The RNA virus, hepatitis E virus (HEV) is the most or second-most important cause of acute clinical hepatitis in adults throughout much of Asia, the Middle East, and Africa. In these regions it is an important cause of acute liver failure, especially in pregnant women who have a mortality rate of 20–30%. Until recently, hepatitis E was rarely identified in industrialized countries, but Hepatitis E now is reported increasingly throughout Western Europe, some Eastern European countries, and Japan. Most of these cases are caused by genotype 3, which is endemic in swine, and these cases are thought to be zoonotically acquired. However, transmission routes are not well understood. HEV that infect humans are divided into nonzoonotic (types 1, 2) and zoonotic (types 3, 4) genotypes. HEV cell culture is inefficient and limited, and thus far HEV has been cultured only in human cell lines. The HEV strain Kernow-C1 (genotype 3) isolated from a chronically infected patient was used to identify human, pig, and deer cell lines permissive for infection. Cross-species infections by genotypes 1 and 3 were studied with this set of cultures. Adaptation of the Kernow-C1 strain to growth in human hepatoma cells selected for a rare virus recombinant that contained an insertion of 174 ribonucleotides (58 amino acids) of a human ribosomal protein gene.

https://www.pnas.org/content/pnas/108/6/2438.full.pdf

Cross-species infections of cultured cells by hepatitis E virus and discovery of an infectious virus–host recombinant

“Intrinsic” and “idiosyncratic” drug-induced liver injury reactions are commonly thought to arise by different modes of action. Intrinsic toxicity is reproducible in animals and occurs dose-dependently at sublethal doses. Environmental and genetic sensitivity factors can influence the toxicity of intrinsic hepatotoxicants. Among these is inflammatory stress. For example, exposure of mice to inflammatory bacterial lipopolysaccharide (LPS) causes a leftward shift in the dose-response relationship for acetaminophen hepatotoxicity; that is, acetaminophen toxicity is enhanced by LPS-induced inflammatory stress. Idiosyncratic reactions present themselves very differently than intrinsic ones; they happen in a minority of patients, with variable time of onset and no obvious relationship to drug dose, and they are not reproducible in usual animal tests. Although these characteristics seem to distinguish them from intrinsic reactions, consideration of fundamental principles of dose response can explain the differences. For a drug that causes idiosyncratic hepatotoxicity, the liver may not be a typical target for toxicity because the dose-response curve for hepatotoxicity lies to the right of the lethal dose. However, a sporadically occurring sensitivity factor, such as an inflammatory episode, could shift the dose-response curve for hepatotoxicity to the left, thereby bringing hepatotoxic doses into the therapeutic range. This hypothesis can account for the bizarre characteristics of idiosyncratic reactions and is supported by recent results showing that several drugs associated with human idiosyncratic reactions can be rendered hepatotoxic to rodents upon interaction with an inflammatory stimulus. In light of this view, intrinsic and idiosyncratic reactions may not be that different after all.

https://jpet.aspetjournals.org/content/jpet/early/2009/12/17/jpet.109.162651.full.pdf

Intrinsic versus idiosyncratic drug-induced hepatotoxicity--two villains or one?

Hepatitis E virus (HEV) is a common cause of acute on chronic liver failure (ACLF) in HEV hyperendemic regions with high mortality. Treatment for HEV-induced ACLF is currently not available. Recent...

Ribavirin therapy for hepatitis E virus-induced acute on chronic liver failure: a preliminary report.

Cardiovascular diseases still account for the majority of deaths worldwide, although significant improvements in survival, after being affected by cardiovascular disease, have been achieved in the last decades. Periodontal diseases are also a common global burden. Several studies have shown a link between cardiovascular disease and periodontitis, although evidence is still lacking regarding the direct cause-effect relation. During the 2012 "Periodontitis and systemic diseases" workshop, the available evidence on the association between cardiovascular and periodontal diseases was discussed, covering biologic plausibility and clinical studies. The objective of the present narrative review was to update the previous reviews presented at the 2012 workshop, following similar methodological approaches, aiming to critically assess the available evidence. With regard to biologic plausibility, two aspects were reviewed: (a) for microbiologic mechanisms, assessing periodontal bacteria as a contributing factor to atherosclerosis based on seven "proofs," substantial evidence was found for Proofs 1 through 6, but not for Proof 7 (periodontal bacteria obtained from human atheromas can cause atherosclerosis in animal models), concluding that periodontal pathogens can contribute to atherosclerosis; (b) mechanistic studies, addressing five different inflammatory pathways that could explain the links between periodontitis and cardiovascular disease with the addition of some extra pathways , suggest an association between both entities, based on the presence of higher levels of these inflammatory markers in patients with periodontitis and cardiovascular disease, vs healthy controls, as well as on the evidence that periodontal treatment reduces serum levels of these mediators. When evidence from clinical studies was analyzed, two aspects were covered: (a) epidemiologic studies support the estimation that the incidence of atherosclerotic disease is higher in individuals with periodontitis than in individuals with no reported periodontitis, irrespective of many common risk factors, but with a substantial variability in the definitions used in reporting of exposure to periodontal diseases in different studies; (b) intervention trials have shown that periodontal therapy can reduce serum inflammatory mediators, improve the lipids profile, and induce positive changes in other cardiovascular disease surrogate measures, but no evidence is available to support that adequate periodontal therapy is able to reduce the risk for cardiovascular diseases, or the incidence of cardiovascular disease events in periodontitis patients.

Periodontal diseases and association with atherosclerotic disease.

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis (AVH) globally. It causes large scale epidemics of AVH across the low- and middle income countries in Asia and Africa, and also causes sporadic cases of AVH in the same geographical region. AVH due to HEV is usually an acute, self-limiting illness, similar in clinical presentation to AVH caused by hepatitis A virus (HAV). When HEV causes AVH in patients of chronic liver disease it may worsen rapidly to a syndrome called acute-on-chronic liver failure (ACLF) leading to very high mortality. Acute deterioration of liver function in a patient with compensated chronic liver disease is the characteristic feature of ACLF. The typical disease course of patients with ACLF is the appearance of organ failure, which progresses to multi-organ failure and death. Many publications have reported HEV as one of the leading causes for ACLF from Asia and Africa, where HEV is endemic. The mortality rate of HEV-related ACLF (HEV-ACLF) ranges from 0% to 67% with a median being 34%. These patients require admission in the intensive care unit and they benefit from a team approach of clinicians with expertise in both hepatology and critical care. The goals of treatment are to prevent further deterioration in liver function, reverse precipitating factors, and support failing organs. Liver transplantation is required in selected patients to improve survival and quality of life. One preliminary report suggests that ribavirin may be an effective and safe drug for treatment of HEV-ACLF however this requires validation in large trials.

Hepatitis E and Acute-on-Chronic Liver Failure

Introduction: Hepatitis E virus is a major cause of enterically transmitted hepatitis. Mortality is very high if it is associated with pregnancy, especially during third trimester. This study was carried out to fi nd out the effects of acute HEV hepatitis on Chronic Liver Disease patients of different etiologies. Methods: The consecutive patients of liver cirrhosis with defi nite evidence of recent HEV infection were enrolled in this study. Acute hepatitis was diagnosed by presence of prodromal symptoms and anti-HEV IgM antibody in their serum. The outcomes after superinfection with HEV hepatitis were determined by changes in Child Pugh score, recovery of liver function test, hospital stay and mortality. Results: After exclusion 25 were studied. The etiology of cirrhosis in patients was: alcohol 13, autoimmune hepatitis 3, hepatitis B 2, Budd Chiari syndrome 2, alcohol plus hepatitis B 1, hepatitis C 1, cardiac cirrhosis 1, Wilson’s disease 1 and cryptogenic 1. All patients with no recent decompensation showed signs of decompensation during admission. Seven (28%) patients died. The cause of death was either upper gastrointestinal bleeding or hepatorenal syndrome. Remaining patients had prolonged hospital stay with deterioration of Child-Pugh’s score. Conclusions: Superinfection of HEV in cirrhotic patient causes rapid decompensation. The morbidity and mortality is higher compared to those non-infected patients. Development of hepatorenal syndrome and upper GI bleeding was commonest cause of death. Key Words: acute HEV infection, Chronic liver disease, third trimester pregnancy

/pdf/effect-of-acute-hepatitis-e-infection-in-patients-with-liver-3wtbsz80h5.pdf

Effect of acute hepatitis E infection in patients with liver cirrhosis.

Background Portal hypertensive gastropathy (PHG) is an underappreciated condition in patients with chronic liver disease (CLD). It is a common endoscopic finding in CLD patients, but its relation with esophageal varices (EV) and the severity of the liver disease is controversial. Herein, we aimed to study the prevalence of PHG in CLD patients and to determine its association with EV and the severity of the liver disease. Methods This descriptive, cross-sectional, analytical study was conducted at the Hepatology department, Bir Hospital Kathmandu from 19th March to 30th June 2019. A total of 404 patients with CLD of various etiology fulfilling the inclusion criteria were approached, and informed consent was taken before enrolling in the study. All patients underwent EGD, and the findings related to EV and PHG were noted. The severity of PHG was graded according to the McCormack classification and EV were graded according to the American Association for the study of liver diseases guideline. The severity of liver disease was stratified based on Child-Pugh class and Model for End-Stage Liver Disease (MELD score). Data was entered on Statistical Package for the Social Sciences (SPSS) Version 25 for further analysis. Results Of 404 CLD patients, the mean (±SD) age was 49.14 (±10.5) years. Portal hypertensive gastropathy was observed in 269 (66.6%) patients, of which 80.6% (217) had mild PHG while 19.4% (52) had severe PHG. EV were present in 362 (89.6%) patients. One hundred and thirty-two (36.5%) had small EV, and 230 (63.5%) had large EV. No significant association was observed between grades of gastropathy and size of varices (p = 0.36). There was a non-significant association with the MELD score and other biochemical parameters. However, there were significant associations between Child-Pugh class and PHG and Child-Pugh class and PHG severity, p = 0.001 and p = 0.01 (p <0.05), respectively. Conclusions In our study, the prevalence of PHG in the Nepalese population in CLD is 66.6 %. PHG is significantly associated with the severity of CLD in terms of Child-Pugh class but not associated with MELD. Also, no association has been found with the size of varices.

Prevalence of Portal Hypertensive Gastropathy in Chronic Liver Disease and Correlation with the Severity of Liver disease.

Introduction: Irritable bowel syndrome occurs as recurrent abdominal pain that is related to defecation and associated with change in frequency and/or form of stool. Few Patients with IBS may have organic lesions detectable at colonoscopy.
Methods: A cross sectional study was carried out in 140 consecutive patients of IBS fulfilling the ROME IV criteria. The study was conducted in Gastroenterology unit, Department of Medicine, Bir hospital, Kathmandu from July 2016 to September 2017. All patients underwent full colonoscopy along with biopsy from sigmoid colon and any visibly abnormal areas.
Results: The average age of patients was 37.5 years with 76 (52.8%) males. Forty-two (30%) had IBS-D, 36 (26%) had IBS-C, 31 (22%) had IBS-M and 31 (22%) had IBS-U. Dyspepsia was seen in 16 (11.4%) and fear of TB/Malignancy/IBD was seen in 27 (19.2%). Organic lesions were seen in 39 (27.85%) patients. Nonspecific colitis was seen in 10 (7.1%) followed by ileal erosions in 7 (5%), polyps in 8 (5.7%), hemorrhoids in 6 (4.2%) and diverticula in 3 (2.1%). Only one (0.71%) patient had microscopic colitis and one (0.71%) had malignant lesion seen at histopathological examination. Females with IBS-D had more organic findings than males (P=0.03, RR=4.13, 95% CI=1.21-15.71).
Conclusions: The prevalence of organic lesions in patients with IBS fulfilling ROME IV criteria is 27%. Dyspepsia is the most common comorbidity and fear of TB/malignancy/IBD is the most common reason for seeking health care. Females with IBS-D have a higher risk of detecting organic lesions by colonoscopy and histopathology examination.

/pdf/prevalence-of-organic-colonic-lesions-by-colonoscopy-in-1gu4s89kab.pdf

Prevalence of Organic Colonic Lesions by Colonoscopy in Patients Fulfilling ROME IV Criteria of Irritable Bowel Syndrome.

Introduction : Our clinical experience showed that there has been no decrease in pediatric cases of acute viral hepatitis in Kathmandu. The objective of the study was to analyze the etiology, clinical features, laboratory parameters, sonological findings and other to determine the probable prognostic factors of Acute Viral Hepatitis in pediatric population. Methods : Consecutive patients of suspected Acute Viral Hepatitis, below the age of 15 years, attending the liver clinic between January 2006 and December2010were studied. After clinical examination they were subjected to blood tests and ultrasound examination of abdomen. The patients were divided in 3 age groups; 0–5, 5–10 and 5–15 years. Clinical features, laboratory parameters, ultrasound findings were compared in three age groups. Results : Etiology of Acute Viral Hepatitis was Hepatitis A virus 266 (85%), Hepatitis E virus in 24 (8%), Hepatitis B virus in 15 (5%). In 7(2%) patients etiology was unknown. Three patients went to acute liver failure but improved with conservative treatment. There was no statistical difference in most of the parameters studied in different age groups. Ascites was more common in 5-10 years age group. Patients with secondary bacterial infection, ultrasound evidence of prominent biliary tree and ascites were associated with increased duration of illness. Patients with history of herbal medications had prolonged cholestasis. Conclusions : Hepatitis A is most common cause of Acute Viral Hepatitis in pediatric population. Improper use of herbal medications, secondary bacterial infection and faulty dietary intake was associated with prolonged illness. Patients with prominent biliary radicals should be treated with antibiotics even with normal blood counts for earlier recovery. Keywords : Acute viral hepatitis; hepatitis A; hepatitis E; herbal medications.

/pdf/acute-viral-hepatitis-in-pediatric-age-groups-3esb5du9s5.pdf

Acute Viral Hepatitis in Pediatric Age Groups

Introduction: Chronic periodontitis is an infectious disease resulting in inflammation within the supporting tissues of the teeth, progressive attachment loss, and bone loss. In addition to declining oral health, there is always low grade infection present in periodontitis. Studies show increased levels of systemic biomarkers in periodontal disease such as CRP, which is considered a key-marker of CVD. Research has also shown positive association between BMI and smoking with periodontitis and CRP. The objective of the study was to assess the levels of CRP in patients with and without periodontitis and their relation with BMI and smoking behaviour.Methods: Patients visiting the Dental department of Bir Hospital were invited to participate in the study. Total 31 subjects in each group: Case (periodontitis) and Control (without periodontitis) were selected using convenience sampling technique. All subjects underwent periodontal examination by a single examiner. Serum CRP samples were taken before periodontal treatment. Data analysis was done by SPSS 17 software program.Results: Increase in mean CRP levels in periodontitis (5.8595mg/L) with high statistical significance (p=0.000) in comparison to subjects without periodontitis (1.1214mg/L) was observed. BMI showed positive association with periodontitis (p=0.046) but not with CRP (0.213). Smoking behaviour showed no significant relation with either CRP (p=0.344) or periodontitis (p=0.541).Conclusions: We found highly significant association between periodontitis and CRP levels but not always with BMI and smoking. CRP, which is an established marker for CVD was significantly increased in periodontal infections. Hence, a close interaction among Physician, Periodontist and Patient to prevent adverse health situations is recommended.Keywords: body mass index; cardiovascular disease; c-reactive protein; periodontitis; smoking; systemic inflammation. [PubMed]

/pdf/c-reactive-protein-in-periodontitis-and-its-comparison-with-4q1hk4ul14.pdf

Sudhamshu Kc

Papers

Effect of acute hepatitis E infection in patients with liver cirrhosis.

Prevalence of Portal Hypertensive Gastropathy in Chronic Liver Disease and Correlation with the Severity of Liver disease.

Prevalence of Organic Colonic Lesions by Colonoscopy in Patients Fulfilling ROME IV Criteria of Irritable Bowel Syndrome.

Acute Viral Hepatitis in Pediatric Age Groups

C-reactive Protein in Periodontitis and its Comparison with Body Mass Index and Smoking Behaviour