Hepatitis C-related Cirrhosis Research Articles

New insights into potential biomarkers and their roles in biological processes associated with hepatitis C-related liver cirrhosis by hepatic RNA-seq-based transcriptome profiling

Chronic hepatitis C virus infection is a major cause of mortality due to liver cirrhosis globally. Despite the advances in recent therapeutic strategies, there is yet a high burden of HCV-related cirrhosis worldwide concerning low coverage of newly developed antiviral therapies, insufficient validity of the current diagnostic methods for cirrhosis, and incomplete understanding of the pathogenesis in this stage of liver disease. Hence we aimed to clarify the molecular events in HCV-related cirrhosis and identify a liver-specific gene signature to potentially improve diagnosis and prognosis of the disease.Through RNA-seq transcriptome profiling of liver samples of Iranian patients with HCV-related cirrhosis, the differentially expressed genes (DEGs) were identified and subjected to functional annotation including biological process (BP) and molecular function (MF) analysis and also KEGG pathway enrichment analysis. Furthermore, the validation of RNA-seq data was investigated for seven candidate genes using qRT-PCR. Moreover, the diagnostic and prognostic power of validated DEGs were analyzed in both forms of individual DEG and combined biomarkers through receiver operating characteristic (ROC) analysis. Finally, we explored the pair-wise correlation of these six validated DEGs in a new approach.We identified 838 significant DEGs (padj ˂0.05) enriching 375 and 15 significant terms subjected to BP and MF, respectively (false discovery rate ˂ 0.01) and 46 significant pathways (p-value ˂ 0.05). Most of these biological processes and pathways were related to inflammation, immune responses, and cellular processes participating somewhat in the pathogenesis of liver disease. Interestingly, some neurological-associated genes and pathways were involved in HCV cirrhosis-related neuropsychiatric disorders. Out of seven candidate genes, six DEGs, including inflammation-related genes ISLR, LTB, ZAP70, KLRB1, and neuronal-related genes MOXD1 and Slitrk3 were significantly confirmed by qRT-PCR. There was a close agreement in the expression change results between RNA-seq and qRT-PCR for our candidate genes except for SAA2-SAA4 (P= 0.8). High validity and reproducibility of six novel DEGs as diagnostic and prognostic biomarkers were observed. We also found several pair-wise correlations between validated DEGs.Our findings indicate that the six genes LTB, ZAP70, KLRB1, ISLR, MOXD1, and Slitrk3 could stand as promising biomarkers for diagnosing of HCV-related cirrhosis. However, further studies are recommended to validate the diagnostic potential of these biomarkers and evaluate their capability as targets for the prevention and treatment of cirrhosis disease.

Risk Factors for Progressive Fibrosis and Cirrhosis in Patients With Chronic Hepatitis C in India.

Background Liver cirrhosis (LC) caused by chronic hepatitis C (CHC) infection is a major global public health concern. This study will look at the risk factors for progressive fibrosis and cirrhosis in patients with persistent hepatitis C virus (HCV) infection. Methods In this cohort study, a total of 300 patients were included. We collected comprehensive diagnostic records for the entire study group of 200 people with chronic hepatitis C infection. For the comparison, 100 healthy people were recruited and assessed. FibroScan (Echosens, Paris, France) scores were used to categorize liver fibrosis stages: F0-F1 (no or mild fibrosis, <7 kPa), F2 (moderate fibrosis, 7-8.99 kPa), F3 (significant fibrosis, 9-12.49 kPa), and F4 (cirrhosis, ≥12.5 kPa). Their demographic, biochemical, and serological data were evaluated and compared. Results Most patients were males (47% femalesand 53% males). In the CHC group, the mean age of diagnosis was 37.68±11.57 years, whereasin the chronic hepatitis C-related liver cirrhosis (CHC-LC) group, the mean age was 48.89±12.30 years (p=0.01).Compared to normal individuals, CHC patients had higher body mass index (BMI) (22.37±1.89 versus 21.72±1.95, p=0.01), alanine aminotransferase (ALT) (36.70±7.13 versus 82.78±82.53, p=0.01), and aspartate aminotransferase (AST) (34.96±6.04 versus 80.82±91.77, p=0.01). However,compared to the patients with CHC, the patients with LC have lower platelet (PLT) count (1.51±0.78 versus 1.7±0.41, p=0.01) and higher liver enzymes (AST: 117.7±186.9 versus 80.8±91.7, p=0.01; ALT: 86.71±80.24 versus 82.78±82.53, p=0.01). On regression analysis, higher BMI, older age, low hemoglobin (Hb), and higherbilirubin, ALT, AST, and prothrombin time (PT) were associated with LC. Conclusion It is imperative to shift towardprevention and early intervention as the new approach to managing patients with HCV-related cirrhosis. Cirrhosis should be suspected in older patients with CHCwho are obese and have low platelet counts with higher liver enzymes.

Pediatric and adult liver transplantation in Bahrain: The experiences in a country with no available liver transplant facilities.

Liver transplantation (LT) is a life-saving procedure for patients with end-stage liver disease and has become the standard and most effective treatment method for these patients. There are many indications for LT that vary between countries and settings. The outcome of LT depends on the available facilities and surgical expertise, as well as the types of liver graft donors available. To assess the clinical characteristics of patients from Bahrain who underwent LT overseas, and analyze factors affecting their survival. In this retrospective cohort study, we reviewed the medical records and overseas committee registry information of all pediatric and adult patients who were sent overseas to undergo LT by the Pediatric and Medical Departments of Salmaniya Medical Complex and Bahrain Defence Force Hospital via the Overseas Treatment Office, Ministry of Health, Kingdom of Bahrain, between 1997 and 2023. Demo graphic data, LT indication, donor-recipient relationship, overseas LT center, graft type, post-LT medications, and LT complications, were collected. Outcomes measured included the overall and 5-year LT survival rate. Fisher's exact, Pearson χ2, and Mann-Whitney U tests were used to compare the pediatric and the adults' group in terms of clinical characteristics, donor-recipient relationship, medication, complications, and outcome. Survival analysis was estimated via the Kaplan-Meier's method. Univariate and multivariate analyses were used to detect predictors of survival. Of the 208 eligible patients, 170 (81.7%) were sent overseas to undergo LT while 38 (18.3%) remained on the waiting list. Of the 170 patients, 167 (80.3%) underwent LT and were included in the study. The majority of the patients were Bahraini (91.0%), and most were males (57.5%). One-hundred-and-twenty (71.8%) were adults and 47 (28.3%) were children. The median age at transplant was 50.0 [interquartile range (IQR): 14.9-58.4] years. The main indication for pediatric LT was biliary atresia (31.9%), while that of adult LT was hepatitis C-related cirrhosis (35.0%). Six (3.6%) patients required re-transplantation. Most patients received a living-related liver graft (82%). Pediatric patients received more living and related grafts than adults (P = 0.038 and P = 0.041, respectively), while adult patients received more cadaveric and unrelated grafts. Most patients required long-term immunosuppressive therapy after LT (94.7%), of which tacrolimus was the most prescribed (84.0%), followed by prednisolone (50.7%), which was prescribed more frequently for pediatric patients (P = 0.001). Most patients developed complications (62.4%) with infectious episodes being the most common (38.9%), followed by biliary stricture (19.5%). Tonsilitis and sepsis (n = 12, 8.1% for each) were the most frequent infections. Pediatric patients experienced higher rates of infection, rejection, and early poor graft function than adult patients (P < 0.001, P = 0.003, and P = 0.025, respectively). The median follow-up time was 6.5 (IQR: 2.6-10.6) years. The overall survival rate was 84.4%, the 5-year survival rate, 86.2%, and the mortality rate, 15.6%. Younger patients had significantly better odds of survival (P = 0.019) and patients who survived had significantly longer follow-up periods (P < 0.001). Patients with end-stage liver disease in Bahrain shared characteristics with those from other countries. Since LT facilities are not available, an overseas LT has offered them great hope.

Prediction of Esophageal Varices in Viral Hepatitis C Cirrhosis: Performance of Combined Ultrasonography and Clinical Predictors.

This study is aimed at evaluating the diagnostic performance of clinical predictors and the Doppler ultrasonography in predicting esophageal varices (EV) in patients with hepatitis C-related cirrhosis and exploring the practical predictors of EV. We conducted a prospective study from July 2020 to January 2021, enrolling 65 patients with mild hepatitis C-related cirrhosis. We obtained clinical data and performed grayscale and the Doppler ultrasound to explore the predictors of EV. Esophagogastroduodenoscopy (EGD) was performed as the reference test by the gastroenterologist within a week. The prevalence of EV in the study was 41.5%. Multivariable regression analysis revealed that gender (female, OR = 4.04, p = 0.02), platelet count (<150000 per ml, OR = 3.13, p = 0.09), splenic length (>11 cm, OR = 3.64, p = 0.02), and absent right hepatic vein (RHV) triphasicity (OR = 3.15, p = 0.03) were significant predictors of EV. However, the diagnostic accuracy indices for isolated predictors were not good (AUROC = 0.63-0.66). A combination of these four predictors increases the diagnostic accuracy in predicting the presence of EV (AUROC = 0.80, 95% CI 0.69-0.91). Furthermore, the Doppler assessment of the right hepatic vein waveform showed good reproducibility (κ = 0.76). Combining clinical and Doppler ultrasound features can be used as a screening test for predicting the presence of EV in patients with hepatitis C-related cirrhosis. The practical predictors identified in this study could serve as an alternative to invasive EGD in EV diagnosis. Further studies are needed to explore the diagnostic accuracy of additional noninvasive predictors, such as elastography, to improve EV screening.

Prediction of hepatic decompensation and hepatocellular carcinoma after direct-acting antiviral therapy in patients with hepatitis C-related liver cirrhosis: a cohort study

AimThis study aimed to evaluate the rate of hepatic decompensation and de novo HCC and identify their independent factors in HCV genotype 4-infected patients with compensated liver cirrhosis following successful direct-acting antiviral (DAA) therapy.MethodsThis prospective cohort study included 1789 patients with HCV genotype 4-related compensated liver cirrhosis who achieved viral eradication after DAAs. Baseline and follow-up clinical, laboratory, albumin-bilirubin score (ALBI), and abdominal ultrasound were recorded to detect hepatic decompensation and de novo HCC. Logistic regression was performed to evaluate the variables associated with decompensation and HCC.ResultsDuring the 24-month period of follow-up, 184 (10.28%) patients developed hepatic decompensation. Ascites was the commonest presentation. Baseline serum albumin, bilirubin, and platelet count were the independent factors associated with hepatic decompensation (P-values 0.022, 0.03, and < 0.001, respectively). A formula was developed for the prediction of decompensation using these 3 factors (AUC: 0.641 at cutoff 0.1098969 with a sensitivity of 59.9% and specificity of 61.7%). Pre-treatment ALBI score could predict decompensation at cutoff value − 2.5184, AUC 0.609, sensitivity 58.3%, and specificity 59.7%. Post-treatment ALBI score could predict hepatic decompensation after DAA therapy at cutoff value − 2.9521, AUC 0.597, sensitivity 48.1%, and specificity 75.5%. Sixteen (0.9%) patients developed de novo HCC. Age (odds ratio: 1.061, 95%, confidence interval: 1–1.126) and male gender (OR 3.450, 95% CI 1.105–10.769) were the independent factors associated with the development of de novo HCC but not the ALBI score.ConclusionBaseline demographic and laboratory data could predict hepatic decompensation and HCC in patients with compensated liver cirrhosis after successful DAA therapy

Three cases of immune-related hypopituitarism after atezolizumab-bevacizumab treatment for hepatocellular carcinoma.

We herein report three cases of immune-related hypopituitarism after atezolizumab-bevacizumab treatment for hepatocellular carcinoma (HCC). Case 1 was a man in his 60s with hepatitis C-related liver cirrhosis. He had been diagnosed with HCC and undergone surgical resection. However, HCC recurred 17months after surgery. After 13 cycles of atezolizumab-bevacizumab therapy, general fatigue, appetite loss, and muscle weakness appeared. The plasma levels of adrenocorticotropic hormone (ACTH) and cortisol were decreased. He was diagnosed with central adrenal insufficiency associated with hypopituitarism. Glucocorticoid therapy rapidly improved his symptoms. Case 2 was a man in his 70s with HCC associated with non-alcoholic steatohepatitis (NASH). After eight cycles of atezolizumab-bevacizumab therapy, general fatigue, appetite loss, and muscle weakness appeared. Hyponatremia and eosinophilia were observed. He was also diagnosed with hypopituitarism, and glucocorticoid therapy rapidly improved his symptoms. Case 3 was a man in his 60s with HCC associated with alcoholic liver cirrhosis. After 10 cycles of atezolizumab-bevacizumab therapy, hypopituitarism developed. In these cases, the presence of hyponatremia and/or eosinophilia was useful for making a diagnosis. Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) antibody is reported to be likely to induce hypophysitis two to three months after its administration. In contrast, anti-programmed cell death 1 (PD-1) antibody is likely to induce hypopituitarism six to seven months after its administration. These three patients treated with anti-programmed death ligand 1 (PD-L1) antibody developed hypopituitarism six to nine months later, close to the condition with anti-PD-1 antibody administration. Although immune-related hypopituitarism after atezolizumab-bevacizumab treatment is rare, we should be alert for hypopituitarism developing during atezolizumab-bevacizumab treatment.

Short-term hepatocyte function and portal hypertension outcomes of sofosbuvir/velpatasvir for decompensated hepatitis C-related cirrhosis

BackgroundIt is unclear whether hepatocyte function and/or portal hypertension improves if a sustained virologic response (SVR) is achieved with direct-acting antivirals in patients with decompensated hepatitis C-related cirrhosis.MethodsWe examined the safety and efficacy of a 12-week course of sofosbuvir/velpatasvir (SOF/VEL) in 20 patients with decompensated hepatitis C-related cirrhosis. We also investigated changes in the hepatocyte receptor index (LHL15) and blood clearance index (HH15) by Tc-99 m-galactosyl human serum albumin scintigraphy, liver stiffness measurement (LSM) by transient elastography, and hepatic venous pressure gradient (HVPG) in patients who achieved an SVR at 24 weeks after treatment (SVR24).ResultsOne patient discontinued treatment because of rectal variceal hemorrhage, and 19 patients completed treatment. SVR24 was achieved in 17 patients (89%). Median LHL15 increased from 0.72 pre-treatment to 0.82 after SVR24 (p = 0.012), and median HH15 decreased from 0.82 pre-treatment to 0.76 after SVR24 (p = 0.010). The percentage of patients with LSM ≥ 20 kPa was 90% before treatment and remained at 90% after SVR24. However, the percentage with severe portal hypertension (defined as HVPG ≥ 12 mmHg) decreased from 92% pre-treatment to 58% after SVR24 (p = 0.046). Patients with a decreased HVPG from pre-treatment to after SVR24 had a smaller pre-treatment spleen volume than those with an increased HVPG (median, 252 vs. 537 mL, p = 0.028).ConclusionAchieving SVR24 with SOF/VEL treatment in patients with decompensated hepatitis C-related cirrhosis can be expected to improve hepatocyte function and portal hypertension on short-term follow-up.

The role of serum visfatin and vaspin in hepatocellular carcinoma in hepatitis C-related liver cirrhosis.

To investigate the role of the novel adipokines visfatin and vaspin in hepatitis C virus (HCV)-cirrhotic patients with and without hepatocellular carcinoma (HCC) and their association with tumour characteristics and liver dysfunction. This case-control study was carried out between March 2021 and September 2021. Serum visfatin and vaspin were measured in 67 HCV-cirrhotic patients (37 had HCC, and 30 did not) and 20 healthy individuals using enzyme-linked immunosorbent assay (ELISA). Serum visfatin and vaspin were substantially elevated in HCC patients compared to those without HCC and healthy controls (p = 0.001, < 0.0001, respectively) and significantly associated with hepatic dysfunction. At a cut-off value of 12.1 ng/ml, the sensitivity and specificity of the serum visfatin in detecting HCC were 67.6% and 83.3%, respectively. Serum vaspin at a cut-off value of 321 ng/dl had a sensitivity of 94.6% and specificity of 66.7%. In multivariate regression analysis, serum vaspin and albumin were independent risk factors for HCC development. Patients with Barcelona Clinic Liver Cancer (BCLC) stage D had significantly the highest serum levels of visfatin and vaspin (p = 0.03, 0.008, respectively). Serum visfatin and vaspin were substantially higher in HCC patients, associated with tumour stage, and might be considered as potential biomarkers of HCC, but this should be confirmed in larger independent cohorts of patients with liver cirrhosis. Serum vaspin and albumin were independent risk factors for HCC development. There was a substantial association between visfatin, vaspin, and the severity of the underlying liver dysfunction.

Classification and survival prediction in early-stage cirrhosis by gene expression profiling.

Liver cirrhosis has been increasingly diagnosed at an early stage owing to the non-invasive diagnostic techniques. However, it is difficult to identify patients at high risk of disease progression. Screening cirrhotic patients with poor prognosis who are most in need of surveillance is still challenging. Gene expression data GSE15654 and GSE14520 were downloaded for performing unsupervised clustering analysis. The prognostic differences between the different clusters were explored by Cox regression. Integrative analysis of gene expression signature, immune cell enrichments and clinical characterization was performed for different clusters. Two distinctive subclasses were identified in HCV-related GSE15654, and Kaplan-Meier analysis indicated that subtype 2 had lower survival rates than subtype 1 (p=0.0399). Further analysis revealed subtype 2 had a higher density of follicular T helper cells, resting natural killer cells and M0, M2 macrophages while subtype 1 with a higher fraction of naive B cells, memory B cells, resting memory CD 4T cells, activated natural killer cells and monocytes. 226 differentially expressed genes were identified between the two subtypes, and Reactome analysis showed the mainly enriched pathways were biological oxidations and fatty acid metabolism. Five hub genes (AKT1, RPS16, CDC42, CCND1 and PCBP2) and three significant modules were extracted from the PPI network. The results were validated in HBV-related GSE14520 cohort. We identified two subtypes of patients with different prognosis for hepatitis C-related early-stage liver cirrhosis. Bioinformatics analysis of the gene expression and immune cell profile may provide fresh insight into understanding the prognosis difference.

Renoportal Anastomosis and Its Complications: A Complex Case Report

Renoportal anastomosis (RPA) is an effective technique in cases of complex portal vein thrombosis with the presence of a splenorenal shunt. The objective of this report is to describe the possible complications related to RPA. A 50-year-old man with alcohol-related and hepatitis C-related cirrhosis and 2 hepatocellular carcinomas underwent liver transplant. He presented a portal vein thrombosis Yerdel IV, a splenorenal shunt, and another shunt between the inferior mesenteric vein (IMV) and the perirectal plexus. During surgery, the flow of the left renal vein was 891 mL/min, and this rose to 1050 mL/min after IMV clamping. RPA was made through iliac vein graft interposition, and the IMV was ligated. Portal flow was 832 mL/min but drastically decreased because of mesenteric root compression. After finishing the liver transplant, a renoiliac graft percutaneous transhepatic stent was put in place. The patient presented graft dysfunction and acute kidney injury. On postoperative day +18, a second stent was put in place because of a thrombosis in the splenomesenteric confluence. The patient subsequently presented partial distal rethrombosis and a pancreaticoduodenal arteriovenous fistula, which required several embolizations. The patient developed ascites, recurrent gastrointestinal bleeding, and persistent bacterial peritonitis. Finally, a modified Sugiura procedure (without splenectomy) was performed, achieving a portal flow of 1800 mL/min. However, the patient developed sepsis and multiorgan failure, and died on postoperative day +70. Despite long-term patient and graft survival within accepted limits after LT, RPA is a challenging technique not exempt from complications.

Assessment of Serum Interleukin 8 in Hepatitis C-related Cirrhosis with Itching

Assessment of Serum Interleukin 8 in Hepatitis C-related Cirrhosis with Itching

Impact of Sarcopenia on Short-Term Complications and Survival After Liver Transplant.

Sarcopenia is a common entity in cirrhosis with significant morbidity and mortality. However,the effects of sarcopenia on the risk of complications and survival after liver transplant remain controversial.We aimed to evaluate the effect of sarcopenia on survival and complications after liver transplant. Our study cohort included 61 adult patients with hepatitis C-related cirrhosis who underwent living donor liver transplant. Pretransplant clinical and anthropometric assessments included body mass index, hand grip, mid-arm circumference, triceps skin fold thickness, and gait speed. Sarcopenia was determined by computed tomography using the skeletal muscle index at the third lumbar vertebra cut-off value of <38.5 cm2/m2 for women and <52.4 cm2/m2 for men; these patients were then followed up for 6 months after transplant to determine survival and complications. At time of liver transplant, sarcopenia was present in 27/61 patients (44.3%). At follow-up after transplant, sarcopenia was found in 14 patients (30.4%) among 46 survivors; all patients who survived were male patients. Among patients with sarcopenia posttransplant, 12 had sarcopenia before transplant and 2 developed sarcopenia after transplant. Liver dysfunction, lower triceps skin fold thickness, recent infections, and sarcopenia pretransplant were associatedwithposttransplant complications, especially infection(42.8%) and prolonged intensive careunit stay. Age and pretransplant sarcopenia were found to be independent predictors of posttransplant mortality. Sarcopenia is a common entity in patients with cirrhosis who are on liver transplant wait lists and may continue after liver transplant. De novo sarcopenia after liver transplant is also a common finding. Sarcopenia can affect patient outcomes, including prolonged intensive care unit stay and poor short-term survival.

Assessment of Serum Interleukin 8 in Hepatitis C-Related Cirrhosis with Itching

Assessment of Serum Interleukin 8 in Hepatitis C-Related Cirrhosis with Itching

Necrotic lesions of the hands

An 82-year-old man with a history of end-stage renal disease due to glomerulonephritis requiring haemodialysis, hepatitis C-related liver cirrhosis and hypertensive cardiomyopathy presented with painful and necrotic lesions of both his hands. He had no other symptoms. [...]

CHRIST: CD44-Incorporated Hepatocellular Carcinoma Risk Index Scoring Tool-A Novel Prognostic Scoring System for Hepatocellular Carcinoma Development and Aggressiveness.

CD44 has been demonstrated to play a pivotal role in regulating tumor cell progression, including hepatocellular carcinoma (HCC) development. Here, we aimed to establish a scoring system to evaluate the risk of developing HCC utilizing CD44-rs187115 SNP polymorphism. A prospective cohort of 120 individuals was enrolled in four groups: 19 non-metastatic HCC patients, 21 metastatic, 40 patients with hepatitis C-related cirrhosis, and 40 controls. Allelic discrimination of the CD44-rs187115 gene polymorphism was assessed using TaqMan genotyping assay. HCC patients with CT/CC genotypes were more likely to have aggressive malignancy compared to TT carriers. A significant correlation was noted between the existence of CT/CC genotypes and tumor size, multicentricity, infiltration, portal vein thrombosis, and metastasis. A CD44-incorporated Hepatocellular Carcinoma Risk Index Scoring Tool (CHRIST) was formulated utilizing clinical and genetic variables. A score > 3 for HCC development demonstrated 87.5% sensitivity, 72.5% specificity, and a 76% positive predictive value (PPV) and 85% negative predictive value (NPV). Furthermore, a score > 5 for HCC metastasis demonstrated 90.4% sensitivity, 68.4% specificity, a 76% PPV and 86% NPV. A similarly significant score was noted following a six-month re-evaluation. We conclude that CD44-rs187115 may serve as a reliable prognostic biomarker for HCC and that the CHRIST prognostic model is highly predictive of the development of HCC and metastatic HCC.

Two cases of rapid progression of esophageal varices after atezolizumab-bevacizumab treatment for hepatocellular carcinoma.

We report two cases of rapid progression of esophageal varices after atezolizumab-bevacizumab treatment for hepatocellular carcinoma (HCC). Case 1: a man in his 60s with hepatitis C-related liver cirrhosis after viral eradication by direct acting antiviral. He was diagnosed with HCC 8years previously. He had undergone surgical resection 4 times, radio-frequency ablation (RFA) several times, and transcatheter arterial chemoembolization (TACE). However, HCC progressed and could not be controlled by locoregional treatment. Systemic chemotherapy was, therefore, selected. Atezolizumab-bevacizumab was administered after lenvatinib and sorafenib failure. Before starting treatment, his liver function was preserved (Child-Pugh score 5 and class A). His alpha fetoprotein and des-gamma-carboxyprothrombin levels were 3.6ng/mL and 443 mAU/mL, respectively. Esophagogastroduodenoscopy showed no remarkable esophageal varices before atezolizumab-bevacizumab treatment. Nine months after the initiation of atezolizumab-bevacizumab, the patient was admitted for hematemesis from esophageal varices. The disease control of HCC was classified as stable disease (SD) for the liver and lung metastases, and partial response for the lymph node metastases. Neither AST nor ALT was markedly elevated in the clinical course. Endoscopic variceal ligation (EVL) for the spurting point of large esophageal varices with red wale signs was able to successfully achieve hemostasis. Atezolizumab-bevacizumab was stopped and additional EVL eradicated the esophageal varices. However, the post-banding ulcer was prolonged in comparison to usual cases. Case 2: a man in his 60s with hepatitis C-related liver cirrhosis after viral eradication by direct acting antiviral therapy. He was diagnosed with HCC 6years previously. He had received RFA 2 times and TACE 7 times. Atezolizumab-bevacizumab was administered after lenvatinib failure. The disease control of HCC was classified as SD; however, the esophageal varices ruptured after 15 courses of atezolizumab-bevacizumab. Neither AST nor ALT were markedly elevated in the clinical course. The esophageal varices of these patients did not require treatment before atezolizumab-bevacizumab; however, they rapidly worsened and ruptured during atezolizumab-bevacizumab treatment. Although rare, similar cases with rapid progression of portal hypertension after atezolizumab-bevacizumab have been reported. We should pay attention to the worsening of esophageal varices during atezolizumab-bevacizumab treatment and poor wound healing after EVL.

Direct acting antiviral治療後に原発不明癌を発症し急激な転機を辿ったC型肝硬変の1例

Direct acting antiviral治療後に原発不明癌を発症し急激な転機を辿ったC型肝硬変の1例

Laboratory Profile of COVID-19 Patients with Hepatitis C-Related Liver Cirrhosis.

Patients with cirrhosis are known to have multiple comorbidities and impaired organ system functioning due to alterations caused by chronic liver failure. In the past two years, since the COVID-19 pandemic started, several studies have described the affinity of SARS-CoV-2 with the liver and biliary cells. Considering hepatitis C as a significant independent factor for cirrhosis in Romania, this research was built on the premises that this certain group of patients is susceptible to alterations of their serum parameters that are yet to be described, which might be useful in the management of COVID-19 in these individuals. A retrospective cohort study was developed at a tertiary hospital for infectious disease in Romania, which included a total of 242 patients with hepatitis C cirrhosis across two years, out of which 46 patients were infected with SARS-CoV-2. Stratification by patient weight and COVID-19 status identified several important laboratory serum tests as predictors for acute-on-chronic liver failure and risk for intensive care unit admission. Thus, white blood cell count, lymphocyte count, ferritin, hypoglycemia, prothrombin time, and HCV viral load were independent risk factors for ACLF in patients with COVID-19. High PT, creatinine, BUN, and HCV viral load were the strongest predictors for ICU admission. Inflammatory markers and parameters of gas exchange were also observed as risk factors for ACLF and ICU admission, including procalcitonin, CRP, IL-6, and D-dimers. Our study questions and confirms the health impact of COVID-19 on patients with cirrhosis and whether their laboratory profile significantly changes due to SARS-CoV-2 infection.

Diagnostic role of procalcitonin serum level in hepatitis C virus-infected patients with spontaneous bacterial peritonitis

ObjectiveWe aimed at the evaluation of the role of quantification of serum procalcitonin (PCT) in the detection of spontaneous bacterial peritonitis (SBP) in hepatitis C-related cirrhosis before and after initiation of antibiotic therapy.BackgroundSBP is a lethal consequence of advanced cirrhosis. The outcome is heavily affected by early detection and treatment. PCT has been evaluated during acute bacterial infections and sepsis.Patients and methodsWe included 60 patients with ascites due to hepatitis C-related cirrhosis, who were divided in two groups: group 1 included 40 naïve patients with SBP, and group 2 included 20 patients with sterile ascites as a control. After history taking and clinical examination, full blood count, liver test profile, and renal functions were done. Moreover, C-reactive protein and erythrocyte sedimentation rate levels were measured. Serum PCT was measured by immunoassay. Diagnostic ascitic sample analysis was done for the polymorphonuclear leukocyte (PMNL) count, albumin levels, and ascetic fluid culture.ResultsSerum PCT was significantly elevated in group 1 before treatment than after treatment, as well as when compared with group 2. There was no statistically significant correlation between the change in the C-reactive protein level and that of the serum PCT before and after treatment in group 1. There is no significant correlation between increases in the serum PCT and the results of bacterial growth of ascetic fluid culture group before and after treatment.ConclusionPCT levels in the serum appear to provide a good diagnostic certainty in the diagnosis of SBP in cirrhotic patients at a cutoff value of 0.17 ng/ml for patients with either culture-positive or negative SBP.

Successful Eradication of Hepatitis-C Virus with Sofosbuvir based Antiviral treatment results in improvement in quality of life in cirrhotic patients.

Objectives:To document improvement in quality of life in patients with Hepatitis-C related cirrhosis after successful eradication of the virus.Methods:In this observational cohort study conducted at Fatima Memorial Hospital from September 2015 to July 2017, patients with HCV were assessed for improvement in quality of life by using FACIT-F questionnaire. We compared the Quality of life (QOL) score before the start of treatment with DAAs and after achieving SVR12 in various aspects of quality of life including physical, emotional, functional and social well-being.Results:A total of 71 patients, 52 (73%) were CTP class A, 18 (25%) in B and one (1.4%) in C. The mean score of QOL before AVT was 23.93±7.04 and after achieving SVR it was 36.83±6.36 (P-value <0.001). In the subcategories, score of functional wellbeing, physical well-being and social wellbeing were significantly improved except emotional wellbeing scores. All scores improved across the spectrum of patients in the CTP class A and B. There was only one patient in the CTP-C class.Conclusion:Chronic HCV infection complicated by cirrhosis causes a significant decline in quality of life. There was a marked improvement in the functional, social and physical health of the patients after eradication of Hepatitis-C with anti-viral therapy except emotional health of the individuals.