Relative information from thermal infrared imagery via unoccupied aerial vehicle informs simulations and spatially-distributed assessments of stream temperature.

Stream temperature is a measure of water quality that reflects the balance of atmospheric heat exchange at the air-water interface and gains or losses of water along a stream reach. In urban areas, stormwater sewers deliver water with varying magnitude and temperature to streams at variable timescales. Understanding the impacts of stormwater through space and time is therefore difficult to do with conventional approaches like in situ sensors. To study the impacts of stormwater on creek water temperatures, we combined in situ water temperature observations with thermal infrared (TIR) imagery collected via unoccupied aerial vehicle (UAV). Imagery was collected in May, June, and July of 2017. As ongoing work with UAV-based TIR suggests that this imagery is prone to poor accuracy, we focused on creating several data products beyond absolute water temperatures that can be used to assess temporal and spatial water temperature variations. In particular, TIR data products were used to extract the length of the observed stormwater plume as well as the width of the creek cross-section impacted by stormwater. From these values, we conclude that relatively narrow stormwater plumes affecting a small fraction of creek width can alter creek water temperatures for considerable distances downstream. We also applied TIR data to constrain results of a deterministic stream temperature model (HFLUX 3.0) that simulates the physical processes affecting stream heat exchanges. Stormwater plume lengths obtained from TIR imagery were used to refine spatially-distributed simulations, demonstrating that relative temperature information obtained from UAV imagery can provide useful calibration targets for stream temperature models. Overall, our work demonstrates the added value of UAV datasets for understanding urban stream temperatures, calibrating water quality models, and for modeling and monitoring of the impact of spatially explicit hydrologic processes on stream temperature.

Physical deconditioning is the common denominator in both obese and overweight subjects with nonalcoholic steatohepatitis.

BACKGROUND: Obesity and decreased physical activity mirror increasing prevalence of nonalcoholic fatty liver disease (NAFLD). AIM: We aimed to investigate associations between aerobic fitness, anthropometrics and disease parameters in patients with nonalcoholic steatohepatitis (NASH). We hypothesised that NASH subjects have lower aerobic power and capacity than untrained, sedentary, normal subjects. METHODS: Forty subjects (60% obese, 40% overweight) with biopsy-confirmed NASH and NAFLD activity score (NAS) ≥4 were enrolled in a clinical trial where anthropometrics, laboratories, liver fat content by MRI, activity, and aerobic fitness by cycle ergometry data were obtained. RESULTS: NASH subjects were significantly deconditioned compared to 148 untrained, sedentary, healthy subjects from our laboratory in aerobic power (VO2peak) (NASH 16.8 ± 6.6 vs control 28.4 ± 10.6 mL/kg/min, P < 0.0001) and capacity (VO2 at lactate threshold [LT]) (NASH 8.3 ± 2.5 vs control 14.1 ± 5.9 mL/kg/min, P < 0.0001). NASH subjects' fitness was comparable to the "least fit" tertile of controls: VO2peak [NASH 16.8 ± 6.6 vs "least fit" 17.3 ± 3.3, P = 0.64]) and VO2 at LT (NASH 8.3 ± 2.5 vs "least fit" 9.3 ± 2.1, P = 0.31). Fitness was similar in obese compared to overweight subjects (adjusted for gender) and was not correlated with visceral adiposity or NAS. Engaging in dedicated cardiovascular activity correlated with higher VO2peak and VO2peak at LT. CONCLUSIONS: Aerobic deconditioning was universally present in NASH subjects. NASH subjects' fitness was similar to our laboratory's "least fit" untrained, sedentary control subjects. Further research investigating NASH patients' ability to improve low baseline aerobic fitness is warranted.

Direct Oral Anticoagulants in Cirrhosis Patients Pose Similar Risks of Bleeding When Compared to Traditional Anticoagulation.

BACKGROUND AND AIMS: Direct oral anticoagulants (DOAC) are important new anticoagulant therapies that are not well studied in patients with chronic liver disease. The aim of this study was to compare rates of bleeding in cirrhosis patients treated with DOAC (factor Xa inhibitors: rivaroxaban and apixaban) to those in cirrhosis patients treated with traditional anticoagulation (warfarin and low molecular weight heparin). METHODS: We identified a total of 39 patients with cirrhosis who received anticoagulation therapy over a 3-year period (20 DOAC and 19 traditional anticoagulation) from a research database. Medical records were reviewed to obtain clinical data to compare between the groups. RESULTS: Clinical characteristics between the two groups were similar. There were three documented bleeding events in the traditional anticoagulation group and four bleeding events in the DOAC group (p = 0.9). There were two major bleeding events in the traditional anticoagulation group and one major bleeding event in the DOAC group. There were no documented reports of drug-induced liver injury during this study period. Among all patients, no significant predictors of bleeding were identified using univariate regression and Cox proportional hazard modeling. CONCLUSIONS: This is the first clinical study evaluating the use of DOAC in patients with cirrhosis. DOAC display similar safety characteristics when compared to traditional anticoagulation in patients with cirrhosis and are potentially attractive agents for anticoagulation therapy. Larger studies are now needed to better understand the safety and efficacy of these agents in cirrhosis.

The International Normalized Ratio (INR) in the MELD score: problems and solutions.

The Model for End-Stage Liver Disease (MELD) score is widely used to prioritize patients for liver transplantation. One of the pitfalls of the MELD score is the interlaboratory variability in all three components of the score (INR, bilirubin, creatinine). The interlaboratory variability in the INR has the largest impact on the MELD score, with a mean difference of around 5 MELD points in most studies. During the 3rd conference on Coagulopathy and Liver disease, a multidisciplinary group of scientists and physicians discussed possible solutions for the INR problem in the MELD score with the intention to provide a constructive contribution to the international debate on this issue. Here we will discuss possible solutions and highlight advantages and disadvantages.

Does hepatocellular carcinoma in non-alcoholic steatohepatitis exist in cirrhotic and non-cirrhotic patients?

Non-alcoholic steatohepatitis (NASH) has been associated with hepatocellular carcinoma (HCC) often arising in histologically advanced disease when steatohepatitis is not active (cryptogenic cirrhosis). Our objective was to characterize patients with HCC and active, histologically defined steatohepatitis. Among 394 patients with HCC detected by ultrasound imaging over 8 years and staged by the Barcelona Clinic Liver Cancer (BCLC) criteria, we identified 7 cases (1.7 percent) with HCC occurring in the setting of active biopsy-proven NASH. All were negative for other liver diseases such as hepatitis C, hepatitis B, autoimmune hepatitis, Wilson disease, and hemochromatosis. The patients (4 males and 3 females, age 63 ± 13 years) were either overweight (4) or obese (3); 57 percent were diabetic and 28.5 percent had dyslipidemia. Cirrhosis was present in 6 of 7 patients, but 1 patient had well-differentiated HCC in the setting of NASH without cirrhosis (fibrosis stage 1) based on repeated liver biopsies, the absence of portal hypertension by clinical and radiographic evaluations and by direct surgical inspection. Among the cirrhotic patients, 71.4 percent were clinically staged as Child A and 14.2 percent as Child B. Tumor size ranged from 1.0 to 5.2 cm and 5 of 7 patients were classified as early stage; 46 percent of all nodules were hyper-echoic and 57 percent were <3 cm. HCC was well differentiated in 1/6 and moderately differentiated in 5/6. Alpha-fetoprotein was <100 ng/mL in all patients. HCC in patients with active steatohepatitis is often multifocal, may precede clinically advanced disease and occurs without diagnostic levels of alpha-fetoprotein. Importantly, HCC may occur in NASH in the absence of cirrhosis. More aggressive screening of NASH patients may be warranted.

Does hepatocellular carcinoma in non-alcoholic steatohepatitis exist in cirrhotic and non-cirrhotic patients?

Non-alcoholic steatohepatitis (NASH) has been associated with hepatocellular carcinoma (HCC) often arising in histologically advanced disease when steatohepatitis is not active (cryptogenic cirrhosis). Our objective was to characterize patients with HCC and active, histologically defined steatohepatitis. Among 394 patients with HCC detected by ultrasound imaging over 8 years and staged by the Barcelona Clinic Liver Cancer (BCLC) criteria, we identified 7 cases (1.7%) with HCC occurring in the setting of active biopsy-proven NASH. All were negative for other liver diseases such as hepatitis C, hepatitis B, autoimmune hepatitis, Wilson disease, and hemochromatosis. The patients (4 males and 3 females, age 63 +/- 13 years) were either overweight (4) or obese (3); 57% were diabetic and 28.5% had dyslipidemia. Cirrhosis was present in 6 of 7 patients, but 1 patient had well-differentiated HCC in the setting of NASH without cirrhosis (fibrosis stage 1) based on repeated liver biopsies, the absence of portal hypertension by clinical and radiographic evaluations and by direct surgical inspection. Among the cirrhotic patients, 71.4% were clinically staged as Child A and 14.2% as Child B. Tumor size ranged from 1.0 to 5.2 cm and 5 of 7 patients were classified as early stage; 46% of all nodules were hyper-echoic and 57% were <3 cm. HCC was well differentiated in 1/6 and moderately differentiated in 5/6. Alpha-fetoprotein was <100 ng/mL in all patients. HCC in patients with active steatohepatitis is often multifocal, may precede clinically advanced disease and occurs without diagnostic levels of alpha-fetoprotein. Importantly, HCC may occur in NASH in the absence of cirrhosis. More aggressive screening of NASH patients may be warranted.

Hypercoagulation and thrombophilia in liver disease.

A complex balance exists between endogenous procoagulants and the anticoagulant system in liver disease patients. Hypercoagulable events occur in cirrhosis patients despite the well-known bleeding diathesis of liver disease. These events may be clinically evident, such as in portal vein thrombosis or pulmonary embolism, but these conditions may also be a silent contributor to certain disease states, such as portopulmonary hypertension or parenchymal extinction with liver atrophy as well as thrombosis of extracorporeal circuits in dialysis or liver assist devices. Moreover, liver disease-related hypercoagulability may contribute to vascular disease in the increasingly common condition of non-alcoholic fatty liver disease. Despite the incidence of these problems, there are few widely accessible and practical laboratory tests to evaluate the risk of a hypercoagulable event in cirrhosis patients. Furthermore, there is little research on the use of commonly accepted anticoagulants in patients with liver disease. This article is a result of an international symposium on coagulation disorders in liver disease and addresses several areas of specific interest in hypercoagulation in liver disease. Critical areas lacking clinical information are highlighted and future areas of research interest are defined with an aim to foster clinical research in this field.

Review article: the prothrombin time test as a measure of bleeding risk and prognosis in liver disease.

BACKGROUND: Prothrombin time (PT)-derived international normalized ratio (INR) is used to assess bleeding risk and prognosis in cirrhosis, and to guide management of associated coagulation disturbances. Recent studies cast doubt on the validity of the assumptions that form the basis for these applications. AIMS: To review and critique the use of the PT-INR in cirrhosis. METHODS: Search of the literature. RESULTS: In cirrhosis, there is a decrease in both pro- and anti-coagulants. The PT-INR measures only the activity of procoagulants and fails to capture changes in anticoagulants. It is therefore not surprising that the PT does not predict the bleeding risk. The PT-INR provides a robust measure of liver function but recent data showed INR inter-laboratory variability in this setting. This is not surprising as the INR was validated to normalize results for patients on vitamin-K antagonists, not for cirrhosis. This limitation was not appreciated, but the INR is used to construct the model for end-stage liver disease score to prioritize patients for liver transplantation. Reports showed that model for end-stage liver disease is modified by the thromboplastin used for testing. CONCLUSIONS: Alternate tests to predict bleeding risk should be developed. The potential for misuse of the PT-INR should drive the development of alternate algorithms for organ allocation.

Enbucrilate for gastric varices: extended experience in 92 patients.

AIM: We assessed N-2-butyl-cyanoacrylate (enbucrilate) in 92 patients with gastric variceal bleeding under an FDA-approved investigation. These results extend our prior report of the first 44 patients. METHOD: Injection was performed with enbucrilate and ethiodol (1:1). Eighty patients had portal hypertension and 12 had splenic vein thrombosis. RESULTS: In the portal hypertensive group, re-bleeding from gastric varices was seen in 4 of 80 (5%) from 0 to 72 h, 5 of 76 (6.5%) from > 72 h to 3 months and 9 of 51 (17%) from > 3 months to 1 year. Re-bleeding and survival were significantly related to the Child-Pugh class. In the splenic vein thrombosis group (n = 12), there was early rebleeding in 2 (17%) patients from 0 to 72 h, 1 (8%) from > 72 h to 3 months and none in the chronic phase (> 3 months to 1 year) although 1-year survival in this group was only 6 (50%) due to the underlying malignancy in most. Serious embolization was suspected in 2 patients (2%). CONCLUSION: Enbucrilate offers an important intervention in gastric variceal bleeding which should be further studied in the US. A randomized trial is warranted to compare this intervention to radiological therapy.

Myositis, microvesicular hepatitis, and progression to cirrhosis from troglitazone added to simvastatin.

A 68-year-old woman, with type 2 diabetes mellitus, hypercholesterolemia, and prior long-term simvastatin therapy, self-resumed troglitazone after running out of metformin. She developed an acute severe hepatitis with microvesicular steatosis and mysositis. There was subsequent resolution of the myositis but progression of the hepatitis to symptomatic cirrhosis over a period of 12 weeks. Both troglitazone and simvastatin are metabolized by cytochrome P-450 3A4. Troglitazone typically induces metabolism of drugs metabolized by this cytochrome so that simple simvastatin toxicity seems less likely to have been involved. The association with myositis, the severity of the hepatitis with progression to cirrhosis, and the presence of microvesicular steatosis suggests altered mitochondrial metabolism, which has been described with each agent, as the underlying pathogenic mechanism. Although troglitazone (Rezulin) has been withdrawn from the market, other similar agents are available for therapy of type 2 diabetes mellitus. Increased awareness of a potential interaction between these two classes of drugs is warranted.

A pilot study of a thiazolidinedione, troglitazone, in nonalcoholic steatohepatitis.

OBJECTIVES: Troglitazone is a thiazolidinedione and peroxisome proliferator-activated receptor gamma (PPARgamma) ligand used to treat diabetes mellitus type II. Because hyperinsulinemia may be a factor in nonalcoholic steatohepatitis (NASH), we postulated that troglitazone could have beneficial effects in this disorder. Our study was initiated before reports of idiosyncratic hepatitis induced by this agent and was completed before its recent withdrawal from the market. METHODS: We studied 10 female patients (age 44 +/- 16) with histological NASH. All but two were obese (mean body mass index, BMI = 38 +/- 6). One had type 2 diabetes, and three had well-compensated cirrhosis with NASH. Troglitazone was given at a dose of 400 mg/day for < or = 6 months. Responders (defined as normal ALT at the end of treatment) were rebiopsied. Paired specimens were compared in blinded fashion. Mitochondria were quantitated using ultrathin electron microscopy. RESULTS: Seven of ten patients responded with normal ALT at the end of treatment. One of three nonresponders initially normalized ALT but returned to pretreatment level at 3 months. In this patient, therapy was stopped, and the ALT has remained at the baseline level with no other clinical or laboratory findings. In the responders, ALT fell from 87 +/- 38 before to 39 +/- 9 at the end of treatment (p = 0.01), and AST decreased from 77 +/- 23 to 30 +/- 8 (p = 0.002). Biopsy comparisons before and after therapy showed persistent steatohepatitis in all cases, although four of seven showed a one-point improvement in the necroinflammatory grade. Electron microscopy revealed elongation of the mitochondria after therapy. CONCLUSIONS: Normal ALT was seen in 70% of NASH patients at the end of treatment, but this biochemical response was associated with only mild histological improvement, and all follow-up biopsies had evidence of NASH. Normalization of the liver enzymes in patients with NASH who are treated with thiazolidinediones should be viewed with reservation. Follow-up biopsy is essential to evaluate the efficacy of these agents, which, at the histological level, appears to be relatively modest.

Imaging and clinical characteristics of focal atrophy of segments 2 and 3 in primary sclerosing cholangitis.

BACKGROUND AND AIMS: Focal atrophy in primary sclerosing cholangitis (PSC) is usually thought to result from severe biliary stricture and focal biliary cirrhosis. Atrophy of the left lateral segments (segments 2 and 3) are striking when observed grossly. This type of atrophy may be subtle on cross-sectional imaging and by endoscopic retrograde cholangiopancreatography (ERCP) because of the peripheral location and compensatory hypertrophy of other parts of the liver. We examined 44 consecutive PSC patients to determine the incidence and clinical characteristics of this abnormality, and to correlate imaging studies with the gross appearance. METHODS: We reviewed all cases of PSC encountered over a 3 year period ascertained from the liver disease registry. Magnetic resonance imaging or CT images were re-examined for evidence of segment 2 and 3 atrophy. RESULTS: Four of 44 patients had focal segment 2 and 3 atrophy. These four had been confirmed laparoscopically or by inspection of the liver explant. The remaining segments of the liver were relatively spared of injury in two of the patients, and three of the four patients had preserved synthetic function without evidence of portal hypertension. While the abnormality is clearly visible on cross-sectional imaging, its peripheral location caused it to be an unobtrusive. Likewise, ERCP did not clearly reveal the abnormality on initial inspection. CONCLUSIONS: We conclude that focal atrophy of segments 2 and 3 is a sometimes early and subtle finding in PSC that may be overlooked in cross-sectional imaging or ERCP unless specifically sought.