Some genetic association studies have investigated the potential role of patatin-like phospholipase domain-containing-3 (PNPLA3) polymorphisms in chronic liver disease, retrieving inconsistent results. Therefore, we performed a meta-analysis to further explore PNPLA3 rs738409 in a large pooled population with chronic liver disease.

Eligible studies were selected from PubMed, Embase, and CNKI databases. Studies heterogeneity was assessed using I2 statistics: when I2 >50% the random effects model was used to pool the data; otherwise, a fixed effects model was used.

In total, 36 studies were selected, comprising 14,855 cases and 12,510 controls. The analysis showed that rs738409 was significantly associated with chronic liver disease in the general population (dominant model: P < 0.0001, OR=1.62, 95% CI=1.43–1.83, I2=81.2%; recessive model: p<0.0001, OR=2.01, 95% CI=1.75–2.30, I2=74.1%; allele model: P=0.001, OR=1.53, 95% CI=1.39–1.68, I2=84.8%). These significant correlations were further confirmed in Asian and Caucasian populations. A stratified analysis also showed a positive correlation between rs738409 and hepatocellular carcinoma (HCC), cirrhosis, and non-alcoholic fatty liver disease (NAFLD), but not with chronic hepatitis B infection or alcoholic liver disease.

Altogether, PNPLA3 rs738409 may help identify individuals at higher susceptibility to chronic liver disease, in particular for HCC, cirrhosis, and NAFLD.

To explore the characteristics of traditional Chinese medicine (TCM) and the efficacy of traditional Chinese materia medica in patients with positive results in virus retests in the recovery period of the Coronavirus Disease 2019 (COVID-19). The clinical symptoms, tongue features, and lung computed tomography (CT) findings before and after treatment were recorded in detail by case series observation. The clinical symptoms of three patients with moderate COVID-19 who retested positive improved after combined TCM and symptomatic treatment. Lung CT showed that the inflammation resolved or improved progressively. Two patients continuously showed negative results in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid retests, and were in complete remission and discharged. There was a persistence of positive results in SARS-CoV-2 nucleic acid tests in one patient. Our experience is that the TCM treatment approaches of strengthening body resistance and eliminating pathogenic factors, cultivating earth, and generating metal, as well as eliminating dampness and resolving phlegm achieved good clinical effects in patients with COVID-19 who retested positive.

Increasing evidence has shown that epigenetics is closely related to the pathogenesis of nonalcoholic fatty pancreatic disease. Epigenetic modification processes, such as DNA methylation and protein acetylation and methylation, have been extensively studied. The epigenetic state of cells regulates nutrients as well as the proliferation and development of beta cells. Decreases in the mass of beta cells are likely to cause diabetes. Recent studies have shown that epigenetic modifications play important roles in the development and progression of cancer. Although DNA methylation, histone modification, microRNAs, and long noncoding RNAs have been preliminarily confirmed to participate in the development of pancreatic cancer, their roles in the pathogenesis of this disease need further study. In this paper, the roles of the various epigenetic modification processes in the pathogenesis of nonalcoholic fatty pancreatic disease and pancreatic cancer are reviewed.

Hepatitis B core antigen (HBcAg) reflects viral replication and is the target of T cells which can reflect the progression of liver disease. We aim to evaluate the relationship between Peginterferon alfa-2a (Peg-IFNα-2a) and the expression intensity of hepatitis B core antigen in chronic hepatitis B (CHB) patients in this study. 207 patients were enrolled with HBeAg-positive CHB and performed liver biopsy to determine the expression intensity of HBcAg detected by immunocytochemistry. All patients received 180μg of Peg-IFNα-2a once weekly for 48 weeks. We evaluated therapy response after 48 weeks of Peg-IFNα-2a therapy. All patients were divided into four groups (0 point group, 1 point group,2 point group,3 point group)by the expression intensity of HBcAg. Statistics on 207 patients, 118 (57.00%) had over 66% HBcAg expression (3 point group), 30 (14.49%) had 34%-66% HBcAg expression (2 point group), 45(21.74%) cases had 5%-33% HBcAg expression (1 point group), while only 14 (6.76%) had less than 5% HBcAg (0 point group). 0 point group has the lowest baseline HBV DNA among the four groups (P < 0.01). The degrees of baseline Liver tissue inflammation and fibrosis among the four groups have no difference(P > 0.05). The combination response was significantly higher in the 0 point group than in the 3 point group (57.1 % and 18.6 %, P < 0.01) after 48 weeks of Peg-IFNα-2a therapy. In conclusion, CHB patients at lower expression intensity of HBcAg have a better response to Peg-IFNα-2a therapy than at higher expression intensity of HBcAg.

Chronic hepatitis B (CHB) affects more than 257 million individuals with high liver-related morbidity and mortality worldwide. This review summarizes research progress and reflection on new drugs for the treatment of CHB. Some available HBV therapeutic strategies and their corresponding stages of development from preclinical to various clinical phases are indicated in this article. Through this review, the author aims to give us a comprehensive understanding of the global research trends and the latest progress of new drugs for treating chronic hepatitis B, so as to gain useful enlightenment.

Coronavirus disease 2019 (COVID-19) is a global epidemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Many digestive symptoms have been reported in patients infected with this virus, however, the relationship between the intestinal microbiota and SARS-CoV-2 remains unknown. This review aims to elucidate the interaction between intestinal microbiota and SARS-CoV-2, and review the mechanism of interaction between these two items as well as the effects of probiotics. This review further discusses various studies on gastrointestinal symptoms and changes in intestinal microbiota in COVID-19 patients. To further understand the mechanism, we focused on the role of angiotensin converting enzyme 2 and transmembrane protease serine 2 in this viral infection. There is a correlation between many diseases and dysbiosis of intestinal microbiota. SARS-CoV-2 can lead to dysbiosis of intestinal microbiota through a variety of mechanisms, with a decrease in the abundance and diversity of probiotics and an increase in that of pathogenic bacteria. Dysbiosis of intestinal microbiota results in the translocation of intestinal flora, aggravation of systemic inflammation, and lung injury. Modulating the intestinal microbiota ameliorates digestive symptoms and pathology in infectious respiratory diseases. Intestinal microbiota and SARS-CoV-2 interact through a variety of mechanisms; SARS-CoV-2 can cause dysbiosis of the intestinal microbiota, while dysbiosis of intestinal microbiota, in turn, aggravates COVID-19.

Nonalcoholic fatty liver disease (NAFLD) is a global epidemic that is likely to become the most common cause of chronic liver disease in the next decade, worldwide. Though numerous drugs have been evaluated in clinical trials, most of them have returned inconclusive results and shown poorly-tolerated adverse effects. None of the drugs have been approved by the Food and Drug Administration for treating biopsy-proven non-alcoholic steatohepatitis (NASH). Vitamin E and pioglitazone have been extensively used in treatment of biopsy-proven nondiabetic NASH patients. Although some amelioration of inflammation has been seen, these drugs did not improve the fibrosis component of NASH. Therefore, dietary modification and weight reduction have remained the cornerstone of treatment of NASH; moreover, they have shown to improve histological activity as well as fibrosis. The search for an ideal drug or ‘Holy Grail’ within this landscape of possible agents continues, as weight reduction is achieved only in less than 10% of patients. In this current review, we summarize the drugs for NASH which are under investigation, and we provide a critical analysis of their up-to-date results and outcomes.

Accumulated studies have reported the key role of circulating fetuin-A in the development and progression of nonalcoholic fatty liver disease (NAFLD) but the results have not been consistent. In this study, we performed a systematic review and meta-analysis to explore the relationship between circulating fetuin-A level and the development and classification of NAFLD.

The PubMed, EMBASE, and Cochrane Library databases were searched to obtain the potentially relevant studies up to May 2020. Standardized mean differences (SMD) and 95% confidence intervals of circulating fetuin-A levels were extracted and summarized. Sensitivity, subgroup analysis and meta-regression analysis were performed to investigate the potential heterogeneity. Association of circulating fetuin-A level with classification of NAFLD was also reviewed.

A total of 17 studies were included, composed of 1,755 NAFLD patients and 2,010 healthy controls. Meta-analysis results showed that NAFLD patients had higher circulating fetuin-A level (SMD=0.43, 95% confidence interval [CI]: 0.22–0.63, p<0.001) than controls. Subgroup analysis indicated that circulating fetuin-A level was markedly increased in adult NAFLD patients (SMD=0.48, 95% CI: 0.24–0.72, p<0.001) and not in pediatric/adolescent patients compared to controls. Circulating fetuin-A level was markedly increased in ultrasound-proven NAFLD pediatric/adolescent patients (SMD=0.42, 95% CI: 0.12–0.72, p=0.007), other than in the liver biopsy-proven NAFLD pediatric/adolescent patients. Body mass index might be the influencing factor to the heterogeneity in adult patients. Circulating fetuin-A level was not associated with the classification of NAFL vs. nonalcoholic steatohepatitis (NASH). Whether the circulating fetuin-A level was associated with the development of fibrosis remains controversial.

Circulating fetuin-A level was significantly higher in NAFLD patients and was not associated with the classification of NAFL vs. NASH. Whether the circulating fetuin-A level was associated with the development of fibrosis remains controversial.

Aminotransferases are commonly found to be elevated in patients with celiac disease in association with two different types of liver dysfunction: cryptogenic liver disorders and autoimmune disorders. The purpose of this review is to discuss the mechanisms by which aminotransferases become elevated in celiac disease, clinical manifestations, and response to gluten-free diet. Many studies have shown that celiac patients with cryptogenic liver disease have normalization in aminotransferases, intestinal histologic improvement and serologic resolution after 6–12 months of strict gluten-free diet. In patients with an underlying autoimmune liver disease, simultaneous treatment for both conditions resulted in normalized elevated aminotransferases. The literature suggests that intestinal permeability may be at least one of the mechanisms by which liver damage occurs. Patients with celiac disease should have liver enzymes routinely checked and treated with a strict gluten-free diet if found to be abnormal. Lack of improvement in patients who have strictly adhered to gluten-free diet should prompt further workup for other causes of liver disease.

Occult hepatitis B infection is characterized by loss of hepatitis B surface antigen (HBsAg) and persistence of low levels of hepatitis B virus (HBV) replication that may or may not be detectable in plasma/serum. We present a case of HBV reactivation in a male patient who underwent orthotopic liver transplant for hepatocellular carcinoma secondary to active hepatitis C (HCV) infection. Pre-transplant, he was HBsAg-negative and hepatitis B core antibody-positive, with an undetectable HBV viral load that was incidentally found to be positive at a very low HBV viral load on the day of transplant. Post-transplant, his HBsAg remained undetectable, with an undetectable HBV viral load, until eradication of his HCV infection with direct acting antiviral agents. After eradication of HCV, there was reactivation of HBV, with a high viral load and emergence of serum HBsAg. A deep sequencing genetic analysis of his HBV both pre- and post-transplant revealed the presence of a mutation in the “a” determinant of the HBV surface antigen. The role of HBV genotype ‘a’ determinant mutation in HBV reactivation post-transplant is unknown and needs further examination. Our experience suggests a possible role for antiviral prophylaxis in these patients or monitoring of HBV viral loads post-transplant.

Overall mortality among U.S. adults has been stable in past years; however, racial disparity influenced 10 leading causes of death or age-specific mortality in Blacks or African Americans. Unfortunately, the trends in sex- and race-adjusted age-standardized cause-specific mortality are poorly understood.

We here aimed to identify the underlying causes of death (UCD) with sex- and race-adjusted, and age-standardized mortality that has changed in recent years. We extracted the data of UCD from the Multiple Cause of Death database of the Centers for Disease Control and Prevention (CDC). Multivariable log-linear regression models were used to estimate trends in sex- and race-adjusted, and age-standardized mortality of UCD during 2013–2017.

A total of 31,029,133 deaths were identified. Among the list of 113 UCDs compiled by the CDC, there were 29 UCDs exhibiting an upward trend, 33 UCDs exhibiting a downward trend and 56 UCDs with no significant trends. The 2 UCDs with the largest annual percent change were both nutrition related (annual percent change [APC] = 17.73, 95% CI [15.13–20.33] for malnutrition, and APC = 17.49, 95% CI [14.94–20.04] for Nutritional deficiencies), followed by accidental poisoning and exposure to noxious substances. The 4 UCDs with the largest decreasing APC were viral hepatitis (APC = −11.71), chronic and unspecified bronchitis (APC = −8.26), emphysema (APC = −7.11) and human immunodeficiency virus disease (APC = −7.10).

This study thus reports UCDs with changing mortality in recent years after sex- and race-adjustments and age-standardizations. More effort and resources should focus on understanding, preventing and controling the mortality linked to these UCDs. Continuous monitoring of mortality trends is recommended.

Systemic lupus erythematosus (SLE) is a systemic disease which affects mainly young females and can cause life-threatening conditions. Pleural effusion can occur in SLE patients and usually tends to be mild and bilateral. This report aims to highlight the clinical presentation and medical management of massive unilateral pleural effusions in SLE patients. Here we report a 35-year-old female diagnosed with SLE for six years. She presented with shortness of breath, severe pleuritic chest pain, and fatigue. Her clinical examination showed signs of massive pleural effusion on the right side which was confirmed later by a chest x-ray and computer tomography of the chest. An echocardiography and abdominal ultrasound indicated no pericardial effusion and no ascites. A pleural fluid analysis showed exudative fluid. Sputum culture and polymerase chain reaction on blood sample for Mycobacterium tuberculosis were negative. She was also edematous and pale but not cyanotic or jaundiced. The treatment included blood transfusions, antibiotics, rituximab, azathioprine, and hydroxychloroquine. The pleural effusion responded well to rituximab, and she was discharged after two months in good condition.

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.