Peritoneal tuberculosis (PTB), although rarer than its pulmonary counterpart, is a serious health concern in regions of the world with high tuberculosis prevalence. Individuals with baseline immunocompromise condition, whether acquired or medically induced, are at greatest risk for experiencing PTB. While medical treatment of the condition is similar to that of the pulmonary disease, the generally immunocompromised state of those infected with PTB, along with a lack of highly sensitive and specific testing methods make early diagnosis difficult. This review discusses the risks factors, clinical features, diagnostic methods, and treatment options for PTB.

Background and Aims: Dengue infection is a major health burden, which can result in mild self-limited febrile illness to highly fatal hemorrhagic disease. There is paucity of literature describing the manifestations of dengue in patients with underlying liver disease. We studied and compared the manifestations of this tropical infection in patients with and without liver disease.

Methods: Patients with serologically-confirmed dengue infection were included in this retrospective study, obtained for over a period of 1 year. Demographic and laboratory variables were compared for the individuals with no underlying liver disease (Group A, n = 71), chronic hepatitis (Group B, n = 12), and cirrhosis (Group C, n = 12).

Results: Males predominated the study population (61%), with a higher mean age in the cirrhotic group. The most common clinical manifestation was classical dengue fever, seen in 89 individuals. Two presented as dengue hemorrhagic fever (1 each in Group A and Group B), 1 presented as acute liver failure, and 3 as acute-on-chronic liver failure. Hemoconcentration was less evident in Group C as compared to Group A and Group B (p < 0.001). Patients in Group C had significantly prolonged International Normalized Ratio (INR) and enhanced thrombocytopenia compared to patients in Group A and Group B. Patients in Group C also required prolonged hospital stay (Group A: 4.83 ± 2.88, Group B: 7.33 ± 2.3, Group C: 13 ± 5 days; p < 0.001). Three patients expired in Group C compared to the 1 in Group A and none in Group B (p = 0.01). On univariate analysis, hemoglobin, albumin, INR, and bilirubin predicted development of liver failure. On multivariate analysis, INR and bilirubin predicted development of liver failure.

Conclusions: Dengue infection can have varied manifestations, ranging from simple fever to acute-on-chronic liver failure and acute liver failure. Cirrhotic patients lack classical features of dengue and have relatively poor prognosis. Dengue should be suspected as a cause of liver failure in endemic areas, where no etiological cause is discernible.

Background and Aims: Colorectal cancer is associated with non-alcoholic fatty liver disease (NAFLD) and other metabolic syndromes, such as obesity, abnormal blood glucose, and dyslipidemia. The relationship of NAFLD and colorectal adenoma, which is the precursor of colorectal cancer, is worthy of discussion. The aim of this study was to investigate the association between colorectal adenoma and NAFLD, colorectal adenoma and metabolic syndrome in a Chinese Han population.

Methods: This retrospective study analyzed the relationship between NAFLD and colorectal adenoma in 1089 patients in Qingdao municipal hospital. Subjects were divided into a colorectal adenoma group (n = 267) and a control group (n = 822). NAFLD and the controlled attenuation parameter (CAP) value were determined by abdominal ultrasound and FibroScan.

Results: Patients with NAFLD in the colorectal adenoma group and the control group represented 142 cases (53.2%) and 360 cases (43.8%), respectively. The mean CAP value in the colorectal adenoma group was significantly higher than that in the control group. The values of body mass index, triglyceride, high-density lipoprotein cholesterol, aspartate aminotransferase, fasting plasma glucose, and uric acid were also significantly higher in the colorectal adenoma group than in the control group. Multifactor logistic regression analysis showed that the sex, NAFLD, CAP, body mass index, triglyceride, aspartate aminotransferase, and fasting plasma glucose were significant risk factors for colorectal adenoma. Besides, NAFLD and CAP value were significant risk factors for colorectal adenoma in males but not in females.

Conclusions: NAFLD and metabolic syndrome were tightly associated with the risk of colorectal adenoma in this Chinese Han population. The effect of NAFLD on colorectal adenoma was prominent in males rather than in females.

In the non-human immunodeficiency virus infected population, cryptococcosis occurs primarily in people who are functionally immunosuppressed, including patients who have undergone solid organ transplantation requiring immunosuppressive medications, are on corticosteroids, or have renal failure or cirrhosis. Cryptococcal meningitis poses a particular challenge in the setting of cirrhosis because its clinical presentation can mimic hepatic encephalopathy. Here, we describe two patients with decompensated cirrhosis, both with a known history of hepatic encephalopathy who had lumbar punctures and were found to have cryptococcal meningitis. The first patient had a subacute fluctuating change in mental status, while the second patient had progressive subacute headaches, gait disturbance, and hearing loss. Both patients were treated with amphotericin B and flucytosine induction, but only the second survived to maintenance therapy. These cases demonstrate the importance of having a high index of suspicion for cryptococcal meningitis in cirrhosis and having a low threshold for performing a lumbar puncture when altered mental status or other neurologic complaints are not fully explained by hepatic encephalopathy. We also provide a brief review of the pathobiology of cryptococcal infection in cirrhosis and highlight the challenges in therapy.

Hepatitis C virus (HCV) has been shown to affect many tissues other than liver. However, of the many extrahepatic manifestations (EMs) that have been associated with HCV, including cryoglobulinemia, lymphoma, insulin resistance, type 2 diabetes and neurological disorders, only a few have been shown to be directly related to HCV infection of extrahepatic tissues. HCV-triggered immune-mediated mechanisms account for most of the EMs. It is estimated that up to 74% of patients with chronic hepatitis C can develop at least one EM. All HCV patients with EMs should be considered for antiviral therapy, although not all will resolve with sustained virological response.

Background and Aims: Hepatitis C (HCV) is a medical and public health concern. Once infected individuals are identified, management includes not only education but also the use of antiviral therapy. Although screening for HCV is readily available, barriers exist which prevent assessment and treatment in individuals potentially infected with HCV.

Methods: This is a retrospective study of patients screened for HCV within the University of California, Los Angeles Health Care System between February 22 and July 9, 2018. We defined linkage to care as: 1) confirmatory HCV RNA test after screening HCV antibody test found a positive result; and 2) follow-up appointment for treatment was established with a specialist. Demographic and baseline laboratory values were collected. Factors potentially associated with prohibiting linkage of care were evaluated.

Results: During the study period, 17,512 individuals were screened for HCV. A total of 238 (1.35%) were found to have detectable HCV antibodies. Of the individuals with detectable HCV antibodies, 48 (20%) did not undergo confirmatory testing with viral levels. Of the 190 individuals who underwent further testing, 70 patients were noted to be viremic. Among them, 17 of the 70 (24%) were not linked to a specialist for further care. Younger patients (p = 0.02) and people who inject drugs (p = 0.02) were less likely to be referred for specialty care.

Conclusions: The results of our study highlight that younger patients and people who inject drugs are less likely to be referred to specialty care for HCV treatment. Efforts are needed to engage these populations.

Background and Aims: As the major energy source for mammalian cells, mitochondria have been the subject of numerous studies. However, the isolation and purification of healthy mitochondria, especially from fresh tissue, remains challenging. The most popular methods and kits involve various centrifugation steps which require substantial time and equipment but do not consistently provide pure preparations of functional mitochondria. The aim of this study was to determine whether methods could be devised to improve the purity and yield of functional mitochondria from fresh tissue.

Methods: Fresh mouse liver was homogenized, and cells lysed. Particle size analysis, quantitation of mitochondrial DNA, mitochondrial oxygen consumption, and purity of mitochondria (by electron microscopy) were measured in samples after various purification steps and significant differences determined.

Results: A two-step procedure consisting of centrifugation followed by filtration through 1.2μ and 0.8μ filters resulted in uniform mitochondrial preparations with diameters between 520–540 nm, and approximately 5-times more pure samples. The mitochondria thus obtained had oxygen consumption and sensitivities to mitochondrial inhibitors that were indistinguishable from those purified by centrifugation alone. Electron microscopy confirmed the presence of more uniform and 4–5 times greater concentrations of mitochondria compared to centrifugation alone.

Conclusions: A two-step procedure consisting of sequential centrifugation followed by filtration is a rapid method for the production of highly purified, uniform and functional mitochondria.

Drug-induced cholestasis represents a form of drug-induced liver disease that can lead to severe impairment of liver function. Numerous drugs have been shown to cause cholestasis and consequently bile duct toxicity. However, there is still lack of therapeutic tools that can prevent progression to advanced stages of liver injury. This review focuses on the various pathological mechanisms by which drugs express their hepatotoxic effects, as well as consequences of increased bile acid and toxin accumulation in the hepatocytes.

Nonalcoholic fatty liver disease (NAFLD) is significantly on the rise, which will seriously affect human health; yet, there is no approved drug for the treatment of NAFLD currently. Recently, more and more studies have demonstrated that intestinal bacteria affect liver function through the gut-liver axis, and that the imbalance of intestinal bacterial composition is essential in the pathogenesis of NAFLD. Correcting intestinal bacterial imbalance, therefore, may prevent the development and attenuate the progression of NAFLD. Fecal microbiota transplantation (FMT) is considered the most effective method to correct intestinal bacteria imbalance, but its therapeutic role in NAFLD has not been established. Moreover, the potential molecular mechanisms of FMT for NAFLD have not been elucidated. This review paper summarizes the currently available experimental and clinical research results on the therapeutic effects of FMT for NAFLD. In addition, the underlying molecular mechanisms are proposed, which would provide theoretical support for FMT as a useful modality for the treatment of NAFLD.

Curcumin is a polyphenol present in turmeric and is credited with anti-inflammatory, antioxidant, and chemoprotective properties. Questions remain surrounding curcumin’s bioavailability and the mechanism by which it may exert neuroprotective effects. Following PRISMA 2009 guidelines, a systematic review was conducted to identify randomized, placebo-controlled trials investigating the effects of curcumin supplementation on cognitive function in older adults (>50 years). Five databases were searched (CINAHL, Cochrane Library, PubMed, SCOPUS, Web of Science) with five studies identified, each using different forms of curcumin and validated cognitive screening measures, meeting inclusion criteria. Curcumin doses ranged from between 90 and 4,000 mg/day, with significant improvements found in three of the five studies. Firstly, the most recent study found improvements with 90 mg of curcumin twice daily in tests of selective reminding (p = 0.002), visual memory (p = 0.01), and attention (p < 0.0001) over 18 months in non-demented individuals. The second study found improvement in Montreal Cognitive Assessment tool with 1,500 mg/day curcumin over 52 weeks (p = 0.02). Another study found improvement in serial three subtraction task responses after 4 weeks compared with the placebo group (p = 0.044). Of the adverse events reported (n = 58), gastrointestinal symptoms were most common (n = 34). Before curcumin can be recommended to treat or reduce rates of cognitive decline, well-designed trials with standardization in dose, method of assessing cognition, and duration, are required to determine the most bioavailable form of curcumin with minimal adverse effects.

Nonalcoholic fatty liver disease (NAFLD) is the accumulation of fat in the liver in the absence of secondary causes. NAFLD is a multifactorial disease that results from the interaction of genetic predisposition and metabolic, inflammatory and environmental factors. Among these factors, dysregulation of gut microbiome has been linked to the development of fatty liver disease. The microbiome composition can be modified by dietary habits leading to gut microbiome dysbiosis, especially when a diet is rich in saturated fats, animal products and fructose sugars. Different species of bacteria in the gut metabolize nutrients differently, triggering different pathways that contribute to the accumulation of fat within the liver and triggering inflammatory cascades that promote liver damage. In this review, we summarize the current understanding of the roles of gut microbiota in mediating NAFLD development and discuss possible gut microbiota-targeted therapies for NAFLD. We summarize experimental and clinical evidence, and draw conclusions on the therapeutic potential of manipulating gut microbiota to decrease the incidence and prevalence of fatty liver disease.

Background and Aims: Rifampicin (RFP) and isoniazid (INH) are widely used as anti-tuberculosis agents. However, the mechanisms underlying the involvement of reactive oxygen species and mitochondria in RFP- and INH-related hepatotoxicity have not been established yet. This study aimed to observe the intracellular mechanisms leading to mitochondrial dysfunction and morphological changes in RFP- and INH-induced hepatocyte injury.

Methods: Cell injury, changes in mitochondrial function, and expression and activation of dynamin related protein 1 (Drp1), known as the main protein for mitochondrial fission, were analyzed in cultured QSG7701 cells exposed to RFP and INH.

Results: INH and RFP treatment induced pronounced hepatocyte injury and increased cell death. In the similar context of aspartate aminotransferase elevation and adenosine triphosphate synthesis decrease, changes in mitochondrial membrane permeability and reactive oxygen species in hepatocytes induced by RFP were significantly different from those induced by INH (p < 0.05). Particularly, we observed the overactivation and mitochondrial translocation of Drp1 in RFP-induced cell injury, which was not occurred with exposure to INH.

Conclusions: RFP-induced hepatotoxicity may be closely related to mitochondrial dysfunction and Drp1-mediated mitochondrial fission.

Orthotopic liver transplantation is the definitive treatment for end-stage liver disease and hepatocellular carcinomas. Biliary complications are the most common complications seen after transplantation, with an incidence of 10–25%. These complications are seen both in deceased donor liver transplant and living donor liver transplant. Endoscopic treatment of biliary complications with endoscopic retrograde cholangiopancreatography (commonly known as ERCP) has become a mainstay in the management post-transplantation. The success rate has reached 80% in an experienced endoscopist’s hands. If unsuccessful with ERCP, percutaneous transhepatic cholangiography can be an alternative therapy. Early recognition and treatment has been shown to improve morbidity and mortality in post-liver transplant patients. The focus of this review will be a learned discussion on the types, diagnosis, and treatment of biliary complications post-orthotopic liver transplantation.

Background and Aims: The management of post-endoscopic variceal ligation (EVL) bleeding ulcers (PEBUs) is currently based on local expertise and patients liver disease status. The present retrospective study investigated associations between the endoscopic morphology of PEBUs and patient outcomes.

Methods: Patients underwent EVL (primary or secondary), from January 2015 to January 2018, in two tertiary care hospitals in India (ILBS New Delhi and Dharamshila Narayana New Delhi). Mortality rates were determined at post-EVL day five and week six. PEBUs were typified based on Jamwal & Sarin classification system as follows: A, ulcer with active spurting; B, ulcer with ooze; C, ulcer base with visible vessel or clot; and D, clean or pigmented base.

Results: Of 3854 EVL procedures, 141 (3.6%) patients developed PEBU, and 46/141 (32.6%) suffered mortality. Among the former, the PEBU types A, B, C, and D accounted for 17.7, 26.2, 36.3, and 19.8%, respectively. Of those who died, 39.1, 30.4, 21.7, and 8.8% had PEBU types A, B, C, and D. Treatments included transjugular intrahepatic portosystemic shunts (TIPS), esophageal self-expandable metal stent (SEMS), glue and sclerosant injection, Sengstaken-Blakemore tube placement and liver transplant. On univariate analysis, no correlation with hepatic venous pressure gradient, TIPS placement, size of varices, or number of bands was found. The Model for End-Stage Liver Disease (MELD)-sodium score correlated positively with outcome. After adjusting for MELD-sodium score, mortality was best predicted by type-A ulcer (p = 0.024; OR 8.95, CI 1.34–59.72).

Conclusions: PEBU occurred in 3.6% of a large EVL cohort. Stratifying patients based on PEBU type can help predict outcomes, independent of the MELD-sodium score. Classifying PEBUs by endoscopic morphology may inform treatment strategies, and warrants further validation.

Hepatic abscesses are an uncommon extra-intestinal manifestation of inflammatory bowel disease, the incidence of which has been estimated to be approximately 7 per 10,000 patients with inflammatory bowel disease. It is unclear whether patients with Crohn’s disease or patients with ulcerative colitis (UC) are at higher risk of developing this complication. Based on case reports, most cases are found in Crohn’s disease; however, a recent cohort study showed an increased risk in UC instead. Hepatic abscesses in the pediatric population are rare, and there have been no reported cases of hepatic abscesses in a pediatric patient with UC. We describe herein a pediatric patient with UC who developed hepatic abscesses and portal vein thrombosis. This patient also had an extended time in remission from his UC despite being off of immunosuppressive therapies, and we speculate on how his clinical course and treatment strategies may have contributed to this.

Compositae species are applied as whole or part of the feed stock for animals and poultry. However, rabbits display varied preferences in their consumption of these plants, following the order of: Melanthera scandens (MS) > Synedrella nodiflora (SN) > Aspilia africana (AA) > Ageratum conyzoides (AC). This preference profile may be due to variation in chemical composition, flavor or toxicity of the plants. The rabbits in our farm feed on 100% MS or SN with excellent performance. This study, therefore, is set to: obtain the methanol extract of these plants, screen them for their antibacterial activity, determine their toxicity and investigate the chemical composition of their n-hexane fraction (volatile constituents).

Crushed leaves of MS, AC, AA and SN were extracted with methanol using soxhlet extraction technique to obtain the methanol extract of each plant. Phytochemical examination, antibacterial activity determination (using the agar-well diffusion technique) and toxicity studies (using experimental white albino mice) were carried out on the methanol extracts. Vacuum liquid chromatography (VLC) fractionation of each extract was carried out. The n-hexane fractions obtained from the VLC fractionation were subjected to gas chromatography-mass spectroscopy (GC-MS) analysis and the chemical constituents were identified.

Phytochemical screening showed the presence of alkaloids, steroids and tannins in all the extracts. The extracts exhibited varying degrees of antibacterial activities against bacterial strains used for this study. AC showed activity against tested microbes, having zones of inhibition ranging from 10 mm and 22 mm, with the exception of Bacillus stearothermophilus and Pseudomonas fluorescens. MS inhibited the growth of the microbes, having zones of inhibition ranging from 12 mm and 20 mm, with the exception of Bacillus anthracis, Bacillus stearothermophilus, Clostridium sporogens and Enterococcus faecalis. AA did not show activity against four of the tested microbes: Bacillus anthracis, Klebsiella pneumonia, Pseudomonas fluorescens and Enterococcus faecalis. SN however, inhibited the growth of all the bacterial strains tested, with the exception of Escherichia coli only. On the other hand, when streptomycin was used as a positive control, the growth of all the bacterial strains was inhibited, having zones of inhibition ranging from 15 mm and 22 mm. Toxicity study showed that the extracts were not toxic at the concentrations of 10 mg/kg through 1,000 mg/kg; however, at higher concentrations of 1,600 mg/kg through 2,500 mg/kg, the extracts became toxic. The LD50 was determined to be 1,275 mg/kg for all the extracts. GC-MS analysis showed the presence of 4-tetradecene in all of the extracts, except AC.

The varied preferences observed in rabbit consumption of these plants definitely have nothing to do with toxicity. The presence of various fatty acids and unsaturated hydrocarbons in the volatile components of the extracts, which influence the flavor, may be responsible for the wellness of rabbits and their relative preferences in consumption.