Pre-existing Cirrhosis Research Articles

Approach to the patient with acute severe autoimmune hepatitis.

SummaryAutoimmune hepatitis is associated with varied clinical presentations and natural history, as well as somewhat unpredictable treatment responses. Understanding how to stratify patients who require further escalation of therapy will help clinicians manage these patients. The presentation of acute severe autoimmune hepatitis (AS-AIH) is relatively uncommon, although its prevalence is potentially greater than currently perceived. Previous studies consist of small retrospective single-centre series and are not directly comparable due to the diversity of presentations, disease definitions and non-standardised treatment regimens. We define AS-AIH as those who present acutely with AIH and are icteric with an international normalised ratio ≥1.5 and no evidence of hepatic encephalopathy. Those with hepatic encephalopathy should be defined as having AS-AIH with acute liver failure. In this review, we provide a structured practical approach for diagnosing and managing this unique group of patients.

Predicting outcome in liver patients admitted to intensive care: A dual-centre non-specialist hospital external validation of the Liver injury and Failure evaluation score

Acute hepatic dysfunction in the critically ill population with pre-existing liver cirrhosis is associated with a high mortality. Several prediction models have been developed to risk stratify patients with liver disease. This UK dual-centre non-specialist hospital retrospective study (2015-2019) externally validated the Liver injury and Failure evaluation score (incorporating lactate, bilirubin and International Normalised Ratio), alongside two other general intensive care unit prediction models (Intensive Care National Audit and Research Centre and Acute Physiology and Chronic Health Evaluation II). Inclusion criteria matched a recent UK-wide study including at least one of biopsy proven cirrhosis, imaging suggestive of cirrhosis, hepatic encephalopathy or portal hypertension. One hundred and ninety-nine admissions met inclusion criteria over the study period (n = 169), mean age 57( ±13). In-hospital mortality was 40% in this cohort compared to 18% of all intensive care unit individuals during the same period. Variceal bleeding was associated with a lower short-term (18% versus 47%, P < 0.001, odds ratio 0.3 (95% confidence interval 0.1-0.5)) and longer-term mortality (log rank P = 0.015). In-patient mortality was higher in cases requiring renal replacement therapy (82% versus 29%, odds ratio 11.1 (95% confidence interval 4.6-26.9), P < 0.001) or ventilation (47% versus 32%, odds ratio 1.9 (1.1-3.4), P = 0.03). For in-patient mortality, area under the receiver operating characteristic curves were Liver injury and Failure evaluation 0.69 (95% confidence interval 0.62-0.77), Intensive Care National Audit and Research Centre 0.80 (0.74-0.86) and Acute Physiology and Chronic Health Evaluation II 0.73 (0.65-0.81). Forty-one per cent of cases were alive at one-year follow-up. Area under the receiver operating characteristic curves for one-year survival were Liver injury and Failure evaluation 0.69 (0.61-0.77), Intensive Care National Audit and Research Centre 0.75 (0.67-0.82) and Acute Physiology and Chronic Health Evaluation II 0.69 (0.61-0.77). This first Liver injury and Failure evaluation score validation in a UK non-specialist hospital setting suggests this parsimonious, easy to calculate model may have utility in prediction of short-term and one-year mortality. As with previous studies variceal haemorrhage was associated with lower mortality.

Mortality and morbidity of locally acquired hepatitis E in the national Scottish cohort: a multicentre retrospective study.

Hepatitis E virus (HEV) is the most common acute viral hepatitis in Scotland. Little is known about the burden of morbidity and mortality, which can be high in chronic liver disease or immunocompromised states. To record the morbidity and mortality of HEV in Scotland. Demographic, clinical and laboratory data were collected retrospectively from all cases of HEV reported to virology departments across nine NHS health boards, between January 2013 and January 2018. Five hundred and eleven cases were included (Mean age 62, 64% male). 58 (11%) cases had pre-existing cirrhosis and 110 (21%) had diabetes. Three hundred and three patients required admission (59%), totalling 2747 inpatient bed days. Seventeen (3.3%) HEV-related deaths were recorded. Factors that predicted mortality included haematological malignancy (OR 51.56, 95% CI 3.40-782.83, P=0.005), cirrhosis (OR 41.85, 95% CI 2.85-594.16, P=0.006), higher serum bilirubin (OR 1.01, 95% CI 1.01-1.02, P=0.011) and chronic HEV infection (OR 0.02, 95% CI 0.02-0.28, P<0.001). HEV infection affected 35 transplant patients of 106 total immunosuppressed patients (21%). Of these, 25 patients received Ribavirin therapy with a sustained virological remission of 76%. Thirty-five (6.7%) patients developed acute or acute-on-chronic liver failure with two requiring transplant. Thirty-seven (7.2%) patients reported neurological complications with 10 developing neuralgic amyotrophy, 6 Guillain-Barré and 2 encephalitis. Forty-four (8.6%) patients developed acute kidney injury. In Scotland, HEV causes a significant burden of inpatient admissions, organ failure and death. Cirrhosis and haematological malignancy are significant predictors of mortality. Neurological and renal complications occur in a significant minority.

The Predictive Scoring Systems for Outcomes of Heart Transplantation in Patients with Pre-Existing Liver Cirrhosis

There are few data assessing factors and clinical outcomes in patients with liver cirrhosis for heart transplantation. The aim of this study was to compare the Model for End-Stage Liver Disease (MELD) score, the MELD-XI score and Child-Turcotte-Pugh (CTP) score risk prediction in cirrhotic patients undergoing heart transplantation. Between 1994 and 2018, forty-nine consecutive patients (19 men and 30 women, median age 46 years, range 12-68 years) had liver cirrhosis, among 170 patients underwent heart transplantations in our institution. Potential preoperative predictors of outcomes, as well as preoperative MELD score, MELD-XI score and CTP classification were calculated. Causes of heart failure were dilated cardiomyopathy in 26, ischemic disease in 7, congenital heart disease in 6 and valvular heart disease 7 patients. Cause of liver cirrhosis was majority of cardiac origin, except hepatitis in two and alcoholism in one patient. The median follow-up duration was 45.2 months. The MELD score (p=0.010) and MELD-XI score (p=<0.001) were significantly differed between survivors and non-survivors. Cox regression analysis showed high MELD score (HR 1.211; 95% CI, 1.059-1.386; p=0.005), MELD-XI score (HR, 1.184; 95% CI, 1.042-1.345; p=0.010) and CTP score (HR, 1.694; 95% CI, 1.040-2.760; p=0.034) were associated with the risk of all-cause mortality. Receiver operating characteristic (ROC) curve analysis revealed the optimal cut-off value of MELD, MELD-XI and CTP score was 12.2, 12.0 and 7.5, respectively (sensitivity: 69.2 vs. 61.5 vs. 69.2%, specificity 68.6 vs. 60.0 vs. 62.9%) for all-cause mortality (AUC: 0.745 vs. 0.690, 0.729). The patients with advanced heart failure and liver cirrhosis were high mortality and morbidity of heart transplantation. However, these scoring systems can be a tool to risk-stratification for liver cirrhotic patients undergoing heart transplantation.

Altered Microbiota Diversity and Bile Acid Signaling in Cirrhotic and Noncirrhotic NASH-HCC.

OBJECTIVES:The precipitous increase in nonalcoholic steatohepatitis (NASH) is accompanied by a dramatic increase in the incidence of NASH-related hepatocellular carcinoma (HCC). HCC in NASH has a higher propensity to arise without pre-existing cirrhosis compared with other chronic liver diseases.METHODS:To identify the potential links between liver and gut in NASH-related hepatocarcinogenesis, we compared the gut microbiota and mediators of bile acid (BA) signaling in the absence or presence of cirrhosis through the analysis of stool and serum samples from patients with NASH non-HCC and NASH-HCC and healthy volunteers.RESULTS:Serum levels of total and individual BA were higher in NASH compared with healthy controls. Furthermore, serum levels of the primary conjugated BAs glycine-conjugated cholic acid, taurine-conjugated cholic acid, glycine-conjugated chenodeoxycholic acid, and taurine-conjugated chenodeoxycholic acid were significantly increased in cirrhotic vs noncirrhotic patients, independent of the occurrence of HCC. By contrast, serum FGF19 levels were higher in patients with NASH-HCC and associated with tumor markers as well as an attenuation of BA synthesis. Specific alterations in the gut microbiome were found for several bacteria involved in the BA metabolism including Bacteroides and Lactobacilli. Specifically, the abundance of Lactobacilli was associated with progressive disease, serum BA levels, and liver injury in NASH and NASH-HCC.DISCUSSION:Here, we demonstrate a clear association of the altered gut microbiota and primary conjugated BA composition in cirrhotic and noncirrhotic patients with NASH-HCC. Microbiota-associated alterations in BA homeostasis and farnesoid X receptor signaling, via FGF19, might thus contribute to fibrogenesis, liver injury, and tumorigenesis in NASH-HCC.

Nucleos(t)ide Analogues for Reducing Hepatocellular Carcinoma in Chronic Hepatitis B Patients: A Systematic Review and Meta-Analysis.

Background/AimsStudies have shown that nucleos(t)ide analogue (NA) treatment can reduce the risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients, but it is unclear which NA is most effective. We performed a meta-analysis and systematic review comparing the efficacies of NAs in CHB patients.MethodsWe searched literature databases for randomized controlled trials (RCTs) and observational studies that analyzed the hepatic biochemical response, virological response, seroconversion rate, drug resistance rate, and HCC incidence rate in CHB patients treated with NAs. Meta-analyses were performed with RevMan and Stata/SE software.ResultsTwelve cohort studies and one RCT were selected, in which entecavir (ETV), lamivudine (LAM), telbivudine (LdT), and/or tenofovir disoproxil fumarate (TDF) were evaluated in CHB patients. The meta-analysis showed that ETV was superior to LAM with regard to the HCC incidence (p<0.001), biochemical response (p=0.001), virological response (p=0.02), and drug resistance (p<0.001), and ETV was superior to LdT with regard to the virological response (p<0.001) and drug resistance (p<0.001). We found no significant difference between ETV and TDF with regard to the HCC incidence (p=0.08), biochemical response (p=0.39), virological response (p=0.31), serological conversion (p=0.38), or drug resistance (p=0.95). NA-treated patients with pre-existing cirrhosis had a 5.49 times greater incidence of HCC than those without cirrhosis (p<0.001).ConclusionsETV or TDF should be used for long-term first-line monotherapy in CHB patients according to the current guidelines. Standardized protocols are needed for future studies of ETV and TDF to facilitate conclusive comparisons. Patients with cirrhosis are at significantly elevated risk for HCC, despite the benefits of NA treatment.

1117 Same Day, Walk-In Ultrasound Appointments Improve Hepatocellular Carcinoma Screening Rates in Patients With Cirrhosis at a Veterans Affairs Center

INTRODUCTION: The incidence of hepatocellular carcinoma (HCC) is rapidly increasing in the United States and 80% have pre-existing cirrhosis. It is imperative to implement effective screening programs to detect clinically silent or early stage HCC in patients with cirrhosis to improve cancer-related mortality. The 2018 American Association for the Study of Liver Diseases (AASLD) Guidelines recommends surveillance using ultrasound (US), with or without alpha fetal protein (AFP), every 6 months. Prior studies have shown low HCC surveillance rates of approximately 20% among eligible patients in clinical practice. Our aim is to improve the HCC surveillance rate at our local Veterans Affairs Medical Center (VAMC). METHODS: We developed a process map and an apparent cause analysis (fishbone) to identify the barriers to HCC screening. We implemented a quality improvement initiative and collected the HCC screening compliance rates on a monthly basis on all eligible patients with cirrhosis seen at a local VAMC between January 2018 and February 2019. RESULTS: Based on our process map (Figure 1) and apparent cause analysis (Figure 2), the barriers to HCC screening at our local VAMC included the lack of a set protocol in our radiology department for limited ultrasound scans which limited patient access and compliance, such as the schedulers’ inability to reach patients for ultrasound appointments and patients’ no-show on ultrasound appointments. Our primary intervention was to institute same day walk-in ultrasounds, such that patients could go directly from their liver clinic appointment to the radiology department for a dedicated HCC screening ultrasound, without the need for patients to fast or return on a different date. At the start of the study period in January 2018, the HCC screening compliance rate was 39.6%, with 195/324 patients overdue. The same day walk-in ultrasound was implemented on 31 July 2018, at a time when the compliance rate was 42.1%. Six months after the intervention, the compliance rate in February 2019 was 66% with just 90/215 patients overdue for their ultrasounds. (Figure 2) CONCLUSION: It is standard of care to provide biannual screening ultrasounds for HCC surveillance in patients with cirrhosis. At our local VAMC, providing patients with same day walk-in ultrasounds to coincide with their liver clinic appointment days eliminated a number of barriers to HCC screening and lead to an increase in compliance.

2282 Hepatocellular Carcinoma With Rare Duodenal Metastases

INTRODUCTION: Hepatocellular carcinoma is a decompensation of cirrhosis. We present a patient with HCC, presenting with anemia, found to have metastatic disease to the duodenum. CASE DESCRIPTION/METHODS: 67 y/o male with hepatitis C cirrhosis, complicated by HCC, presented with anemia and melena. HCC was diagnosed 1 year prior, with a 3.8 cm left lobe lesion, portal venous thrombus, and a LIRADS-4 right lobe lesion, initiated on palliative chemotherapy. Recent MRI demonstrated infiltrative HCC involving nearly the entire left lobe of the liver; tumor and bland thrombus within the portal system involving the confluence of the portal veins, left, and to a lesser extent, right portal vein. Exam revealed guaiac positive brown stool. Labs revealed hemoglobin 6.0 g/dL (baseline 12g/dL), MCV 93, BUN 17 mg/dL, Cr 1.2 mg/dL. Endoscopy demonstrated 3 superficial duodenal bulb ulcers, 2mm-3mm, with a visible vessel, treated; no varices seen. Repeat EGD demonstrated multiple closely associated pedunculated polypoid lesions with superimposed ulcerations with irregular appearing surrounding mucosa; biopsies without evidence of malignancy. Given the abnormal appearance, repeat EGD with biopsies was performed, revealing metastatic hepatocellular carcinoma in multiple fragments of the duodenal mucosa. DISCUSSION: Hepatocellular carcinoma is the most common primary liver malignancy. The most significant risk factor for HCC is pre-existing cirrhosis. Lung, bone and lymph nodes are the most common metastatic sites of HCC; metastatic disease to the duodenum is exceedingly rare (1). Of &gt;7000 cases of HCC identified in Taiwan between 1996-2009, &lt; 1%, or just 21 cases, revealed duodenal disease (1). GI involvement is most frequently a result of direct invasion by contiguous tumor, with right lobe disease most commonly extending to the duodenum and left lobe disease most commonly extending to the stomach (1). Rarely, as seen in our patient, duodenal disease can be a location of metastatic disease without direct contact. Wall thickening appreciated on imaging should prompt consideration of gastrointestinal involvement. It has been suggested that portal vein thrombosis may be an indication of hematogenous spread of tumor, in addition to being a poor prognostic indicator. Duodenal masses, ulcerations or bleeding should raise suspicion for duodenal metastasis, and portends a very poor prognosis.

2441 Hepatotoxicity by Methoxsalen: The Innocuous Culprit

INTRODUCTION: Drug-induced liver injury (DILI) is the second most common cause of acute liver failure; 15-20% cases of DILI can be attributed to damage caused by herbal or dietary supplements. Methoxsalen, commonly known as psoralen, is the active ingredient in Bakuchi seeds and is used for treatment of vitiligo and psoriasis. DILI caused by Psoralen is rare, with only three cases reported in literature. This case demonstrates the importance of eliciting a history of herbal supplement use in patients with acute liver failure and the need for regulation of herbal supplements. CASE DESCRIPTION/METHODS: A 60-year-old female presented with two-week history of jaundice and right upper quadrant pain (RUQ). She started taking Bakuchi seeds four weeks prior to presentation and would apply it topically and consume it daily. Patient denied history of alcohol use, blood transfusions, or illicit drug use. Physical exam was notable for scleral icterus and jaundice. Labs revealed abnormal liver function tests (LFTs) (Figure 1) with a peak total bilirubin of 19 mg/dL and a MELD-Na on admission of 19. Work up revealed positive anti-smooth muscle antibodies and AFP elevation to 15.9 ng/mL. Pertinent negatives included viral hepatitis serologies, HSV, EBV, factor V activity, and hemochromatosis. A RUQ ultrasound showed no abnormalities. An MRI abdomen was done which revealed mild periportal edema and mildly dilated common bile duct without choledocholithiasis or obvious mass. Given concerns for DILI, patient was started on acetylcysteine. Hospital course was complicated by episodes of confusion; an ammonia level was elevated at 75 umol/l. Patient was started on lactulose. Because patient's LFTs improved with a stabe PT/INR of 12/1.2, she did not meet criteria for a liver transplant. A liver biopsy was performed which revealed submassive necrosis and collapse; hepatitis with plasma cells and eosinophils with significant cholestasis. Given biopsy results consistent with DILI, patient was discharged on oral prednisone and lactulose to follow up with hepatology in one week. DISCUSSION: LFT abnormalities were seen in 2% to 12% of subjects taking psoralen; the elevations were mild-moderate in severity, asymptomatic and self-limited in course with recovery of LFT seen in 6 to 8 weeks. However, severe jaundice and death from hepatic failure has been described in patients with preexisting cirrhosis. This case emphasizes the need for increased surveillance to formulate guidelines regarding regulation and use of herbal supplements.

3173 Spontaneous HBsAg Seroclearance in a Patient With Chronic Hepatitis B: Do We Need Surveillance?

INTRODUCTION: Hepatitis B virus (HBV) infection is a global health problem despite an effective vaccination program, routine antenatal screening, and perinatal care. Among the individuals infected with the HBV, about 5 % of adults and 90% of children become chronic carriers. A small percentage of carriers undergo spontaneous seroclearance of Hepatitis B surface antigen (HBsAg). We present a case of spontaneous HBsAg seroclearance in a chronic hepatitis B carrier. CASE DESCRIPTION/METHODS: A 60-year-old Hispanic male with a history of chronic hepatitis B presented to the hepatology clinic for regular follow-up. He was asymptomatic with no stigmata of chronic liver disease. He had been followed in the clinic for nine years. He was HBsAg positive, hepatitis B surface antibody detectable at 6.9 mIU/ml, hepatitis B e antigen (HBeAg) negative, hepatitis B e antibody positive, undetectable HBV DNA levels, and alpha-fetoprotein 17.2 ng/ml. He persistently had normal liver enzymes. Five months after the last positive HBsAg, routine serology showed loss of HBsAg. CT Abdomen with contrast liver protocol showed no evidence of cirrhosis and hepatocellular carcinoma (HCC). The liver biopsy showed no evidence of fibrosis. The patient is on surveillance with a follow-up in 6 months for repeat serology. DISCUSSION: Chronic hepatitis B carriers are at risk of developing decompensated liver cirrhosis and hepatocellular carcinoma. The rate of HBsAg spontaneous seroclearance is estimated to be 1–3% per year. The long-term outcome after HBsAg seroclearance is excellent if there is no pre-existing cirrhosis or viral superinfection. HBsAg carriers who are negative for HBeAg or negative for HBV DNA are more likely to clear HBsAg from serum. AASLD guidelines recommend HCC surveillance in chronic hepatitis B infection, but its usefulness in patients after HBsAg seroclearance without any liver injury remains controversial. Few retrospective studies recommend surveillance in high-risk patients, which include male patients, patients with cirrhosis, HCV superinfection, age ≥50 years at the time of seroclearance and family history of HCC. Surveillance in patients who do not have any risk factors may not be cost effective as the incidence of adverse liver events among them is rare. Our patient had chronic hepatitis B for nine years and underwent spontaneous seroclearance of HBsAg with negative HBeAg and undetectable HBV DNA. He has no evidence of cirrhosis or viral superinfection, thus having a favorable long-term prognosis.

Can we stop nucleoside analogues before HBsAg loss?

Most of the current guidelines and the existing data suggest that long-term therapy with nucleos(t)ide analogue(s) [NA(s)] may be stopped in carefully selected chronic hepatitis B patients who remain HBsAg positive. In particular, NA(s) may be discontinued in such patients without pre-existing cirrhosis who achieved long-term on-therapy virological remission (>12months of HBeAg seroconversion and HBV DNA undetectability for initially HBeAg-positive cases; ≥3years of HBV DNA undetectability for HBeAg-negative cases) and are expected to remain under close follow-up after NA(s) discontinuation. The majority of patients will develop post-NA(s) virological relapses and a proportion of them will have biochemical relapses and occasionally flares, but prompt retreatment can reintroduce remission. No reliable predictor(s) of post-NA(s) relapses have been identified so far. HBsAg loss develops in a progressively increasing proportion of chronic hepatitis B patients who discontinue NA(s) with HBsAg loss rates being higher in Caucasian patients with HBeAg-negative chronic hepatitis B. Follow-up at least every 3months for the first year seems to be appropriate for all chronic hepatitis B patients who discontinue NA(s), while HBeAg-negative patients need to be followed more closely (monthly) during the first 3months. Predefined criteria for retreatment are quite important, and the best candidates for retreatment are probably the patients with persistent (≥3months) liver disease activity and those with severe flares.

Primary Hepatic Follicular Lymphoma Presenting as Sub-acute Liver Failure: A Case Report and Review of the Literature.

Sub-acute liver failure is a term that describes the relatively sudden loss of liver function, usually >21 days and <26 weeks, with impaired synthetic function and associated encephalopathy in a person with no pre-existing liver disease or cirrhosis. It is commonly caused by viruses and drugs, less so by malignancy. Our patient is a 71-year-old Japanese man who presented with signs of sub-acute liver failure. A subsequent liver biopsy demonstrated involvement by B-cell non-Hodgkin lymphoma. Evaluation of the bone marrow demonstrated significant marrow involvement by B-cell lymphoma. The fluorescence in situ hybridization (FISH) returned positive for t(14; 18). Noted was the patient’s clinical presentation of cholestasis secondary to hepatic lymphoma with no evidence of lymphadenopathy or peripheralized lymphoma. Given the disease distribution, the overall findings are consistent with primary hepatic follicular lymphoma as described in few case reports and small case series in the literature.

45 Threshold dose for focal liver reaction

Purpose Patient who underwent liver stereotactic body radiation therapy (SBRT) show a signal intensity alteration in follow-up imaging known as focal liver reaction (FLR). This study aims at evaluating dose threshold for FLR after SBRT. Methods 22 patients (13 metastasis, 9 hepatocellular carcinomas [hcc]) underwent SBRT with 48 or 60 Gy in 3 fractions. After therapy patients had, according to clinical protocols, follow-up imaging studies (12 CT and 32 MRI) at 3, 6, 9, 12, 18, 24 and 30 months. For each follow-up the region of signal alteration, if present, was classified as FLR, residual or recurrent disease, and contoured. In case of FLR, the planning images were registered to the follow up using deformable registration, and planning dose was mapped to the follow up applying the registration matrix. The isodose that better fits the FLR (dose threshold) was found, and the conformality index between dose threshold and FLR computed. The figure shows the dose threshold as a function of cancer type and follow up time. Results Threshold dose is higher for metastasis than for hcc (8 Gy at 3–6 months, 12 Gy at 9–12 months), and shows an increase up to 9 months followed by a decrease at 12 month. Cases at 18 or more months are too few or broad to be significant. The table shows threshold doses with their uncertainties – cases with just one samples are excluded. Conclusions hcc’s show FLR for lower doses, which can be justified by pre-existing cirrhosis. Since higher isodoses are embedded in lower ones, follow-up lesion size has an inverse correlation with dose threshold; therefore, there is a decrease of the lesion in the first 9 months followed by an increase 3 months later. Threshold doses are consistent with literature data.

The impact of direct-acting antiviral therapy for hepatitis C on hepatocellular carcinoma risk.

Direct-acting antiviral agents (DAAs) eradicate hepatitis C virus (HCV) infection in the majority of patients. We critically evaluated the impact of DAAs on hepatocellular carcinoma (HCC) risk, a major complication of HCV infection. Large cohort studies show that patients who achieve sustained virologic response (SVR) with DAAs have a significantly lower risk of developing de novo HCC than patients who fail treatment or remain untreated. Furthermore, reduction in HCC risk is similar whether SVR is achieved with DAAs or interferon (IFN). However, DAA-induced SVR does not eliminate HCC risk entirely. Therefore, patients with pre-existing cirrhosis require ongoing surveillance even after SVR is achieved.Early, descriptive, uncontrolled reports suggested that DAAs may increase the risk of recurrent HCC. While studying HCC recurrence presents major methodologic challenges, larger studies containing appropriate comparison control groups largely refuted these concerns. Recent studies provide evidence that DAA-induced SVR reduces HCC risk.

Incidence and Risk Factors of Coagulation Profile Derangement After Liver Surgery: Implications for the Use of Epidural Analgesia-A Retrospective Cohort Study.

Hepatic surgery is a major abdominal surgery. Epidural analgesia may decrease the incidence of postoperative morbidities. Hemostatic disorders frequently occur after hepatic resection. Insertion or withdrawal (whether accidental or not) of an epidural catheter during coagulopathic state may cause an epidural hematoma. The aim of the study is to determine the incidence of coagulopathy after hepatectomy, interfering with epidural catheter removal, and to identify the risk factors related to coagulopathy. We performed a retrospective review of a prospective, multicenter, observational database including patients over 18 years old with a history of liver resection. Main collected data were the following: age, preexisting cirrhosis, Child-Pugh class, preoperative and postoperative coagulation profiles, extent of liver resection, blood loss, blood products transfused during surgery. International normalized ratio (INR) ≥1.5 and/or platelet count <80,000/mm defined coagulopathy according to the neuraxial anesthesia guidelines. A logistic regression analysis was performed to assess the association between selected factors and a coagulopathic state after hepatic resection. One thousand three hundred seventy-one patients were assessed. Seven hundred fifty-nine patients had data available about postoperative coagulopathy, which was observed in 53.5% [95% confidence interval, 50.0-57.1]. Maximum derangement in INR occurred on the first postoperative day, and platelet count reached a trough peak on postoperative days 2 and 3. In the multivariable analysis, preexisting hepatic cirrhosis (odds ratio [OR] = 2.49 [1.38-4.51]; P = .003), preoperative INR ≥1.3 (OR = 2.39 [1.10-5.17]; P = .027), preoperative platelet count <150 G/L (OR = 3.03 [1.77-5.20]; P = .004), major hepatectomy (OR = 2.96 [2.07-4.23]; P < .001), and estimated intraoperative blood loss ≥1000 mL (OR = 1.85 [1.08-3.18]; P = .025) were associated with postoperative coagulopathy. Coagulopathy is frequent (53.5% [95% confidence interval, 50.0-57.1]) after liver resection. Epidural analgesia seems safe in patients undergoing minor hepatic resection without preexisting hepatic cirrhosis, showing a normal preoperative INR and platelet count.

Dynamic noninvasive markers predict hepatocellular carcinoma in chronic hepatitis C patients without sustained virological response after interferon-based therapy: Prioritize who needs urgent direct-acting antiviral agents.

Some patients with hepatitis C virus (HCV) infections who fail to achieve sustained virological responses (SVRs) after interferon (IFN) therapy do not develop hepatocellular carcinoma (HCC). Risk stratification of these patients may help identify those who would benefit most from treatment with direct-acting antivirals (DAAs).A total of 552 HCV-infected patients with non-SVR status were enrolled. Laboratory data before and after IFN treatment were analyzed to determine the relationship of changes in serum markers with development of HCC during the 7-year study period.HCC developed in 93 patients. The risk factors for HCC were pre-existing liver cirrhosis, low hemoglobin level at baseline, low pretreatment platelet count, high post-treatment alpha-fetoprotein (AFP) level (≥15 ng/mL), and high post-treatment Fibrosis 4 (FIB4) index (>3.25). For patients without pre-existing cirrhosis, those with high post-treatment AFP level and FIB4 index had the highest risk of HCC (1 year: 6.7%; 3 years: 10.9%; 5 years: 29.7%), followed by those with high post-treatment AFP level and low post-treatment FIB4 index (5 years: 25%), and those with low post-treatment AFP level and high post-treatment FIB4 index (1 year: 3.7%; 3 years: 5.2%; 5 years: 10.6%). The risk was even lower for patients with low post-treatment AFP level and FIB4 index (1 year: 0%; 3 years: 0.4%; 5 years: 2.5%). None of the patients with FIB4 indexes consistently below 1.45 developed HCC.The combined use of post-treatment AFP level and FIB4 index was useful for risk stratification of HCV-infected patients with non-SVR status after IFN therapy. These data may help clinicians to identify patients who most urgently need DAA treatment.

Statin use and the risk of hepatocellular carcinoma in patients at high risk: A nationwide nested case-control study

Statins are widely used to treat hypercholesterolemia. Statins may prevent hepatocellular carcinoma (HCC), but have not yet been fully studied, particularly in patients at high risk. Therefore, we investigated the risk of HCC after statin use in the whole general population and evaluated the effects of preexisting diabetes mellitus (DM) and liver cirrhosis (LC) on that risk. A nationwide, nested case-control study was conducted with data from the National Health Insurance Service Physical Health Examination Cohort 2002-2013 in the Republic of Korea. Individuals diagnosed with HCC were matched to controls based on the time of the follow-up, sex, and age at index date. Odds ratios (ORs) and 95% confidence intervals (CIs) for HCC associated with statin use were analyzed by multivariable conditional logistic regression analyses. In total, 1,642 HCC cases were matched to 8,210 control individuals from 514,866 participants. Statin use was associated with reduced risk of HCC development (adjusted OR [AOR] 0.44; 95% CI 0.33-0.58) compared with nonusers. The reduction in risk was significant in the presence (AOR 0.28; 95% CI 0.17-0.46) and absence of DM (AOR 0.53; 95% CI 0.39-0.73) and in the presence (AOR 0.39; 95% CI 0.26-0.60) and absence of LC (AOR 0.42; 95% CI 0.32-0.57). Statin use also significantly reduced the risk of HCC among patients with DM, without chronic complications (AOR 0.19; 95% CI 0.08-0.46) or with chronic complications (AOR 0.34; 95% CI 0.19-0.64), compared to nonusers. Statin use may have a beneficial inhibitory effect on HCC development, particularly in patients with DM or LC, at high risk of HCC. In this longitudinal nationwide population-based nested case-control study, the association between statin use and the risk of HCC was investigated in Asian populations. Herein, we noted a beneficial effect of statin use on the development of HCC in the general population and individuals at high risk of HCC (i.e. those with diabetes or liver cirrhosis).

Hyperuricemia is associated with an increased prevalence of paroxysmal atrial fibrillation in patients with type 2 diabetes referred for clinically indicated 24-h Holter monitoring.

Several studies have reported an association between hyperuricemia and increased risk of permanent atrial fibrillation (AF) in patients with and without type 2 diabetes mellitus (T2DM). Currently, no published data are available on the relationship between hyperuricemia and risk of paroxysmal AF. We retrospectively evaluated 245 T2DM outpatients without pre-existing AF, cancer, cirrhosis and end-stage renal disease, who underwent a 24-h ECG-Holter monitoring for various clinical indications. Hyperuricemia was defined as a serum uric acid level >7mg/dl for men and >6mg/dl for women or allopurinol use. The diagnosis of paroxysmal AF was confirmed in affected individuals on the basis of 24-h ECG-Holter monitoring by experienced cardiologists. Hyperuricemia was observed in 59 (24.1%) patients, whereas paroxysmal AF was found in 11 (4.5%) patients. The prevalence of paroxysmal AF was higher in patients with hyperuricemia than in those without hyperuricemia (10.2 vs. 2.7%, p=0.026). Logistic regression analysis showed that hyperuricemia was associated with an increased risk of prevalent paroxysmal AF. This association remained significant even after adjustment for age, metabolic syndrome and chronic kidney disease (adjusted-odds ratio 4.01, 95% CI 1.08-14.9; p=0.039). Similar results were found when we used serum uric acid levels as a continuous measure. This study shows for the first time that hyperuricemia is independently associated with an approximately fourfold increased risk of prevalent paroxysmal AF in patients with T2DM. These findings may partly explain the increased risk of permanent atrial fibrillation and cardiovascular death observed among patients with hyperuricemia.

Azathioprine and 6-Mercaptopurine-induced Liver Injury: Clinical Features and Outcomes.

The objective of the study was to define the clinical, biochemical, and histologic features of liver injury from thiopurines. Azathioprine (Aza) and 6-mercaptopurine (6-MP) can cause liver injury, but no large series exist. Clinical and laboratory data and 6-month outcomes of patients with thiopurine hepatotoxicity from the Drug-Induced Liver Injury Network Prospective Study were analyzed. Twenty-two patients were identified, 12 due to Aza and 10 due to 6-MP, with a median age of 55 years; the majority were female (68%). Inflammatory bowel disease was the indication in 55%, and the median thiopurine dose was 150 (range, 25 to 300) mg daily. The median latency to onset was 75 (range, 3 to 2584) days. Injury first arose after a dose escalation in 59% of patients, the median latency after dose increase being 44 (range, 3 to 254) days. At onset, the median alanine aminotransferase level was 210 U/L, alkaline phosphatase was 151 U/L, and bilirubin was 7.4 mg/dL (peak, 13.4 mg/dL). There were no major differences between Aza and 6-MP cases, but anicteric cases typically had nonspecific symptoms and a hepatocellular pattern of enzyme elevations, whereas icteric cases experienced cholestatic hepatitis with modest enzyme elevations in a mixed pattern. One patient with preexisting cirrhosis required liver transplantation; all others resolved clinically. One patient still had moderate alkaline phosphatase elevations 2 years after onset. Nearly three-quarters of patients with thiopurine-induced liver injury present with self-limited, cholestatic hepatitis, typically within 3 months of starting or a dose increase. The prognosis is favorable except in patients with preexisting cirrhosis.

Clinical implication of occult hepatitis B infection

Occult hepatitis B infection (OBI) can be found in three different clinical groups of patients according to the documentation of the history of hepatitis B virus (HBV) exposure. They are patients with definite history of apparently self-limiting acute hepatitis B infection, patients with known chronic hepatitis B (CHB) infection with loss of hepatitis B surface antigen (HBsAg) (HBsAg seroclearance) and patients without prior history of hepatitis B infection. The second group likely contributes the largest group of patient population in OBI. These patients have same rate of development of end-staged liver disease including cirrhosis-related complications and hepatocellular carcinoma (HCC) if HBsAg seroclearance occurs when there is pre-existing cirrhosis or at the age older than 50 years. Nevertheless, majority of the patients with OBI usually have normal liver biochemistry and histology. The intrahepatic HBV DNA is detectable in almost all the patients whereas the covalently closed circular (ccc)DNA and pre-genomic RNA levels are usually very low. With regard to the clinical implications, HBV transmission from the blood products of occult hepatitis B donors is possible as demonstrated in animal and human experiments, although the actual HBV transmission rate in human is quite low especially in anti-HBs positive recipients. HBV can also be transmitted to the recipients through organ transplantation especially liver transplantation from occult hepatitis B donors. OBI may be an accelerating risk factor for development of HCC in patients with chronic hepatitis C infection and patients with alcoholic liver disease. Importantly, OBI may also contribute to a great extent in patients with cryptogenic cause of HCC. In another scenario, patients with OBI may have severe hepatitis B reactivation with a surge of viral replication and hence clinical hepatitis and mortality. This phenomenon is more commonly seen in patients receiving immunosuppressive therapy especially anti-CD monoclonal antibody. Patients receiving haematopoetic stem cell transplantation also carry a high risk of hepatitis B reactivation. Prompt antiviral therapy at the time of detectable HBV DNA upon interval monitoring is very effective in controlling hepatitis B viral replication and therefore is associated with a hepatitis-free recovery.