Hypogammaglobulinemia, a new risk factor for hepatitis B virus reactivation : about two cases.

Reactivation of the hepatitis B virus (HBV) with immunosuppressive status has been well established, mainly due to medications such as immunosuppressive therapy like cytotoxic chemotherapy, rituximab and biologic therapy, immunosuppression after solid and bone-marrow transplantation or long-term corticosteroids therapy. We report here two cases of HBV reactivation due to global hypogammaglobulinemia. Regular HBV serologic screening and PCR for HBV-DNA should be applied for each patient with primary immunosuppressive status and history of chronic HBV infection. The necessity of a preemptive treatment remains debated.

Pathophysiological changes of the liver-muscle axis in end-stage liver disease: what is the right target?

Liver diseases and in particular end stage liver diseases are frequently complicated by muscle modifications that are linked to worse clinical outcome. In addition, recent studies have demonstrated the negative impact of these muscle changes on liver function leading to the hypothesis of a bidirectional relationship referred in the literature as "muscle-liver axis". In a context of evolution towards a more holistic and less organocentric vision of medicine, studying frailty, myosteatosis and sarcopenia and their underlying pathophysiological mechanisms has led to many publications in the last five years. These studies are describing several pathophysiological mechanisms, highlighting the extremely complex character of this relationship. This review aims to summarize these mechanisms as well as potential therapeutic targets, independently of liver disease etiology.

Intrahepatic Portal Vein Aneurysm: A Case Report of an Uncanny Late Complication of Liver Transplantation.

BACKGROUND: Whereas chronic rejection, opportunistic infections, post-transplant lymphoproliferative disorder, hemophagocytic lymphohistiocytosis, biliary tract issues, and cardiovascular side effects of immunosuppressive drugs are frequently reported as late complications in liver transplanted patients, intrahepatic portal venous aneurysm following liver transplantation remains exceptional and unusual. CASE REPORT: We report the case of a 25-year-old man who underwent a liver transplantation in 1997 because he had glycogen storage disease type 4. The patient developed a late postoperative complication, an intrahepatic portal aneurysm, and 2 episodes of acute cholangitis. DISCUSSION: By reviewing and scoping the literature, we tried to spotlight the best therapeutic attitude concerning the management of this rare complication.

Malnutrition is highly prevalent in hospitalized cirrhotic patients and associates with a poor outcome.

Background and study aims: The role of malnutrition on the prognosis of hospitalized cirrhotic patients is incompletely studied. Our aim was to determine the prevalence of malnutrition, functional scores and their impact on prognosis of hospitalized cirrhotic patients. Patients and methods: This retrospective study included all patients with cirrhosis hospitalized in the gastroenterology unit at Saint-Luc university hospital, Brussels between April 2014 and September 2014. Nutritional status was evaluated according to minimum clinical summary diagnostic criteria. Cirrhosis-related complications or death occurrence were analysed in a one-year follow-up. Results: 95 cirrhotic patients were assessed for nutritional status and outcomes. Malnutrition affected 45.3% of patients and was more frequent with the severity of cirrhosis: 29% in Child-Pugh A, 48.8% in Child-Pugh B and 72.2% in Child-Pugh C patients. 58.9% of patients developed cirrhosis-related complications (60.7% in the malnutrition group vs. 39.3%, p<0.001, OR 5.06, IC95 1.90-14.58) and 33.7% of patients died (68.75% vs. 31.25%, p=0.002, OR 4.33, IC95 1.62-12.28). Adjusting for age, sodium, MELD, Charlson index, hepatocellular carcinoma, platelets, diabetes, prognostic nutritional index and Braden scale, malnutrition was significantly associated with higher mortality and morbidity rates with an OR of 3.56 (CI95 1.55-8.16) and 2.09 (CI95 1.16-3.77) respectively. Braden scale was significantly associated with higher mortality (p=0.027, OR 1.25, CI95 1.03-1.52) whereas prognostic nutritional index was associated with higher morbidity (p=0.001, OR 0.94, CI95 0.90-0.98). Conclusion: Malnutrition is highly prevalent in hospitalized cirrhotic patients. Malnutrition, low prognostic nutritional index and low Braden scale are associated with poor outcomes in cirrhosis.

The use of autologous peritoneum in surgery of portal hypertension: H-shape splenorenal shunt using simple layer peritoneal tube.

The management of portal hypertension complicated by iterative gastro-intestinal bleeding remains challenging, especially in a low-income environment. Interventional radiology and endoscopic treatments are not always accessible, and a definitive surgical option may prove to be lifesaving. We report a new technique of surgical portosystemic shunt that can be performed in all contexts. We describe the surgical technique of a H-shaped splenorenal shunt using autologous rolled up peritoneum as a vascular graft.

Exceptional manifestation of Madelung's disease after liver transplantation.

Unlike simple obesity, Madelung's disease (MD) is a rare disease characterized by symmetric accumulation of massive adipose tissue on the neck, the superior part of the trunk and limbs, leading to a pathognomonic cosmetic deformity. Here, we report an extremely rare case of MD associated with bilateral gynecomastia in a 61-year-old man, with a history of recent liver transplantation for alcoholic liver disease (ALD).

Innovations in liver transplantation in 2020, position of the Belgian Liver Intestine Advisory Committee (BeLIAC).

Liver transplantation (LT) remains the only curative option for patients suffering from end-stage liver disease, acute liver failure and selected hepatocellular carcinomas and access to the LT-waiting list is limited to certain strict indications. However, LT has shown survival advantages for patients in certain indications such as acute alcoholic hepatitis, hepatocellular carcinoma outside Milan criteria and colorectal cancer metastases. These newer indications increase the pressure in an already difficult context of organ shortage. Strategies to increase the transplantable organ pool are therefore needed. We will discuss here the use of HCV positive grafts as the use of normothermic isolated liver perfusion. Belgian Liver Intestine Advisory Committee (BeLIAC) from the Belgian Transplant Society (BTS) aims to guarantee the balance between the new indications and the available resources.

Risk of hepatocellular carcinoma and fibrosis evolution in hepatitis C patients with severe fibrosis or cirrhosis treated with direct acting antiviral agents.

Background and study aims: Cirrhosis associated to chronic hepatitis C virus (HCV) is one of the leading cause of hepatocellular carcinoma (HCC). The goal of our study was to evaluate first the risk and determinants of HCC and second the evolution of fibrosis in patients treated for HCV with advanced fibrosis stages who achieved sustained virological response (SVR) after direct-acting antivirals (DAA) treatment. Patients and methods: We conducted a prospective study on HCV patients with F3 or F4 Metavir fibrosis scores treated with DAA between October 2014 and February 2017. The annual incidence rate for HCC was calculated. We used Cox regression model in order to identify factors associated with HCC. Transient elastography (TE) was performed 12 and 24 months after the end of DAA treatment and non-invasive liver fibrosis biomarkers were performed twice a year during follow-up. Results: 143 patients with severe fibrosis or cirrhosis were enrolled in the study. 6 patients developed HCC. The annual incidence rate of HCC in our cohort was 2.7 per 100 patients. Risk factors associated with HCC after DAA were genotype 2 and steatosis. Overall TE values significantly decreased after DAA treatment with a median value prior to treatment of 16.9 kPa to a median of 10.8 kPa 24 months after the end of the treatment. Biological fibrosis scores also significantly decreased following viral eradication. Conclusions: DAA treatment does not seem to be associated with HCC promotion after HCV eradication in patients with severe fibrosis stages. DAA-induced SVR is associated with a reduced estimation of fibrosis.

Liver transplantation during the COVID-19 epidemic : recommendations from the Belgian Liver Intestine Transplant Committee (BeLIAC).

Since January 2020, the Novel Coronavirus Disease 2019 (COVID-19) pandemic has dramatically impacted the world. In March 2020, the COVID-19 epidemic reached Belgium creating uncertainty towards all aspects of life. There has been an impressive capacity and solidarity of all healthcare professionals to acutely reconvert facilities to treat these patients. In the context of liver transplantation (LTx), concerns are raised about organ donation shortage and safety, the ethics of using limited healthcare resources for LTx, selection criteria for LTx during the epidemic and the risk of de novo COVID-19 infection on the waiting list and after LTx. BeLIAC makes several recommendations to try to mitigate the deleterious effect that this epidemic has/will have on donation and LTx, taking into account the available resources, and trying to maximize patients and healthcare professionals' safety.

Acute liver graft cellular rejection after interferon-free antiviral treatment for HCV infection. Is there a risk? A warning about three cases.

All patients transplanted for hepatitis C (HCV)- related cirrhosis will experience a recurrence of the viral disease on the liver graft with an accelerated course of the disease and a progression to advanced liver fibrosis in up to 50% of the patients at 5 years post-liver transplantation. HCV infection is a high risk for graft lost. We report here three cases of patients transplanted for hepatocellular carcinoma on HCV-related cirrhosis. All cases experienced an acute cellular rejection after the end of HCV therapy with direct acting antivirals (DAAs). We thus advocate for a close monitoring of tacrolimus and liver tests even a few months after the end of the treatment. Clinicians using DAAs after liver transplantation should be aware of the dynamics of tacrolimus levels during therapy and immunological changes that can occur even several weeks (or months) after the end of DAA treatment.

Early high levels of regulatory T cells and T helper 1 may predict the progression of recurrent hepatitis C after liver transplantation.

BACKGROUND: Immune response failure against hepatitis C virus (HCV) has been associated with an increased regulatory T cell (Treg) activity. After liver transplantation (LT), 80% of patients experience an accelerated progression of hepatitis C recurrence. The aim of this work was to assess the involvement of Tregs, T helper (Th) 1, 2 and 17 cells in recurrent hepatitis C. METHODS: Peripheral blood cells obtained before and one month after LT from 22 recipients were analysed. Forty-four key molecules related to Treg, Th1, 2 and 17 responses, were evaluated using qRT-PCR. Liver recipients were classified in two groups according to graft fibrosis evaluated by the METAVIR score on the biopsy performed one year after LT (mild: F ≤ 1, n = 13; severe: F > 1, n = 9). Patients developing a severe recurrence were compared with patients with a mild recurrence. RESULTS: mRNA levels of Treg markers obtained one month after LT were significantly increased in patients with a severe disease course when compared to patients with a mild recurrence. Markers of the Th1 response were elevated in the same group. No differences in the markers determined before LT were observed. CONCLUSION: These findings suggest that Treg, induced by a multifactorial process, which could include a strong Th1 response itself, may play a role in suppressing the early antiviral response, leading to a severe recurrence of hepatitis C.

Regulatory T cell therapy: An option to induce operational tolerance in liver transplantation.

Regulatory T cells (Treg) may play an important role in operational (clinical) tolerance (OT), a stable graft function without immunosuppression in an otherwise immunocompetent host, that is spontaneously observed in some patients many years after transplantation. Several ongoing clinical trials are currently testing the effects of donor-specific or non-specific Treg infusion with the goal to induce this state of OT a few months after liver transplantation (LT). The preliminary results of two of these trials have been recently published, and raise a number of comments and issues: (1) These two papers demonstrate that a 100 to 1000-fold ex-vivo expansion of Treg is possible in humans after 2 weeks of culture. The optimal human Treg dose is however not clearly established, and might be higher than the dose that would be expected from translating murine data. (2) A lot of concerns are remaining regarding the Treg purity before expansion, the Treg stability during in vitro culture and the in vivo fate of infused cells. A strict monitoring of Treg should thus be done at each step. (3) Since Treg may play a detrimental role in some conditions, such as viral diseases and cancer, potential LT recipients with such diseases should probably be excluded from the initial trials of Treg infusion. (4) The follow-up of tolerant liver recipients should include repeated liver biopsies and detection of autoantibodies and humoral response, in addition to conventional liver graft assessment, in order to prevent the development of immune complications related to immunosuppression withdrawal. (5) The final issue raised by Treg therapy in LT is the choice of the immunosuppressive regimen used before tapering or withdrawal, appropriate to preserve OT establishment.

D-lactic acidosis: an unusual cause of encephalopathy in a patient with short bowel syndrome.

A 24-year-old woman with a short bowel syndrome following post-ischemic small bowel resection, developed several episodes of lethargy, echolalia and ataxia. D-lactic acidosis was identified as the cause of neurological disturbances. This infrequent disorder can be precipitated by intake of a large amount of sugars, in patients with short bowel syndrome. It should be suspected in the presence of metabolic acidosis with increased anion gap and a normal level of L-lactic acid. The diagnosis relies on the specific dosage of D-lactic stereoisomer. Proper management involves rehydration, diet adaptation and oral administration of poorly absorbed antibiotics in order to modify the colonic flora responsible for D-lactic production.

Irritable bowel syndrome: the role of the intestinal microbiota, pathogenesis and therapeutic targets.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that predominantly affects women and accounts for up to 40% of the gastroenterology unit outpatient visits. The pathophysiology is complex and multifactorial. In the present review we will focus on the role of intestinal dysbiosis in its pathogenesis and treatment. Post-infectious IBS (PI-IBS) can put light on the mechanisms underlying IBS. Modified commensal gut flora may lead to mucosal inflammation. Several changes such as an increase in mucosal cellularity (enterochromaffin cells, lamina propria T lymphocytes and mast cells), modified pro-inflammatory/anti-inflammatory cytokine balance and disordered neurotransmission have been observed. The normal microbiota is an essential factor in health. A modification of the flora, such as small intestinal bacterial overgrowth (SIBO) is thought to play a pathogenic role in IBS. Changes in the composition of the luminal and mucosal colonic flora have been linked to IBS. It is not clear however, whether these changes are a cause or a consequence of the syndrome. The comprehension of the interaction between the dysbiotic microbiota and the host will probably lead to the development of focused therapies. Based on these assumptions, treatments modulating the microbiota have been investigated. On the one hand several probiotics have shown a reduction in IBS symptoms by an immunomodulatory and analgesic effects. On the other hand antibiotic treatment has proven efficacy in treating IBS with or without associated SIBO. Due to its complex pathophysiology, treating IBS nowadays implies multiple approaches, one of which may be modulation of the intestinal flora.

Determinants of growth in diabetic pubertal subjects.

OBJECTIVE: To analyze the relationship among metabolic control, IGF-I, and growth in pubertal diabetic subjects. RESEARCH DESIGN AND METHODS: In 72 diabetic children, we have studied the pattern of change of IGF-I, IGF-I SD score, IGF binding protein (BP)-1, and growth rate in different pubertal stages and have analyzed their relation to age sex, weight/length index, HbA1c, insulin concentration, insulin dose, and dehydroepiandrosteronesulfate (DHEAS). RESULTS: The serum IGF-I values increased up to Tanner stage 4 and thereafter decreased, whereas IGFBP-1 showed the inverse pattern. When transforming the IGF-I values into SD scores, correcting for age, sex, and pubertal stage, it was shown that the deviation from normal values increased with increasing pubertal stage in boys, but was equal in stages 3-5 in girls. Using multiple regression analysis, HbA1c, insulin dose, and DHEAS were significantly correlated to IGF-I SD score (R2 = 0.253, P = 0.001). IGFBP-I levels in the afternoon were within normal range. LogIGFBP-1 showed an inverse correlation, to insulin concentration in single correlation (r = -0.26, P = 0.02). In single correlation, growth rate correlated significantly to insulin dose (r = 0.25, P = 0.03). In a multiple regression analysis, only DHEAS and IGF-I SD score were found to be significantly correlated to growth rate (R2 = 0.370, P < 0.001). The 18 adolescents who had reached their final height did not deviate from their target final height, according to their recorded growth since birth. CONCLUSIONS: In a group of fairly well-controlled diabetic children, the normal increase in IGF-I during puberty is blunted. Despite decreased IGF-I levels, target final height was attained, probably because of adequate insulin compensation leading to normal IGFBP-l, thus adequate bioavailability of IGF-I. Our results point out the importance of sufficient exogenous insulin in the period of rapid linear growth.

Fatal outcome of disseminated Mycobacterium avium infection in childhood. A case of primary incompetent monocyte/macrophage function?

Disseminated BCG infection rarely heals, and disseminated disease caused by the Mycobacterium avium complex usually has a poor prognosis with a short time to death. The case of a boy who died after 9 years of diagnosed disseminated M. avium complex infection is described. He showed no signs of previously known immunodeficiency except an incompetent primary monocyte/macrophage function. This case has been commented on in Acta Paediatrica Scandinavia (1982) as "the first infant to survive a generalized BCG infection".

Relations between age, metabolic control, disease adjustment and psychological aspects in insulin-dependent diabetes mellitus.

The relations between age, metabolic control, disease adjustment, and psychological factors in boys and girls with recently diagnosed insulin-dependent diabetes mellitus (IDDM) were studied. Older girls had significant higher postremission glycosylated haemoglobin A (Hb AIc) levels (p = 0.008). Girls with more hospitalizations had a lower developmental level (p = 0.05), and had significantly more problems in the behavioural rating (p = 0.05). Boys with more hospitalizations had a more external locus of control (p = 0.01), more difficulties with disease adjustment, more emotional problems, and were also clinically assessed as having more behavioural problems. Boys showing more difficulties in psychological adjustment to the disease also had higher postremission Hb AIc levels (p = 0.02). Although Swedish children with IDDM of short disease duration do not differ from healthy children in important psychological aspects, older girls and a small group of problematic younger boys are at risk of developing metabolic imbalance after a short disease duration.