Practical approach to non-alcoholic fatty liver disease in patients with diabetes.

The prevalence of Type 2 diabetes is expected to increase in parallel with obesity rates and the ageing population. Recent studies show that Type 2 diabetes is associated with a twofold increase in the risk of non-alcoholic fatty liver disease, a leading cause of chronic liver disease. Individuals with non-alcoholic steatohepatitis, a more advanced stage of non-alcoholic fatty liver disease, are specifically at risk of developing fibrosis/cirrhosis (end-stage liver disease) and hepatocellular carcinoma; therefore, identifying individuals (with Type 2 diabetes) who are likely to develop hepatic complications is paramount. In the present clinical review, we discuss the potential impact of non-alcoholic fatty liver disease diagnosis on Type 2 diabetes, and the putative risk factors for developing non-alcoholic steatohepatitis and non-alcoholic steatohepatitis fibrosis. We highlight the limitations of currently used tools in non-alcoholic fatty liver disease diagnosis and staging, and provide an insight into future developments in the field. We present an example of a non-alcoholic fatty liver disease screening protocol and discuss the therapeutic options currently available to our patients.

Systematic review: Clostridium difficile and inflammatory bowel disease.

BACKGROUND: There is increasing concern about the apparently rising incidence and worsening outcome of Clostridium difficile infection (CDI) associated with inflammatory bowel disease (IBD). We have systematically reviewed the literature to evaluate the incidence, risk factors, endoscopic features, treatment and outcome of CDI complicating IBD. AIM: To systematically review: clostridium difficile & inflammatory bowel disease. METHODS: Structured searches of Pubmed up to September 2010 for original, cross-sectional, cohort and case-controlled studies were undertaken. RESULTS: Of 407 studies, 42 met the inclusion criteria: their heterogeneity precluded formal meta-analysis. CDI is commoner in active IBD, particularly ulcerative colitis, than in controls. Certainty about a temporal trend to its increasing incidence in IBD is compromised by possible detection bias and miscoding. Risk factors include immunosuppressants and antibiotics, the latter less commonly than in controls. Endoscopy rarely shows pseudomembranes and is unhelpful for diagnosing CDI in IBD. There are no controlled therapeutic trials of CDI in IBD. In large studies, outcome of CDI in hospitalised IBD patients appears worse than in controls. CONCLUSIONS: The complication of IBD by Clostridium difficile infection has received increasing attention in the past decade, but whether its incidence is really increasing or its outcome worsening remains unproven. Therapeutic trials of Clostridium difficile infection in IBD are lacking and are needed urgently.

Systematic review: outcome of compensated cirrhosis due to chronic hepatitis C infection.

BACKGROUND: Most studies evaluating chronic hepatitis C virus (HCV) natural history have taken the development of cirrhosis as an end-point. AIM: To perform a systematic review of the literature to establish the outcome of compensated HCV cirrhosis. METHODS: A systematic literature review was performed. Only data regarding HCV mono-infected patients were included. Weighted mean annual percentage rates for death/transplantation, decompensation of cirrhosis and development of HCC were calculated. RESULTS: Thirteen papers were included. Despite some heterogeneity, we extracted data relating to 2386 patients. In compensated HCV cirrhosis, the estimated annual rate of death/transplantation is 4.58%, that of decompensation is 6.37% per and that of HCC, 3.36%. When compared with studies of untreated patients, studies that included treated patients reported significantly lower mean annual percentage rates of HCC (2.52% vs. 4.79%, P = 0.02), but not decompensation (5.34% vs. 7.88%, P = 0.026) and death/transplantation (3.79% vs. 4.62%, P = 0.25). CONCLUSIONS: These rates highlight the need for continued vigilance for the occurrence of HCC, while confirming the relatively slow progress of compensated HCV cirrhosis. Heterogeneity in reporting means that these data may underestimate the rate of disease progression, particularly HCC development. It will be important to ensure clearer distinction between treatment responses in future studies.

Genomic imbalances in 70 snap-frozen cervical squamous intraepithelial lesions: associations with lesion grade, state of the HPV16 E2 gene and clinical outcome.

Host genomic abnormalities may determine the natural history of cervical squamous intraepithelial lesions (SILs). We undertook comparative genomic hybridisation analysis of epithelium carefully microdissected from 70 cervical SILs, the largest series to date. In contrast to previous studies, we used frozen sections for optimal DNA quality and examined whether patterns of DNA copy number imbalance (CNI) are characteristic of SIL grade, human papillomavirus (HPV) status and postoperative recurrence. We identified more CNIs in cervical SIL than previously described, with more CNIs per case in high-grade squamous intraepithelial lesion (HG-SIL) than in low-grade squamous intraepithelial lesion (LG-SIL) (P=0.04). While some CNIs were seen at similar frequencies in HG-SIL and LG-SIL, others, including gain on 1q, 3q and 16q, were found frequently in HG-SIL but not in LG-SIL. There were significantly more CNIs per case in HG-SILs showing loss of the HPV16 E2 gene (a repressor of viral oncogene transcription) (P=0.026) and in HG-SILs that subsequently recurred (P=0.04). Our data are consistent with sequential acquisition of CNIs in cervical SIL progression. Higher frequency of CNI in association with E2 gene loss supports in vitro evidence that high-risk HPV integration is associated with genomic instability. Further investigation of the clinical value of specific host genomic abnormalities in cervical SIL is warranted.

Altered expression of desmosomal components in high-grade squamous intraepithelial lesions of the cervix.

We have used immunohistochemistry to test the hypothesis that components of the desmosome are disrupted during neoplastic progression of squamous epithelial cells in the uterine cervix. Sections of normal cervix and squamous intraepithelial lesions (SILs) were immunostained for desmosomal proteins and glycoproteins, and results were assessed using a semi-quantitative grading system. No difference between normal cervix and low-grade SIL (LSIL) was found. A significant reduction in expression of desmogleins was seen between high-grade SIL (HSIL) and LSIL (P<0.01) and normal cervix (P<0.001). Desmocollin expression was not reduced significantly, although scores showed significantly greater variation in HSIL compared with LSIL (P<0.05) and normal cervix (P<0.05). There was no significant difference in desmoplakin expression among the three groups. The results suggest that there may be sequential disruption of desmosomal function during neoplastic progression of cervical squamous intraepithelial cells, with downregulation of desmogleins during the progression from LSIL to HSIL and loss of desmocollin expression occurring in some cases of established HSIL.