Background: Even with current standard treatment after variceal bleeding which includes combination of nonselective b-blockers and repeated endoscopic variceal ligation, the risk of rebleeding and mortality are high. Statins exhibit an antifibrotic effect and improves HVPG. We evaluated whether addition of simvastatin to carvedilol plus EVL therapy reduces variceal rebleeds or death in patients with cirrhosis. Method: Patients with a variceal bleed 5 to 10 days before were randomly assigned to groups A [carvedilol (n = 69)] or group B [carvedilol (maximum dose - 12.5mg), and simvastatin (40mg/day) (n = 65)]. Primary end points were variceal rebleeding or death. Secondary end points were new complications of portal hypertension and serious adverse effects of drugs. Results: During a mean follow-up of 49.05 ± 25.74 weeks, composite end point i.e. rebleeding or death developed in 23 patients (33.3%) in group A and 12 patients (18.5%) in group B [HR for simvastatin = 0.512; 95% CI: 0.254 – 1.030; p = 0.06]. In subgroup analysis by excluding patients of Child C class, 18 patients (34.6%) in group A and 7 patients (13.6%) in group B developed composite end point [HR for simvastatin = 0.369; 95% CI: 0.154 – 0.887; p = 0.026]. 17.4% and 15.4% patients in group A and B developed additional secondary complication [HR = 0.86; 95% CI: 0.345-2.161; p = 0.75). No simvastatin induced significant adverse effects were found. Conclusion: Addition of simvastatin to carvedilol and EVL may reduce the rebleeding and death in patients with less advance liver disease.

Hepatitis C Virus (HCV) infection is usually treated with direct acting antivirals (DAAs) for 12 weeks. In treatment naive patients with genotype (GT) 1 infection without cirrhosis and baseline viral load < 6 million, 8 weeks of Ledipasvir/Sofosbuvir (LDV/SOF) is an option. Eight weeks with Glecaprevir/Pibrentasvir (GLE/PIB) is an option for patients with GT 1 through 6 without cirrhosis. Our objective was to evaluate achievement of Sustained Virologic Response (SVR) after 8 weeks of LDV/SOF or GLE/PIB in our HCV-infected veterans. Patients with HCV infection that received GLE/PIB or LDV/SOF for a planned 8 weeks of therapy in the past four years were reviewed (January 2015-September 2018). Treatment outcomes were evaluated through medical record review. Two hundred sixty-five veterans were initiated on 8 weeks of therapy with either GLE/PIB or LDV/SOF. Of these, 231 (87%) were initiated on 8 weeks of LDV/SOF and 34 (13%) were initiated on 8 weeks of GLE/PIB. The majority of patients had GT 1 (93%) infection. One hundred and ninety-five veterans who completed 8 weeks of LDV/SOF and 30 veterans on GLE/PIB had follow-up viral loads. The overall SVR was 95%. Treatment with GLE/PIB resulted in a higher SVR rate (100%) compared to LDV/SOF (95%). Elderly patients had similar SVR rates. Treatment with 8 weeks of DAA is effective in our veteran population and showed an SVR rate similar to literature reports. The SVR for patients treated with 8 weeks LDV/SOF was slightly lower than the SVR for GLE/PIB; however, the GLE/PIB population was smaller

Hepatocellular carcinoma (HCC) is characterized by high morbidity, high recurrence, and high mortality rates. In China, the morbidity of HCC is fifth among all malignant tumors and HCC is the third most common cause of cancer-related deaths. Most HCC patients also have liver cirrhosis. Surgery is the sole curative method for HCC; however, many patients are diagnosed with HCC during its advanced stages so radical resection can no longer be performed. Therefore, the proportion of patients who undergo radical hepatectomy is less than 30%. Patients with mildly advanced HCC cannot undergo hepatectomy and thus transcatheter arterial chemoembolization (TACE) and/or biological targeted therapy are alternative options. However, data on the effects of TACE therapy or biological targeted therapy are limited. Therefore, an investigation of multimodal and individualized treatments is critical to ensure the best treatment. In June 2018, we treated an advanced HCC patient with multiple metastases and right portal vein tumor thrombus. The patient exhibited partial remission after undergoing treatment with TACE and crizotinib capsules for 1 month. The case and a literature review are reported here.

Radiofrequency ablation is one of the most commonly used therapies for potentially curative small hepatocellular carcinoma. Although radiofrequency is usually a safe procedure, severe and potentially fatal complications can happen. This is a case of a 72 years old woman with cirrhosis secondary to Metabolic Associated Fatty Liver Disease (MAFLD), who presented recurrent hydrothorax after treating hepatocellular carcinoma (HCC) with radiofrequency ablation (RFA), and in which diaphragmatic perforation was subsequently diagnosed. We reviewed the differential diagnosis and management in a pleural effusion after a radiofrequency procedure. Although diaphragmatic perforation is an uncommon complication after RFA procedure, this case aims to help clinicians being aware of non-habitual complications.

Objectives: There are variations in therapeutic regimens of different liver diseases. The accurate diagnosis ensures prompt recovery from these diseases. The present study aimed to evaluate the underlying causes of unexplained signs and symptoms associated with liver diseases through biopsies. Methods: A retrospective study was conducted in a public child care specialty of Lahore, Pakistan. The data was collected from medical records of the patients who were index hospitalized with unexplained clinical presentation of liver disease between 1st July, 2017 and 31st December, 2017. Data were analyzed by using Statistical Packages for Social Sciences (IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.), and Microsoft Excel (MS Office 2010). Results: Overall, the records of 53 patients were selected for the study. Most of them were 11 to 15 years of age. The patients were presented with unexplained hepatomegaly (60.4%) and jaundice (40.7%) during index hospitalization which made them eligible for liver biopsy (LB). The findings of LB revealed that the underlying causes of liver diseases in most of the cases were metabolic (33.9%) and inflammatory disorders (22.6%). Majority of the patients were ≤4 years of age, however cryptogenic cirrhosis (39.1%) was commonly found in >10 years of age. Although most of the patients were suffering from metabolic disorders (p-value=0.07) and liver cirrhosis (p-value=0.08) but these were not statistically significant. Conclusions: LB was beneficial in evaluating the etiologies of unexplained signs and symptoms of liver diseases. It was found that glycogen storage diseases and liver cirrhosis were the most common etiologies of liver diseases among pediatric patients. But etiologies like metabolic and inflammatory diseases were insignificantly associated with gender.

Background: The measures are being put in place for the management of Hepatitis B virus (HBV) infection in Hargeisa, Somaliland among pregnant women remain the most vulnerable to develop chronic hepatitis. Routine screening in pregnant women is therefore necessary for effective control. However, the performance of the commonly used the HBsAg sero test strips has been available. Also, identifying the risk factors of transmission in pregnant women is importance for the implementation of preventive measures. Hence, the goal of this study was to determining seroprevalence and associated risk factors with HBV infection among pregnant women. Material & Methods: The study area was carried out at Hargeisa group hospital in Somaliland from May 2018 up to December 2018. The researcher was collected research pregnancy woman data through questionnaire & used diagnostics methods such as Hepatitis B surface antigen (HBsAg) test, antibodies test (HBsAb) by used anti-card test and ELIZA system. In order to find specific full information’s about patients & relationship the associated risk factors with hepatitis B in pregnancy. Data processed and analyzed by used both words and SPSS package. The sample size investigated was 80 patients. Of these, 28 were excluded; among the reasons for exclusion were prior HBV vaccination and known HBsAg sero-positive status. Aims of Study: The study was designed & aimed to determine seroprevalence and associated factors of HBV infection among pregnant women. To assess and establish if there is significant relationship between blood transfusion and hepatitis B virus at Hargeisa group hospital (HGH). Results and Discussion: The results in the current study shown that the pregnancy with hepatitis BV and it relation with appeared some symptoms in our study was 24(46.15%) of patients appeared they have cirrhosis symptom, 12(23.08%) of patients answered they have liver failure, while 9(17.31%) of patients appeared yellowish of eyes & skin and 5(9.62%) showed hepatic cancer. Overall, HBV prevalence: HBsAg was detected in fifteen 15(31.3%) of the participants while all fifteen (100%) had total HBcAb (both IgM and IgG). Of the HBsAg sero-positive women, 26(42.7%) were positive for HBeAg; eight (13.3%) were positive for HBeAb and four 4(9%) were negative for both HBeAg and HBeAb which was close similar with other previous studies. On the other hand, We found identify statistically significant p-values < 0.05 and high relationship between HBV and some demographic and clinical risk factors such as blood transfusions, levels of knowledge about HBV infection in addition to age and marital status. Conclusion: The results of this study showed that the seroprevalence of HBV infections in pregnant women and it relationship with blood transfusion in Hargeisa Group Hospital, Hargeisa, Somaliland is high. However, further studies are needed to assess the role of other demographic and clinical risk. Urgent action is required to improve hepatitis B infection control measures to reduce dependence on blood transfusions and make new policies for treatment of anemia in HGH

Hepatitis B virus (HBV) is one of the world’s major infectious diseases with 350 million people who are chronic carriers of HBV [1]. Significant minorities go on to develop liver cirrhosis or hepatocellular carcinoma and over 1 million die annually from HBV-diseased liver. Janahi E. at faculty of science, Bahrain University, Bahrain has submitted the following information [2], on HBV-genome organization as part of his Ph.D. degree (2007) in Imperial College, England. HBV genomic organization has 4 Open Reading Frames (ORFs) i.e. Pre-S/S Gene, Pre-C/C ORF, P ORF and X ORF. Regulatory Elements has 4 promoters (pre S2, pre S1, C promoters and X promoters), Pregenomic RNA, Enhancers (Enh 1 and Enh 2) where they are involved in cccDNA formation, Glococorticoid-Responsive Element which is located in X ORF and P ORF overlapping, Polyadenylation Signal (Direct Repeat 1 (DR1) and Direct Repeat 2 (DR2)), Epsilon-Stem Loop and Post-Transcriptional Regulatory Element. HBV genotype D is prevalent in our Middle East area. The HBV genome is a partially relaxed-circular dsDNA molecule consisting of a full length strand (minus strand) with a single unique nick and a complementary (positive strand) of variable length. HBV is considered as a para-retrovirus because its replication involves the reverse transcription of an intermediate-RNA function, of pre-genomic RNA (pgRNA). Replication of HBV genome starts with the encapsidation of the pgRNA and encodes HBV polymerase into an immature nucleocapsid formed by the viral core antigen.

Background: The main cause of adrenal insufficiency (AI) in paediatric patients is prolonged treatment with corticosteroids. Determination of plasma cortisol (PC) during ACTH test is the most used adrenal function indicator in clinical practice. However, determination of salivary cortisol (SC), a simple test especially useful in children in order to avoid invasive procedures, can be used as an alternative technique for the diagnosis of adrenal disease. Methods: A two-year prospective study (January 2014-January 2016) in paediatric patients (2-18 years of age) treated with corticosteroids for more than fifteen days, who were investigated for suspected AI. Low-dose ACTH test was used to determine adrenal function and samples for SC and PC were obtained simultaneously in basal situation and during the test (at 30, 60 and 90 minutes). Results: 230 samples (118 PC-112 SC) of 30 studies belonging to 20 patients (4 males), mean age 10.93 years ± 3.69 SD. Pearson’s correlation coefficient showed a positive correlation between PC and SC (r = 0.618, p < 0.001). All the studies with some determination of PC higher than 18 μg/dL (n = 8) had a SC peak higher than 0.61 μg/dL with a specificity of 66.67% and a sensitivity of 93.94% (ROC analysis). Conclusion: Measurement of SC is a less invasive, easier and quicker test than PC to measure plasma free cortisol levels. In our study, a SC peak in low-dose ACTH test higher than 0.61 μg/dL was able to discriminate patients without AI, and proved to be a useful tool in the initial evaluation of children with suspected AI.Introduction The activation of the hypothalamic-pituitary-adrenal axis in response to critical illness and the resulting release of cortisol from the adrenal cortex are essential to stress adaptation. Adrenal insufficiency (AI) is described as the inability of adrenal glands to produce an appropriate hormonal secretion not only under stress but also in basal situation. Therefore, a low baseline plasma cortisol (PC) (< 5 μg/dL) and a poor cortisol response to stimulation with exogenous adrenocorticotropic hormone (peak < 18 μg/dL) are some of the defining criteria of this condition [1,2]. It is well known that the main cause of AI in paediatric patients is prolonged treatment with exogenous corticosteroids, which is an iatrogenic cause derived from the increasing complexity of paediatric pathologies and the increased use of prolonged high-dose corticosteroid therapy. In clinical practice, adrenal function is usually assessed by the total PC (determined by low-dose ACTH test). This implies the placement of a vascular access which is often a traumatic experience for children. PC includes protein-bound fraction and serum-free cortisol. The latter constitutes the biologically active form of the hormone and is responsible for glucocorticoid activity on peripheral organs. Most of the circulating cortisol is bound to plasma proteins (over 90%), such as cortisol-binding globulin (CBG) and albumin, whereas only about 10% of circulating cortisol is free. Hence, the measurement of plasma-free cortisol level has been considered more representative of adrenal function (especially in critically ill adults and children) [1,2], because some conditions, such as hypoalbuminaemia or hypoproteinaemia (frequent in critically ill patients or in patients with cirrhosis), may lead to misinterpretation of adrenal function with an overestimation of the prevalence of AI. But the direct measurement of free PC is a laboratory-dependent and time-consuming procedure that is not available for routine use. Salivary cortisol (SC) is one of the several indirect methods available to determine free PC [3], as SC levels accurately reflect free PC [4] even in cases of hypoalbuminaemia or CBG abnormality [1,5]. For this reason, in the last years, this technique (SC) has been introduced as a non-invasive tool in the diagnosis of adrenal cortical disorders, for its simplicity and applicability in the paediatric population. However, few studies to date have evaluated the usefulness of SC as a diagnostic method in children with AI. No interactions between exogenous corticoids and SC have been described [6]. The aim of the present study was to assess the usefulness of determining salivary cortisol levels as a diagnostic tool in children with suspected secondary iatrogenic AI. 

The case is that of 83 year-old African American man with hypertension, hepatitis C induced decompensated cirrhosis with ascites, end-stage renal disease (ESRD) on hemodialysis, fluid overload with peripheral edema and chronic hypotension. The patient was referred to the dialysis access center of Pittsburgh, PA for evaluation of his prolonged bleeding from the left upper arm brachial-basilic arterial-venous fistula (BBAVF).

The objective was to assess the antioxidant effect of melatonin (MLT) on liver and lung tissues of animals with bile duct ligation (BDL)-induced hepato-pulmonary syndrome (HPS). A model of BDL-induced biliary cirrhosis was used in male Wistar rats. Results suggest that MLT has an antioxidant effect on liver and lung tissues in animals with BDL-induced HPS by higher activity of antioxidant enzymes in the group HPS treated with MLT and the histological analysis of lung parenchyma showing decreased damage in this same group, including other analysis described below.

Non-alcoholic fatty liver disease (NAFLD) is a condition that is associated with cirrhosis and hepatocellular carcinoma, and is increasing in prevalence worldwide. Sleep disruptions are commonly seen in NAFLD, and the disease process is associated with sleep disorders, including obstructive sleep apnea, circadian rhythm disorders, and insufficient sleep. The intermittent hypoxia seen in obstructive sleep apnea may contribute to fibrotic changes in the liver.A major component of this linkage may be related to gut microbiome changes. One notable change is increase in Bacteroidetes/Firmicutes ratio, and decrease in flora that ferment fiber into anti-inflammatory short-chain fatty acids. Several therapeutic options exist for NAFLD that target both sleep and NAFLD, including non-pharmacological factors, such as lifestyle modification (mainly diet and exercise). Pharmacological options include melatonin, Vitamin E, thiazolidinediones, and fecal microbiota transplantation.Core tipThe pathogenesis of non-alcoholic fatty liver disease is closely tied to sleep and circadian rhythm abnormalities, through shared inflammatory pathways and altered metabolism. This review explores the pathogenesis of NAFLD in the context of sleep and circadian abnormalities. The associated inflammatory response is linked to changes in gut-microbiome interactions that contribute to the disease process. Understanding of this linkage has implications for various therapies for disease mitigation.

Increased levels of bilirubin in blood serum may result from numerous physical conditions including hepatitis, cirrhosis, enzyme deficiency, drug reactions, autoimmune disorders and physiological trauma. No presumptive test for high bilirubin levels in blood serum stains currently exists, which could prove useful in the assessment of crime scenes involving victims with one of the above disorders. Here, the use of ultraviolet 365 (UV 365) is described as a simple, nondestructive method for the detection of blood serum containing elevated levels of bilirubin.

Background: Liver Transplantation (LT) is the definitive treatment for Autoimmune Hepatitis (AIH) in patients with decompensated cirrhosis, liver failure and hepatocellular carcinoma. Outcomes of LT in AIH among black-Africans are not well-defined. We performed a single-center retrospective-review of adult LT patients. The study period was from 1st August 2004-31st August 2019. The primary aim was to document 1- & 5- year patient and graft survival. A secondary aim was to compare the survival of black-Africans to Caucasians. Data was analyzed using survival-analysis. Results: A total of 56 LT were performed for AIH. Sixty-seven percent (n = 38/56) had confirmed AIH on explant histology. Of these, the majority i.e., 79% (30/38) were female and 21% (8/38) were male. There were equal numbers of black-African 42% (n = 16/38) and Caucasian 42% (n = 16/38) patients. Rejection was four-times higher in black-Africans as compared to Caucasians. Forty-four percent (n = 17/38) had an acute rejection episode and 13% (5/38) had chronic rejection. Recurrence was found in four black-African females. Post-LT patient survival at 1- and 5- years was 86.5% and 80.7%, and graft survival was 94% and 70.8% respectively. The 5- year patient survival was insignificantly lower for black-Africans (73.9%) as compared to Caucasians (83.7%) (p - value 0.26, CI 6.3 - 12.2). Five-year graft survival was significantly lower among black-Africans (55%) as compared to Caucasians (84.8%) (p - value 0.003 CI 3.8 - 8.1)Conclusion: Black-Africans had a four-fold higher rate of rejection compared to Caucasians. Recurrent AIH was only found in patients of black ethnicity. Similar 1- & 5- year patient survival rates were observed between the two ethnicities. The 5-year graft survival among black-Africans was significantly lower than Caucasians.

This article aims to provide what lung disorders can be caused by liver cirrhosis and also explain the pathophysiology of each etiologies. Regardless of preexisting lung illness, patients suffering from liver cirrhosis, especially decompensated liver cirrhosis can develop distinct pulmonary complications. Liver cirrhosis patients should be assessed for hepatopulmonary syndrome (HPS), portopulmonary hypertension (PoPH), hepatic hydrothorax (HH), and spontaneous bacterial empyema (SBEM)  which are the most clinically significant pulmonary consequences, in particular when dyspnea develops in conjunction with hepatic cirrhosis. These entities differ in terms of pathophysiology, clinical characteristics, diagnosis, and suitable treatment options. This emphasizes the need for a specific diagnostic algorithm in liver cirrhosis patients presenting with dyspnea or other pulmonary symptoms. These pulmonary complications might be rare in patients with liver cirrhosis and portal hypertension but these complications might carry significant morbidity and mortality risks and, therefore, strong clinical suspicion is required to make an early accurate diagnosis. There are several medical therapies available for each condition in multiple studies but most of the treatments and procedures don’t have a significant benefit or have short-lived benefits. The only treatment that changes the clinical prognosis of decompensated cirrhosis effectively in the long term is liver transplantation. However, liver transplantation also needs careful consideration as in some cases it might increase the risk of morbidity and mortality.

Background and aim: Cirrhosis leads to sarcopenia and to life-threatening complications in decompensated stages. The objective of this study is to show the impact of the loss of muscle mass and function on hepatic decompensations. Methods: Our study compares a group of cirrhotic patients with controls matched with the same sex and age. A questionnaire was created to collect demographic, anthropometric, and cirrhosis characteristics. Several CT scan sections were analyzed and the average measurements have been grouped into tertiles to estimate the impact on cirrhotic complications.Results: Our study included 33 controls and 33 cirrhotic patients of which 59.4% had NASH. Anthropometric characteristics were similar in cirrhotics men and women. Grip strength was significantly lower in cirrhotic men. Using the skeletal muscle index we found 39.39% of cirrhotic patients were sarcopenic mostly men 84.61%. In Cirrhotic men, the density of the psoas and paravertebral muscles was lower than in controls. In women psoas and paravertebral muscle areas were comparable and the total muscle surface in cirrhotic patients was higher. There was a negative correlation between this surface and the density of the psoas (r = -0.293 p = 0.017) indicating the presence of myosteatosis in women. Analysing tertile groups showed a significantly higher incidence of complications related to liver disease and liver failure in patients with the psoas and paravertebral muscle density in the lowest tertile and in the frail population according to the frailty index.Conclusion: Cirrhotic patients have myosteatosis and sarcopenia associated with a higher incidence of complications related to hepatic failure.

Introduction: Bleeding from varices is a severe complication in patients with cirrhosis. Despite its treatment has been well established in the last three decades the mortality can be still high. This study compares the epidemiological features and the bleeding-related outcomes of a group of patients published about ten years ago with a more recent group of 168 consecutive patients. Methods: The diagnosis, the treatment, and the main outcomes (5-day failure, 5-day and 6-week rebleeding, 5-day and 6-week mortality) of variceal bleeding were evaluated according to the current guidelines.Results: The number of patients with cirrhosis admitted for variceal bleeding every year has progressively decreased in the last ten years. The age sex and severity of liver disease, evaluated with Child Pugh and MELD scores, were comparable in the two series. In the more recent series, there were significantly fewer patients with HCV infection and more patients with alcohol-related cirrhosis. The main outcomes of bleeding were comparable too. Overall, at 6 weeks 36.4% of patients did not overcome the bleeding episode. Conclusion: The decreasing incidence of bleeding from varices is likely attributable to antiviral treatment of HCV and HBV and the larger diffusion of beta-blockers in primary prophylaxis. Despite the larger application of the gold standard therapy, the mortality of variceal bleeding remains high in patients with cirrhosis.