International Journal of Hepatology最新文献

Background: Direct-acting antiviral (DAA) drugs have been highly effective in the treatment of chronic hepatitis C (CHC) infection. We aim to evaluate the treatment response of Sofosbuvir based DAA in CHC patients with compensated liver cirrhosis as limited data exists in the real-world community setting.

Methods: All the CHC patients with compensated liver cirrhosis treated with Sofosbuvir based DAAs between January 2014 and December 2017 in a community clinic setting were retrospectively analyzed. Pretreatment baseline patient characteristics, treatment efficacy with the sustained virologic response at 12 weeks posttreatment (SVR12), and adverse reactions were assessed.

Results: One hundred and twelve patients with CHC infection and concurrent compensated cirrhosis were included in the study. Black patients represented the majority of the study population (64%). Eighty-seven patients were treated with Ledipasvir/Sofosbuvir (LDV/SOF) ±Ribavirin and 25 patients were treated with Sofosbuvir/Velpatasvir (SOF/VEL). Overall, SVR 12 after treatment was achieved in 90% in patients who received one of the two DAA regimens (89.7% in LDV/SOF group and 92% in SOF/VEL group). SVR 12 did not vary based on age, sex, body mass index, baseline HCV viral load, HCV/HIV coinfection, type of genotype, and prior treatment status. Apart from a low platelet count, there were no other factors associated with a statistical difference in SVR 12(p=0.002) between the two regimens. Fatigue (35%) was the most common adverse effect and no patients discontinued treatment due to adverse effects.

Conclusion: In the community care setting, Sofosbuvir based DAAs are safe, effective with high overall SVR, and well tolerated in patients with CHC patients with compensated liver cirrhosis.

Aim: Nonalcoholic steatohepatitis (NASH) is the consequence of insulin resistance, fatty acid accumulation, oxidative stress, and lipotoxicity. We hypothesize that an increase in the inflammatory adipokine NOV decreases antioxidant Heme Oxygenase 1 (HO-1) levels in adipose and hepatic tissue, resulting in the development of NASH in obese mice.

Methods: Mice were fed a high fat diet (HFD) and obese animals were administered an HO-1 inducer with or without an inhibitor of HO activity to examine levels of adipose-derived NOV and possible links between increased synthesis of inflammatory adipokines and hepatic pathology.

Results: NASH mice displayed decreased HO-1 levels and HO activity, increased levels of hepatic heme, NOV, MMP2, hepcidin, and increased NAS scores and hepatic fibrosis. Increased HO-1 levels are associated with a decrease in NOV, improved hepatic NAS score, ameliorated fibrosis, and increases in mitochondrial integrity and insulin receptor phosphorylation. Adipose tissue function is disrupted in obesity as evidenced by an increase in proinflammatory molecules such as NOV and a decrease in adiponectin. Importantly, increased HO-1 levels are associated with a decrease of NOV, increased adiponectin levels, and increased levels of thermogenic and mitochondrial signaling associated genes in adipose tissue.

Conclusions: These results suggest that the metabolic abnormalities in NASH are driven by decreased levels of hepatic HO-1 that is associated with an increase in the adipose-derived proinflammatory adipokine NOV in our obese mouse model of NASH. Concurrently, induction of HO-1 provides protection against insulin resistance as seen by increased insulin receptor phosphorylation. Pharmacological increases in HO-1 associated with decreases in NOV may offer a potential therapeutic approach in preventing fibrosis, mitochondrial dysfunction, and the development of NASH.

Background: Newer oral anticoagulants (NOACs) are being utilized increasingly for the treatment of venous thromboembolism (VTE). NOAC use is the standard of care for stroke prophylaxis in nonvalvular atrial fibrillation and treatment of acute VTE involving extremities and pulmonary embolism. In contrast, most guidelines in the literature support the treatment of acute portal vein thrombosis (PVT) with low molecular weight heparin (LMWH) and vitamin K antagonists (VKA). Literature evaluating NOAC use in the treatment of acute portal vein thrombosis is sparse. This review focuses on the safety and efficacy of the use of NOACs in the treatment of acute PVT in patients, with or without concomitant cirrhosis, based on the most recent data available in the current literature.

Methods: A systematic review was conducted through a series of advanced searches in the following medical databases: PubMed, BioMed Central, Cochrane, and Google Scholar. Keywords utilized were as follows: NOAC, DOAC (direct oral anticoagulants), portal vein thrombosis, rivaroxaban, apixaban, dabigatran, and edoxaban. Articles related to newer anticoagulant use in patients with portal vein thrombosis were included.

Results: The adverse events, including bleeding events (major and minor) and the failure of anticoagulation (propagation of thrombus or recurrence of PVT), are similar between the NOACs and traditional anticoagulants for the treatment of acute PVT, irrespective of the presence of cirrhosis.

Conclusions: Newer oral anticoagulants are safe and efficacious alternatives to traditional anticoagulation with low molecular weight heparin and vitamin K antagonists in the treatment of acute portal vein thrombosis with or without cirrhosis.

Background: To examine the association between low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels and liver enzyme functions.

Methods: The National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2012 was used to examine the association between liver enzymes and lipid levels amongst adults in the United States.

Results: Sixteen percent adults had ALT > 40 U/L, 11% had AST > 40 U/L, and 96% had ALP > 120 U/L. Age, gender, and race/ethnicity showed significant association with LDL, HDL, and triglycerides levels. LDL greater than borderline high was associated with little over two times higher odds of elevated ALT (OR: 2.33, 95% CI: 2.17, 2.53, p ≤ 0.001) and AST (OR: 2.79, 95% CI: 2.55, 3.06, p ≤ 0.001). High HDL was associated with 50% higher odds for elevated ALT (OR: 1.51, 95% CI: 1.39, 1.64, p ≤ 0.001) and over two-and-half fold elevated AST (OR: 2.77, 95% CI: 2.47, 3.11, p ≤ 0.001). LDL-C, HDL-C, and triglycerides were found to be good predictor of elevated ALT, AST, and ALP levels. Similarly, old age and female gender were significant predictor of elevated ALT and AST (p ≤ 0.001).

Conclusions: Underlying hepatic pathophysiology from dyslipidemia deserves further exploration due to its potential effects on hepatic drug metabolism/detoxification.

Single clove garlic is the product of atypical bulbing process of garlic under specific conditions. Therefore, the number of researches on single clove garlic bioactivity is limited. Recently, the hepatoprotective effect of single clove garlic has been demonstrated. In this study, we investigated amelioration of single clove black garlic aqueous extract, a processed product from single clove garlic, on dyslipidemia and hepatitis induced by chronic administration of CCl₄. Mice were randomly divided into four groups: control, extract control, CCl₄ intoxication, and coadministrated CCl₄ and extract group. Mice were orally given a dose of 1 ml/kg body weight of CCl₄ for 28 days twice a week to establish chronic liver injury model. To evaluate the hepatoprotective effect of single clove black garlic, mice were cotreated with CCl₄ and single clove black garlic extract (200 mg/kg body weight) via gastric gauge for 30 days. Cotreatment with CCl₄ and extract could improve the changes of body weight, liver weight, and relative liver weight as compared to CCl₄ intoxicated mice. Single clove black garlic ameliorated dyslipidemia and the elevation of ALT and AST levels induced by chronic CCl₄ intoxication. Histological studies revealed that single clove black garlic could prevent mononuclear cells infiltration and hepatocyte necrosis.

Objective: Lao PDR is one of the most highly endemic countries for hepatitis B in Asia and the second country for liver cancer incidence. Therefore, the follow-up of infected individuals through predictive serological markers is of utmost importance to monitor the progression of the pathology and take the decision on treatment.

Methods: A retrospective-descriptive cohort study was conducted on 3,857 HBV-infected patients. Information about infection status (viral load, VL), liver function (aminotransferases), and treatments was recorded.

Results: M/F sex ratio was 1.77 for a median age of 37. Patients under 37 displayed higher VL than older ones and men had higher VL than women. Initial VL ranged from <50 IU/mL to 2.5 10¹³ IU/mL. Median aminotransferase values were 45.5 U/L for ALAT and 44 U/L for ASAT, ranging from <8 to >2,000 U/L. Men had higher aminotransferase than women. Globally 20% of patients received treatment (mainly immunostimulant and reverse-transcriptase inhibitors); 11% had high levels of VL and liver enzymes, but only 2% of them were treated.

Conclusion: Public health decisions should be taken urgently to rationalise vaccination and provide fair access to early diagnosis and treatment; otherwise the burden of HBV-associated diseases will be overwhelming for Laos in the near future.

Background and aims: As indicated by the World Health Organization (WHO), Egypt is positioned as the country with the world's highest prevalence of Hepatitis C virus (HCV). HCV is transmitted through unexamined blood transfusions, different employments of syringes, and poor cleansing, as per the WHO. Our study aimed at screening and management of chronic hepatitis C genotype 4 infected patients in Bardeen village, Sharkeya Governorate, Egypt, with Sofosbuvir plus Daclatasvir, as well as estimating the safety and efficacy of that regimen.

Methods: Screening of adult patients in Bardeen village was done from March 2016 till November 2016 using hepatitis C virus antibodies by third-generation ELISA testing. Positive results were confirmed by PCR. Patients eligible for treatment received Sofosbuvir 400 mg and Daclatasvir 60 mg daily for 12 weeks and were assessed for sustained virologic response at 12 weeks following the end of treatment (SVR 12).

Results: Out of 2047 subjects screened for hepatitis C virus, 249 (12.2%) showed positive results. 221 out of those 249 subjects (88.7%) had detectable RNA by PCR. Treatment of eligible patients (183 patients) with Sofosbuvir plus Daclatasvir for 12 weeks resulted in 96% achievement of sustained virologic response at week 12. Adverse events were tolerable.

Conclusion: Sofosbuvir plus Daclatasvir regimen is safe and effective for treatment of chronic hepatitis C Genotype 4 infected patients with minimal adverse events. HCV eradication program implemented in Egypt can be a model for other countries with HCV and limited resources. The availability of generic drugs in Egypt will help much in eradication of the virus.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used medication in several countries, including Thailand. NSAIDs have been associated with hepatic side effects; however, the frequency of these side effects is uncertain.

Aim of the review: To systematically review published literature on randomized, controlled trials that assessed the risk of clinically significant hepatotoxicity associated with NSAIDs.

Methods: Searches of bibliographic databases EMBASE, PubMed, and the Cochrane Library were conducted up to July 30, 2016, to identify randomized controlled trials of ibuprofen, naproxen, diclofenac, piroxicam, meloxicam, mefenamic acid, indomethacin, celecoxib, and etoricoxib in adults with any disease that provide information on hepatotoxicity outcomes.

Results: Among the 698 studies, 18 studies met the selection criteria. However, only 8 studies regarding three NSAIDs (celecoxib, etoricoxib, and diclofenac) demonstrated clinically significant hepatotoxic evidence based on hepatotoxicity justification criteria. Of all the hepatotoxicity events found from the above-mentioned three NSAIDs, diclofenac had the highest proportion, which ranged from 0.015 to 4.3 (×10^-2), followed by celecoxib, which ranged from 0.13 to 0.38 (×10^-2), and etoricoxib, which ranged from 0.005 to 0.930 (×10^-2).

Conclusion: Diclofenac had higher rates of hepatotoxic evidence compared to other NSAIDs. Hepatotoxic evidence is mostly demonstrated as aminotransferase elevation, while liver-related hospitalization or discontinuation was very low.

Background and aims: Psychiatric or substance use disorders are barriers to successful HCV antiviral treatment. In a randomized, controlled trial (RCT), the effects of HCV Integrated Care (IC) for increasing treatment rates and sustained viral response (SVR) were studied with direct acting antivirals (DAA).

Methods: In 2012-13, VA patients, whose screening was positive for depression, PTSD, or substance use (N = 79), were randomized to IC or Usual Care (UC). IC consisted of brief psychological interventions and case management. The primary endpoint was SVR among patients followed for an average of 16.6 months.

Results: 42% of the study participants were previously homeless and 79% had HCV genotype 1. Twice as many IC participants (45%) initiated treatment compared with UC participants (23%) (χ² = 4.59, p = 0.032). Among those treated, SVR rates did not significantly differ (IC: 12/18 = 67%; UC: 5/9 = 55%; p = 0.23). Among all randomized participants, IC participants trended toward better SVR rates (30.0% versus 12.8% in UC; p = 0.07).

Conclusions: Although first-generation DAAs are no longer used, this smaller RCT helps confirm the results of a larger multisite RCT showing that Integrated Care results in higher treatment initiation and SVR rates among HCV-infected persons with comorbid psychological disorders. Integrated mental health services can facilitate treatment among the most challenging HCV patients, many of whom have not been successfully treated. This trial is registered with ClinicalTrials.gov number NCT00722423.

Background. Although the advantages of laparoscopic cholecystectomy (LC) over open cholecystectomy are immediately obvious and appreciated, several patients need a postoperative hospital stay of more than 24 hours. Thus, the predictive factors for this longer stay need to be investigated. The aim of this study was to identify the causes of a long hospital stay after LC. Methods. This is a retrospective cohort study with 500 successful elective LC patients being included in the analysis. Short hospital stay was defined as being discharged within 24 hours after the operation, whereas long hospital stay was defined as the need for a stay of more than 24 hours after the operation. Results. Using multivariable analysis, ten independent predictive factors were identified for a long hospital stay. These included patients with cirrhosis, patients with a history of previous acute cholecystitis, cholangitis, or pancreatitis, patients on anticoagulation with warfarin, patients with standard-pressure pneumoperitoneum, patients who had been given metoclopramide as an intraoperative antiemetic drug, patients who had been using abdominal drain, patients who had numeric rating scale for pain > 3, patients with an oral analgesia requirement > 2 doses, complications, and private ward admission. Conclusions. LC difficulties were important predictive factors for a long hospital stay, as well as medication and operative factors.