Background and Aims: The association between portal-systemic shunt and hepatocellular carcinoma (HCC) development in patients who have cirrhosis is still controversial. This systematic review with meta-analysis was performed to systematically clarify the potential role of portal-systemic shunt in the development of HCC.

Methods: The PubMed, Embase, and Cochrane Library databases were searched for potentially eligible literature. Meta-analysis with random-effects model was performed to combine the incidence rates of HCC after portal-systemic shunt. Finally, seven studies were included. In the present review, we mainly focused on 859 patients (365 in the transjugular intrahepatic portal-systemic shunt (TIPS) group and 494 in the non-TIPS group) from five studies to analyze incidence rates after TIPS.

Results: At the end of follow-up, there were 66 (18%, 66/365) patients who developed HCC after TIPS intervention and 63 (13%, 63/494) patients who developed HCC after non-TIPS treatments. Pooled estimates with random-effects model did not demonstrate a significant increase of incidence of HCC after TIPS (risk ratio: 1.37 [confidence interval (CI): 0.96 to 1.97]; p = 0.08) compared with non-TIPS treatments. Subgroup analyses for those patients with transplanted liver also did not detect a significant difference between the TIPS group and non-TIPS group (risk ratio: 1.10 [CI: 0.59 to 2.07]; p = 0.75).

Conclusions: Current evidence suggests that portal-systemic shunt is not associated with a higher risk of HCC development in cirrhotic patients.

Background and Aims: Acetaminophen (APAP) is the leading cause of drug overdose and hepatotoxicity worldwide, including in Thailand. Patterns of overdose and hospital management are known to have significant impacts on the outcomes of APAP overdose, and these factors vary from country to country. Therefore, this study aimed to analyze clinical characteristics of Thai patients with APAP overdose in terms of overdose patterns, clinical presentation, treatment and outcomes.

Methods: In this retrospective analytical study, medical records of adult patients hospitalized with a diagnosis of APAP overdose at Rajavithi Hospital, Bangkok, between January 2013 and December 2017 were reviewed.

Results: A total of 184 patients diagnosed with APAP overdose were included. The median age was 22 (15–76) years and the majority were female (79.9%). Most overdoses were intended self-poisoning ingestion (90.8%) with a median dose of 10.5 g (4.5–50). A total of 121 patients were treated with N-acetylcysteine with a median visit-to-N-acetylcysteine time of 2 (0.5–15) h. Overall, 15.6% developed mild hepatotoxicity (aspartate aminotransferase or alanine aminotransferase >3 times the upper limit of normal), 6.4% developed severe hepatotoxicity (aspartate aminotransferase or alanine aminotransferase >10 times the upper limit of normal and international normalized ratio >2.0) and 3 patients developed acute liver failure (1 patient resolved spontaneously and 2 patients, neither of whom had a liver transplant, died). Significant predictors for hepatotoxicity included older age, chronic alcohol drinking, repeated taking of medication for more than 8 h (staggered ingestion), long duration between ingestion and hospital visit, alcohol coingestion, abdominal pain symptoms, and acute kidney injury.

Conclusions: Most cases of APAP overdose in Thailand appear to be young women with intentional ingestion. With prompt management, most patients (76.4%) did not develop significant hepatotoxicity; nevertheless, despite N-acetylcysteine therapy, hepatotoxicity including acute liver failure was observed in a small proportion of patients, particularly those with unintentional overdose and chronic alcohol drinking.

Hepatitis B virus (HBV) immunization is safe and has been accepted worldwide as a routine practice. The target of such vaccination is to induce the immune response in the host, resulting in the prevention of replication of HBV. There are several immunological and clinical factors which determine the clinical efficacy and safety of the HBV vaccine. In this article we have highlighted the response of the host immune system to HBV vaccination (immunogenicity), efficacy, and safety of the vaccine, issues with booster dosing, paths of development (preclinical and clinical) of the HBV vaccine, novel and upcoming strategies for improvement of HBV vaccination, and the concept of therapeutic HBV vaccination. The different aspects and regulatory recommendations pertaining to HBV vaccine development are also discussed. The new strategies for improvement of HBV vaccination include pre-S1 and pre-S2 portions of the HBV surface antigen, increasing the antigen dose, accelerated vaccination schedules, alternative vaccination route, use of adjuvants like immunostimulatory DNA sequences, etc. Therapeutic vaccination is being explored for initiation of a multifunctional and multispecific T cell response against the major HBV antigens and also effective activation of humoral immunity for viral control.

Background and Aims: Hepatitis C virus (HCV)-infected organs are underutilized. We aimed to assess the safety and efficacy of direct-acting antiviral agents (DAAs) therapy in HCV viremic patients who are transplanted with a liver from a HCV viremic donor.

Methods: We conducted a retrospective study, including patients seen from July 2015 to April 2017. HCV viremic patients transplanted with a liver from a HCV viremic donor and subsequently treated with DAAs were included. Outcomes assessed included undetectable viral load at 12 weeks after completing DAA therapy (sustained virologic response, SVR12), adverse events, and interactions with immunosuppression.

Results: Twenty-four HCV viremic recipients received livers from HCV viremic donors. Median age was 63 years, and the majority (79.2%) were genotype 1a. Donors and recipients were viremic at the time of transplant. Median modified model for end-stage liver disease score was 19, and median time on the waitlist was 81 days. Median time from transplant to initiation of DAA therapy was 123 days. Several DAA regimens were used and 15 (62.5%) patients did not receive ribavirin. Treatment duration ranged from 12 to 24 weeks. Twenty-three (95.8%) patients achieved SVR12. Five (20.8%) patients developed adverse events; however, none required DAA discontinuation.

Conclusions: DAA therapy was efficacious and well tolerated in HCV viremic recipients who underwent liver transplantation from a HCV viremic donor.

The role of radiotherapy in the treatment of hepatocellular carcinoma (HCC) has evolved over the past few decades with the advancement of technology and improved imaging. Radiotherapy can offer high local control rates in unresectable HCC, including cases with major vascular involvement, and can provide a modality to help bridge patients to potentially curative resection or transplantation. In metastatic cases, radiotherapy can provide good palliation. This review focuses on the common radiotherapy treatment modalities used for HCC, provides outcome comparisons of these radiotherapy techniques to outcomes with other treatment modalities for HCC, and highlights the discrepancy of the role of radiotherapy in HCC amongst the current available treatment guidelines.

We report here a case of a 54-year-old man who developed subarachnoid hemorrhage following cardiopulmonary resuscitation. Both computed tomography scans performed respectively within 24 h and on day 3 indicated a normal physical condition. The computed tomography scan conducted 7 days after the cardiopulmonary resuscitation revealed diffuse cerebral edema and subarachnoid hemorrhage. The existence of blood in cerebrospinal fluid was confirmed by lumbar puncture. We propose that ischemia/reperfusion response plays an important role in the development of post-resuscitation subarachnoid hemorrhage.

Background and Aims: The metabolic acid-base disorders have a high incidence of acute kidney injury (AKI) in critically ill cirrhotic patients (CICPs). The aims of our study were to ascertain the composition of metabolic acidosis of CICPs with AKI and explore its relationship with hospital mortality.

Methods: Three-hundred and eighty consecutive CICPs with AKI were eligible for the cohort study. Demographic, clinical and laboratory parameters were recorded and arterial acid-base state was analyzed by the Stewart and Gilfix methodology.

Results: Net metabolic acidosis, lactic acidosis, acidosis owing to unmeasured anions, acidemia, and dilutional acidosis were less frequent in the non-survival group compared to the survival group of CICPs. The presence of acidemia, acidosis owing to unmeasured anions, and lactic acidosis were independently associated with increased risk of intensive care unit 30-day mortality, with hazard ratios of 2.11 (95% confidence interval (CI): 1.43–3.12), 3.38 (95% CI: 2.36–4.84), and 2.16 (95% CI: 1.47–3.35), respectively. After full adjustment for confounders, the relationship between acidosis owing to unmeasured anions with hospital mortality was still significant, with hazard ratio of 2.29 (95% CI: 1.22–4.30). Furthermore, arterial lactate concentration in combination with chronic liver failure-sequential organ failure assessment and BEUMA had the strongest ability to differentiate 30-day mortality (area under the receiver operating characteristic curve: 0.79, 95% CI: 0.74–0.83).

Conclusions: CICPs with AKI exhibit a complex metabolic acidosis during intensive care unit admission. Lactic acidosis and BEUMA, novel markers of acid-base disorders, show promise in predicting mortality rate of CICPs with AKI.

This study aimed to examine the difference in expression of matrix metalloproteinases (MMPs) in ameloblastoma and other benign tumors or normal tissue of the jaw, and ameloblastic carcinoma, and to investigate the correlation of expression of MMPs with patient prognosis.

Studies were identified in the major electronic databases (Medline, EMBASE and Cochrane Library) using the keywords “matrix metalloproteinases” and “ameloblastoma” OR “ameloblastic carcinoma”, and a quantitative meta-analysis was conducted.

Fourteen studies were included in this systematic review. Twelve studies representing a total number of 471 cases qualified for the meta-analysis. The analysis revealed a higher MMP-2 expression in ameloblastoma than in the other benign odontogenic tumors, showing a significant inter-group difference (odds ratio [OR]: 5.33; 95% confidence interval (CI): [1.36, 25.62]; p = 0.02). A lower MMP-2 expression was found for the ameloblastoma than in the ameloblastic carcinoma, with a non-significant inter-group difference (OR: 0.12; 95% CI: [0.01, 1.02]; p = 0.05). Finally, a lower MMP-9 expression was found for the follicular subgroup compared to that in other subgroups of ameloblastoma, showing a significant inter-group difference (OR: 0.15; 95% CI: [0.05, 0.48]; p = 0.001).

We found that MMP-2 expression in ameloblastoma is higher than that in other benign tumors or normal tissue of jaw, and that MMP-9 expression in the follicular subgroup of ameloblastoma is lower than that in other pathology subgroups of ameloblastoma. What is more important, the MMPs expression in ameloblastoma was found to be significantly correlated with many clinicopathologic features of ameloblastoma. However, some limitations weakened the power of this meta-analysis.

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.