
In a previous study on this HEV epidemic in Chattogram (Chittagong), Bangladesh, we found that among 230 of our patients 24 (10.4%) had developed ALF. Four (1.8%) among them died due to multiorgan failure with acute kidney injury, and all were pregnant [17].
Other studies in Bangladesh also found that women, especially pregnant women, were more susceptible to HEV-induced ALF and had worse outcome when they developed ALF [4, 5]. Moreover, in another Bangladeshi study, the authors observed that mortality approached 75% when women in the second and third trimester of pregnancy developed HEV-induced ALF [5].
In prospective studies comparing HEV hepatitis and non-HEV hepatitis in India, the authors observed that 55–70% of pregnant subjects with HEV hepatitis and 10–20% of pregnant subjects with non-HEV hepatitis developed liver failure [27, 28]. Furthermore, a study in China also found that 15–60% of the pregnant subjects with acute HEV hepatitis developed ALF [29].
On the other hand, in a study in India, which included 20 years’ data from a single tertiary centre, the authors observed that pregnant and non-pregnant subjects had equal chances of developing HEV-induced ALF [30]. In that study, which compared 249 (38.5%) pregnant subjects with 341 non-pregnant women and girls and 425 men and boys, aged 15 to 45 years, the authors found that the mortality rate of pregnant women and girls (53.8%) was similar to age-matched non-pregnant women and girls (57.2%), men and boys (57.9%) (P = 0.572). The authors also observed that the clinical and biochemical profile, disease intensity and sequelae were also comparable in those three study groups. Although a significantly higher percentage of ALF was attributable to HEV among pregnant subjects (59.4%) in comparison to both non-pregnant women and girls (30.4%) and men and boys (23.1%), (P < 0.001), the outcome of HEV-induced ALF had no association with the gender and pregnancy status of the subjects (P = 0.103). Furthermore, the mortality of pregnant subjects in HEV-induced ALF of 51% (74/145) and non-HEV-induced ALF of 54.7% (52/95) was not significant (P > 0.1). In addition, the authors also found that the outcome in HEV-induced ALF in pregnant subjects was not associated with the trimester of pregnancy.
Shalimar and colleagues in their study observed that the increased HEV-induced ALF and resulting mortality might be due to the increased susceptibility of women, especially pregnant women, to HEV infection during an epidemic in affected populations [31]. Moreover, the authors found that after the development of ALF, the prognosis was not dependent on pregnancy status.
According to a study in Bangladesh [7], cerebral oedema found in 48 (71.6%) among 67 subjects was the most important cause of death in the ALF patients. Acharya and co-workers in a study in India [25], which included 423 consecutive patients with ALF due to hepatotropic viruses (predominantly non-A, non-B), found that the presence of cerebral oedema was an independent predictor of adverse outcome.
We found that 12 (60%) among our 20 subjects showed clinical features of raised ICP. Ten (50%) subjects received mannitol infusion. HE deteriorated in two (10%) out of 10 subjects who received mannitol and 6 (30%) out of 10 subjects who did not receive mannitol. GCS deteriorated in one (5%) out of 10 subjects who received and 5 (25%) out of 10 subjects who did not receive mannitol. Although the outcome was not found to be statistically significant for either HE worsening (p= 0.085) or GCS deterioration (p= 0.070), the reason for this can be explained by the small sample size of the study.
Canalese and co-workers compared the effects of prophylactic dexamethasone and mannitol infusion to revert cerebral oedema in subjects with ALF with HE grade IV in a randomised controlled clinical trial. Cerebral oedema resolved significantly more frequently in 17 among 34 subjects who received mannitol and in 17 among 34 subjects who did not (p<0001) [9]. Survival was also found to be significantly better in subjects that received mannitol (p 0.008).
Acharya and colleagues [6] in India found that outcome of ALF in pregnant subjects was similar to that in non-pregnant subjects and one-third of ALF patients survived with aggressive conservative therapy. Our study also found that the outcome in pregnant and non-pregnant subject was not statistically significantly different. Moreover, HE worsened in 8 (40%) and GCS deteriorated in 6 (30%) of our subjects during the 5 days. More than 60% of our patients showed clinical improvement with conservative therapy.
Shalimar and his colleagues also observed that MELD, an ALF study group model, and King’s College Hospital criteria failed to predict outcome in HEV-induced ALF. In our study, six patients (30%) met King’s College Criteria for liver transplantation. Four (66.67%) among those 6 patients developed deterioration of their encephalopathy grades (Fisher’s exact =0.018), and 5 (83.33%) developed deterioration of GCS (Fisher’s exact=0.002) [8].
Limitations of our study
Most of our patients were transferred from different inpatient units—medicine, obstetrics and surgery when they were diagnosed as having HEV-induced ALF. We could not take a detailed history from the patients or look for other causes which could have modified the clinical illness in our subjects owing to cerebral obtundation. Furthermore, we could not test for HEV RNA and detect the HEV genotype in our subjects, owing to resource issues.
Moreover, we diagnosed raised ICP, based on clinical parameters, which may not be optimum in some cases, again owing to lack of resources. The sensitivity and specificity of clinical parameters for the diagnosis of raised ICP in the settings of ALF are low. Neurological examination and clinically establishing raised ICP in these patients can be challenging [24].