A Case of Gastrointestinal Stromal Tumour (GIST) in the Duodenum in a Young Adult.

Gastrointestinal stromal tumours (GISTs) are rare gastrointestinal (GI) malignancies, but the most prevalent mesenchymal tumours of the GI tract arise from the interstitial cells of Cajal. They account for 1-3% of all GI malignancies, and only 3-5% of all cases of GIST are located at the duodenal. We present a case of a young adult who presented to the ED with symptoms of GI bleeding.

Long-term Outcome of Autoimmune Hepatitis: Consecutive Patient Cohort and Data on the Second Twenty Years.

BACKGROUND: Mortality rates for autoimmune hepatitis (AIH) vary. Data are lacking beyond 20 years follow-up. AIMS: Analysis of a consecutively recruited large AIH cohort from a single non-transplant tertiary centre in England and an overlapping cohort, already followed for ≥ 20 years. METHODS: We assessed 330 patients presenting 1987-2016 and 65 patients presenting 1971-96 already followed for 20 years. RESULTS: Death/liver transplant rate was 51±4% (all-cause) and 21±4% (liver-related) over 20 years and was independently associated with: decompensation and lower serum ALT at diagnosis; and failure of serum ALT normalisation and higher relapse rate. There was excess mortality over the first year. Patients (n = 65) already followed for twenty years had similar subsequent rates of relapse, disease progression and mortality, to those followed from diagnosis. Azathioprine-intolerant patients (n = 23) switching to Mycophenolate did not have higher mortality over 4(1-17) years, than patients continuing Azathioprine. Following immunosuppression withdrawal (n = 26), six (23% patients) relapsed with no liver-related deaths over 2.3(0-23.1) years. CONCLUSIONS: In this consecutive autoimmune hepatitis cohort, mortality was similar to that in national registry studies, disease progression continued after 20 years, and immunosuppression withdrawal did not compromise survival.

Histopathologist and clinician interface in diagnosis and management of autoimmune hepatitis.

Diagnosis of AIH is based on a combination of clinical, laboratory and histological information. It has been formalised by diagnostic scoring systems, to which liver biopsy contributes substantially. Diagnostic biopsy is thus, desirable in nearly all patients. An adequate biopsy size, provision by clinicians of adequate information to histopathologists and active discussion at regular meetings are all important for accurate histological diagnosis. Recently, the specificity of some features previously thought to suggest AIH has been questioned, and new recommendations for histological diagnosis have been proposed, although not yet validated. The histology of acutely presenting AIH and that of severe or fulminant AIH include some characteristic features. Primary biliary cholangitis, primary sclerosing cholangitis and non-alcoholic fatty liver disease may co-exist with AIH on biopsy. Liver biopsy also enables grading of severity of inflammation and staging of fibrosis. Presence of cirrhosis is a poor prognostic marker. Repeat liver biopsy after achieving biochemical remission, although not performed routinely, enables assessment of (a) histological remission, a favourable prognostic indicator and (b) fibrosis progression. It can thus help determine further management.

Delayed hepatic necrosis in a cystic fibrosis patient taking Elexacaftor/Tezacaftor/Ivacaftor (Kaftrio).

The introduction of Cystic Fibrosis Trans Regulatory modulator (CFTRm) drugs has seen a transformation in Cystic Fibrosis (CF) treatment. This has led to a significant improvement in lung function and quality of life with the potential for a real impact on life expectancy. Transient mild to moderate hepatic transaminitis is a well-known side effect of CFTRm drugs, which often improves on cessation and may not recur following the re-institution of the drug. We describe a case of transaminitis developing nine months after the initiation of Kaftrio, which progressed to liver necrosis despite stopping Kaftrio and took many months to resolve. The patient had experienced significant improvement in lung function and overall health while on Kaftrio and deteriorated when it was stopped. He was keen to restart; however, Kaftrio was not reinstated due to the potential risk of acute liver failure.

Length of Barrett's esophagus in the presence of low-grade dysplasia, high-grade dysplasia, and adenocarcinoma.

INTRODUCTION: The identification and follow-up of ultra-short Barrett's esophagus (BE) is controversial. BE surveillance guidelines emphasize mainly on long-segment BE. However, in practice a substantial proportion of esophageal adenocarcinoma (EAC) are found close to the gastro-esophageal junction (GEJ). Our study aims to chart the length of BE when low-grade dysplasia (LGD), high-grade dysplasia (HGD) and EAC arise in BE. METHODS: Endoscopic findings from all cases with a diagnosis of LGD and HGD in BE between June 2014 and June 2019, and 100 consecutive cases of EAC diagnosed between June 2018 and August 2019, were reviewed. Additionally, 438 consecutive gastroscopies were reviewed to identify 100 cases of non-dysplastic BE. RESULTS: 99 cases of LGD and 61 cases of HGD were reviewed. LGD and HGD when diagnosed, was located in BE ≤ 1 cm in 20% and 18% cases, respectively. LGD and HGD when diagnosed, was located in BE ≤ 3 cm in 48.5% and 40.9% cases, respectively. LGD and HGD when diagnosed in BE ≤ 3 cm was found at index endoscopy in 67% and 42% cases, respectively. Of the 100 cases of EAC, only 23 had concurrent visible BE, with BE higher than the level of EAC in seven. EAC when found, had its proximal extent ≤ 1 cm from GEJ in 22% and ≤ 3 cm from GEJ in 40% cases. Of the 100 non-dysplastic BE, 53% were ≤ 1 cm and 78% were ≤ 3 cm long. CONCLUSION: Almost 20% of all dysplasia in BE occurs in BE < 1 cm. Over 40% occurs in BE < 3 cm. Similarly, 20% of EAC occurs within 1 cm of GEJ and 40% occur within 3 cm. A majority of dysplasia diagnosed within 3 cm of the GEJ is found on index endoscopy. We propose that all lengths of columnar lined epithelium above the GEJ are recognized as BE and subjected to a thorough biopsy protocol.

Lisinopril-Induced Liver Injury: An Unusual Presentation and Literature Review.

Lisinopril is an angiotensin converting enzyme inhibitor (ACE-I) that has been on market for more than 25 years. ACE-I are usually well tolerated and rarely have serious or life-threatening side effects. We describe an unusual presentation of fulminant hepatic cholestasis probably secondary to lisinopril. To our knowledge, this is the second case report which shows lisinopril-induced liver injury though a cholestatic mechanism. The patient was a 59-year-old woman with type 2 diabetes, a high body mass index and hypertension, who presented with a 5-week history of jaundice and itching. She had been started on lisinopril for diabetic nephropathy 8 weeks before admission. Other causes for cholestasis had been excluded through non-invasive immunology and virology screening, an ultrasound of the liver, magnetic resonance cholangiopancreatography and a liver biopsy. The biopsy was consistent with drug-induced liver injury. Lisinopril was stopped 2 weeks before admission. The patient's hospital stay was complicated by contrast nephropathy and influenza A which were both treated appropriately. Unfortunately, the liver cholestasis did not completely resolve following withdrawal of lisinopril and the patient died after 4 months. A literature search yielded only six other reported cases of lisinopril-induced liver injury. Five cases described hepatocellular damage and one showed cholestatic injury. LEARNING POINTS: Angiotensin converting enzyme inhibitors (ACE-I) rarely have serious or life-threatening side effects.Lisinopril-induced liver injury can present as hepatocellular or cholestatic injury.Severe hepatotoxicity secondary to lisinopril can be life threatening irrespective of the liver injury pattern.

Fat clearance of upper gastrointestinal resection specimens increases lymph node yield and may result in nodal upstaging.

INTRODUCTION: Lymph node retrieval and quantification is an important element in staging upper gastrointestinal cancers. Our department introduced fat clearance for oesophagectomy and gastrectomy specimens in 2014. This study assessed the impact of this change on lymph node yield and upstaging. METHODS: We reviewed histopathology data for upper gastrointestinal resection specimens. Patient demographics, clinical, macroscopic and microscopic data were compared with a historical cohort who did not undergo fat clearance. RESULTS: Of 158 patients, 133 resection specimens received fat clearance resulting in a significantly higher lymph node yield than the historical cohort (22 vs 13 lymph nodes, p<0.0001). Fat clearance found additional positive nodes in 24.1% of patients and increased the number of cases achieving a minimum node yield of 15. Nodes found by fat clearance caused upstaging in 15% of the cohort. DISCUSSION: Fat clearance increases node yield in upper gastrointestinal resection specimens and may cause nodal upstaging.

Long-Term Prognostic Significance of Persisting Histological Activity Despite Biochemical Remission in Autoimmune Hepatitis.

OBJECTIVES: Biochemical remission is widely considered a satisfactory treatment end point in autoimmune hepatitis (AIH). The significance of persisting histological activity despite biochemical remission is unknown. We aimed to assess the frequency and prognostic significance of persisting histological inflammation in patients with AIH who had achieved biochemical remission with treatment. METHODS: We studied 120 patients (median age at diagnosis 57 years; 81% female) with AIH by International Criteria (59% definite), who received immunosuppressive treatment and underwent a follow-up liver biopsy after at least 6 months of sustained biochemical remission (defined as normal serum ALT and globulin). RESULTS: Fifty-five patients (46%) had persisting histological activity (Ishak histological activity index (HAI) ≥4). These patients had higher serum ALT (24 vs. 18 IU/l, P=0.003) and AST (27 vs. 23 IU/l, P=0.03) at the time of follow-up biopsy, compared with patients who achieved histological remission (HAI ≤3). They had less frequent regression of fibrosis on follow-up biopsy compared with those achieving histological remission (32 vs. 60%, P=0.004) and had excess mortality (standardized mortality ratio 1.4 vs. 0.7, P<0.05). The excess mortality was due to liver disease. On multivariate analysis, persisting histological activity was independently associated with all-cause death/transplantation (HR 3.1 (95% CI 1.2-8.1); P=0.02); an association with liver-related death/transplantation fell short of significance (HR 9.7 (95% CI 0.84-111.6; P=0.07). CONCLUSIONS: Persisting histological activity, despite biochemical remission, is frequent in patients with treated AIH and is associated with lower rates of fibrosis regression and reduced long-term survival.

Long-term outcomes of patients with autoimmune hepatitis managed at a nontransplant center.

BACKGROUND & AIMS: The long-term outcomes of patients treated for autoimmune hepatitis (AIH) are considered to be good. However, follow-up data beyond 10 years are limited and confined to tertiary referral centers. We assessed long-term outcomes and determinants of outcome in patients with AIH from a nontransplant center. METHODS: We studied 245 patients (204 women; median age, 56 years; range, 2.5-87 years) with AIH (167 definite by International AIH Group criteria) managed at a single nontransplant center from 1971 to 2007. RESULTS: 229 patients (93%) achieved normal serum levels of alanine aminotransferase within 12 months after treatment. After a median follow-up period of 9.4 years (range, 0.01-36 years), 11 patients received liver transplants (2 subsequently died). Seventy other patients died (30 from liver disease), 15 were censored (moved away, defaulted, or developed primary biliary cirrhosis), and 149 were still being followed up on December 31, 2007. Survival rates from all-cause death or transplantation were 82%±3% and 48%±5% after 10 and 20 years, respectively, and from liver-related death or transplantation were 91%±2% and 70%±5%, respectively. The standardized mortality ratio was 1.63 for all-cause death (95% confidence interval [CI], 1.25-2.02), 1.86 also considering liver transplant as "death" (95% CI, 1.49-2.26), and 0.91 for non-liver-related death (95% CI, 0.62-1.19). By Cox regression analysis, liver decompensation, cirrhosis at any time, failure to normalize levels of alanine aminotransferase within 12 months, and >4 relapses per decade were significantly associated with liver-related death or transplant. CONCLUSIONS: Despite a good initial response to immunosuppression, long-term mortality of patients with AIH is greater than that of the general population.

Spectrum of liver histology in presumed decompensated alcoholic liver disease.

BACKGROUND: In presumed decompensated alcoholic liver disease (ALD; liver decompensation, heavy alcohol intake, and negative results of noninvasive screening for other causes), liver biopsy is often performed to assess severity of liver injury and to rule out other liver diseases. AIM: The aim of the study is to describe the spectrum of liver histology in such patients. METHODS: We reviewed all patients with presumed decompensated ALD seen between 1998 and 2004, in whom liver tissue was available for histology (N = 110). RESULTS: A total of 104 of the 110 patients had at least one of the histological features suggestive of ALD: fat, Mallory's hyalin, neutrophilic infiltrate, and hepatocyte ballooning. These features were more prevalent in tissue obtained within a month after presentation with decompensation than in that obtained before decompensation or more than 1 month after. These features were also associated with more severe liver dysfunction. Histology revealed a major additional diagnosis (Budd-Chiari syndrome) in only one case. In 41 patients biopsied within a month of first presentation with decompensation, Child score and Maddrey discriminant function (DF), but none of the histological features, were predictive of survival by Cox multivariate analysis. Of the 26 of these 41 patients with a Maddrey DF >32, 22 (85%) had alcoholic hepatitis. CONCLUSIONS: In patients with presumed decompensated ALD, other liver diseases are uncommon. Routine liver biopsy is of limited added value but biopsy should be considered in those in whom the noninvasive workup, or failure to recover despite abstinence, raises the possibility of other liver diseases.

Gastric sarcoidosis mimicking irritable bowel syndrome--cause not association?

Sarcoidosis is a systemic disease of unknown aetiology that may affect any organ in the body. The gastrointestinal tract however is only rarely affected outside the liver. Symptoms may be non-specific. Irritable bowel syndrome (IBS) is a common diagnosis. The recognition of IBS is aided by the use of the Rome II criteria - in the absence of organic disease. We describe the first case of a patient with gastric sarcoidosis who presented with IBS symptoms but subsequently responded to immunosuppressive therapy.

HFE genotypes in decompensated alcoholic liver disease: phenotypic expression and comparison with heavy drinking and with normal controls.

OBJECTIVES: Predisposition to alcoholic liver disease (ALD) may be partly genetic. Heterozygosity for the HFE mutations C282Y and/or H63D has been associated with more severe disease in several liver conditions. Studies in ALD have not used controls matched for alcohol consumption and results have been conflicting. METHODS: HFE genotyping was performed in two Caucasian heavy-drinking cohorts (>60 units/wk (M) or 40 units/wk (F) for >5 yr): (a) 254 patients with decompensated ALD (Child's grade B or C), (b) 130 controls with similar alcohol consumption but without liver disease. Results in males were also compared with those from another study of healthy male blood donors. RESULTS: (1) Genotype distributions for the C282Y and H63D mutations were similar in ALD patients, heavy-drinking controls, and healthy blood donors. (2) ALD patients with and without HFE mutations had similar disease severity, age at presentation, and alcohol consumption. (3) Increased serum ferritin and % transferrin saturation were seen in 63% and 29% of ALD patients, regardless of HFE genotype; the increased % transferrin saturation was due to reduced unsaturated iron binding capacity, rather than increased serum iron. (4) Stainable liver iron was present in 52% of patients; grade was greater in patients with two HFE mutations than in those with one or with none. (5) Only the two C282Y homozygote patients had substantial iron overload. CONCLUSIONS: Although serum iron abnormalities are common, C282Y and H63D mutation frequencies were not increased in heavy drinkers with decompensated liver disease. HFE mutations, although modestly influencing liver iron, do not predispose to clinically significant ALD.