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Background: Cardiovascular disease and especially hypertension are a growing problem among people living with HIV (PLHIV) on antiretroviral therapy (ART) in sub-Saharan Africa. Objectives: As robust data on hypertension phenotypes associated with distinct cardiovascular risks among PLHIV are limited, we aimed to assess the frequency of white-coat (WCH), masked (MH) hypertension, and blood pressure dipping-patterns in a group of Malawian PLHIV. Methods: As part of the prospective Lighthouse-Tenofovir-Cohort-Study, we analyzed clinical, laboratory and 24-h-ambulatory blood pressure monitoring (ABPM) data of PLHIV from urban Lilongwe with treated or untreated hypertension or raised office blood pressure (OBP) during routine study-visits. Results: 118 PLHIV were included and data of 117 participants could be analyzed. Twenty-four-hour ABPM normotension was found in a total of 73 PLHIV including 14/37 on antihypertensive treatment (37.8%). Using strict definitions, i.e. normal OBP plus normal mean BP for all periods of ABPM, controlled hypertension was found in only 4/37 (10.8%) PLHIV on antihypertensive treatment while true normotension was observed in 10/24 untreated patients (41.7%) with previously diagnosed hypertension and 22/56 patients (39.3%) without a medical history of hypertension. WCH with normal BP during all periods of 24-h-ABPM was identified in 12/64 OBP-hypertensive PLHIV (18.8%), primarily in patients with grade 1 hypertension (11/41 patients; 26.8%). MH was found in 17/53 PLHIV with OBP-normotension (32.1%), predominantly in patients with high normal BP (11/20 patients; 55%). The estimated glomerular filtration rate tended to be lower in MH compared to strictly defined normotensive PLHIV (92.0 +/- 20.4 vs. 104.8 +/- 15.7 ml/min/m(2)). 64.1 percent of PLHIV (59.5% with 24-h hypertension and 66.7% with 24-h normotension) had abnormal systolic dipping. Conclusion: The high prevalence of WCH and MH with signs of early renal end-organ damage and an abnormal

Maternal obesity is associated with an increased risk of hepatic metabolic dysfunction for both mother and offspring and targeted interventions to address this growing metabolic disease burden are urgently needed. This study investigates whether maternal exercise (ME) could reverse the detrimental effects of hepatic metabolic dysfunction in obese dams and their offspring while focusing on the AMP-activated protein kinase (AMPK), representing a key regulator of hepatic metabolism. In a mouse model of maternal western-style-diet (WSD)-induced obesity, we established an exercise intervention of voluntary wheel-running before and during pregnancy and analyzed its effects on hepatic energy metabolism during developmental organ programming. ME prevented WSD-induced hepatic steatosis in obese dams by alterations of key hepatic metabolic processes, including activation of hepatic ss-oxidation and inhibition of lipogenesis following increased AMPK and peroxisome-proliferator-activated-receptor-gamma-coactivator-1 alpha (PGC-1 alpha)-signaling. Offspring of exercised dams exhibited a comparable hepatic metabolic signature to their mothers with increased AMPK-PGC1 alpha-activity and beneficial changes in hepatic lipid metabolism and were protected from WSD-induced adipose tissue accumulation and hepatic steatosis in later life. In conclusion, this study demonstrates that ME provides a promising strategy to improve the metabolic health of both obese mothers and their offspring and highlights AMPK as a potential metabolic target for therapeutic interventions.

Overconsumption of carbohydrates and lipids are well known to cause nonalcoholic fatty liver disease (NAFLD), while the role of nutritional protein intake is less clear. In Western diet, meat and other animal products are the main protein source, with varying concentrations of specific amino acids. Whether the amount or composition of protein intake is associated with a higher risk for disease severity has not yet been examined. In this study, we investigated associations of dietary components with histological disease activity by analyzing detailed 14-day food records in a cohort of 61 patients with biopsy-proven NAFLD. Furthermore, we used 16S ribosomal RNA gene sequencing to detect associations with different abundances of the gut microbiota with dietary patterns. Patients with definite nonalcoholic steatohepatitis (NAFLD activity score of 5-8 on liver biopsy) had a significantly higher daily relative intake of protein compared with patients with a NAFLD activity score of 0-4 (18.0% vs. 15.8% of daily protein-based calories, P = 0.018). After adjustment for several potentially confounding factors, a higher protein intake (>= 17.3% of daily protein-based calories) remained associated with definite nonalcoholic steatohepatitis, with an odds ratio of 5.09 (95% confidence interval 1.22-21.25, P = 0.026). This association was driven primarily by serine, glycine, arginine, proline, phenylalanine, and methionine. A higher protein intake correlated with a lower Bacteroides abundance and an altered abundance of several other bacterial taxa. Conclusion: A high protein intake was independently associated with more active and severe histological disease activity in patients with NAFLD. Further studies are needed to investigate the potential harmful role of dietary amino acids on NAFLD, with special attention to meat as their major source.

Background and Aim Several studies observed alterations in the gut microbiota in patients with non-alcoholic fatty liver disease (NAFLD). However, analyzed patient populations and methods strongly differ among these studies. The aim of this study was to prove the reproducibility of published results and to provide a detailed overview of all findings in our NAFLD cohort using next generation sequencing methods. Methods The individual taxonomic microbiota composition of fecal samples from 90 NAFLD patients and 21 healthy controls was analyzed using 16S rRNA gene sequencing. Study participants were grouped according to their disease stage and compared regarding their gut microbiota composition. Studies were identified from PubMed listed publications, and the results were compared with the findings in our cohort. Results Results from 13 identified studies were compared with our data. A decreased abundance of the Bacteroidetes and Ruminococcaceae as well as an increased abundance of Lactobacillaceae and Veillonellaceae and Dorea were the most frequently reported changes among NAFLD patients in 4/13, 5/13, 4/13, 2/13, and 3/13 studies, respectively. Even though these alterations in the gut microbiota composition were also observed in our patient cohort, the majority of published differences could not be reproduced, neither in our own nor in other NAFLD cohort studies. Conclusion Despite repeatedly reproduced abundance patterns of specific bacteria, the heterogeneous study results did not reveal a consistent disease specific gut microbiota signature. Further prospective studies with homogenous patient cohorts and standardized methods are necessary to phenotype NAFLD by the gut microbiota.

Cardiogenic shock is a life-threatening condition that is frequently associated with acute hepatic dysfunction. Due to low cardiac output resulting in end-organ hypoperfusion and hypoxia, different types of liver dysfunction can develop, such as hypoxic hepatitis or acute liver failure. A very serious and late sequela is the secondary sclerosing cholangitis in critically patients. Clinical management of acute hepatic dysfunction involves the stabilization of cardiac output to improve hepatic perfusion and the optimization of liver oxygenation. However, despite maximum efforts in supportive treatment, the outcome of patients with cardiogenic shock and concomitant hepatic dysfunction remains poor.

Background and aims:Adenoma detection rate (ADR) is a key quality indicator for colonoscopy; however, it is cumbersome to obtain. We investigated if detection rates (DRs) for adenomas, serrated polyps (SPs) and clinically relevant SP (crSPDR) can be accurately estimated by individualized DR ratios (DRRs) in a multicenter primary colonoscopy screening cohort of average-risk individuals. Methods:DRRs were calculated by dividing DRs for a certain polyp entity by polyp detection rate (PDR) for each endoscopist individually on the basis of his/her first 50 (DRR50) and 100 (DRR100) consecutive colonoscopies. DRs were estimated for each endoscopist by multiplying his/her DRR for a certain polyp entity with his/her PDR of subsequent colonoscopies in groups of 50 (DRR50) and 100 (DRR100) consecutive colonoscopies. Estimated and actual DRs were compared. Results:Estimated DRs showed a strong correlation with actual DRs for adenomas (r = 0.86 and 0.87; eachp< .001), SPs (r = 0.85 and 0.91; eachp< .001) and crSPs (r = 0.82 and 0.86; eachp< .001) using DRRs derived from first 50 and 100 consecutive colonoscopies. Corresponding root mean square error (RMSE) between individual estimated and actual DRs using DRR(50)and DRR(100)was 5.3(+/- 4.6)% and 4.5(+/- 4.8)% for adenomas, 5.2(+/- 4.1)% and 3.9(+/- 2.8)% for SP, 3.1(+/- 3.1)% and 2.8(+/- 2.5)% for crSP, respectively. RMSE was not significantly different between DRR(50)and DRR(100)for ADR (p= .445), SPDR (p= .178) and crSP (p= .544). Conclusions:DR for all relevant polyp entities can be accurately estimated by using individual DRRs. This approach may enable endoscopists to easily track their performance measures in daily routine.

Sepsis represents a life-threatening condition that frequently accompanies acute hepatic dysfunction. As a result of systemic inflammation, immune dysregulation, and microcirculatory derangements, different types of liver dysfunction can occur, such as hypoxic hepatitis, sepsis-associated cholestasis, or liver failure. A very serious and late sequela is secondary sclerosing cholangitis of the critically ill patient. Clinical management of sepsis-related liver dysfunction includes the rapid identification and treatment of the suspected underlying infection, hemodynamic stabilization to improve hepatic perfusion, and the optimization of oxygen delivery to the liver. Despite maximum efforts in supportive treatment, the outcome of patients with sepsis or septic shock and concomitant severe hepatic dysfunction remains very poor.

BACKGROUND & AIMS: Alterations in the gut microbiome have been associated with the severity of nonalcoholic fatty liver disease (NAFLD). Previous studies focused exclusively on the bacteria in the microbiome; we investigated changes in the viral microbiome (virome) in patients with NAFLD. METHODS: In a prospective, cross-sectional, observational study, we extracted RNA and DNA virus-like particles from fecal samples from 73 patients with NAFLD: 29 patients had an NAFLD Activity Score (NAS) of 0-4, 44 patients had an NAS of 5-8 or liver cirrhosis (LCI), 37 patients had F0-F1 fibrosis, and 36 patients had F2-F4 fibrosis. As controls, 9 individuals without liver disease and 13 patients with mild primary biliary cholangitis were included in the analysis. We performed shotgun metagenomic sequencing of virus-like particles. RESULTS: Patients with NAFLD and NAS 5-8/LCI had a significant decrease in intestinal viral diversity compared with patients with NAFLD and NAS 0-4 or control individuals. The presence of more advanced NAFLD was associated with a significant reduction in the proportion of bacteriophages compared with other intestinal viruses. Using multivariate logistic regression analysis with leave-1-out cross validation, we developed a model, including a viral diversity index and simple clinical variables, that identified patients with NAS 5-8/LCI with an area under the curve of 0.95 (95% confidence interval, 0.91-0.99) and F2-F4 fibrosis with an area under the curve of 0.88 (95% confidence interval, 0.80-0.95). Addition of data on viral diversity significantly improved multivariate models, including those based on only clinical parameters or bacterial diversity. CONCLUSIONS: In a study of fecal viromes from patients with NAFLD and control individuals, we associated histologic markers of NAFLD severity with significant decreases in viral diversity and proportion of bacteriophages. We developed a model based on fecal viral diversity and clinical data that identifies

Objective: International guidelines recommend hepatocellular carcinoma (HCC) surveillance with ultrasound in high-risk patients with chronic liver diseases. However, there is low-strength evidence about the effects on mortality. The aim of our study was to assess the impact of surveillance on the clinical course and survival of HCC patients seen at a tertiary referral center in Germany. Material and methods: We retrospectively evaluated the data of 401 HCC patients, who presented to our clinic between 1997 and 2015. Two groups were compared regarding patient and disease outcomes: one group included patients who received at least two ultrasound examinations for surveillance purposes prior to first diagnosis (n = 111). The other group consisted of patients with HCC at first presentation without foregoing HCC surveillance (n = 290). Results: Median follow-up in the surveillance group was 76 months (range 4-310 months). Patients in the surveillance group had smaller median tumor sizes (3.5 cm vs. 4.5 cm; p < .001), fulfilled more often Milan criteria (64% vs. 42%; p < .001) and received more often liver transplantation (27% vs. 9%, p < .001) when compared with the non-surveillance group. However, HCC surveillance was not associated with an improved survival (14 months in the surveillance group vs. 12 months in the non-surveillance group, p = .375), hazard ratio regarding overall mortality for the surveillance group: 0.80 (95% CI: 0.62-1.04, p = .09). Conclusions: HCC surveillance with ultrasound led to the detection of earlier disease stages but was not significantly associated with improved survival. Further prospective and long-term studies are needed to clarify benefits and harms of HCC surveillance programs on mortality.

Background and Aim: Several studies observed alterations in the gut microbiota in patients with non‐alcoholic fatty liver disease (NAFLD). However, analyzed patient populations and methods strongly differ among these studies. The aim of this study was to prove the reproducibility of published results and to provide a detailed overview of all findings in our NAFLD cohort using next generation sequencing methods. Methods: The individual taxonomic microbiota composition of fecal samples from 90 NAFLD patients and 21 healthy controls was analyzed using 16S rRNA gene sequencing. Study participants were grouped according to their disease stage and compared regarding their gut microbiota composition. Studies were identified from PubMed listed publications, and the results were compared with the findings in our cohort. Results: Results from 13 identified studies were compared with our data. A decreased abundance of the Bacteroidetes and Ruminococcaceae as well as an increased abundance of Lactobacillaceae and Veillonellaceae and Dorea were the most frequently reported changes among NAFLD patients in 4/13, 5/13, 4/13, 2/13, and 3/13 studies, respectively. Even though these alterations in the gut microbiota composition were also observed in our patient cohort, the majority of published differences could not be reproduced, neither in our own nor in other NAFLD cohort studies. Conclusion: Despite repeatedly reproduced abundance patterns of specific bacteria, the heterogeneous study results did not reveal a consistent disease specific gut microbiota signature. Further prospective studies with homogenous patient cohorts and standardized methods are necessary to phenotype NAFLD by the gut microbiota.

BackgroundCronkhite-Canada syndrome is a rare disease of unknown etiology and the optimal treatment for this syndrome is unknown.Case presentationWe present the case of a man who at the age of 66.0years was diagnosed with Cronkhite-Canada syndrome (CCS). In addition to watery diarrhea, alopecia, and a complete loss of toenails and fingernails, the patient had been suffering from dysgeusia and rapid weight loss of more than 10.0kg within a few months. The patient had recently incurred a distal radius fracture. During the initial endoscopy an extensive polyposis of the stomach and jejunum was found. The diagnosis of CCS was made and after initiation of a steroid therapy his diarrhea improved immediately. A discontinuation of the steroid therapy was not possible and mesalazine (1000mgt.i.d.) was added to prednisolone (10.0mg/d). This therapy led to a remission within 6.0months with weight gain and normalization of serum albumin levels. The prednisolone dose was reduced to 7.5mg/d. During the following year, the steroids could be further reduced and nails had regrown again. Within three years, all polyps had disappeared and the steroid therapy was finished while the dosage of mesalazine was reduced in a stepwise fashion. Four years later, the mesalazine was stopped and more than 14.0years after the initial diagnosis the patient is still in complete remission without any treatment.ConclusionThe optimal treatment for CCS is unknown. In our case, the initial combination therapy of corticosteroids plus mesalazine followed by a mesalazine monotherapy has led to a remarkable long-lasting remission with complete resolution of all intestinal polyps.

Cardiogenic shock is a life-threatening condition that is frequently associated with acute hepatic dysfunction. Due to low cardiac output resulting in end-organ hypoperfusion and hypoxia, different types of liver dysfunction can develop, such as hypoxic hepatitis or acute liver failure. A very serious and late sequela is the secondary sclerosing cholangitis in critically patients. Clinical management of acute hepatic dysfunction involves the stabilization of cardiac output to improve hepatic perfusion and the optimization of liver oxygenation. However, despite maximum efforts in supportive treatment, the outcome of patients with cardiogenic shock and concomitant hepatic dysfunction remains poor.

Cardiovascular diseases such as arterial hypertension contribute substantially to morbidity and mortality in sub-Saharan Africa. 24-hour ambulatory blood pressure monitoring (24-h-ABPM) is the most accurate method for confirming a diagnosis of hypertension. As part of the ongoing prospective LighTen Cohort Study we sought to determine the feasibility of 24-h-ABPM in HIV+-patients on antiretroviral therapy and its role in diagnosing and managing hypertension. Office blood pressure values and 24-h-ABPM data of 34 adult HIV+-patients and 20 HIV--controls were analyzed. Despite taking antihypertensive medication, blood pressure was controlled in only one fourth of patients and controls. 24-h-ABPM turned out to be feasible in resource-limited settings like Malawi. It allowed the identification of patients with unfavourable cardiovascular prognosis due to disturbed nocturnal blood pressure dipping as well as patients with white-coat hypertension and probably low cardiovascular risk.

Background: In a previous publication, a FIB-4 cutoff value of >= 1.25, which had been determined in an Asian population, did not allow reliable prediction of the development of hepatocellular carcinoma (HCC) in a patient collective with chronic hepatitis B (CHB) of predominantly non-Asian descent. Objectives: Here, we aimed to validate the modified FIB-4 cutoff values as a means of stratifying the HCC risk in a non-Asian cohort seen at an outpatient university hospital liver unit in Germany. Methods: We retrospectively analyzed 350 adult patients with CHB infection. We recorded demographics, laboratory parameters, results from liver imaging, serological hepatitis B markers, antiviral treatment, and histology. We separated patients into two groups based on individual FIB-4 levels. We, then, analyzed the patients' hazard ratios for HCC and adjusted it for sex, age, antiviral medication, duration of CHB infection, body mass index, alcohol consumption, and type 2 diabetes. An additional sub-analysis was performed by including only non-cirrhotic patients to determine the validity of the proposed cutoffs in that cohort. Results: The median duration of follow-up was 8.9 years with a range of 1- 21.3 years. Our patients were 65% males. In comparison with patients that had a low FIB-4 (< 0.3635), those with elevated FIB-4 (>= 0.3635) had an HCC incidence hazard ratio of 11.67 (95% confidence interval (CI): 2.73 - 49.96; P = 0.001) and an adjusted hazard ratio of 7.90 (95% CI: 1.58 - 39.39; P = 0.012). Elevated FIB-4 non-cirrhotic patients had a hazard ratio (HR) of 15.88 (95% CI: 2.04 - 123.20) for HCC incidence (P < 0.0001) and an adjusted HR of 11.99 (95% CI:1.36 -105.72) (P = 0.001). Conclusions: A FIB-4 value of < 0.3635 appears to be a clinical indicator for a low likelihood of HCC incidence in non-Asian patients with CHB with or without cirrhosis. Further studies in patients of diverse descent are necessary to prove its utility as a clinical tool in this setting.