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The latest medical research on Gastroenterology

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Clinical outcomes after surgical decompression of median arcuate ligament syndrome-An observational study.

Indian Journal of Gastroenterology

Median arcuate ligament syndrome is caused by compression and stenosis of the celiac artery. Incision of the median arcuate ligament improves persistent abdominal symptoms. The study aimed at evaluating the outcomes in patients who underwent median arcuate ligament syndrome decompression using a self-report questionnaire.

This single-center retrospective study included patients with median arcuate ligament syndrome who underwent decompression surgery between April 2021 and February 2023. The medical records were retrospectively reviewed.

Ten patients were included in the study. Laparotomy and laparoscopic surgeries were performed in seven and three patients, respectively. The median operation time was 147 minutes. The median hospitalization period after the operation was seven days. The degrees of celiac artery stenosis before and after surgery were compared and the per cent diameter stenosis did not significantly improve; five of 10 patients (50%) had > 50% stenosis in the celiac artery after the operation. Compared to the baseline, the scores of upper gastrointestinal symptoms significantly improved during the six months' period (p < 0.001). Additionally, we evaluated the influence of post-operative per cent diameter stenosis and divided the patients into two groups (≥ 50% vs, < 50%). The scores of upper gastrointestinal (GI) symptoms in both groups improved significantly from baseline. However, the symptomatic improvement at six months in the post-operative per cent diameter stenosis < 50% group was significantly greater than that in the ≥ 50% group (p = 0.016). The scores of lower gastrointestinal symptoms did not change significantly during the six-month period.

Decompression surgery for median arcuate ligament syndrome could improve upper gastrointestinal symptoms regardless of the post-operative per cent diameter stenosis.

Clinical profile of adult and pediatric patients with hepatic Wilson's disease.

Indian Journal of Gastroenterology

The clinical profile varies in patients with Wilson's disease (WD). There is paucity of data regarding adult and pediatric patients with hepatic WD.

As many as 140 consecutive patients diagnosed with hepatic WD between December 2006 and January 2021 were included in the study. Data was collected regarding the demographic parameters, clinical presentation, extrahepatic organ involvement, liver histology and laboratory investigations. Adult and children (0-14 years) with hepatic WD were compared regarding these features.

Eighty-eight adults and 52 children were included in the study. The median age of presentation was 17 years (range: 1.1-42 years). Male preponderance was seen (adult 68/88, 69%; children 40/52, 77%). Adults as compared to children presented more commonly as cirrhosis (52/88 vs. 15/52, p = 0.0005) and with hepatic decompensation (35/88 vs. 9/52, p = 0.005). Presentation with acute-on-chronic liver failure (ACLF) was more common in children (10/52 vs. 2/88, p = 0.0005). Twenty-eight-day mortality was 50% (5/10) in children and none in adults presenting with ACLF. Nazer's Prognostic Index (≥ 7) and New Wilson Index were more accurate in predicting mortality among children with ACLF with AUROC 1, while AARC (APASL ACLF Research Consortium) was less accurate with AUROC 0.45. Liver histology findings were similar in adults and children. Extrahepatic involvement was also similar. (8/88 in adults vs. 3/52 children, p value 0.48).

Most patients with WD present as cirrhosis in adulthood. ACLF is more common in children. Nazer's prognostic index and new Wilson Index score are accurate in predicting mortality in children with ACLF.

Targeting cellular cathepsins inhibits hepatitis E virus entry.

Hepatology

The hepatitis E virus (HEV) is estimated to be responsible for 70,000 deaths annually, yet therapy options remain limited. In the pursuit of effective antiviral therapies, targeting viral entry holds promise and has proven effective for other viruses. However, the precise mechanisms and host factors required during HEV entry remain unclear. Cellular proteases have emerged as host factors required for viral surface protein activation and productive cell entry by many viruses. Hence, we investigated the functional requirement and therapeutic potentials of cellular proteases during HEV infection.

Using our established HEV cell culture model and subgenomic HEV replicons, we found that blocking lysosomal cathepsins (CTS) with small molecule inhibitors, impedes HEV infection without affecting replication. Most importantly, the pan-cathepsin inhibitor K11777 suppressed HEV infections with an EC50 of ~ 0.01 nM. Inhibition by K11777, devoid of notable toxicity in hepatoma cells, was also observed in HepaRG and primary human hepatocytes. Furthermore, through time-of-addition and RNAscope experiments, we confirmed that HEV entry is blocked by inhibition of cathepsins. Cathepsin L (CTSL) knockout cells were less permissive to HEV, suggesting that CTSL is critical for HEV infection. Finally, we observed cleavage of the glycosylated ORF2 protein and virus particles by recombinant CTSL.

In summary, our study highlights the pivotal role of lysosomal cathepsins, especially CTSL, in the HEV entry process. The profound anti-HEV efficacy of the pan-cathepsin inhibitor, K11777, especially with its notable safety profile in primary cells, further underscores its potential as a therapeutic candidate.

Efficacy of long-term albumin therapy in the treatment of decompensated cirrhosis.

Indian Journal of Gastroenterology

Decompensated liver cirrhosis has a poor prognosis, with a median overall survival of two to four years, which is worse than for many oncological disorders. These patients are highly susceptible to infections due to increased systemic inflammation leading to kidney failure and death. The aim was to study the efficacy of albumin in reducing episodes of decompensation, preventing bacterial infection, kidney dysfunction and mortality.

Study involved patients with Child B or C cirrhosis with an albumin level below 3.0 g/dL, who were administered 20% human albumin weekly with standard medical treatment (SMT) for three months or till serum albumin levels were 4.0 g/dL (whichever is earlier) and compared with age and sex-matched controls who received only SMT. The primary end-point was six-month mortality and the secondary end-points were reduction in infections, kidney dysfunction, ascites recurrence, hepatic encephalopathy (HE), gastrointestinal (GI) bleed and complications of cirrhosis.

From September 2021 to January 2023, 88 cases and 86 controls were taken and followed up for six months. Overall, six-month survival was not statistically significant between groups (95.1% vs. 91.9%; p = 0·330). The incidence of recurrence of ascites (34.09% vs. 59.3%, p < 0.001), kidney dysfunction (6.8% vs. 24.4%, p < 0.001), HE (15.9% vs, 37.2%, p = 0.015), spontaneous bacterial peritonitis (SBP) (3.4% vs 17.4%, p = 0.002) and non-SBP infections (7.9% vs. 18.6%, p = 0.038) were significantly less in cases as compared with controls; however, GI bleed (14.8% vs. 17.4%, p = 0.632) was not statistically significant.

Long-term human albumin acts as a disease-modifying treatment in patients with decompensated cirrhosis.

Overview of acute liver failure in India.

Indian Journal of Gastroenterology

Acute liver failure (ALF) is an infrequent, but serious complication subsequent to severe acute liver injury (sALI) due to various hepatotoxic agen...

Epidemiology, screening, and Co-management of type 2 diabetes mellitus and Metabolic-dysfunction associated steatotic liver disease.

Hepatology

Metabolic-dysfunction associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is increasingly re...

Lumen-apposing metal stents: A primer on indications and technical tips.

Indian Journal of Gastroenterology

Lumen-apposing metal stents have ushered a new frontier for interventional endoscopic ultrasound. Initial use for the drainage of pancreatic fluid ...

Effect of Menstrual Cycle and Menopause on Human Gastric Electrophysiology.

Am J Physiol

Chronic gastroduodenal symptoms disproportionately affect females of childbearing age; however, the effect of menstrual cycling on gastric electrop...

Acute liver failure histopathology: A 5-year retrospective study.

Indian Journal of Gastroenterology

Acute liver failure (ALF) is a rare, life-threatening disease of diverse etiology. It is defined as severe acute liver injury for fewer than 26 weeks' duration with encephalopathy and impaired synthetic function (international normalized ratio [INR] of 1.5 or higher) in a patient without cirrhosis or pre-existing liver disease. The diagnosis rests mainly on the clinical ground with wide range of pathological features. The present study seeks to explore the diverse histological patterns observed in cases for ALF and assess their usefulness in determining the underlying causes for the condition.

A retrospective cross-sectional study was conducted among patients of ALF who underwent liver transplant and transjugular liver biopsy over a five-year period. From 1082 explant liver and 2446 liver biopsies, 22 cases of ALF (10 explants and 12 liver biopsies) were included in the study. Clinical and laboratory details were retrieved and histological findings were reviewed.

Age ranged from 10 to 72 years (mean age, 40 years). There was a female predominance with a male:female ratio of 1:1.7. The commonest cause for ALF was virus-induced hepatocellular damage in 36.3% (eight patients), followed by autoimmune hepatitis in 22.7% (five patients), drug-induced liver injury (DILI) in 18.1% (four patients), cryptogenic in 13.6% (three patients) and ischemic injury secondary to large vein thrombosis in 9.0% (two) patients. The histological patterns identified were categorized into six categories. A more comprehensive morphological evaluation was conducted specifically for cases of ALF associated with autoimmune hepatitis (AIH) and compared with other cases of ALF.

In summary, our present study illustrates a morphological overlap in various patterns for the purpose of etiological assessment. In cases of AIH ALF, the presence of portal plasma cell infiltrate and central perivenulitis were identified as significant histological features to guide diagnosis.

Plasma exchange improves survival in acute liver failure - An updated systematic review and meta-analysis focussed on comparing within single etiology.

Indian Journal of Gastroenterology

Therapeutic plasma exchange (PLEX) is increasingly used in patients with acute liver failure (ALF) as either stand-alone therapy or bridge to liver transplantation. Etiology plays a major role in prognosis of these patients and benefit of PLEX may consequently differ across etiologies. This systematic review and meta-analysis aims to evaluate the efficacy of PLEX in treating ALF, focussing on studies with single etiology.

We conducted a systematic literature search and identified studies comparing PLEX vs. standard medical therapy (SMT) for patients with ALF across all age groups. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42023442383). Pooled risk-ratios were determined by Mantel-Haenszel method within a random effect model. Primary outcome was mortality at ≤ 60-days and 90 days. Secondary outcome was adverse events attributable to PLEX.

Eight studies (pooled sample size in PLEX arm: 284; randomized trials: 2; Comparative cohorts: 6) with retrievable data on ALF were included in this systematic review. Analysis showed that PLEX was associated with significant reduction in mortality at ≤ 60-days (RR 0.64; CI, 0.51-0.80; P < 0.001) and at 90-days (RR 0.67; CI, 0.50-0.90; P = 0.008) as compared to SMT. On sub-group analysis, the survival benefit was noted irrespective of the volume of plasma exchanged during PLEX. Three studies (pooled sample size in PLEX arm: 110; all comparative cohorts) were identified, which included patients with a single etiology for ALF. These studies included patients with Wilson's disease, rodenticidal hepatotoxicity and acute fatty liver of pregnancy. Pooled analysis of studies with single etiology ALF showed better reduction in ≤ 90-day mortality with PLEX (RR 0.53; CI, 0.37-0.74; P < 0.001). Studies reported no major side-effects attributable to PLEX.

PLEX is safe and improves survival, independent of the volumes utilized, in patients with ALF as compared to standard medical treatment. The survival benefit is especially pronounced in studies restricted to single etiology.

Acute liver failure in pregnancy.

Indian Journal of Gastroenterology

Liver function abnormalities are noted in a minority of pregnancies with multiple causes for the same. A small proportion of these develop severe l...

Gut-liver Axis: Recent concepts in pathophysiology in alcohol-associated liver disease.

Hepatology

The growing recognition of the role of the gut microbiome's impact on alcohol-related diseases, especially in alcohol-associated liver disease, emp...