A meta-analysis of the effects of glucagon-like-peptide 1 receptor agonist (GLP1-RA) in nonalcoholic fatty liver disease (NAFLD) with type 2 diabetes (T2D).

Treatment options for nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D), two conditions which coexist, are limited though weight loss is an important strategy to improve outcomes in either disease. Glucagon-like peptide 1 receptor agonist (GLP1-RA) present a novel option to treat this dual disease by their salutary effects on glycaemic control and weight reduction. Eight randomized controlled trials on T2D and NAFLD from the Cochrane Library, Embase, and PubMed were included in this meta-analysis. The Comprehensive Meta-Analysis Software version 3 was used to calculate the effect size. In a pooled population of 615 patients-297 on GLP1-RA and 318 in the control arm, GLP1-RA produced a significant improvement in alanine aminotransferase [standardised mean difference (SDM), - 0.56, 95% CI - 0.88 to - 0.25, P < 0.01], aspartate aminotransferase (SDM, - 0.44, SE, 95% CI - 0.64 to - 0.24, P < 0.01), gamma glutaryl transaminase (SDM, - 0.60, 95% CI - 0.86 to - 0.34, P < 0.01) and reduction in liver fat content (LFC) (SDM, - 0.43, 95% CI - 0.74 to - 0.12, P < 0.01), as well as glycosylated haemoglobin (SDM, - 0.40, 95% CI, - 0.61 to - 0.19, P < 0.01) and weight (SDM, - 0.66, 95% CI, - 0.88 to - 0.44, P < 0.01), in comparison to standard of care or placebo. Significant improvement in biopsy resolution was also seen in the GLP1-RA arm (Rate Ratio, 6.60, 95% CI 2.67 to 16.29, P < 0.01). This is possibly the first meta-analysis conducted exclusively in patients with T2D and NAFLD which presents a strong signal that GLP1-RA, improve liver function and histology by improving glycaemia, reducing body weight and hepatic fat, which in turn reduces hepatic inflammation.Trial Registration: PROSPERO (ID: CRD42021228824).

Meta-analysis of the effects of sodium glucose cotransporter 2 inhibitors in non-alcoholic fatty liver disease patients with type 2 diabetes.

BACKGROUND AND AIM: Sodium glucose cotransporter 2 inhibitors (SGLT-2i), by way of their unique mode of action, present an attractive strategy for the treatment of type 2 diabetes and non-alcoholic fatty liver disease (NAFLD), which often coexist and may lead to severe complications. However, the evidence for treatment with SGLT-2i is limited to small heterogeneous studies. Therefore, this meta-analysis was conducted to deduce the effects of SGLT-2i in NAFLD with type 2 diabetes (T2D). METHODS: A web-based search identified nine randomized controlled trials from the Cochrane Library, Embase, and PubMed for this meta-analysis. The Comprehensive Meta-Analysis Software version 3 was used to calculate the effect size. RESULT: The outcomes of interest were analyzed from a pooled population of 11 369 patients-7281 on SGLT-2i and 4088 in the control arm. SGLT-2i therapy produced a statistically significant improvement in alanine aminotransferase [standardised mean difference (SDM), -0.21, 95% confidence interval (CI), -0.32 to -0.10, P < 0.01], aspartate aminotransferase (Standardised mean difference (SDM), -0.15, 95% CI, -0.24 to -0.07, P < 0.01), and liver fat as measured by proton density fat fraction (SDM, -0.98, 95% CI, -1.53 to -0.44, P < 0.01) in comparison to standard of care or placebo. In addition, there was a significant reduction in glycosylated hemoglobin (SDM, -0.37, 95% CI, -0.60 to -0.14, P < 0.01) and weight (SDM, -0.58, 95% CI, -0.93 to -0.23, P < 0.01) in the SGLT-2i arm. CONCLUSION: This meta-analysis provides a convincing signal that SGLT-2i have a salutary effect on NAFLD in type 2 diabetes (T2D), probably driven by an improvement of glycemia and body weight, which in turn attenuates hepatic inflammation and hepatic fat accumulation.

Hepatocellular carcinoma in India.

Cancers of the liver are one of the commonest cancers that occur in the world, the commonest of which is the hepatocellular carcinoma (HCC). It is considered to be the 5th commonest cancer in the world. In the areas that are endemic for hepatitis B and C, it is extremely common. Unfortunately, India which is an endemic zone for hepatitis B, there has been no comprehensive analyzed data for HCC. Incidence of HCC in India occurs at two peaks, one at a young age between 40 to 55 years and another above 60 years. Eighty per cent of all HCCs occurring in India occur with cirrhosis of liver in the background and 60% of all these cases are hepatitis B positive carriers. Symptoms are reflective of late presentation with advanced disease. Surgery, the only curative modulus available, unfortunately is not possible in 95% of HCC patients. Majority of the patients are treated with palliative and supportive care and life spans are limited. Sorafenib is used in a small section of patients. Characterization of HCC with molecular sub-typing is the need of the hour.

Investigating the morphology of the proximal femur of the Indian population towards designing more suitable THR implants.

There are considerable variations in the femoral geometry of populations across different geographical locations and ethnic groups. The osteological parameters of the proximal femur are very important for the design of suitably sized prostheses of total hip replacement (THR), especially for cementless implantation. Though total hip prostheses in different sizes are available from manufacturers, best-fit implants are often unavailable for Indian patients. To produce hip prostheses of suitable sizes and shapes for Indian patients, important osteological parameters of the proximal femur in the Indian population are needed. In this study, 100 computed tomography (CT) images of hip joints of members of the Indian population were collected, and 20 anatomical parameters of the proximal femur were analyzed. The mean values of these parameters were compared with those of the populations of a few other countries that were available from the literature. The parameter comparison was also performed between males and females in our subsample of the Indian population. Finally, values of the important parameters were grouped suitably for future design of standard sizes of THR implants for the Indian population. We found variations in the morphology of the proximal femur between the Indian population and that of other countries, which illustrates a need for standardizing THR implant sizes for the Indian population, especially for cementless implantation. The variations of a few important parameters of the proximal femur also occur between the male and female Indian populations. This study is likely to be a significant step toward designing suitably sized cementless THR implants for the Indian population.

Suspected intestinal tuberculosis might be Crohn's disease.

In this case report we provide evidence that supports a link between mycobacteria and Crohn's disease. The patient in question, KG, presented on three separate occasions over a ten years period with features suggestive of intestinal tuberculosis. He was treated successfully on each occasion with antimycobacterial drugs. When he presented a fourth time with the same symptoms, he was diagnosed with Crohn's disease based on findings from endoscopy, histology and CT. Subsequently he was treated with a course of steroids and made a full recovery. This case adds weight to the theory that mycobateria has an aetiological role in Crohn's disease.

Hyperlactataemia and lactic acidosis during antiretroviral therapy: relevance, reproducibility and possible risk factors.

OBJECTIVE: To evaluate the prevalence, outcome and possible risk factors for hyperlactataemia and lactic acidosis in HIV-positive persons receiving antiretroviral therapy. METHODS: Cross-sectional and longitudinal data from a prospectively collected clinical database. Associations with antiretroviral regimen, clinical and laboratory parameters were assessed using univariate and multivariate Cox's proportional hazards model. RESULTS: Patients naive to therapy and patients on current therapy for a minimum of 4 months were assessed. Median lactate was 1.1 mol/l in 253 untreated individuals and 1.4 mmol/l in 1239 patients stable on therapy for at least 4 months. At least two on-therapy samples were available for 750 of the 1239 individuals, taken a median 92 days apart. Lactate measurement showed a low positive predictive value of 38.9% but a high negative predictive value (98%) for normal values. Lactate was elevated > or = 2.4 mmol/l in 102 individuals on at least one occasion. In the multivariate Cox's proportional hazards model, no demographic characteristics were associated with hyperlactataemia. Didanosine-containing regimens doubled the relative hazard of hyperlactataemia compared with those sparing didanosine. Abacavir-containing regimens reduced the hazard of hyperlactataemia. Choice of thymidine analogue did not influence risk. Hyperlactataemia was associated with acid-base disturbance. Use of didanosine and female sex were over-represented amongst nine patients with severe hyperlactataemia (> 5 mmol/l) or lactic acidosis. CONCLUSIONS: Screening of lactate is of limited use in asymptomatic individuals on antiretroviral therapy. Raised lactate represents part of a spectrum of lactate and acid-base disturbance that infrequently includes lactic acidosis. Didanosine appears associated with an increased risk of hyperlactataemia.