Patients with nonalcoholic steatohepatitis (NASH) are at higher risk of progression to advanced stages of fibrosis, cirrhosis, hepatocellular carcinoma and other end-stage liver disease complications. When addressing treatment of NASH, we have limited approved options, and the mainstay of therapy is lifestyle intervention. Extensive research and revelation in the field of pathogenesis of NASH has offered new possibilities of treatment and emerging new drugs that are being tested currently in numerous preclinical and clinical trials. These drugs target almost all steps in the pathogenesis of NASH to improve insulin sensitivity, glucose and lipid metabolism, to inhibit de novo lipogenesis and delivery of lipids to the liver, and to influence apoptosis, inflammation and fibrogenesis. Although NASH is a multifactorial disease, in the future we could identify the predominating pathological mechanism and, by choosing the most appropriate specific medication, tailor the treatment for every patient individually.

Multidisciplinary teams (MDTs) have been widely used for the diagnosis, treatment and management of cancer patients and other patients with complex diseases and conditions. The decisions of MDTs have not always been the best options as MDTs in general may encourage overtreatment. From MDT to holistic integrative medicine (HIM), a multidisciplinary working model should be established to formulate an individualized and integrated healthcare plan to achieve an optimal effect using a holistic view and integrative thinking.

Amyloidosis is a group of rare, serious disorders caused by deposition of amyloid protein in tissues, such as the kidney, heart and brain. However, there is no case reported from Sudan. Here, we report one male case of renal amyloidosis, possibly secondary to abdominal tuberculosis (Tb). A male, 30 years of age, complained of systemic body swelling, shortness of breath, and decreased urine output with abnormal color for 2 months. He had been diagnosed with abdominal Tb 10 years prior, for which he received systemic anti-Tb treatment. Clinical examination exhibited anasarca, particularly in the abdomen. Abdominal ultrasound indicated massive ascites, and echocardiography indicated the ejection fraction reduced to 60%. Renal biopsy revealed renal amyloidosis. The patient was treated with ceftriaxone, furosemide, prednisolone, pantoprazole, spironolactone, calcium and mycophenolate mofetil, and his condition improved. The patient was discharged 2 weeks after treatments. Hence, this is the first case of renal amyloidosis, possibly secondary to abdominal Tb, in Sudan. This case report should serve as an alert to physicians working in high-prevalence Tb regions.

Dengue infection may lead to various sequels, such as undifferentiated fever, dengue fever, or dengue hemorrhagic fever, progressive illness, and death. It also causes significant economic burden associated with healthcare costs and loss of labor. Usually, the treatment of dengue infection is supportive therapy and not a specific treatment, while it is often clinically difficult to predict whether dengue-infected patients will progress to severe disease or not. We propose integrated management strategies for early dengue virus infection based on our 5-year experience in early management of dengue infection, literature reviews, and research studies (over the last 10 years). This proposal consists of 4 aspects: (1) rehydration with oral rehydration therapy; (2) reduction of the proinflammatory cytokines, including tumor necrosis factor-α and interleukin-6 with oral cytokine inhibitors (i.e. pentoxifylline and doxycycline); (3) inhibition of dengue virus replication, viral load reduction, nonstructural protein 1 antigen clearance with doxycycline and ivermectin; and (4) restoration of the immune function by vitamin D and zinc supplementation. The major benefit of these drugs and supplements is that they are already approved by regulatory bodies, affordable, and clinically safe. They result in better clinical and laboratory outcomes, including reductions in hospitalization and cost of treatment. Another benefit is that this strategy may be used for other virus-induced hypercytokinemia, such as coronavirus disease and Ebola.

Nontumoral portal vein thrombosis (PVT) is an increasingly recognized complication in patients with cirrhosis. Substantial evidence shows that portal flow stasis, complex thrombophilic disorders, and exogenous factors leading to endothelial dysfunction have emerged as key factors in the pathogenesis of PVT. The contribution of PVT to hepatic decompensation and mortality in cirrhosis is debatable; however, the presence of an advanced PVT increases operative complexity and decreases survival after transplantation. The therapeutic decision for PVT is often determined by the duration and extent of thrombosis, the presence of symptoms, and liver transplant eligibility. Evidence from several cohorts has demonstrated that anticoagulation treatment with vitamin K antagonist or low molecular weight heparin can achieve recanalization of the portal vein, which is associated with a reduction in portal hypertension-related events and improved survival in cirrhotic patients with PVT. Consequently, interest in direct oral anticoagulants for PVT is increasing, but clinical data in cirrhosis are limited. Although the most feared consequence of anticoagulation is bleeding, most studies indicate that anticoagulation therapy for PVT in cirrhosis appears relatively safe. Interestingly, the data showed that transjugular intrahepatic portosystemic shunt represents an effective adjunctive therapy for PVT in cirrhotic patients with symptomatic portal hypertension if anticoagulation is ineffective. Insufficient evidence regarding the optimal timing, modality, and duration of therapy makes nontumoral PVT a challenging consequence of cirrhosis. In this review, we summarize the current literature and provide a potential algorithm for the management of PVT in patients with cirrhosis.

The novel coronavirus 2019 (COVID-19) was reported by the World Health Organization in December 2019, and since then it has progressed into a worldwide pandemic, causing significant morbidity and mortality. Gastrointestinal symptoms of COVID-19 and elevated liver chemistries are seen in up to 50% of infected patients. Recent reports have suggested a high mortality rate for COVID-19 in patients with pre-existing liver disease, having an associated mortality of 39.8%. Alcoholic liver disease is a significant cause of morbidity and mortality in New Mexico (USA), and we report here the clinical course and characteristics of three cases of patients with alcoholic cirrhosis who were admitted to our hospital with COVID-19.

VS-105, a novel vitamin D receptor agonist with significantly less hypercalcemic side effects than calcitriol, is a useful tool to investigate whether or not a vitamin D receptor agonist at non-hypercalcemic doses could improve bone mineral density (BMD).

VS-105 and calcitriol were evaluated in an ovariectomized (OVX) osteoporosis rat model and in calvariae bone organ culture.

Treatment of OVX rats by VS-105 (0.1, 0.2 or 0.5 µg/kg, intraperitoneal, 3×/week, for 90 days) significantly improved BMD in the L3 lumbar vertebra in a dose-dependent manner (sham vs. OVX/vehicle: 324 ± 14 vs. 279 ± 10 mg/cm2; VS-105 at 0.1, 0.2 and 0.5 µg/kg: 306 ± 9, 329 ± 12, and 327 ± 10 mg/cm2, respectively) without affecting serum calcium (Ca). Calcitriol at 0.1 µg/kg significantly increased BMD but it also increased serum Ca. VS-105 and calcitriol at the test doses significantly suppressed serum parathyroid hormone and promoted tibia bone growth. With respect to biomarkers of bone remodeling, calcitriol and VS-105 both significantly elevated serum osteocalcin. In the calvariae bone organ culture, net Ca release was significantly less in VS-105-treated groups (vs. calcitriol).

VS-105 is efficacious in improving BMD in a dose range that does not affect serum Ca in OVX rats; the improvement in BMD by VS-105 is attributable to increased osteoblastic activity and reduced osteoclastic bone resorption.

Background and Aims: Hispanic patients with primary biliary cholangitis (PBC) have reduced rates of biochemical response to ursodeoxycholic acid (UDCA) and increased risk of disease progression compared to non-Hispanic patients. In this study, we sought to identify differences in demographics, comorbidities, environmental risk factors and socioeconomic status between Hispanic and non-Hispanic patients with PBC.

Methods: In a case control study, we analyzed data from Hispanic (n=37 females and 1 male) and non-Hispanic (n=54 females and 4 males) patients with PBC seen at the University of Miami/Jackson Memorial Hospital from January 1998 through January 2013. Data were obtained by filling out a questionnaire either via phone call, mail, or e-mail. Odds ratios were calculated to measure the association between exposure and outcomes.

Results: Baseline demographics, environmental risk factors and comorbidities were similar between Hispanic and non-Hispanic patients with PBC. Hispanic patients were less likely to be married and fewer Hispanics had education beyond high school level compared to non-Hispanics. Sixty four percent of Hispanic patients had a household income of less than $50000, compared to 19.5% of non-Hispanics. Fewer Hispanic patients with PBC had health insurance coverage compared to non-Hispanics (86.5% vs. 98.1%; odds ratio: 0.1, 95% confidence interval: 0-0.9).

Conclusions: Differences in disease severity and response to therapy observed in prior studies could not be explained by environmental exposures. In addition to genetic variation, socioeconomic discrepancies (access to care) may further explain these differences.

Annona squamosa (A. squamosa) is a medicinal plant, used in ethnomedicinal treatment of various ailments. However, there is a dearth of information on the chemical constituents of this plant’s fruit pod and chemical parameters of the seed oil. The objectives of this study were, therefore, to determine the chemical characteristics and biological activities of extracts of the fruit pod and seed oil of A. squamosa.

Crude methanol extract of the dried and pulverized fruit pod were partitioned using n-hexane and dichloromethane (DCM), the fractions concentrated in-vacuo to yield n-hexane and DCM fractions of the fruit pod. The n-hexane extract of the dried ground seed was concentrated in vacuo to afford the seed oil. The fractions and the seed oil were subjected to gas chromatography-mass spectroscopy (GC-MS) analysis. The seed oil was characterized for chemical properties using standard methods. The seed oil, crude methanol extract of seed pod and fractions were assayed for antibacterial properties using both Gram-positive and Gram-negative bacteria. The seed oil was also examined for antioxidant activity.

The results from chemical analyses of the seed oil indicated that acid value, iodine value, saponification value and total phenol were 1.91 (as % oleic acid), 109.8 g I2/kg, 204.8 g KOH/kg and 36.2 mg gallic acid equivalent (GAE)/kg, respectively. GC-MS analysis revealed the presence of 14, 8 and 15 compounds in n-hexane and DCM fractions of the fruit pod and seed oil, respectively. Of the compounds identified, octadec-9-enoic acid, 9,10-dehydroisolongifolene and androsterone were the most abundant. The extracts displayed broad spectrum antibacterial activity against the 13 bacterial strains tested, except for Bacillus polymyxa, Enterococcus faecalis and Bacillus cereus, which were resistant to the n-hexane and DCM fractions of the fruit pod.

The findings in this study indicated that the extracts and oil of A. squamosa contain bioactive compounds which have antibacterial and antioxidant properties, and the oil could be applied both as industrial and edible oil.

Chronic liver disease (CLD) is an under-recognized epidemic that continues to increase in prevalence and is a major health concern. Silymarin, the active compound of Silybum marianum (Milk thistle), has historically been used in CLD. A significant barrier to silymarin use is its poor bioavailability. Attempts at improving the bioavailability of silymarin have led to a better understanding of formulation methods, pharmacokinetics, dosing, and associated drug interactions. Clinically, silymarin exerts its hepatoprotective effects through antioxidative, antifibrotic, anti-inflammatory, antitoxin, and anticancerous mechanisms of actions. Despite the use of silymarin being extensively studied in alcoholic liver disease, metabolic-associated fatty liver disease, viral hepatitis, and drug-induced liver injury, the overall efficacy of silymarin remains unclear and more research is warranted to better elucidate the role of silymarin in CLD, specifically regarding its anti-inflammatory effects. Here, we review the current biochemical and clinical evidence regarding silymarin in CLD.

Background and Aims: Long-term data on cell-based therapies, including hematopoietic stem cell infusion in cirrhosis, are sparse and lacking.

Methods: Patients with cirrhosis of non-viral etiology received either standard-of-care (n = 23) or autologous CD34+ cell infusion through the hepatic artery (n = 22). Study patients received granulocyte colony-stimulating factor (commonly known as G-CSF) injections at 520 µgm per day for 3 days, followed by leukapheresis and CD34+ cell infusion into the hepatic artery. The Control group received standard-of-care treatment.

Results: Mean CD34+ cell count on the third day of G-CSF injection was 27.00 ± 20.43 cells/µL 81.84 ± 11.99 viability and purity of 80-90%. Significant improvement in the model of end-stage liver disease (commonly known as MELD) score (15.75 ± 5.13 vs. 19.94 ± 6.68, p = 0.04) was noted at end of 3 months and 1 year (15.5 ± 5.3 vs. 19.8 ± 6.4, p = 0.04) but was not statistically different at end of the second (17.2 ± 5.5 vs. 20.3 ± 6.8, p = 0.17) and third-year (18.4 ± 6.1 vs. 21.3 ± 6.4, p = 0.25). No difference in mortality (6/23 vs. 5/23) was noted.

Conclusions: Autologous CD34+ cell infusion effectively improved liver function and MELD score up to 1 year but the sustained benefit was not maintained at the end of 3 years, possibly due to ongoing progression of the underlying disease.

Background and Aims: Coronary artery disease (CAD) is a major cause of morbidity and mortality in patients with non-alcoholic fatty liver disease (NAFLD). Previous studies have suggested that TCF7L2 rs7903146 was related to the risk of developing NAFLD but the conclusions are not consistent and no related study has been conducted in Chinese populations. The aim of this study was to investigate the association between TCF7L2 rs7903146 and the risk of developing NAFLD and CAD in a Chinese Han population.

Methods:TCF7L2 rs7903146 genotypes were measured by the MALDI-TOF-MS from 143 NAFLD patients, 159 CAD patients, 131 NAFLD + CAD patients, and 212 healthy controls. The demographic data and serum lipid profiles of all subjects were collected. The distributions of genotype and allele frequency in each group were also tested. Logistic regression was used to investigate the risk of TCF7L2 rs7903146 with NAFLD and CAD. All statistical analyses were conducted using SPSS 23.0.

Results: There were no significant differences in the distributions of TCF7L2 rs7903146 genotype and allele frequency in each of the two groups, and the TCF7L2 rs7903146 CT + TT genotype did not increase the risk of developing NAFLD, CAD, and NAFLD + CAD. Except for body mass index in the control group, the differences of clinical parameters between the TCF7L2 rs7903146 T allele carriers and non-carriers in each group were not significant. In the non-obese group, the TCF7L2 rs7903146 CT + TT genotype was a protective factor for the development of NAFLD in the non-obese subjects (odds ratio=0.359, 95% confidence interval: 0.134-0.961, p = 0.041).

Conclusions:TCF7L2 rs7903146 was not associated with the risk of developing NAFLD, CAD, and NAFLD + CAD in the Chinese Han population. In the non-obese population, the TCF7L2 rs7903146 CT + TT genotype was a protective factor against the development of NAFLD.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) induced a worldwide pandemic. The main clinical manifestations of COVID-19 patients have been fever, cough, dyspnea, and other respiratory symptoms. However, some patients’ initial symptoms have been nausea, vomiting, diarrhea and other gastrointestinal symptoms, and SARS-CoV-2 RNA could be found in their stool samples. Studies have shown that the gastrointestinal tract highly-expressed angiotensin-converting enzyme 2 is used by SARS-CoV-2 to enter cells. Therefore, exploring the damage caused by SARS-CoV-2 to the gastrointestinal tract and whether it could replicate in the gastrointestinal tract and transmit through fecal-oral route has significance for the diagnosis, treatment and prevention of COVID-19. We combined the current clinical data about COVID-19 patients with gastrointestinal symptoms as well as its pathogenic mechanism and prevention methods herein to review the relationship between the disease and gastrointestinal symptoms.

The severe acute respiratory syndrome corona virus-2 (referred to as SARS CoV2) pandemic had a great impact on public life in general as well as on populations with pre-existing disease and co-morbidities. Liver transplant and immunosuppressant medication predisposes to more severe disease and is often associated with poor outcome. The clinical features, disease course, treatment and process of modulating the immunosuppression is challenging. Here, we describe the clinical presentation, treatment and outcomes in six liver transplant recipients. Out of those six patients, three had mild, one had moderate and one had severe COVID-19, and one was asymptomatic. The immunosuppression minimization or withdrawal was done based upon the clinical severity. Consideration of tocilizumab and/o convalescent plasma as well as antivirals i.e. remdesvir done in severe cases. The routine practice of prophylactic anticoagulation, consideration of repurposed drugs (i.e. teicoplanin and doxycycline), and watchful monitoring of asymptomatic recipients helped to achieve an uneventful recovery.

Duchenne muscular dystrophy (DMD) is a fatal X-linked genetic disease of the neuromuscular system and is the most serious type of muscular dystrophy in humans. The disease is characterized by progressive muscular atrophy and a poor prognosis. The incidence rate is 1/3500, and symptoms appear at age of 5 years-old. Some patients present with abnormal aminotransferases as the first symptom. In addition to the clinical characteristics and genetic history, electromyography examination, muscle biopsy, serum enzyme examination, and measures of creatine kinase (CK), CK isoenzyme, and serum lactate dehydrogenase are important features of auxiliary examination. Clinicians who encounter unknown causes of transaminitis should consider the possibility of DMD. We describe here a 3 year-old pediatric patient with increased aminotransferases who had elevated CK and a family genetic history but without liver damage on computed tomography. He was suspected as having inherited the disorder and was finally diagnosed as having DMD by next-generation sequencing.

Background and Aims: In the REALM (Randomized, Observational Study of Entecavir to Assess Long-Term Outcomes Associated with Nucleoside/Nucleotide Monotherapy for Patients with Chronic HBV Infection) study, 12,378 patients with chronic hepatitis B virus (HBV) infection received up to 10 years of randomized therapy with entecavir or another HBV nucleos(t)ide analogue. Monitored clinical outcome events (COEs) included malignant neoplasms, HBV disease progression events, and deaths. An external event adjudication committee (EAC) was convened to provide real-time review of reported COEs to optimize data quality, and minimize potential adverse effects of the large cohort, interdisciplinary outcome assessments, geographic scope, and long duration. Methods: The EAC comprised an international group of hepatologists and oncologists with expertise in diagnosis of targeted COEs. The EAC reviewed and adjudicated COEs according to prospectively defined diagnostic criteria captured in the EAC charter. Operational processes, including data collection and query procedures, were implemented to optimize efficiency of data recovery to maximize capture of adjudicated COEs, the primary study outcome measure. Results: A total of 1724 COEs were reported and 1465 of these events were adjudicated by the EAC as reported by the investigators (85.0% overall concordance). Concordance by COE type varied: deaths, 99.6%; hepatocellular carcinoma (HCC), 83.3%; non-HCC malignancies, 88.0%; non-HCC HBV disease progression, 68.2%. Reasons for lack of concordance were most commonly lack of adequate supporting data to support an adjudicated diagnosis or evidence that the event pre-dated the study. Conclusions: The REALM EAC performed a critical role in ensuring data quality and consistency; EAC performance was facilitated by well-defined diagnostic criteria, effective data capture, and efficient operational processes.

Trial registration: ClinicalTrials.gov NCT00388674.

Direct-acting antiviral (DAA) therapy is often well-tolerated, and adverse events from DAA therapy are uncommon. We report a case of a woman who underwent orthotopic liver transplant for chronic hepatitis C infection and later developed alloimmune hepatitis shortly after starting DAA therapy for recurrent hepatitis C infection. The patient developed acute alloimmune hepatitis approximately 2 weeks after starting treatment with sofosbuvir, velpatasvir, and voxilaprevir. This case report proposes a dysregulation of immune surveillance due to the DAA stimulation of host immunity and rapid elimination of hepatitis C viral load as a precipitating factor for the alloimmune process, leading to alloimmune hepatitis in a post-transplant patient who starts on DAA.

Globally, hepatitis B virus (HBV) infection and its related liver diseases account for 780,000 deaths every year. Outcomes of HBV infection depend on the interaction between the virus and host immune system. It is becoming increasingly apparent that Kupffer cells (KCs), the largest population of resident and monocyte-derived macrophages in the liver, contribute to HBV infection in various aspects. These cells play an important role not only in the anti-HBV immunity including virus recognition, cytokine production to directly inhibit viral replication and recruitment and activation of other immune cells involved in virus clearance but also in HBV outcome and progression, such as persistent infection and development of end-stage liver diseases. Since liver macrophages play multiple roles in HBV infection, they are directly targeted by HBV to benefit its life cycle. In the present review, we briefly outline the current advances of research of macrophages, especially the studies of their phenotypes, in chronic HBV infection.