Unstable Recompensation: An Intermediate Subtype in Patients With HBV-Related Decompensated Cirrhosis.

Natural history of chronic hepatitis B virus infection: What determines prognosis after cirrhotic decompensation?

Trends in decompensated cirrhosis and hepatocellular carcinoma among people with a hepatitis B notification in New South Wales

Management of patients with hepatitis B virus-induced cirrhosis

Viral Hepatitis in Liver Transplantation

To compare the efficacy of Lamivudine (LAM) monotherapy and combination therapy with Adefovir Dipivoxil (ADV) for patients with hepatitis B virus (HBV) -related decompensated cirrhosis for 2 years. A total of 115 patients with HBV-related decompensated cirrhosis were erolled in this study, among 60 patients were treated with LAM combined with ADV and 55 were treated with LAM. The liver and kidney functions, HBV DNA, HBV-M, AFP, Ultrasond or CT scan of liver were tested every 1-3months. the treatment efficacy was evaluated by month 12 and 24. By month 12, the HBV DNA negative rates of combination therapy group and LAM monotherapy group were 51.1% (45 cases) and 47.5% (40 cases) respectively, by month 24 the rates were 86.7% and 60.0% respectively. By month 24 the HBeAg negative rates of combination therapy group and LAM monotherapy group were 43.5% and 30.0% respectively, with significant difference existed between the two therapy groups (P values is less than 0.05). By month 24, the ALT normalization rates of the two groups were 88.9% and 72.5% respectively. Viral breakthrough happened in 2 cases (4.4%) by month 12 and 3 cases (6.7%) by month 24 in LAM and ADV combination group, but no viral resistance observed. Viral breakthrough happened in 9 cases (22.5%) by month 12 and 15 cases (37.5%) by month 24 in LAM monotherapy group with viral resistance observed in 7 cases (17.5%) by month 12 and 13 cases (32.5) by month 24. Significant difference existed between the two groups (P is less than 0.05). Improvement of liver function was more obviously in the combination group. The accumulative total mortality or liver transplantation rate were 16.7% and 20.0% respectively in combination therapy group and LAM monotheapy group. No renal dysfunction observed in both groups. LAM combined with ADV is better choice for patients with HBV-related decompensated cirrhosis as compared to LAM monotherapy.

The Editor, Sir, Hepatitis B virus (HBV)-related decompensated cirrhosis is an end-stage liver disease; antiviral therapy can improve the prognosis in these patients (1). Entecavir (ETV) is considered an ideal drug for nucleotide and nucleoside-naive patients with decompensated cirrhosis due to its rapid and potent antiviral effects and low risk of resistance, but clinical data on the safety in these patients with severely impaired liver function are limited. A 58-year old Chinese male was diagnosed with chronic HBV in 2009, but he had not received any treatment for HBV at that time. He presented with HBV-related decompensated cirrhosis, including ascites and splenomegaly. The initial laboratory tests showed elevated liver tests and the serum HBV DNA level was 4.15 × 107 copies/mL. He was diagnosed with HBeAg-positive chronic HBV-related decompensated cirrhosis and his model for end-stage liver disease (MELD) score was 18. He was treated with 0.5 mg ETV daily and was evaluated for liver transplantation. After one month of therapy with ETV, he had a significant reduction in serum HBV DNA (9.70 × 103 copies/mL) and the MELD score remained stable. After receiving two months of ETV therapy, he was admitted to hospital with diarrhoea, abdominal pain, vomiting and fever. His body temperature was 37.2 °C, his pulse 120 beats per minute, respiratory rate 20 breaths per minute and blood pressure 110/70 mmHg. The physical examination revealed yellow sclera, abdominal tenderness and rebound pain, shifting dullness and active bowel sounds. The white blood cell count was 4.15 × 109/L, the neutrophil ratio 85.1%, haemoglobin 104 g/L, and the platelet count 71 × 109/L. The arterial pH value was 7.17, the oxygen pressure 23.3 kPa, the carbon dioxide pressure 3.2 kPa, the oxygen saturation 99%, the base excess −18.1 mmol/L, and the lactate level > 15 mmol/L. Empiric medical treatment for infection, prevention of further insult to the liver, and maintaining water, electrolyte and acid base balance was initiated, but the patient's condition rapidly deteriorated, and he eventually died 15 hours after admission. Two days later, the blood culture showed the presence of Escherichia coli. All of the approved oral nucleotide and nucleoside analogues for HBV carry a ‘black box’ warning in their labelling regarding potential mitochondrial toxicity that can manifest itself as lactic acidosis, myopathy, neuropathy, or even hepatotoxicity (1). The MELD score has been reported in association with lactic acidosis during ETV treatment (2). However, some recent studies observed only one adverse event of lactic acidosis in an ETV treated patient, and the event was resolved without interruption of drug. It is worth noting that two of these studies included patients with a worse liver function (median MELD score 17.1 and 15.3, respectively in the study by Liaw et al (3); 16.1 ± 4.3 and 16.7 ± 4.1, respectively in the report by Hyun et al (4)). Moreover, a small study found that the risk of lactic acidosis was not increased in patients with HBV decompensated cirrhosis with high MELD score who received ETV, compared with patients with non-HBV decompensated cirrhosis (5). The report from Germany also showed that the white blood counts of the patients with MELD scores ≥ 20 were significantly higher than those with MELD scores ≤ 17 (9.28 ± 3.06/nL vs 5.87 ± 2.43/nL, t = 2.41, p < 0.05, using SPSS version 13.0). Thus the patients with high MELD scores could have some unrevealed infections. In conclusion, even if more high-quality and well-designed studies are needed to confirm the correlation between ETV and lactic acidosis, prevention of infection in patients with HBV-related decompensated cirrhosis and severely impaired liver function should be more emphasized. Once these patients develop lactic acidosis, infection must be first excluded or controlled in a timely manner.

The effect of viral suppression on long-term disease outcome after decompensation in patients with hepatitis B virus (HBV)-related cirrhosis has not been established. The aim of this study was to determine the long-term effect of antiviral therapy (AVT) in patients with HBV-related decompensated cirrhosis. This was a multicenter, prospective, inception cohort study of 707 patients who presented with first-onset decompensated complications, including 284 untreated and 423 antiviral-treated patients (58 previously treated, 253 with early treatment, and 112 with delayed treatment). The primary endpoint was 5-year liver transplantation (LT)-free survival. Secondary endpoints included virological response (VR) and serological response and improvement in liver function. Despite baseline high HBV activity and worse liver function, antiviral-treated patients had significantly better transplant-free survival than untreated patients (5-year survival rates of 59.7% vs. 46.0%, respectively), with more apparent benefits from antivirals in Child-Turcotte-Pugh class B/C and high-viremia groups. The rate of VR and hepatitis B e antigen seroconversion at 5 years in antiviral-treated patients was 14.2% and 49.1%, respectively. A significant improvement in liver function was observed in treated versus untreated patients, with 33.9% of treated patients delisted for LT. Patients with early treatment had better clinical outcomes than those with delayed treatment. Survival was dependent on antiviral response, being significantly better in responders than in nonresponders or untreated cases. The initial benefit of AVT was negated over time in nonresponders. Antiviral treatment and maintained VR remained independently predictive of survival. The study results were corroborated by propensity score-matching analysis. AVT significantly modifies the natural history of decompensated cirrhosis, improving liver function and increasing survival. The results underscore the importance of promptly administering potent antiviral drugs to patients under consideration for LT.

Antiviral therapy (AVT) is the mainstay of hepatitis B virus (HBV) management. We investigated whether AVT improves the outcomes of HBV-related decompensated cirrhosis and undetectable HBV-DNA. Between 2000 and 2017, treatment-naïve patients with HBV-related decompensated cirrhosis and undetectable HBV-DNA were recruited from two tertiary hospitals. The endpoints included death and hepatocellular carcinoma (HCC). A total of 429 patients were analyzed (50 and 379 patients in the AVT and non-AVT groups, respectively). Patients in the AVT group were significantly younger and had higher alanine aminotransferase and alpha-fetoprotein levels than those in the non-AVT group (all P<0.05). During follow-up (median 49.6months), 98 patients died and 105 developed HCC. The cumulative incidence rates of death (2.0%, 4.1%, and 6.4%, and 4.9%, 7.2%, and 10.2% at 6months, 1year, and 2years, respectively) and HCC (8.6%, 15.8%, and 26.4% vs 1.6%, 7.7%, and 24.4% at 1, 2, and 5years, respectively) were statistically comparable between the AVT and non-AVT groups (all P>0.05). Using Cox regression analysis, AVT was not significantly associated with death nor HCC (all P>0.05). Similar results were observed after balancing baseline characteristics with inverse probability of treatment weighting. In the non-AVT group, the cumulative incidence rates of HBV-DNA detection at 6months, 1year, and 2years were 2.0%, 3.1%, and 6.4%, respectively. Antiviral therapy did not attenuate the risk of death nor HCC in patients with HBV-related decompensated cirrhosis and undetectable HBV-DNA.

Effects of Virologic Response to Treatment on Short- and Long-term Outcomes of Patients With Chronic Hepatitis B Virus Infection and Decompensated Cirrhosis

Entecavie (ETV) has a potent antiviral effect and low rates of resistance in hepatitis B virus (HBV) and is the first-line monotherapy in patients with HBV-related decompensated cirrhosis. We evaluated the efficacy of 12 months treatment with ETV and tried to determine predictive factors of response. Forty-five consecutive decompensated cirrhotic patients who received ETV (0.5 mg/day) for more than six months were included. All patients were positive for HBV DNA, and the Child-Turcotte-Pugh (CTP) scores were over 8 point. Seventeen patients were HBeAg-positive. CTP score, model for end-stage liver disease (MELD) score, serum markers of liver function and HBV DNA were assessed every 3 months. ETV treatment for 12 months resulted in improvement of CTP and MELD scores. Pre-treatment mean CTP and MELD score were decreased from 10.1 (±2.0) and 13.48 (±4.05) to 7.24 (±2.0) and 9.68 (±4.85) at 12 months, respectively. The 1-year cumulative rates of HBV DNA negativity and HBeAg loss were 88.9% and 52.9%, respectively, by intention-to-treat analysis. Thirty-two (71.1%) showed improvement in CTP score. Eleven patients did not show change, and 2 patients got worse. The AST/ALT, albumin, bilrubin, prothrombin time were significantly normalized within six months. The good responder group had high level of prothrombin time than the poor responder group (p=0.004). Our result shows that entecavir can improve liver function in about 70% of patients with HBV related decompensated liver cirrhosis. INR may be a predictive factor of good response with entecavir in these patients.

The development of nuleos(t)ide analogues (NAs) has dramatically changed the natural history of chronic hepatitis B virus (HBV) infection. In this study, we compared patients with HBV-related decompensated cirrhosis with and without NA therapy in terms of hepatocarcinogenesis and all-cause, liver-related, and non-liver-related mortality. This study enrolled 160 patients with decompensated cirrhosis, 78 of whom were treated with NA therapy (NA group) and 82 of whom were not (non-NA group). Propensity score matching and inverse probability weighting were performed to adjust the baseline characteristics in the NA and non-NA groups. Liver-related and non-liver-related mortality were analysed using the competing risks IPW cumulative incidence functions estimator. The Cox proportional hazards model and the Fine and Gray proportional hazards model were used to analyse factors associated with hepatocarcinogenesis and all-cause, liver-related, and non-liver-related mortality. HBV DNA ≥20,000 IU/ml (adjusted hazard ratio [aHR], 8.440) and dyslipidemia (aHR, 0.178) were independently associated with hepatocarcinogenesis. HBV DNA ≥20,000 IU/ml (aHR, 4.360) and non-NA group (aHR, 4.802) were independently associated with all-cause mortality. Diabetes mellitus (aHR, 4.925), FIB-4 score >3.6 (aHR, 4.151), non-NA group (aHR, 9.180), presence of dyslipidemia (aHR, 0.182) and male gender (aHR, 3.045) were independently associated with liver-related mortality. HBV DNA ≥20,000 IU/ml (aHR, 3.216) and high age (aHR, 2.692) were independently associated with non-liver-related mortality. Although the cumulative incidence rate of hepatocarcinogenesis and non-liver-related mortality was not reduced by NA therapy, viral suppression reduced liver-related mortality in patients with DC.

Blood routine examination is an inexpensive, routinely performed clinical project, which includes many blood parameters. Hepatitis B virus (HBV) infection may have significant effects on blood parameters in decompensated patients with hepatitis B cirrhosis. However, details were not quite clear yet. A total of 207 HBV‐related decompensated cirrhosis (HBV‐DeCi) patients were included in this retrospective analysis. The included patients were subdivided into three groups: 44 patients with HBsAg, HBeAg, and HbcAb positive were set as Group I; 122 patients with HBsAg, HBeAb, and HbcAb positive were set as Group II; 41 patients with HBsAb, HBeAb, and HbcAb positive were set as Group III. Blood parameters, including platelet (PLT) count, mean platelet volume (MPV), lymphocyte count, leukocyte count and MPV/lymphocyte ratio (MPVLR), lymphocyte/ leukocyte ratio (LLR), platelet/leukocyte ratio (PLR) were analyzed respectively. The correlation between mentioned parameters and the HBV infection were characterized respectively. The values of PLT, MPVLR, and PLR in Group I and II were lower than that in Group III. Group II has a much higher LLR than that in Group I and III. HBV does have significantly effect on blood parameters in HBV‐DeCi patients. Effective treatment must be applied to achieve cirrhosis recompensation promptly.

Most cases of hepatocellular carcinoma (HCC) are associated with cirrhosis related to chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Changes in the time trends of HCC and most variations in its age-, sex-, and race-specific rates among different regions are likely to be related to differences in hepatitis viruses that are most prevalent in a population, the timing of their spread, and the ages of the individuals the viruses infect. Environmental, host genetic, and viral factors can affect the risk of HCC in individuals with HBV or HCV infection. This review summarizes the risk factors for HCC among HBV- or HCV-infected individuals, based on findings from epidemiologic studies and meta-analyses, as well as determinants of patient outcome and the HCC disease burden, globally and in the United States.

Surveillance for Hepatocellular Carcinoma in Patients With Cirrhosis

Liver cancer is the second leading cause of cancer death worldwide, responsible for an estimated 746,000 deaths and 782,000 new cases in 2012 [1]. The countries in the Western Pacific region accounts for 64% and China alone accounts for 51% of the new liver cancer cases and deaths each year. Approximately 80% of hepatocellular carcinoma (HCC), the most common type of liver cancer, is associated with viral hepatitis [1]. In countries with high prevalence of hepatitis B virus (HBV) infection, such as China, up to 80% of HCC is associated with hepatitis B [2]. Liver cancer carries a poor prognosis with a global mortality to incidence ratio of 0.95 [1]. In the USA, the 1-year survival rate remains less than 50% [3]. Asians and Pacific Islanders have the highest incidence of HCC among the different racial/ethnic groups. While every individual with chronic hepatitis B infection (CHB) or HBV carrier is at risk for developing HCC, disease progression leading to cirrhosis is associated with the greatest risk [2]. In an effort to improve survival through early detection of HCC, the American Association for the Study of Liver Diseases recommended HCC screening with abdominal ultrasound (US) at 6–12 month intervals of HBV carriers considered at increased risk for HCC, including those with cirrhosis, family history of liver cancer and Asian male HBV carriers above the age of 40 [4,5]. However, it remains controversial whether population-wide HCC screening of CHB patients results in a reduction in HCC mortality particularly in resource-constraint regions of the world that have the highest burden of HCC. The only two randomized trials available to date are both from China [6,7]. A population-based study in the city of Shanghai, conducted by the Liver Cancer Institute of Fudan University, reported 1-year HCC survival rates improved from 31.2% in the control group to 65.9% in the screened group among 18,816 CHB patients aged 35–59 years with or without cirrhosis, who were randomized into either a group using US and AFP screening every 6 months or a control group [6]. The second study from a rural setting in Qidong, using AFP screening every 6 months without US, did not show any improvement in survival [7]. According to the National Cancer Institute [8], screening for HCC