Incidence Of Hepatic Decompensation Research Articles

Impact of GLP-1RA on the Risk of Adverse Liver Outcomes Among Patients With Alcohol-Associated Liver Disease and Type 2 Diabetes.

We sought to characterise the impact of GLP-1RA on adverse liver outcomes (ALO) among patients with alcohol-associated liver disease (ALD) and Type 2 diabetes mellitus (T2DM). Patients with T2DM newly diagnosed with ALD between 2013 and 2020 were identified using IBM MarketScan database and were categorised by GLP-1RA exposure. Overlap propensity score weighting (OPSW) followed by Poisson regression models was used to analyse adjusted risk of ALO, a composite endpoint defined by first occurrence of hepatic decompensation (HD), portal hypertension (PH), hepatocellular carcinoma (HCC) or liver transplantation (LT) relative to GLP-1RA. Among 14 730 patients, most individuals were male (n = 9752, 66.2%) with median age of 57 (IQR 52-61) years; 2.2% (n = 317) of patients had GLP-1RA exposure. Overall, 32.0% (n = 4717) of patients experienced HD, 15.9% (n = 2345) had PH, 3.8% (n = 563) developed HCC, while 2.5% (n = 374) underwent transplantation. Non-GLP-1RA patients had higher incidence of HD (32.2% vs. 22.4%) and HCC (3.9% vs. 0.3%) versus patients taking GLP-1RA (both p < 0.001); in contrast, there was no difference in incidence of PH (14.5% vs. 16.0%) and LT (1.3% vs. 2.6%) (both p > 0.05). After OPSW, overall incidence of ALO was lower in GLP-1RA cohort (GLP-1RA: 12.0%, 95%CI 9.0-16.0 vs. non-GLP-1RA: 21.0%, 95%CI 20.0-22.0) with an absolute incidence risk reduction of 9.0% (95%CI 3.0%-15.0%) associated with GLP-1RA. GLP-1RA was most strongly associated with lower likelihood of HD with reduced adjusted incidence rate of 0.56 (95%CI 0.36-0.86) relative to non-GLP-1RA individuals. GLP-1RA may have a hepatoprotective impact among patients with ALD and T2DM.

High Prevalence and Clinical Relevance of Intrapulmonary Vascular Dilatations in Patients Undergoing TIPS Implantation

Background and AimsConsiderate patient selection is vital to ensure best possible outcomes after transjugular intrahepatic portosystemic shunt (TIPS) insertion. However, data regarding the impact of intrapulmonary vascular dilatations (IPVD) or hepatopulmonary syndrome (HPS) on the clinical course after TIPS implantation is lacking. Hence, this study aimed to investigate the relevance of IPVD and HPS in patients undergoing TIPS implantation. MethodsContrast enhanced echocardiography and blood gas analysis were utilized to determine presence of IPVD and HPS. Multivariable competing risk analyses were performed to evaluate cardiac decompensation (CD), hepatic decompensation (HD) and liver transplant (LTx)-free survival within one-year of follow up. ResultsOverall, 265 patients were included, of whom 136 had IPVD and 71 fulfilled the HPS criteria. Patients with IPVD had lower Freiburg index of post-TIPS survival (FIPS) scores, lower creatinine and more often received a TIPS because of variceal bleeding. Presence of IPVD was associated with a significantly higher incidence of CD (HR: 1.756 95%CI: 1.011-3.048 p=0.046) and HD (HR: 1.841 95%CI: 1.255-2.701 p=0.002). However, LTx-free survival was comparable between patients with and without IPVD (HR: 1.081 95%CI: 0.630-1.855, p=0.780). Patients with HPS displayed a trend towards more CD (HR: 1.708 95%CI: 0.935-3.122, p=0.082) and HD (HR: 1.458 95%CI: 0.934-2.275, p=0.097) that failed to reach statistical significance. LTx-free survival did not differ in those with HPS compared to patients without HPS, respectively (HR: 1.052 95%CI: 0.577-1.921, p=0.870). ConclusionScreening for IPVD before TIPS implantation could help to further identify patients at higher risk of cardiac and hepatic decompensation.

“NASH-Worldwide the Commonest Aetiology of Liver Cirrhosis”- a Review Article

NAFLD is defined by the presence of fat in the liver (&gt;5% hepatocytes show macrovesicular steatosis) without evidence of other causes of fat accumulation in the liver such as alcohol use (&lt; 20 g/d for women and &lt;30 g/d for men), hepatitis C or certain medications. The spectrum of disease includes NAFL, NASH, cirrhosis and HCC. Disease progression depends on stages of fibrosis. Patients are usually referred with incidentally noted hepatic steatosis on imaging or elevated liver enzymes. Although liver biopsy is the gold standard for diagnosis but worldwide it’s much under practiced and several non invasive tests are currently recommended to identify at risk NASH (≥ stage 2 fibrosis) or advance fibrosis who are at highest risk of developing to cirrhosis. Screening in high-risk populations - T2DM, obesity with metabolic complications, a family history of cirrhosis or significant alcohol use allows for interventions that may prevent future hepatic complications. Currently, about 38% of the global population has a diagnosis of NAFLD. The incidence of hepatic decompensation, HCC and death related to NASH cirrhosis are expected to increase 2-to 3-fold by 2030. NASH- cirrhosis is already the leading indication of liver transplantation worldwide. Currently no specific treatments is licensed for NASH, lifestyle modification and exercise, primarily weight loss is the key to management. The rising clinical and economic burden of NAFLD has highlighted the need for a streamlined approach to prevention, diagnosis, and treatment of the disease that has been discussed in this narrative review. Bangabandhu Sheikh Mujib Med. Coll. J. 2023;2(2):112-126.

Continuing Medical Education Questions: September 2023.

Article Title: Incidence of hepatic decompensation after nucleos(t)ide analog withdrawal: Results from a large, international, multi-ethnic cohort of patients with chronic hepatitis B (RETRACT-B study).

Predictive Value of [99mTc]-MAA-Based Dosimetry in Hepatocellular Carcinoma Patients Treated with [90Y]-TARE: A Single-Center Experience.

Transarterial radioembolization is a well-established method for the treatment of hepatocellular carcinoma. The tolerability and incidence of hepatic decompensation are related to the doses delivered to the tumor and healthy liver. This retrospective study was performed at our center to evaluate whether tumor- and healthy-liver-absorbed dose levels in TARE are predictive of tumor response according to the mRECIST 1.1 criteria and overall survival. One hundred and six patients with hepatocellular carcinoma were treated with [90Y]-loaded resin microspheres and completed the follow-up. The dose delivered to each compartment was calculated using a compartmental model. The model was based on [99mTc]-labelled albumin aggregate images obtained before the start of therapy. Tumor response was assessed after three months of treatment. Kaplan-Meier analysis was used to assess survival. The mean age of our population was 66 ± 13 years with a majority being BCLC B tumors. Forty-two patients presented with portal vein thrombosis. The response rate was 57% in the overall population and 59% in patients with thrombosis. Target-to-background (TBR) values measured on initial [99mTc]MAA-SPECT-imaging and tumor model dosimetric values were associated with tumor response (p < 0.001 and p = 0.009, respectively). A dosimetric threshold of 136.5 Gy was predictive of tumor response with a sensitivity of 84.2% and specificity of 89.4%. Overall survival was 24.1 months [IQR 13.1-36.4] for patients who responded to treatment compared to 10.4 months [IQR 6.3-15.9] for the remaining patients (p = 0.022). In this cohort, the initial [99mTc]MAA imaging is predictive of response and survival. The dosimetry prior to the application of TARE can be used for treatment planning and our results also suggest that the therapy is well-tolerated. In particular, hepatic decompensation can be predicted even in the presence of PVT.

From the Editor’s Desk...

From the Editor’s Desk...

Acoustic radiation force impulse to measure liver stiffness and predict hepatic decompensation in pregnancy with cirrhosis: A cohort study

Background and study aimsPregnancy in association with cirrhosis is a rather uncommon and highly risky situation for both mother and child. We aim to study all factors and the utility of liver stiffness (LS) measurement by Acoustic Radiation Force Impulse elastography (ARFI) to predict hepatic decompensation in pregnant cirrhotic patients. Patients and methodsWe prospectively recruited 224 pregnant women at the multidisciplinary clinic of liver disease with pregnancy, Cairo University. LS was measured using ARFI (Siemens ACUSON S3000 ultrasound system) during the second trimester and 8–12 weeks post-delivery. The outcome of pregnancy and the incidence of hepatic decompensation were assessed. ResultsOur cohort comprised 128 normal pregnancies, 37 patients with pregnancy-related liver disease (Intrahepatic cholestasis (n = 6), preeclampsia (n = 23), and hyperemesis gravidarum (n = 8)) and 59 patients with an established chronic liver disease not related to pregnancy. In all patients, LS significantly decreased after delivery from 1.19 m/s to 0.94 m/s (P < 0.001). In multivariate analysis, LS was an independent predictor for the outcome of pregnancy in all patients (odds ratio (OR) = 5.442 (3.01–6.82), cut-off = 1.21 m/s). Patients with cirrhosis, mean LS was 1.57 ± 0.66 m/s and 26 (44%) patients had hepatic decompensation (hepatocellular jaundice (n = 8), ascites (n = 9) and variceal bleeding (n = 6)). In multivariate analysis; LS, platelets, albumin, and bilirubin were independent predictors of decompensation post-delivery and the OR for LS was 6.141(4.32–7.98). The optimal cut off value of LS to predict decompensation was 1.46 m/s (8.4 kPa) with AUROC of 0.827. ConclusionLS can be used to predict hepatic decompensation after delivery in pregnant women with manifest cirrhosis.

Validation of a standardized CT protocol for the evaluation of varices and porto-systemic shunts in cirrhotic patients

PurposeThe aim of the present study was to propose and validate a standardized CT protocol for evaluating all the types of portosystemic collaterals (P-SC), including gastroesophageal varices and spontaneous portosystemic shunts (SPSS), and to evaluate the prognostic role of portal hypertension CT features for the prediction of the hepatic decompensation risk in cirrhotic patients. MethodsA retrospective cohort study of 184 advanced chronic liver disease who underwent CT scan between January 2014 and December 2017. Patients with an interval > 6 months between the imaging, elastometric, endoscopic and biochemical evaluation were excluded, as well as patients with previous transjugular intrahepatic portosystemic shunt (TIPS), liver transplantation (LT) or terminal medical conditions. Data on liver disease history, co-morbidities, endoscopic and radiologic findings were collected. The incidence of hepatic decompensation and other events, such as portal vein thrombosis, HCC, TIPS placement, LT, death, and its cause, were also recorded.The procedure was performed at baseline and after the administration of contrast agent using a multiphasic technique and bolus tracking. Two senior radiologists working in different centres and a non-expert radiologist reviewed all CT examinations, to evaluate both intra-observer and inter-observer variability of the CT protocol and to obtain an external validation. The radiological variables were evaluated using both univariate and adjusted multivariate competing risk regression models. ResultsBoth intra-observer and inter-observer agreement were excellent in detection and measurement of almost all types of P-SC. The presence of SPSS, a spleen diameter > 16 cm, a portal vein diameter > 17 mm and the presence of ascites resulted independent predictors of decompensation-free survival for cirrhotic patients and were incorporated in an easy-to-use score (AUROC = 0.799, p-value = 0.732) which can the risk of decompensation at 5 years, ranking it as low (11.3%), moderate (35.6%) or high (70.8%). ConclusionsThe CT protocol commonly performed during the HCC surveillance program for cirrhotic patients is valid for detecting all types of P-SC. The radiological score identified to predict the decompensation-free survival for cirrhotic patients could be an easy-to-use clinical tool.

Hepatitis B reactivation and outcomes in persons treated with directly acting antiviral agents against hepatitis C virus: results from ERCHIVES.

Higher risk of hepatitis B reactivation (HBV-r) has been reported in patients with hepatitis C treated with newer directly acting antiviral agents (DAAs). To determine the proportion of persons who develop HBV-r and its clinical consequences among DAA treated vs pegylated interferon/ribavirin (PEG/RBV) treated persons. We calculated the proportion of persons who developed HBV viral reactivation (HBV-r; new detectable HBV DNA or increase of >1 log10 ); serum alanine aminotransferase flare (>5 times baseline); all-cause mortality and hepatic decompensation in persons treated with a newer DAA regimen or PEG/RBV. Kaplan-Meier curves were used to demonstrate survival and hepatic decompensation by treatment group and HBV-r. In 34 632 persons treated with DAA and 23 475 treated with PEG/RBV, HBV-r rate per 1000 person-years was 30.04 (10.41, 49.67) and 25.42 (95% CI 17.23, 33.62) respectively (P = .8). When stratified by SVR or by baseline HBsAg status, HBV-r was not different between groups. Kaplan-Meier survival curves comparing each regimen stratified by presence or absence of HBV-r did not demonstrate a significant difference in incidence of hepatic decompensation over time. For overall survival, there was no difference between PEG/RBV treated persons with or without HBV-r. For DAA treated persons, those with HBV-r had a shortened survival, though the numbers at risk were small. HBV-r is relatively uncommon after DAA therapy and not higher than among those treated with a PEG/RBV regimen. The small numbers of persons treated with a DAA regimen who do develop HBV-r have a shortened survival compared to those without HBV-r.

Clinical Events After Cessation of Lamivudine Therapy in Patients Recovered From Hepatitis B Flare With Hepatic Decompensation

Before guidelines were issued, many patients with hepatitis B flare and hepatic decompensation had discontinued lamivudine therapy instead of indefinite therapy. We investigated their outcomes. We performed a retrospective cohort study of 263 consecutive patients with chronic hepatitis B (94 with cirrhosis) who recovered from a flare of hepatitis with hepatic decompensation and were followed after cessation of lamivudine therapy. Clinical events that occurred during the follow-up period were assessed by chart review and analysis of results from retrospective assays. The mean duration of lamivudine therapy was 12.1 ± 8.6 months; data were collected from patients for 89.1 ± 38.7 months after therapy ended. In the first year off therapy, 29.9% of patients had clinical relapse, 16.2% had hepatitis flares, and 8.2% had hepatic decompensation. There was no significant difference in the incidence of hepatic decompensation between patients with and without cirrhosis. Hepatocellular carcinoma developed in 14 patients 20-109 months after cessation of therapy, with 5-year cumulative incidence of 5.2% in patients with cirrhosis. Three patients with cirrhosis died of hepatic decompensation 38-76 months after cessation of therapy (5-year cumulative mortality, 2.9%). Multivariate analyses showed that men were more likely than women to have recurrence of hepatic decompensation (hazard ratio [HR], 4.339; P = .014). Liver cirrhosis (HR, 2.766; P = .041) and age (HR, 1.054; P = .023) increased risk for hepatocellular carcinoma. Cessation of lamivudine therapy after recovery from hepatitis B flare with decompensation was safe for most patients. However, 8.2% develop decompensation within 1 year and can be rescued by timely retreatment. With close monitoring, the stopping strategy could be a feasible alternative to indefinite therapy, especially in low resource settings.

Prognostic factors of hepatic decompensation and hepatocellular carcinoma in patients with transfusion‐acquired HCV infection

Aim of this study was to assess if host (immunogenetic traits, age, sex), exogenous (alcohol) or viral factors (viral type, past HBV infection) might affect the progression of chronic hepatitis C to liver decompensation or the development of HCC in a cohort of patients exposed to a single blood transfusion prior to the introduction of anti-HCV screening. Two hundred and forty-eight patients with a history of a single exposure to blood or blood products prior to 1990 were retrospectively considered. Patients were devoid of other risk factors of liver disease or immunosuppression and naïve to antiviral therapies. Eight baseline variables were assessed: age at transfusion, sex, HBV core antibody, immunogenetic profile (DRB1*11, DRB1*1104, DRB1*07), HCV genotype and alcohol consumption. The follow-up was 22 (SD: 11) years. Sixty-eight patients (27%) progressed to hepatic decompensation over a median period of 22.5 years (IQR: 14-30) and 41 patients (16%) developed HCC over a median period of 31 years (IQR: 24-38). The cumulative incidence of liver failure was 0.4% (95% CI: 0.1-3.1), 4.9% (95% CI: 2.6-9.3) and 16.2% (95% CI: 10.4-24.7) at 10, 20 and 30 years after blood transfusion respectively. By univariate analysis, only age at transfusion was correlated with the risk of decompensation. Stratifying the age of transfusion by tertiles, the incidence of hepatic decompensation was 0.7% per year in patients transfused at ≤24 years of age as compared to 1.2% and 1.9% per year in those transfused at 25-35 and >36 years of age respectively (HR: 5.5, 95% CI: 2.78-10.7, P<0.001). The risk of HCC development was correlated by univariate analysis with age at transfusion (as continuous variable, HR: 1.12, 95% CI: 1.08-1.16 per year of age, P<0.001, >36 compared to ≤24 years, HR: 10.3, 95% CI: 3.9-26.9, P<0.001) and male sex (HR: 4.2, 95% CI: 1.7-10, P=0.001). Multivariate analysis confirmed age at transfusion and male sex as independent predictors of HCC development [HR: 1.12 per year (95% CI: 1.08-1.16), P<0.001 and HR: 5.4 (95% CI: 2.2-13.2), P<0.001 respectively]. In patients with transfusion-acquired HCV infection, age at transfusion affects the risk for hepatic decompensation. Age at transfusion and male sex are independent risk factors for HCC development.

Chronic cirrhotic hepatitis B patients with a high incidence of hepatic decompensation after viral breakthrough with lamivudine-resistant mutants and during rescue treatment

Objective. To compare the rate of biochemical and hepatic decompensation after viral breakthrough (V-BT) caused by lamivudine (LMV)-resistant HBV mutants and during rescue treatment for patients with liver cirrhosis (LC) and chronic hepatitis B (CHB). Material and methods. We reviewed the medical records of 205 CHB patients who developed V-BT with LMV-resistant HBV mutants (134 in the CHB group, 71 in the LC group). Results. Sixty-five of the 205 patients had an alanine aminotransferase (ALAT) flare-up (32%) and 21 (10%) had hepatic decompensation. The ALAT flare-up among the CHB and LC groups occurred in 43 (32%) and 22 patients (31%), respectively, and there was no significant difference between the two groups. Hepatic decompensation occurred in 5 (4%) and 16 (23%) patients with CHB and LC, respectively, and these differences were significant (p=0.001). A total of 187 patients were treated by rescue therapy (CHB 121, LC 66) and 13 cases with hepatic decompensation occurred only in LC patients during rescue therapy. Among them, 11 patients had serum ALAT levels two times higher than the upper normal limit (UNL) and the HBV-DNA was more than 107 copies/ml at the baseline of rescue therapy. In contrast, the cumulative ALAT normalization and viral response rates were reached significantly earlier in patients with a serum HBV-DNA of ≤107 copies/ml compared with those with an HBV-DNA >107 copies/ml (p=0.0221 and 0.0002, respectively). Conclusion. Earlier rescue therapy for cirrhotic patients with genotypic resistance due to LMV-resistant mutants may improve patient outcome.

Long term hepatitis B therapy with lamivudine: a major step forward but can we do even better?

Lamivudine for patients with chronic hepatitis B and advanced liver disease. Liaw YF, Sung JJY, Chow WC, Farrell G, Lee C-Z, Yuen H, et al. Background The effectiveness of antiviral therapy in preventing disease progression in patients with chronic hepatitis B and advanced fibrosis or cirrhosis is unknown. Methods Patients with chronic hepatitis B who had histologically confirmed cirrhosis or advanced fibrosis were randomly assigned in a 2:1 ratio to receive lamivudine (100mg per day) or placebo for a maximum of five years. Of 651 patients, 436 were assigned to receive lamivudine and 215 to receive placebo. The primary end point was time to disease progression, defined by hepatic decompensation, hepatocellular carcinoma, spontaneous bacterial peritonitis, bleeding gastroesophageal varices, or death related to liver disease. An independent data and safety monitoring board monitored the progress of the study and performed interim analyses of the data. Results We randomly assigned 651 patients (98% Asian and 85% male) to receive lamivudine or placebo. The study was terminated after a median duration of treatment of 32.4 months (range, 0–42) owing to a significant difference between treatment groups in the number of end points reached. End points were reached by 7.8% of the patients receiving lamivudine and 17.7% of those receiving placebo (hazard ratio for disease progression, 0.45, P =0.0001). The Child–Pugh score increased in 3.4% of the patients receiving lamivudine and 8.8% of those receiving placebo (hazard ratio, 0.45, P =0.02), whereas hepatocellular carcinoma occurred in 3.9% of those in the lamivudine group and 7.4% of those in the placebo group (hazard ratio, 0.49; P =0.047). Genotypic resistance YMDD mutations developed in 49% of the patients treated with lamivudine, and the Child–Pugh score was more likely to increase in patients with these mutations than in the other patients treated with lamivudine (7 vs 1%). Overall, 12% of the patients in the lamivudine group and 18% of the patients in the placebo group reported serious adverse events. Conclusions Continuous treatment with lamivudine delays clinical progression in patients with chronic hepatitis B and advanced fibrosis or cirrhosis by significantly reducing the incidence of hepatic decompensation and the risk of hepatocellular carcinoma. [Abstract reproduced by permission of New Engl J Med 2004; 351:1521–31].

Effectiveness of interferon alfa on incidence of hepatocellular carcinoma and decompensation in cirrhosis type C

Background/Aims: The role of interferon alfa treatment in improving morbidity endpoints in patients with chronic hepatitis C infection is currently under debate. The aim of this study was to evaluate the effectiveness of interferon in preventing hepatocellular carcinoma and decompensation in cirrhosis type C.Methods: A retrospective cohort study was carried out on 329 consecutive Caucasians patients with cirrhosis followed for a mean period of 5 years at seven tertiary care university hospitals. Inclusion criteria were biopsy-proven cirrhosis, anti-HCV positivity, abnormal serum aminotransferase levels and absence of complications of cirrhosis.Results: The yearly incidence of hepatocellular carcinoma was 2.3% for 136 untreated patients and 1.0% for 193 patients treated with interferon alfa. The yearly incidence of hepatic decompensation was 5.7 for untreated and 1.4 for the treated patients. Fourteen (7%) of 193 treated patients showed sustained aminotransferase normalization and none of them developed complications of cirrhosis. At enrollment, untreated patients were older and had more sever liver disease than patients treated with interferon. After adjustment for clinical and serologic differences at entry between treated and untreated patients, the 5-year estimated probability of the occurrence of hepatocellular carcinoma was 2.1% and 2.7% and of decompensation was 7% and 11% for treated and untreated cases, respectively.Conclusions: This analysis did not detect any significant benefit of interferon alfa on morbidity in patients with compensated cirrhosis type C, although it suggests a reduction in complications of cirrhosis for those with a sustained response to therapy, and it indicates the need for better therapies.

Severe clinical rebound upon withdrawal of corticosteroid before interferon therapy: Incidence and risk factors

To analyse the incidence and risk factors of clinical rebound and hepatic decompensation during or upon withdrawal of prednisolone pretreatment before interferon (IFN) therapy, two series of Taiwanese patients with chronic viral hepatitis from two independent randomized controlled trails were compared. Group 1 included 41 patients with chronic hepatitis B who were pretreated with daily prednisolone (30 mg) for 3 weeks, 15 mg for 1 week and no prednisolone for 2 weeks prior to lymphoblastoid IFN therapy. Group 2 consisted of 59 patients with chronic hepatitis B who were pretreated with daily prednisolone (40 mg) for 2 weeks, 30 mg prednisolone for 2 weeks, 20 mg prednisolone for 2 weeks and no prednisolone for 2 weeks prior to INF alpha-2a therapy. Clinical rebound developed more frequently in group 2 (67.8%) than in group 1 patients (41.5%; P < 0.01). The peak serum transaminase levels of group 1 and 2 patients during clinical rebound were similar. Icteric and symptomatic clinical rebound occurred in four (one cirrhotic) group 2 patients. The incidence of hepatic decompensation was 3.4% in group 2 patients, or 5.0% in group 2 patients with clinical rebound. Patients pretreated with a higher dose (40 mg) of prednisolone (odds ratio 3.0; 95% CI 1.3-6.6; P < 0.01) and non-cirrhotic patients (odds ratio 6.2; 95% CI 1.2-32.1; P < 0.02) tended to suffer from clinical rebound more frequently. However, once clinical rebound develops in cirrhotic patients, the relative risk of decompensation is 16 times that of non-cirrhotic patients. These results suggest that clinicians should be cautious in prescribing a short course of corticosteroids for patients with chronic viral hepatitis, because hepatic decompensation might occur in Oriental people with or without cirrhosis.