Evaluation and Management of Chronic Cholestatic Liver Diseases.

Cholestasis is defined as stagnation or a marked reduction in bile secretion and flow. Cholestatic jaundice can thus be classified as intrahepatic or extrahepatic cholestatic, depending on the level of obstruction to bile flow. It is important to recognize the complications of cholestatic in patients with chronic cholestatic liver disease. The two most common complications of cholestasis are pruritus and fatigue, with the former being the most responsive to treatment. Cholestyramine is the first-line treatment for cholestatic pruritus. Rifampicin and oral opioid antagonist naltrexone are extremely effective second-line treatments. To date, there are no specific treatments for chronic cholestatic fatigue management. Osteoporosis is a complication that can arise in chronic cholestatic conditions. It appears to be more prominent in individuals with cholestatic liver disease than in patients with other chronic liver diseases with an increased risk of fracture. The evaluation of osteoporosis in individuals with chronic cholestasis is similar to that in the general population. Antiresorptive agents such as bisphosphonates are the first-line treatment choice for osteoporosis in patients with chronic cholestasis. Other less common complications include dyslipidemia, fat-soluble vitamin deficiency, and steatorrhea. Understanding and treating these conditions can have a significant impact on the morbidity and quality of life in this group of patients. This review aimed to provide further information about the complications of chronic cholestasis and to highlight evidence-based test practices for the evaluation and effective management of these complications.

Efficacy of probiotics in the treatment of minimal hepatic encephalopathy: A systematic review and meta-analysis.

Aim of the study: Patients with minimal hepatic encephalopathy (MHE) have no recognizable clinical symptoms of hepatic encephalopathy (HE), but the mild cognitive and psychomotor deficits have been shown to negatively affect their daily functioning and quality of life. Treatment with probiotics has shown benefit in some clinical trials. This review aimed to systematically analyze the efficacy of probiotics in the treatment of MHE. Material and methods: A systematic search of the electronic databases PubMed, Science Direct, and Cochrane Library was conducted for randomized controlled trials (RCTs) in adult patients with MHE who had been given probiotics intervention. The primary outcomes were reversal of MHE and improvement of neuropsychometric tests, while the secondary outcome was the reduction of serum ammonia. Results: Nine RCTs involving 776 MHE patients were included, consisting of 311 patients receiving probiotics and 465 patients receiving comparator (placebo or no treatment, lactulose, L-ornithine L-aspartate [LOLA], or rifaximin). The meta-analysis showed that probiotics significantly reversed MHE (OR = 3.95, p < 0.0001, 95% CI: 2.05 to 7.60) compared with placebo or no treatment. Probiotics also significantly reduced serum ammonia compared with placebo (pooled mean difference -25.94, p = 0.04, 95% CI: -50.21 to -1.66). However when compared to lactulose and LOLA, probiotics did not show a significant difference in reversal of MHE or reduction of serum ammonia levels. Conclusions: Probiotics were more effective in reversal of MHE and reduced serum ammonia levels in patients with MHE compared to placebo or no treatment, but not more effective than lactulose or LOLA.

Diabetes and fatty liver: Involvement of incretin and its benefit for fatty liver management.

Fatty liver disease is defined as liver condition characterized by hepatic steatosis, closely related to pathological conditions in type 2 diabetes and obesity. The high prevalence of fatty liver disease in obese patients with type 2 diabetes reached 70%, reflecting the importance of these conditions with fatty liver. Although the exact pathological mechanism of fatty liver disease, specifically non-alcoholic fatty liver disease (NAFLD) remains not completely revealed, insulin resistance is suggested as the major mechanism that bridged the development of NAFLD. Indeed, loss of the incretin effect leads to insulin resistance. Since incretin is closely related to insulin resistance and the resistance of insulin associated with the development of fatty liver disease, this pathway suggested a potential me-chanism that explains the association between type 2 diabetes and NAFLD. Furthermore, recent studies indicated that NAFLD is associated with impaired glucagon-like peptide-1, resulting in decreased incretin effect. Nevertheless, improving the incretin effect becomes a reasonable approach to manage fatty liver disease. This review elucidates the involvement of incretin in fatty liver disease and recent studies of incretin as the management for fatty liver disease.

Antimicrobial Resistance Profile by Metagenomic and Metatranscriptomic Approach in Clinical Practice: Opportunity and Challenge.

The burden of bacterial resistance to antibiotics affects several key sectors in the world, including healthcare, the government, and the economic sector. Resistant bacterial infection is associated with prolonged hospital stays, direct costs, and costs due to loss of productivity, which will cause policy makers to adjust their policies. Current widely performed procedures for the identification of antibiotic-resistant bacteria rely on culture-based methodology. However, some resistance determinants, such as free-floating DNA of resistance genes, are outside the bacterial genome, which could be potentially transferred under antibiotic exposure. Metagenomic and metatranscriptomic approaches to profiling antibiotic resistance offer several advantages to overcome the limitations of the culture-based approach. These methodologies enhance the probability of detecting resistance determinant genes inside and outside the bacterial genome and novel resistance genes yet pose inherent challenges in availability, validity, expert usability, and cost. Despite these challenges, such molecular-based and bioinformatics technologies offer an exquisite advantage in improving clinicians' diagnoses and the management of resistant infectious diseases in humans. This review provides a comprehensive overview of next-generation sequencing technologies, metagenomics, and metatranscriptomics in assessing antimicrobial resistance profiles.

Additional treatment of vitamin D for improvement of insulin resistance in non-alcoholic fatty liver disease patients: a systematic review and meta-analysis.

Insulin resistance provides an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Several studies already evaluate vitamin D supplementation for NAFLD patients in relation to insulin resistance. The results obtained still carry conflicting results. This study aimed to evaluate the effect of additional treatment of vitamin D for the improvement of insulin resistance in NAFLD patients. Relevant literatures were obtained from PubMed, Google Scholar, COCHRANE, and Science Direct database. The obtained studies were analyzed using fixed effect model or random effect model. Seven eligible studies with a total of 735 participants were included. Vitamin D supplementation improves insulin resistance in NAFLD patients, marked by reduced Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), with pooled mean difference - 1.06 (p = 0.0006; 95% CI - 1.66 to - 0.45). Vitamin D supplementation increase the level of vitamin D serum with pooled mean difference of 17.45 (p = 0.0002; 95% CI 8.33 to 26.56). Vitamin D supplementation decrease ALT levels, with pooled mean difference of - 4.44 (p = 0.02; 95% CI - 8.24 to - 0.65). No effect was observed for AST levels. Vitamin D supplementation provides beneficial effects on the improvement of insulin resistance in NAFLD patients. This supplementation may reduce HOMA-IR in such patients. It may serve as a potential adjunctive treatment for NAFLD patients.

Serum pepsinogen level as a biomarker for atrophy, reflux esophagitis, and gastric cancer screening in Indonesia.

Background: Chronic dyspepsia's symptoms are frequently seen in primary to tertiary healthcare in Indonesia. This study aimed to describe the potential usability of pepsinogen (PG) values in determining gastric mucosal conditions, including superficial gastritis and atrophic gastritis. Materials and Methods: We recruited 646 adult dyspeptic patients and then analyzed PG values (including PGI, PGII, and PGI/II ratio) with endoscopic findings, gastric mucosal damages, and Helicobacter pylori infection. The gastric mucosal damage and H. pylori infection were evaluated using histological examination based on the updated Sydney system. Results: Among 646 enrolled patients, 308 (47.2%), 212 (32.8%), 91 (14.1%), 34 (5.2%), and 1 (0.2%) patient were diagnosed with normal mucosa, gastritis, reflux esophagitis, peptic ulcer disease, and gastric cancer, respectively. Significant differences in PGI, PGII, and PGI/II ratio values were observed among ethnic groups (all P < 0.01). The PGI and PGII levels were significantly higher and PGI/II was significantly lower in H. pylori-infected patients than in uninfected ones (all P < 0.001). The optimal cutoff value for PGII and PGI/II was 12.45 ng/mL with an area under the curve (AUC) value of 0.755 (0.702-0.811), sensitivity 59.3%, and specificity 77.1%; and 4.75 with AUC value of 0.821 (0.763-0.855), sensitivity 81.5%, and specificity 78.7%, respectively, to determine moderate-severe atrophy. Conclusion: Serum PG levels, a useful biomarker, represent the endoscopic findings, especially for reflux esophagitis. In addition, the benefits of PG values detecting atrophic gastritis were limited to moderate-severe atrophic gastritis. This usefulness requires careful attention for several ethnic groups in Indonesia.

Hepatitis C Seroconversion Remains High among Patients with Regular Hemodialysis: Study of Associated Risk Factors.

Methods: An analytical cross-sectional study involving patients from 2 dialysis units (1 referral hospital and 1 private dialysis unit) in Denpasar, Bali, Indonesia, from January 2020 to December 2021. We evaluated age, gender, duration of hemodialysis, vascular access, history of transfusion, history of surgery, diabetes mellitus, hepatitis B, human immunodeficiency virus (HIV) infection, and type of dialyzer as possible risk factors of hepatitis C seroconversion among hemodialysis patients. Results: A total of 338 hemodialysis patients were enrolled in this study. We found hepatitis C seroconversion in 94 patients (27.8%), all of which occurred after regular dialysis was started. Vascular access type (OR 42.07, 95% CI 5.757-307.472) and dialyzer reuse (OR 8.324, 95% CI 4.319-16.044) were showing a statistically significant association with hepatitis C seroconversion. A separate analysis on each dialysis unit found common evidence that the duration of dialysis was significantly associated with hepatitis C infection among hemodialysis patients. Conclusion: Hepatitis C seroconversion among dialysis patients remains high. Factors related to the dialysis procedure itself played a major role in transmitting the virus.

Massive hemobilia caused by rupture of gastroduodenal artery pseudoaneurysm, a delayed complication of laparoscopic cholecystectomy: a case report.

BACKGROUND: Hemobilia is a rare cause of upper gastrointestinal bleeding that originates from the biliary tract. It is infrequently considered in diagnosis, especially in the absence of abdominal trauma or history of hepatopancreatobiliary procedure, such as cholecystectomy, which can cause arterial pseudoaneurysm. Prompt diagnosis is crucial because its management strategy is distinct from other types of upper gastrointestinal bleeding. Here, we present a case of massive hemobilia caused by the rupture of a gastroduodenal artery pseudoaneurysm in a patient with a history of laparoscopic cholecystectomy 3 years prior to presentation. CASE PRESENTATION: A 44-year-old Indonesian female presented to the emergency department with complaint of hematemesis and melena accompanied by abdominal pain and icterus. History of an abdominal trauma was denied. However, she reported having undergone a laparoscopic cholecystectomy 3 years prior to presentation. On physical examination, we found anemic conjunctiva and icteric sclera. Nonvariceal bleeding was suspected, but esophagogastroduodenoscopy showed a blood clot at the ampulla of Vater. Angiography showed contrast extravasation from a gastroduodenal artery pseudoaneurysm. The patient underwent pseudoaneurysm ligation and excision surgery to stop the bleeding. After surgery, the patient's vital signs were stable, and there was no sign of rebleeding. CONCLUSION: Gastroduodenal artery pseudoaneurysm is a rare complication of laparoscopic cholecystectomy. The prolonged time interval, as compared with other postcholecystectomy hemobilia cases, resulted in hemobilia not being considered as an etiology of the gastrointestinal bleeding at presentation. Hemobilia should be considered as a possible etiology of gastrointestinal bleeding in patients with history of cholecystectomy, regardless of the time interval between the invasive procedure and onset of bleeding.

Proton pump inhibitor on susceptibility to COVID-19 and its severity: a systematic review and meta-analysis.

BACKGROUND: The negative impacts of proton pump inhibitor (PPI), including the risk of pneumonia and mortality, have been reported previously. This meta-analysis aimed to address the current interest of whether the administration of PPI could increase the susceptibility and risk of poor outcome in COVID-19. METHODS: We performed a systematic literature search from PubMed, Embase, EBSCOhost, and EuropePMC databases up until 3 December 2020. The main outcome was composite poor outcome which comprised of mortality and severe COVID-19. Severe COVID-19 in this study was defined as patients with COVID-19 that fulfill the criteria for severe CAP, including the need for intensive unit care or mechanical ventilation. The secondary outcome was susceptibility, based on cohort comparing COVID-19 positive and COVID-19 negative participants. RESULTS: There were a total of 290,455 patients from 12 studies in this meta-analysis. PPI use was associated with increased composite poor outcome (OR 1.85 [1.13, 3.03], p = 0.014; I2 90.26%). Meta-regression analysis indicate that the association does not vary by age (OR 0.97 [0.92, 1.02], p = 0.244), male (OR 1.05 [0.99, 1.11], p = 0.091), hypertension (OR 9.98 [0.95, 1.02], p = 0.317), diabetes (OR 0.99 [0.93, 1.05], p = 0.699), chronic kidney disease (OR 1.01 [0.93, 1.10], p = 0.756), non-steroidal anti-inflammatory drug use (OR 1.02 [0.96, 1.09], p = 0.499), and pre-admission/in-hospital PPI use (OR 0.77 [0.26, 2.31], p = 0.644). PPI use was not associated with the susceptibility to COVID-19 (OR 1.56 [0.48, 5.05], p = 0.46; I2 99.7%). CONCLUSION: This meta-analysis showed a potential association between PPI use and composite poor outcome, but not susceptibility. PROSPERO ID: CRD42020224286.

CYP2C19 Polymorphisms in Indonesia: Comparison among Ethnicities and the Association with Clinical Outcomes.

CYP2C19 polymorphisms are important factors for proton pump inhibitor-based therapy. We examined the CYP2C19 genotypes and analyzed the distribution among ethnicities and clinical outcomes in Indonesia. We employed the polymerase chain reaction-restriction fragment length polymorphism method to determine the CYP2C19 genotypes and evaluated inflammation severity with the updated Sydney system. For CYP2C19*2, 46.4% were the homozygous wild-type allele, 14.5% were the homozygous mutated allele, and 39.2% were the heterozygous allele. For CYP2C19*3, 88.6% were the homozygous wild-type allele, 2.4% were the homozygous mutated allele, and 9.0% were the heterozygous allele. Overall, the prevalence of rapid, intermediate, and poor metabolizers in Indonesia was 38.5, 41.6, and 19.9%, respectively. In the poor metabolizer group, the frequency of allele *2 (78.8%) was higher than the frequency of allele *3 (21.2%). The Papuan had a significantly higher likelihood of possessing poor metabolizers than the Balinese (OR 11.0; P = 0.002). The prevalence of poor metabolizers was lower compared with the rapid and intermediate metabolizers among patients with gastritis and gastroesophageal reflux disease. Intermediate metabolizers had the highest prevalence, followed by rapid metabolizers and poor metabolizers. Dosage adjustment should therefore be considered when administering proton pump inhibitor-based therapy in Indonesia.

Analysis of risks of gastric cancer by gastric mucosa among Indonesian ethnic groups.

Indonesia is a big country with multiethnic populations whose gastric cancer risks have not been elucidated. We performed a nationwide survey and obtained histological specimens from 1053 individuals in 19 cities across the country. We examined the gastric mucosa, the topography, the atrophic gastritis risk factors, and the gastric cancer risk scores. Almost half (46.1%) of the patients with dyspeptic symptoms had histological abnormalities; chronic (36.3%) and atrophic gastritis (28.9%) being the most frequent. Individuals of the Timor ethnicity had the highest prevalence of acute (52.6%) and chronic gastritis (68.4%), even those negative for H. pylori. Our topographic analysis showed the majority of patients had predominantly antral acute and chronic gastritis. A multivariate logistic regression model showed age (Odds ratio [OR], 1.107), Timor ethnicity (OR, 8.531), and H. pylori infection (OR, 22.643) as independent risk factors for presence of atrophic gastritis. In addition, the gastric cancer risk score was highest in those from Timor, Papuan, and Bugis ethnic populations. Overall, Indonesia is a low-risk gastric cancer country. However, several ethnic groups displayed severe gastric mucosa symptoms suggesting policy makers should focus on those ethnic groups to perform gastric cancer screenings and to eradicate H. pylori.

Alternative eradication regimens for Helicobacter pylori infection in Indonesian regions with high metronidazole and levofloxacin resistance.

BACKGROUND: The prevalence of Helicobacter pylori resistance to metronidazole and clarithromycin is high in Indonesia. Moreover, the increasing levofloxacin resistance rates in the absence of bismuth treatment in Indonesia has led to the use of other antibiotics as alternative regimens. METHODS: We determined the minimum inhibitory concentrations (MICs) of five alternative antibiotics for H. pylori (rifaximin, rifabutin, furazolidone, garenoxacin, and sitafloxacin) using the agar dilution method and assessed mutations associated with antibiotic resistance using next-generation sequencing. RESULT: Analysis of 106 strains isolated from 1039 adult dyspeptic patients revealed that none of the strains were furazolidone-resistant. All strains were also sensitive to rifabutin and sitafloxacin. In contrast, the rates of resistance to rifaximin and garenoxacin were high (38.9% and 6.7%, respectively). The strains isolated from patients on Java Island had the highest resistance rates to garenoxacin and rifaximin. In addition, the resistance was distributed evenly among the ethnic groups, ranging between 25.0% and 69.2%. Except for rifaximin, for which the resistance rate was 38.9%, the other four antibiotics could be successfully employed to eradicate levofloxacin- and metronidazole-resistant H. pylori infections in vitro. Interestingly, garenoxacin-sensitive strains were found in regions with high clarithromycin resistance rates such as Bali and Papua Islands. In contrast, rifaximin might not be considered as an alternative antibiotic in regions with high clarithromycin resistance. There was an inconsistent association between gyrA and gyrB mutations and garenoxacin resistance. We confirmed that the I837V (replacement of isoleucine at position 837 with valine), A2414T/V, Q2079K and K2068R were the predominant rpoB point mutations. There was an association between vacA genotypes of H. pylori and rifaximin resistance (P = 0.048). CONCLUSION: furazolidone-, rifabutin-, and sitafloxacin-based therapies might be considered as alternative regimens to eradicate H. pylori in Indonesia, including regions with high metronidazole and clarithromycin resistance rates. Moreover, sitafloxacin but not garenoxacin should be considered for eradication of levofloxacin-resistant strains.

The identification and characterization of novel rat hepatitis E virus strains in Bali and Sumbawa, Indonesia.

All three genetic groups of ratHEV have been found in Indonesia, suggesting the presence of additional variants of ratHEV in unexamined areas of Indonesia. A total of 242 wild rats were captured in Bali and Sumbawa, Indonesia, during 2014-2016. Among them, 4.1% were seropositive for anti-ratHEV IgG and two (0.8%) had detectable ratHEV RNA: ratESUMBAWA-140L and ratEBali2016D-047L, sharing 84.9-85.4% and 86.9-92.1% nucleotide identity with the reported G2 strains, respectively. The provisional criteria supported the notion that the ratEBali2016D-047L and ratESUMBAWA-140L strains were novel G2 variants. These results suggested the spatial distribution of further divergent ratHEV strains in Indonesia.

Gastric mucosal status in populations with a low prevalence of Helicobacter pylori in Indonesia.

In Indonesia, endoscopy services are limited and studies about gastric mucosal status by using pepsinogens (PGs) are rare. We measured PG levels, and calculated the best cutoff and predictive values for discriminating gastric mucosal status among ethnic groups in Indonesia. We collected gastric biopsy specimens and sera from 233 patients with dyspepsia living in three Indonesian islands. When ≥5.5 U/mL was used as the best cutoff value of Helicobacter pylori antibody titer, 8.6% (20 of 233) were positive for H. pylori infection. PG I and II levels were higher among smokers, and PG I was higher in alcohol drinkers than in their counterparts. PG II level was significantly higher, whereas PG I/II ratios were lower in H. pylori-positive than in H. pylori-negative patients. PG I/II ratios showed a significant inverse correlation with the inflammation and atrophy scores of the antrum. The best cutoff values of PG I/II were 4.05 and 3.55 for discriminating chronic and atrophic gastritis, respectively. PG I, PG II, and PG I/II ratios were significantly lower in subjects from Bangli than in those from Makassar and Surabaya, and concordant with the ABC group distribution; however, group D (H. pylori negative/PG positive) was the lowest in subjects from Bangli. In conclusion, validation of indirect methods is necessary before their application. We confirmed that serum PG level is a useful biomarker determining chronic gastritis, but a modest sensitivity for atrophic gastritis in Indonesia. The ABC method should be used with caution in areas with a low prevalence of H. pylori.

Surveillance of Helicobacter pylori Antibiotic Susceptibility in Indonesia: Different Resistance Types among Regions and with Novel Genetic Mutations.

Information regarding Helicobacter pylori antibiotic resistance in Indonesia was previously inadequate. We assessed antibiotic susceptibility for H. pylori in Indonesia, and determined the association between virulence genes or genetic mutations and antibiotic resistance. We recruited 849 dyspeptic patients who underwent endoscopy in 11 cities in Indonesia. E-test was used to determine the minimum inhibitory concentration of five antibiotics. PCR-based sequencing assessed mutations in 23S rRNA, rdxA, gyrA, gyrB, and virulence genes. Next generation sequencing was used to obtain full-length sequences of 23S rRNA, infB, and rpl22. We cultured 77 strains and identified 9.1% with clarithromycin resistance. Low prevalence was also found for amoxicillin and tetracycline resistance (5.2% and 2.6%, respectively). In contrast, high resistance rates to metronidazole (46.7%) and levofloxacin (31.2%) were demonstrated. Strains isolated from Sumatera Island had significantly higher metronidazole resistance than those from other locations. Metronidazole resistant strains had highly distributed rdxA amino acid substitutions and the 23S rRNA A2143G mutation was associated with clarithromycin resistance (42.9%). However, one strain with the highest MIC value had a novel mutation in rpl22 without an A2143G mutation. Mutation at Asn-87 and/or Asp-91 of gyrA was associated with levofloxacin-resistance and was related to gyrB mutations. In conclusions, although this is a pilot study for a larger survey, our current data show that Indonesian strains had the high prevalence of metronidazole and levofloxacin resistance with low prevalence of clarithromycin, amoxicillin, and tetracycline resistance. Nevertheless, clarithromycin- or metronidazole-based triple therapy should be administered with caution in some regions of Indonesia.

The complete genomes of subgenotype IA hepatitis A virus strains from four different islands in Indonesia form a phylogenetic cluster.

Despite the high endemicity of hepatitis A virus (HAV) in Indonesia, genetic information on those HAV strains is limited. Serum samples obtained from 76 individuals during outbreaks of hepatitis A in Jember (East Java) in 2006 and Tangerang (West Java) in 2007 and those from 82 patients with acute hepatitis in Solo (Central Java), Denpasar on Bali Island, Mataram on Lombok Island, and Makassar on Sulawesi Island in 2003 or 2007 were tested for the presence of HAV RNA by reverse transcription PCR with primers targeting the VP1-2B region (481 nucleotides, primer sequences at both ends excluded). Overall, 34 serum samples had detectable HAV RNA, including at least one viremic sample from each of the six regions. These 34 strains were 96.3-100 % identical to each other and formed a phylogenetic cluster within genotype IA. Six representative HAV isolates from each region shared 98.3-98.9 % identity over the entire genome and constituted a IA sublineage with a bootstrap value of 100 %, consisting of only Indonesian strains. HAV strains recovered from Japanese patients who were presumed to have contracted HAV infection while visiting Indonesia were closest to the Indonesian IA HAV strains obtained in the present study, with a high identity of 99.5-99.7 %, supporting the Indonesian origin of the imported strains. These results indicate that genetic analysis of HAV strains indigenous to HAV-endemic countries, including Indonesia, are useful for tracing infectious sources in imported cases of acute hepatitis A and for defining the epidemiological features of HAV infection in that country.

Albumin infusion in liver cirrhotic patients.

Albumin infusions have been used for many years in the management of patients with decompensated cirrhosis in an attempt to reduce the formation of ascites, to improve circulatory and renal function, or in SBP patients. While some of these indications for albumin infusions are supported by the results of randomised studies, others are based on clinical experience and have not been proved in prospective investigations. Therefore, the use of albumin infusions in patients with cirrhosis is still controversial. However, despite the controversies, the use of albumin at least has been proven to be safe. Some guidelines recommended the use of albumin infusion in decompensated cirrhosis with spontaneous bacterial peritonitis, hepatorenal syndrome, large volume parecentesis and decompensated cirrhosis with complications.

Malignant mesenterial mesothelioma in stroke patients.

Mesothel is the cell lining of serosal surface of the pleura, peritoneum, pericardium, and testis. Malignant mesothelioma is a highly aggressive tumor from mesothel that has a tendency to grow rapidly and invade locally. Although the incidence of malignant mesenterial mesothelioma is not so high, the case fatality rate is very high. The aim of this case report is to report the rare and difficult case with several complications. A Balinese man, 64 years old, came with chief complaint of weakness, abdominal enlargement, and nausea, with history of previous liver disease. On physical examination were found a decrease of conciousness, subfebrile, abdominal distension, ascites, negative traube space, and paralysis of the left side of the body. Laboratory examination results showed leukocytosis, hypochromic-micrositic anemia, trombocytosis, hypoalbuminemia, increase of alkaline phosphatase, and mild hyponatremia. Abdominal USG showed intraperitoneal mass which some of them attach to abdominal wall, possibly from mesenterium and ascites, esophagogastroduodenoscopy (EGD) revealed reflux esofagitis and anthral erossive gastritis, skull CT scan showed small infarction at left parietal medulla and right basal ganglia, cytology showed spreaded and grouped mesothel with reactive lymphocyte and amorph back ground. FNAB result showed malignant mesothelioma, and normal colonoscopy. Based on the above data, the diagnoses were malignant mesenterial mesothelioma, reflux esofagitis and anthral erossive gastritis, and non hemorrhagic stroke. Malignant mesenterial mesothelioma should be considered in patient with the combination of unexplained ascites and abdominal pain. Although the result of treatment is very disappointing, the patient had to be treated optimally to increase quality of life.

Identification of genotype 4 hepatitis E virus strains from a patient with acute hepatitis E and farm pigs in Bali, Indonesia.

A previous study revealed that antibodies to hepatitis E virus (HEV) (anti-HEV) are highly prevalent among healthy individuals and farm pigs in Bali, Indonesia, and suggested that HEV infection may occur via zoonosis among Balinese people. However, there were no reports of acute hepatitis E in Bali. To elucidate whether Balinese HEV strains recovered from infected humans and pigs have significant sequence similarity, serum samples obtained from 57 patients (age, mean +/- standard deviation, 31.1 +/- 11.9 years) with sporadic acute hepatitis and from one hundred and one 2- or 3-month-old farm pigs in Bali were tested for anti-HEV and HEV RNA. Among the 57 patients, 2 (3.5%) had high-titer IgM/IgA class anti-HEV antibodies and one of them had detectable HEV RNA (BaliE03-46). Overall, 58 pigs (57.4%) tested positive for anti-HEV, while 5 pigs (5.0%) had detectable HEV RNA. Based on the 412-nucleotide sequence within open reading frame 2, the BaliE03-46 isolate and the 5 swine HEV isolates recovered from the viremic pigs were phylogenetically classified in genotype 4, but were only 77.3-90.8% identical to the genotype 4 HEV isolates reported thus far in China, India, Japan, Taiwan, and Vietnam. The BaliE03-46 isolate of human origin shared high identities of 97.3-98.3% with 4 of the 5 Balinese swine isolates, but differed by 16.1% from the remaining swine isolate. These results suggest that indigenous HEV strains of genotype 4 with marked heterogeneity are circulating in Bali, Indonesia, and that pigs are reservoirs of HEV for Balinese people who have a habit of ingesting uncooked pigs.

Prevalence of antibodies to hepatitis E virus among apparently healthy humans and pigs in Bali, Indonesia: Identification of a pig infected with a genotype 4 hepatitis E virus.

In Indonesia where hepatitis E virus (HEV) is believed to be highly endemic, only three outbreaks of HEV transmission have been documented to date in restricted areas (West Kalimantan and East Java). A total of 1,115 serum samples collected from apparently healthy individuals in Bali, Lombok, and Surabaya in Indonesia in 1996 where epidemic HEV transmissions have never been reported, were tested for IgG class antibodies to HEV (anti-HEV). In Bali, anti-HEV was detected in 20% (54/276) of the tested population, in remarkable contrast with 4% (17/446) in Lombok and 0.5% (2/393) in Surabaya. On the other hand, antibodies to hepatitis A virus were highly prevalent in all three regions (95% in Bali, 90% in Lombok, and 89% in Surabaya). Although the majority of the population in Indonesia is Moslem, Balinese people are mostly Hindu and have a habit of consuming pork. Therefore, serum samples were obtained from the 99 farm pigs in Bali and tested for anti-HEV and HEV RNA. The sera from 71 pigs (72%) were positive for anti-HEV and a 2-month-old pig had detectable HEV RNA. The swine HEV isolate recovered from the viremic pig was named SB66-Bali. The SB66-Bali isolate was most closely related to the genotype 4 isolates from China, India, Japan, and Taiwan, but shared only 82.6-90.0% identity in the common 241-412 nucleotides within open reading frame 2 (ORF2). These results indicate that a presumably indigenous HEV strain(s) is circulating in Bali, Indonesia and that HEV infection may occur via zoonosis even in developing countries.