Isolated for the first time in 1982 from human gastric biopsy, Helicobacter pylori is responsible for gastritis, peptic ulcer, and gastric cancer. A pathogenicity island acquired by horizontal transfer, coding for a type IV secretion system, is a major determinant of virulence. The infection is now treated with antibiotics, and vaccines are in preparation. The geographic distribution suggests coevolution of man and Helicobacter pylori.

https://science.sciencemag.org/content/sci/284/5418/1328.full.pdf

Helicobacter pylori virulence and genetic geography.

Hepatitis B is one of the most common infectious diseases globally. It has been estimated that there are 350 million chronic hepatitis B virus (HBV) carriers worldwide. The prevalence of chronic HBV infection varies geographically, from high (>8%), intermediate (2-7%) to low (<2%) prevalence. HBeAg-negative chronic hepatitis B (e-CHB) and occult HBV infection are two special clinical entities, and the prevalence and clinical implications remain to be explored. The predominant routes of transmission vary according to the endemicity of the HBV infection. In areas with high HBV endemicity, perinatal transmission is the main route of transmission, whereas in areas with low HBV endemicity, sexual contact amongst high-risk adults is the predominant route. HBV has been classified into 7 genotypes, i.e. A to G, based on the divergence of entire genome sequence and HBV genotypes have distinct geographical distributions. Three main strategies have been approved to be effective in preventing HBV infection. They are behavior modification, passive immunoprophylaxis, and active immunization. The implement of mass HBV immunization program is recommended by the WHO since 1991, and has dramatically decreased the prevalence of HBV infection and HCC in many countries.

/pdf/epidemiology-and-prevention-of-hepatitis-b-virus-infection-2nyquxecg4.pdf

Epidemiology and Prevention of Hepatitis B Virus Infection.

Nonalcoholic fatty liver disease (NAFLD) and its inflammatory and often progressive subtype nonalcoholic steatohepatitis (NASH) are becoming the leading cause of liver-related morbidity and mortality worldwide, and a primary indication for liver transplantation. The pathophysiology of NASH is multifactorial and not yet completely understood; however, innate immunity is a major contributing factor in which liver-resident macrophages (Kupffer cells) and recruited macrophages play a central part in disease progression. In this Review, we assess the evidence for macrophage involvement in the development of steatosis, inflammation and fibrosis in NASH. In this process, not only the polarization of liver macrophages towards a pro-inflammatory phenotype is important, but adipose tissue macrophages, especially in the visceral compartment, also contribute to disease severity and insulin resistance. Macrophage activation is mediated by factors such as endotoxins and translocated bacteria owing to increased intestinal permeability, factors released from damaged or lipoapoptotic hepatocytes, as well as alterations in gut microbiota and defined nutritional components, including certain free fatty acids, cholesterol and their metabolites. Reflecting the important role of macrophages in NASH, we also review studies investigating drugs that target macrophage recruitment to the liver, macrophage polarization and their inflammatory effects as potential treatment options for patients with NASH.

The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

https://www.journal-of-hepatology.eu/article/S0168-8278(09)00170-6/pdf

Kupffer cells in non-alcoholic fatty liver disease: the emerging view.

Steatosis of the liver may arise from a variety of conditions, but the molecular basis for lipid droplet formation is poorly understood. Although a certain amount of lipid storage may even be hepatoprotective, prolonged lipid storage can result in an activation of inflammatory reactions and loss of metabolic competency. Apart from drug-induced steatosis, certain metabolic disorders associated with obesity, insulin resistance, and hyperlipidemia give also rise to nonalcoholic fatty liver diseases (NAFLD). It is noteworthy that advanced stages of nonalcoholic hepatic steatosis and steatohepatitis (NASH) result ultimately in fibrosis and cirrhosis. In this regard, the lipid droplets (LDs) have been discovered to be metabolically highly active structures that play major roles in lipid transport, sorting, and signaling cascades. In particular, LDs maintain a dynamic communication with the endoplasmic reticulum (ER) and the plasma membrane via sphingolipid-enriched domains of the plasma membrane-the lipid rafts. These microdomains frequently harbor receptor tyrosine kinases and other signaling molecules and connect extracellular events with intracellular signaling cascades. Here, we review recent knowledge on the molecular mechanisms of drug and metabolically induced hepatic steatosis and its progression to steatohepatitis (NASH). The contribution of cytokines and other signaling molecules, as well as activity of nuclear receptors, lipids, transcription factors, and endocrine mediators toward cellular dysfunction and progression of steatotic liver disease to NASH is specifically addressed, as is the cross-talk of different cell types in the pathogenesis of NAFLD. Furthermore, we provide an overview of recent therapeutic approaches in NASH therapy and discuss new as well as putative targets for pharmacological interventions.

Molecular Mechanisms and Therapeutic Targets in Steatosis and Steatohepatitis

Background and Aims:  The spectrum of non-alcoholic fatty liver disease (NAFLD) ranges from simple steatosis to severe steatohepatitis (NASH). The aim of our study was to identify clinical predictors distinguishing NASH from steatosis and to study the pathogenesis of NASH in a young Korean population.



Methods:  Clinical and biochemical variables from 39 biopsied NAFLD patients were retrospectively analyzed. All liver biopsy specimens were immunohistochemically examined for Kupffer cells (CD68, CD14), as well as expression of tumor necrosis factor-alpha (TNF-α) and mitochondrial uncoupling protein 2 (UCP-2).



Results:  There were no significant differences in serum biochemistry between the two groups (15 steatosis vs 24 NASH). There was a significant difference between the body mass index (BMI) values (kg/m2) of the NASH (28.4 ± 3.4 kg/m2) and steatosis (25.8 ± 2.8 kg/m2) patients (P < 0.025), with a BMI of 28.9 kg/m2 representing the best threshold for distinguishing NASH from steatosis patients. BMI was significantly related to the degree of fibrosis (P < 0.01). CD68+ Kupffer cells were more common in the livers of NASH patients (P < 0.05), and TNF-α and UCP-2 were expressed in all NASH specimens and were related with the severity of inflammation and fibrosis (P < 0.05).



Conclusions:  BMI could be used to distinguish NASH from steatosis in younger Korean patients. A high BMI with a low alanine aminotransferase (ALT) value tended to suggest the presence of severe fibrosis in NASH, while the number of CD68+ Kupffer cells and the staining intensity of TNF-α and UCP-2 were correlated with general pathologic severity in patients with NAFLD.

Predictors reflecting the pathological severity of non-alcoholic fatty liver disease: Comprehensive study of clinical and immunohistochemical findings in younger Asian patients

Precore and core promoter mutations of hepatitis B virus and hepatitis B e antigen-negative chronic hepatitis B in Korea.

BACKGROUND Irritable bowel syndrome is one of the most commonly encountered gastrointestinal disorders, for which there are no established diagnostic criteria Thus, a diagnosis of IBS is made by exclusion of any organic diseases Recently, important attempts for the positive diagnosis of irritable bowel syndrome by questionnaire surveys of physical symptoms have been made We performed a questionnaire survey to evaluate the diagnostic value of the Manning criteria and to observe the major symptoms in irritable bowel syndrome METHODS A symptom questionnaire which consisted of 22 items, including 6 cardinal symptoms of the Manning criteria, were answered by 172 outpatients who had gastrointestinal complaints According to a final diagnosis based on independent clinical evaluation, all patients were categorized in three groups: irritable bowel syndrome group, nonulcer dyspepsia group and organic gastrointestinal disease group The results of the questionnaire were analyzed for each group RESULTS The sensitivity and specificity of the Manning criteria for the diagnosis of irritable bowel syndrome were 67% and 70% if three or more items were regarded as positive The mean score and overall frequency of the Manning criteria were significantly higher in irritable bowel syndrome group than in nonuclear dyspepsia (p < 001) or organic gastrointestinal disease group (p < 005) Among subgroups of the irritable bowel syndrome group, the pain-predominant subgroup showed a significantly higher score and overall frequency than the painless subgroup (p < 005) CONCLUSIONS The Manning criteria would be useful as a simple and reliable backup tool for the diagnosis of irritable bowel syndrome and seem to be more useful in pain-predominant subgroup More detailed history-taking should prevent unnecessary extensive investigations for the diagnosis of irritable bowel syndrome

Manning Criteria in Irritable Bowel Syndrome: Its Diagnostic Significance

Background: Helicobacter pylori strains possessing the cagA gene have been postulated to have a disease-specific relationship to peptic ulcer. The purpose of this study was to investigate the relationship between the infection with Helicobacter pylori expressing the cagA gene and the development of peptic ulcer diseases in Korean patients. Methods: Genomic DNA and bacterial mRNA in the gastric mucosa were amplified by polymerase chain reaction (PCR) and reverse transcription PCR, using synthetic oligonucleotide primers to cagA genes to compare the prevalence of cagA genes in 35 patients with non-ulcer gastritis and 99 patients with gastric or duodenal ulcer disease (53 and 46, respectively). Two different primer sets for the cagA gene were used. The first primer set amplified a 298-bp region (nucleotides 1751-2048), and the second set amplified a 349-bp region (nucleotides 1228-1249). Results: The expected 298- and 349-bp PCR amplicons were identified as follows: 1) 32 (91.4%) and 30 (85.7%) of 35 non-ulc...

Infection with Helicobacter pylori Expressing the cagA Gene Is Not Associated with an Increased Risk of Developing Peptic Ulcer Diseases in Korean Patients

Background The aims of our study were to determine the correlation of the strain variation and degree of homogeneity of infecting Helicobacter pylori (H. pylori) with their disease outcomes, and the relevance of duodenal H. pylori expression of cagA and/or vacA gene to the development of duodenal ulcer in Korean patients. Methods One hundred and twenty bacterial colonies isolated from different anatomical sites of the stomach and duodenum were used. The study population was consisted of 40 Korean patients, 21 with duodenal ulcer, 7 with gastric ulcer, 3 with combined gastric and duodenal ulcer, and 9 with chronic gastritis. Genomic characteristics of each strain were analyzed by random amplified polymorphic DNA (RAPD) fingerprinting. The cagA and vacA genes were detected by polymerase chain reaction (PCR). Results PCR-based RAPD was proved to be a reliable method for the discrimination of individual bacterial genomic characteristics. Genomic fingerprinting showed a varying degree of inter- and intra-patient variation. Thirteen patients (32.5%) were colonized by a single strain throughout the corpus, antrum and duodenum, whereas the other 27 (67.5%) harbored multiple H. pylori strains. Thirty-six isolates (90.0%) each from the corpus and antrum, and 34 (85.0%) from the duodenum, expressed the cagA gene. The prevalence of duodenal H. pylori expression of the cagA gene was not different between patients with chronic gastritis and those with duodenal ulcer. All isolates were positive for both genes vacA s1 and vacA s1a. Conclusion These results suggested that many of the H. pylori-infected Korean patients were actually colonized with mixed populations of different H. pylori strains and that the prevalence of duodenal H. pylori expression of the cagA and/or vacA gene was not correlated with the development of duodenal ulcer in Korean patients.

High prevalence of multiple strain colonization of Helicobacter pylori in Korean patients: DNA diversity among clinical isolates from the gastric corpus, antrum and duodenum.

Sill Moo Park

Papers

Predictors reflecting the pathological severity of non-alcoholic fatty liver disease: Comprehensive study of clinical and immunohistochemical findings in younger Asian patients

Precore and core promoter mutations of hepatitis B virus and hepatitis B e antigen-negative chronic hepatitis B in Korea.

Manning Criteria in Irritable Bowel Syndrome: Its Diagnostic Significance

Infection with Helicobacter pylori Expressing the cagA Gene Is Not Associated with an Increased Risk of Developing Peptic Ulcer Diseases in Korean Patients

High prevalence of multiple strain colonization of Helicobacter pylori in Korean patients: DNA diversity among clinical isolates from the gastric corpus, antrum and duodenum.