Improvement of quantitative testing of liver function in patients with chronic hepatitis C after installment of antiviral therapy

MM： To investigate if and to what extent antiviral therapy influenced a broad panel of quantitative testing of liver function （QTLF）. METHODS： Fifty patients with chronic hepatitis C were either treated with interferon （n = 8）, interferon/ribavirin （n = 19） or peg-interferon/ribavirin （n = 23）. Quantitative testing of liver function, including aminopyrine breath test （ABT）, galactose elimination capacity （GEC）, sorbitol clearance （SCI） and indocyanine green clearance （ICG） was performed before and 3 mo after initiation of antiviral therapy. RESULTS： After 3 mo of antiviral treatment, 36 patients showed normal transaminases and were negative for HCVRNA, 14 patients did not respond to therapy. ABT and GEC as parameters of microsomal and cytosolic liver function were reduced in all patients before therapy initiation and returned to normal values in the 36 therapy responders after 3 too. Parameters of liver perfusion （SCl and ICG） were not affected by antiviral therapy. In the 14 non-responders, no changes in QTLF values were observed during the treatment period. CONCLUSION： ICG and SCI remained unaffected in patients with chronic hepatitis C, while ABT and GEC were significantly compromised. ABT and GEC normalized in responders to antiviral therapy. Early determination of ABT and GEC may differentiate responders from non-responders to antiviral treatment in hepatitis C.

Advances in hepatitis C therapy: What is the current state-what come's next?

Chronic hepatitis C virus(HCV) infection affects 80-160 million people worldwide and is one of the leading causes of chronic liver disease.It is only a few years ago that standard treatment regimes were based on pegylated interferon alpha and ribavirin.However,treatment of HCV has undergone a revolutionary change in recent years.The admission of the nucleotide polymerase inhibitor Sofosbuvir enabled an interferon-free regimen with direct antiviral agents(DAA).Meanwhile seven DAAs are available and can be applied in several combinations for 8 to 24 wk depending on HCV genotype and patient characteristics such as cirrhosis and chronic renal failure.High rates of sustained virological response(SVR) rates can be achieved with these novel drugs.Even in difficult to treat populations such as patients with liver cirrhosis,HCV-human immunodeficiency virus co-infections,after liver transplantion,or with chronic kidney disease comparable high rates of SVR can be achieved.The anticipated 2nd generation DAAs are strikingly effective in patients so far classified as difficult to treat including decompensated liver cirrhosis or posttransplant patients.These 2nd generations DAAs will have higher resistance barriers,higher antiviral effects and a pan-genotypic spectrum.This review highlights the current state of the art of antiviral treatment in hepatitis Cand gives an outlook for upcoming therapies.

Comparison of Hemospray~? and Endoclot? for the treatment of gastrointestinal bleeding

BACKGROUND Gastrointestinal(GI) bleeding is a common indication for endoscopy. For refractory cases, hemostatic powders(HP) represent "touch-free" agents.AIM To analyze short term(ST-within 72 h-) and long-term(LT-within 30 d-) success for achieving hemostasis with HP and to directly compare the two agents Hemospray(HS) and Endoclot(EC).METHODS HP was applied in 154 consecutive patients(mean age 67 years) with GI bleeding.Patients were followed up for 1 mo(mean follow-up: 3.2 mo).RESULTS Majority of applications were in upper GI tract(89%) with following bleeding sources: peptic ulcer disease(35%), esophageal varices(7%), tumor bleeding(11.7%), reflux esophagitis(8.7%), diffuse bleeding and erosions(15.3%). Overall ST success was achieved in 125 patients(81%) and LT success in 81 patients(67%). Re-bleeding occurred in 27% of all patients. In 72 patients(47%), HP was applied as a salvage hemostatic therapy, here ST and LT success were 81% and64%, with re-bleeding in 32%. As a primary hemostatic therapy, ST and LT success were 82% and 69%, with re-bleeding occurring in 22%. HS was more frequently applied for upper GI bleeding(P = 0.04)CONCLUSION Both HP allow for effective hemostasis with no differences in ST, LT success and re-bleeding.

Combined inhibitors of angiogenesis and histone deacetylase:Efficacy in rat hepatoma

AIM:To evaluate the antitumoral effect of combined inhibitors of angiogenesis and histone deacetylases in an experimental rat hepatoma model.METHODS:MH7777A hepatoma cells were injected into the liver of male Buffalo rats.After 7 d treatment with the vascular endothelial growth factor receptor antagonist PTK787/ZK222584(PTK/ZK),the histone deacetylase inhibitor MS-275,tamoxifen(TAM) and/or retinoic acid was initiated(n ≥ 8 animals/group).Natural tumor development was shown in untreated control groups(control 1 with n = 12,control 2 with n = 8).The control groups were initiated at different time points to demonstrate the stability of the hepatoma model.For documentation of possible side effects,we documented any change in body weight,loss of fur and diarrhea.After 21 d treatment,the rats were euthanized.Main target parameters were tumor size and metastasis rate.Additionally,immunohistochemistry for the proliferating cell nuclear antigen(PCNA) and TdT-mediated dUTP-biotin nick end labeling(TUNEL) assay were performed.RESULTS:The control groups developed large tumor nodules with extrahepatic tumor burden in the lung and abdominal organs(control 1:6.18 cm3 ± 4.14 cm3 and control 2:8.0 cm3 ± 4.44 cm3 28 d after tumor cell injection).The tumor volume did not differ significantly in the control groups(P = 0.13).As single agents MS-275 and PTK/ZK reduced tumor volume by 58.6% ± 2.6% and 48.7% ± 3.2% vs control group 1,which was significant only for MS-275(P = 0.025).The combination of MS-275 and PTK/ZK induced a nearly complete and highly significant tumor shrinkage by 90.3% ± 1%(P = 0.005).Addition of TAM showed no further efficacy,while quadruple therapy with retinoic acid increased antitumoral efficacy(tumor reduction by 93 ± 1%) and side effects.PCNA positive cells were not significantly reduced by the single agents,while dual therapy(MS-275 and PTK/ZK) and quadruple therapy reduced the PCNA-positive cell fraction significantly by 9.1 and 20.6% vs control 1(P < 0.05).The number of TUNEL-positive cells,markers for ongoing apoptosis,was increased significantly by the single agents(control 1:6.9%,PTK/ZK:11.4%,MS-275:12.2% with P < 0.05 vs control 1).The fraction of TUNEL-positive cells was upregulated highly significantly by dual therapy(18.4%) and quadruple therapy(24.8%,P < 0.01 vs control 1).For the proliferating(PCNA positive) and apoptotic cell fraction,quadruple therapy was significantly superior to dual therapy(P = 0.01).CONCLUSION:Combined PTK/ZK and MS-275 were highly effective in this hepatoma model.Quadruple therapy enhanced the effects microscopically,but not macroscopically.These results should be investigated further.

Retrograde inspection vs standard forward view for the detection of colorectal adenomas during colonoscopy: A back-to-back randomized clinical trial

BACKGROUND The adenoma detection rate(ADR)is inversely associated with the incidence of interval colorectal cancer and serves as a benchmark quality criterion during screening colonoscopy.However,adenoma miss rates reach up to 26%and studies have shown that a second inspection of the right colon in retroflected view(RFV)can increase ADR.AIM To assess whether inspection of the whole colon in RFV compared to standard forward view(SFV)can increase ADR.METHODS Patients presenting for screening or surveillance colonoscopy were invited to participate in this randomized controlled trial and randomized into two arms.In RFV arm colonoscopy was initially performed with SFV,followed by a second inspection of the whole colon in RFV.In the SFV arm first withdrawal was performed with SFV,followed by a second inspection of the whole colon again with SFV.Number,size and morphology of polyps found during first and second inspection in each colonic segment were recorded and all polyps were removed and sent for histopathology in separate containers.RESULTS Two hundred and five patients were randomly assigned to the RFV(n=101)and SFV(n=104)arm.In the RFV arm,both polyp detection rate(PDR)and ADR were increased under second inspection in RFV(PDR 1st SFV:39.8%,PDR 2nd RFV:46.6%;ADR 1st SFV:35.2%,ADR 2nd RFV:42%).Likewise,in the SFV arm,PDR and ADR were increased under second inspection(PDR 1st SFV:37.5%,PDR 2nd SFV:46.6%;ADR 1st SFV:34.1%,ADR 2nd SFV:44.3%)with no significant differences in ADR and PDR between the SFV and RFV arm.Mean number of adenomas per patient(APP)was increased in the RFV and SFV(APP RFV arm:1st SFV:1.71;2nd RFV:2.38;APP SFV arm:1st SFV:1.83,2nd SFV:2.2).The majority of adenomas additionally found during second inspection in RFV or in SFV were located in the transverse and left-sided colon and were>5 mm in size.CONCLUSION Second inspection of the whole colon leads to increased adenoma detection with no differences between SFV and RFV.Hence,increased detection is most likely a feature of the second inspection itself but not of the inspection mode.