Hepatocellular Injury In Patients Research Articles

Propofol/Dexmedetomidine versus Desflaurane Effects on Post Hepatectomy Hepatocellular Injury

Abstract Objective The Pringle maneuver used during hepatectomy causes ischemic reperfusion injury to the liver remnant. In this study, we compared the effect of maintenance of general anesthesia with propofol dexmedetomidine intravenous infusion versus desflurane inhalational anesthesia on post hepatectomy hepatocellular injury in patients undergoing partial hepatectomy during the first six postoperative days. Method Group A (15 patients) received total intravenous anesthesia with a combination of propofol and dexmedetomidine for anesthesia maintenance. and Group B (15 patients) received desflurane for anesthesia maintenance. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum albumin, serum bilirubin, prothrombin time and international normalized ratio (INR) were measured before surgery and at 1, 3, and 6 days after surgery. Results Transaminase levels, which were comparable in both groups, peaked between the first and the third postoperative days. Peak alanine aminotransferase was 224.27±29.7 and 318.20±52.5 U/L in the group A and group B, respectively (P < 0.001). Peak aspartate aminotransferase was 265.60±22.3 U/L in group A and 349.27±56.1 U/L in group B (P < 0.001). Albumin levels at day one showed no significant differences between both groups but at days 3 and 6, group A showed significantly higher albumin levels than group B. Other liver function tests including serum albumin, total and direct bilirubin, PT and INR showed lower values in propofol/dexmedetomidine group. Conclusion The main finding of this study is that propofol/dexmedetomidine as a technique for maintenance of anesthesia resulted in less hepatocellular injury and better hepatic functions than desflurane in patients undergoing partial hepatectomy during the first 6 postoperative days.

Choledocholithiasis Can Present with Marked Transaminases Elevation: Systematic Review and Meta-Analysis.

Extreme transaminase elevation > 1000 international units per liter (IU/L) is typically caused by hepatocellular injury due to ischemia, drugs, or viral infection. Acute choledocholithiasis can also present with marked transaminase elevation mimicking severe hepatocellular injury, contrary to the presumed cholestatic pattern. We searched PubMed/Medline, EMBASE, Cochrane Library, and Google Scholar for studies reporting the proportion of marked elevation of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1000IU/L in patients with common bile duct (CBD) stones. A proportion meta-analysis with a corresponding 95% confidence interval (CI) was used to pool the proportion of patients with extreme transaminase elevation. I2 was used to examine heterogeneity. We used CMA software utilizing a random effect model for statistical analysis. Three studies (n = 1328 patients) were included in our analysis. The reported frequency of ALT or AST > 1000IU/L in choledocholithiasis patients ranged between 6 and 9.6%, with pooled frequency of 7.8% (95% CI 5.5-10.8%, I2 61%). The frequency of patients with ALT or AST > 500IU/L was higher, ranging between 28 and 47%, with pooled frequency of 33.1% (95% CI 25.3-42%, I2 88%). This is the first meta-analysis to study prevalence of severe hepatocellular injury in patients with CBD stones. Results revealed that approximately one-third of patients with choledocholithiasis present with ALT or AST > 500IU/L. Furthermore, levels > 1000IU/L are not uncommon. An elaborate work-up for alternative etiologies of severe transaminase elevation is likely unwarranted in cases with clear evidence of choledocholithiasis.

Propofol/dexmedetomidine Versus Desflaurane Effects on Post Hepatectomy Hepatocellular Injury

ABSTRACT Objective The Pringle maneuver used during hepatectomy causes ischemic reperfusion injury to the liver remnant. In this study, we compared the effect of maintenance of general anesthesia with propofol dexmedetomidine intravenous infusion versus desflurane inhalational anesthesia on post-hepatectomy hepatocellular injury in patients undergoing partial hepatectomy during the first six postoperative days. Methods Group A (15 patients) received total intravenous anesthesia with a combination of propofol and dexmedetomidine for anesthesia maintenance, and group B (15 patients) received desflurane for anesthesia maintenance. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum albumin, serum bilirubin, prothrombin time (PT), and international normalized ratio (INR) were measured before surgery and at 1, 3, and 6 days after surgery. Results Transaminase levels, which were comparable in both groups, peaked between the first and the third postoperative days. The peak ALT was 224.27 ± 29.7 and 318.20 ± 52.5 U/L in group A and group B, respectively (P < 0.001). The peak AST was 265.60 ± 22.3 U/L in group A and 349.27 ± 56.1 U/L in group B (P < 0.001). Albumin levels at day 1 showed no significant differences between both groups, but at days 3 and 6, group A showed significantly higher albumin levels than group B. Other liver function tests including serum albumin, total and direct bilirubin, PT, and INR showed lower values in the propofol/dexmedetomidine group. Conclusion The main finding of this study is that propofol/dexmedetomidine as a technique for the maintenance of anesthesia resulted in less hepatocellular injury and better hepatic functions than desflurane in patients undergoing partial hepatectomy during the first six postoperative days.

A STUDY ON CLINICAL CHARACTERISTICS OF ACUTE CHOLECYSTITIS AND ITS RELATION WITH ELEVATED LIVER ENZYMES AND BILIRUBIN

ntroduction: Acute cholecystitis is the most common complication in a gallstone disease and remains one of the most common medical problems leading to surgical intervention. The clinical picture of the patients with acute cholecystitis is further complicated by deranged liver function tests due to inammatory process induced by cholecystitis.74Liver damage in patients with gallstones is thought to be the result of chronic extra hepatic biliary tract obstruction with or without repeated episodes of cholangitis.69However, a few studies have reported the presence of hepatocellular injury in patients with acute cholecystitis without choledocholithiasis.70,38We conducted this study further to demonstrate any relation of gallstones with deranged liver function. This tertiary clinic based prospective observational study on 100 patients of gallMethods: stone disease diagnosed on imaging, was conducted at the Department of Surgery, Silchar Medical College and Hospital from 7th June 2018 to 6th June 2019.All routine tests with special reference to Total Leucocyte and Differential Leucocyte counts and Liver function tests- with special reference to serum bilirubin and fraction, Serum AST, ALT, ALP,GGT were obtained and statistical analysis performed to demonstrate their inter- relationship with gallstone disease. On the day of admission (day-0), 32 patients (15.62% male &amp; 84.37% female) had increased level ofResult: AST. Similarly, ALT was increased in 49 patients (20.4% male &amp; 79.59% female), ALP was increased in 32 patients (15.62% male &amp; 84.37% female), GGT was increased in 38 patients (26.31% male &amp; 73.6% female).All four liver enzymes were increased in 32% patients (12.5% male &amp; 87.5% female). Total Bilirubin was increased in 17 patients out of which 35.29% were Male and 64.7% were Female. Direct Bilirubin was increased in 26% patients (9 Males and 17 Females). Total Leucocytic count was increased in 60 patients out of which 14(23.3%) were Males and 46(76.6%) were Females. On the day of admission, AST was found to be in the range of 19U/L- 116U/L in the study population with a mean value of 48.10+27.59 and median value of 37.50.ALT was found to be in the range of 3U/L-141U/L in the study population with a mean value of 56.33+33.75 and median value of 40. ALP was found to be in the range of 60U/L-234U/L in the study population with a mean value of 117.58+39.64 and median value of 100.50. GGT was found to be in the range of 22U/L- 154U/L in the study population with a mean value of 74.66+30.05 and median value of 69.50. The mean values of Liver enzymes, Bilirubin (Total &amp; Direct) and TLC were found to be signicantly decreased on 6 weeks after admission. Liver enzymes and bilirubin tend to marginally increase in few cases of acute cholecystitis asConclusion: a result of the inammatory process. However, this increase is transient and the levels come down to normal once the inammatory process of acute cholecystitis subsides.

Autophagy alleviates amiodarone-induced hepatotoxicity

Amiodarone is a widely used antiarrhythmic drug that can cause the development of steatohepatitis as well as liver fibrosis and cirrhosis. The molecular mechanisms of amiodarone-mediated liver injury remain largely unknown. We therefore analyzed amiodarone-mediated hepatocellular injury in patients with chronic heart failure, in primary hepatocytes and HepG2 cells. We found that amiodarone-treated patients with chronic heart failure revealed significantly higher serum levels of caspase-cleaved keratin-18, an apoptosis biomarker, compared to healthy individuals or patients not receiving amiodarone. Furthermore, amiodarone treatment of hepatocytes resulted in apoptosis associated with lipid accumulation and ER-stress induction. Liver cell steatosis was accompanied by enhanced de novo lipogenesis which, after reaching peak levels, declined together with decreased activation of ER stress. The decline of amiodarone-mediated lipotoxicity was associated with protective autophagy induction. In contrast, in hepatocytes treated with the autophagy inhibitor chloroquine as well as in autophagy gene (ATG5 or ATG7)-deficient hepatocytes, amiodarone-triggered toxicity was increased. In conclusion, we demonstrate that amiodarone induces lipid accumulation associated with ER stress and apoptosis in hepatocytes, which is mirrored by increased keratin-18 fragment serum levels in amiodarone-treated patients. Autophagy reduces amiodarone-mediated lipotoxicity and could provide a therapeutic strategy for protection from drug-induced liver injury.

Serum glutamate dehydrogenase activity enables early detection of liver injury in subjects with underlying muscle impairments

Serum activities of alanine and aspartate aminotransferases (ALT and AST) are used as gold standard biomarkers for the diagnosis of hepatocellular injury. Since ALT and AST lack liver specificity, the diagnosis of the onset of hepatocellular injury in patients with underlying muscle impairments is severely limited. Thus, we evaluated the potential of glutamate dehydrogenase (GLDH) as a liver specific alternative biomarker of hepatocellular injury. In our study, serum GLDH in subjects with Duchene muscular dystrophy (DMD) was equivalent to serum GLDH in age matched healthy subjects, while serum ALT was increased 20-fold in DMD subjects. Furthermore, serum GLDH in 131 subjects with variety of muscle impairments was similar to serum GLDH of healthy subjects while serum ALT corelated with serum creatine kinase, a widely accepted biomarker of muscle impairment. In addition, significant elevations of ALT, AST, and CK were observed in a case of a patient with rhabdomyolysis, while serum GLDH stayed within the normal range until the onset of hypoxia-induced liver injury. In a mouse model of DMD (DMDmdx), serum GLDH but not serum ALT clearly correlated with the degree of acetaminophen-induced liver injury. Taken together, our data support the utility of serum GLDH as a liver-specific biomarker of liver injury that has a potential to improve diagnosis of hepatocellular injury in patients with underlying muscle impairments. In drug development, GLDH may have utility as a biomarker of drug induced liver injury in clinical trials of new therapies to treat muscle diseases such as DMD.

Independent Association of Physical Activity with Nonalcoholic Fatty Liver Disease and Alanine Aminotransferase Levels.

The aim of the current study was to examine the independent association of physical activity with nonalcoholic fatty liver disease (NAFLD) and aminotransferases while adjusting for obesity and diet. Cross-sectional data from 32,391 participants aged ≥20 years in the Korea National Health and Nutrition Examination Surveys (KNHANES) was analyzed by logistic regression models and general linear models. Physical activity was assessed from the questionnaire by health-enhancing physical activity (HEPA). The physical activity was negatively associated with NAFLD and lean NAFLD after adjustment for multiple factors with an odds ratio of 0.7 (95% CI, 0.6–0.8) and 0.5 (95% CI, 0.4–0.7) comparing the most active (HEPA active) and the least active (inactive) participants. Among the participants with NAFLD, physical activity also showed an independent negative association with alanine aminotransferase (ALT) levels but not with aspartate aminotransferase levels. These independent associations were not observed when comparing the minimally active and inactive participants except for the risk of lean NAFLD. Physical activity is independently associated with the degree of hepatocellular injury in patients with NAFLD as well as the risk of NAFLD and lean NAFLD in the general population. Sufficiently active physical activity greater than a minimally active level may be needed to lower the risk of NAFLD and ALT levels.

Graft-derived macrophage migration inhibitory factor correlates with hepatocellular injury in patients undergoing liver transplantation.

Human liver grafts release MIF in proportion to hepatocellular injury. Greater MIF concentrations in effluent and recipient's serum are associated with EAD after liver transplantation.

Issue Highlights

Issue Highlights

Exercise-based Interventions for Nonalcoholic Fatty Liver Disease: A Meta-analysis and Meta-regression.

The burden of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. We performed a meta-analysis to determine the effectiveness of exercise-based lifestyle interventions on liver-specific end points in populations with NAFLD and underlying metabolic disorders such as obesity, type 2 diabetes, or metabolic syndrome. We searched PubMed-MEDLINE, Embase, and the Cochrane Central register through October 21, 2015 for randomized trials of exercise-based lifestyle interventions on end points such as intrahepatic lipid content and blood levels of alanine and aspartate aminotransferases. Effect sizes are reported as standardized mean difference and weighted mean difference values. To investigate heterogeneity, we performed sensitivity and meta-regression analyses. Results were reported according to the PRISMA statement. We analyzed data from 28 trials. Physical activity, independently from diet change, was associated with a significant reduction in intrahepatic lipid content (standardized mean difference, -0.69; 95% confidence interval [CI], -0.90 to -0.48) and with reductions in alanine aminotransferase (weighted mean difference, -3.30 IU/L; 95% CI, 5.57 to -1.04) and aspartate aminotransferase (weighted mean difference, -4.85 IU/L; 95% CI, -8.68 to -1.02). By meta-regression, we found individuals with increasing body mass index to be increasingly more likely to benefit from the intervention (beta coefficient= -0.10; P= .037). We recorded no effect modification by variables related to the intensity of the intervention. In a meta-analysis of randomized trials, we found strong evidence that physical activity reduces intrahepatic lipid content and markers of hepatocellular injury in patients with NAFLD. This effect correlated with baseline body mass index.

Levofloxacin-Induced Hepatotoxicity and Death

Drug-induced hepatotoxicity is a major cause of hepatocellular injury in patients admitting to emergency services with acute liver failure. Hepatic necrosis may be at varying degrees from mild elevations in transaminases to fulminant hepatitis, and even death. The case of a 53-year-old female patient with toxic hepatitis due to levofloxacin and multiple organ failure secondary to toxic hepatitis is presented. Patient suffered itching, redness, and rash after receiving a single dose of 750 mg of levofloxacin tablets for pulmonary infection 10 days ago. Skin lesions had regressed within 3 days, but desquamation formed all over the body. After the fifth day of drug intake, complaints of abdominal pain, vomiting, and yellowing in skin color had started. The patient was referred to our emergency department with these complaints 10 days after drug intake. Patient was thought as a candidate for liver transplant, but cardiopulmonary arrest occurred, and the patient died before she could be referred to a transplant center. This case is important because hepatotoxicity and death due to levofloxacin is uncommon in the literature.

Clinical spectrum and therapeutic approach to hepatocellular injury in patients with hyperthyroidism

Liver dysfunction in patients with hyperthyroidism includes abnormalities associated with the effects of thyroid hormone excess, those secondary to drug-induced liver injury, and changes resulting from concomitant liver disease. Our goal was to describe clinical, biochemical, and histopathological patterns in patients suffering from hyperthyroidism and concomitant liver dysfunction and to propose an algorithm of procedures to facilitate diagnosis and management of such cases. This study describes seven patients with liver biochemistry abnormalities detected after diagnosis of hyperthyroidism and one with undiagnosed decompensated hyperthyroidism and acute hepatitis. Two patients showed autoantibody reactivity which, together with liver histology, suggested the diagnosis of classic autoimmune hepatitis. Three patients experienced hepatotoxicity induced by propylthiouracil, the manifestations of which ranged from a benign course after drug withdrawal in one, a longstanding course in another suggesting drug-induced autoimmune hepatitis, and a more severe clinical condition with acute liver failure in a third patient, requiring liver transplantation. The three remaining patients showed no precipitating factors other than thyroid hyperactivity itself. They could be interpreted as having a thyroid storm with different clinical presentations. In conclusion, this series of patients illustrates the most frequent patterns of hepatocellular damage associated with hyperthyroidism and provides an algorithm for their diagnosis and treatment.

Thiazolidinedione for the Treatment of NASH: A Meta-Analysis

Purpose: To systematically review the effect of TZD's on change in fibrosis, liver function test, degree of steatosis and hepatocellular injury in patients with NASH. Methods: We searched the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and reference lists of retrieved articles for relevant studies through October 2009. Studies were included if NASH was confirmed by biopsy and if it had a placebo arm. Primary end points were changes in fibrosis, liver function test, degree of steatosis and hepatocellular injury. Weighted Mean Difference (WMD) for changes in fibrosis with primary end point liver function tests, degree of steatosis, and hepatocellular injury were estimated using fixed and random effects meta-analysis. Results: Six relevant studies (enrolling 331 patients) out of twelve identified studies were included in the final analysis. When compared to patients treated with placebo patients treated with TZD's had a significant decrease in mean ALT (WMD -8.82, 95% CI; -12.63, -5.02), mean AST (WMD -3.75, 95% CI; -6.11, -1.38), and mean steatosis (WMD -0.48, 95% CI; -0.54, -0.43) at follow up. Patients treated with placebo had a non-significant increase in fibrosis (OR 1.49, 95% CI; 0.65, 3.39) and a significant increase in hepatocellular injury (OR 2.46, 95% CI; 1.21, 5.01) at follow up compared to those treated with TZD's. Conclusion: NASH patients treated with TZD's significantly improved in hepatocellular injury, liver function test and steatosis however there was a nonsignificant improvement in fibrosis compared to those treated with placebo. TZD's may be a new weapon in the armamentarium against NASH however more RCT's with longer duration of therapy are needed confirm this finding.

The effect of isoflurane or propofol anaesthesia on liver injury after partial hepatectomy in cirrhotic patients

SummaryThis study compared the effect of isoflurane or propofol anaesthesia on postoperative hepatocellular injury, liver function and pro‐inflammatory cytokine concentrations in 60 cirrhotic patients, after partial hepatectomy using Pringle’s manoeuvre. In the isoflurane group postoperatively, both mean (SD) aspartate aminotransferase (day 1: 197 (123) U.l−1 vs 261 (143) U.l−1; p = 0.01; day 3: 465 (258) U.l−1 vs 578 (311) U.l−1; p = 0.02) and alanine aminotransferase (day 1: 575 (312) U.l−1 vs 714 (434) U.l−1; p = 0.04 and day 3: 776 (443) U.l−1 vs 898 (746) U.l−1; p = 0.03) were significantly lower compared with the propofol group. Mean (SD) postoperative white cell count was significantly lower with isoflurane than propofol (day 1: 12 (4) × 103.mm−1 vs 16 (4) × 103.mm−1; p = 0.01 and day 3: 10 (6) × 103.mm−1; vs 14 (4); p = 0.01). Tumour necrosis factor‐α (day 1) and interleukin‐1 (days 1 and 3) concentrations were significantly lower with isoflurane. Compared with propofol, isoflurane is associated with an attenuated postoperative inflammatory response and less postoperative hepatocellular injury in patients having this procedure.

Clinical trial: the efficacy and safety of oral PF‐03491390, a pancaspase inhibitor – a randomized placebo‐controlled study in patients with chronic hepatitis C

Elevated serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) reflect hepatocellular injury in patients with chronic hepatitis C virus (HCV). Increased apoptosis and activated caspases are present in these patients. PF-03491390 inhibits multiple caspases and lowers serum AST and ALT levels in patients with chronic liver diseases. To determine if treatment with an oral pancaspase inhibitor could reduce serum AST and ALT in patients with HCV. Double-blind, randomized, placebo-controlled, parallel-dose study in 204 patients treated with placebo or PF-03491390 (5, 25 or 50 mg) orally twice daily (b.d.) for up to 12 weeks. Serum AST and ALT were monitored weekly. Significant reductions in serum AST and ALT were observed within 1 week of initiating PF-03491390 in all treatment groups (P < 0.0001). These reductions in AST and ALT were maintained throughout the 12 week treatment period and returned to baseline levels when PF-03491390 was discontinued. Increasing the dose did not further lower AST or ALT. The most frequently reported adverse events were headache and fatigue. PF-03491390 significantly reduced serum AST and ALT levels in patients with chronic HCV, and was well tolerated over 12 weeks.

Acute transient hepatocellular injury in cholelithiasis and cholecystitis without evidence of choledocholithiasis

To investigate acute transient hepatocellular injury in patients with cholelithiasis and cholecystitis but no evidence of choledocholithiasis. The medical records of patients with cholelithiasis who underwent cholecystectomy between July 2003 and June 2007 were retrospectively reviewed. Imaging studies to detect common bile duct (CBD) stones were performed in 186 patients, who constituted the study population. Biochemical liver tests before and after surgery, and with the presence or absence of CBD stones were analyzed. In 96 patients with cholelithiasis and cholecystitis without evidence of CBD stones, 49 (51.0%) had an alanine aminotransferase level elevated to 2-3 times the upper limit of normal, and 40 (41.2%) had an elevated aspartate aminotransferase level. Similar manifestations of hepatocellular injury were, as would be expected, even more obvious in the 90 patients with CBD stones. These markers of hepatocellular injury resolved almost completely within 2 wk to 1 mo after cholecystectomy. Compared to 59 patients with histologically less severe cholecystitis in the group undergoing urgent surgery (total 74 patients), the 15 patients with a gangrenous gallbladder had a higher mean level of total bilirubin (1.14 +/- 1.27 mg/dL vs 2.66 +/- 1.97 mg/dL, P < 0.001) and white cell count (9480 +/- 4681/microL vs 12840 +/- 5273/microL, P = 0.018). Acute hepatocellular injury in cholelithiasis and cholecystitis without choledocholithiasis is mild and transient. Hyperbilirubinemia and leukocytosis may predict severe inflammatory changes in the gallbladder.

Liver Manipulation Causes Hepatocyte Injury and Precedes Systemic Inflammation in Patients Undergoing Liver Resection

BackgroundLiver failure following liver surgery is caused by an insufficient functioning remnant cell mass. This can be due to insufficient liver volume and can be aggravated by additional cell death during or after surgery. The aim of this study was to elucidate the causes of hepatocellular injury in patients undergoing liver resection.MethodsMarkers of hepatocyte injury (AST, GSTα, and L-FABP) and inflammation (IL-6) were measured in plasma of patients undergoing liver resection with and without intermittent inflow occlusion. To study the separate involvement of the intestines and the liver in systemic L-FABP release, arteriovenous concentration differences for L-FABP were measured.ResultsDuring liver manipulation, liver injury markers increased significantly. Arterial plasma levels and transhepatic and transintestinal concentration gradients of L-FABP indicated that this increase was exclusively due to hepatic and not due to intestinal release. Intermittent hepatic inflow occlusion, anesthesia, and liver transection did not further enhance arterial L-FABP and GSTα levels. Hepatocyte injury was followed by an inflammatory response.ConclusionsThis study shows that liver manipulation is a leading cause of hepatocyte injury during liver surgery. A potential causal relation between liver manipulation and systemic inflammation remains to be established; but since the inflammatory response is apparently initiated early during major abdominal surgery, interventions aimed at reducing postoperative inflammation and related complications should be started early during surgery or beforehand.

Correlation of serum aminotransferases with HCV RNA levels and histological findings in patients with chronic hepatitis C

To investigate whether HCV RNA levels can be considered to be predictors of hepatocellular injury in patients with chronic hepatitis C, and whether aminotransferase levels are markers of liver damage. We performed a retrospective study on 112 patients with chronic hepatitis C. For each patient, we considered the baseline alanine aminotransferase (ALT) and serum aspartate transaminase (AST) levels, baseline HCV RNA, HCV genotype, histological evaluation and the mean aminotransferase levels measured in the 6 months following liver biopsy. We found a statistically significant correlation between HCV RNA and aminotransferase levels measured during the follow-up (AST: r = 0.24, P = 0.01; ALT: r = 0.27, P = 0.004). We also observed a statistically significant correlation between HCV RNA levels and histological activity index (HAI) (r = 0.25, P = 0.008), as well as between the HAI and both baseline AST (r = 0.34, P = 0.0002) and ALT levels (r = 0.23, P = 0.01). These findings were confirmed by the mean aminotransferase values during follow-up. In the regression analysis, the fibrosis score was significantly and independently associated with baseline AST and ALT values. Our results demonstrate a statistically significant correlation of aminotransferase values with the histological parameters, and an even stronger correlation with the AST values. Our study therefore suggests that aminotransferase values, especially AST, may correlate with liver damage.

Clinical significance of SEN-virus on interferon response in chronic hepatitis C patients.

A novel virus, SEN-virus (SENV), was recently discovered. It has been reported as a candidate for a non-A-E hepatitis virus. However, much is still unknown about the clinical significance of SENV. The aim of the present study was to clarify the clinical significance of SENV in patients coinfected with SENV and hepatitis C virus (HCV). The 52 subjects had chronic hepatitis C and had undergone interferon (IFN) therapy. SEN virus DNA was investigated by using polymerase chain reaction with SENV-specific primers, which we designed to detect all strains of SENV. Additionally, SENV-D and -H were detected by consensus primers. Thirty-five patients were SENV-DNA positive and 22 patients were SENV-D- or -H-positive before IFN therapy. After IFN therapy, in the HCV-RNA eradication group, all cases normalized their serum alanine aminotransferase (ALT). However, in the no eradication group, the ALT no-response rate was 68.7%. In contrast, in the SENV eradication group, the ALT no-response rate was 51.9%, and in the no eradication group, it was 37.5%. Also, in the SENV-D and -H eradication group, the ALT no-response rate was 54.5%, and in the no eradication group, it was 36.4%. The changes in ALT after IFN therapy were significantly correlated with the changes in HCV RNA, but no correlation was found with the SENV DNA presence. Hepatocellular injury in patients with chronic hepatitis who are coinfected with HCV and SENV appears to primarily be caused by HCV, and is less attributable to SENV.

The presence of an intrahepatic cytotoxic T lymphocyte response is associated with low viral load in patients with chronic hepatitis C virus infection

Background/Aims : The role of cytotoxic T lymphocytes (CTL) in limiting viral replication and producing hepatocellular injury in patients with chronic hepatitis C virus (HCV) infection is controversial. Methods : Intrahepatic and peripheral blood HCV-specific CTL activity against the entire HCV polyprotein was assessed in 26 patients. CTL responses were assessed after effector lymphocytes were re-stimulated for 6 days in vitro using HCV-vaccinia virus-infected autologous cells expressing HCV antigens. Serum and hepatic viral loads were measured and immunohistochemistry for CD3 and CD8 was performed to localise and enumerate effector cells in liver. Results : A positive CTL response was detected in 39/52 (75%) of assays conducted with intrahepatic mononuclear cells and 21/52 (40%) of peripheral blood assays ( P<0.001). The presence of an intrahepatic CTL response was associated with low hepatic viral load ( P=0.004). Hepatic lobular infiltration by CD8 +T cells correlated weakly with serum alanine aminotransferase levels ( r=0.42, P=0.04) and no relationship was demonstrated between CTL activity and histological evidence of liver damage. Conclusions : HCV-specific CTL activity is found more commonly in liver than in blood. An inverse relationship between CTL responses and viral load supports the hypothesis that HCV-specific CTL limit viral replication in patients with chronic HCV infection.