Clinical significance and impact of gastric non-Helicobacter pylori Helicobacter species in gastric disease.

BACKGROUND: Gastric non-Helicobacter pylori Helicobacter (NHPH) species naturally associated with animals have been linked with gastric disease in human patients. AIM: The prevalence and clinical significance of zoonotic gastric NHPHs was determined in large and well-defined, H. pylori-negative, gastric patient populations. METHODS: Patients were retrospectively (n = 464) and prospectively (n = 65) included for gastric biopsy collection: chronic gastritis (CG), peptic ulcer disease and gastric MALT lymphoma, without identified aetiology. PCR and sequencing was performed for the detection of gastric Helicobacter species. Retrospectively, asymptomatic gastric bypass patients (n = 38) were included as controls. Prospectively, additional saliva samples and symptom and risk factor questionnaires were collected. In this group, patients with gastric NHPH infection were administered standard H. pylori eradication therapy and underwent follow-up gastroscopy post-therapy. RESULTS: In the retrospective samples, the prevalence of gastric NHPHs was 29.1%, while no gastric NHPHs were detected in control biopsies. In the prospective cohort, a similar proportion tested positive: 27.7% in gastric tissue and 20.6% in saliva. The sensitivity and accuracy for the detection of gastric NHPHs in saliva compared to gastric tissue was 27.8% and 69.8% respectively. Following eradication therapy, clinical remission was registered in 12 of 17 patients, histological remission in seven of nine and eradication in four of eight patients. CONCLUSION: These findings suggest a pathophysiological involvement of NHPHs in gastric disease. Patients presenting with gastric complaints may benefit from routine PCR testing for zoonotic gastric NHPHs.

Efficacy and safety of glecaprevir/pibrentasvir in patients with HCV genotype 5/6: An integrated analysis of phase 2/3 studies.

BACKGROUND & AIMS: Hepatitis C virus (HCV) has high genetic diversity with six major genotypes (GT) GT1-6 and global distribution. HCV GT5 and 6 are rare with < 10 million people infected worldwide. Data on direct-acting antiviral use in these rare HCV genotypes are limited. The study aimed to evaluate the efficacy and safety of glecaprevir/pibrentasvir (G/P) in a pooled analysis of phase 2/3 trials in HCV GT5 or 6-infected patients without cirrhosis or with compensated cirrhosis. METHODS: Patients with chronic HCV GT5 or 6 infection received oral G/P (300 mg/120 mg) once daily for 8 or 12 weeks. The primary efficacy endpoint was sustained virological response at post-treatment week 12 (SVR12) in the intention-to-treat population. RESULTS: One hundred eighty-one patients were evaluated; 56 with HCV GT5 and 125 with HCV GT6. The majority were treatment-naïve (88%) and non-cirrhotic (85%). Overall SVR12 rate with 8- or 12-week G/P treatment was 98% (178/181). Eight-week treatment with G/P yielded SVR12 rates of 95% (21/22) in HCV GT5- and 99% (69/70) in HCV GT6-infected non-cirrhotic patients. Eight- and 12-week treatment of patients with compensated cirrhosis achieved SVR12 rates of 100% (10/10) and 94% (17/18) respectively. The G/P regimen was well-tolerated; 3% (6/181) Grade 3 or higher adverse events, and no serious adverse events were attributed to G/P or led to study drug discontinuation. CONCLUSIONS: This integrated dataset demonstrates a high SVR12 rate following 8-week G/P treatment in patients with HCV GT5 (96%) or GT6 (99%) infection without cirrhosis or with compensated cirrhosis.

Alcohol intake increases the risk of HCC in hepatitis C virus-related compensated cirrhosis: A prospective study.

BACKGROUND & AIMS: Whether alcohol intake increases the risk of complications in patients with HCV-related cirrhosis remains unclear. The aim of this study was to determine the impact of alcohol intake and viral eradication on the risk of hepatocellular carcinoma (HCC), decompensation of cirrhosis and death. METHODS: Data on alcohol intake and viral eradication were prospectively collected in 192 patients with compensated HCV-related cirrhosis. RESULTS: 74 patients consumed alcohol (median alcohol intake: 15g/day); 68 reached viral eradication. During a median follow-up of 58months, 33 patients developed HCC, 53 experienced at least one decompensation event, and 39 died. The 5-year cumulative incidence rate of HCC was 10.6% (95% CI: 4.6-16.6) in abstainers vs. 23.8% (95% CI: 13.5-34.1) in consumers (p=0.087), and 2.0% (95% CI: 0-5.8) vs. 21.7% (95% CI: 14.2-29.2) in patients with and without viral eradication (p=0.002), respectively. The lowest risk of HCC was observed for patients without alcohol intake and with viral eradication (0%) followed by patients with alcohol intake and viral eradication (6.2% [95% CI: 0-18.4]), patients without alcohol intake and no viral eradication (15.9% [95% CI: 7.1-24.7]), and patients with alcohol intake and no viral eradication (29.2% [95% CI: 16.5-41.9]) (p=0.009). In multivariate analysis, lack of viral eradication and alcohol consumption were associated with the risk of HCC (hazard ratio for alcohol consumption: 3.43, 95% CI: 1.49-7.92, p=0.004). Alcohol intake did not influence the risk of decompensation or death. CONCLUSIONS: Light-to-moderate alcohol intake increases the risk of HCC in patients with HCV-related cirrhosis. Patient care should include measures to ensure abstinence. LAY SUMMARY: Whether alcohol intake increases the risk of complications in patients with HCV-related cirrhosis remains unclear. In this prospective study, light-to-moderate alcohol intake was associated with the risk of hepatocellular carcinoma in multivariate analysis. No patients who did not use alcohol and who reached viral eradication developed hepatocellular carcinoma during follow-up. The risk of hepatocellular carcinoma increased with alcohol intake or in patients without viral eradication and was highest when alcohol intake was present in the absence of viral eradication. Patients with HCV-related cirrhosis should be strongly advised against any alcohol intake. Patient care should include measures to ensure abstinence.

Liver Fibrosis Associated with Iron Accumulation Due to Long-Term Heme-Arginate Treatment in Acute Intermittent Porphyria: A Case Series.

Acute intermittent porphyria (AIP) is an autosomal dominant disorder of heme biosynthesis due to a mutation in the porphobilinogen deaminase gene. The mutation causes a deficiency in the porphobilinogen deaminase enzyme, thereby causing an accumulation of heme precursors (δ-aminolevulinic acid and porphobilinogen). These neurotoxic heme precursors elicit acute neurovisceral attacks, which can be treated with heme-arginate infusions. Some patients require heme-arginate infusions on a regular basis for many years, which ultimately leads to an iron accumulation (increased serum ferritin and iron accumulation in the liver, spleen, and bone marrow on MRI). We report three AIP patients, who developed iron accumulation (with serum ferritin up to 7,850 microgram/liter) due to multiple heme-arginate infusions. We report for the first time that the iron accumulation in these patients was associated with fibrosis on liver histology. CONCLUSION: Regular heme-arginate treatment in AIP does not only lead to increased serum ferritin but may also induce liver fibrosis. This should be taken into account, when weighing the risks and benefits of repeated heme-arginate treatment against the risk and benefits of treating refractory AIP by liver transplantation.

Efficacy of interferon-based antiviral therapy in patients with chronic hepatitis C infected with genotype 5: a meta-analysis of two large prospective clinical trials.

The characteristics and response rate to pegylated interferon and ribavirin (PEG-INF + RBV) of patients with chronic hepatitis C infected with genotype 5 are poorly documented. A meta-analysis of two large phase III/IV prospective randomized clinical trials conducted in Belgium in patients with chronic hepatitis C (n = 1,073 patients) was performed in order to compare the response to antiviral therapy of hepatitis C virus (HCV) genotype 5 with that of other HCV genotypes. A subset of HCV-1 infected patients selected from within the study database were selected to match the HCV-5 sample for known prognostic factors. In Belgium HCV-5 is responsible for a significant minority of cases of chronic hepatitis C CHC (4.5%) and is characterized by a more advanced age (58.4 years), a high frequency of cirrhosis (27.7%), a specific mode of HCV acquisition, and a particular geographic origin (66.7% of patients from West Flanders). The primary comparative analysis showed that response to treatment with PEG-INF + RBV of HCV-5 is similar to HCV-1 and lower compared to HCV-2/3. The analysis of the matched patient subgroup demonstrates that the HCV-5 "intrinsic sensitivity" to PEG-IFN + RBV therapy is identical to HCV-1, with a sustained virological response of 55% in both groups. In contrast to previous publications, this meta-analysis suggests that HCV-5 response to treatment is closer to HCV-1 than to HCV-2/3 and suggests that in Belgium HCV-5 infection should be treated with the same antiviral regimen as HCV-1.

Postsurgery activation of dormant liver micrometastasis: a case report and review of literature.

BACKGROUND: We present the case of a 55-year-old woman who underwent a Whipple procedure for pancreatic adenocarcinoma. The preoperative work-up showed no signs of liver metastasis and confirmed the patient's operability, but at less than 40 days postoperatively there were diffuse liver metastasis present on CT. This rapid evolution raises the question whether current staging systems are adequate in determining a patient's operability. It also suggests an interaction between the primary tumor and the host and the existence of disseminated tumor cells. DISCUSSION: In this article, we give an explanation for the clinical evolution presented in our case using the "integrated organ" and the "concomitant resistance" hypotheses. We believe that, if these theories continue to prove their viability, the search for disseminated tumor cells will be essential for good clinical practice in this type of pathology.

Congenital veno-venous malformations of the liver: widely variable clinical presentations.

BACKGROUND AND AIM: Congenital portosystemic veno-venous malformations are rare abnomalities that often remain undiagnosed. Typically they are classified by their anatomical characteristics according to Morgan (extrahepatic, Abernethy malformations type Ia,b and II) and Park (intrahepatic, types 1-4). However, their clinical presentation is less dependent on the anatomical type. METHOD: We reviewed the clinical characteristics of six cases drawn from our files (from 1970 to 2006). RESULTS: One patient, a 25-year-old male, had extrahepatic shunting whereby the liver receives only arterial blood because the portal vein (PV) connects with the inferior caval vein (ICV) (Abernethy Ib); he presented with episodes of jaundice and pruritus. Three patients had extrahepatic shunting with patent intrahepatic portal veins, but with shunting of splenomesenterial blood towards the ICV (Abernethy II); these included a 66-year-old male with hepatic encephalopathy, a 17-year-old female with (porto?-)pulmonary hypertension without portal hypertension, and a 33-year-old female with epidsodes of acute pain secondary to spontaneous bleeding within a primary liver tumor. Two patients had intrahepatic shunting; these included an 8-year-old boy who was diagnosed incidentally during work-up for abnormal liver enzymes with a communication between right PV and ICV (Park type 1), and a 59-year-old male with multiple PV-ICV-shunts in several liver segments (Park, type 4) who presented with hepatic encephalopathy. CONCLUSION: Patients often present with signs of hepatic shunting (encephalopathy, pulmonary hypertension, hepatopulmonary syndrome, and/or hypoglycemia) with relative sparing of the synthetic liver function in the absence of portal hypertension. Some shunts present with space-occupying lesions (focal nodular hyperplasia, hepatocellular carcinoma, nodular regenerative hyperplasia, etc.) or biliary atresia. Finally, some cases are detected incidentally.