Clinical expression of insulin resistance in hepatitis C and B virus-related chronic hepatitis:Differences and similarities

AIM:To investigate the prevalence of the clinical parameters of insulin resistance and diabetes in patients affected by chronic hepatitis C(CHC) or chronic hepatitis B(CHB) . METHODS:We retrospectively evaluated 852 consecutive patients(726 CHC and 126 CHB) who had undergone liver biopsy.We recorded age,sex,ALT,type 2 diabetes and/or metabolic syndrome(MS) ,body mass index(BMI) ,and apparent disease duration(ADD) . RESULTS:Age,ADD,BMI,prevalence of MS and diabetes in patients with mild/moderate liver fibrosis were significantly higher in CHC.However,the degree of steatosis and liver fibrosis evaluated in liver biopsies did not differ between CHC and CHB patients.At multivariate analysis,age,sex,BMI,ALT and diabetes were independent risk factors for liver fibrosis in CHC,whereas only age was related to liver fibrosis in CHB. We also evaluated the association between significant steatosis(>30%) and age,sex,BMI,diabetes,MS and liver fibrosis.Diabetes,BMI and liver fibrosis were associated with steatosis>30%in CHC,whereas only age and BMI were related to steatosis in CHB. CONCLUSION:These data may indicate that hepatitis C virus infection is a risk factor for insulin resistance.

Intrahepatic vascular changes in non-alcoholic fatty liver disease: potential role of insulin-resistance and endothelial dysfunction

Metabolic syndrome is a cluster of several clinical conditions characterized by insulin-resistance and high cardiovascular risk. Non-alcoholic fatty liver disease is the liver expression of the metabolic syndrome, and insulin resistance can be a frequent comorbidity in several chronic liver diseases, in particular hepatitis C virus infection and/or cirrhosis. Several studies have demonstrated that insulin action is not only relevant for glucose control, but also for vascular homeostasis. Insulin regulates nitric oxide production, which mediates to a large degree the vasodilating, antiinflammatory and antithrombotic properties of a healthy endothelium, guaranteeing organ perfusion. The effects of insulin on the liver microvasculature and the effects of IR on sinusoidal endothelial cells have been studied in animal models of non-alcoholic fatty liver disease. The hypotheses derived from these studies and the potential translation of these results into humans are critically discussed in this review.

Therapeutic and clinical aspects of portal vein thrombosis in patients with cirrhosis

Portal vein thrombosis(PVT) is a frequent complication in cirrhosis, particularly in advanced stages of the disease. As for general venous thromboembolism, risk factors for PVT are slow blood flow, vessel wall damage and hypercoagulability, all features of advanced cirrhosis. Actually, the old dogma of a hemorrhagic tendency in cirrhosis has been challenged by new laboratory tools and the clinical evidence that venous thrombosis also occurs in cirrhosis. The impaired hepatic synthesis of both pro- and anticoagulants leads to a rebalanced hemostasis, more liable to be tipped towards thrombosis or even bleeding. Conventional anticoagulant drugs(low molecular weight heparin or vitamin K antagonists) may be used in cirrhosis patients with PVT, particularly in those eligible for liver transplantation, to prevent thrombosis progression thus permitting/facilitating liver transplant. However, several doubts exist on the level of anticoagulation achieved as estimated by coagulation tests, on the efficacy of treatment monitoring and on the correct timing for discontinuation in non-transplant candidates, while in transplant candidates there is expert consensus on continuing anticoagulation until transplantation. The recent introduction of direct acting oral anticoagulant drugs(DOACs) in other clinical settings generates much interest on their possible application in patients with cirrhosis and PVT. However, DOACs were not evaluated yet in patients with liver disease and cannot be recommended for the present time.

Cirrhosis and portal hypertension: The importance of risk stratification, the role of hepatic venous pressure gradient measurement

Portal hypertension is the main prognostic factor in cirrhosis. The recent emergence of potent antiviral drugs and new algorithm of treatment for the management of complications due to portal hypertension have sensibly changed our perception of cirrhosis that can be now considered as a multistage liver disease whose mortality risk can be reduced by a tailored approachfor any stage of risk. Experts recommend to move toward a pathophysiological classification of cirrhosis that considers both structural and functional changes. The hepatic venous pressure gradient HVPG, is the reference gold standard to estimate the severity of portal hypertension in cirrhosis. It correlates with both structural and functional changes that occur in cirrhosis and carries valuable prognostic information to stratify the mortality risk. This article provides a general overview of the pathophysiology and natural course of cirrhosis and portal hypertension. We propose a simplified classification of cirrhosis based on low, intermediate and high mortality stage. The prognostic information provided by HVPG is presented according to each stage. A comparison with prognostic models based on clinical and endoscopic variables is discussed in order to evidence the additional contribute given by HVPG on top of other clinical and instrumental variables widely used in clinical practice.

Use of non-selective beta blockers in cirrhosis:The evidence we need before closing(or not) the window

Non selective beta blockers(NSBBs)are used in primary and secondary prophylaxis of portal hypertensionrelated bleeding in patients with cirrhosis.The efficacy of NSBBs treatment is predicted by hemodynamic response in term of reduction of the hepatic venouspressure gradient(HVPG)below 12 mm Hg or at least20%of the basal value.Nevertheless a relevant number of patients who do not achieve this HVPG reduction during NSBBs therapy do not bleed during follow up;this evidence suggests an additional non-hemodynamic advantage of NSBBs treatment to modify the natural history of cirrhosis.Recent studies have questioned the efficacy and safety of NSBBs in patients with advanced stage of liver disease characterized by refractory ascites and/or spontaneous bacterial peritonitis.These studies have suggested the existence of a defined and limited period to modify the natural history of cirrhosis by NSBBs:the"window hypothesis".According with this hypothesis,patients with cirrhosis benefit from the use of NSBBs from the appearance of varices up to the development of an advanced stage of cirrhosis.Indeed,in patients with refractory ascites and/or spontaneous bacterial peritonitis the hemodynamic effects of NSBBs may expose to a high risk of further complications such as renal insufficiency and/or death.Methodological concerns and contrasting results counterbalance the evidence produced up to now on this issue and are the main topic of this editorial.